Hepatitis C virus (HCV) and hepatitis B virus (HBV) co-infection can be encountered in either virus endemic countries. Co-infection can also be found in populations at risk of parenteral transmission. Previous studies demonstrated a high risk of liver disease progression in patients with HCV/HBV co-infection; thus, they should be treated aggressively. Previous evidence recommended therapy combining peginterferon (pegIFN) alfa and ribavirin for co-infected patients with positive HCV RNA. Recent trials further advise using direct-acting antivirals (DAAs) for the clearance of HCV in the co-infected patients. Reactivation of HBV has been observed in patients post-intervention, with higher risks and earlier onset in those having had HCV cured by DAA- versus pegIFN-based therapy. The mechanism of HBV reactivation is an interesting but unsolved puzzle. Our recent study revealed that in vitro HBV replication was suppressed by HCV co-infection; HBV suppression was attenuated when interferon signaling was blocked. In vivo, the HBV viremia, initially suppressed by the presence of HCV super-infection, rebounded following HCV clearance by DAA treatment and was accompanied by a reduced hepatic interferon response. In summary, major achievements in the treatment of HCV/HBV co-infection have been accomplished over the past 20 years. Future clinical trials should address measures to reduce or prevent HBV reactivation post HCV cure.
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