PD-1/PD-L1 blockade as part of combination strategies toward functional cure of chronic hepatitis B
In brief
PD-1 blocker plus pegylated interferon cures 30% of chronic hepatitis B
Early trials in patients already suppressed on nucleos(t)ide analogues showed that adding a PD-1/PD-L1 inhibitor markedly lowered hepatitis B surface antigen levels, and when combined with pegylated interferon, about 30% achieved sustained loss of HBsAg-a functional cure. The approach still needs optimal dosing, patient selection, and safety data from larger trials.
- Journal
- Frontiers in immunology (Q1)
- Published
- 9 July 2026
- Study design
- Narrative review / expert opinion
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Mei Li, Dandan Feng, Juanjuan Shi, Shuangsuo Dang, Xiaoli Jia, Wenjun Wang
- PMID
- 42495600
- DOI
- 10.3389/fimmu.2026.1831739
Why clinicians should know about it
- Picked for Hepatology (top studies of the week, 26 July 2026).
- Picked for Immunology and Allergy (paper of the day, 25 July 2026).
Abstract
Chronic hepatitis B (CHB) affects 260 million people worldwide. Despite advances in antiviral therapies, functional cure, characterized by sustained loss of hepatitis B surface antigen (HBsAg) and durable viral control after treatment cessation, remains infrequent. The PD-1/PD-L1 immune checkpoint pathway plays an important role in the exhaustion of hepatitis B virus (HBV)-specific T cells, thereby limiting the immune system's ability to clear HBV. Blocking the PD-1/PD-L1 pathway has emerged as a promising strategy to overcome this immune exhaustion to some extent and reinvigorate antiviral T-cell responses in CHB patients. Early clinical trials, particularly among patients who have achieved viral suppression with nucleos(t)ide analogues, have demonstrated that PD-1/PD-L1 inhibitors can significantly reduce HBsAg levels. Notably, a subset of patients has achieved functional cure, particularly among those with low baseline HBsAg levels. These effects have been further enhanced in combination with pegylated interferon, resulting in a functional cure rate of 30%. While challenges remain, such as optimizing dosing regimens, selecting patients, identifying response predictors and managing immune-related adverse events, these findings emphasize the potential of combination regimens involving PD-1/PD-L1 blockade as a means of achieving a functional cure in CHB patients. Future large-scale randomized controlled trials are essential to fully assess the approach's efficacy and safety, and to refine its clinical application.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.