Guidelines for avoiding risks resulting from discontinuation of nucleos(t)ide analogues in patients with chronic hepatitis B Short running title: Guidelines to discontinue NUCs

Since nucleos(t)ide analogues (NUC) can lead to rapid reduction in 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 NUCs and there are some problems such as emergence of resistant strains and hepatitis relapse resulting from discontinuation of treatment. One of the reasons is that NUCs 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 NUCs in patients with hepatitis B, it is considered that NUCs should not be easily discontinued since discontinuation often results in hepatitis relapse. However, it has not been clearly revealed when and how hepatitis relapses after discontinuation. Although there are not a few patients without hepatitis relapse after discontinuation or with mild relapse and finally in 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 those in English as a review article.