This prospective study investigated viral and host markers after stopping long-term therapy with nucleos(t)ide analogues in noncirrhotic patients with hepatitis B e antigen-negative chronic hepatitis B. After stopping therapy, 13 of 15 patients experienced a virological relapse. Rebound of hepatitis B virus DNA and hepatitis B core-related antigen was associated with induction of plasma tumor necrosis factor, interleukin (IL) 10 , IL-12p70, CXCL10 and subsequent decline in hepatitis B surface antigen (HBsAg), with 20% HBsAg loss after long-term follow-up. The peak levels of hepatitis B virus DNA and hepatitis B core-related antigen after cessation of therapy were positively correlated with the level of HBsAg decline at week 48. Thus, stopping or interrupting NA treatment should be further investigated as a strategy to accelerate HBsAg loss.

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Increased NK cell function is associated with active hepatitis and HBsAg seroclearance following structured NA cessation. This adds to our knowledge of the immunological events that develop following cessation of NA treatment in CHB.

HEV-specific T-cell responses are detectable against the entire HEV genome including the non-structural proteins. HEV-specific T-cell responses are associated with control of HEV infection. These findings have implications for the design of HEV vaccines.

Abbreviations: aa, amino acid; ALT, alanine aminotransferase; AUC, area under the curve; CHB, chronic hepatitis B; CI, confidence interval; ELISA, enzyme-linked immunosorbent assay;HBeAg, hepatitis B e antigen; HBs, hepatitis B surface (protein); HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; LAM, lamivudine; LLOQ, lower limit of quantification;PegIFN, peginterferon alfa-2a; qHBsAg, quantitative hepatitis B surface antigen; ROC, receiver operating characteristic; SC, seroconversion; SHBs/MHBs/LHBs, small/middle/large hepatitis B surface (protein); SVP, subviral particle. Abstract Background & Aims: Hepatitis B virus (HBV) contains three viral surface proteins, large, middle and small hepatitis B surface protein (LHBs, MHBs, SHBs). Proportions of LHBs and MHBs are lower in patients with inactive vs active chronic infection. Interferon alfa may convert hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) to an inactive carrier state, but prediction of sustained response is unsatisfactory. The aim of this study was to test the hypothesis that quantification of MHBs and LHBs may allow for a better prognosis of therapeutic response than total hepatitis B surface antigen (HBsAg) concentration. Methods: Hepatitis B surface proteins were measured before and during peginterferon alfa-2a therapy in serum from 127 Asian patients with HBeAg-positive CHB. Sustained response was defined as HBeAg seroconversion 24 weeks post-treatment.Results: Mean total HBs levels were significantly lower in responders vs nonresponders at all time points (P < .05) and decreased steadily during the initial 24 weeks treatment (by 1.16 vs 0.86 ng/mL in responders/nonresponders respectively) with unchanged relative proportions. Genotype B had a two-fold higher proportion of LHBs than genotype C (13% vs 6%). HBV DNA, HBeAg, HBsAg and HBs protein levels predicted response equally well but not optimally (area under the receiver operating characteristic curve values >0.70). Conclusions:Hepatitis B surface protein levels differ by HBV genotype. However, quantification of HBs proteins has no advantage over the already established HBsAg assays to predict response to peginterferon alfa-2a therapy in HBeAg-positive patients. K E Y W O R D SHBs proteins, HBsAg, peginterferon alfa-2a, predictors of response, subviral particles | 325 RINKER Et al.

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