Off-treatment virologic relapse and outcomes of re-treatment in chronic hepatitis B patients who achieved complete viral suppression with oral nucleos(t)ide analogs

Abstract

BackgroundThe durability of off-treatment virologic responses has not been fully elucidated in chronic hepatitis B (CHB) patients who have previously achieved complete virologic suppression with nucleos(t)ide analog (NA) therapy. This study aimed to assess off-treatment virologic relapse rates and to characterize the outcomes of subsequent re-treatment in CHB patients who have discontinued oral NA following complete virologic suppression.MethodsNinety-five CHB patients who showed complete virologic suppression were withdrawn from NAs: entecavir, lamivudine, and clevudine in 67, 15, and 13 patients, respectively. Consolidation therapy was given for 6 and 12 months for HBeAg-positive and -negative CHB, respectively, before cessation. Virologic relapse was managed with the same NA that had induced complete virologic response before discontinuation.ResultsThe cumulative rates of virologic relapse at 12 and 24 months were 73.8% and 87.1%, respectively. The relapse rates were independent of HBeAg positivity, HBeAg seroconversion, and type of oral NA. In a multivariate analysis, duration of oral NA therapy was the only significant predicting factor associated with off-treatment virologic relapse. Although the majority of patients regained complete virologic suppression, some patients did not respond to re-treatment with the initial NA and developed genotypic resistance.ConclusionsNA consolidation therapy for 6 and 12 months is associated with high off-treatment virologic relapse in HBeAg-positive and -negative CHB patients, respectively. Drugs with high genetic barriers to resistance should be considered as a rescue therapy for off-treatment relapse in CHB.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2334-14-439) contains supplementary material, which is available to authorized users.

5-year efficacy of entecavir in Indian patients with chronic hepatitis B

“…Some studies have found longer time to and lower rate of HBV DNA negativity in the subgroups of patients with e antigen positivity and higher baseline HBV DNA level [11,13,15,17], but others have not as in our study [18,19]. Studies have also found that previous NA exposure, age more than 60 years and the presence of cirrhosis do not influence viral suppression during prolonged therapy as our study [4,13,18,20].…”

“…This indicates its ineffectiveness in clearing the cccDNA which is regarded as the hallmark of complete viral [5,7,16,19]. In such studies, a HBV DNA cutoff level of 20 to 2000 IU/mL was considered for stopping or restarting therapy.…”

Discontinuation of oral antivirals in chronic hepatitis B: A systematic review

“…The literature search initially identified 972 papers; of those, 25 fulfilled the inclusion and exclusion criteria for this review (http://onlinelibrary.wiley.com/doi/10.1002/hep.28438/suppinfo). The main characteristics of the included studies and patients are presented in Tables and .…”

“…In total, 2332 (each study contribution from 11 to 401) patients were included in the 25 studies. All but one were cohort studies (three prospective, one retrospective‐prospective, and 20 retrospective, while one was a randomized study comparing the effects of 12 versus 24 months of additional therapy after response to lamivudine in HBeAg‐negative CHB . One study was found to have high quality, 14 to have acceptable quality, and 10 to have low quality based on their risk of bias assessments (http://onlinelibrary.wiley.com/doi/10.1002/hep.28438/suppinfo).…”

“…Eight studies included only HBeAg‐positive, 11 only HBeAg‐negative, and six both HBeAg‐positive and HBeAg‐negative patients. There were 1217 (52.2%) HBeAg‐positive and 1115 (47.8%) HBeAg‐negative patients.…”