HEPATITIS C

Hepatitis C is a viral infection of the liver which had been referred to as parenterally transmitted or "non-A, non-B" hepatitis until identification of the causative agent in 1989. The discovery and characterization of the hepatitis C virus led to the understanding of its primary role in post-transfusion hepatitis and its tendency to induce persistent infection.

Hepatitis C has been identified as the most common cause of post-transfusion hepatitis worldwide, accounting for approximately 90% of this disease in Japan, USA and Western Europe.

Pathogen

The pathogen hepatitis C virus (HCV) is one of the 5 viruses (A,B,C,D and E), which together account for the vast majority of cases of viral hepatitis. It is an enveloped RNA virus in the flaviviridae family which appears to have a narrow host range. Humans and chimpanzees are the only known species susceptible to infection, with both species developing similar disease.

The potentially important feature of the virus is the relatively high mutability of its genome, which in turn is probably related to the high propensity (80%) of inducing chronic infection. HCV is clustered into 6 distinct genotypes which may be important in determining the severity of the disease and the response to treatment.

Prevalence

HCV infection is widespread throughout the world. WHO has recently published the first global estimate of HCV prevalence, which suggests that up to 3% of the world's population has been infected with HCV. There may be more than 170 million chronic carriers at risk of developing liver cirrhosis and/or liver cancer. Published studies on the prevalence of hepatitis C in various subgroups of the population worldwide showed rates from 0% to 70%: in many countries, for example, the prevalence of HCV is very high among drug users.

Incubation Period

The incubation period of HCV infection before the onset of clinical symptoms ranges from 15 to 150 days.

Symptoms

In acute infections, the most common symptoms are fatigue and jaundice; however, the vast majority of cases (up to 90%), even those with chronic disease, are asymptomatic.

Chronic infection and consequences

It is estimated today that about 20% of patients with chronic infections develop cirrhosis, and that 1% to 5% of cirrhotic individuals will develop cancer of the liver during the next 10 years.

Hepatitis C exacerbates the severity of underlying liver disease when it coexists with other hepatic conditions. About 40% to 60% of alcoholics with cirrhosis are infected with HCV, whereas only 5% to 20% of alcoholics without liver pathology have anti-HCV antibodies.

Another important complication of hepatitis C infection is cancer of the liver (primary hepatocellular carcinoma, HCC). Most patients suffering from HCC in the absence of hepatitis B infection have evidence of hepatitis C infection. The mechanisms by which HCV infection leads to liver cancer are still unclear.

Period of communicability

Unknown, since knowledge of the natural history of the disease is limited and the onset of infection is often unrecognized, except in post-transfusion cases.

Means of Transmission

Transmission through transfusions with blood not screened for HCV, through the use of inadequately sterilized or unsterilized equipment, or through needle-sharing among drug-users, is well documented.

Sexual and perinatal transmission may also occur, although less frequently, and studies to better understand these potential means of transmission are underway. Other modes of transmission such as those linked to social, cultural and behavioural practices using percutaneous procedures (e.g. ear and body piercing, circumcision, tattooing) may be important.

HCV is not as infectious as hepatitis B or HIV. Although the risk of perinatal transmission may increase when the mother is co-infected with HIV, further study is required to quantify this risk. In over 40% of cases the risk factor(s) cannot be identified. In some studies, the careful assessment of past exposure to percutaneous intervention with inadequately sterilized material has reduced the number of cases with unidentified risk factors to 10%.

Diagnosis

HCV is diagnosed serologically by detection of specific antibodies by means of the enzyme immunosorbent assay (EIA). However, false positives are common in first generation tests whereas second generation EIAs have substantially reduced false positive results. Therefore, supplementary tests such as the recombinant immunoblot assay (RIBA) must be carried out when possible. The presence of HCV RNA in serum indicates the presence of active infection and a potential for transmission of the infection and/or the development of chronic liver disease.

Treatment

Treatment with interferon is effective in about 20% of patients. Ribavirin shows some promise as an antiviral agent against HCV when used in combination with interferon, but does not appear to be effective when used alone. Studies on combination therapy are under way, but the cost of such treatment will be high. There is no evidence that glucosteroids are beneficial.

Prevention

Measures to prevent HCV infection include:

• Universal screening of blood and blood products;
• Effective use of universal precautions and barrier techniques (such as the use of sterile equipment and the wearing of gloves);
• Destruction of disposable needles and adequate sterilization of reusable material such as surgical or dental instruments;
• Promotion of public education about the risks of using unsterilized material.

Vaccine

There is no vaccine against HCV. Research is in progress but the high mutability of hepatitis C genome complicates its development. Lack of knowledge of any protective immune response following HCV infection also impedes vaccine research. It is not known whether the immune system is able to eliminate this virus. Some studies, however, have shown the presence of virus-neutralizing antibodies in patients with HCV infection. In the absence of a vaccine, all precautions to prevent infection by other means must be taken.

For further information, contact WHO's Office of Public Information, Geneva. Telephone (41 22) 791 2584. Fax (41 22) 791 4858. E-Mail: inf@who.int

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