Viral kinetics in patients with chronic hepatitis B treated with combination therapy with PEG-IFN and nucleoside analogues

Background and aim: Little is known on the effects of combination therapy with PEG-IFN and Nucleoside Analogues on intrahepatic viral kinetics in HBeAg negative patients. The aim of this study was to evaluate serum and intrahepatic parameters related to active viral replication in a group of patients treated with antivirals, and their correlation with viremia. Material and methods: 10 patients with anti-HBe Pos. Active Chronic Hepatitis B were enrolled in the study: 4 received Pegasys 180 μg/week and Adefovir 10 mg/die, 6 Pegasys 180 μg/week and lamivudine 100 mg/die for 48 weeks. We evaluated serum virological parameters and aminotransferases during treatment and after 6 months of follow-up (FU). In five patients undergoing liver biopsy before and at the end of treatment we measured intrahepatic parameters of replicative activity (HBV-DNA, cccDNA) and of virion productivity (cccDNA/HBV-DNA). Results: Virological and biochemical response at the end of treatment was obtained in 10/10 100%) and 3/10 patients respectively. Nine patients had virological relapse during FU. Anti-HBs seroconversion was observed in one patient. A good correlation was found between intrahepatic HBV-DNA, cccDNA concentrations and serum HBV-DNA before treatment. At the end of treatment we observed significative reduction but not disappearance of intrahepatic HBV-DNA and cccDNA despite negative viremia. cccDNA/HBVDNA ratio was increased in 40% (2/5) patients at the end of treatment. Conclusions: Our study confirms the efficacy of combination therapy on viral suppression and, rarely, seroconversion, even if rates of relapse after therapy are high. Viremia reduction, that was present in all patients at the end of treatment, reflects total intrahepatic HBV-DNA and cccDNA load reduction with a shift towards a non replicative setting.