Hepatitis C is a viral infection of the liver which had been referred to as parenterally¹ transmitted "non A, non B hepatitis" until identification of the causative agent in 1989. The discovery and characterization of the hepatitis C virus (HCV) led to the understanding of its primary role in post-transfusion hepatitis and its tendency to induce persistent infection.

HCV is a major cause of acute hepatitis and chronic liver disease, including cirrhosis² and liver cancer. Globally, an estimated 170 million persons are chronically infected with HCV and 3 to 4 million persons are newly infected each year. HCV is spread primarily by direct contact with human blood. The major causes of HCV infection worldwide are use of unscreened blood transfusions, and re-use of needles and syringes that have not been adequately sterilized.

No vaccine is currently available to prevent hepatitis C and treatment for chronic hepatitis C is too costly for most persons in developing countries to afford. Thus, from a global perspective, the greatest impact on hepatitis C disease burden will likely be achieved by focusing efforts on reducing the risk of HCV transmission from nosocomial ³exposures (e.g. blood transfusions, unsafe injection practices) and high-risk behaviours (e.g. injection drug use).

Pathogen

Hepatitis C virus (HCV) is one of the 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.

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

Clinical features of acute infection

The incubation period of HCV infection before the onset of clinical symptoms ranges from 15 to 150 days. In acute infections, the most common symptoms are fatigue and jaundice; however, the majority of cases (between 60% and 70%), even those that develop chronic infection, are asymptomatic.

Chronic infection and consequences

About 80% of newly infected patients progress to develop chronic infection. Cirrhosis develops in about 10% to 20% of persons with chronic infection, and liver cancer develops in 1% to 5% of persons with chronic infection over a period of 20 to 30 years. Most patients suffering from liver cancer who do not have hepatitis B virus infection have evidence of HCV infection. The mechanisms by which HCV infection leads to liver cancer are still unclear. Hepatitis C also exacerbates the severity of underlying liver disease when it coexists with other hepatic conditions. In particular, liver disease progresses more rapidly among persons with alcoholic liver disease and HCV infection.

Means of transmission

HCV is spread primarily by direct contact with human blood. Transmission through blood transfusions that are not screened for HCV infection, through the reuse of inadequately sterilized needles, syringes or other medical equipment, or through needle-sharing among drug-users, is well documented. Sexual and perinatal transmission may also occur, although less frequently. Other modes of transmission such as social, cultural, and behavioural practices using percutaneous procedures (e.g. ear and body piercing, circumcision, tattooing) can occur if inadequately sterilized equipment is used. HCV is not spread by sneezing, hugging, coughing, food or water, sharing eating utensils, or casual contact.

In both developed and developing countries, high risk groups include injecting drug users, recipients of unscreened blood, haemophiliacs, dialysis patients and persons with multiple sex partners who engage in unprotected sex.

In developed countries, it is estimated that 90% of persons with chronic HCV infection are current and former injecting drug users and those with a history of transfusion of unscreened blood or blood products.

In many developing countries, where unscreened blood and blood products are still being used, the major means of transmission are unsterilized injection equipment and unscreened blood transfusions. In addition, people who use traditional scarification and circumcision practices are at risk if they use or re-use unsterilized tools.

Prevalence

WHO estimates that about 170 million people, 3% of the world's population, are infected with HCV and are at risk of developing liver cirrhosis and/or liver cancer. The prevalence of HCV infection in some countries in Africa, the Eastern Mediterranean, South-East Asia and the Western Pacific (when prevalence data are available) is high compared to some countries in North America and Europe.

Table 1: Hepatitis C estimated prevalence and number infected by WHO Region

Source: Weekly Epidemiological Record. N° 49, 10 December 1999, WHO

Diagnosis

Diagnostic tests for HCV are used to prevent infection through screening of donor blood and plasma, to establish the clinical diagnosis and to make better decisions regarding medical management of a patient. Diagnostic tests commercially available today are based on Enzyme immunosorbant assays (EIA) for the detection of HCV specific antibodies. EIAs can detect more than 95% of chronically infected patients but can detect only 50% to 70% of acute infections.

A recombinant immunoblot assay (RIBA) that identifies antibodies which react with individual HCV antigens is often used as a supplemental test for confirmation of a positive EIA result.

Testing for HCV circulating by amplification tests RNA (e.g. polymerase chain reaction or PCR, branched DNA assay) is also being utilized for confirmation of serological results as well as for assessing the effectiveness of antiviral therapy. A positive result indicates the presence of active infection and a potential for spread of the infection and or/the development of chronic liver disease.

Treatment

Antiviral drugs such as interferon taken alone or in combination with ribavirin, can be used for the treatment of persons with chronic hepatitis C, but the cost of treatment is very high. Treatment with interferon alone is effective in about 10% to 20% of patients. Interferon combined with ribavirin is effective in about 30% to 50% of patients. Ribavirin does not appear to be effective when used alone.

Prevention

There is no vaccine against HCV. Research is in progress but the high mutability of the HCV genome complicates vaccine 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 the 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 must be taken including:

• Screening and testing of blood and organ donors;
• Virus inactivation of plasma derived products;
• Implementation and maintenance of infection control practices in health care settings, including appropriate sterilization of medical and dental equipment;
• Promotion of behaviour change among the general public and health care workers to reduce overuse of injections and to use safe injection practices; andRisk reduction counselling for persons with high-risk drug and sexual practices.