This module will discuss the epidemiology, pathophysiology, and transmission of the hepatitis C virus, and the clinical course and treatment of hepatitis C infection.
After finishing this module, the learner will be able to:
Hepatitis C is an infectious disease of the liver and a common cause of liver fibrosis, cirrhosis, and liver cancer. The hepatitis C virus was a cause of hepatitis for decades, but it was not isolated and identified until 1989 (Alter, 2011; Choo et al., 1989). Prior to that, cases of hepatitis that were not caused by the hepatitis A virus or by the hepatitis B virus were classified as non-A, non-B hepatitis.
Sensitive and targeted screening tests have greatly reduced the risk for transmission of hepatitis C and new, highly effective treatments are now available. However, hepatitis C infections are still a major cause of morbidity; the public health burden of hepatitis C infections is growing and this increase is expected to continue. (Ly, Hughes, Jiles, & Holmberg, 2016; Tholey & Ahn, 2015; Davis, Alter, El-Serag, & Poynard, 2010). Nurses now and in years to come will need to understand hepatitis C transmission, complications, and treatments.
Hepatitis C is the most common blood-borne disease in the United States (Gross et al, 2016). There are approximately 3.5 million Americans who are chronically infected with hepatitis C (CDC, 2016). However, this figure is almost certainly an under estimate according to Edlin, Eckhardt, Shu, Holmberg, & Swan (2015) as it does not include many people from at-risk populations who are likely to be infected (Allison, Chaiang, & Rubin (2016); He et al., 2016; Shire & Shermana, 2015). Many people who are infected with hepatitis C have not been diagnosed (Sayiner et al., 2016).
Infections with hepatitis C have been associated with a 15-fold to 20-fold increased risk of hepatocellular carcinoma (Tholey & Ahn, 2015). The incidence of this cancer in the United States is rising, in part due to hepatitis C infections and in part due to the increase in the prevalence of liver cancer risk factors such as diabetes, fatty liver, and infections with hepatitis B and human immunodeficiency virus (Tholey & Ahn, 2015). Cirrhosis that is secondary to hepatitis C infection is the leading cause of liver transplantation in the United States (CDC, 2016; Dhingra, Ward, & Thung, 2016). From 2003 to 2013 the mortality rate associated with hepatitis C has been rising according to Ly et al. (2016) and surpasses the mortality rate from HIV (Mahajan, Xing, & Liu, 2014). Extra-hepatic complications caused by hepatitis C are common and an infection with the virus can negatively affect the progression of chronic diseases such as atherosclerosis and diabetes and increase the risk of mortality.
The progression from infection with the hepatitis C virus to fibrosis, cirrhosis, liver failure, and/or hepatocellular cancer takes decades. Presently, there is no vaccine for hepatitis C. The number of people needing medical care for the complications associated with hepatitis C has increased in the past few years, and the number of cases are expected to increase dramatically in the next 20 to 30 years (Ly et al., 2016; Tholey & Ahn, 2015; Davis et al., 2010).
A 57-year-old male has made an appointment with his primary care physician. He is in good health, has no major medical problems, he has no history of psychiatric illnesses, and he does not take any prescription medications. He is moderately overweight, drinks alcohol (occasionally to excess), and smokes. The patient has no specific problems, but he will be starting a new job that requires strenuous activity and his employer has requested that he be examined by a physician to determine if he can tolerate this level of physical stress.
During the interview, the man admits to the physician that as a young man he had experimented with IV drugs for a brief period of time, but has not used any illicit substances for over 35 years. Laboratory tests reveal that his serum AST is 115 IU/L and his serum ALT is 190 IU/L; these levels are considered moderate elevations. A test for hepatitis C antibodies is positive and hepatitis C RNA is detected, as well, genotype 1a. A Fibroscan of his liver reveals a mild level of fibrosis but no cirrhosis. He does not have an infection with HIV, hepatitis A, or hepatitis B and his CBC, 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 presence of, or risk for depression.
The physician tells the patient that because he is male, because he has probably had the infection for a long time 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 he should receive treatment for the hepatitis C infection. She prescribes ledipasivir/sofobuvir (Trade name 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 hepatitis C is transmitted, and he is instructed on how to avoid transmission of the virus.
After four weeks of drug therapy there is no detectable hepatitis C 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 hepatitis C 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 the life style modifications, continue safe sex practices, and continue to avoid behaviors that may put him at risk for reinfection.
The hepatitis C virus is an RNA virus. RNA viruses (e.g., HIV, hepatitis C, Ebola) use RNA to replicate; they have very high replication rates, are genetically very diverse, and mutate very quickly (Lauring & Andino, 2010). These qualities, among other characteristics of the hepatitis C virus, make it very difficult for the host’s immune system to eradicate the virus or for therapeutic drugs to be effective in treating an infection with hepatitis C. Although the body and the liver react to an infection with a strong cellular and humoral immune response, the virus rapidly replicates and only 25% of all people who are infected spontaneously clear the virus. It is not known exactly why the virus survives despite this immune response, but it is persistence and the chronic infection that is so common is due to a complex, multi-factorial host-virus interaction (Wang et al., Jul 2011; Wang, Keck, & Foung, Nov 2011; Lauring & Andino, 2010). Once the infection becomes chronic, the virus damages hepatocytes and stimulates an inflammatory response; the result is fibrosis which can progress to cirrhosis, liver failure, and/or liver cancer.
There are six major hepatitis C genotypes, genotypes 1 through 6, and there are more than 100 subspecies (Bostan & Mahmood, 2010). The most common genotype worldwide is type 1, and this is the most common genotype in the United States (CDC, 2016; Chopra, October 2015, Manos, Shvachko, Murphy, Arduino & Shire, 2012). Approximately 75% of all patients in the United States with a hepatitis C virus infection are infected with the type I genotype and approximately 25% are infected with genotype 2 or 3 (Manos, Shvachko, Murphy, Arduino, & Shire, 2012; Schiff, 2011).
Genotype is an important factor in the prognosis of a hepatitis infection. Hepatitis genotype has been associated with response to treatment, the risk of fibrosis and steatosis, and mortality rate (Campos-Varela et al., 2015). In addition, the American Association for the Study of Liver Disease and the Infectious Diseases Society of America (2016) have established treatment protocols that differ depending on genotype and some of the genotypes are more easily treated than others (CDC, 2016).
Transmission of the hepatitis C virus is caused by exposure to infected blood, sexual contact, and mother-to-child transmission. In approximately 10%-20% of all cases of hepatitis C, the cause of the infection cannot be identified (Dhawan, 2013; Pondé, 2011).
The primary mode of transmission of hepatitis C is by exposure to infected blood. In the US and in other developed countries this happens most often by IV drug use when people share needles (CDC, 2016; Valerio, Goldberg, & Lewsey, 2015). The Centers for Disease Control and Prevention (CDC) (2016) has estimated that approximately one-third of people between the ages of 18-30 who use IV drugs are infected with hepatitis C, and the rate of infection is approximately 70% - 90% in older persons who used, or still use IV drugs.
Sexual transmission of hepatitis C is a somewhat controversial topic. Hepatitis C virus RNA has been isolated in semen and cervical smears but not consistently (Bradshaw et al., 2015; Wang et al., 2011; Tohme & Holmberg, 2010). Anal sexual intercourse and sexual practices that involve exposure to blood and/or tissue trauma clearly increase the risk of transmission of the virus (Page & Nelson, 2016; Gorgos, 2013; Halfon, 2013). The CDC notes that these sex practices are considered risk factors for hepatitis C. Sexual transmission of hepatitis C in monogamous, heterosexual couples appears to be very rare. Terrault et al. (2013) estimated that the incidence rate of hepatitis C transmission rate in this population to be 0.07% per year or approximately 1 per 190,000 sexual contacts. The CDC’s 2015 Sexually Transmitted Diseases Guidelines notes that sexual contact is an inefficient means of hepatitis C virus transmission (Workowski & Bolan, 2015). However, the Guidelines also note that sexual transmission can occur, especially in people who are also infected with HIV, and that couples should be counseled regarding safe sex practices.
A study by Tohme & Holmberg (2010) showed concurrent HIV infection sharply increases the risk of sexual transmission of hepatitis C, especially among men who have sex with men (Gamage et al., 2011). People who have multiple partners are at increased risk for hepatitis C transmission, and exposure to genital ulcerations and the presence of a sexually transmitted disease also increases the risk of sexual transmission of hepatitis C (Thome et al., 2010).
Hepatitis C virus is not transmitted very often or (seemingly) very efficiently through occupational exposures to blood. Transmission from patients to healthcare workers has been reported rarely, but more than half these cases had other risk factors (Pearlman, 2004). Approximately 39% of all hepatitis C infections in healthcare workers are considered to be occupational (Strasser et al., 2013). The risk for hepatitis C infection after a needle stick or sharps exposure to HCV-positive blood is approximately 1.8% (range: 0–10%) (Strasser et al., 2013).
Transmission rarely occurs from mucous membrane exposures to infected blood (Hosoglu et al., 2003). Furthermore, no transmission to healthcare professionals has been documented from intact or non-intact skin exposures to blood. Hepatitis C virus has been found in ascites, menstrual fluid, saliva, semen, spinal fluid, and urine. Transmission of the hepatitis C virus from these fluids has not been reported, but if there was a parenteral exposure to ascites, spinal fluid, or one of these other fluids or if someone was exposed to a large amount of one of these fluids, transmission could possibly occur (Henderson, 2003).
Hepatitis C virus has been reported to survive on environmental surfaces and remain infectious for six weeks (Paintsil, Binka, Patel, Lindenbach, & Heimer, 2014). Depending on the type of syringe and other factors, the hepatitis C virus can remain viable in syringes for up to 63 days (Binka, Paintsil, Patel, Lindenbach, & Heimer, 2015).
The risk for transmission of hepatitis by a blood transfusion has been estimated to be one chance per 2 million transfused units (CDC, 2016).
Hepatitis C is not transmitted by insect bites, food, water, inhalation, or causal contact (CDC, 2016). It is not transmitted in household living situations unless there is contact with infected blood, e.g., sharing toothbrushes or razors.
Mother-to-child vertical transmission of hepatitis C is the most common cause of pediatric hepatitis C infections (Bal & Petrova, 2016). Tovo, Calitri, Scolfaro, Gabiano, & Garazzino (2016) reports that worldwide the prevalence of pediatric hepatitis C infections has been estimated to be approximately 5%, but this rate is much lower in the United States (El-Shabrawi & Kamal, 2013). Each year in the US there are approximately 8,000 new cases of pediatric hepatitis C infection and the risk of mother-to-child transmission has been estimated to be 4.3% (Khaderi, Shepherd, Goss, & Leung, 2014). There is no evidence that hepatitis C can be transmitted through breastfeeding (Tovo, Calitri, Scolfaro, Gabiano, & Garazzino 2016; Dunkelberg, Berkley, Theil, & Leslie, 2014).
Factors that increase the risk for developing hepatitis C are listed in Table 1 (Novo-Veleiro et al., 2016; Lee, Conniff, Kraus, & Schrager, 2015; Caiffa, Zocratto, & Osimani, 2011; Thome et al, 2010; Macías et al, 2008):
|Alcohol consumption/alcoholic liver disease|
|Blood transfusion before 1992|
|Born between 1945 and 1965|
|Born to a mother who is infected with hepatitis C|
|Inhalational drug use|
|Intravenous drug use, current or past|
|Percutaneous exposure to infected blood|
|Poor infection control|
|Risky sexual behavior|
|Solid organ or tissue recipient|
The issues of mother-to-child transmission, percutaneous exposure, and sexual transmission were previously discussed, and some of the risk factors listed in Table 1 are clearly related to behaviors that may accompany a life situation. An infection with HIV as a risk factor for hepatitis C infection will be discussed later in the module.
Blood transfusions before 1992 impart a risk because accurate, reliable methods for screening blood for hepatitis C were not available before then.
A birth date between 1945 and 1962 is considered a risk factor for several reasons: Seventy-five percent of all people who have a hepatitis C infection were born between those dates and as will be discussed later, most of these people have an asymptomatic infection; people born between those dates would be more likely to receive a transfusion before blood supplies could be screened for hepatitis C and; for many years there was no blood test that could detect the virus in people who were infected (CDC, 2015).
Nosocomial infections with hepatitis C are rare (Saludes, Esteve, Casas, Ausina, & Martó, 2013).Long-term hemodialysis is a risk factor for hepatitis C and transmission of the virus in this clinical setting is very unusual but has been reported: between 2014 and 2015 the CDC was contacted about 36 cases of acute hepatitis C infection that occurred in 19 different hemodialysis clinics (Am J Transplant, 2016). Poor compliance with infection control procedures were identified at these facilities and this is a common finding in nosocomial hepatitis C infections (Branch-Elliman, Weiss, Balter, Bornschlegel, & Philips, 2013). But, in some cases no breach of infection control practices can be identified (Fabrizi & Messa, 2015).
The issue of alcohol consumption/alcoholic liver disease and hepatitis C deserves special mention because of the high prevalence of alcohol use and abuse. Alcohol abuse appears to increase viral replication and blunt the body’s immune response, and it has been estimated that 30%-40% of patients who have alcoholic liver disease have hepatitis C (Testino, Leone, & Borro, 2016).
The prevalence of hepatitis C infection is much higher in alcoholic patients than in the general population. Novo-Veleiro et al. (2016) found a 16.32% prevalence of hepatitis C in alcoholics; this is compared to the 1.3% prevalence rate for the general population. Excess alcohol consumption and infection with hepatitis C increases the development of liver cirrhosis and increases the risk for hepatocellular carcinoma (Testino et al., 2016).
An acute infection with hepatitis C can cause mild flu-like symptoms and occasionally the patient will have abdominal pain, anorexia, dark urine, and jaundice, but in most cases acute infections go unnoticed and undiagnosed (Westbrook & Dusheiko, 2014). Approximately 25% of hepatitis C infections spontaneously resolve: the virus is cleared, and there are no clinical consequences (CDC 2016; Lee et al., 2015; Westbrook & Dusheiko, 2014).
If the virus is not cleared within six months, the infection is considered to be chronic, and the progression of chronic hepatitis C infections is a decades-long process characterized by inflammation and fibrosis and in some cases, cirrhosis and liver cancer (Dhingra et al, 2016). However, it should be stressed that in majority of cases this process is very, very slow. Patients who are infected with hepatitis C will have the virus for decades but remain asymptomatic and the liver transaminases may, from time to time, be only mildly elevated. The natural history of hepatitis C infections is illustrated below (CDC, 2016; Lee et al., 2015). These figures are approximate.
For every 100 persons infected with hepatitis C:
As with acute infections, many chronic infections go unnoticed and undiagnosed and it is not unusual for a patient to be diagnosed when they have end-stage liver disease complications (Westbrook & Dusheiko, 2014).
The risk of developing cirrhosis, the development of fibrosis, and the development of other complications over 30 years of infection is approximately 5-25% (Schiff, 2011). The level of risk is by the following factors (Westbrook & Dusheiko, 2014).
Concurrent infection with hepatitis C and hepatitis B is relatively common. It is not clear at this point if an infection with hepatitis B has a negative influence on the clinical course of a hepatitis C infection; there is some evidence that it does not (Jang, et al., 2011), but some authors feel that it may (Fernandez-Rodriguez, Gutierrez, Lledó, & Casas, 2011).
The exact mortality rate of hepatitis C is uncertain. There is evidence that a diagnosis of hepatitis C infection is independently associated with a higher rate of mortality (Sayiner et al., 2016; Mahajan et al., 2014), even if added risk factors such IV drug use and HIV infection are not present (Grebely & Dore, 2011).
It was traditionally thought that most people infected with hepatitis C did not die from the disease, but from complications of other unrelated pathologies.
However, this position has been challenged in recent years, and some researchers such as Mahajan et al. (2014) believe that an infection with hepatitis C itself greatly increases the risk for premature death and that the true mortality risk associated with hepatitis C infection is greatly underestimated (Ly et al., 2016). Regardless of the actual effect of hepatitis C on mortality, an infection with the virus can cause many extra-hepatic complications and may accelerate the progression of common disease such as diabetes and heart disease.
Fibrosis and cirrhosis are common consequence of hepatitis C infection. Fibrosis is the less serious of the two and it is defined as the formation of fibrous tissue, an increase in the amount of the extracellular collagen supporting framework of the liver. Fibrosis occurs as local, chronic inflammation that causes a cycle of damage and repair. The histological definition of cirrhosis is a diffuse hepatic process characterized by fibrosis and conversion of normal liver architecture into structurally abnormal nodules interlacing bands of fibrous tissue in the liver. Fibrosis is the first step in the development of cirrhosis. Fibrosis is potentially reversible; cirrhosis is not. The risk for developing fibrosis is not associated with the genotype or the viral load (Rosen, 2011). Once the patient has developed cirrhosis, she/he is at risk for hepatic decompensation and portal hypertension and complications such as esophageal varices and hepatic encephalopathy (Wang, D’Souza, & Jacobson, 2016).
Table 2 lists hepatitis C screening guidelines that are recommended by the CDC and the American Association for the Study of Liver Diseases/ Infectious Diseases Society of America (AASLD/ISDA).
|All adults born from 1945 to 1965, irrespective of risk factors|
|Anyone who received clotting factor concentrates before 1987|
|Anyone who received a blood transfusion or an organ transplant before July 1992|
|Anyone who received a blood transfusion and was notified that the blood donor later tested positive for hepatitis C|
|Anyone infected with HIV|
|Children born to a mother who has a hepatitis C infection|
|Current IV drug users|
|Former IV drug users, regardless of pattern of use|
|Healthcare workers or others who suffered a needle stick or sharps injury or a mucosal exposure to hepatitis C positive blood|
|Long-term hemodialysis patients|
Differences in the CDC and AASLD/ISDA guidelines are discussed below.
The CDC recommends screening for people who have persistently abnormal alanine aminotransferase (ALT) levels. The CDC notes that persons for whom hepatitis C testing is of uncertain need includes people who use intranasal cocaine; other non-injecting illegal drug users; anyone who has a history of body piercing or tattoos; anyone with a history of multiple sex partners or sexually transmitted diseases, and; long-term steady sex partners of people who have hepatitis C (CDC, October, 2015).
The AASLD recommends screening for anyone with history of intranasal illicit drug use; anyone who was tattooed in an unregulated setting; and anyone who was ever incarcerated (AASLD/ISDA, 2016).
Diagnosing hepatitis C is a three step process (Terrault et al., 2015; Lee et al., 2015):
Serologic testing can detect anti-hepatitis C antibodies as soon as eight weeks after an exposure and most people will sero-convert two to six months after an exposure (Terrault et al., 2015).
Hepatitis C RNA can be detected a soon as two weeks after an exposure. False negative RNA testing is uncommon (Lee et al., 2015).
If the serologic testing is negative the patient does not have hepatitis C. If the serologic testing is positive and the RNA testing is positive, the patient has a hepatitis C infection (Terrault et al., 2015; Lee et al., 2015).
If the serologic testing is positive but the RNA testing is negative, there are three possibilities (Terrault et al., 2015; Lee et al., 2015):
If the serologic testing is positive and the RNA test is negative, the RNA test should be repeated in four to six months; this will discriminate an acute infection from a recovered infection (Lee et al., 2015).
Patients can have a hepatitis C infection and have a negative serologic test. If there is a suspicion that a patient was recently exposed to hepatitis C or if the patient is immunocompromised (e.g., patients on chronic hemodialysis, transplant recipients, and patients infected with HIV) then RNA testing should be done even if the serologic testing is negative (Terrault et al., 2015).
After confirmation of an infection and genotyping the patient should be assessed for the level of liver damage and the staging of fibrosis. This is a very important step as the degree of fibrosis can be used to predict the progression and outcomes of any particular case (AASLD/ISDA, 2016). Assessment of liver damage and fibrosis will guide treatment decisions and establish the level of risk for certain complications; it is done invasively by a liver biopsy or non-invasively by using the patient history and physical examination, by serologic, or by ultrasound-based transient elastography. Serologic testing and ultrasound-based transient elastography are often done together.
A liver biopsy has long been considered to be the gold standard for evaluating the level of liver damage. The procedure is invasive so there are risks for bleeding, infection, and pain. Complications of the procedure seldom happen and death is rare, but sampling and observer errors are not uncommon and given that the size of the tissue sample represents 1/50,000 of the liver itself, this is not surprising (Wong, 2013). Research by Amarapurkar & Amarapurkar (2015) finds that liver biopsies have a 10%-20% sampling error, there is a 15%-30% chance of underestimating the degree of cirrhosis, and intra- and inter-observer agreement is 60%-90%. Liver biopsy is useful if the patient has a large degree of steatosis or inflammation, if he/she has cirrhosis or other evidence of significant liver damage (Harrison, 2015), or to detect the presence of other liver disease, the patient may have such as alcoholic hepatitis, but in most cases it is not the first choice (Chopra & Arora, September 2015). Non-invasive diagnostic tests can determine the level of fibrosis and liver biopsy can be reserved for those cases where there is a need to confirm advanced liver damage (Harrison, 2015).
Non-invasive assessment of the degree of liver damage can be done by using the patient history, physical examination, serologic testing (with routine blood tests or specialized blood tests), or radiologic testing, the last being done by, conventional ultrasound or the FibroScan (Curry & Afdhal, 2016; Stasi & Milani, 2016; Chopra & Arora, September 2015; Lee et al., 2015).
The patient history and the physical examination are obviously important parts of diagnosing and assessment but these are not sensitive or specific.
Routine laboratory tests such as the measurement of AST and ALT are not sensitive or specific.
Researchers have investigated using routinely available blood tests in combination with serum markers that directly or indirectly reflect the buildup and /or breakdown of fibrotic tissue, and some of these testing schemes have shown a satisfactory level of accuracy for detecting fibrosis (Stasi & Milani, 2016). For example, the Fibrotest uses measurements of alpha-2 macroglobulin, haptoglobin, apoliporotein A1, gamma-glutamyl transpeptidase (GGT), total bilirubin, and ALT along with the patient’s age and gender and these values are used in a formula that predicts the degree of fibrosis. Fibrotest, Hepascore, and FibroSpect are proprietary marker tests that are used in the United States. These tests and others like them are not considered to be stand-alone tests for the detection of fibrosis and are used in combination with elastography (Curry & Afdhal, 2016).
Ultrasound-based transient elastography using the FibroScan is the most studied of the radiologic assessment methods used to detect liver fibrosis. Ultrasound-based transient elastography measures the stiffness of liver tissue, thus providing an indirect measurement of liver fibrosis. Dietrich (2015) shows this technique to be 70% sensitive and 84% specific for diagnosing significant fibrosis and it has been reported to have a high level of inter-observer agreement (Afdahl et al., 2015).
Ultrasound-based transient elastography does, of course, have limitations. It may not be able to detect fibrosis in patients who are obese or who have ascites (Lee et al., 2015); it may over-estimate liver stiffness if there is acute inflammation in the liver (Castéra et al., 2010); inter-observer agreement appears to decrease if there is a low level of fibrosis; it is not widely available; the accuracy is dependent on operator skill and experience, and; there are many other clinical factors that can cause inaccurate results (Perazzo, Veloso, Grinzstein, Hyde, & Castro, 2015; Pang et al., 2014; Wong, 2013).
Additional tests that should be done during the initial work-up should include a BUN and creatinine, complete blood count (CBC), liver transaminases, assessment of the liver’s synthetic function by measuring albumin, bilirubin, international normalized ratio (INR), and prothrombin time, glucose, lipid panel, thyroid function tests, vitamin D level, and checking for hepatitis A, hepatitis B, and HIV (Terrault et al., 2015). Women of child-bearing age should be checked for pregnancy. The physician may want to measure a serum α-fetoprotein level: this can be a marker for hepatocellular cancer (White et al., 2015). A low level of vitamin D in patients who have hepatitis C has been associated with certain extra-hepatic complications and severe fibrosis (Melo-Villar et al., 2015).
Extra-hepatic complications of hepatitis C are common. Gill, Ghazinian, Manch, & Gish (2016) writes that between 40% and 74% of patients who have chronic hepatitis C will develop at least one extra-hepatic complication and these complications may negatively affect the progression of chronic conditions such as cardiovascular disease.
Fortunately, a sustained virological response (SVR) - a cure - can reverse and/or prevent some of these complications and reduce mortality (Knobler et al., 2016; Vanni, Bugianesi, & Saracco, 2016; Tholey & Ahn, 2015; Viganò & Colombo, 2015; Westbrook & Dusheiko, 2014).
Hepatitis C infection causes insulin resistance in the liver and the peripheral tissues (Knobler & Malnick, 2016; Kralj et al., 2016). According to Viganò & Colombo (2015), diabetes is much more common in patients with chronic hepatitis C than in the general population. This association was first noted and confirmed shortly after the hepatitis C virus was first isolated (Allison, Wreghitt, Palmer, & Alexander, 1994). Even when the factors of age, obesity, and smoking are considered, hepatitis C increases the risk of developing diabetes and insulin resistance (Gill et al., 2016). The literature survey by Gill et al. (2016) found that the incidence of diabetes in patients who had hepatitis C was 28%, much higher than the general population, and that people who had hepatitis C were 11 times more likely to develop diabetes than people who did not have the infection. Diabetes and insulin resistance associated with hepatitis C infection increases the progression of liver fibrosis (Hsu et al., 2010). The association between chronic hepatitis C and diabetes is further emphasized by the finding that the risk of developing diabetes can be greatly reduced by successful treatment of hepatitis C (Viganò & Colombo, 2015). The mechanisms by which hepatitis C induces insulin resistance have not been completely explained but they probably involve a disruption in insulin signaling, changes in lipid metabolism, and an increased production of inflammatory cytokines (Knobler & Malnick, 2016; Kralj et al., 2016; Eslam, Khattab, & Harris, 2011).
The risk of developing hepatocellular carcinoma is 15 to 20 times higher for people infected with hepatitis C than for those who are not (Tholey & Ahn, 2015).The incidence of this cancer in the United States is rising, in part due to hepatitis C infections and in part due to presence of other risk factors for hepatocellular carcinoma, e.g., alcohol use, cirrhosis, diabetes, fatty liver, HIV infection, smoking, and infections with hepatitis B and HIV (Tholey & Ahn, 2015; Nash, Woodall, Brown, Davies, & Alexander, 2010). Treatment of hepatitis C with interferon reduces the risk of developing hepatocellular cancer but it is not known whether the second generation direct-acting anti-virals that are currently the treatment of choice have the same effect (Tholey & Ahn, 2015).
People who are infected with hepatitis C have an increased risk for the development of renal disease (Gill et al., 2016; Fabrizi & Messa, 2015; Ozkok & Yildiz, 2014; Morales, Kamar, & Rostaing, 2012). The most common cause of renal damage in patients with a hepatitis C infection is membranoproliferative glomerulonephritis (Fabrizi & Messa, 2015). Membranoproliferative glomerulonephritis is a form of nephritis that, in the context of hepatitis C infection, is usually caused by type II mixed cryogolubulinemia (Gill et al., 2016; Ozkok & Yildiz, 2014). Cryoglobulinemia is an immune-mediated process that causes deposition of immune complexes into the endothelium of small and medium-sized arteries and veins, resulting in widespread inflammation and vasculitis. The incidence of membranoproliferative glomerulonephritis associated with hepatitis C has been estimated to be approximately 40% (McGuire et al., 2006).
Glomerular disease in patients infected with hepatitis C is typically characterized by acute nephritis, hypertension, microscopic hematuria, nephritic syndrome, and proteinuria. (Fabrizi & Messa, 2105; Ozkok & Yildiz, 2014).
Mixed cryoglobulinemia is one the most common extrahepatic complication of hepatitis C infection. The disease is an immune-mediated process that causes deposition of immune complexes into the endothelium of small and medium-sized arteries and veins. This results in widespread inflammation and vasculitis. Cryoglobulinemia affects approximately 10%-70% of people with a hepatitis C infection, and the presence of the disease increases the risk of developing cirrhosis (Charles & Dustin, 2009). Hepatitis C is the cause of approximately 80% - 90% of all cases of mixed cryoglobulinemia (Cacoub et al., 2016; Sise et al., 2016).
The signs and symptoms of mixed cryoglobulinemia vary depending on the organs that are affected. The clinical presentation can be mild, with arthralgia and purpura, or it can be severe and cause significant and life-threatening organ damage (Cacoub et al., 2106). Cutaneous signs and symptoms are the most common clinical signs of mixed cryoglobulinemia (Garcovich, Garcovich, Capizzi, & Zocco, 2015).
Cutaneous complications of hepatitis C include diseases that are caused by the infection; diseases that are possibly associated with hepatitis C, and; diseases for which the association with hepatitis C is considered anecdotal: the reader is referred to Dedania & Wu (2015) for a complete list. The three cutaneous diseases that are caused by infection with hepatitis C are mixed cryoglobulinemia, lichen planus, and porphyria cutanea tarda (Dedania & Wu, 2015).
Cutaneous signs and symptoms of mixed cryoglobulinemia include leg ulcers, purpura, pruritus, Raynaud phenomenon, and urticaria (Dedania & Wu, 2015; Garcovich et al., 2015).
Lichen planus is an inflammatory disorder that affects the skin and the mucous membranes of the esophagus, eyes, genitals, mouth, respiratory tract, and urinary tract. Cutaneous signs and symptoms of lichen planus include discolored papules and skin and mucous membrane lesions (Dedania & Wu, 2015).
Porphyria cutanea tarda is caused by a disorder of enzymes that help produce heme and porphyrins. Porphyria cutanea tarda is characterized by hypo- or hyperpigmentation, skin rash, a variety of cutaneous lesions such as blisters, bullae, erosions, and vesicles, and many other cutaneous abnormalities (Dedania & Wu, 2105; Garcovich et al., 2015).
Infection with HIV is not caused by infection with hepatitis C, but giventhat coinfection with hepatitis C and HIV is very common and especially so in certain populations it should be discussed.
Someone who is infected with HIV is six times more likely to be infected with hepatitis C (Platt et al., 2016). Approximately one-third of all people infected with HIV are also infected with hepatitis C (Bichoupan, Deiterich, & Martel- Laferrière, 2014). The rate of hepatitis C/HIV co-infection in intravenous drug users has been reported to be > 80% (Platt et al., 2016). Furthermore, it is significantly higher in men who have sex with men than in the general population. The high incidence of concurrent infection with hepatitis C and HIV in these populations can be explained in part by IV drug use (the risk of percutaneous transmission of hepatitis C is 10 times higher than that of HIV), and unsafe, risky sex practices.
Concurrent infection with these viruses has very serious implications. An acute hepatitis C infection is more likely to become chronic; hepatitis C replication is increased; the hepatitis C virus is more easily transmitted; the viral load of hepatitis C in blood or semen is higher; liver damage occurs more often and progresses more quickly; mortality rates are higher, and; the response to treatment is attenuated (Platt et al., 2016; Chen, Feeney, & Chung, 2014; Hagan et al., 2014; van de Laar, Paxton, Zorgdrager, Cornelissenm & de Vries, 2011).
These adverse effects of hepatitis C/HIV co-infection may be caused by HIV-induced suppression of the immune system, infection of and damage to the hepatocytes by HIV, and/or an increase in hepatic and systemic inflammation but the mechanisms by which these processes occur is not completely understood (Chen et al., 2104; Page, Nelson, & Kelleher, 2011).
Hepatitis C is treated with drug therapy and every patient who has hepatitis C, with the exception of people who have an expected life span of < 12 months, should be considered for treatment (Chopra & Arora, September, 2015).
The latest iteration of direct acting antiviral drugs have produced a cure rate of > 90% (and in many cases a higher cure rate) and a sustained virologic response (SVR), the definition of cure, has many benefits (AASLD/ISDA, 2016; Chopra & Arora, September 2015; Westbrook & Desheiko, 2014):
These benefits and cure rates are relatively new developments. Drug therapy for hepatitis C has gone through five stages and with each one the cure rate has improved (Wang et al., 2016). The first treatment for hepatitis C was injectable interferon and the cure rate was 15%. Following that, patients were treated with interferon and ribavirin and the cure rate was 28%. Pegylated interferon and ribavirin cured 44% of all patients and in the fourth stage of hepatitis C drug therapy, first generation direct-acting antivirals, given together with interferon, and ribavirin, produced a cure rate of 75%. However, the interferon-based therapies, and especially the interferon/ribavirin/first generation direct-acting antiviral regimen, caused many side effects and adverse effects. Some of these were quite serious and these drugs had to be taken for 11 months. As a result, almost 25% of all patients who were on these regimens could not complete the course of treatment either because of the adverse effects or because they simply could not tolerate the therapy. In contrast, the second generation direct-acting antivirals typically cause a few mild and tolerable side effects, they are oral medications that are taken once a day, and the duration of treatment is usually 2 weeks.
This module will only outline the care of treatment-naive adult patients who have a genotype 1a uncomplicated hepatitis C infection, without advanced liver damage, and who are prescribed second generation direct-acting antiviral drugs. There are obviously many more clinical situations to consider: treatment experienced patients, partial responders, patients who have cirrhosis, patients with other genotypes, and patients with chronic medical conditions that influence how drug therapy is applied. However, it is beyond the scope of this module to discuss them all and the reader is referred to the 2016 AASLD/ISDA treatment guidelines. These are available on the HCVGuidelines.org website.
The direct-acting antivirals interrupt hepatitis C virus replication, each of them doing so by a different mechanism. The AASLD/IDSA treatment regimens for the second generation direct-acting antiviral are listed below. These regimens have equivalent success rates but they have not been directly compared.
Each of these regimens has been categorized as Class I and Category A, except for daclatasvir plus sofosbuvir which is category B.
Class I indicates that there is evidence and/or general agreement that a given diagnostic evaluation, procedure, or treatment is beneficial and effective. Category A indicates that the evidence for effectiveness of the therapy was derived from multiple randomized clinical trials, meta-analyses, or their equivalent. Category B indicates that the data for the effectiveness of the therapy was derived from a single randomized trial, nonrandomized studies, or their equivalent (AASLD/IDSA, 2016).
The regimens listed in table 3 are for patients who have chronic infection with genotype 1a, are treatment naïve, and who do not have cirrhosis.
|Elbasvir 50 mg/grazoprevir 100 mg for 12 weeks. This therapy should be used for patients in whom no baseline high fold-change NS5A RAVs for elbasvir aredetected; this would indicate a genetic variation that would negatively affect drug therapy.|
|Ledipasvir 90 mg/sofosbuvir 400 mg for 12 weeks.|
|Paritaprevir 150 mg/ritonavir 100 mg/ombitasvir 25 mg. This is given along with dasabuvir (250 mg, twice a day) and ribavirin (weight-dosed) for 12 weeks.|
|Simeprevir 150 mg and sofosbuvir 400 mg for 12 weeks.|
|Daclatasvir 60 mg and sofosbuvir 400 mg.|
The treatment regimen is 12 weeks. Viral load is checked during therapy (The prescriber determines when this is done) and three months after the last dose. If there is no virus detected three months after the last dose, this is considered to be a SVR and the risk of relapse is very small.
The second generation direct-acting antivirals are generally well tolerated. Asthenia, headache, insomnia, fatigue, nausea, and skin rashes are some of the common side effects of these drugs and are typically minor (Pockros, 2016).
Drug interactions are numerous and potentially serious. Amiodarone, antacids, anti-epileptics, anti-retrovirals, and lipid-lowering medications (the statins) are of particular concern; check package inserts or a drug information source for specifics for each drug.
Patients who are infected with hepatitis C should receive vaccinations for hepatitis A and hepatitis B, and if the patient has cirrhosis he/she should be given the pneumococcal vaccine.
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. Patients should be told that a SVR does not mean that re-infection cannot happen.
Alcohol use should be discouraged, and excessive use of alcohol should be avoided completely. There is no specific diet that must be followed. However, if the patient is overweight or obese, he/she should be encouraged to lose weight and exercise because obesity and the metabolic syndrome can cause insulin resistance which, in turn, can increase the progression of fibrosis (AASLD/IDSA, 2016). Smoking cessation is also important as smoking has been associated with fibrosis (Chopra & Pockros, March, 2015).
Nursing care of patients who have hepatitis C has been greatly simplified by the use of the second generation direct-acting antivirals. 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 hepatitis C has, to a large degree, shifted from physical care to education and support: education about life style issues relevant to hepatitis C, 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 hepatitis C will involve:
Hepatitis C is chronic infection of the liver that increases the risk of mortality, causes serious extra-hepatic complications, it is an important cause of liver cancer, and a hepatitis C infection can negatively affect the progression of many common, chronic diseases.
Hepatitis C is the most common blood-borne disease in the United States and the number of people needing and seeking treatment will increase in the next several decades. Highly effective and well tolerated drug therapy has been developed and hepatitis C is now considered a curable disease. However, treating all of the people who will need it will be a significant challenge for several reasons: many people who have the infection remain undiagnosed; the clinical progression of hepatitis C is almost always silent; the prevalence of factors such as diabetes and obesity that negatively affect the progression of hepatitis C are increasing, and; the second generation direct-acting antivirals are very, very expensive.
Despite these challenges, the outlook is very good for patients whose infection is detected and who are able to receive the latest treatment. The cure rates are > 90%, the course of treatment is 12 weeks, and the drugs are comparatively benign. The challenge for healthcare professionals and patients is now to realize that life style factors can worsen an infection with hepatitis C, and to maintain optimal health patients need to change health habits: abstain from alcohol, exercise, lose weight, and stop smoking.
Afdhal, N.H., Bacon, B.R., Patel, K., Lawitz, E. J., Gordon, S.C., Nelson, D.R.,…McHutchison, J.G. (2015). Accuracy of fibroscan, compared with histology, in analysis of liver fibrosis in patients with hepatitis B or C: a United States multicenter study. Clin Gastroenterol Hepatol, 13(4), 772-779.
Allison, W.E., Chiang, W., & Rubin, A, (2016). Hepatitis C virus infection in the 1945-1965 birth cohort (baby boomers) in a large urban ED. Am J Emerg Med, 34(4),697-701.
Allison, M.E., Wreghitt, T., Palmer C.R. & Alexander, G.J. (1994). Evidence for a link between hepatitis C virus infection and diabetes mellitus in a cirrhotic population. Jf Hepato, 21(6), 1135-1139
Alter, M.J. (2011). HCV routes of transmission: What goes around comes around. Semin Liver Dis, 31(4), 340-346.
Amarapurkar, D., & Amarapurkar, A. (2015). Indications of liver biopsy in the era of noninvasive assessment of liver fibrosis. J Clin Exp Hepatol, 5(4),314-319.
AASLD/IDSA - American Association For The Study Of Liver Diseases/ Infectious Diseases Society of America. Recommendations for Testing, Managing, and Treating Hepatitis C. February 24, 2016. Accessed April 23, 2016 (Visit Source).
Am J Transplant. (2016). CDC urging dialysis providers and facilities to assess and improve infection control practices to stop hepatitis C virus transmission in patients undergoing hemodialysis. Am J Transplant, 16(5), 1633-1634. [No authors listed]
Bal, A., & Petrova, A. (2016). Single clinical practice's report of testing initiation, antibody clearance, and transmission of hepatitis C virus (HCV) in infants of chronically HCV-infected mothers. Open Forum Infect Dis. 2016 Feb 8;3(1):ofw021. doi: 10.1093/ofid/ofw021. eCollection 2016.
Bichoupan, K., Dieterich, D.T., & Martel-Laferrière,V. (2014). HIV-hepatitis C virus co-infection in the era of direct-acting antivirals. Curr HIV/AIDS Rep, 11(3):241-249.
Binka, M., Paintsil, E., Patel, A., Lindenbach, B.D., & Heimer. R. (2015). Disinfection of syringes contaminated with hepatitis C virus by rinsing with household products. Open Forum Infect Dis, 2015 Feb 23;2(1):ofv017. doi: 10.1093/ofid/ofv017. eCollection 2015.
Binka, M., Paintsil, E., Patel, A., Lindenbach, B.D., & Heimer R. (2015). Survival of hepatitis C virus in syringes is dependent on the design of the syringe-needle and dead space volume. PLoS One. 2015 Nov 4;10(11):e0139737. doi: 10.1371/journal.pone.0139737. eCollection 2015.
Bostan, N., & Mahmood, T. (2010). An overview about hepatitis C: A devastating virus. Crit Rev Microbiol, 36(2), 91-133.
Bradshaw, D., Lamoury, F., Catlett, B., Applegate, T.L., Mcallister, J., Dore, G.J.,…Danta, M. (2015). A comparison of seminal hepatitis C virus (HCV) RNA levels during recent and chronic HCV infection in HIV-infected and HIV-uninfected individuals. J Infect Dis, 211(5), 736-743.
Branch-Elliman, W., Weiss, D., Balter, S., Bornschlegel, K., & Phillips. M. (2013). Hepatitis C transmission due to contamination of multi-dose medication vials: Summary of an outbreak and a call to action. Am J Infect Control, 41(1), 92-94.
Cacoub, P., Comarmond, C., Domont, F., Savey, L., Desbois, A.C., & Saadoun. D. (2016). Extrahepatic manifestations of chronic hepatitis C virus infection. Ther Adv Infect Dis, 3(1), 3-14.
Caiaffa, W.T., Zocratto, K.F., & Osimani, M.L, (2011). Hepatitis C virus among non-injecting cocaine users (NICUs) in South America: can injectors be a bridge? Addiction. 2011 Jan;106(1):143-51. doi: 10.1111/j.1360-0443.2010.03118.x. Epub 2010 Oct 19.
Campos-Varela I., Lai J.C., Verna E.C., O’Leary, J.G., Todd Stravitz, R., Forman, L.M.,…Terrault, N.A. (2015). Hepatitis C genotype influences post-liver transplant outcomes. Transplantation,99(4):835-840.
Castéra, L., Foucher, J., Bernard P.H.,et al. (2010). Pitfalls of liver stiffness measurement: a 5-year prospective study of 13,369 examinations. Hepatology. 51,(3),828-835.
Centers for Disease Control and Prevention. (2015). Viral Hepatitis – Hepatitis C. Testing Recommendations for Hepatitis C Virus. October 15, 2015. Accessed May 3, 2016 (Visit Source).
Centers for Disease Control and Prevention. (2015). Viral Hepatitis - Recommendations for Specific Populations and Settings. People born 1945-1965 & hepatitis C. May 31, 2015. Accessed May 2, 2016 (Visit Source).
Centers for Disease Control and Prevention. (2016). Viral Hepatitis - Hepatitis C Information. Hepatitis C FAQs For Health Professionals. March 11, 2016. Accessed April 26, 2016 (Visit Source).
Charles, E.D., & Dustin L.B. (2009). Hepatitis C virus-induced cryoglobulinemia. Kidney Int, 76(8), 818-824.
Chen, J.Y., Feeney, E.R., & Chung, R.T. (2014). HCV and HIV co-infection: mechanisms and management. Nat Rev Gastroenterol Hepatol. 2014,11(6),362-371.
Chopra S., & Pockros, P.J. (2015). Overview of the management of chronic hepatitis C virus infection. UpToDate. March 30, 2015. Accessed April 25, 2016 (Visit Source).
Chopra, S., & Arora, S. (2015). Patient evaluation and selection for antiviral therapy for chronic hepatitis C virus infection. UpToDate. September 11, 2015. Accessed April 29, 2016 (Visit Source).
Chopra, S. (2015). Characteristics of the hepatitis C virus. UpToDate. October 14, 2015. Accessed April 17, 2016 (Visit Source).
Curry, M.P., & Afdhal, N.H. (2016). Noninvasive assessment of hepatic fibrosis: Overview of serologic and radiographic tests. UpToDate. March 1, 2016. Accessed May 3, 2016 (Visit Source).
Choo, Q.L., Kuo, G., Weiner, A.J., Overby, L.R., Bradley, D.W., & Houghton, M. (1989). Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science, 244 (4902), 359 - 362.
Davis, G.L., Alter, M.J., El-Serag, H., Poynard, T., & Jennings L.W. (2010). Aging of hepatitis C virus (HCV)-infected persons in the United States: A multiple cohort model of HCV prevalence and disease progression. Gastroenterology, 138(2), 513-521.
Dedania, B., & Wu, G.Y. (2015). Dermatologic extrahepatic manifestations of hepatitis C. J Clin Transl Hepatol, 3(2),127-133.
Dhawan, V. K. (2013). Hepatitis C. eMedicine, September 18, 2013. Retrieved 10/25/13 (Visit Source).
Dhingra, S., Ward, S.C., & Thung, S.N. (2016). Liver pathology of hepatitis C, beyond grading and staging of the disease. World J Gastroenterol, 22(4),1357-1366
Dietrich, C.F. (2015). Non-invasive assessment of hepatic fibrosis: Ultrasound-based elastography. UpToDate. October 15, 2015. Accessed May 3, 2016 (Visit Source).
Dunkelberg, J.C., Berkley, E.M., Thiel, K.W., & Leslie, K.K. (2014). Hepatitis B and C in pregnancy: a review and recommendations for care. J Perinatol, 34(12), 882-891.
Edlin, B.R., Eckhardt, B.J., Shu, M.A., Holmberg, S.D., & Swan. T. (2015). Toward a more accurate estimate of the prevalence of hepatitis C in the United States. Hepatology, 62(5),1353-1363.
El-Shabrawi, M.H., & Kamal, N.M. (2013). Burden of pediatric hepatitis C. World J Gastroenterol,19(44),7880-7888.
Eslam, M., Khattab, M.A., & Harrison, S.A. (2011). Insulin resistance and hepatitis C: An evolving story. Gut, 60(8), 1139-1151.
Fabrizi, F., & Messa, P. (2015). Transmission of hepatitis C virus in dialysis units: a systematic review of reports on outbreaks. Int J Artif Organs, 38(9), 471- 480.
Fernandez-Rodriguez, C.M., Gutierrez M.L., Lledó, J.L., & Casas, M.L. (2011). Influence of hepatitis B virus infection in chronic hepatitis C outcomes. World Jf Gastroenterol, 17(12), 1558-1562.
Gamage, D.G., Read, T.R.H., Bradshaw, C.S., Hocking, J.S., Howley, K., Chen, M.Y., & Fairley, C. (2011). Incidence of hepatitis-C among HIV infected men who have sex with men (MSM) attending a sexual health service: a cohort study. BMC Infect Disease, Feb. 3;11:39.
Garcovich, S., Garcovich, M., Capizzi, R., Gasbarrini, A., & Zocco. M.A. (2015). Cutaneous manifestations of hepatitis C in the era of new antiviral agents. World J Hepatol, ,7(27), 2740-2748
Gill, K., Ghazinian, H., Manch R., & Gish, R. (2016). Hepatitis C virus as a systemic disease: reaching beyond the liver. Hepatol Int,10(3):415-423.
Gorgos, L. (2013). Sexual transmission of viral hepatitis. Infect Dis Clin North Am, 27(4), 811-836.
Grebely, J., & Dore, G.J. (2011). What is killing people with hepatitis C virus infection? Semin Liver Dis, 31(4),331-339.
Gross, C., Akoth E., Price, A., Kattakuzhy, S., Silk, R., & Rosenthal, E. (2016). HIC/HCV co-infection: Overcoming barriers to treatment. J Assoc Nurses AIDS Care. 2016 Feb 20. pii: S1055-3290(16)00048-0. doi: 10.1016/j.jana.2016.02.009. [Epub ahead of print]
Hagan, H., Neurer, J., Jordan, A.E., Des Jarlais, D.C., Wu, J., Dombrowski, J.,…Kessler, J. (2014). Hepatitis C virus infection among HIV-positive men who have sex with men: protocol for a systematic review and meta-analysis. Syst Rev, Mar 26;3:31. doi: 10.1186/2046-4053-3-31
Halfon, P. (2013). Sexual transmission of HCV among monogamous couples: be careful with reassuring messages. Hepatology, 58(3), 1190-1191.
Harrison, S.S. (2015). Utilization of FibroScan testing in hepatitis C virus management. Gastroenterol Hepatol (N Y), 11(3),187-189
He, T., Li, K., Roberts, M.S., Spaulding, A.C., Ayer, T., Grefenstette, J.J., & Chhatwal, J. (2016). Prevention of hepatitis C by screening and treatment in U.S. prisons. Ann Intern Med,164(2):84-92.
Henderson, D. K. (2003). Managing occupational risks for hepatitis C transmission in the healthcare setting. Clin Microbiol Rev, 16 (3), 546-568.
Hosoglu, S., Celen, M.C., Akalin, S., Geyik, M.F., Soyoral, Y., & Kara, I.H. (2003). Transmission of hepatitis C by blood splash into conjunctiva in a nurse. Amer J Infect Control. 31(8), 502-504.
Hsu, C.S., Liu, C.H., Liu, C.J., Chen, C.L., Hwang, J.J., Lai, M.Y.,…Kao, J.H. (2010). Association of metabolic profiles with hepatic fibrosis in chronic hepatitis C patients with genotype 1 or 2 infection. J Gastroenterol Hepatol. 25(5), 970-977.
Jang, J.Y., Jeong, S.W., Cheon, S.R., Lee, S.H., Kim, S.G., Cheon, Y.K.,…Kim, B.S. (2011). Clinical significance of occult hepatitis B virus infection in chronic hepatitis C patients. Korean J Hepatol, 17(3), 206-212.
Khaderi, S., Shepherd, R., Goss, J.A., & Leung, D.H. (2014). Hepatitis C in the pediatric population: transmission, natural history, treatment and liver transplantation. World J Gastroenterol, 20(32),11281-11286.
Knobler, H., & Malnick, S. (2016). Hepatitis C and insulin action: An intimate relationship. World J Hepatol, 8(2),131-138.
Kralj, D., Jukic, L.V., Stojsavljevic, S., Duvnjak, M., Smolic M,, & Curcic, I.B. (2016). Hepatitis C virus, insulin resistance, and steatosis. J Clin Transl Hepatol, 28,4(1), o66-75.
Lauring, A.S., & Andino, R. (2010). Quasispecies theory and the behavior of RNA viruses. PLoS Pathogens, 6(7), e1001005.
Lee, J., Conniff, J., Kraus, C., & Schrager. S. (2015). A brief clinical update on hepatitis C – the essentials. WMJ, 114(6), 263-269.
Ly, K.N., Hughes, E.M., Jiles, R.B., & Holmberg, S.D. (2016). Rising mortality associated with hepatitis C virus in the United States, 2003-2013. Clin Infect Dis. 2016 Mar 1. pii: ciw111. [Epub ahead of print]
Macías, J., Palacios, R.B., Claro, E., Vargara. S., Mira, J.A., Merchante, N.,…Pineda, J.A. (2008). High prevalence of hepatitis C virus infection among noninjecting drug users: association with sharing the inhalation implements of crack. Liver Int, 28(6), 781-786.
Mahajan, R., Xing, J., & Liu, S.J. (2014). Mortality among persons in care with hepatitis C virus infection: the Chronic Hepatitis Cohort Study (CHeCS), 2006-2010. Clin Infect Dis, 58(8),1055-1061
Manos, M.M., Shvachko, V.A., Murphy, R.C., Arduino, J.M., &Shire, N.J. (2012). Distribution of hepatitis C virus genotypes in a diverse US integrated health care population. J Med Virol, 84(11), 1744-1750.
McGuire, B.M., Julian, B.A., Bynon, J.S., Cook, W.J., King, S.J., Curtis, J.J.,…Eckhoff, D.E. (2006). Brief communication: Glomerulonephritis in patients with hepatitis C cirrhosis undergoing liver transplantation. Ann Internal Med,144(10), 735-741.
Melo-Villar, L., Lampe, E., de Almeida, A.J., Scalioni, L.P., Lewis-Ximenez, L.L., Miguel, J.Cl,…Romero-Gomez, M. (2015). Hypovitaminosis D and its relation to demographic and laboratory data among hepatitis C patients. Ann Hepatol, 14(4), 457-463.
Morales, J.M., Kamar, N., & Rostaing L. (2012) Hepatitis C and renal disease: epidemiology, diagnosis, pathogenesis, and therapy. Contrib Nephrol, 176, 10-23.
Mukherjee, S, & Dhawan, V.K. (2010). Hepatitis C. eMedicine, June 25, 2010. Retrieved March 14, 2012 (Visit Source).
Nash, K.L., Woodall, T., Brown, A.S.M., Davies, S.E., & Alexander, G.J.M. (2010). Hepatocellular carcinoma in patients with chronic hepatitis C virus infection without cirrhosis. World Jf Gastroenterol, 16(32), 4061-4065.
Novo-Veleiro, I., Alvela-Suárez, L., Chamorro, A.J., Gonzáles-Sarmiento, R., Laso, F., & Marcos, M. (2016). Alcoholic liver disease and hepatitis C virus infection. World J Gastroenterol, 22(4), 1411-1120.
Ozkok, A., & Yildiz, A. (2014). Hepatitis C virus associated glomerulopathies. World J Gastroenterol, 20(24),7544-7554.
Page, E.E., Nelson, M., & Kelleher, P. (2011). HIV and hepatitis C co-infection: pathogenesis and microbial translocation. Curr Opin HIV AIDS, 6(6), 472-477.
Page, E.E., & Nelson, M. Heptatis C and sex. (2016) Clin Med (London)), 16(2), 189-192.
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. J Infect Dis, 209(8),1205-1211.
Pang, J.X., Pradhan, F., Zimmer, S., Niu, S., Crotty, P., Tracey, J.,…Myers, R. (2014). The feasibility and reliability of transient elastography using Fibroscan®: a practice audit of 2335 examinations. Can J Gastroenterol Hepatol, 28(3), 143-149.
Pearlman, B. (2004). Hepatitis C infection: A clinical review. South Med J, 97 (4) 365-376.
Perazzo, H., Veloso, V.G., Grinzstein, B., Hyde, C., & Castro, R. (2015). Factors that could impact on liver fibrosis staging by transient elastography. Int J Hepatol, 2015;2015:624596. doi: 10.1155/2015/624596. Epub 2015 Dec 6.
Platt, L., Easterbrook, P., Gower, E., McDonald, B., Sabin, K., McGowan, C.,…Vickerman, P. (2016). Prevalence and burden of HCV co-infection in people living with HIV: a global systematic review and meta-analysis. Lancet Infect Dis. 2016 Feb 24. pii: S1473-3099(15)00485-5. doi: 10.1016/S1473-3099(15)00485-5. [Epub ahead of print]
Pockros, P.J. (2016). Direct-acting antivirals for the treatment of hepatitis C virus infection. UpToDate. February 9, 2016. Accessed May 5, 2016 (Visit Source).
Pondé, R.A. (2011). Hidden hazards of HCV transmission. Med Microbiol Immunol, 200,(1), 7-11.
Rosen, H.R. (2011). Chronic hepatitis C infection. New Eng J Med, 364(25), 2429-2438
Saludes, V., Esteve, M., Casas, I., Ausina, V., Martró, E. (2013). Hepatitis C virus transmission during colonoscopy evidenced by phylogenetic analysis. J Clin Virol, 57(3),263-266.
Sayiner, M., Wymer, M., Golabi, P., Ford, J., Srishord, I., & Younossi, Z.M. (2016.
Presence of hepatitis C (HCV) infection in Baby Boomers with Medicare is independently associated with mortality and resource utilisation. Aliment Pharmacol Ther, 43(10),1060-1068.
Schiff, E.R. (2011). Diagnosing and treating hepatitis C virus infection. Am J Manag Care, 17(Suppl. 4), S108-S115.
Shire, N.J., & Shermna,. K.E. (2015). Epidemiology of hepatitis C virus. A battle of new frontiers. Gastroenterol Clin North Am. 44(4), 699-716
Sise, M.E., Bloom, A.K., Wisocky, J., Lin, M.V., Gustafson, J.L., Lundquist, A.L.,…Chung, R., (2016). Treatment of hepatitis C virus-associated mixed cryoglobulinemia with direct-acting antiviral agents. Hepatology, 63(2),408-417
Stasi, C., & Milani, S. (2016). Non-invasive assessment of liver fibrosis: Between prediction/prevention of outcomes and cost-effectiveness. World J Gastroenterol, 22(4),1711-1720
Strasser, M., Aigner, E., Schmid, I., Stadlmayr, A., Niederseer, D., Patsch, W., & Datz, C. (2013). Risk of hepatitis C virus transmission from patient to healthcare worker: A prospective, observational study. Infect Control Hosp Epidemiol. 34 (7), 759-761.
Terrault, N.A., Dodge, J.L., Murphy, E.L., Tavis, J.E., Kiss, A., Levin, T.R.,…Alter, M.J. (2013). Sexual transmission of hepatitis C virus among monogamous heterosexual couples: the HCV partners study. Hepatology, 57(3):881-889.
Testino, G., Leone, S., & Borro, P.(2016). Alcoholic liver disease and the hepatitis C virus: an overview and a point of view. Minerva Med. 2016 Mar 24. [Epub ahead of print]
Tholey, D.M., & Ahn, J. (2015). Impact of hepatitis C virus infection on hepatocellular carcinoma. Gastroenterol Clin North Am. 44(4), 761-773.
Tohme, R.A., & Holmberg, S.D. (2010). Is sexual contact a major mode of hepatitis C virus transmission? Heptalology, 52(4),1497-1505.
Tovo, P.A., Calitri, C., Scolfaro, C., Gabiano, C., & Garazzino, S. (2016). Vertically acquired hepatitis C virus infection: Correlates of transmission and disease progression. World J Gastroenterol, 22(4),1382-1392.
Valerio, H., Goldberg, D.J., & Lewsey J. (2015). Evidence of continued injecting drug use after attaining sustained treatment-induced clearance of the hepatitis C virus: Implications for reinfection. Drug Alcohol Depend, Sept 1;154:125-131.
Vanni, E., Bugianesi, E., & Saracco, G. (2016). Treatment of type 2 diabetes mellitus by viral eradication in chronic hepatitis C: Myth or reality? Dig Liver Dis, 48(2),105-111.
van de Laar, T.J.W., Paxton, W.A., Zorgdrager, F., Cornelissen, M., & de Vries H.J.C. (2011). Sexual transmission of hepatitis C virus in human immunodeficiency virus-negative men who have sex with men: A series of care reports. Sex Transm Dis, 38(2), 102-104.
Viganò, M., & Colombo. M. (2015). Extrahepatic manifestations of hepatitis C virus. Gastroenterol Clin North Am, 44(4), 775-791.
Wang, Y., Keck, Z.Y., & Foung, S.K.H. (2011). Neutralizing antibody response to hepatitis C virus. Viruses, 3(11), 2127-2145.
Wang, J.H., Pianko, M.J., Ke, X., Herskovic,A., Hershow, R., Colter, S.J.,…Rong, L. (2011). Characterization of antigenic variants of hepatitis C virus in immune evasion. Virol J, 8, 377-388.
Wang, C.C., Cook, L., Tapia, K.A., Holte, S., Krows, M., Bagabag, A.,…Jerome, K.R. (2011). Cervicovaginal shedding of hepatitis C viral RNA is associated with the presence of menstrual or other blood in cervicovaginal fluids. J Clin Virol, 50(1), 4-7.
Wang, L.S., D'Souza, L.S., & Jacobson, I.M. (2016). Hepatitis C - A clinical review. J Med Virol, 2016 Apr 20. doi: 10.1002/jmv.24554. [Epub ahead of print]
Westbrook, R.H., & Dusheiko, G. (2014). Natural history of hepatitis C. J Hepatol, 61(1 Suppl), S58-S68.
White, D.L., Richardson, P., Tayoub, N., Davila, J.A., Kanwal, F., & El-Serag, H.B. (2015). The updated model: An adjusted serum alpha-fetoprotein-based algorithm for hepatocellular carcinoma detection with hepatitis C virus-related cirrhosis. Gastroenterology, 149(7), 1986-1987.
Wong, G.L. (2013). Update of liver fibrosis and steatosis with transient elastography (Fibroscan). Gastroenterol Rep (Oxf), 1(1),19-26.
Workowski, K.A., & Bolan,. G.A. (2015). Sexually Transmitted Diseases Treatment Gudelines, 2015. MMWR, 64(3), 1-140.
This course is applicable for the following professions:
Advanced Registered Nurse Practitioner (ARNP), Certified Registered Nurse Anesthetist (CRNA), Clinical Nurse Specialist (CNS), Licensed Practical Nurse (LPN), Licensed Vocational Nurses (LVN), Midwife (MW), Registered Nurse (RN)
Advance Practice Nurse Pharmacology Credit, CPD: Practice Effectively, CPD: Preserve Safety, Infection Control/Disease, Medical Surgical