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.     

High genomic similarity between European type hepatitis E virus subgenotype 3e strains isolated from an acute hepatitis patient and a wild boar in Mie,Japan

A 67‐year‐old male living in Tsu city, Mie prefecture, Japan was referred to our hospital for further examination of acute liver injury and was diagnosed as having clinical hepatitis E virus (HEV) infection in January 2010. The HEV strain (HE‐JA11‐1701) isolated from the patient belonged to genotype 3 and European‐type subgenotype 3e. It was presumed that the patient had been infected from a wild boar (Sus scrofa leucomystax) because he consumed meat/viscera from a wild boar that he had captured himself as a hunter approximately 2 months before disease onset. A specimen of the boar meat/viscera that the patient had ingested was not available. However, the HE‐JA11‐1701 strain was 99.8% identical within the 412‐nucleotide sequence of the open reading frame 2 region to a HEV strain (JBOAR012‐Mie08) that had been recovered from a wild boar captured near the patient's hunting area in 2008. A phylogenetic analysis confirmed that the two HEV strains had a close genetic relationship and were segregated into subgenotype 3e, supported by a high bootstrap value of 99%. Of note, the HE‐JA11‐1701 and JBOAR012‐Mie08 strains were remotely related to the 3e strains reported in Japan and European countries, with a nucleotide difference of 7.9–13.9%, reinforcing the uniqueness of the 3e strains obtained in the present study. These results strongly support our speculation that the patient developed acute hepatitis E via consumption of HEV‐infected boar meat/viscera. Genetic analyses of HEV strains are useful for tracing infectious sources in sporadic cases of acute hepatitis E.     

Disseminated Cunninghamella bertholletiae infection with septic pulmonary embolism after allogeneic bone marrow transplantation

Mucormycosis in immunocompromised patients is often reported. We report a patient who developed non‐thrombotic pulmonary embolism due to Cunninghamella bertholletiae after allogeneic stem cell transplantation.