Letter to the editor: Hepatitis B virus reactivation in immune checkpoint inhibitor‐based combination therapies for hepatocellular carcinoma

作者：Zhi‐Cheng Jin, Jian‐Jian Chen, Biao Luo, Weihua Zhang, Gao‐Jun Teng · 发表于：Hepatology · 年份：2022 · DOI：10.1002/hep.32672 · 研究领域：Hepatitis B Virus Studies、Cancer Immunotherapy and Biomarkers、Hepatocellular Carcinoma Treatment and Prognosis

To the editor, We read with great interest the article by Papatheodoridi et al.1 that systematically reviewed data on hepatitis B virus (HBV) reactivation in patients who were Hepatitis B surface antigen (HBsAg) positive with hepatocellular carcinoma (HCC) receiving different therapy. Prophylactic antiviral treatment should be performed regardless of HCC treatment. However, there are a few reservations that are worth further in‐depth discussion. The risk and exact mechahnism of HBV reactivation induced by immune checkpoint inhibitors (ICIs) in HCC remain unclear and are still a matter of discussion. The programmed death‐1/programmed death‐ligand 1 (PD‐1/PD‐L1) axis plays an important role not only in cancer immune evasion but also in hepatitis virus infection. Blocking PD‐1/PD‐L1 axis can partially restore the defective HBV‐specific T and B cell responses. A pilot study found that nivolumab correlates with HBsAg levels declining in patients with chronic hepatitis B.2 Nevertheless, in the Asian cohort of the CheckMate 040 trial of nivolumab in adults with advanced HCC, 11% (5/47) of patients with HBV had >1 log increase in HBV DNA.3 This paradoxical effect might be explained by ICI treatment disrupting immune homeostasis, resulting in viral reactivation rather than expected viral suppression. Six studies included 366 patients treated with systemic therapy and provided reactivation data in this review. First, there was one data extraction error. Among them, one study (reference...