Hepatitis C infection by polymerase chain reaction in alcoholics: False- positive ELISA results and the influence of infection on a clinical prognostic score

Antibody to hepatitis C as measured by the ELISA method is common in alcoholics. The presence of antibody to C 100-3 has been associated with more advanced disease. However, few studies have investigated the clinical significance of hepatitis C infection as defined by the presence of circulating viral RNA in alcoholics. We have prospectively examined 48 consecutive alcoholic patients for the presence of antibody to hepatitis C by an ELISA for antibody to the C100-3 antigen and by the reverse transcriptase polymerase chain reaction (PCR) using nested primers for the 5' nontranslated region of the viral RNA. Patients with liver disease were scored for disease severity by the combined clinical and laboratory index (CCLI). Overall, 12 of 48 patients (25%) were ELISA positive and eight of 48 (16%) were PCR positive. Among the 34 patients with liver disease, 10 (29%) were ELISA positive and six (18%) were PCR positive. All PCR-positive patients were also ELISA positive. There was no significant difference in the disease severity score (CCLI) or the duration of clinical disease in PCR-positive versus PCR- negative patients with liver disease. However, PCR-positive patients were significantly younger (43 ± 6 vs. 55 ± 10 yr, p = 0.001), indicating an earlier onset of severe disease in PCR-positive patients. There were no false-negative ELISA tests in either those with or those without liver disease. Among the 34 patients with liver disease, four of 10 patients with positive antibody were negative by PCR. Neither individual immunoglobulin levels (IgG, IgM, IgA) nor total globulins were significantly different between the ELISA-positive/PCR-negative patients and ELISA-positive/PCR- positive patients. When the entire group of 34 patients with liver disease was considered, we could not detect a significant correlation between ELISA absorbance and total globulins, and only a weak correlation between absorbance and immunoglobulin G (ρ = 0.49). These data show that the majority of alcoholic patients with liver disease and positive antibody to hepatitis C also have demonstrable viremia by PCR, and may require further evaluation and treatment. Elevated immunoglobulins in these patients do not correlate strongly with ELISA absorbance for anti-HCV. The presence of clinically advanced disease at a significantly younger age in the PCR- positive group is consistent with the concept of synergy between active viral infection and alcohol abuse in the development of liver disease in alcoholic patients.