Given preliminary estimates that one in five patients with severe mental illness is infected with HCV, a strong argument can be made that all such persons should be screened for the virus. Certainly, all patients known to be infected with HIV should be screened for anti-HCV antibodies as part of their initial evaluation, as should those with high-risk behavior. HCV is primarily spread through infected blood and is therefore a common complication of injection drug use. HCV may be spread by maternal fetal transmission and by noninjected drug use activities as well. Risk for sexual transmission is low but not absent. In a significant minority of cases the mode of transmission is unknown. Like HIV, rates of HCV in the United States are higher in African Americans and Latinos than among Caucasians.

HCV infection should be confirmed with qualitative PCR assay if the patient is at low risk and the diagnosis seems in doubt. Moreover, there is a small but measurable false negative rate for antibody testing in patients who are severely immunosuppressed.

Basic Overview of Course of Illness and Treatment of HCV
Approximately 4 million persons in the United States and probably more than 100 million persons worldwide are infected with HCV. The virus has the unique ability to cause persistent infection in a majority of infected people. The immunological correlates of protection and viral clearance and the pathogenesis of liver injury are yet to be defined, but recent studies suggest the importance of cell-mediated immune responses. Although a large proportion of infected persons become chronic carriers, most have relatively mild disease with slow progression.

However, chronic and progressive HCV carries significant morbidity and mortality and is a major cause of cirrhosis, end-stage liver disease, and liver cancer. Development of an effective HCV vaccine is not imminent, but recent advances in technology and basic knowledge of molecular virology and immunology may engender novel approaches to the fundamental problems encountered in vaccine development. Vaccines continue to be pursued, since current therapy for HCV is poorly tolerated and not effective for a substantial number of patients.

Natural History of HCV Disease
Acute HCV disease is usually asymptomatic, but 25%­35% of patients develop some constitutional symptoms or jaundice. Serum alanine aminotransferase (ALT) levels frequently rise, fluctuate, and fall again, suggesting recovery from the acute phase. Following acute infection, however, HCV is not easily cleared by the immune system, and 75%­80% of acute HCV infections become chronic, as evidenced by persistent or intermittent HCV viremia.

Patients infected with HCV should be advised to minimize or preferably discontinue intake of alcohol. Chronic HCV infection can cause inflammatory infiltration, particularly of the portal tracts, as well as focal liver cell necrosis and fibrosis that bridges between portal tracts. Hepatitis C is the leading cause of liver transplantation in the United States. About 10%­20% of patients progress to cirrhosis within 20­30 years of infection, and among those with cirrhosis, 1%­4% per year will develop hepatocellular carcinoma.

Immunosuppression associated with HIV appears to significantly alter the natural history and clinical course of HCV, with HCV-associated cirrhosis occurring more frequently in patients with HCV­HIV co-infection (33%) than in HCV alone (11%). People with HCV do not tolerate HAART as well, which can interfere with effective HIV treatment. Data indicate that liver failure due to HCV is the leading non-AIDS cause of death in HIV-infected individuals (Community Research Initiative on AIDS 2000; Vento et al. 1998). All patients co-infected with HCV and HIV, or infected with either virus alone, should be screened for immunity to hepatitis A and B; and if not immune, they should be immunized with both hepatitis A vaccine and hepatitis B vaccine. Acute infection with hepatitis A virus, normally a relatively benign and self-limited disease, is more likely to result in fulminant hepatic necrosis in the presence of HCV infection or any other chronic liver disease (Vento et al. 1998). Hepatitis A vaccine is safe for HIV-infected patients, and more than two-thirds of HIVinfected patients immunized with hepatitis A vaccine develop a protective antibody response. Patients without antibody protection for hepatitis A and B viruses can receive a combined vaccine that confers protection against both viruses.

Milton L. Wainberg, M.D.
Francine Cournos, M.D.
Karen McKinnon, M.A.
Alan Berkman, M.D.

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