Occult hepatitis B virus (HBV) infection is common in chronic hepatitis C patient. However, its significance and consequences are still unclear. The aim of this study was to evaluate the prevalence of occult HBV among HCV chronic carriers in France and to assess its impact on liver histology and response to antiviral therapy. To this end a cohort of 203 patients with chronic hepatitis C without hepatitis B surface antigen (HBsAg) has been examined. Serum HBV-DNA was detected using a highly sensitive PCR with primers located in the S and X genes. HBV viraemia levels were further determined by real-time PCR. Results showed that 47 of 203 (23%) patients had occult HBV infection with a low HBV load (102–104 copies/ml) but significantly higher HCV-RNA titers (P < 0.05). No significant difference in age, gender, serum ALT level, HCV genotypes, and the presence of anti-HBc was observed between patients with or without HBV-DNA. When compared histologically, patients with occult HBV infection had higher activity (A2-A3 in 53% vs. 38%, P < 0.01) and more advanced fibrosis (60% vs. 33%, P < 0.001) than HBV-DNA negative cases. Sustained response to combination therapy against Chronic hepatitis C was achieved in 11 (28%) of 40 HBV-DNA positive cases, compared with 65 (45%) of the 144 HBV-DNA negative cases (P < 0.05). Among the 144 HBV-DNA negative HCV patients those with genotype 1 responded less frequently to therapy as compared to other genotypes infected patients (38% vs. 55%, P < 0.05). Surprisingly, when considering all patients studied, irrespective to the HBV-DNA status no significant difference was observed in response to combination therapy regarding HCV genotypes (39% vs. 44%, P > 0.05). In conclusion, HBV-DNA is found in 1/4 of French chronic hepatitis C patients regardless of the presence of anti-HBc. Such an occult HBV co-infection is associated with more severe liver disease, higher HCV viral load and decreased response to antiviral therapy irrespective of HCV genotypes. J. Med. Virol. 79: 1075–1081, 2007. © 2007 Wiley-Liss, Inc.