Patients with chronic hepatitis C frequently have antibodies to the hepatitis B core antigen (anti-HBc), indicative of prior hepatitis B virus (HBV) infection. In these patients, persistence of HBV may exacerbate liver injury and diminish the response to treatment. The aim of this study was to evaluate the relationship between previous HBV infection and liver histology and the sustained virologic response (SVR) to interferon (IFN)-based therapy in patients with chronic hepatitis C. A total of 132 HBsAg-negative, treatment-naive patients were evaluated. Using multiple logistic regression analysis, the impact of anti-HBc-positivity on the rate of SVR was determined. Progression to bridging fibrosis or cirrhosis was assessed using Cox proportional hazards regression and Kaplan-Meier survival analysis. The median age of the patients was 47 years (IQR, 37-60), 57% were male, and 73% had genotypes 1, 4, 5, or 6. Fifty-one patients (39%) were anti-HBc-positive. The prevalence of moderate to severe necroinflammatory activity (P = 0.36) and progression to bridging fibrosis or cirrhosis (log-rank P = 0.83) was similar between anti-HBc-positive and -negative patients. After a median of 48 weeks (IQR, 26-52) of therapy (IFN, n = 116; IFN and ribavirin, n = 16), 23 patients (17%) achieved a SVR; the rate of response was similar in anti-HBc-positive and -negative patients (18%vs 17%, P = 1.00). After controlling for age, gender, genotype, fibrosis, and treatment regimen, anti-HBc status did not independently affect the rate of SVR (anti-HBc-positive vs negative: odds ratio, 1.36; 95% confidence interval, 0.45 to 4.06; P = 0.58). In conclusion, previous HBV infection does not affect liver histology or the response to IFN-based therapy in patients with chronic hepatitis C.