Virologic response is not durable after adefovir discontinuation in lamivudine-resistant chronic hepatitis B patients

Abstract

Background/AimsWe investigated the durability of the biochemical and virologic responses after adefovir (ADV) discontinuation in lamivudine-resistant (LMV-R) chronic hepatitis B (CHB) patients, and the outcomes of ADV discontinuation compared to that of ADV maintenance.MethodsThe indication for ADV treatment cessation was an undetectable level of hepatitis B virus (HBV) DNA documented on two occasions at least 6 months apart. All patients received additional ADV for at least 12 months after the confirmation of undetectable HBV DNA (Cobas TaqMan PCR assay, <70 copies/mL). Of 36 patients who had a sufficient ADV therapeutic effect, 19 discontinued ADV treatment, while the others maintained it. A virologic rebound was arbitrarily defined as the redetection of HBV DNA at a level higher than 105 copies/mL.ResultsIn the ADV discontinuation group, ADV treatment and additional therapy were administered for medians of 33 months (range, 12-47 months) and 18 months, respectively. The patients were followed for a median of 12 months (range, 3-30 months) after ADV cessation. During that period, 18 of 19 patients (95%) experienced viral relapse. Viral rebound was observed in six patients (32%). However, 12 of 18 patients (67%) exhibited serum HBV DNA levels of less than 105 copies/mL. Biochemical relapses were observed in four of the six patients with viral rebound. In the ADV maintenance group, patients were treated for a median of 53 months (range, 31-85 months), and 9 patients (53%) experienced viral breakthrough.ConclusionsDuring short-term follow-up after ADV discontinuation, most patients (95%) exhibited viral relapse, whereas and viral breakthrough occurred in about half of patients (53%) maintained on ADV therapy. Therefore, the durability of virologic response after ADV discontinuation in LMV-R patients was unsatisfactory. In addition, and viral breakthrough was not infrequent in the ADV continuation group.

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.…”

“…The majority of studies included patients from East Asia, two studies included Caucasian patients, and one study had a mixed patient population . The majority of patients in all studies were males.…”

“…VR was based on HBV DNA levels <200 IU/mL (or 1000 cp/mL) in seven, < 2000 IU/mL (or 10,000 cp/mL) in 15, and <20,000 IU/mL (or 100,000 cp/mL) in three studies. The mean duration of VR before NA discontinuation was <12 months in three, 12‐24 months in 13, and >24 months in six studies, while it was 12 or 24 months in one, 21 or 33 months in one, and 10 or 14 months in another study. The duration of consolidation therapy after HBeAg seroconversion was <12 months in three, ≥ 12 months in 10, and 0 or 16 months in one of the studies including initially HBeAg‐positive patients (Table ).…”