Baseline Value Of Intrahepatic HBV DNA Over CccDNA Predicts Patient’s Response To Interferon Therapy

Methodology for accurate quantification of intra-hepatic cccDNA has long been a technical challenge,yet is highly demanded in the clinic.Here,we developed a sensitive method for quantification of intrahepatic cccDNA in liver biopsies from patients,which allowed to predict patient’s response to interferon therapy at baseline.Twenty-five patients with HBeAg+ CHB were recruited and liver biopsies were obtained at baseline and 1-year after interferon treatment,respectively.Both intrahepatic cccDNA and HBV DNA were absolutely quantified by a droplet digital PCR amplification system.Patients were categorized as either responder or non-responder group based on their HBeAg status 1-year after interferon therapy.Levels of both intrahepatic HBV DNA and HBV cccDNA were significantly reduced after interferon treatment in the responders,but not the non-responders,in comparison with their levels at baseline.Baseline values of intrahepatic HBV DNA over cccDNA significantly correlated with patient’s response to PEG-IFN therapy(P=0.000).In addition,HBeAg seroconversion also correlates with a significant reduction in intrahepatic pgRNA production in the responders after interferon therapy(P=0.030).In conclusion,our results suggest that baseline value of intrahepatic HBV DNA over cccDNA may be a preferable indicator for selecting appropriate patients for IFN-based therapy in the clinic.