Letter: Hepatotoxicity in Malignancies Under ICIs Treatment

We had the pleasure of reading the research article by Hung et al. [1] We sincerely appreciate their meticulous work and significant contributions, and we hope to offer some constructive suggestions for future research. Firstly, the article provides a comprehensive account of the patients' baseline data and outlines the baseline demographic characteristics of the study population, which is commendable. However, the authors have not adequately processed the data. It is clear that the hepatocellular carcinoma (HCC) cohort had significantly higher baseline alanine aminotransferase (ALT) levels and a greater proportion of hepatitis B surface antigen (HBsAg)-positive patients compared to the non-HCC cohort, indicating that the HCC group was more predisposed to liver events. This makes it difficult to accurately conclude that liver events were caused by immune checkpoint inhibitors (ICIs). Hence, we recommend the authors adopt a prospective study design to better control for variables, or use methods such as propensity score matching to minimise confounding bias [2]. Secondly, solely reporting HBsAg positivity is insufficient. HBsAg positivity indicates the presence of hepatitis B virus (HBV) infection but does not necessarily reflect the activity level of the virus. Higher levels of viral activity are often associated with more severe liver damage. We recommend including additional indicators, such as hepatitis B e antigen (HBeAg) status and HBV DNA levels, to provide a more comprehensive assessment of viral activity [3]. Additionally, several critical confounding factors have not been considered, such as underlying comorbidities (e.g., diabetes, hypertension and fatty liver disease), concurrent treatments (e.g., chemotherapy and targeted therapy), tumour size and staging. A detailed analysis of these factors would further strengthen the reliability and robustness of the study's conclusions [4]. Furthermore, the article identifies ALT > 40 U/L as an independent risk factor for hepatitis flare following ICI therapy but does not delve into the specific causes of this abnormality, such as viral activity or immune-related damage. Comprehensive virological assessments, including the measurement of HBV DNA levels and HBeAg status, could provide greater clarity on whether the ALT elevation is driven by active viral replication. In conclusion, this study provides valuable insights into the risk of liver events in HCC patients receiving ICI therapy. Future research should strive to thoroughly elucidate the mechanisms underlying liver events associated with ICI treatment, optimise clinical management strategies and improve the safety and effectiveness of patient care. Yue Zou: writing – review and editing, writing – original draft. Zhengyu Zhang: writing – review and editing, writing – original draft. Jianjun He: investigation, conceptualization. The authors declare no conflicts of interest. This article is linked to Hung et al paper. To view this article, visit https://doi.org/10.1111/apt.18403. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.