Long-term outcomes after nucleos(t)ide analogue discontinuation in HBeAg-positive chronic hepatitis B patients

Abstract

Nucleos(t)ide analogue (NUC) resistance is an important clinical risk resulting from long-term therapy in chronic hepatitis B (CHB) management. Discontinuation of NUCs is a feasible strategy to reduce resistance. We aimed to observe the outcomes after NUC withdrawal in HBeAg-positive CHB patients. A total of 97 patients (11 patients with HBsAg loss and 86 patients with sustained HBeAg seroconversion) were enrolled. HBV DNA levels and alanine aminotransferase (ALT) levels were monitored regularly after discontinuation. Relapse was defined as HBV DNA levels >2000 IU/mL in at least two determinations more than 4 weeks apart. HBeAg seroconversion was achieved within 48 weeks (interquartile range (IQR), 24-72 weeks). The time on consolidation therapy was 96 weeks (IQR, 84-144 weeks). No relapses occurred for HBsAg loss patients. Evidence of relapse was observed in 9.3% of HBeAg seroconversion patients. All relapse cases occurred within 48 weeks after discontinuation. The time to relapse was 33 ± 15 weeks. Elevation of HBV DNA and ALT levels over baseline were only observed in 12.5% of relapse patients. There were no significant differences in baseline characteristics (sex, HBV genotype, age or ALT levels) or time on consolidation therapy between patients with relapse or sustained response. NUC discontinuation in HBeAg-positive CHB patients is feasible after achieving HBeAg seroconversion at a minimum of 24 weeks. There is further benefit to prolonging the time on consolidation therapy to reduce relapse. More than 48 weeks of sustained response is a predictive marker for long-term sustained response.

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 ).…”