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Hepatitis C: Beyond the Basics

2.5 Contact Hours including 2.5 Advanced Pharmacology Hours
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This peer reviewed course is applicable for the following professions:
Advanced Practice Registered Nurse (APRN), Certified Nurse Midwife, Certified Nurse Practitioner, Certified Registered Nurse Anesthetist (CRNA), Certified Registered Nurse Practitioner, Clinical Nurse Specialist (CNS), Licensed Practical Nurse (LPN), Licensed Vocational Nurses (LVN), Midwife (MW), Nursing Student, Occupational Therapist (OT), Occupational Therapist Assistant (OTA), Physical Therapist (PT), Physical Therapist Assistant (PTA), Registered Nurse (RN), Registered Nurse Practitioner
This course will be updated or discontinued on or before Saturday, June 13, 2026

Nationally Accredited

CEUFast, Inc. is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation. ANCC Provider number #P0274.



FPTA Approval: CE24-767379. Accreditation of this course does not necessarily imply the FPTA supports the views of the presenter or the sponsors.
Outcomes

≥ 92% of participants will know how to care for a patient with hepatitis C.

Objectives

After completing this course, the participant will be able to meet the following objectives:

  1. Summarize how hepatitis C is transmitted.
  2. Identify risk factors for hepatitis C transmission.
  3. Explain the two outcomes of acute exposure to hepatitis C.
  4. Determine the spontaneous clearance rate of acute hepatitis C exposure.
  5. Differentiate screening recommendations and tests used for diagnosing hepatitis C.
  6. Identify three extrahepatic complications of hepatitis C.
  7. Recommend drug therapy used to treat hepatitis C.
  8. Identify a United States (U.S.) Boxed Warning for direct-acting antiviral drugs used for hepatitis.
  9. Outline one lifestyle modification recommended for hepatitis C patients.
CEUFast Inc. and the course planners for this educational activity do not have any relevant financial relationship(s) to disclose with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

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Hepatitis C: Beyond the Basics
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Author:    Dana Bartlett (RN, BSN, MA, MA, CSPI)

Introduction

Hepatitis C is a ribonucleic acid (RNA) virus that infects the liver. The hepatitis C virus (HCV) was isolated and identified in 1989 (Houghton, 2019). Before that, there was a strong suspicion of the presence of another hepatitis virus, aside from hepatitis A (HAV) and hepatitis B (HBV), that was causing hepatitis, and these cases were called non-A/non-B hepatitis (Houghton, 2019). (Note: Hepatitis means liver inflammation. Many viruses can cause hepatitis, hepatitis can be an autoimmune disease, and drugs and toxins can cause hepatitis).

HCV is a significant U.S. public health problem and the most commonly reported bloodborne infection in the U.S. (Kaufman et al., 2021). In 2021, there were 39.8 new cases of chronic HCV per 100,000 (Centers for Disease Control and Prevention [CDC], 2023a), and the number of acute HCV cases increased by 129% from 2014 to 2021 (CDC, 2023c). The incidence of chronic cases has decreased. In 2020, it was 40.7 (CDC, 2022), but acute cases have increased, and 65% to 85% of patients who have acute HCV develop chronic HCV (Friedman, 2024a; Martinello et al., 2023).

Targeted screening and highly effective direct-acting antiviral drugs (DAAs) have decreased the incidence of chronic HCV infections, and these drugs have a cure rate of ≥ 95% (Martinello et al., 2023). Still, testing and drug therapy must be done to be effective, and there is evidence that the efforts to do that, for many reasons, have not been consistent. Wester et al. (2023) analyzed data from > 1.7 million American adults who had had an HCV infection. The authors concluded that there is a need for more access to diagnosis, treatment, and prevention resources, and there were ". . . substantial gaps in cures nearly a decade since highly effective direct-acting antiviral (DAA) agents" (Wester et al., 2023). The well-publicized opioid epidemic.

has contributed to the number of HCV infections in the U.S. (Park et al., 2023), and people who have a substance use disorder (SUD) are less likely to receive DAA therapy (Park et al., 2023).

Note: The primary focus of this module is chronic HCV.

Case Study

A 57-year-old male made an appointment with his primary care physician. The patient has no specific complaints or problems. However, he will be starting a new job that requires strenuous activity, and his employer has requested that a physician examine him to determine if he can tolerate this level of physical stress.

He is in good health, has no major medical problems, has no history of psychiatric illnesses, and does not take any prescription medications. He is moderately overweight (BMI of 27.6), drinks alcohol (occasionally to excess), and smokes one pack of cigarettes a day.

During the interview, the man admitted that as a young man, he had used intravenous (IV) drugs – heroin and occasionally cocaine ─ for a brief period but had not used any illicit substances for over 35 years. Laboratory tests reveal that his serum aspartate aminotransferase (AST) is 115 international units (IU)/liter (L), and his serum ALT is 190 IU/L; these levels are considered moderate elevations, and there are no previous tests for comparison. A test for hepatitis C antibodies is positive, and hepatitis C RNA is detected, genotype 1a. A fibroscan of his liver reveals a mild level of fibrosis but no cirrhosis. He does not have human immunodeficiency virus HIV, hepatitis A, or hepatitis B infection, and his complete blood count (CBC), international normalized ratio (INR), prothrombin time, vitamin D level, thyroid studies, and renal function tests were normal. His serum cholesterol is mildly elevated. The office screening test does not reveal the presence of or risk for depression.

The physician tells the patient it is likely that he has had hepatitis C for many years, and because he is overweight, occasionally drinks to excess, and smokes, he is at risk for progression to cirrhosis and possibly liver cancer. The physician recommends treatment with antiviral therapy, and the patient agrees. She prescribes ledipasvir/sofosbuvir (Harvoni®) one tablet a day for 12 weeks. The patient is advised that he may experience minor side effects such as diarrhea, fatigue, headache, insomnia, and nausea but that most patients tolerate the drug very well, and discontinuation because of adverse effects is very uncommon. He is enrolled in a smoking cessation program, provided with a weight reduction diet and an exercise program, and advised to stop drinking alcohol. He is also counseled on safe sex practices, given information on how HCV is transmitted, and instructed on how to avoid transmitting the virus. The physician stresses the importance of adherence to the drug regimen. The patient is instructed to contact the physician if he has any intolerable or unusual signs or symptoms, especially if he develops symptoms indicative of liver damage, e.g., ascites and jaundice.

After four weeks of drug therapy, there is no detectable HCV RNA, and the liver transaminases are within normal limits. Aside from occasional episodes of nausea, the patient has no somatic complaints, and his mood is good. Twelve weeks after finishing the drug regimen, there is no detectable HCV RNA, and his liver transaminases and all other blood tests are within normal limits. The patient has a sustained virologic response (SVR), and because his risk profile is low, the physician informs the patient that he is effectively cured; the risk of a relapse is very, very low. He is encouraged to continue with lifestyle modifications, continue safe sex practices, and continue to avoid behaviors that may put him at risk for reinfection. Because he had only mild fibrosis and no evidence of cirrhosis, no specific follow-up testing is needed.

Transmission of Hepatitis C Virus

HCV is transmitted by exposure to infected blood (CDC, 2023b; Friedman, 2024a). This can happen in many ways: blood transfusion, body piercing, during pregnancy and childbirth, healthcare exposures/patients and healthcare personnel, hemodialysis, IV drug use, household contact, e.g., sharing toothbrushes or razor, sharing needles and injection equipment during IV drug use, organ transplantation, unprotected sex, and tattooing (CDC, 2023b; Dienstag, 2022a; Friedman, 2024a). People who are homeless, immunosuppressed, incarcerated, hemophiliacs treated with clotting factors before 1987, people who had a blood transfusion or organ transplantation before July 1992, healthcare and emergency medical services personnel, people who have an HIV infection, and patients who have been recipients of blood or an organ that is infected with HCV have a higher than average risk of HCV infection (Dienstag, 2022a; Friedman, 2024a). In many cases, the transmission mode cannot be identified (Friedman, 2024a; Pfaender et al., 2018).

Exposure to Infected Blood

In the U.S., injection drug use and sharing injection equipment are the most common ways that people are exposed to HCV-infected blood and that HCV infections occur (CDC, 2022; Loy et al., 2024). HCV is very common in IV drug users worldwide (Artenie et al., 2023) and in the U.S. (CDC, 2023b; Chapin-Bardales et al., 2024; Ozga et al., 2022; Rogers-Brown et al., 2022). Chapin-Bardales et al. (2024) found that in 10 U.S. metropolitan areas, 44.2% of IV drug users had an RNA-confirmed HCV infection, and 40.3% had a chronic HCV infection confirmed by the presence of HCV RNA or HCV antibodies. The 2021 Hepatitis C Surveillance found that in 1,449 cases of acute HCV infection in which a risk factor profile was available, 57% of the infected persons had used IV drugs (CDC, 2023c).

The risk of hepatitis C transmission and infection from a needle stick injury or splash contact appears to be very low (Egro et al., 2017; Kacem et al., 2022; Lee et al., 2017; Naggie et al., 2017). Egro et al. (2017) retrospectively reviewed 1,361 cases of healthcare workers who had been exposed to hepatitis C-contaminated blood (72.7%) or other body fluids. There were 885 percutaneous and 476 mucous membrane exposures, and two employees had seroconverted, with a transmission rate of 0.1%. In the study by Kacem et al. (2022), two of 844 healthcare workers who had had occupational exposure to blood developed an HCV infection, and the study by Lee et al. (2017) reported one HCV infection after 126 exposures. Naggie et al. (2017) reviewed 12 studies (1992 to 2012) that described 3,929 healthcare occupational exposures to hepatitis C. Most of the cases were needlestick injuries, and the transmission rate of hepatitis C was 0-10%. In three of the studies, there were no incidents of hepatitis C transmission, and in 11 of the 12, the rate of transmission was in the single digits.

Iatrogenic and nosocomial HCV infections can be caused by dental procedures, endoscopic procedures, surgeries, and other invasive procedures (Henriot et al., 2022; Henriot et al., 2024). Hepatitis C infections in healthcare settings are typically caused by poor compliance with the procedures and requirements of Standard Precautions (CDC, 2023b).

The risk of HCV transmission from a transfusion of blood or blood products has been estimated to be < 1 in every two million units (CDC, 2023b).

The prevalence of HCV infection in hemodialysis patients is high (Dharmesti et al., 2022; Kenfack-Momo et al., 2024; Nguyen et al., 2019). In the U.S., from 2008 to 2018, 22 HCV outbreaks in hemodialysis centers resulted in 104 HCV infections (National Center for HIV/AIDS et al., 2020). In all 22 outbreaks, disinfection and environmental cleaning practices were not followed, and Standard Precautions were not properly used (National Center for HIV/AIDS et al., 2020).

Organ transplantation from HCV-infected donors has resulted in HCV infection in the recipients: An HCV transmission rate as high as 82% has been reported (Woolley et al., 2019). The use of DAAs, however, has significantly decreased this risk (Elbeshbeshy et al., 2024; Shetty et al., 2023), and there is an acceptable post-operative rate of survival (Elbeshbeshy et al., 2024; Kwon et al., 2023) and graft rejection (Elbeshbeshy et al., 2024).

Horizontal transmission of HCV can occur between family members and household contacts (Kushner et al., 2019; Sherief et al., 2019). This is caused by the sharing of personal care items that can be contaminated with infected blood, like glucose monitors, nail clippers, razors, and toothbrushes (CDC, 2023b; Kushner et al., 2019; Sherief et al., 2019) or providing direct care to someone who has an HCV infection (Sherief et al., 2019), or some other type of parenteral or percutaneous exposure to HCV-infected blood (CDC, 2023b).

Body piercing and tattooing can transmit HCV (CDC, 2023b; Tohme & Holmberg, 2012). If body piercing and tattooing are done by an experienced, professional practitioner, the risk of HCV transmission is likely nil (CDC, 2023b; Tohme & Holmberg, 2012), but the risk is high if body piercing and tattooing are done informally by an acquaintance or a friend (CDC, 2023b; Tohme & Holmberg, 2012).

Sexual Transmission

HCV RNA has been detected in cervical secretions and menstrual blood (Wang et al., 2011), saliva, and semen (Chromy et al., 2020; Lloyd & Franco, 2023). Transmission of HCV between monogamous heterosexuals by unprotected sexual contact, oral, rectal, or vaginal, appears to be very rare (Lloyd & Franco, 2023). If there is exposure to blood, transmission of HCV can occur from unprotected sexual contact (Lloyd & Franco, 2023). The prevalence of HCV in men who have sex with men (MSM) is three times that of the general population (Jin et al., 2021), and MSM who are infected with HIV are especially likely to develop HCV infection from sexual activity (Lloyd & Franco, 2023).

No information on HCV transmission in women who have sex with women was located.

Mother-To-Child Transmission

The rate of mother-to-fetus transmission of HCV has been estimated to be 5% (Martinello et al., 2023) to 6% (Chen et al., 2023) and twice that if a mother has poorly controlled HIV (Chen et al., 2023). Infection with HCV has been associated with an increased risk of cesarean delivery (Arditi et al., 2023; Chen et al., 2023), preterm birth (Arditi et al., 2023; Chen et al., 2023), fetal distress, poor fetal growth, and fetal death (Chen et al., 2023). Chen et al. (2023) did a cross-sectional study of U.S. data from 1998 to 2018, and the authors did not find that HCV infection increased the risk of gestational diabetes, eclampsia, preeclampsia, or stillbirth (Chen et al., 2023). A similar study by Arditi et al. (2023) found that HCV infection increased the risk of severe maternal morbidities (The CDC defines these as morbidities that happen during delivery hospitalizations like acute myocardial infarction, heart failure, and shock). Still, Chen et al. (2023) noted that this study may not have accounted for SUDs in the patients, and SUDs are a risk factor for poor pregnancy outcomes (Chen et al., 2023).

HCV RNA and HCV antibodies have been detected in breast milk (Blauvelt et al., 2024; Grasch et al., 2024), and there have been some reports of HCV transmission via breast milk (Blauvelt et al., 2024). However, HCV viral activity is limited by the free fatty acids in breast milk (Grasch et al., 2024). No significant association between breastfeeding and HCV infection has been found (Blauvelt et al., 2024), and breastfeeding has not been associated with a higher risk of mother-to-child HCV transmission (Grasch et al., 2024). The American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, the CDC, and the Society for Maternal-Fetal Medicine do not feel that HCV infection is a contraindication to breastfeeding (Grasch et al., 2024). If the mother has an HCV infection and her nipples are cracked and/or bleeding, she should not breastfeed until her nipples have healed (CDC, 2023a).

Possible Modes of Transmission

Infectious levels of HCV RNA have been detected in cerebrospinal fluid, saliva, sweat, tears, urine, and other body fluids (Pfaender et al., 2018). There are no documented cases of hepatitis C transmission after contact with these fluids; this may be because the fluids contain a relatively low viral load compared to blood (Naggie et al., 2017), but the possibility of transmission after contact with these fluids cannot be ruled out (Pfaender et al., 2018).

Infectious HCV can survive on environmental surfaces and used syringes (Doerrbecker et al., 2011; Paintsil et al., 2014; Paintsil et al., 2010).

HCV is not transmitted by coughing, casual physical contact like holding hands or hugging, sharing eating or drinking utensils, or food or water (CDC, 2023b). Hepatitis C is not transmitted by insect bites (CDC, 2023b).

Risk Factors for Developing Hepatitis C

Factors that increase the risk of developing hepatitis C are listed in Table 1.

Table 1: Risk Factors for Hepatitis C Infection
  • Alcohol abuse, past or present (Xu et al., 2021).
  • Children born to a mother infected with HCV (Chen et al., 2023; Martinello et al., 2023).
  • African American ethnicity (Hoff et al., 2023; Office of Minority Health [OMH], 2022).
  • Healthcare, emergency medical services, and public service personnel (Dienstag, 2022a; Friedman, 2024a).
  • HIV infection (Abu-Freha et al., 2022).
  • Injection drug use (CDC, 2022; Loy et al., 2024).
  • Intranasal illicit drug use (Mata-Martin et al., 2022).
  • Hemodialysis (Dharmesti et al., 2022; Kenfack-Momo et al., 2024; Nguyen et al., 2019).
  • Men who have sex with men (Jin et al., 2021; Lloyd & Franco, 2023).
  • People who are or have ever been incarcerated (Dienstag, 2022a).
  • People who have had a percutaneous or parenteral exposure to blood in an unregulated setting, e.g., unregulated tattooing (CDC, 2023b; Tohme & Holmberg, 2012).
  • Prior recipients of blood transfusion(s) or an organ transplant, including persons who were notified that they received blood from a donor who later tested positive for HCV, or received a transfusion of blood or blood components, or underwent an organ transplant before July 1992, or received clotting factor concentrates produced before 1987 (Dienstag, 2022a; Friedman, 2024a).
  • Sharing personal care items (CDC, 2023b; Kushner et al., 2019; Sherief et al., 2019).

Infection with HCV is much more common in people who abuse alcohol or are heavy drinkers (Xu et al., 2021). The prevalence of infection in people who abuse alcohol has been estimated to be 4.6% to 55.6% (Xu et al., 2021). Heavy alcohol use is an independent risk factor for the progression of HCV infection (Xu et al., 2021) and the development of liver cancer, cirrhosis, and fibrosis (Xu et al., 2021). Xu et al. (2021) wrote: "In summary, no safe level of alcohol intake has been established for patients with HCV. Even light-to-moderate alcohol use can exert a synergistic effect with viral hepatitis, leading to the rapid progression of liver disease."

Birthdates from 1945 to 1965 had been considered a risk factor for hepatitis C because three-fourths of chronic HCV cases occurred in people born during that time (Smith et al., 2012). However, in the U.S., most HCV infections are now caused by injection drug use and occur in young adults aged 20 to 39 (CDC, 2023c; USPSTF, 2020).

Marijuana use has not been associated with an increased risk of developing hepatitis C. Still, research has found an association between chronic/daily use of marijuana in patients infected with hepatitis C and increased severity of fibrosis and steatosis (abnormal accumulation of fat in the liver), the progression of the disease, and a higher level of hepatitis C RNA (Rashid et al., 2019; Terrault, 2018).

Smoking increases the risk of developing liver cancer in patients who have an HCV infection (Shadi et al., 2024).

Obesity is the most important risk factor for the development of non-alcoholic fatty liver disease (NAFLD), and NAFLD increases the rate of progression of fibrosis in patients who have viral hepatitis (Mukhtar & Fox, 2020).

Natural History of Hepatitis C Infections

An HCV infection begins with acute exposure, and acute exposure is followed by one of three outcomes.

  1. Acute infection and spontaneous viral clearance: Between 15% to 35% of people who have an acute HCV infection will have spontaneous clearance of the virus (Friedman, 2024a; Liu & Kao, 2023; Martinello et al., 2023). Children whose mothers had HCV infection have a spontaneous clearance rate of 25% to 40% by age three (Ades et al., 2023). Spontaneous clearance is more likely in female patients (Martinello et al., 2023; Negro, 2020; World Health Organization [WHO], 2023), young patients (Martinello et al., 2023; WHO, 2023), patients who have genotype 1 (WHO, 2023), and patients who have acute hepatitis with jaundice (Martinello et al., 2023; WHO, 2023). Spontaneous clearance does not confer immunity and HCV reinfection can happen (WHO, 2023).
  2. Fulminant hepatitis and liver failure can occur, but these are very rare (Liu & Kao, 2023; Martinello et al., 2023; Odenwald & Paul, 2022).
  3. Chronic infection: Most people who have asymptomatic HCV infection will not have spontaneous viral clearance, and they will develop a chronic infection (Kumar, 2022; Tada et al., 2019). Chronic HCV infection is a progressive disease, and patients can develop cirrhosis, fibrosis, and hepatocellular carcinoma or HCC (Butt et al., 2021; Dienstag, 2022b; Friedman, 2024a; Negro, 2020; Odenwald & Paul, 2022; Tada et al., 2019). These complications often occur decades after the initial infection (Kumar, 2022). Still, the natural history of chronic hepatitis C is not well characterized (Tada et al., 2019) and is very variable (Negro, 2020), particularly in terms of when these serious complications may occur. The incidence of these complications is not insignificant (Butt et al., 2021; Negro, 2020, Tada et al., 2019), and chronic HCV infection is a major cause of cirrhosis and HCC (Tada et al., 2019). In addition, chronic hepatitis C causes multiple different extrahepatic complications (Dienstag, 2022a).

Acute Hepatitis C Infection

The incubation period of HCV varies from two to 12 weeks (Liu & Kao, 2023) or six to seven weeks (Friedman, 2024a). Most patients are asymptomatic (Friedman, 2024a; Liu & Kao, 2023; Martinello et al., 2023; Odenwald & Paul, 2022). Symptomatic patients have abdominal pain, anorexia, diarrhea, fever, headache, jaundice, malaise, nausea, and vomiting (Kumar, 2022; Liu & Kao, 2023; Martinello et al., 2023; Negro, 2020). Hepatitis C RNA can usually be detected within one to two weeks (Liu & Kao, 2023). Anti-HCV antibody seroconversion is usually seen two to 12 weeks after the infection (Martinello et al., 2023). The anti-HCV antibodies may be from an acute infection, a chronic infection, or a spontaneously cleared infection (Kumar, 2022). Serum transaminase elevations begin about four weeks after exposure to the virus (Liu & Kao, 2023), the levels can be > 5 to 10 times the upper limit of normal (Martinello et al., 2023), and the serum transaminase and HCV RNA levels can fluctuate quite a bit (Liu & Kao, 2023).

Factors that favor spontaneous viral clearance include (but are not limited to) symptomatic infection (Feld, 2022), a significant viral decline after the plateau of HCV-RNA (Liu & Kao, 2023), chronic or resolved hepatitis B infection, female gender, no HIV infection, genotype 1, young age when the infection occurred, and white ethnicity (Feld, 2022; Liu & Kao, 2023).

Factors that increase the risk of developing chronic HCV are HIV infection, an immunocompromised condition (Martinello et al., 2023), and risky behavior, e.g., continued IV drug use.

Reinfection can occur after spontaneous viral clearance (Munaric et al., 2023), after successful treatment with DAAs (Tsai et al., 2023), or if the patient continues with risky behaviors like IV drug use (Tsai et al., 2023). Reinfection is defined as ". . . recurrent viremia after its clearance either spontaneously or as a result of treatment" (Munaric et al., 2023). Reinfection after viral clearance is associated with lower peak viremia and a higher likelihood of re-clearance (Feld, 2022).

The CDC's case definition of acute HCV infection is outlined below (CDC, 2021).

Demographics: The patient is > 36 months of age unless they had perinatal exposure.

Clinical criteria: One or more of the following clinical criteria are present.

Jaundice, or peak elevated total bilirubin level ≥ 3.0 milligrams (mg)/ deciliter (dL), or peak elevated serum alanine transaminases (ALT) level > 200 IU/L, and the patient does not have another more likely diagnosis like alcohol use, another type of viral hepatitis, or advanced liver disease caused by chronic HCV infection.

Laboratory criteria: A positive HCV detection test, e.g., a positive HCV RNA nucleic acid test that includes genotype testing, qualitative testing, and quantitative testing, or a positive test for HCV antigens.

Cases are classified as probable or confirmed.

Probable case: A probable case meets the clinical criteria, there is presumptive laboratory evidence, and an HCV detection test has not been reported, and there is no documentation within the previous 12 months that an HCV-RNA test or anti-HCV conversion test has been done.

Confirmed case: The clinical and laboratory criteria have been met, or the patient had a documented negative anti-HCV antibody test followed within 12 months by a positive anti-HCV antibody test, and there is not another likely diagnosis, or there is a documented negative anti-HCV antibody test or a negative hepatitis C virus detection test (in someone without a prior diagnosis of HCV infection) followed within 12 months by a positive hepatitis C virus detection test (HCV RNA test conversion) in the absence of a more likely diagnosis.

Chronic Hepatitis Infection

A hepatitis C infection that has not been spontaneously cleared by six months is considered chronic (Liu & Kao, 2023). Most people who have a chronic HCV infection are asymptomatic until cirrhosis or advanced fibrosis have developed (Odenwald & Paul, 2022), and chronic hepatitis C ". . . is clinically(italics added) indistinguishable from chronic hepatitis due to other causes" (Friedman, 2024b). Serum transaminases are normal in 40% of people who are chronically infected (Friedman, 2024b). If symptoms occur, they are non-specific, like abdominal pain and anorexia. Some symptoms are caused by extrahepatic complications or comorbidities (Chopra, 2024). Chronic hepatitis C can, for some patients, be debilitating, and patients may have cognitive dysfunctions and depression (Radkowski et al., 2023), fatigue, and sleep disturbances (Chopra, 2024). Fibrosis and cirrhosis typically develop slowly over several decades (Dienstag, 2022b; Erman et al., 2018; Erman et al., 2019; Thien et al., 2008), and the prevalence of cirrhosis after 20 years of infection has been reported to be 16% to 25% (Dienstag, 2022b; Erman et al., 2018; Thien et al., 2008).

The progression to cirrhosis is very variable (Negro, 2020). Factors that increase the risk of developing cirrhosis are listed in Table 2.

Table 2: Risk Factors for Cirrhosis
  • Age > 40 years when the infection occurred (Chopra, 2024; Friedman, 2024b).
  • Alcohol abuse (Friedman, 2024b).
  • Diabetes mellitus with insulin resistance (Chopra, 2024) and obesity (Chopra, 2024).
  • Duration of the infection; the longer the duration, the greater the risk (Dienstag, 2022b).
  • Hepatitis B infection (Odenwald & Paul, 2022).
  • HIV infection (Chopra, 2024; Negro, 2020).
  • High level of fibrosis and inflammation (Chopra, 2024).
  • Male gender (Friedman, 2024a).
  • Certain immunosuppression conditions (Chopra, 2024).
  • Preexisting liver disease (Friedman, 2024a).

Cirrhotic patients can remain clinically stable for many years with no serious signs and symptoms of liver damage (McDonald et al., 2017; Viveiros & Ryou, 2022); this is called compensated cirrhosis. Decompensated cirrhosis is an acute or non-acute deterioration of liver function (D'Amico et al., 2022) that is characterized by serious complications: ascites, esophageal varices, variceal bleeding, hepatic encephalopathy, hepato-renal syndrome, and jaundice (D'Amico et al., 2022; Fujiyama et al., 2021; Mansour & McPherson, 2018; McDonald et al., 2017; Viveiros & Ryou, 2022), and cirrhotic patients have a high risk of decompensation (Odenwald & Paul, 2022). For patients who have chronic hepatitis C, the risk of developing decompensated cirrhosis has been estimated to be 3.9% per year (Chopra, 2024) and 3% to 6% per year (McDonald et al., 2017), and it has been estimated that 30% of cirrhotic patients will develop decompensated cirrhosis within ten years (McDonald et al., 2017). Decompensated cirrhosis is associated with a very poor prognosis (D'Amico et al., 2022), particularly long-term prognosis, e.g., a 10-year and 20-year survival rate of 9.1% and 4.1%, respectively (Fujiyama et al., 2021).

Screening for Hepatitis C

The American Association for the Study of Liver Diseases (AASLD) and The Infectious Diseases Society of America (IDSA) recommend universal hepatitis C screening (Bhattacharya et al., 2023). Screening should be done with anti-HCV antibody testing and ". . . with reflex HCV RNA testing to establish the presence of active infection (as opposed to spontaneous or treatment-induced viral clearance)" (Bhattacharya et al., 2023). The United States Preventive Services Task Force (USPSTF) recommends one-time testing with an anti-HCV antibody test, followed by confirmatory polymerase chain reaction testing for asymptomatic adults aged 18 to 79 years, including pregnant persons without liver disease (USPSTF, 2020). The USPSTF also recommends that HCV screening should be considered for persons < 18 years of age and persons > 79 years of age who have a high risk of infection, e.g., current or past IV drug use (USPSTF, 2020).

(Note: Polymerase chain reaction test detects HCV RNA. Reflex HCV RNA testing is a test for the presence of HCV RNA that is done if the anti-HCV antibody test is positive.)

Screening is an important public health tool. Acute and chronic HCV infections often do not cause symptoms worldwide (Tsai et al., 2023); in the U.S. (Kasting et al., 2022; Veeramachaneni et al., 2021), many infected people do not know they are infected, and screening level is often sub-optimal (Tsai et al., 2023). Screening increases the number of cases, and the AASLD/IDSA Guidelines state, "Universal screening is a crucial and necessary component of any HCV elimination strategy because it is the entry point into the HCV continuum of care" (Bhattacharya et al., 2023).

Diagnosing Acute Hepatitis C

Hepatitis C is diagnosed by testing for HCV RNA and anti-HCV antibodies (Feld, 2022); serum transaminases should also be measured. Genotype testing can be done, and it is reasonable to do so but not necessary (Feld, 2022). (Note: Genotyping and its impact on DAA therapy regimens will be discussed in the treatment section. Patients who have signs and symptoms of HCV infection and/or have had high-risk exposure should be tested.

The laboratory testing procedure for acute hepatitis C diagnosis is outlined below (Feld, 2022).

  1. HCV RNA positive and anti-HCV antibody is positive – The patient has an acute or chronic infection. If the RNA or antibody tests were negative in the prior six months, the patient has an acute infection. If the RNA or antibody tests were not negative in the prior six months and the patient has had a recent high-risk exposure or a fluctuating HCV RNA test of > 1 log when the test is repeated, the patient likely has an acute infection. If that risk factor and that laboratory test result are not present, the patient likely has a chronic infection.
  2. HCV RNA positive and anti-HCV antibody is negative – The patient has an acute infection.
  3. HCV RNA negative and anti-HCV antibody is positive – The HCV RNA should be remeasured in 12 weeks. If the repeat HCV RNA is positive, the patient has an acute infection. If the repeat HCV RNA test is negative, the patient had an infection, but it was cleared.
  4. HCV RNA negative and anti-HCV antibody is negative – An infection is unlikely.

Hepatitis C RNA can be detected within several days (Dienstag, 2022a; Feld, 2022), one to two weeks (Liu & Kao, 2023; National Clinician Consultation Center, 2021), and up to eight weeks (Feld, 2022) after an exposure. Anti-HCV antibodies can usually be detected within eight to 11 weeks (National Clinician Consultation Center, 2021), and seroconversion occurs in most patients within two to six months after exposure (Feld, 2022). Hemodialysis patients, patients who have an HIV infection, patients who are going through organ transplantation, or who are severely immunocompromised may not produce a measurable level of anti-HCV antibodies (Feld, 2022) or seroconversion may take up to a year (Liu & Kao, 2023). The results of anti-HCV-antibody testing must be interpreted carefully. A positive anti-HCV antibody test indicates the presence of the antibodies, but it may reflect:

  1. An infection that was spontaneously cleared or
  2. An acute or early chronic infection.

A negative test can occur if a patient has been infected, but spontaneous clearance occurs, and the antibody level goes below the detectable limit (Feld, 2022).

Diagnosing Chronic Hepatitis C

This section and the next will discuss the process of diagnosing chronic HCV and the evaluation of patients who have chronic HCV. Patient selection to determine who should be tested for the presence of hepatitis C was discussed in the screening section.

The diagnostic process has two components:

  1. Anti-HCV antibody and HCV RNA testing, and
  2. Measuring serum transaminases and blood tests like INR that reflect liver function (Abu-Freha et al., 2022; Chopra & Arora, 2024b; Liu & Zucker, 2022).

The second component can be done at the clinician's discretion.

If the anti-HCV antibody test is negative, the patient does not have chronic HCV (Chopra & Arora, 2024b). However, HCV RNA testing should be done for hemodialysis patients, patients who have an HIV infection, patients who are severely immunocompromised, and transplant patients (Chopra & Arora, 2024b), even if the anti-HCV antibody test was negative, as these patients may have a false-negative antibody test (Chopra & Arora, 2024b).

If the anti-HCV antibody test and the HCV RNA test are positive, the patient likely has chronic HCV (Chopra & Arora, 2024b). Positive results on both tests could be caused by an acute infection (Chopra & Arora, 2024b), and this has important implications, e.g., waiting to see if spontaneous viral clearance occurs or beginning the process of DAA therapy. In this situation, clinicians must take a good medical history, particularly of patient risk factors and possible exposures, and the patient's recent state of health, and carefully review any previous laboratory test results.

If the anti-HCV test is positive and the HCV RNA is negative, the patient does not have chronic hepatitis C: They had an infection, and there was viral clearance (Chopra & Arora, 2024b). False negatives and false positives can occur (Chopra & Arora, 2024b), like transfusion with blood that has anti-HCV antibodies and an HCV RNA level that is below the detection limit of the test.

Chronic Hepatitis C: Initial Evaluation

If a patient has chronic HCV, they should be evaluated for the presence of:

  1. Cirrhosis and decompensated cirrhosis,
  2. Laboratory evidence of liver damage/liver dysfunction or cirrhosis,
  3. Fibrosis, and
  4. Comorbidities that are pertinent to treatment (Chopra & Arora, 2024a).

Note: Hepatic decompensation is defined as cirrhosis and deterioration of liver function, and it is characterized by ascites, esophageal varices, hepatic encephalopathy, hepato-renal syndrome, jaundice, and variceal bleeding (Mansour & McPherson, 2018). Cirrhosis and fibrosis are explained below.

  1. The presence of cirrhosis/decompensated cirrhosis is determined by a medical history and a physical examination. Medical history: Determine if the patient has lifestyle factors that may cause liver disease or accelerate the progression of chronic HCV (See Table 2), if the patient has signs and symptoms of hepatitis C infection and/or cirrhosis, and if they have previously been treated for HCV (Chopra & Arora, 2024a).
    1. Physical examination: Look for signs and symptoms of cirrhosis, including (but not limited to) anorexia, fatigue, firm liver when palpated, umbilical hernia, spider telangiectasias (blue, red, or purple, thin dilated blood vessels on the surface of the skin), splenomegaly, weakness, and weight loss (Chopra & Arora, 2024a; Friedman, 2024b). Remember: The signs and symptoms of cirrhosis are non-specific, and not all cirrhotic patients are symptomatic (Chopra & Arora, 2024a). The patient should also be examined for signs and symptoms of decompensated cirrhosis: Ascites, esophageal variceal bleeding, hepatic encephalopathy, hepato-renal syndrome, and jaundice (D'Amico et al., 2022; Fujiyama et al., 2021; Mansour & McPherson, 2018; McDonald et al., 2017; Viveiros & Ryou, 2022).
  2. Laboratory evidence of liver damage/dysfunction: Measure serum transaminases, serum albumin and bilirubin, INR, and prothrombin time (PT) (Chopra & Arora, 2024b). For laboratory evidence of cirrhosis, a CBC, including a platelet count, should be done because anemia and thrombocytopenia are common in cirrhosis, and the white blood cell count (WBC) can be abnormal, either high or low (Friedman, 2024b). The PT and the INR may be elevated (Chopra & Arora, 2024a; Friedman, 2024b), and measures of hepatic damage, alkaline phosphatase, serum bilirubin, and serum transaminases may be elevated (Friedman, 2024b).
  3. Fibrosis: Assess the patient for the presence and severity of fibrosis (Abu-Freha et al., 2022; Chopra & Arora, 2024b; Liu & Zucker, 2022). Fibrosis can progress to cirrhosis, and the level and severity of fibrosis can be used to determine prognosis (Chopra & Arora, 2024a) and help determine which therapy should be used (Bhattacharya et al., 2023; Chopra & Arora, 2024a).

Acute or chronic liver injury initiates inflammation and repair. The repair process causes the formation of non-functional scar tissue, called fibrosis (Lee, 2024a; Friedman, 2024b; Smith et al., 2012; Zuñiga-Aguilar & Ramírez-Fernández, 2022). Fibrosis is a dynamic and potentially reversible process (Smith et al., 2012; Zuñiga-Aguilar & Ramírez-Fernández, 2022). However, if the offending agent – in this case, HCV  –  remains and inflammation and repair continue, fibrosis can progress to cirrhosis, which is the last stage of inflammatory liver damage (Lee, 2024b; Zuñiga-Aguilar & Ramírez-Fernández, 2022). Cirrhosis is characterized by changes in hepatic architecture that cause abnormal hepatic functioning and the replacement of normal hepatocytes with dysfunctional liver tissue, and in some patients, cirrhosis progresses and may cause serious complications (D'Amico et al., 2022; Fujiyama et al., 2021; Mansour & McPherson, 2018; McDonald et al., 2017; Viveiros & Ryou, 2022).

The presence and severity of fibrosis can be determined by non-invasive or invasive testing (Bojanic et al., 2023). The non-invasive tests are physical or serologic; they can be used alone or together (Bojanic et al., 2023). (Phlebotomy is invasive but minimally so; for this discussion, it is categorized as non-invasive). The serologic tests are direct or indirect markers of fibrosis; they can be combined (Bojanic et al., 2023). See Tables 3-5 for lists of these tests (Bojanic et al., 2023; Bukhari et al., 2021).

The lists in Tables 3-5 are not and cannot be all-inclusive, and a discussion about these tests, i.e., comparison of benefits and limitations and which one should be used, when, and for whom is far beyond the scope of this module.

Elastography tests use an instrument that emits ultrasonic impulses (Bojanic et al., 2023). The liver tissue moves in response to the impulses; the movement is measured, and the results indicate the stiffness of the liver tissue and the degree of fibrosis (Bojanic et al., 2023).

Direct serologic tests measure levels of compounds like collagen that are part of hepatic fibrosis and liver scarring or compounds like collagenases that break down liver damage and remove scar tissue (Bojanic et al., 2023). Indirect serologic tests combine blood test measurements to calculate a score that indirectly measures the level of fibrosis. Example: The AST to platelet index ratio (APRI) test. HCV infection can cause AST elevation and thrombocytopenia. Using the APRI calculator, an AST of 550 units (U)/L and a platelet count of 125,000 x 103microliter(µL) would be an APRI score of 11, suggesting that the patient has severe fibrosis or cirrhosis (Lok, n.d.).

Table 3: Physical Tests of Liver Fibrosis
  • 2D shear wave elastography (2D-SWE)
  • Magnetic resonance elastography (MRE)
  • point shear wave elastography (p-SWE)
  • Transient elastography (TE)
Table 4: Direct Serologic Tests of Liver Fibrosis
  • Collagens, glycoproteins, and polysaccharides
  • Collagenases and collagenase inhibitors
  • Chemokines and cytokines
Table 5: Indirect Serologic Tests of Liver Fibrosis
  • Aspartate aminotransferase to alanine aminotransferase ratio (AAR)
  • AST to platelet ratio index (APRI)
  • Fibrosis 4 (FIB-4)
  • Forns score

A liver biopsy is an invasive, direct physical measurement of fibrosis. Liver biopsy provides direct evidence of fibrosis and severity of fibrosis, but serologic tests and non-invasive physical measures can, as well (Abu-Freha et al., 2022; Chopra, 2023; Fagala & Shpak, 2023), and in some ways, these tests are better than liver biopsy (Chopra, 2023; Fagala & Shpak, 2023). In addition, DAA therapy is so effective that precisely staging the level of fibrosis from HCV infection is no longer very important (Chopra & Arora, 2024b). Liver biopsy only samples a small area of liver tissue; it is expensive and invasive, and there can be levels of sampling errors (Chopra & Arora, 2024b). Liver biopsy can be used if the diagnosis of HCV infection cannot be determined by other methods (Chopra & Arora, 2024a) and to diagnose a concurrently occurring liver disease (Chopra & Arora, 2024a).

Fibrosis is often staged by the meta-analysis of histological data in viral hepatitis (METAVIR) system (Lee, 2024b); the histological activity determines the level of inflammation (Lee, 2024b). There are other scoring systems for fibrosis staging; METAVIR was designed and validated specifically for HCV (Fiel, 2024).

Table 6: METAVIR System Scoring
Histologic activityFibrosis
  • A0 = no activity
  • A1 = mild activity
  • A2 = moderate activity
  • A3 = severe activity
  • F0 = no fibrosis
  • F1 = portal fibrosis without septa
  • F2 = portal fibrosis with rare septa
  • F3 = numerous septa without cirrhosis
  • F4 = cirrhosis

Evaluation: Imaging

Ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) can be used to detect ascites, nodules, splenomegaly, and varices, assess the patency of hepatic blood vessels, and determine liver morphology and size (Friedman, 2024b; Liu & Zucker, 2022).

Evaluation: Genotype Testing

There are six major HCV genotypes and > 50 subtypes of the major HCV genotypes (Dienstag, 2022a). In the U.S., 70% of HCV infections are from genotype 1, and the rest are from genotypes 2 and 3 (Dienstag, 2022a). The common DAA regimens are effective treatments for all six genotypes (Chopra & Arora, 2024a). In most cases, genotyping is not needed as part of the pretreatment evaluation (Chopra & Arora, 2024a).

Extrahepatic Complications of Hepatitis C Infection

Extrahepatic complications are common in patients infected with HCV (Ružić et al., 2023), and essentially every organ system can be affected (Faccioli et al., 2021; Garg et al., 2024; Mazzaro et al., 2021; Songtanin & Nugent, 2022).

Neurocognitive and Psychiatric Disorders

Neurocognitive and psychiatric disorders are common in people who have HCV (Mazzaro et al., 2021; Ružić et al., 2023; Yeoh et al., 2018). Commonly occurring psychiatric disorders are depression and fatigue (Faccioli et al., 2021; Mazzaro et al., 2021; Yeoh et al., 2018). The causes of these complications are not completely understood (Ružić et al., 2023). There are four possibilities, and each one may influence another.

  1. A direct effect of the infection (Faccioli et al., 2021; Mazzaro et al., 2021; Ružić et al., 2023).
  2. Secondary comorbidities associated with HCV infection include diabetes mellitus and insulin resistance, metabolic syndrome, arthritis, and motor and sensory neuropathies (Faccioli et al., 2021).
  3. A natural response, i.e., depression, fatigue, to the physical and psychological stress of a chronic illness, the signs and symptoms of hepatitis C, and the associated comorbidities (Faccioli et al., 2021; Yeoh et al., 2018).
  4. Exacerbation of preexisting psychiatric disorders (Faccioli et al., 2021; Monaco et al., 2015; Yeoh et al., 2018).

Neurocognitive disorders affect 50% of patients who have HCV (Ružić et al., 2023). These include difficulty concentrating, deficits in executive and psychomotor function, attention deficit, reduced working memory, and difficulty with verbal learning (Ružić et al., 2023). Depression is five times more common in people who have hepatitis C than in the general population (Mazzaro et al., 2021), and Yeoh et al. (2018) noted that infected patients, even in the very early stages of the disease, have more depressive symptoms than uninfected people (Yeoh et al., 2018). HCV is much more common in people who have psychiatric disorders than in the general population (Faccioli et al., 2021). It could be that the physical and psychological stress of having a chronic disease explains, in part, the high level of depression in patients with HCV (Faccioli et al., 2021; Monaco et al., 2015; Yeoh et al., 2018).

Fatigue is the most common symptom of HCV (Faccioli et al., 2021; Mazzaro et al., 2021; Yeoh et al., 2018), affecting up to 80% of patients (Faccioli et al., 2021; Mazzaro et al., 2021, Yeoh et al., 2018). Patients feel mentally and physically fatigued and exhausted (Faccioli et al., 2021; Mazzaro et al., 2021), they feel that their quality of life is diminished (Faccioli et al., 2021; Yeoh et al., 2108), and many of these patients report having signs and symptoms like malaise, muscle pain, muscle weakness, and difficulty sleeping (Faccioli et al., 2021).

Diabetes Mellitus

Diabetes mellitus (DM) is a risk factor for HCV (Chaudhari et al., 2021; Songtanin & Nugent, 2022), and HCV is more common in people who have type 2 DM (T2DM) than in those who do not (Bradley et al., 2020; Chopra, 2023; Prasa et al., 2023; Songtanin & Nugent, 2022). Chronic HCV has been consistently associated with T2DM (Mazzaro et al., 2021; Songtanin & Nugent, 2022) and pre-diabetes (Mazzaro et al., 2021). HCV infection increases hepatic and peripheral insulin resistance (Chaudhari et al., 2021; Songtanin & Nugent, 2022) and causes down-regulation of glucose transporter 2 receptors (Chaudhari et al., 2021). Insulin resistance in these patients is associated with an increased risk of developing HCC (Chaudhari et al., 2021; Konishi et al., 2023; Songtanin & Nugent, 2022), increased progression of fibrosis, and resistance to DAA therapy (Songtanin & Nugent, 2022).

Mixed Cryoglobulinemia

Mixed cryoglobulinemia is one of the most common extrahepatic complications of HCV (Covic et al., 2023). Mixed cryoglobulinemia is an immune system-mediated process that causes the formation of cryoglobulins (Mazzaro et al., 2021), proteins that are a mix of immunoglobulins and complement or just immunoglobulin. The cryoglobulins are deposited in small and medium-sized blood vessels, causing vasculitis, endothelial damage, obstruction, and organ damage (Mazzaro et al., 2021). The pathophysiologic mechanism of hepatitis C-associated cryoglobulinemia is not completely understood: It may be caused by immune system stimulation (Songtanin & Nugent, 2022), or it could be an autoimmune disorder (Covic et al., 2023). Mixed cryoglobulinemia is a serious complication. It has been associated with significantly increased morbidity and mortality (Songtanin & Nugent, 2022), and cryoglobulinemic vasculitis caused by hepatitis C has a 5-year mortality rate of 25% (Songtanin & Nugent, 2022).

More than 90% of patients who have mixed essential cryoglobulinemia have HCV (Chopra, 2024d; Lee et al., 2017), > 50% of patients who have HCV have circulating cryoglobulins (Chopra, 2023), and 40-60% of patients with chronic HCV infection have mixed cryoglobulinemia.

Hepatitis C-associated mixed cryoglobulinemia causes dermatologic, neurologic, musculoskeletal, renal, and vascular complications (Chopra, 2024d; Mazzaro et al., 2021; Songtanin & Nugent, 2022).

The most common clinical sign is palpable purpura on the legs caused by vasculitis (Chopra, 2023; Mazzaro et al., 2021; Songtanin & Nugent, 2022). Palpable purpura causes pain, petechiae, ulceration, and, rarely, necrosis (Chopra, 2024d).

Nervous system vasculitis manifests in asymmetric painful neuropathy (Chopra, 2023; Mazzaro et al., 2021), typically in the legs (Chopra, 2023; Mazzaro et al., 2021). Central nervous system vasculitis can occur, causing cognitive impairment, epilepsy, and stroke, but this is rare (Mazzaro et al., 2021). Arthralgias affects 50% to 70 % of all patients (Mazzaro et al., 2021). Approximately 35% of patients who have hepatitis-associated mixed cryoglobulinemia develop glomerulonephritis (Songtanin & Nugent, 2022).

Cardiovascular

HCV has been associated with an increased risk of clinical and subclinical atherosclerosis, cardiovascular disease, and adverse cardiovascular events (Chopra, 2023; Mazzaro et al., 2021; Nevola et al., 2021; Ramadan et al., 2022) and an increased risk of death from cardiovascular events (Nevola et al., 2021). People who have HCV appear to have a higher risk than uninfected persons of developing coronary artery atherosclerosis (Ramadan et al., 2022), carotid artery atherosclerosis (Mazzaro et al., 2021), and suffering an ischemic stroke and a thromboembolic event (Mazzaro et al., 2021; Ramadan et al., 2022).

Cardiovascular disease and hepatitis disease are indirectly linked by metabolic complications of HCV infection: DM, increased insulin resistance, and metabolic syndrome, all of which are risk factors for cardiovascular disease, are common complications of HCV (Chaudari et al., 2021; Mazzaro et al., 2021; Songtanin & Nugent, 2022). In addition, research suggests that chronic low-grade inflammation caused by HCV is atherogenic (Mazzaro et al., 2021), HCV directly infects thrombi (Mazzaro et al., 2021; Songtanin & Nugent, 2022) and increases their size and instability (Mazzaro et al., 2021), and HCV causes endothelial dysfunction, further increasing the risk of atherosclerosis (Mazzaro et al., 2021).

Hepatocellular Cancer

HCV infection is the most common cause of cirrhosis (Tapper & Parikh, 2023), and cirrhosis, caused by any liver disease, including HCV, is the strongest risk factor for HCC (Singal et al., 2023). Approximately 34% of HCC cases in the U.S. are caused by HCV infection (Abdelhamed & El-Kassas, 2023), and people who have HCV are 15 to 20 times more likely to develop HCC than people who are not infected (Abdelhamed & El-Kassas, 2023). Risk factors for HCC are cirrhosis (Singal et al., 2023), fibrosis (Lazarus et al., 2023), insulin resistance caused by hepatitis C (Chaudhari et al., 2021; Konishi et al., 2023; Songtanin & Nugent, 2022), and severe liver disease, alcohol use, obesity, sedentary lifestyle, and smoking (Lazarus et al., 2023). In patients who have HCV and cirrhosis, 1% to 4% per year will develop HCC (Abdelhamed & El-Kassas, 2023). Therapy with DAAs and SVR decreases the risk of HCC (Abdelhamed & El-Kassas, 2023).

HCV has also been proven to cause B-cell non-Hodgkin lymphomas and has been associated with an increased risk of other cancers (Nyberg et al., 2020).

Hepatitis C and HIV Co-infection

  

Co-infection with HCV and HIV is common (Laiwatthanapaisan & Sirinawasatien, 2021; Radwan et al., 2019) because of the same transmission routes (Falade-Nwulia et al., 2024; Radwan et al., 2019) and similar risk factors for transmission.

Concurrent HCV and HIV infection are associated with bad clinical outcomes (Radwan et al., 2019). Hepatitis C and HIV co-infection:

  1. Increases the progression of fibrosis (Laiwatthanapaisan & Sirinawasatien, 2021) and the progression of liver disease to liver failure (Falade-Nwulia et al., 2024),
  2. Increases the risk of HCC (Falade-Nwulia et al., 2024; Laiwatthanapaisan & Sirinawasatien, 2021),
  3. Increases the risk of cirrhosis (Chapin-Bardales et al., 2024),
  4. Increases the risk of extrahepatic organ dysfunction (Jatt et al., 2021), and
  5. Increases all-cause mortality and liver-related mortality (Chapin-Bardales et al., 2024; Falade-Nwulia et al., 2024; Jatt et al., 2021).

Treatment: Acute Hepatitis C

Patients who have acute hepatitis C should be treated with DAA therapy unless there is a contraindication to doing so (Ghany et al., 2020; Dienstag, 2022b; Feld, 2022), and waiting for spontaneous recovery and viral clearance is not recommended (Ghany et al., 2020; Feld, 2022; Dienstag, 2022b). Primary reasons for this recommendation are:

  1. Patients who have acute hepatitis C and develop chronic hepatitis C – a not insubstantial risk ─ may be lost to follow-up,
  2. They may transmit HCV,
  3. There is always the potential that a severe HCV infection may occur (Feld, 2022), and
  4. Withholding treatment is a missed chance to prevent progression of fibrosis and the development of complications (Dienstag, 2022b).

Treatment should begin as soon as possible or when viremia is found (Feld, 2022). The recommended treatment regimen for a patient who has acute hepatitis C is the same one that is used to treat non-cirrhotic patients who have chronic hepatitis C and who are treatment-naive (Bhattacharya et al., 2023; Dienstag, 2022b; Feld, 2022). This treatment regimen is called the simplified algorithm for HCV treatment, more formally, the Simplified HCV Treatment for Treatment-Naive Adults Without Cirrhosis (Ghany et al., 2020; Bhattacharya et al., 2023). The regimen will be covered in the section Chronic Hepatitis C: Treatment. It can be viewed here.

Pre-treat evaluation and testing, monitoring during DAA therapy, and post-treatment evaluation for this patient population are the same as for patients who have chronic hepatitis C, and those topics will be discussed in the Chronic Hepatitis C section.

Ineligibilities for this treatment regimen are listed in Table 7 (Ghany et al., 2020).

Table 7: Ineligibility for the Simplified HCV Treatment for Treatment-Naive Patients Without Cirrhosis
  • Cirrhosis
  • Current pregnancy
  • HBsAg positive
  • Known or possible HCC
  • Liver transplantation
  • Prior treatment for HCV

Patients who are not treated should be evaluated at the six-month point to determine if they have chronic HCV (Feld, 2022). If spontaneous clearance occurs, it usually happens within 12 weeks; if a patient wants to forgo treatment and wait for 12 weeks, remeasure the HCV RNA level, and if needed, treatment can be done then (Feld, 2022).

Chronic Hepatitis C: Treatment

There are three types of DAAs: NS3/4A protease inhibitors, NS5B polymerase inhibitors, and NS5A protein inhibitors (Kiser, 2023). The DAAs eliminate HCV by inhibiting viral growth, viral replication, and viral maturation (Kiser, 2023). The NS3/4A protease inhibitors inhibit an enzyme that is involved in viral replication (Kiser, 2023). The NS5B drugs affect the function of an enzyme that HCV needs to synthesize RNA (Kiser, 2023).

The latest DAAs are very effective, safe, and well-tolerated (Bhattacharya et al., 2023), the duration of treatment is brief compared to the older interferon-based therapy, and viral clearance is > 95% (Dienstag, 2022b; Martinello et al., 2023). HCV has been called the only chronic viral infection that can be cured (Pol & Lagave, 2019).

There are multiple DAA treatment regimens: The regimens are prescribed based on genotype and the presence or absence of cirrhosis and hepatic decompensation (Ghany et al., 2020). These treatment regimens are designed for patients who have chronic HCV and who have not been previously treated with a DAA, interferon, peginterferon, and/or ribavirin (Ghany et al., 2020).

Most patients are eligible for one of the two simplified regimens: 1) Simplified Pangenotypic HCV Treatment for Treatment-Naïve Adults without Cirrhosis, and 2) Simplified Pangenotypic HCV Treatment for Treatment-Naïve Adults With Compensated Cirrhosis (Ghany et al., 2020).

The pretreatment recommendations, recommendations for patient monitoring during DAA therapy, and the recommendations for post-treatment assessment and follow-up are essentially the same for both variations of the Simplified Pangenotypic HCV Treatment for Treatment-Naïve Adults, without and with compensated cirrhosis.

In the treatment regimen for patients who have compensated cirrhosis, the eligibility and non-eligibility requirements and the pretreatment assessment recommendations are slightly different.

Simplified Pangenotypic HCV Treatment for Treatment-Naïve Adults without Cirrhosis

This treatment regimen can be used for patients who have any genotype (Ghany et al., 2020).

The ineligibilities for the Simplified Pangenotypic HCV Treatment for Treatment-Naïve Adults without Cirrhosis are listed in Table 8.

This regimen uses either of these DAAs (Ghany et al., 2020):

  • Glecaprevir/pibrentasvir.
  • Sofosbuvir/velpatasvir.

Pretreatment Assessment and Testing

The tests listed below should be done before starting DAA therapy. The HBV, HIV, and HCV tests can be done at any time before starting therapy; the others should be done within six months of starting DAA therapy (Ghany et al., 2020).

  • CBC
  • Hepatic function tests: Albumin, AST, ALT, direct and total bilirubin
  • Estimated glomerular filtration rate (eGFR)
  • Hepatitis B surface antigen
  • HIV antigen and antibody test
  • HCV RNA quantitative test
  • Women of childbearing age should have a pregnancy test and they should be informed of the risks of HCV medication.

Note: Dienstag (2022b) notes that the five oral DAAs that are used are pangenotypic, but the author recommends pretreatment genotyping (Dienstag, 2022b); the AASLD/IDSA does not. The Simplified Pangenotypic HCV Treatment for Treatment-Naïve Adults without Cirrhosis can be used for patients who have genotypes 1, 2, 3, 4, 5, or 6.

An assessment for the presence of cirrhosis should be done (Ghany et al., 2020). The patient has cirrhosis if the Fibrosis-4 Index (FIB-4) score is > 3.25 or if they have:

  1. A test that indicates the presence of cirrhosis, e.g., a Fibroscan score > 12.5 kilopascal (kPa), or
  2. Serologic testing above the cutoff points that indicate the presence of cirrhosis, or
  3. Clinical evidence of cirrhosis, or
  4. A previously done liver biopsy that showed cirrhosis (Ghany et al., 2020). A liver biopsy is not needed (Ghany et al., 2020).

A FIB-4 calculator can be accessed here.

A complete medication profile should be done, including over-the-counter medications, herbal medications, and supplements (Ghany et al., 2020).

The potential for drug-drug interactions between the patient's medications and the DAA drugs should be investigated (Ghany et al., 2020). The AASLD/IDSA recommends AASLD/IDSA guidance or the University of Liverpool drug interaction checker. It is particularly important to check for drug-drug interactions if the patient has an HIV infection (Ghany et al., 2020). Patients who have an HIV infection should not receive the simplified HCV treatment if they are taking tenofovir disoproxil fumarate (TDF) and have an eGFR < 60 mL/min (Ghany et al., 2020).

Glecaprevir/Pibrentasvir: Drug Profile

Glecaprevir/pibrentasvir is supplied as a tablet with 100 mg of glecaprevir and 40 mg of pibrentasvir. The trade name is Mavyret.®

Dose: Three tablets, taken at the same time once a day, taken with food for eight weeks. If the patient misses a dose and it has been < 18 hours from the usual time, take a dose as soon as possible and then take a dose at the usual time. If it has been > 18 hours from the usual time of administration, skip the missed dose and take a dose at the usual time (Muir & Graham, 2024).

Kidney impairment: No dosing adjustments are needed for patients with kidney impairment (Muir & Graham, 2024).

Hepatic impairment: No dosing adjustment is needed if the patient has a mild impairment (Child-Pugh [CP] class A). Glecaprevir/pibrentasvir is contraindicated if a patient has moderate or severe hepatic impairment (Child-Pugh class B or C) or has a history of hepatic decompensation (Muir & Graham, 2024).

The Child-Pugh, aka the Child-Turcotte-Pugh (CPT), is a scoring system that is used to predict mortality in people who have cirrhosis (Tsoris & Marlar, 2023). The Child-Pugh classification system measures albumin, bilirubin, and PT or INR. It assigns a point score to each test result, and the total score is categorized as class A, B, or C. The class can be used to determine the one-year survival rate in patients who have cirrhosis. A Child-Turcotte-Pugh Calculator can be viewed here.

Contraindications: The AASLD/IDSA contraindications for using the Simplified HCV Treatment for Treatment-Naive Patients Without Cirrhosis are listed in Table 9. Contraindications vis-a-vis hepatic issues were covered. The manufacturer's prescribing information states that concurrent use of glecaprevir/pibrentasvir and atazanavir or rifampin is contraindicated (Mavyret, 2023). (This contraindication was confirmed by using the University of Liverpool HEP Drug Interactions website.)

US Boxed Warning: HBV reactivation has been reported in HCV/HBV coinfected patients who were receiving or had completed treatment with DAAs and were not receiving HBV antiviral therapy; some cases have resulted in fulminant hepatitis, hepatic failure, and death (Muir & Graham, 2024). Test all patients for evidence of current or prior HBV infection before initiation of treatment; monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during treatment and post-treatment follow-up. Initiate treatment for HBV infection as clinically indicated (Muir & Graham, 2024).

Warnings:

  1. DM,
  2. hepatic decompensation, and
  3. hepatic failure.

In patients who have DM, a rapid decrease in HCV RNA from DAA therapy may improve glucose metabolism. It could cause symptomatic hypoglycemia if antidiabetic medications are continued and dose adjustments aren't made (Muir & Graham, 2024). Research has shown that DAA therapy may cause hypoglycemia (Zhou et al., 2022) and hyperglycemia (Hung et al., 2023). Diabetic patients who are taking DAAs should be informed of the risk of symptomatic hypoglycemia (Ghany et al., 2020), and glycemic monitoring should be done during the first three months of DAA therapy (Ghany et al., 2020; Hung et al., 2023; Muir & Graham, 2024).

Cases of hepatic decompensation and hepatic failure, including fatal cases, have been reported with the use of DAAs. These usually occur within the first four weeks after treatment has begun, and they usually happen to patients who have serious liver impairment (Muir & Graham, 2024). The LiverTox website states: "In large randomized controlled trials, serum aminotransferase levels decreased rapidly during Mavyret therapy and there were only rare instances of late, de novo elevations in ALT and AST that were usually mild-to-moderate in degree and rising to more than 5 times in less than 1% of treated subjects. In addition, Mavyret has been linked to only rare instances of hepatic decompensation during the treatment of patients with preexisting cirrhosis (<1%) . . . While 8 to 16 weeks of therapy with Mavyret can be associated with transient mild-to-moderate serum aminotransferase elevations, it has not been convincingly linked to cases of clinically apparent idiosyncratic liver injury. In addition, Mavyret should be permanently discontinued if jaundice or symptoms of liver injury arise, or if serum ALT or AST levels are persistently above 5 times" the upper limit of normal (National Library of Medicine, 2022).

Adverse reactions: > 10%, nausea; 1% to 10%, diarrhea, pruritus, and bilirubin increase of ≥ 2x the upper limit of normal (Muir & Graham, 2024).

Drug-drug interactions: The Lexicomp® database lists 174 drug-drug interactions for glecaprevir/pibrentasvir, and 43 are category X, i.e., glecaprevir/pibrentasvir and the drug in question should never be used concurrently (Muir & Graham, 2024). Before starting DAA therapy and whenever a new (for the patient) drug is prescribed, checking for a drug-drug interaction must be done.

Pregnancy and breastfeeding: The information on DAAs and pregnancy is scant (Ghany et al., 2020; Muir & Graham, 2024). The AASLD recommends that DAA therapy during pregnancy or continuing DAA therapy when a patient becomes pregnant be considered on a case-by-case basis and after consideration of the benefits and risks (Ghany et al., 2020).

Glecaprevir and pibrentasvir have not been studied in nursing mothers (National Library of Medicine, 2023a; National Library of Medicine, 2023b). Both drugs have a very high level of protein binding, 97.5% and > 99%, respectively, so any amounts in breast milk would likely be very low (National Library of Medicine, 2023a; National Library of Medicine, 2023b). Nursing mothers should not breastfeed if their nipples are bleeding or cracked (CDC, 2023a; National Library of Medicine, 2023a; National Library of Medicine, 2023b).

Infants whose mothers have HCV should be tested for the presence of HCV RNA (National Library of Medicine, 2023a; National Library of Medicine, 2023b).

Sofosbuvir/Velpatasvir Drug Profile

Sofosbuvir/velpatasvir is supplied as an oral tablet that contains 400 mg sofosbuvir and 100 mg velpatasvir. The trade name is Epclusa®.

Dose: One tablet once a day for 12 weeks, with or without food (Muir & Graham, 2024).

Kidney impairment: No dosing adjustments are needed (Muir & Graham, 2024).

Hepatic impairment: Child-Pugh class A, B, or C, mild, moderate, or severe; no dosing adjustment is needed (UpToDate, 2024). Serum transaminases should be monitored.

ALT increases < 10-fold, and the patient is asymptomatic; remeasure ALT every two weeks, and if the ALT continues to be elevated, consider discontinuing use (Muir & Graham, 2024).

ALT increases < 10-fold, and the patient:

  1. has jaundice, nausea, vomiting, weakness, or
  2. alkaline phosphatase, bilirubin, or INR are significantly increased, discontinue use (Muir & Graham, 2024).

If at any time the ALT is ≥ 10-fold increased, discontinue use (Muir & Graham, 2024).

Contraindications: The AASLD/IDSA contraindications for using the Simplified HCV Treatment for Treatment-Naive Patients Without Cirrhosis are listed in Table 9. Contraindications vis-a-vis hepatic issues were covered. Concurrent use of Epclusa® and ribavirin is contraindicated (Muir & Graham, 2024).

U.S. Boxed Warning: HBV reactivation has been reported in HCV/HBV coinfected patients who were receiving or had completed treatment with HCV direct-acting antivirals and were not receiving HBV antiviral therapy; some cases have resulted in fulminant hepatitis, hepatic failure, and death. Test all patients for evidence of current or prior HBV infection before initiation of treatment; monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during treatment and post-treatment follow-up. Initiate treatment for HBV infection as clinically indicated (Muir & Graham, 2024).

Warnings: Diabetes, concurrent use of amiodarone.

In patients who have DM, a rapid decrease in HCV RNA from DAA therapy may improve glucose metabolism. It could cause symptomatic hypoglycemia if antidiabetic medications are continued and dose adjustments aren't made (Muir & Graham, 2024). Research has shown that DAA therapy in diabetic HCV patients may cause hypoglycemia (Zhou et al., 2022) and hyperglycemia (Hung et al., 2023). Diabetic patients who are taking DAAs should be informed of the risk of symptomatic hypoglycemia (Ghany et al., 2020), and glycemic monitoring should be done during the first three months of DAA therapy (Ghany et al., 2020; Hung et al., 2023; Muir & Graham, 2024).

Concurrent use of amiodarone and sofosbuvir is not recommended (Muir & Graham, 2024). Nine post-marketing reports and three case reports have described symptomatic bradycardia when these drugs are used together (Monoe et al., 2020; Muir & Graham, 2024). The onset is hours to days, but it has occurred after several weeks, as well (Muir & Graham, 2024), and severe bradycardia (Monoe et al., 2020; Muir & Graham, 2024), and a fatality has been reported. In seven of the nine post-marketing reports, the patient was also taking a beta-blocker (Muir & Graham, 2024).

Adverse reactions: > 10%, headache, fatigue; 1% to 10%, asthenia, depressed mood, insomnia, nausea, serum creatine kinase ≥ 10x upper limit of normal, skin rash, serum lipase ≥ 3x upper limit of normal (Muir & Graham, 2024).

Drug-drug interactions: The Lexicomp® database lists 115 drug-drug interactions for sofosbuvir/velpatasvir, and 30 are category X, i.e., sofosbuvir/velpatasvir and the drug in question should never be used concurrently (Muir & Graham, 2024). Before starting DAA therapy and whenever a new (for the patient) drug is prescribed, checking for a drug-drug interaction must be done.

Pregnancy and breastfeeding: The information on DAAs and pregnancy is scant (Ghany et al., 2020), and there is very little information on sofosbuvir/velpatasvir and pregnancy (Muir & Graham, 2024). The AASLD recommends that DAA therapy during pregnancy or continuing DAA therapy when a patient becomes pregnant be considered on a case-by-case basis and after consideration of the benefits and risks (Ghany et al., 2020).

Sofosbuvir and velpatasvir have not been studied in nursing mothers (National Library of Medicine, 2023c; National Library of Medicine, 2023d). Both drugs have a very high level of protein binding, so any amounts of the drugs in breast milk would likely be very low (National Library of Medicine, 2023c; National Library of Medicine, 2023d). Nursing mothers should not breastfeed if their nipples are bleeding or cracked (CDC, 2023a; National Library of Medicine, 2023c; National Library of Medicine, 2023d).

Infants whose mothers have hepatitis C should be tested for the presence of HCV RNA (National Library of Medicine, 2023c; National Library of Medicine, 2023d).

In-Treatment Monitoring

Diabetic patients should be informed that they could develop symptomatic hypoglycemia, and hypoglycemic monitoring is recommended (Ghany et al., 2020).

Inform patients taking warfarin that their anticoagulation status could change, and monitoring the INR is recommended (Ghany et al., 2020).

No other laboratory monitoring is required (Ghany et al., 2020).

Post-Treatment Evaluation

Measure HCV RNA and hepatic function 12 weeks after DAA therapy has ended. If the HCV RNA is negative but serum transaminases are elevated, investigate for another cause of liver injury (Ghany et al., 2020). If the patient has an SVR 12 weeks after the end of treatment, 97% to 100% of these patients are considered cured (Chopra & Pockros, 2024), and no follow-up is needed. Counsel patients about risky behavior vis-à-vis HCV transmission (Ghany et al., 2020).

If an SVR is not achieved, the patient should be referred to a specialist, a CBC, a hepatic function panel, an INR should be measured every six to 12 months, and the patient should be advised not to drink alcohol (Ghany et al., 2020).

Simplified HCV Treatment Algorithm for Treatment-Naive Adults With Compensated Cirrhosis

This treatment regimen is for adults who have chronic hepatitis C of any genotype and who are treatment-naïve (Ghany et al., 2020). Eligibility requirements and ineligibility conditions are listed in Tables 8 and 9, respectively (Ghany et al., 2020).

For genotypes 1 through 6, this regimen uses glecaprevir/pibrentasvir.

For genotypes 1, 2, 4, 5, or 6, sofosbuvir/velpatasvir can be used. Patients who have genotype 3 need baseline NS5A resistance-associated substitution (RAS) testing. If the Y93H is negative, sofosbuvir/velpatasvir can be used. If Y93H is present, another approach will be needed (Ghany et al., 2020), and more information is available here.

Note: Y93H is an HCV mutation, an RAS that causes resistance to velpatasvir (Green and Roytman, 2022).

Glecaprevir/pibrentasvir and sofosbuvir/velpatasvir were discussed in the previous section, and the doses are the same for patients with decompensated cirrhosis or without (Ghany et al., 2020).

Table 8: Eligibility for Simplified HCV Treatment Algorithm for Treatment-Naive Adults With Decompensated Cirrhosis
  • Chronic hepatitis C and compensated cirrhosis, Child-Pugh class A
  • Cirrhosis on liver biopsy: A pretreatment liver biopsy is not required
  • Cirrhosis as documented by a FIB-4 score > 4, or any of the following: TE test that showed cirrhosis, e.g., FibroScan score of > 12.5 kPa, non-invasive serologic test results that are above the cutoff point for cirrhosis, or clinical evidence of cirrhosis
(Ghany et al., 2020)
Table 9: Ineligibility for the Simplified HCV Treatment for Treatment-Naive Patients With Decompensated Cirrhosis
  • Current pregnancy
  • Current or prior episode of decompensated cirrhosis – Child-Turcotte-Pugh score ≥ 7, Class B or C (Ascites, hepatic encephalopathy, total bilirubin > 2.0 mg/dL, albumin ≤ 3.5 g/dL, ≥ or INR 1.7)
  • End-stage renal disease, eGFR <30 mL/min/m2
  • HBsAg positive
  • Known or possible HCC
  • Liver transplantation
  • Prior treatment for HCV
(Ghany et al., 2020)

Pretreatment Assessment and Testing

Within six months of starting DAA therapy, these tests should be done: The HBV, HIV, and HCV tests can be done any time before starting therapy (Ghany et al., 2020).

  • CBC
  • Hepatic function tests: Albumin, AST, ALT, direct and total bilirubin
  • eGFR
  • Hepatitis B surface antigen
  • HIV antigen and antibody test
  • HCV RNA quantitative test
  • Ultrasound of the liver: This is for detecting HCC and subclinical ascites
  • Women of childbearing age should have a pregnancy test and they should be informed of the risks of HCV medication.

Note: Dienstag (2022b) notes that the five oral DAAs that are used are pangenotypic, but he recommends pretreatment genotyping (Dienstag, 2022b): The AASLD/IDSA does not. The Simplified Pangenotypic HCV Treatment for Treatment-Naïve Adults without Cirrhosis can be used for patients who have genotypes 1, 2, 3, 4, 5, or 6.

The CTP score should be calculated. A CTP calculator can be viewed here.

An assessment for the presence of cirrhosis should be done (Ghany et al., 2020). If the patient has a FIB-4 score > 3.25 or if they have:

  1. A TE test that indicates the presence of cirrhosis, e.g., a Fibroscan score > 12.5 kPa, or
  2. Serologic testing above the cutoff points that indicate the presence of cirrhosis, or
  3. Clinical evidence of cirrhosis, or
  4. A previously done liver biopsy that showed cirrhosis. A liver biopsy is not needed (Ghany et al., 2020).

A complete medication profile should be done, including over-the-counter medications, herbal medications, and supplements (Ghany et al., 2020).

The potential for drug-drug interactions between the patient's medications and the DAA drugs should be investigated (Ghany et al., 2020). The AASLD/IDSA recommends AASLD/IDSA guidance or the University of Liverpool drug interaction checker. It is particularly important to check for drug-drug interactions if the patient has an HIV infection (Ghany et al., 2020). Patients who have an HIV infection should not receive the simplified HCV treatment if they are taking (TDF) and have an eGFR < 60 mL/min (Ghany et al., 2020).

In-Treatment Monitoring

Some providers will monitor for the development of hepatic decompensation as this can (rarely occur in patients who have cirrhosis and are receiving DAA therapy. If there is clinical evidence of liver damage, the patient should be referred to a specialist (Ghany et al., 2020).

Diabetic patients should be informed that they could develop symptomatic hypoglycemia, and hypoglycemic monitoring is recommended (Ghany et al., 2020).

Inform patients who are taking warfarin that their anticoagulation status could change, and monitoring the INR is recommended (Ghany et al., 2020).

Adherence to the Treatment Regimen

Poor adherence to DAA therapy, i.e., not completing the full course or skipping doses, could decrease the SVR and/or cause treatment failure (Doica et al., 2023). At this time, there is no known level of adherence to DAA therapy that is essential for obtaining a cure (Turcu-Stiolaca et al., 2021).

Post-treatment Evaluation

Measure HCV RNA and hepatic function tests 12 weeks after DAA therapy has ended. If the HCV RNA is negative but serum transaminases are elevated, investigate for another cause of liver injury (Ghany et al., 2020). If the patient has an SVR 12 weeks after treatment, 97% to 100% of patients with a 12-week SVR are considered cured (Chopra & Pockros, 2024).

An ultrasound, with or without alpha-fetoprotein testing, should be done every six months to check for the presence of HCC, and an upper endoscopy to check for the presence of esophageal varices should be done (Ghany et al., 2020).

Counsel patients about risky behavior vis-à-vis HCV transmission (Ghany et al., 2020), and at-risk patients should have HCV RNA measured every year. Patients should not drink alcohol (Ghany et al., 2020).

If an SVR was not achieved, the patient should be referred to a specialist. An ultrasound, with or without alpha-fetoprotein testing, should be done every six months to check for the presence of HCC, a CBC, a hepatic function panel, and an INR should be measured every six to 12 months, and the patient should be advised not to drink alcohol (Ghany et al., 2020).

Hepatitis C and Hepatitis B Co-infection Treatment

The AASLD/IDSA simplified treatment guidelines state that if the patient is positive for hepatitis B surface antigen (HBsAg), acute or chronically infected, direct-acting antivirals are contraindicated (Ghany et al., 2020). Chopra & Pockros (2024) recommend that if the HBsAg is positive and the patient meets the treatment criteria, HBV antiviral therapy should be started (Chopra & Pockros, 2024).

Hepatitis C and HIV Co-infection Treatment

For patients who have HCV and HIV infection, the DAAs are safe and effective (Ghany et al., 2020; Rockstroh, 2024), and the SVR that is attained is comparable to that of patients who have HCV infection alone (Ghany et al., 2020; Rockstroh, 2024).

A simplified treatment program for HCV/HIV co-infection has been successfully used and is recommended (Rockstroh, 2024): glecaprevir/pibrentasvir for eight weeks or sofosbuvir/velpatasvir for 12 weeks. If the patient has genotype C and has cirrhosis, administer glecaprevir/pibrentasvir for eight weeks (Rockstroh, 2024). If the patient has decompensated cirrhosis, a specialist should be consulted (Rockstroh, 2024). If a patient is not receiving anti-retroviral therapy (ART), wait four to six weeks before beginning ART (Rockstroh, 2024).It is very important to check for drug-drug interactions before starting DAA therapy in patients who have an HIV infection (Ghany et al., 2020).

Hepatitis C and Pregnancy

There is very little information on the use of DAAs during pregnancy (Ghany et al., 2020). Women of childbearing age who have hepatitis C and who are not pregnant should be informed of the benefits of DAA therapy, and if they become infected during pregnancy, the risks and benefits of DAA therapy should be considered on a case-by-case basis (Ghany et al., 2020).

Pregnant women should be tested for hepatitis C (Ghany et al., 2020). If the patient has a positive HCV antibody test, HCV RNA and routine liver function tests should be done (Ghany et al., 2020).

Pregnancy does not seem to influence the course of HCV infection (Ghany et al., 2020). Serum transaminases do rise, peak in the third trimester, and return to normal after birth. Some patients develop intrahepatic cholestasis of pregnancy, aka ICP (Ghany et al., 2020), a condition that has been associated with adverse fetal and maternal outcomes (Ghany et al., 2020; Hobson et al., 2022). If the patient has jaundice or pruritus, ". . . there should be a high index of suspicion for intrahepatic cholestasis of pregnancy . . .  ; all patients with this syndrome should be immediately referred to a high-risk obstetrical specialist for monitoring and treatment" (Ghany et al., 2020).

During perinatal care and delivery, diagnostic testing should be done by amniocentesis, not chorionic villus sampling, and episiotomies, internal fetal monitoring, and prolonged membrane rupture should be avoided (Ghany et al., 2020).

Hepatitis C and Decompensated Cirrhosis: Treatment

The use of DAAs and specific DAAs to treat patients who have chronic hepatitis C and decompensated cirrhosis, Child-Pugh class B or C, is controversial. In 2019, the U.S. Food & Drug Administration (FDA) issued a warning stating that rare cases of serious liver injury had occurred in patients who had advanced liver disease and had been treated with Mayvret® (glecaprevir and pibrentasvir), Vosevi® (sofosbuvir, velpatasvir, and voxilaprevir), and Zepatier® (elbasvir and grazoprevir)(FDA, 2019). The prescribing information for these drugs states that hepatic decompensation/failure had been reported in patients who had Child-Pugh class B or C who had been treated with HCV NS3/4A protease inhibitors, e.g., glecaprevir, grazoprevir, voxilaprevir. The AASLD/IDSA recommends referring these patients to a specialist, ideally in a liver transplant center (Ghany et al., 2020). According to the AASLD/IDSA, most patients who have decompensated cirrhosis and who receive DAA therapy do have clinical and laboratory evidence of improvement, the rate of SVR is less than in patients without decompensated cirrhosis, and DAA therapy may or may not improve the risk of complications and long-term survival (Ghany et al., 2020). Information on the topic, including recommended DAA regimens, can be viewed on the AASLD/IDSA HCV website here.

Hepatitis C and Hepatocellular Cancer: Treatment

DAAs have been shown to prevent HCC in patients who have hepatitis C (Ito & Nguyen, 2023), including patients who have decompensated cirrhosis (Ito & Nguyen, 2023). They are also safe and effective for patients who have HCC (Ito & Nguyen, 2023), and DAA does not increase the risk of HCC incidence or recurrence (Chopra & Arora, 2024b; Ito & Nyguen, 2023). Treatment of HCC caused by HCV should be completed before DAA therapy is begun (Chopra, 2023; Ito & Ngyuen, 2023). The DAA therapy regimens for patients who have HCV and HCC are no different than those for the general population (Chopra & Arora, 2024a).

Treatment Failure: Retreatment

Patients who did not have a 12-week SVR can be re-treated, and there are several options (Bhattacharya et al., 2023; Graf et al., 2024).

Vosevi® is a combination of voxilaprevir, velpatasvir, and sofosbuvir that has labeled uses for treating:

  1. Patients who have genotype 1, 2, 3, 4, 5, or 6 and who were treated with a regimen that included an NS5A inhibitor, and
  2. Patients who have genotype 1a or 3 and have been treated with a regimen that included sofosbuvir but not an NS5A inhibitor (Vosevi, 2019).

Other recommended DAA regimens are listed below (Bhattacharya et al., 2023).

  1. Sofosbuvir-based treatment failure without cirrhosis or with compensated cirrhosis.
    1. Genotypes 1 to 6: Sofosbuvir/velpatasvir/voxilaprevir, 12 weeks. For genotype 3 infection with compensated cirrhosis, add weight-based ribavirin if there are no contraindications.
    2. Genotypes 1, 2, 4, 5: Glecaprevir/pibrentasvir, 16 weeks. This regimen is not recommended for patients with prior exposure to an NS5A inhibitor plus NS3/4A protease inhibitor regimen, e.g., elbasvir and grazoprevir.
      1. Note: Ribavirin is a nucleoside anti-HCV drug; it was used with interferon in the first several iterations of HCV treatment.
  2. Glecaprevir/pibrentasvir treatment failure without cirrhosis or with compensated cirrhosis.
    1. Genotypes 1-6: Glecaprevir/pibrentasvir +sofosbuvir + weight-based ribavirin, 16 weeks.
    2. Genotypes 1-6: Sofosbuvir/velpatasvir/voxilaprevir, 12 weeks.  For patients with compensated cirrhosis, adding weight-based ribavirin is recommended.
  3. Sofosbuvir/velpatasvir/voxilaprevir or sofosbuvir + glecaprevir/pibrentasvir treatment failure without cirrhosis or with compensated cirrhosis.
    1. Genotypes 1-6: Glecaprevir/pibrentasvir + sofosbuvir + weight-based ribavirin, 16 weeks. Twenty-four weeks of treatment should be considered for extremely difficult cases like genotype 3 infection with compensated cirrhosis or failure of the sofosbuvir + glecaprevir/pibrentasvir therapy.
    2. Genotypes 1-6: Sofosbuvir/velpatasvir/voxilaprevir + weight-based ribavirin, 24 weeks.
  4. Sofosbuvir- or NS5A inhibitor-based treatment failure with decompensated cirrhosis.
    1. Genotypes 1-6: Sofosbuvir/velpatasvir + weight-based ribavirin, 24 weeks. A low starting dose initial dose of ribavirin ─ 600 mg ─ is recommended for patients with CTP class C cirrhosis. The dose can be increased as tolerated.
    2. Genotypes 1, 4, 5, 6: Ledipasvir/sofosbuvir + weight-based ribavirin, 24 weeks. A low starting initial dose of ribavirin ─ 600 mg ─ is recommended for patients with CTP class C cirrhosis. The dose can be increased as tolerated.

Patient Education

Transmission of the virus: Patients should be instructed not to share personal care items like toothbrushes and razors that may be contaminated with blood.

Sexual transmission of HCV between monogamous heterosexual partners who are not IV drug users appears very uncommon, and barrier protection is not recommended. Patients should be counseled on safe sex practices, and they should be given information on how hepatitis C is transmitted and instructed on how to avoid transmission of the virus.

People who have multiple sexual partners and MSM should be encouraged to use condoms.

Injection drug users should be advised not to share needles or injection drug equipment.

HCV is not transmitted by casual physical contact, coughing, food or water, sneezing, or sharing eating utensils.

Alcohol: No amount of alcohol has been established as safe for patients who have hepatitis C. Excess alcohol consumption can cause cirrhosis, and it has been strongly associated with the development and progression of fibrosis and hepatocellular cancer. Patients should be advised to abstain from drinking alcohol, and patients who have an alcohol use disorder should be referred for treatment.

Drug-drug interactions: Patients should be told that drug-drug interactions can negatively influence the effectiveness of DAAs, and potentially significant interactions can occur between over-the-counter medications and dietary/herbal supplements and DAAs. Do not take a new medication or supplement without informing the provider or another healthcare professional.

Patients who take antidiabetic medications or warfarin should be instructed that the antiviral medications can cause hypoglycemia or hyperglycemia and can reduce the anticoagulant effects of warfarin.

Employment: People who have hepatitis C should not be restricted from employment. Infected healthcare workers need only to follow infection control procedures and use Standard Precautions.

Marijuana: Patients should be advised to abstain from using marijuana.

Medications: Patients should not take an over-the-counter medication, dietary supplement, or herbal product unless their provider or healthcare professional determines that doing so is safe.

Obesity: Patients who are obese should be advised to lose weight.

Reinfection: An SVR does not provide immunity against reinfection with hepatitis C, either from the same genotype or the other genotypes. Patients should be instructed to contact their provider or another healthcare professional if they may have been reinfected.

Smoking: Smoking cessation should be encouraged.

Substance use: Patients who are IV drug users have a significant risk of infection and reinfection. These patients should be referred to a SUD treatment program and have routine follow-up laboratory testing (Ghany et al., 2020).

Treatment adherence: Patients should be advised that non-compliance with the treatment regimen could cause treatment failure.

Treatment - Adverse effects: The adverse effects of the direct-acting antivirals are mild and usually well tolerated. Patients should be instructed to contact their provider or another healthcare professional if they have any signs or symptoms that are new, unusual, severe, intolerable, or that interfere with activities of daily living. They should contact their healthcare provider or another healthcare professional if they develop any signs or symptoms indicative of liver damage.

Exposure to Hepatitis C

The genetic diversity and rapid rate of mutation have prevented the development of an HCV vaccine (Dienstag, 2022a), and there is no effective prophylactic treatment for acute exposures like a needle stick (Feld, 2022; National Clinician Consultation Center, 2021). The CDC's recommendations for acute, discrete, and possible exposures to HCV, like a needle stick, are listed below (Moorman et al., 2020).

  1. The source's HCV status should be determined by an HCV RNA test (preferable) or an anti-HCV antibody test, and if that is positive, with a confirmatory HCV RNA test.
  2. The exposed person's HCV status should be determined with an HCV RNA test. This should be done as soon as possible, preferably within 48 hours.
  3. If the source was HCV RNA positive or anti-HCV was positive, but HCV RNA was not obtained, or if the source's HCV status can't be determined, the exposed person should have an HCV RNA test done at three to six weeks post-exposure.
  4. If the HCV RNA is positive, the exposed person should be referred to care.
  5. If the HCV RNA test is negative, the exposed person should have an anti-HCV antibody test done at four to six months post-exposure.

Nursing Care

Nursing care for patients who have HCV has been greatly simplified by the use of up-to-date DAAs. The course of therapy has been reduced from 44 weeks to 12 weeks, the risk of serious drug-induced complications has been dramatically reduced, and unlike interferon-based regimens, the side effects of these drugs are mild and well-tolerated.

These changes mean that the focus of nursing care for patients who have HCV has, to a large degree, shifted from physical care to education and support: education about lifestyle issues relevant to HCV and support that helps and encourages patients to make the changes that are necessary for continued good health.

Nursing care for a patient who has HCV will involve:

  • Knowledge of the extrahepatic complications of HCV.
  • Knowledge of the signs, symptoms, and complications of cirrhosis.
  • Knowledge of the medications and their potential side effects.
  • Patient education, specifically about extrahepatic complications of HCV and the safe and effective use of antiviral drugs.
  • Patient education, specifically about the risks of alcohol use/abuse, diabetes, obesity, and smoking, about HCV.
  • Support and education, specifically about the beneficial effects of alcohol abstinence, exercise, smoking cessation, and weight loss about HCV.
  • Assess the patient's level of knowledge regarding HCV transmission and behaviors that can put them at risk for reinfection.

Conclusion

HCV is a chronic liver infection that can cause liver damage, cirrhosis, and liver cancer, and HCV can also cause serious extrahepatic complications in essentially every organ system. HCV is one of the most common bloodborne diseases in the United States. HCV is an important cause of liver cancer; it may be a contributing cause of many common chronic diseases.

The HCV was first isolated and identified in 1989. For many years, the available treatments were lengthy, i.e., almost one year of drug therapy, not highly effective, and they caused very unpleasant and occasionally very serious adverse effects. DAAs have decreased the incidence of chronic HCV infections and offered a cure rate of 95% to 100%, the treatment regimens are much shorter, and the drugs are well tolerated.

However, HCV is still a major public health problem, and the continued use of illicit drugs and the opioid epidemic have contributed to the persistence of a disease that can be cured. Another issue that contributes to the failure to eliminate HCV is the nature of the disease. Chronic HCV seldom causes signs and symptoms, and the disease progresses silently for decades, so many infected people do not know they have HCV. Also, the progression of liver fibrosis and liver damage caused by HCV is negatively affected by comorbidities and common lifestyle issues like alcohol abuse, obesity, and smoking.

Fortunately, the treatment of HCV has been greatly simplified. The currently available direct-acting antivirals are highly effective. The treatment regimens typically use oral medications taken once a day for 12 weeks, and serious adverse effects are uncommon. Simplified treatment plans that can be initiated and monitored by physicians, advanced practice registered nurses, and nurse practitioners are easily available. In many cases, HCV can be cured, liver damage can be prevented, or if it is present, it can be reversed, and extrahepatic complications can be prevented and reversed.

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Implicit Bias Statement

CEUFast, Inc. is committed to furthering diversity, equity, and inclusion (DEI). While reflecting on this course content, CEUFast, Inc. would like you to consider your individual perspective and question your own biases. Remember, implicit bias is a form of bias that impacts our practice as healthcare professionals. Implicit bias occurs when we have automatic prejudices, judgments, and/or a general attitude towards a person or a group of people based on associated stereotypes we have formed over time. These automatic thoughts occur without our conscious knowledge and without our intentional desire to discriminate. The concern with implicit bias is that this can impact our actions and decisions with our workplace leadership, colleagues, and even our patients. While it is our universal goal to treat everyone equally, our implicit biases can influence our interactions, assessments, communication, prioritization, and decision-making concerning patients, which can ultimately adversely impact health outcomes. It is important to keep this in mind in order to intentionally work to self-identify our own risk areas where our implicit biases might influence our behaviors. Together, we can cease perpetuating stereotypes and remind each other to remain mindful to help avoid reacting according to biases that are contrary to our conscious beliefs and values.

References

  • Abdelhamed, W. & El-Kassas, M. (2023). Hepatocellular carcinoma and hepatitis C virus treatments: The bold and the beautiful. Journal of Viral Hepatitis, 30(2), 148–159. Visit Source.
  • Abu-Freha, N., Mathew Jacob, B., Elhoashla, A., Afawi, Z., Abu-Hammad, T., Elsana, F., Paz, S., & Etzion, O. (2022). Chronic hepatitis C: Diagnosis and treatment made easy. The European Journal of General Practice, 28(1), 102–108. Visit Source.
  • Ades, A. E., Gordon, F., Scott, K., Collins, I. J., Thorne, C., Pembrey, L., Chappell, E., Mariné-Barjoan, E., Butler, K., Indolfi, G., Gibb, D. M., & Judd, A. (2023). Spontaneous clearance of vertically acquired hepatitis C infection: Implications for testing and treatment. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 76(5), 913–991. Visit Source.
  • Arditi, B., Emont, J., Friedman, A. M., D'Alton, M. E., & Wen, T. (2023). Deliveries among patients with maternal hepatitis C virus infection in the United States, 2000-2019. Obstetrics and Gynecology, 141(4), 828–836. Visit Source.
  • Artenie, A., Stone, J., Fraser, H., Stewart, D., Arum, C., Lim, A.G., McNaughton, A.L., Trickey, A., Ward, Z., Abramovitz, D., Alary, M., Astemborski, J., Bruneau, J., Clipman, S.J., Coffin, C.S., Croxford, S., DeBeck. K., Emanuel. E., Hayashi, K., . . . HIV and HCV Incidence Review Collaborative Group. (2023). Incidence of HIV and hepatitis virus among people who inject drugs, and associations with age and sex or gender: A global systematic review and meta-analysis. Lancet Gastroenterology & Hepatology, 8(6), 533-552. Visit Source.
  • Bhattacharya, D., Aronsohn, A., Price, J., Lo Re, V., & AASLD-IDSA HCV Guidance Panel. (2023). Hepatitis C guidance 2023 update: AASLD-IDSA recommendations for testing, managing, and treating hepatitis C virus infection. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, ciad319. Visit Source.
  • Blauvelt, C. A., Turcios, S., Wen, T., Boscardin, J., & Seidman, D. (2024). Breastfeeding initiation in people with hepatitis C virus infection in the United States. Obstetrics and Gynecology, 143(5), 683–689. Visit Source.
  • Bojanic, K., Bogojevic, M. S., Vukadin, S., Sikora, R., Ivanac, G., Lucic, N. R., Smolic, M., Tabll, A. A., Wu, G. Y., & Smolic, R. (2023). Noninvasive fibrosis assessment in chronic hepatitis C infection: An update. Journal of Clinical and Translational Hepatology, 11(5), 1228–1238. Visit Source.
  • Bradley, H., Hall, E. W., Rosenthal, E. M., Sullivan, P. S., Ryerson, A. B., & Rosenberg, E. S. (2020). Hepatitis C virus prevalence in 50 U.S. States and D.C. by sex, birth cohort, and race: 2013-2016. Hepatology Communications, 4(3), 355–370. Visit Source.
  • Bukhari, T., Jafri, L., Majid, H., Ahmed, S., Khan, A. H. H., Abid, S., Raza, A., & Siddiqui, I. (2021). Diagnostic accuracy of the forns score for liver cirrhosis in patients with chronic viral hepatitis. Cureus, 13(4), e14477. Visit Source.
  • Butt, A. A., Yan, P., & ERCHIVES Study Team. (2021). Natural history of Hepatitis C virus infection in a large national seroconversion cohort in the direct-acting antiviral agent era: Results from ERCHIVES. Journal of Viral Hepatitis, 28(6), 916–924. Visit Source.
  • Centers for Disease Control Prevention (CDC). (2021). Hepatitis C, acute 2020 case definition. Centers for Disease Control and Prevention. Visit Source.
  • Centers for Disease Control and Prevention (CDC). (2022). Hepatitis C surveillance 2020. Centers for Disease Control and Prevention. Visit Source.
  • Centers for Disease Control and Prevention (CDC). (2023a). Hepatitis B or C infections. Centers for Disease Control and Prevention. Visit Source.
  • Centers for Disease Control and Prevention (CDC). (2023b). Hepatitis C questions and answers for health professionals. Centers for Disease Control and Prevention. Visit Source.
  • Centers for Disease Control and Prevention (CDC). (2023c). Hepatitis C surveillance 2021. Centers for Disease Control and Prevention. Visit Source.
  • Chapin-Bardales, J., Asher, A., Broz, D., Teshale, E., Mixson-Hayden, T., Poe, A., Handanagic, S., Blanco, C., Wejnert, C., & NHBS HCV Study Group. (2024). Hepatitis C virus infection and co-infection with HIV among persons who inject drugs in 10 U.S. cities-National HIV behavioral surveillance, 2018. The International Journal on Drug Policy, 104387. Visit Source.
  • Chaudhari, R., Fouda, S., Sainu, A., & Pappachan, J. M. (2021). Metabolic complications of hepatitis C virus infection. World Journal of Gastroenterology, 27(13), 1267–1282. Visit Source.
  • Chen, P. H., Johnson, L., Limketkai, B. N., Jusuf, E., Sun, J., Kim, B., Price, J. C., & Woreta, T. A. (2023). Trends in the prevalence of hepatitis C infection during pregnancy and maternal-infant outcomes in the US, 1998 to 2018. JAMA Network Open, 6(7), e2324770. Visit Source.
  • Chopra, S. (2023). Extrahepatic manifestations of hepatitis C virus infection. UpToDate. Retrieved April 12, 2024. Visit Source.
  • Chopra, S. (2024). Clinical manifestations and natural history of chronic hepatitis C infection. UpToDate. Retrieved April 3, 2024. Visit Source.
  • Chopra, S. & Arora, S. (2024a). Patient evaluation and selection for antiviral therapy for chronic hepatitis C infection. UpToDate. Retrieved April 7, 2024. Visit Source.
  • Chopra, S. & Arora, S. (2024b). Screening and diagnosis of chronic hepatitis C infection. UpToDate. Retrieved April 4, 2024. Visit Source.
  • Chopra, S. & Pockros, P. (2024). Overview of the management of chronic hepatitis C. UpToDate. Retrieved April 17, 2024. Visit Source.
  • Chromy, D., Schmidt, R., Mandorfer, M., Lang, G. F., Bauer, D., Schwabl, P., Popow-Kraupp, T., Reiberger, T., & Mayer, F. (2020). Hepatitis C virus RNA is commonly detectable in rectal and nasal fluids of patients with high viremia. Clinical infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 71(5), 1292–1299. Visit Source.
  • Covic, A., Caruntu, I. D., Burlacu, A., Giusca, S. E., Covic, A., Stefan, A. E., Brinza, C., & Ismail, G. (2023). Therapeutic potential of rituximab in managing hepatitis C-Associated Cryoglobulinemic Vasculitis: A systematic review. Journal of Clinical Medicine, 12(21), 6806. Visit Source.
  • D'Amico, G., Bernardi, M., & Angeli, P. (2022). Towards a new definition of decompensated cirrhosis. Journal of Hepatology, 76(1), 202–207. Visit Source.
  • Dharmesti, N. W. W., Wibawa, I. D. N., & Kandarini, Y. (2022). Hepatitis C seroconversion remains high among patients with regular hemodialysis: Study of associated risk factors. International Journal of Hepatology, 2022, 8109977. Visit Source.
  • Dienstag, J. L. (2022a). Chapter 339: Acute Viral Hepatitis. In J. Loscalzo, A. Fauci, D. Kasper, S. Hauser, D. Longo, & J.L. Jameson (Eds.). Harrison’s Principles of Internal Medicine, (21st ed.). McGraw-Hill.  Online edition. Visit Source.
  • Dienstag, J.L. (2022b). Chapter 341: Chronic Hepatitis. In J. Loscalzo, A. Fauci, D. Kasper, S. Hauser, D. Longo, & J.L. Jameson (Eds.). Harrison’s Principles of Internal Medicine, (21st ed.). McGraw-Hill.  Online edition. Visit Source.
  • Doerrbecker, J., Friesland, M., Ciesek, S., Erichsen, T. J., Mateu-Gelabert, P., Steinmann, J., Steinmann, J., Pietschmann, T., & Steinmann, E. (2011). Inactivation and survival of hepatitis C virus on inanimate surfaces. The Journal of Infectious Diseases, 204(12), 1830–1838. Visit Source.
  • Doica, I. P., Turcu-Stiolica, A., Ungureanu, B. S., Florescu, D. N., Rogoveanu, I., & Gheonea, D. I. (2023). Association between direct-acting agents adherence and health-related quality of life of patients with hepatitis C. Current Health Sciences Journal, 49(3), 312–318. Visit Source.
  • Elbeshbeshy, H., Modi, N., Patel, T., Matthews, I., Kampert, T., Lee, J., Okeke, R., Caliskan, Y., Fleetwood, V., Varma, C., Gabris, B., Bastani, B., Rub, F.A.A., Guenette, A., Befeler, A, Agbim, U., Desai, R., Alsabbagh, E., Qureshi, K. . . . Nazzal, M. (2024). Outcomes of kidney, liver, and simultaneous liver and kidney transplants from hepatitis C infected donors to hepatitis c naïve recipients: A large single-center experience. Clinical Transplantation, 38(1):e15161. Visit Source.
  • Egro, F. M., Nwaiwu, C. A., Smith, S., Harper, J. D., & Spiess, A. M. (2017). Seroconversion rates among health care workers exposed to hepatitis C virus-contaminated body fluids: The University of Pittsburgh 13-year experience. American Journal of Infection Control, 45(9), 1001–1005. Visit Source.
  • Erman, A., Sathya, A., Nam, A., Bielecki, J. M., Feld, J. J., Thein, H. H., Wong, W. W. L., Grootendorst, P., & Krahn, M. D. (2018). Estimating chronic hepatitis C prognosis using transient elastography-based liver stiffness: A systematic review and meta-analysis. Journal of Viral Hepatitis, 25(5), 502–513. Visit Source.
  • Erman, A., Krahn, M. D., Hansen, T., Wong, J., Bielecki, J. M., Feld, J. J., Wong, W. W. L., Grootendorst, P., & Thein, H. H. (2019). Estimation of fibrosis progression rates for chronic hepatitis C: A systematic review and meta-analysis update. BMJ Open, 9(11), e027491. Visit Source.
  • Faccioli, J., Nardelli, S., Gioia, S., Riggio, O., & Ridola, L. (2021). Neurological and psychiatric effects of hepatitis C virus infection. World Journal of Gastroenterology, 27(29), 4846–4861. Visit Source.
  • Fagala, M. D., & Shpak, Y. (2023). Implementing better standard instruments for detecting cirrhosis in hepatitis C patients. Cureus, 15(9), e44597. Visit Source.
  • Falade-Nwulia, O., Lesko, C. R., Fojo, A. T., Keruly, J. C., Moore, R. D., Sutcliffe, C. G., Mehta, S. H., Chander, G., Thomas, D. L., & Sulkowski, M. (2024). Hepatitis C treatment in people with HIV: Potential to eliminate disease and disparity. The Journal of Infectious Diseases, 229(3), 775–779. Visit Source.
  • Feld, J. J. (2022). Clinical manifestations, diagnosis, and treatment of acute hepatitis C infection in adults. UpToDate. Retrieved April 3, 2024. Visit Source.
  • Fiel, M. I. (2024). Histologic scoring systems for chronic liver disease. UpToDate. Retrieved April 11, 2024. Visit Source.
  • Friedman, L. S. (2024a). 18-04: Acute Hepatitis C & Other Causes of Acute Viral Hepatitis.  In M.A. Papadakis, S.J. McPhee, M.R. Rabow, K.R. McQuaid & M. Ghandhi (Eds.). Current Medical Diagnosis & Treatment 2024. McGraw-Hill. Online edition. Retrieved April 5, 2024. Visit Source.
  • Friedman, L. S. (2024b). 18-11: Cirrhosis. In M.A. Papadakis, S.J. McPhee, M.W. Rabow, K.R. McQuaid & M. Ghandi (Eds). Current Medical Diagnosis & Treatment, 2024. McGraw-Hill. Online edition.
  • Fujiyama, S., Akuta, N., Sezaki, H., Kobayashi, M., Kawamura, Y., Hosaka, T., Kobayashi, M., Saitoh, S., Suzuki, F., Suzuki, Y., Arase, Y., Ikeda, K., & Kumada, H. (2021). Mortality rates and risk factors in 1412 Japanese patients with decompensated hepatitis C virus-related cirrhosis: A retrospective long-term cohort study. BMC Gastroenterology, 21(1), 189. Visit Source.
  • Garg, B., Arbabi, A., & Kirkland, P. A. (2024). Extrahepatic manifestations of chronic hepatitis C virus (HCV) infection. Cureus, 16(3), e57343. Visit Source.
  • Ghany, M. G., Morgan, T. R., & AASLD-IDSA Hepatitis C Guidance Panel. (2020). Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases-Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Hepatology (Baltimore, Md.), 71(2), 686–721. Visit Source.
  • Graf, C., D’Ambrosio, R., Degasperi, E., Paolucci, S., Llaneras, J., Vermehren, J., Dultz, G., Peiffer, K-H., Finkelmeir, F., Hermann, E., Zeuzem, S., Buti, M., Lampertico, P., Dietz, J. & Sarrazin, C. (2024). Real-world effectiveness of voxilaprevir/velpatasvir/sofosbuvir in patients following DAA failure. JHEP Reports, 6(3):100994. Visit Source.
  • Grasch, J.L., de Voest, J.A., Saade, G.R., Hughes, B.L., Reddy, U.M., Costantine, M.M., Chien, E.K., Tita, A.T.N., Thorp Jr., J.M., Metz, T.D., Wapner, R.J., Sabharwal, K., Simhan, H.N., Swamy, G.K., Heyborne, K.D., Sibai, B.M., Grobman, W.A., El-Sayed, Y.Y., Casey, B.M. & Parry, S. (2024). Breastfeeding initiation, duration, and associated factors among people with hepatitis C virus infection. Obstetrics and Gynecology, 143(3), 449-455. Visit Source.
  • Green, V., & Roytman, M. (2022). Treatment-resistant hepatitis C viral infection: A case report and literature review. Case Reports in Hepatology, 2022, 3556780. Visit Source.
  • Henriot, P., Castry, M., Luong Nguyen, L. B., Shimakawa, Y., Jean, K., & Temime, L. (2022). Meta-analysis: risk of hepatitis C virus infection associated with hospital-based invasive procedures. Alimentary Pharmacology & Therapeutics, 56(4), 558–569. Visit Source.
  • Henriot, P., Anwar, W. A., El Gaafary, M., Abdo, S., Rafik, M., Hussein, W. M., Sos, D., Magdy, I., Jean, K., & Temime, L. (2024). Preventing iatrogenic HCV infection: A quantitative risk assessment based on observational data in an Egyptian hospital. PLOS Global Public Health, 4(2), e0002821. Visit Source.
  • Hobson, S., Gandhi, S., & Sobel, M. (2022). Intrahepatic cholestasis of pregnancy. Canadian Medical Association Journal, 194(48), E1650. Visit Source.
  • Hoff, E., Warden, A., Taylor, R., & Nijhawan, A. E. (2023). Hepatitis C epidemiology in a large urban jail: A changing demographic. Public Health Reports, 138(2), 248–258. Visit Source.
  • Houghton, M. (2019). Hepatitis C virus: 30 years after its discovery. Cold Spring Harbor Perspectives in Medicine, 9(12), a037069. Visit Source.
  • Hung, H. Y., Lai, H. H., Lin, H. C., & Chen, C. Y. (2023). The impact of sofosbuvir/velpatasvir/voxilaprevir treatment on serum hyperglycemia in hepatitis C virus infections: A systematic review and meta-analysis. Annals of Medicine, 55(1), 463–479. Visit Source.
  • Ito, T., & Nguyen, M. H. (2023). Perspectives on the underlying etiology of HCC and its effects on treatment outcomes. Journal of Hepatocellular Carcinoma, 10, 413–428. Visit Source.
  • Jatt, L. P., Gandhi, M. M., Guo, R., Sukhija-Cohen, A., Bhattacharya, D., Tseng, C. H., & Chew, K. W. (2021). Barriers to hepatitis C direct-acting antiviral therapy among HIV/hepatitis C virus-coinfected persons. Journal of Gastroenterology and Hepatology, 36(4), 1095–1102. Visit Source.
  • Jin, F., Dore, G. J., Matthews, G., Luhmann, N., Macdonald, V., Bajis, S., Baggaley, R., Mathers, B., Verster, A., & Grulich, A. E. (2021). Prevalence and incidence of hepatitis C virus infection in men who have sex with men: A systematic review and meta-analysis. The Lancet. Gastroenterology & Hepatology, 6(1), 39–56. Visit Source.
  • Kacem, M., Dhouib, W., Bennasrallah, C., Zemni, I., Abroug, H., Ben Fredj, M., Guedich, A., Safer, L., Ben Alaya, N., Mastouri, M., Bouanene, I., & Sriha Belguith, A. (2022). Occupational exposure to hepatitis C virus infection and associated factors among healthcare workers in Fattouma Bourguiba University Hospital, Tunisia. PloS One, 17(9), e0274609. Visit Source.
  • Kasting, M. L., Christy, S. M., Reich, R. R., Rathwell, J. A., Roetzheim, R. G., Vadaparampil, S. T., & Giuliano, A. R. (2022). Hepatitis C virus screening: Factors associated with test completion in a large academic health care system. Public Health Report, 137(6), 1136–1145. Visit Source.
  • Kaufman, H. W., Bull-Otterson, L., Meyer, W. A., 3rd, Huang, X., Doshani, M., Thompson, W. W., Osinubi, A., Khan, M. A., Harris, A. M., Gupta, N., Van Handel, M., Wester, C., Mermin, J., & Nelson, N. P. (2021). Decreases in hepatitis C testing and treatment during the COVID-19 pandemic. American Journal of Preventive Medicine, 61(3), 369–376. Visit Source.
  • Kenfack-Momo, R., Ngounoue, M.D., Kenmoe, S., Takuissu, G.R., Ebogo-Belobo, J.T., Kengne-Ndé, C., Mbaga, D.S., Zeuko'o Menkem, E., Lontuo Fogang, R., Tchatchouang, S., Ndzie Ondigui, J..L, Kame-Ngasse, G.I., Kenfack-Zanguim, J., Magoudjou-Pekam, J.N., Bowo-Ngandji, A., Mahamat, M., Nkie Esemu, S., Ndip, L. & Njouom, R. (2024). Global epidemiology of hepatitis C virus in dialysis patients: A systematic review and meta-analysis. PLoS One, 19(2):e0284169. Visit Source.
  • Kiser, J. (2023). Chapter 63: Treatment of Viral Hepatitis (HBV/HCV). In L.L. Brunton & B.C. Knollman (Eds.). Goodman & Gilman's: The Pharmacological Basis of Therapeutics (14th ed.). McGraw-Hill. Online edition. Visit Source.
  • Konishi, F., Miyake, T., Watanabe, T., Tokumoto, Y., Furukawa, S., Matsuura, B., Yoshida, O., Miyazaki, M., Shiomi, A., Kanzaki, S., Nakaguchi, H., Nakamura, Y., Imai, Y., Koizumi, M., Yamamoto, Y., Koizumi, Y., Hirooka, M., Takeshita, E., Kumagi, T. . . . Hiasa, Y. (2023). Association of abnormal glucose tolerance with liver-related disease and cardiovascular diseases in patients with chronic hepatitis C. Hepatology Research,53(9), 806-814. Visit Source.
  • Kumar, S. (2022). Hepatitis C, Acute. Merck Manual Professional Edition. Visit Source.
  • Kushner, T., Sperling, R. S., & Dieterich, D. (2019). Family counseling for hepatitis B and hepatitis C. Clinical Liver Disease, 13(4), 93–97. Visit Source.
  • Kwon, J. H., Hill, M. A., Patel, R., Tedford, R. J., Hashmi, Z. A., Shorbaji, K., Huckaby, L. V., Welch, B. A., & Kilic, A. (2023). Outcomes of over 1000 heart transplants using hepatitis C-Positive donors in the modern era. The Annals of Thoracic Surgery, 115(2), 493–500. Visit Source.
  • Laiwatthanapaisan, R., & Sirinawasatien, A. (2021). Current treatment for hepatitis C virus/Human immunodeficiency virus coinfection in adults. World Journal of Clinical Cases, 9(18), 4491–4499. Visit Source.
  • Lazarus, J. V., Picchio, C. A., & Colombo, M. (2023). Hepatocellular carcinoma prevention in the era of hepatitis C elimination. International Journal of Molecular Sciences, 24(18), 14404. Visit Source.
  • Lee, J. H., Cho, J., Kim, Y. J., Im, S. H., Jang, E. S., Kim, J. W., Kim, H. B., & Jeong, S. H. (2017). Occupational blood exposures in health care workers: Incidence, characteristics, and transmission of bloodborne pathogens in South Korea. BMC Public Health, 17(1), 827. Visit Source.
  • Lee, T. H. (2024a). Cirrhosis. Merck Manual Professional Edition. Visit Source.
  • Lee, T. H. (2024b). Hepatic fibrosis. Merck Manual Professional Edition. Visit Source.
  • Liu, C. H., & Kao, J. H. (2023). Acute hepatitis C virus infection: Clinical update and remaining challenges. Clinical and Molecular Hepatology, 29(3), 623–642. Visit Source.
  • Liu, A.F. & Zucker S.D. (2022). Chapter 41: Viral Hepatitis. S. Friedman, R.S. Blumberg & J.R. Saltzman, eds. Greenberger's CURRENT Diagnosis & Treatment Gastroenterology, Hepatology, & Endoscopy, (4th ed.). McGraw-Hill. Online edition. Visit Source.
  • Lloyd, A. R., & Franco, R. A. (2023). Sexual transmission of viral hepatitis. Infectious Disease Clinics of North America, 37(2), 335–349. Visit Source.
  • Lok, A. (n.d.). AST to patelet ratio index (APRI). MD+Calc. Visit Source.
  • Loy, D. E., Kamis, K., Kanatser, R., & Rowan, S. E. (2024). Barriers to hepatitis C treatment and interest in telemedicine-based care among clients of a syringe access program. Open Forum Infectious Diseases, 11(3), ofae088. Visit Source.
  • Mansour, D., & McPherson, S. (2018). Management of decompensated cirrhosis. Clinical Medicine, 18(Suppl 2), s60–s65. Visit Source.
  • Martinello, M., Naggie, S., Rockstroh, J. K., & Matthews, G. V. (2023). Direct-acting antiviral therapy for treatment of acute and recent hepatitis C virus infection: A narrative review. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 77(Suppl 3), S238–S244. Visit Source.
  • Mata-Marin, J., de Pablos-Leal, A.A., Mauss, S., Arroyo-Anduiza, C.I., Rodriguez-Evaristo, M.S., Uribe-Noguéz  de Los Ángeles Berrospe-Silva, M., Lara-Castañeda, J.C., Pérez-Barragán, E. & Gaytán-Martínez, J. (2022). Risk factors for HCV Transmission in HIV-positive men who have sex with men in Mexico. PLoS One, 17(7), e0269977. Visit Source.
  • Mavyret. (2023). Highlights of prescribing information. RxAbbieVie. Visit Source.
  • Mazzaro, C., Quartuccio, L., Adinolfi, L. E., Roccatello, D., Pozzato, G., Nevola, R., Tonizzo, M., Gitto, S., Andreone, P., & Gattei, V. (2021). A review on extrahepatic manifestations of chronic hepatitis C virus infection and the impact of direct-acting antiviral therapy. Viruses, 13(11), 2249. Visit Source.
  • McDonald, S. A., Innes, H. A., Aspinall, E., Hayes, P. C., Alavi, M., Valerio, H., Goldberg, D. J., & Hutchinson, S. J. (2017). Prognosis of 1169 hepatitis C chronically infected patients with decompensated cirrhosis in the predirect-acting antiviral era. Journal of Viral Hepatitis, 24(4), 295–303. Visit Source.
  • Monaco, S., Mariotto, S., Ferrari, S., Calabrese, M., Zanusso, G., Gajofatto, A., Sansonno, D. & Dammacco, F. (2015).  Hepatitis C virus-associated neurocognitive and neuropsychiatric disorders: Advances in 2015. World Journal of Gastroenterology, 21(42), 11974 -11983. Visit Source.
  • Monoe, C., Shimizu, H., Kitaguchi, K., & Funakoshi, H. (2020). Severe bradycardia Induced by Sofosbuvir and Amiodarone which resolved after the Discontinuation of Both Drugs. Internal Medicine, 59(20), 2619–2622. Visit Source.
  • Moorman, A.C., de Pero, M., Goldschmidt, R., Chu, C., Kuhar, D., Henderson, D.K., Naggie, S., Kamili, s., Spradling, P.R., Gordon, S.C., Russi, M.B. & Teshale, E.H. (2020). Testing and clinical management of health care Personnel potentially exposed to hepatitis C virus — CDC guidance, United States, 2020. Morbidity & Mortality Weekly Reports. Visit Source.
  • Muir, A.J. & Graham, C.S. (2024). Management of chronic hepatitis C virus infection: Initial antiviral therapy in adults. UpToDate. Retrieved April 11, 2024. Visit Source.
  • Mukhtar, N. A., & Fox, R. K. (2020). Hepatitis C virus cure and obesity: Watch the weight. Journal of General Internal Medicine, 35(10), 2836–2837. Visit Source.
  • Munaric, S.C., Traeger, M.W., Menon, V., Latham, N.H., Manoharan, L., Luhmann, N., Baggaley, R., MacDonald, V., Verster, A., Siegfried, N., Conway, B., Klein, M., Bruneau, J., Stoové, M.A., Hellard, M.E. & Doyle, J.S. (2023). Determining reinfection rates by hepatitis C testing interval among key populations: A systematic review and meta-analysis. Liver International, 43(12), 2625-2644. Visit Source.
  • Naggie, S., Holland, D. P., Sulkowski, M. S., & Thomas, D. L. (2017). Hepatitis C virus postexposure prophylaxis in the healthcare worker: Why direct-acting antivirals don't change a thing. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 64(1), 92–99. Visit Source.
  • National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (U.S.). Division of Viral Hepatitis. (2020). Healthcare-associated hepatitis B and C outbreaks (≥ 2 cases) reported to the Centers for Disease Control and Prevention (CDC) 2008-2019. Centers for Disease Control and Prevention. Visit Source.
  • National Clinician Consultation Center. (2021). PEP quick guide for occupational exposures. National Clinician Consultation Center. Visit Source.
  • National Library of Medicine/National Center for Biotechnology Information. (2022). LiverTox. National Library of Medicine/National Center for Biotechnology Information. Visit Source.
  • National Library of Medicine/National Center for Biotechnology Information. (2023a). Glecaprevir. National Library of Medicine/National Center for Biotechnology Information. Visit Source.
  • National Library of Medicine/National Center for Biotechnology Information. (2023b). Pibrentasvir. National Library of Medicine/National Center for Biotechnology Information. Visit Source.
  • National Library of Medicine/National Center for Biotechnology Information. (2023c). Sofosbuvir. National Library of Medicine/National Center for Biotechnology Information. Visit Source.
  • National Library of Medicine/National Center for Biotechnology Information. (2023d). Velpatasvir. National Library of Medicine/National Center for Biotechnology Information. Visit Source.
  • Negro, F. (2020). Natural history of hepatic and extrahepatic hepatitis C virus diseases and impact of Interferon-free HCV therapy. Cold Spring Harbor Perspectives in Medicine, 10(4), a036921. Visit Source.
  • Nevola, R., Acierno, C., Pafundi, P. C., & Adinolfi, L. E. (2021). Chronic hepatitis C infection induces cardiovascular disease and type 2 diabetes: Mechanisms and management. Minerva Medica, 112(2), 188–200. Visit Source.
  • Nguyen, D. B., Bixler, D., & Patel, P. R. (2019). Transmission of hepatitis C virus in the dialysis setting and strategies for its prevention. Seminars in Dialysis, 32(2), 127–134. Visit Source.
  • Nyberg, A. H., Sadikova, E., Cheetham, C., Chiang, K. M., Shi, J. X., Caparosa, S., Younossi, Z. M., & Nyberg, L. M. (2020). Increased cancer rates in patients with chronic hepatitis C. Liver International: Official Journal of the International Association for the Study of the Liver, 40(3), 685–693. Visit Source.
  • Odenwald, M. A., & Paul, S. (2022). Viral hepatitis: Past, present, and future. World Journal of Gastroenterology, 28(14), 1405–1429. Visit Source.
  • Office of Minority Health (OMH). (2022). Hepatitis and African-Americans. U.S. Department of Health and Human Services. Visit Source.
  • Ozga, J. E., Syvertsen, J. L., & Pollini, R. A. (2022). Hepatitis C antibody prevalence, correlates and barriers to care among people who inject drugs in Central California. Journal of Viral Hepatitis, 29(7), 518–528. Visit Source.
  • Paintsil, E., He, H., Peters, C., Lindenbach, B. D., & Heimer, R. (2010). Survival of hepatitis C virus in syringes: Implication for transmission among injection drug users. The Journal of Infectious Diseases, 202(7), 984–990. Visit Source.
  • Paintsil, E., Binka, M., Patel, A., Lindenbach, B. D., & Heimer, R. (2014). Hepatitis C virus maintains infectivity for weeks after drying on inanimate surfaces at room temperature: implications for risks of transmission. The Journal of Infectious Diseases, 209(8), 1205–1211. Visit Source.
  • Park, H., Brown, C., Wilson, D. L., Huang, P. L., Hernández-Con, P., Horne, P., Goodin, A., Joseph, A., Segal, R., Cabrera, R., & Cook, R. L. (2023). Clinician barriers, perceptions, and practices in treating patients with hepatitis C virus and substance use disorder in the United States. Preventive Medicine Reports, 32, 102138. Visit Source.
  • Pfaender, S., Helfritz, F. A., Siddharta, A., Todt, D., Behrendt, P., Heyden, J., Riebesehl, N., Willmann, W., Steinmann, J., Münch, J., Ciesek, S., & Steinmann, E. (2018). Environmental stability and infectivity of hepatitis C virus (HCV) in different human body fluids. Frontiers in Microbiology, 9, 504. Visit Source.
  • Pol, S. & Lagaye, S. (2019). The remarkable history of the hepatitis C virus. Microbes and Infection, 21(5-6), 263–270. Visit Source.
  • Prasa, J., Karim, S. S., Jacob, B., & Mustacchia, P. (2023). Hepatitis C prevalence on the rise but screening at safety net institutions lagging behind. International Journal of Hepatology, 2023, 3650746. Visit Source.
  • Radkowski, M., Kryczka, T., Szymańska-Kotwica, B., Berak, H., Horban, A., Pawłowski, T., Perlejewski, K., & Laskus, T. (2023). Depression and cognitive dysfunction in patients with chronic hepatitis C: Correlation with viral replication in the peripheral blood mononuclear cells and cytokines in serum. International Journal of Molecular Sciences, 24(20), 15351. Visit Source.
  • Radwan, D., Cachay, E., Falade-Nwulia, O., Moore, R. D., Westergaard, R., Mathews, W. C., Aberg, J., Cheever, L., Gebo, K. A., & HIV Research Network. (2019). HCV screening and treatment uptake among patients in HIV care during 2014-2015. Journal of Acquired Immune Deficiency Syndromes (1999), 80(5), 559–567. Visit Source.
  • Ramadan, M. S., Boccia, F., Moretto, S. M., De Gregorio, F., Gagliardi, M., Iossa, D., Durante-Mangoni, E., & Zampino, R. (2022). Cardiovascular risk in patients with chronic hepatitis C treated with direct acting antivirals. Journal of Clinical Medicine, 11(19), 5781. Visit Source.
  • Rashid, W., Patel, V., Ravat, V., Madireddy, S., Jaladi, P. R., Tahir, M., Bhimanadham, N. N., Kuduva Rajan, S., Imran, S., & Patel, R. S. (2019). Problematic cannabis use and risk of complications in patients with chronic hepatitis C. Cureus, 11(8), e5373. Visit Source.
  • Rockstroh, J. K. (2024). Treatment of chronic hepatitis C virus in patients infected with HIV. UpToDate. Retrieved April 17, 2024. Visit Source.
  • Rogers-Brown, J., Sublett, F., Canary, L., Rein, D. B., Bhat, M., Thompson, W. W., Vellozzi, C., & Asher, A. (2022). High-risk injection-related practices associated with anti-HCV positivity among young adults seeking services in three small cities in Wisconsin. Substance Use & Misuse, 57(5), 665–673. Visit Source.
  • Ružić, M., Rajić, N., Nikolašević, Ž., Spasić, A., Pete, M., & Ignjatović, V. B. (2023). Is there a connection between neurocognitive profile in treatment naïve non-cirrhotic HCV patients and level of systemic inflammation?. Journal of Neurovirology, 29(6), 723–730. Visit Source.
  • Shadi, Y., Heshmati, B., & Poorolajal, J. (2024). Interaction between hepatitis B, hepatitis C and smoking in the development of hepatocellular carcinoma: A systematic review and meta-analysis. Journal of Public Health, 46(1), 51–60. Visit Source.
  • Sherief, L. M., Beshir, M. R., Salem, G. M., Sherbiny, H. S., Soliman, A. A., El-Komy, M. A., Arafa, M., & Kamal, N. M. (2019). Intrafamilial transmission of hepatitis C virus among families of infected pediatric oncology patients. The Pediatric Infectious Disease Journal, 38(7), 692–697. Visit Source.
  • Shetty, A., Ariyamuthu, V. K., Gungor, A. B., & Tanriover, B. (2023). Utilization of hepatitis C virus-positive donors in kidney transplantation. Current opinion in organ transplantation, 28(1), 22–28. Visit Source.
  • Singal, A. G., Llovet, J. M., Yarchoan, M., Mehta, N., Heimbach, J.K., Dawson, L. A., Jou, J. H., Kulik, L. M., Agopian, V. G., Marrero, J. A., Mendiratta-Lalaa, M., Brown, D. B., Rillig, W. S., Goyal, L. Wei, A. C. & Taddei, T. H. (2023). AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology, 78(6),1922-1965. Visit Source.
  • Smith, B.D., Morgan, R.L., Beckett, G.A., Falck-Ytter, Y, Holtzman, D., Teo, C-G., Jewett, A., Baack, B., Rein, D.B., Patel, N., Alter, M., Yartel, A., Ward, J.W. & Centers for Disease Control and Prevention. (2012). Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. MMWR Morbidity and Mortality Weekly Report, 61(RR-4),1-32. Visit Source.
  • Songtanin, B., & Nugent, K. (2022). Burden, outcome, and comorbidities of extrahepatic manifestations in hepatitis C virus infection. Biology, 12(1), 23. Visit Source.
  • Tada, T., Toyoda, H., Yasuda, S., Miyake, N., Kumada, T., Kurisu, A., Ohisa, M., Akita, T., & Tanaka, J. (2019). Natural history of liver-related disease in patients with chronic hepatitis C virus infection: An analysis using a Markov chain model. Journal of Medical Virology, 91(10), 1837–1844. Visit Source.
  • Tapper, E. B., & Parikh, N. D. (2023). Diagnosis and management of cirrhosis and its complications: A review. JAMA, 329(18), 1589–1602. Visit Source.
  • Terrault, N.A. (2018). Care of patients following cure of hepatitis C virus infection. Gastroenterol & Hepatology (NY),14(11),629-634. Visit Source.
  • Tohme, R. A., & Holmberg, S. D. (2012). Transmission of hepatitis C virus infection through tattooing and piercing: a critical review. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 54(8), 1167–1178. Visit Source.
  • Tsai, W. C., Chiang, H. C., Chiu, Y. C., Chien, S. C., Cheng, P. N. & Chiu, H. C. (2023). Chronic hepatitis C virus infection: An ongoing challenge in screening and treatment. Life (Basel), 26;13(10):1964. Visit Source.
  • Tsoris, A., & Marlar, C. A. (2023). Use of the Child Pugh Score in liver disease. In StatPearls. StatPearls Publishing. Visit Source.
  • Turcu-Stiolica, A., Doica, I. P., Ungureanu, B. S., Rogoveanu, I., Florescu, D. N., Subtirelu, M. S., & Gheonea, D. I. (2021). Development and validation of a questionnaire to measure medication adherence to direct-acting agents in patients with hepatitis C. Pharmaceutics, 13(10), 1683. Visit Source.
  • United States Preventive Services Task Force (USPSTF). (2020). Final recommendation statement. hepatitis C virus infection in adolescents and adults: Screening. United States Preventive Services Task Force. Visit Source.
  • UpToDate. (2024). Glecaprevir and pibrentasvir: Drug information. Lexicomp.2024. Retrieved April 3, 2024. Visit Source.
  • U.S. Food & Drug Administration (USFDA). (2019). FDA warns about the rare occurrence of serious liver injury with the use of hepatitis C medicines Mavyret, Zepatier, and Vosevi in some patients with advanced liver disease. U.S. Food & Drug Administration. Visit Source.
  • Veeramachaneni, H., Park, B., Blakely, D., Palacio, A., Darby, R., Fluker, S. A., Lyles, R. H., & Miller, L. S. (2021). Differences in inpatient and outpatient hepatitis C virus prevalence and linkage to care rates in a safety net hospital hepatitis C screening program. Journal of Gastroenterology and Hepatology, 36(8), 2285–2291. Visit Source.
  • Viveiros, K. & Ryou, M. (2022). Chapter 47: Portal Hypertension & Esophageal Variceal Hemorrhage.  S. Friedman, R.S. Blumberg & J.R. Saltzman, eds. Greenberger's CURRENT Diagnosis & Treatment Gastroenterology, Hepatology, & Endoscopy, (4th ed.). McGraw-Hill. Online edition. Visit Source.
  • Vosevi. (2019). Highlights of prescribing information. Gilead. Visit Source.
  • Wang, C. C., Cook, L., Tapia, K. A., Holte, S., Krows, M., Bagabag, A., Santos, A., Corey, L., & Jerome, K. R. (2011). Cervicovaginal shedding of hepatitis C viral RNA is associated with the presence of menstrual or other blood in cervicovaginal fluids. Journal of Clinical Virology: The Official Publication of the Pan American Society for Clinical Virology, 50(1), 4–7. Visit Source.
  • Wester, C., Osinubi, A., Kaufman, H. W., Symum, H., Meyer, W. A., 3rd, Huang, X., & Thompson, W. W. (2023). Hepatitis C virus clearance cascade- United States, 2013-2022. MMWR. Morbidity and Mortality Weekly Report, 72(26), 716–720. Visit Source.
  • Woolley, A. E., Singh, S. K., Goldberg, H. J., Mallidi, H. R., Givertz, M. M., Mehra, M. R., Coppolino, A., Kusztos, A. E., Johnson, M. E., Chen, K., Haddad, E. A., Fanikos, J., Harrington, D. P., Camp, P. C., Baden, L. R., & DONATE HCV Trial Team (2019). Heart and lung transplants from HCV-infected donors to uninfected recipients. The New England Journal of Medicine, 380(17), 1606–1617. Visit Source.
  • World Health Organization (WHO). (2023). New recommendation on hepatitis C virus testing and treatment for people at ongoing risk of infection. World Health Organization. Visit Source.
  • Xu, H. Q., Wang, C. G., Zhou, Q., & Gao, Y. H. (2021). Effects of alcohol consumption on viral hepatitis B and C. World Journal of Clinical Cases, 9(33), 10052–10063. Visit Source.
  • Yeoh, S. W., Holmes, A. C. N., Saling, M. M., Everall, I. P., & Nicoll, A. J. (2018). Depression, fatigue and neurocognitive deficits in chronic hepatitis C. Hepatology international, 12(4), 294–304. Visit Source.
  • Zhou, Y., Xie, W., Zheng, C., Liu, L., Chen, Z., & Wang, X. (2022). Hypoglycemia associated with direct-acting anti-hepatitis C virus drugs: An epidemiologic surveillance study of the FDA adverse event reporting system (FAERS). Clinical Endocrinology, 96(5), 690–697. Visit Source.
  • Zuñiga-Aguilar, E., & Ramírez-Fernández, O. (2022). Fibrosis and hepatic regeneration mechanism. Translational Gastroenterology and Hepatology, 7, 9. Visit Source.