Antibody to hepatitis B core antigen and risk for hepatitis C-related hepatocellular carcinoma: a prospective study.

BACKGROUND

Previous exposure to hepatitis B virus (HBV) and occult HBV infection may have an important role in the development of hepatocellular carcinoma (HCC) in patients with chronic liver disease related to hepatitis C virus (HCV).

OBJECTIVE

To prospectively study the association between antibody to hepatitis B core antigen (anti-HBc) and clinical outcomes in patients with HCV-related chronic liver disease.

DESIGN

Prospective observational study.

SETTING

Kyoto University Hospital and 14 regional core hospitals in Japan.

PARTICIPANTS

872 patients with chronic HCV infection (597 with chronic hepatitis and 275 with cirrhosis).

MEASUREMENTS

Incidence of HCC on follow-up (from 1995 to 2005).

RESULTS

Only 846 of the 872 enrolled patients were followed. Hepatocellular carcinoma occurred in 237 of 846 patients (28.0%) during follow-up. Among patients with cirrhosis, HCC was diagnosed in 85 of 141 patients (60.3%) with anti-HBc and 58 of 129 patients (45.0%) without HBV-related serologic markers. Of 224 patients with chronic hepatitis who had interferon monotherapy, 92 (41.1%) had sustained or transient disappearance of HCV RNA. None of the anti-HBc-negative patients who had a virologic response to interferon therapy developed HCC, whereas cancer was diagnosed in 4 of 37 anti-HBc-positive patients (10.8%) with a virologic response to interferon. On multivariate analysis using a Cox proportional hazards model, anti-HBc-positive results on serologic testing was an independent risk factor in patients with cirrhosis (incidence rate ratio, 1.58 [95% CI, 1.12 to 2.22]).

LIMITATIONS

The study included only 1 assessment of smoking and alcohol consumption at study entry and did not precisely determine the duration of smoking or alcohol use.

CONCLUSIONS

Anti-HBc-positive results on serologic testing are a marker of high risk for HCC among patients with HCV-related cirrhosis. Interferon therapy might be less effective in preventing HCC among patients with chronic hepatitis C who are anti-HBc-positive than in those with chronic hepatitis C who are anti-HBc-negative.