HEPATOCELLULAR-CARCINOMA COMPLICATING AUTOIMMUNE HEPATITIS - ROLE OF HEPATITIS-C VIRUS

The risk of hepatocellular carcinoma in autoimmune hepatitis is low, e ven in patients with long-standing cirrhosis. Because of the increasin g recognition of an association of hepatitis C virus (HCV) with autoim mune hepatitis, at least in some geographical areas, and with hepatoce llular carcinoma (HCC) (hepatoma), we have examined eight cases (4 mal e, 4 female) who presented between 1985 and 1993 with hepatoma complic ating autoimmune hepatitis. All had steroid-responsive autoimmune hepa titis with serum anti-smooth muscle and antinuclear autoantibodies. Me dian duration of disease was 17.1 years, and all patients had biopsy-p roven cirrhosis, One patient had a history of intravenous drug abuse, and four had previously received blood transfusions. Serum samples (st ored at -20 degrees C from up to 9 years before diagnosis of hepatoma) were tested for anti-hepatitis C virus antibodies by a second-third-g eneration assay and for HCV RNA by the polymerase chain reaction metho d using primers from the 5'noncoding region. Tissue from liver adjacen t to tumor areas was subjected to polymerase chain reaction along with tissue from previous liver biopsy specimens (taken up to 19 years bef ore diagnosis of hepatoma) in all patients. Six patients had evidence of HCV infection: four seropositive for HCV RNA (two of whom were also anti-HCV positive) and two seronegative for HCV RNA and anti-HCV but with HCV RNA in liver tissue at presentation with hepatoma. Retrospect ive testing showed probable acquisition of HCV through blood transfusi on in the four transfused patients, The findings suggest that HCV may have oncogenic potential and that hepatoma complicating autoimmune hep atitis is associated with unsuspected HCV infection in most cases in o ur series. Screening of liver for HCV RNA should be considered in auto immune hepatitis patients with a previous history of parenteral exposu re to blood, and for hepatoma in those found to have HCV infection.