Immune checkpoints on T and NK cells in the context of HBV infection: Landscape, pathophysiology and therapeutic exploitation

SummaryBackground and AimsFor chronic hepatitis B (CHB) patients, there is still a need to improve hepatitis B surface antigen (HBsAg) clearance rates. This study aimed to assess the predictive effectiveness of soluble programmed cell death‐1 (sPD‐1) and soluble programmed cell death ligand‐1 (sPD‐L1) for HBsAg clearance in HBeAg‐negative CHB patients undergoing peginterferon (Peg‐IFN)‐based antiviral treatment.MethodsThis study encompassed 280 patients undergoing treatment with Peg‐IFNα. Serum levels of sPD‐1 and sPD‐L1 were measured using ELISA kits at baseline, as well as at 12, 24 and 48 weeks. The primary endpoint of the study was the determination of HBsAg clearance at 48 weeks. Logistic regression analysis was employed to identify predictors of HBsAg clearance.ResultsThe clearance group demonstrated significantly lower serum sPD‐L1 levels compared to the non‐clearance group. While both groups exhibited an increase in sPD‐1 levels, only the clearance group showed a rise in sPD‐L1 levels. Multivariate analysis identified sPD‐L1 increase at 24 weeks, and HBsAg decline at 24 weeks as predictors for HBsAg clearance at 48 weeks. The combined use of these indicators showed a predictive performance for HBsAg clearance with an AUROC of 0.907 (95% CI: 0.861–0.953, p < 0.001).ConclusionsThe study revealed an inverse relationship between the trends of sPD‐1/sPD‐L1 and HBsAg clearance during combined IFN and NAs treatment. Moreover, the magnitude of HBsAg reduction and sPD‐L1 increase emerged as significant predictors for HBsAg clearance.

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Hepatitis B reactivation in cancer patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis

Xia,

Zhang,

Chen

et al. 2023

Infect Dis Poverty

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Background Immunotherapy shows promise as a treatment option for various cancers. However, there is growing concern over potential complications from hepatitis B virus (HBV) reactivation after checkpoint blockade immunotherapy. Although most of the previous clinical trials on immune checkpoint inhibitors (ICIs) excluded patients with HBV, a few case reports and retrospective studies of HBV reactivation have been published. The aim of this study is to assess the risk of hepatitis B virus reactivation (HBVr) in patients receiving ICIs for advanced cancer. Methods English and Chinese language literature published prior to April 30, 2023, was searched in PubMed, EMBASE, Web of Science, Cochrane, SinoMed, CNKI and Wanfang Data for studies reporting HBVr rates in cancer patients treated with ICIs. A pooled risk estimate was calculated for HBVr rates with 95% confidence intervals (CI). Results Data from 34 studies including 7126 patients were retrieved and analyzed. The pooled HBVr rate in cancer patients treated with ICIs was 1.3% (I2 = 90.44%, 95% CI: 0.2–2.9%, P < 0.001). Subgroup analysis revealed that patients diagnosed with hepatocellular carcinoma (HCC), HBV carriers, and patients from Asian regions or in developing countries have a higher rate of HBVr. Conclusions Our meta-analysis demonstrated a low risk of HBVr in patients treated with ICIs for advanced cancer. ICI treatment may be safely used in patients with existing HBV infection or chronic hepatitis B, accompanied by regular monitoring and appropriate antiviral prophylaxis if necessary. Graphical Abstract

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Immune checkpoints on T and NK cells in the context of HBV infection: Landscape, pathophysiology and therapeutic exploitation

Cited by 4 publications

References 210 publications

Sofosbuvir (+) daclatasvir (+) ribavirin in Egyptian patients with hepatitis C virus: Therapeutic outcomes and the prognostic role of natural killer cells

Sofosbuvir (+) daclatasvir (+) ribavirin in Egyptian patients with hepatitis C virus: Therapeutic outcomes and the prognostic role of natural killer cells

Serum sPD‐1 and sPD‐L1 as predictive biomarkers for HBsAg clearance in HBeAg‐negative CHB patients undergoing IFN‐based therapy

Hepatitis B reactivation in cancer patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis

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