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Epidemiology

Initially known as non-A non-B hepatitis, hepatitis C is a liver disease caused by the hepatitis C virus (HCV) which was first discovered in 1988. HCV infection is the most common chronic blood borne infection in the United States. 3.9 million Americans have been infected with HCV, the majority of whom are aged 30-49 years. Most persons with HCV infection remain persistently infected and while most will develop some liver damage, they may not feel sick. Some may develop cirrhosis and liver failure which may take years to develop. Others may have virtually no long-term effects.

HCV infection occurs in all populations, however, African Americans have a substantially higher prevalence of HCV infection than do whites.

Transmission

Hepatitis C virus is a blood borne pathogen. As such, it is transmitted in much the same way that hepatitis B virus (HBV) or human immunodeficiency virus (HIV) are transmitted. The modes of transmission for blood borne pathogens are: percutaneous, permucosal and sexual. Hepatitis C is most often found among persons with large or repeated direct percutaneous exposures. This includes the following:

• those who have ever injected illegal drugs, even a few times many years ago;
• hemophiliacs who have received clotting factors produced before 1987;
• transfusion and solid organ recipients prior to July 1992;
• persons on chronic hemodialysis;
• persons with high risk sexual practices (multiple sex partners or sex contact with an HCV-infected person);
• persons who are household contacts of individuals with chronic HCV infection.

Clinical Features and Natural History

The course of acute hepatitis C is variable, although its most characteristic feature is fluctuating alanine aminotransferase (ALT) patterns. Normalization of ALT may occur and suggest full recovery, but is frequently followed later by symptomless ALT elevations, indicating chronic disease. Fulminant hepatic failure following acute HCV infection is rare, and in most patients with fulminant non-A, non-B hepatitis, evidence of HCV infection rarely has been found.

Of every 100 persons infected with HCV, about 85 persons may develop long-term infection, and 70 persons may develop chronic liver disease. Fifteen persons may develop cirrhosis over a period of 20 to 30 years, and 5 persons may die from the consequences of long term infection (liver cancer or cirrhosis).

Screening and Diagnostic Tests

Serologic Assays: The only tests currently approved by the United States Food and Drug Administration (FDA) for diagnosis of HCV infection are those that measure anti-HCV. These tests detect anti-HCV in >97% of infected patients, but do not distinguish between acute, chronic, or resolved infection. As with any screening test, positive predictive value of enzyme immunoassay (EIA) for anti-HCV varies depending on prevalence of infection in the population and is low in populations with an HCV-infection prevalence of <10%. Supplemental testing with a more specific assay (i.e., recombinant immunoblot assay [RIBA^TM]) of a specimen with a positive EIA result prevents reporting of false-positive results, particularly in settings where asymptomatic persons are being tested.

Supplemental test results might be reported as positive, negative, or indeterminate. An anti-HCV-positive person is defined as one whose serologic results are EIA-positive and supplemental (RIBA^TM) -positive. Persons with a negative EIA or a positive EIA and a negative supplemental (RIBA^TM) test result are considered uninfected, unless other evidence exists to indicate HCV infection. Indeterminate supplemental test results have been observed in recently infected persons who are in the process of seroconversion, as well as in persons chronically infected with HCV. Indeterminate anti-HCV results also might indicate a false-positive result, particularly in those persons at low risk for HCV infection.

Nucleic Acid Detection: The diagnosis of HCV infection also can be made by qualitatively detecting HCV RNA using gene amplification techniques (e.g., RT-PCR [reverse transcriptase polymerase chain reaction]). HCV RNA can be detected in serum or plasma within 1-2 weeks after exposure to the virus and weeks before the onset of ALT elevations or the appearance of anti-HCV. Rarely, detection of HCV RNA might be the only evidence of HCV infection. Although RT-PCR assay kits for HCV RNA are available for research purposes from various manufacturers of diagnostic reagents, none have been approved by FDA. In addition, numerous laboratories perform RT-PCR using in-house laboratory methods and reagents.

Although not FDA-approved, RT-PCR assays for HCV infection are used commonly in clinical practice. Most RT-PCR assays have a lower limit of detection on 100-1,000 viral genome copies/mL. With adequate optimization of RT-PCR assays, 75% - 85% of person who are anti-HCV-positive and >95% of persons with acute or chronic hepatitis C will test positive for HCV RNA. Some HCV-infected persons might be only intermittently HCV RNA-positive, particularly those with acute hepatitis C or with end-stage liver disease caused by hepatitis C. To minimize false-negative results, serum must be separated from cellular components within 2-4 hours after collection, and preferable stored frozen at -20 C or -70 C. If shipping is required, frozen samples should be protected from thawing. Because of assay variability, rigorous quality assurance and control should be in place in clinical laboratories performing this assay, and proficiency testing is recommended.

Routine testing for hepatitis C is recommended for the following:

• persons who ever injected illegal drugs, including those who injected once or a few times many years ago;
• persons who were treated for clotting problems with a blood product made before 1987 when more advanced methods for manufacturing the products were developed;
• persons who were notified that they received blood from a donor who later tested positive for hepatitis C;
• persons who received a blood transfusion or solid organ transplant before July 1992 when better testing of blood donors became available;
• long-term kidney dialysis patients; and
• persons who have signs or symptoms of liver disease, for example elevated ALT.

• healthcare workers after exposures to HCV-positive blood on the job, such as exposures due to needle sticks or splashes to the eye; and
• children born to HCV-positive women.

Treatment

A referral to or consultation with a specialist for further evaluation and possible treatment may be considered if a person is anti-HCV positive and has elevated liver enzyme levels. Any physician who manages a person with hepatitis C should be knowledgeable and current on all aspects of the care of a person with hepatitis C.

Interferon alone or in combination with ribavirin have been approved by the FDA for the treatment of patients with chronic hepatitis C. Interferon is administered subcutaneously and ribavirin is given by mouth. Interferon alone works in 10 to 20 persons out of 100; combination therapy works in about 30-40 persons out of 100. Ribavirin, when used alone, does not work.

Most persons have flu-like symptoms (fever, chills, headache, muscle and joint aches, fast heart rate) early in treatment, but these lessen with continued treatment. Later side effects may include tiredness, hair loss, low blood count, trouble with thinking, moodiness, and depression. Severe side effects are rare (seen in less than 2 out of 100 persons). These include thyroid disease, depression with suicidal thoughts, seizures, acute heart or kidney failure, eye and lung problems, hearing loss, and blood infection. Although rare, deaths have occurred due to liver failure or blood infection, mostly in persons with cirrhosis. An important side effect of interferon is worsening of liver disease with treatment, which can be severe and even fatal. Interferon dosage must be reduced in up to 40 out of 100 persons because of severity of side effects, and treatment must be stopped in up to 15 out of 100 persons. Pregnant women should not be treated with interferon.

Prevention Messages and Medical Evaluation

HCV-specific information and prevention messages should be provided to infected persons and individuals at risk by trained personnel in public and private health-care settings. Health-education materials should include:

• general information about HCV infection;
• risk factors for infection, transmission, disease progression, and treatment; and
• detailed prevention messages appropriate for the population being tested.

Persons with High-Risk Drug and Sexual Practices

Regardless of test results, persons who use illegal drugs or have high-risk sexual practices or occupations should be provided with information regarding how to reduce their risk for acquiring bloodborne and sexually transmitted infections or of potentially transmitting infectious agents to others.

Negative Test Results

If their exposure was in the past, persons who test negative for HCV should be reassured.

Indeterminate Test Results

Persons whose HCV test results are indeterminate should be advised that the result is inconclusive, and they should receive appropriate follow-up testing or referral for further testing.

Positive Test Results

Persons who test positive should be provided with information regarding the need for a) preventing further harm to their liver; b) reducing risks for transmitting HCV to others; and c) medical evaluation for chronic liver disease and possible treatment.

To protect their liver from further harm, HCV-positive persons should be advised to:

• not drink alcohol;
• not start any new medicines, including over-the-counter and herbal medicines without checking with their doctor; and
• get vaccinated against hepatitis A if liver disease is found to be present.
• To reduce the risk for transmission to others, HCV-positive persons should be advised to:
• not donate blood, body organs, other tissue, or semen;
• not share toothbrushes, dental appliances, razors, or other personal care articles that might have blood on them; and
• cover cuts and sores on the skin to keep from spreading infectious blood or secretions.

• discuss the risk, which is low but not absent, with their partner (If they want to lower the limited chance of spreading HCV to their partner, they might decide to use barrier precautions [e.g., latex condoms]); and
• discuss with their partner the need for counseling and testing.

• approximately 5 out of every 100 infants born to HCV-infected women become infected. (This occurs at the time of birth, and no treatment exists that can prevent this from happening);
• infants infected with HCV at the time of birth seem to do very well in the first years of life. (More studies are needed to determine if these infants will be affected by the infection as they grow older);
• no evidence exists that mode of delivery is related to transmission. Therefore, determining the need for cesarean delivery versus vaginal delivery should not be made on the basis of HCV infection status;
• limited data regarding breast-feeding indicate that it does not transmit HCV, although HCV-positive mothers should consider abstaining from breast-feeding if their nipples are cracked or bleeding;
• infants born to HCV-positive women should be tested for HCV infection and if positive, evaluated for the presence or development of chronic liver; and
• if an HCV-positive woman has given birth to any children after the woman became infected with HCV, she should consider having the children tested.

• HCV is not spread by sneezing, hugging, coughing, food or water, sharing eating utensils or drinking glasses, or casual contact;
• Persons should not be excluded from work, school, play, child-care or other settings on the basis of their HCV infection status;
• Involvement with a support group might help patients cope with hepatitis C.

• assessment for biochemical evidence of chronic liver disease;
• assessment for severity of disease and possible treatment according to current practice guidelines in consultation with, or by referral to, a specialist knowledgeable in this area;
• determination of need for hepatitis A vaccination.

Sources

Centers for Disease Control and Prevention. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. MMWR 1998;47(No.RR-19).
Hepatitis Branch website - http://www.cdc.gov/ncidod/diseases/hepatitis
Hepatitis Branch hotline - 1-888-4HEPCDC
National Institutes of Health. Consensus Development Conference Panel Statement: Management of Hepatitis C.

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