Predictors of sustained functional cure in hepatitis B envelope antigen‐negative patients achieving hepatitis B surface antigen seroclearance with interferon‐alpha–based therapy

Abstract

Hepatitis B surface antigen (HBsAg) loss is considered a functional cure in chronic hepatitis B (CHB). However, the durability of HBsAg loss after stopping treatment remains unknown. This study aimed to assess the sustained functional cure achieved by interferon therapy in hepatitis B envelope antigen (HBeAg)‐negative CHB patients. In this prospective study, 176 HBeAg‐negative CHB patients with functional cure were enrolled for 12 weeks of cessation treatment, and treatment information and baseline data were collected. Hepatitis B virus (HBV) biomarkers and clinical biochemical indicators were evaluated every 3 months; liver imaging examinations were performed every 3‐6 months during the 48‐week follow‐up. The sustained functional cure was evaluated. After the 48‐week follow‐up, the sustained functional cure rate was 86.63%. The cumulative rates of HBsAg reversion and HBV DNA reversion were 12.79% and 2.33%, respectively. Consolidation treatment ≥ 12 weeks after HBsAg loss achieved a significantly higher rate of sustained functional cure and significantly lower rate of HBsAg reversion than consolidation treatment < 12 weeks (76.19% vs 90.00%, P = 0.022 and 23.81% vs 9.23%, P = 0.014, respectively). Patients with hepatitis B surface antibody (HBsAb) had higher rate of sustained functional cure than patients achieving HBsAg loss but without HBsAb (89.86% vs 73.53%, P = 0.012). Consolidation treatment ≥ 12 weeks (odds ratio [OR] 16.478; 95% confidence interval [CI], 2.135‐127.151; P = 0.007) and high HBsAb levels (OR 8.312; 95% CI, 1.824‐37.881; P = 0.006) were independent predictors of sustained functional cure. Results suggested that 12 weeks of consolidation therapy after HBsAg clearance and elevated HBsAb levels help to improve functional cure.

Durability of hepatitis B surface antigen seroclearance and subsequent risk for hepatocellular carcinoma: A meta‐analysis

“…No significant difference was found ( p = .14). Finally, previous studies have reported that anti‐HBs positivity or high anti‐HBs levels are a predictor of a sustained functional cure 8,11,19 . Ten studies reported the status of anti‐HBs.…”

“…Then, after reading the full texts and evaluating them according to the inclusion and exclusion criteria, 108 studies were excluded; 9 studies lacked full‐text articles, 3 had small sample sizes, 25 reported irrelevant outcomes, 41 provided inadequate data on our outcomes, and 30 failed to exclude patients coinfected with HIV, HCV and/or HDV. Finally, 38 full‐text articles were included in this analysis 8‐45 …”

“…The characteristics of the included studies are shown in Table 1. Twenty‐eight studies came from the Asia‐Pacific regions, 8,11,12,15‐17,19‐26,28,29,31‐35,37,38,40‐42 accounting for the majority of the included studies. Five were from Europe, 9,13,18,36,39 4 were from the Americas, 10,27,30,45 and 1 was a multicentre cohort study 14 .…”

“…Five were from Europe, 9,13,18,36,39 4 were from the Americas, 10,27,30,45 and 1 was a multicentre cohort study 14 . Fifteen studies reported recurrence‐related outcomes after HBsAg seroclearance, 8‐22 14 of which included patients with HBsAg seroclearance after NA treatment and/or common interferon and Peg‐interferon (IFN; Peg‐IFN) treatment. Only 1 study had patients who all spontaneously achieved HBsAg clearance.…”

“…In terms of durability, this analysis of 15 studies, which included 3584 patients with HBsAg seroclearance among 20,167 CHB patients, resulted in a pooled recurrence rate of 6.19% during an average follow‐up of 4.74 years and suggested that HBsAg seroclearance is durable. A few studies reported significant differences in the recurrence rates after HBsAg seroclearance, ranging from zero 13,17 to as high as 13%, 11 which may be related to differences in study regions, subjects and sample size. Five studies reported a higher recurrence rate within one year after HBsAg seroclearance, 8,14,19‐21 and the rate increased slowly or decreased after one year.…”