Guidelines for avoiding risks resulting from discontinuation of nucleoside/nucleotide analogs in patients with chronic hepatitis B

Nucleoside/nucleotide analogs (NUC) can lead to rapid reduction in hepatitis B virus (HBV) DNA levels in blood and normalization of alanine aminotransferase levels in many patients. They also provide histological improvement which results in a reduction in liver carcinogenesis. However, it is difficult to completely remove viruses even by NUC and there are some problems such as emergence of resistant strains and hepatitis relapse resulting from discontinuation of treatment. One of the reasons for this is that NUC reduce the HBV DNA level in blood but have almost no effects on the HBV cccDNA level in hepatocyte nuclei, which are the origins of HBV replication, and HBV cccDNA remains for a long period. For treatment with NUC in patients with hepatitis B, it is considered that NUC should not be easily discontinued because discontinuation often results in hepatitis relapse. However, it has not been clearly revealed when and how hepatitis relapses after discontinuation. Although some patients do not experience hepatitis relapse after discontinuation of NUC, or experience only mild relapse and finally achieve a stable condition, it has not been established how to identify such patients efficiently. We performed research to investigate characteristics of the course after discontinuation of treatment and definition of hepatitis relapse and estimate the relapse rate. “Guidelines for avoiding risks resulting from discontinuation of NUCs 2012” is summarized based on the study results. Because the guidelines are written in Japanese, we explain them in English as a review article.