Hepatitis C

Hepatitis C (HCV) is the most common, chronic bloodborne pathogen in the United States (US) (Pearlman, 2004). According to the Centers for Disease Control (CDC) US statistics, approximately 3.2 million people have chronic HCV infection causing an estimated 8,000-10,000 deaths every year (CDC, 2008).

HCV is most prevalent among people born during 1945-1965. The majority of these people were probably infected during the 1970s and 1980s when HCV infection rates were highest (CDC, 2008). There is a decreasing incidence of HCV in the US. However, because of the significant lag time between infection onset and hepatic symptoms, the prevalence of HCV related chronic liver disease is increasing (Pearlman, 2004). The following are the Center for Disease Control (CDC) statistics about HCV incidence (CDC, 2008, pg. 1).

HCV is transmitted primarily through large or repeated direct percutaneous exposures to blood. Some people are at higher risk of an HCV infection than the general population.

People at increased risk for HCV infection (CDC, 2008, pg. 1):

1. Current or former injection drug users
2. Recipients of clotting factor concentrates made before 1987
3. Recipients of blood transfusions or solid organ transplants before July 1992
4. Chronic hemodialysis clients
5. Persons with known exposures to HCV, such as healthcare workers after needlesticks involving HCV-positive blood recipients of blood or organs from a donor who tested HCV-positive
6. Persons with HIV infection
7. Children born to HCV-positive mothers

The most common transmission means use to be blood transfusion, but that is now rare in the US since blood screening became available in 1992. The occurrence rate of transmission from transfusion is now one chance per two million transfusions (CDC, 2008).

Now the most common means of transmission is injection drug use. One third of injection drug users age 18-30 are HCV infected, but the occurrence in older or previous injection drug users is about 70%-90% (CDC, 2008). The higher prevalence is due to needle sharing during the 1970s and 1980s. Educational initiatives have reduced this transmission mode.

HCV prevalence among healthcare workers is not higher than in the general population. It averages 1%-2%, and is 10 times lower than that for HBV infection. A history of unintentional needle-stick injury was the only occupational risk factor independently associated with HCV infection. The risk for HCV infection after a needlestick or sharps exposure to HCV-positive blood is approximately 1.8% (range: 0%-10%). When healthcare professionals understand and adhere to standard precautions, safe injection practice, and other guidance for reducing bloodborne pathogen exposure risk, transmission in healthcare settings is infrequent (CDC, 2008).

The subject of HCV transmission from a healthcare worker to a client is controversial. Transmission has been reported rarely, but more than half the reported cases had other risk factors (Pearlman, 2004). "CDC's recommendations for prevention and control of HCV infection specify that persons should not be excluded from work, school, play, child care, or other settings on the basis of their HCV infection status. There is no evidence of HCV transmission from food handlers, teachers, or other service providers in the absence of blood-to-blood contact" (CDC, 2008, pg.1).

The average rate of HCV infection among infants born to HCV-positive, HIV negative women is 5%-6%. The average infection rate for infants born to women co-infected with HCV and HIV is higher, at 14% to 17%. Data regarding the relationship between delivery mode and HCV transmission are limited. What is available indicates no difference in infection rates between infants delivered vaginally compared with cesarean-delivered infants. The transmission of HCV infection through breast milk has not been documented. In the studies that have evaluated breastfeeding in infants born to HCV-infected women, the average rate of infection was 4% in both breastfed and bottle-fed infants. Breast-feeding is not contraindicated for HCV-positive mothers unless the nipples are cracked and bleeding.

Transmission can occur during sexual contact with an HCV infected person; but sexual contact is an inefficient means of transmission. The same is true of transmission due to sharing personal items that are contaminated with infectious blood, like toothbrushes and razors (CDC, 2008). The spread of HCV within a household is most likely due to direct percutaneous exposure to the blood of the infected person.

There is no US data indicating that people with exposures to tattooing and body piercing alone are at increased risk of HCV infection (CDC, 1998). In other countries, HCV infection has been associated with folk medicine practices, tattooing, body piercing, and commercial barbering.

Healthcare, emergency medical, and public safety workers should be educated regarding the risk for and prevention of bloodborne infections. Standard precautions and safe injection practice should be implemented to prevent exposure to blood. Protocols should be in place for the reporting and follow-up of percutaneous or permucosal exposures to blood or body fluids.

Healthcare professionals responsible for overseeing clients receiving home infusion-therapy should ensure that clients and caregivers are informed of potential risk for infection with bloodborne pathogens, and should assess their ability to use adequate infection-control practices. Clients and families should receive training with a standardized curriculum that includes appropriate infection-control procedures, and these procedures should be evaluated regularly through home visits.

Intensive efforts must be made to educate new staff and re-educate existing staff regarding hemodialysis-specific infection control practices. Hemodialysis center precautions are more stringent than standard precautions. Isolation of HCV-positive clients during dialysis is neither necessary nor recommended. Routine precautions for the care of all hemodialysis clients (CDC, 1998):

• Clients should have specific dialysis stations assigned to them, and chairs and beds should be cleaned after each use.
• Gloves should be used whenever clients or hemodialysis equipment is touched.
• Sharing among clients of ancillary supplies such as trays, blood pressure cuffs, clamps, scissors, and other nondisposable items should be avoided.
• Nondisposable items should be cleaned or disinfected appropriately between uses.
• Medications and supplies should not be shared among clients, and medication carts should not be used.
• Medications should be prepared and distributed from a centralized area.

The goals of HCV prevention and control efforts are: 1) to reduce the incidence of new infections by reducing HCV transmission; and 2) to reduce the risk of chronic liver disease in HCV-infected individuals through appropriate medical management and counseling (CDC, 2001). These goals can be achieved by identifying persons at risk for infection and providing them with education and risk reduction counseling. The CDC recommends the following comprehensive strategy to prevent and control HCV infection and related disease (CDC, 1998).

As part of a complete medical history for all clients, it is important to obtain a history of high-risk exposures associated with HCV and other bloodborne pathogens, HCV testing, and appropriate medical services including substance abuse treatment. Preventing or changing behaviors and activities that place persons at risk for HCV infection should reduce disease transmission. Appropriate testing, medical management and substance abuse counseling and treatment should reduce the risk of chronic liver disease (CDC, 2001). 

HCV infection can be detected by anti-HCV screening tests (enzyme immunoassay) 4-10 weeks after infection. Anti-HCV can be detected in >97% of persons by 6 months after exposure (CDC, 2008). The following are the laboratory criteria for diagnosis of HCV infection developed by the CDC (2008, pg. 1). Only one criterion need be met to meet the diagnosis:

1. Anti-HCV positive (repeat reactive) by EIA, verified by an additional more specific assay (e.g. RIBA for anti-HCV or nucleic acid testing for HCV RNA),
2. HCV RIBA positive,
3. Nucleic acid test for HCV RNA positive,
4. Report of HCV genotype
5. Anti-HCV screening-test-positive with a signal to cut-off ratio predictive of a true positive as determined for the particular assay (e.g., ≥3.8 for the enzyme immunoassays) as determined and posted by CDC

False positive anti-HCV test is possible. It is important to confirm a positive anti-HCV test with a supplemental test, such as RIBA (recombinant immunoblot assay). False negative tests can also occur. People with early HCV infection might not yet have developed antibody levels high enough that the test can measure. In addition, some persons might lack the immune response necessary for the test to work well. In these persons, further testing such as PCR for HCV RNA may be considered (CDC, 2008). HCV testing is recommended for anyone at increased risk for HCV infection, all persons with HIV infection, and clients with signs or symptoms of liver disease (e.g., abnormal liver enzyme tests) (CDC, 2008).

Infants born to HCV positive mothers should not be tested for anti-HCV until 18 months because the anti-HCV from the mother might last until this age. Testing for HCV RNA could be performed at or after the infant's first well-child visit at age 1-2 months if earlier diagnosis is desired. HCV RNA testing should then be repeated at a subsequent visit, independent of the initial HCV RNA test result (CDC, 2008).

Pregnant women have no greater risk of being infected with HCV than non-pregnant women and interventions to prevent mother-to-child transmission are lacking. Therefore, routine anti-HCV testing of pregnant women is not recommended. Pregnant women should be tested for anti-HCV only if they have risk factors for HCV infection (CDC, 2008).

Institutions should establish policies and procedures for HCV testing of people after percutaneous or permucosal exposures to blood and ensure that all personnel are familiar with these policies and procedures.

IG is not effective for postexposure prophylaxis of HCV. Antiviral agents (e.g., interferon) are not recommended to prevent HCV infection. The mechanisms of the effect of interferon in treating HCV are not understood, and an established infection might need to be present for interferon to be effective.

Limited data indicate that antiviral therapy might be beneficial when started early in the course of HCV infection, but no guidelines exist for administration of therapy during the acute phase of infection. When HCV infection is identified early, the individual should be referred for medical management to a specialist in this area.

People who are newly infected with HCV are usually asymptomatic, so acute HCV is rarely identified or reported (CDC, 2008). 20%-30% of newly infected people have symptoms that can include (CDC, 2008, pg. 1):

• Fever
• Fatigue
• Dark urine
• Clay-colored stool
• Abdominal pain
• Loss of appetite
• Nausea
• Vomiting
• Joint pain
• Jaundice

In symptomatic people, the average time period from exposure to symptom onset is 4-12 weeks (range: 2-24 weeks) (CDC, 2008).

No clinical or epidemiologic features among people with acute infection have been found to be predictive of either persistent infection or chronic liver disease. Most people with chronic HCV infection are asymptomatic. Most are not diagnosed until they are screened for a blood donation or when elevated alanine aminotransferase (ALT, a liver enzyme) levels are detected during routine examinations (CDC, 2008). Those people who are symptomatic have chronic liver disease which can be mild to severe. The liver disease can include cirrhosis and liver cancer. HCV related chronic liver disease is usually insidious and progressed slowly without any symptoms for several decades (CDC, 2008). The leading indication for liver transplants in the US is Chronic HCV infection (CDC, 2008).

Data indicate that increased alcohol intake, being older than 40 at the time of infection, and being male are associated with more severe liver disease. In people with alcoholic liver disease and HCV infection, liver disease progresses more rapidly. Intake of moderate amounts (>10 grams/day) of alcohol in clients with chronic HCV may enhance the disease progression. More severe liver injury observed in people with alcoholic liver disease and HCV infection possibly is attributable to alcohol-induced enhancement of viral replication or increased susceptibility of cells to viral injury.

Extra hepatic manifestations of chronic HCV infection occur in 38% of chronically infected HCV clients (Pearlman, 2004). Cognitive problems may be present even in the absence of clinically significant liver disease or interferon based therapy (Pearlman, 2004). Diabetes mellitus occurs three times more frequently in HCV-infected persons. Other HCV related manifestations include (CDC, 2008):

• Vitiligo
• Cryoglobulinemia
• Membranoproliferative glomerulonephritis
• Non-Hodgkin's lymphoma
• Porphyria cutanea tarda.

Extra hepatic conditions that have been reported but definitive associations of these conditions with HCV infection have not been established include (Pearlman, 2004):

• Seronegative arthritis
• Sjögren syndrome
• Autoimmune thyroiditis
• Lichen planus
• Mooren corneal ulcers
• Idiopathic pulmonary fibrosis (Hamman-Rich syndrome)
• Polyarteritis nodosa
• Aplastic anemia
• B-cell lymphomas

HCV positive clients should be evaluated for chronic liver disease and determination of the need for hepatitis A and hepatitis B vaccination. Assessment of liver functions tests, evaluation of severity of liver disease and possible treatment should be done.

Chronic HCV treatment of choice is a combination therapy of pegylated interferon and ribavirin. The addition of polymerase and protease inhibitors has increased success rates. The treatment objective is a sustained virologic response of undetectable HCV RNA in the client's blood. The combination therapy of interferon and ribavirin is FDA-approved for use in children ages 3-17 years (CDC, 2008).

Genotyping needs to be done with HCV positive clients. There are six distinct HCV genotypes and more than 50 subtypes have been identified. Genotype 1 is the most common HCV genotype in the US (CDC, 2008). Knowing the genotype can help predict the likelihood of treatment response and, in many cases, determine the duration of treatment (CDC, 2008, pg. 1).

Contraindications to treatment with interferon include major depressive illness, cytopenias, hyperthyroidism, renal transplantation, and evidence of autoimmune disease. Interferon usually causes flu-like symptoms early in treatment that diminish with continued treatment. Later side effects include fatigue, bone marrow suppression, and neuropsychiatric effects (e.g., apathy, cognitive changes, irritability, and depression). Up to 20% of clients do not complete the antiviral therapy because they experience significant side effects. In addition, some clients may have conditions, such as severe cirrhosis which prohibit treatment.

Ribavirin can induce hemolytic anemia and can cause problems for clients with pre-existing anemia, bone marrow suppression, or renal failure. These clients should avoid combination therapy. Hemolytic anemia caused by ribavirin can be life threatening for clients with ischemic heart disease or cerebral vascular disease. Ribavirin is teratogenic, and female clients should avoid becoming pregnant during therapy (CDC, 1998).

HCV negative people with ongoing risk factors require counseling concerning ways to reduce their risk for infection, referral to substance abuse treatment if appropriate, and immunization with hepatitis A and hepatitis B vaccines (CDC, 2005). There is no vaccine for HCV, but research is being done to develop a vaccine (CDC, 2008).

Syringe and needle-exchange programs can be effective in reducing the incidence of bloodborne virus transmission and do not encourage the use of illegal drugs. Therefore, to reduce the risk for HCV infection among injecting-drug users, local communities can consider implementing syringe and needle-exchange programs.

Strategies to reduce transmission of HCV have been successful and need to be maintained. Standard precautions, safe injection practice, and infection control practices need to be followed. Healthcare professionals need to continue to educate the public on methods to reduce transmission, ways to deal with an HCV infection, and ways to reduce liver damage if infected.

CDC. (2008). FAQs for Health Professionals. Retrieved 11/15/08 from http://www.cdc.gov/hepatitis/HCV/HCVfaq.htm#section1

CDC. (2008). Hepatitis C Virus Infection, Past or Present. Retrieved 11/15/08 from http://www.cdc.gov/ncphi/disss/nndss/casedef/hepatitisccurrent.htm

CDC. (2008). Statistics and Surveillance. Retrieved 11/15/08 from http://www.cdc.gov/hepatitis/Statistics.htm#section1.

CDC. (2005). Hepatitis C fact sheet. Retrieved January 15, 2005, from www.CDC.gov.

CDC. (2001). National Hepatitis C prevention strategy: A comprehensive strategy for the prevention and control of Hepatitis C virus infection and its consequences. Retrieved January 15, 2005, from www.CDC.gov.

CDC. (1998). Hepatitis C: What Clinicians and Other Health Professionals Need to Know, Centers for MMWR, 47 (No. RR-19).
Pearlman, B. (2004). Hepatitis C infection: A clinical review. Southern Medical Journal. 97(4), 365-376.