Baseline value of intrahepatic HBV DNA over cccDNA predicts patient's response to interferon therapy.
Mu D1,2,3, Yuan FC4, Chen Y1,2, Jiang XY1,2, Yan L1,2,3, Jiang LY1,2, Gong JP4, Zhang DZ1,2,3, Ren H5,6,7, Liao Y8,9,10.
Sci Rep. 2017 Jul 19;7(1):5937. doi: 10.1038/s41598-017-05242-y.
PMID:28725013 DOI:10.1038/s41598-017-05242-y
Abstract
Methodology for accurate quantification of intra-hepatic cccDNA has long been a technical challenge, yet it is highly desired 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 among 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 among 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.