The safety of stopping nucleos(t)ide analogue treatment in patients with HBeAg‐negative chronic hepatitis B

Abstract

Background The rates of hepatitis B surface antigen (HBsAg) seroclearance after stopping nucleos(t)ide analogues (NA) in European (19% in 2 years) and Asian (13% in 6 years) patients with chronic hepatitis B (CHB) vary dramatically. We evaluated the incidence of hepatitis flare and HBsAg seroclearance in hepatitis B e antigen (HBeAg)‐negative Chinese CHB patients who had stopped NA. Methods This was a territory‐wide retrospective study in Hong Kong. We identified HBeAg‐negative CHB patients from January 2000 to December 2017 who had stopped NA treatment for more than 3 months. Hepatitis flare was defined as ALT >2×ULN. Results The 1076 patients were predominantly middle‐aged men (mean age 52 years, male 74.8%) when starting NA; they stopped NA after 82 ± 35 months of treatment. At 44.3 ± 24.6 months after stopping NA, 147 (13.6%) patients had hepatitis flare, which led to resumption of NA; whereas 77 (7.2%) patients had flare but did not resume NA. Decompensation occurred in 7/914 (0.8%) patients. A total of 695 (64.6%) patients remained on NA treatment at the last visit. Eleven patients had achieved HBsAg seroclearance (6 of them had hepatitis flare and 1 of these 6 patients achieved HBsAg seroclearance after NA was restarted). Hepatic events developed in 75/695 (10.8%) patients who had NA resumed vs 43/381 (11.3%) patients who did not resume NA (P = .677). Conclusions Hepatitis flare and retreatment were common in HBeAg‐negative CHB patients who stopped NA treatment; whereas HBsAg seroclearance rarely occurred. Stopping NA to achieve functional cure should not be recommended at this moment.

Hepatitis B surface antigen, core‐related antigen and HBV RNA: Predicting clinical relapse after NA therapy discontinuation

“…Another report from Taiwan also revealed a slightly higher incidence of HBsAg clearance after cessation of NA than with continuation of the therapy, with estimated annual incidences of 1.78% and 0.15% respectively 27 . In a recent real‐world cohort from Hong Kong, the annual incidence rate of HBsAg clearance after stopping NA was 1.7% 28 . In our study, HBsAg clearance rate after NA discontinuation occurred in approximately 2% of patients, which was in agreement with results of most Asian studies but lower than that documented in white populations.…”

Management of patients with liver derangement during the COVID-19 pandemic: an Asia-Pacific position statement

“…Virological or biochemical relapse occur in a substantial proportion of patients with chronic hepatitis B after stopping oral antiviral drugs. 44,45 Given that stopping nucleoside analogues might lead to HBV reactivation and clinical flare, 46 it is not advisable to halt such treatment in patients with COVID-19 (statement 4D; table 1).…”

Transaminase Elevations during Treatment of Chronic Hepatitis B Infection: Safety Considerations and Role in Achieving Functional Cure

“…Transaminase flares following withdrawal of TDF appear to occur earlier than withdrawal from ETV [ 125 ], but withdrawal from ETV or TDF is rarely accompanied by biochemical flare or hepatic decompensation [ 121 , 122 , 126 , 127 ]. Notwithstanding this, these host-mediated flares are not associated with sustained control of viremia, and re-treatment with NUCs is usually required [ 128 ].…”