Okuda Lecture: Challenges of Hepatitis B in the Era of Antiviral Therapy

AbstractNucleos(t) ide analogues (NA) are effective, safe, and convenient antiviral therapy to suppress replication of hepatitis B virus (HBV), which can be translated into improved long ‐term outcome of chronic hepatitis B patients. The current recommended first‐line NA, namely entecavir and tenofovir, are largely free from problems of drug resistance. Nonetheless, there are still a few challenges in the era of NA. First, the risk of hepatocellular carcinoma (HCC) can only be r educed but not eliminated, particularly among cirrhotic patients. For cirrhotic patients who have persistent low level viremia on NA, i.e. partial responders, the risk of HCC is higher than those with complete viral suppression. The best strategy to manage partial responders to entecavir or tenofovi r is uncertain. Second, immune tolerant patients are very difficult to treat with NA. A significant proportion of immune tolerant patients will have detectable viremia despite a few years of continuous NA treatment, and the rate of HBeAg seroconversion is very low. Third, most patients need long‐t erm treatment as NA cannot eliminate covalently closed circular DNA in the hepatocytes. Some patients can consider stop NA according to treatment guidelines, but viral and clinical relapses often occur after treatment cessation. There is no concrete consensus on when one should stop NA in a HBeAg‐ negative patient among different treatment guidelines. New biomarkers such as hepatitis B surface antigen lev...
Source: Journal of Gastroenterology and Hepatology - Category: Gastroenterology Authors: Tags: Solicited Review Source Type: research