Title : Is functional cure possible in chronic hepatitis B? HBsAg loss in chronic hepatitis B in a real-life cohort: A single-Center retrospective study
Abstract:
Background and Aims: Hepatitis B surface antigen (HBsAg) loss is the strongest indicator of functional cure in patients with chronic hepatitis B (CHB) infection; however, its annual incidence remains low in real-life cohorts. In this study, we aimed to determine the frequency of HBsAg loss and its associated clinical characteristics in a single-center, real-life cohort of patients with CHB.
Methods: Patients with HBsAg-positive CHB followed at the Infectious Diseases outpatient clinic of a Faculty of Medicine were retrospectively evaluated. Patients were classified into four disease-stage groups: HBeAg-negative chronic infection (inactive carrier), HBeAg-negative chronic hepatitis, HBeAg-positive chronic infection (immune-tolerant), and HBeAg-positive chronic hepatitis. Demographic data, concomitant viral serology, antiviral treatment status, history of cirrhosis/liver transplantation, and the development of HBsAg loss during follow-up were recorded. In patients who achieved HBsAg loss, the follow-up duration (in years) until loss was also noted.
Result: A total of 474 patients (280 male [59.2%], mean age 49.6 ± 13.8 years) were included in the study. Distribution by disease stage was as follows: 246 (51.9%) inactive carriers, 158 (33.3%) HBeAg-negative chronic hepatitis, 49 (10.3%) HBeAg-positive chronic hepatitis, and 20 (4.2%) immune-tolerant patients. Of the patients, 162 (34.2%) were receiving antiviral treatment; 30 patients (6.4%) had cirrhosis and 13 (2.8%) had a history of liver transplantation.
During follow-up, HBsAg loss was observed in a total of 9 patients (1.9%); the median time to loss was 10 years (range, 1–15 years). Of the patients who achieved HBsAg loss, 8 (88.9%) were inactive carriers at diagnosis, none of whom were receiving treatment; the remaining patient (11.1%) had HBeAg-positive chronic hepatitis and was on treatment. Loss rates by disease stage were 3.3% (8/246) among inactive carriers and 2.0% (1/49) among those with HBeAg-positive chronic hepatitis; no HBsAg loss was observed in the HBeAg-negative chronic hepatitis or immune-tolerant groups during follow-up.
Conclusion: In this single-center, real-life cohort, the rate of HBsAg loss was low (9/474, 1.9%) and occurred predominantly (88.9%) in untreated inactive carriers; among treated patients, HBsAg loss was observed in only a single case (0.6% of the 162 treated patients). This low rate suggests that continuous suppressive nucleos(t)ide analogue therapy itself does not accelerate HBsAg loss, and may instead limit the immunological stimulus required for the immune system to clear HBsAg by suppressing viral replication. The current paradigm in the literature is shifting toward the view that planned discontinuation of treatment in patients meeting appropriate stopping criteria may trigger HBsAg seroconversion through reactivation of the host immune response. Our cohort findings support the hypothesis that planned treatment discontinuation in eligible treated patients may increase functional cure rates, and prospective evaluation of this strategy in this population stands out as a recommended area for future research.
