Infection with the hepatitis C virus is often asymptomatic until liver disease has progressed to cirrhosis or hepatocellular carcinoma. The causative agent for hepatitis C virus was discovered in 1989. Recent studies show the overall prevalence of hepatitis C virus infection in the United States to be approximately 1.4 percent. About 89 percent of persons with hemophilia and about 0.5 percent of blood donors are infected with hepatitis C virus. Morton and Kelen discuss issues encountered in identification and treatment of patients with hepatitis C virus infection.

Hepatitis C is usually transmitted parenterally. The prevalence among intravenous drug users has been reported to be as high as 97 percent in some populations. Other modes of parenteral infection include tattoo needles, organ transplants, intravenous immuneglobulin and occupational exposure. Up to 40 percent of infected patients have no apparent parenteral risk factor. Transmission is thought to occur by sexual contact or by vertical transmission from mother to child. Transmission by simple household contact appears to be very rare.

About 2,200 health care workers seroconvert annually following occupational exposure. Four to 10 percent of persons who sustain a stick with a needle containing hepatitis C–infected blood become infected with the virus. Antibodies to the proteins of hepatitis C virus allow diagnosis of infection using serologic assays. The variation in genotypes accounts for the possibility that a person may have multiple exposures to the hepatitis C virus, even to the original inoculum, and exhibit signs of acute hepatitis each time. Hepatic cellular damage during viral illness results from immunologic and, possibly, direct cytopathic effects.

The enzyme-linked immunosorbent assay (ELISA) has several limitations. Sensitivity was found to be only 81 to 89 percent, and seroconversion was detected an average of 15 to 20 weeks after exposure. Sensivity and specificity of the second-generation ELISA–2 is much improved over the first-generation test, and seroconversion can be detected within one to six weeks after exposure. The second-generation recombinant immunoblot assay (RIBA–2) is used as a confirmation test and correlates well with active viral activity. A third-generation RIBA test seems to offer a small improvement in accuracy. The best available diagnostic test for hepatitis C virus infection is reverse transcriptase–PCR, which detects very low levels of virus in tissue and serum, and has a high sensitivity and specificity. However, this test is quite expensive and not widely available for routine diagnosis. Problems with reproducibility among laboratories has become a major issue. Flawless technique is key to the accuracy of results. Methods for quantitation of hepatitis C RNA recently became available. Currently, the best technique appears to be a combination of ELISA–2 to diagnose and RIBA–2 to confirm infection. Patients at high risk for hepatitis C virus infection and those with unexplained elevation of alanine transaminase levels should be evaluated.

Interferon-alfa_2b is the current therapy for patients with hepatitis C infection, but long-term remission is achieved in fewer than 25 percent of those treated. Positive prognostic indicators include low total viral titer, less severe liver damage and fibrosis, low total body iron, and positive early response to interferon. Current dosage regimens are 3 million to 6 million U administered subcutaneously three times per week for six to 12 months. Ribavirin is another treatment that has been tried with variable success. When used in combination with interferon, it appears to delay relapse but does not appear to effect long-term clearance of hepatitis C virus. Although liver transplantation may eventually be required, reinfection occurs universally. Post-exposure prophylaxis with intravenous immune globulin shows no benefit. Currently, vaccination against hepatitis C virus does not exist.

editor's note: Screening for hepatitis C virus infection is clearly appropriate in high-risk persons and in persons with evidence of unexplained liver inflammation. Screening of asymptomatic lower-risk patients needs to be individualized. Benefits of screening include the possibility of counseling patients about healthier lifestyles, avoiding transmission and instituting appropriate monitoring for liver inflammation. These benefits must be balanced against patient anxiety and insurability. Universal screening for pregnant patients is not recommended because there is no available management plan that would reduce the rate of vertical transmission.—r.s.