[16] These promising results

require further investigation and confirmation in larger, prospective studies. In this issue of Hepatology, Jeng et al. describe the off-treatment durability of response in entecavir-treated, HBeAg-negative HBV patients.[17] It is an observational study of 95 patients who had been treated with entecavir monotherapy and monitored for at least 12 months after treatment cessation according to the APASL stopping rule (undetectable HBV DNA on three occasions at least 6 months apart). During follow-up, virologic GSI-IX datasheet relapse occurred in the majority (58%) of patients. The 1-year rate of clinical relapse, defined as HBV DNA >2,000 IU/mL and ALT >2× the upper limit of normal, was estimated to be 45%. Of the 39 patients with cirrhosis at baseline, 17 experienced clinical relapse, which resulted in hepatic decompensation in 1 patient. Although this study uses a potent nucleoside analog, it has several limitations. First, it probably underestimates the proportion of relapsers, because a potential selection bias exists in this study. One hundred and ninety-three patients were excluded because their post-treatment follow-up duration was less than

48 weeks. The reasons for a short Autophagy Compound Library screening follow-up are not specified, but one might speculate that many patients already experienced relapse and were subsequently retreated before an off-therapy follow-up duration MCE of 12 months was achieved. Second, only the 1-year results are described in the article. According to the figure presented, the incidence of post-treatment relapse is expected to increase further with longer follow-up. It thus appears that the glass is half empty and may become increasingly empty with continued follow-up. Third, the identified predictors of relapse seem to have only limited discriminatory value, which makes them insufficient to be useful in clinical practice. Overall, baseline HBV DNA >200,000 IU/mL was identified as a predictor of

clinical relapse, yet the area under the receiver operating characteristic curve was only 0.611 (P = 0.063). Sensititvity and specificity values were not provided. In the subgroup of patients without cirrhosis, longer consolidation treatment was identified as well. However, approximately one third of patients who received consolidation therapy for more than 64 weeks still experienced clinical relapse. Another interesting observation in this study is that only 9 of 43 (21%) patients experienced spontaneous remission after initial clinical relapse, which is significantly lower, compared to the study of Hadziyannis et al. (55%). A possible explanation might be the shorter period of maintained remission and shorter consolidation therapy. Lower HBsAg levels may play a role as well, although in the Hadziyannis et al.