Discontinuation of nucleos(t)ide analog therapy in hepatitis B e antigen-negative non-cirrhotic chronic hepatitis B patients: A real-life study

Abstract

BACKGROUND

The discontinuation of nucleos(t)ide analog (NUC) therapy remains controversial in hepatitis B e antigen-negative chronic hepatitis B (CHB) patients who have not attained hepatitis B surface antigen loss.

AIM

To assess re-treatment rates and risk factors in non-cirrhotic hepatitis B e antigen-negative CHB patients after the cessation of NUC.

METHODS

Demographic, clinical, and laboratory data were prospectively collected before to and following the discontinuation of NUC.

RESULTS

Eighty-seven patients were included in the follow-up from January 2015 to September 2025; 57 were male, with a mean age of 41.3 ± 10.8 years old. The baseline median values of alanine aminotransferase (ALT) and hepatitis B viral deoxyribonucleic acid (DNA) were 87 IU/L and 37211 IU/mL, respectively. The median histologic fibrosis score was 2. The median length of treatment and consolidation therapy was 69 months and 46 months, respectively. The median duration of follow-up following the cessation of therapy was 39 months. Of the 56 patients deemed qualified for assessment based on the suggested re-treatment criteria, 29 (51.7%) underwent re-treatment. The median duration until relapse was 11 months. The cumulative virological relapse rates, defined as HBV DNA over 2000 IU/mL, were 25%, 52%, 58%, and 61% at 6 months, 12 months, 24 months, and 36 months, respectively. The cumulative retreatment rates at 6 months, 12 months, 24 months, and 36 months were 19%, 25%, 28%, and 35%, respectively. Thirty-eight patients (43%) returned to NUC treatment after an average interval of 9 months (range 1 months to 42 months). The risk factors influencing clinical relapse in patients included gender, baseline HBV DNA levels, treatment method, and alanine aminotransferase and aspartate aminotransferase levels at the end of treatment, Ishak fibrosis score > 2, and at the conclusion of treatment. In multivariate analysis, Ishak fibrosis score > 2 is the unique factor for retreatment.

CONCLUSION

In resource-constrained areas, discontinuing NUC may be considered for early-stage patients with low baseline hepatitis B viral DNA and alanine aminotransferase levels after a lengthy consolidation treatment. A higher pretreatment liver biopsy fibrosis score predicts relapse.

Keywords: Hepatitis B; Treatment; Discontinuation; Relapse; Re-treatment

Core Tip: Prolonged therapy remains the recommended method for patients with chronic hepatitis B. Nonetheless, concerns about treatment adherence and economic strain, particularly in resource-constrained areas, combined with research indicating that virological and clinical remission persists in non-cirrhotic patients after treatment cessation, prompted the development of nucleos(t)ide analog cessation guidelines for specific patients. However, the discontinuation of nucleos(t)ide analog is still a contested question. The median duration until recurrence was 11 months. The cumulative virological relapse rates, defined as chronic hepatitis B deoxyribonucleic acid over 2000 IU/mL, were 25%, 52%, 58%, and 61% at 6 months, 12 months, 24 months, and 36 months, respectively. The cumulative retreatment rates at 6 months, 12 months, 24 months, and 36 months were 19%, 25%, 28%, and 35%, respectively. Histologic fibrosis score > 2 is the unique factor for retreatment.