Immunological biomarkers as indicators for outcome after discontinuation of nucleos(t)ide analogue therapy in patients with HB HB eAg‐negative chronic hepatitis B

摘要

Summary The optimal duration of treatment with nucleos(t)ide analogues ( NA s) for patients with HB eAg‐negative chronic hepatitis B ( CHB ) is unknown. The aim of this study was to identify an immune signature associated with off‐treatment remission to NA therapy. We performed microarray analysis of peripheral blood mononuclear cell ( PBMC s) from six patients with chronic hepatitis B who stopped NA therapy (three with off‐treatment remission, three with relapse) and five patients with chronic HBV infection (previously termed ‘inactive carriers’) served as controls. Results were validated using qRT ‐ PCR on a second group of 21 individuals (17 patients who stopped treatment and four controls). PBMC s from 38 patients on long‐term NA treatment were analysed for potential to stop treatment. Microarray analysis indicated that patients with off‐treatment remission segregated as a distinct out‐group. Twenty‐one genes were selected for subsequent validation. Ten of these were expressed at significantly lower levels in the patients with off‐treatment remission compared to the patients with relapse and predicted remission with AUC of 0.78‐0.92. IFN γ, IL ‐8, FASLG and CCL 4 were the most significant by logistic regression. Twelve (31.6%) of 38 patients on long‐term NA therapy had expression levels of all these four genes below cut‐off values and hence were candidates for stopping treatment. Our data suggest that patients with HB eAg‐negative CHB who remain in off‐treatment remission 3?years after NA cessation have a distinct immune signature and that PBMC RNA levels of IFN γ, IL ‐8, FASLG and CCL 4 may serve as potential biomarkers for stopping NA therapy.