Letter to the Editor: Hepatic decompensation is the major driver of mortality in hepatocellular carcinoma patients treated with atezolizumab plus bevacizumab: The impact of successful antiviral treatment

To the editor, We read with great interest the study by Celsa et al1 examining hepatic decompensation in patients with HCC receiving atezolizumab plus bevacizumab. While providing important insights into outcomes during immunotherapy, several aspects merit further discussion. First, the identification of ALBI grade >1 and nonviral etiology as independent predictors of decompensation raises critical questions about optimal patient selection. Given the strong prognostic impact demonstrated (19-fold increased mortality risk), should we consider more stringent liver function criteria for immunotherapy initiation in nonviral HCC? The study shows that patients with ALBI grade 2/3 and nonviral etiology had a 31% 12-month decompensation risk,1 yet excluding these patients could deny potentially effective therapy. This highlights the need for better risk stratification tools beyond current parameters. Second, the protective effect of successful antiviral therapy (subdistribution HR 0.48) demands further investigation.2 The optimal timing of antiviral therapy relative to immunotherapy initiation remains unclear. Moreover, standardized protocols for managing chronic viral hepatitis during immunotherapy are lacking. In addition, strategies for metabolic risk factor modification in nonviral HCC require prospective evaluation, given limited treatment options for these patients.3,4 Third, while demonstrating that only 14% of decompensated patients received subsequent therapy versus 61% with progression alone, the study could not address whether earlier intervention in high-risk patients might prevent decompensation. Could prophylactic beta-blockers, albumin support, or careful portal pressure monitoring benefit selected patients5? The role of preventive measures needs evaluation through randomized trials. Fourth, the relationship between tumor response and decompensation warrants deeper exploration. Understanding whether early tumor response might prevent later decompensation could inform treatment duration decisions. In addition, the impact of different progression patterns on decompensation risk deserves investigation. Finally, the study raises important questions about monitoring strategies. Should high-risk patients undergo more frequent liver function assessments? What are the optimal intervals for surveillance? How can we better predict and prevent the transition from compensation to decompensation? These questions highlight the need for prospective studies integrating both oncologic and hepatologic endpoints in HCC immunotherapy trials. The findings emphasize that optimizing outcomes requires careful attention to liver function preservation alongside tumor control. Future research should focus on developing comprehensive risk prediction models and evaluating preventive strategies for high-risk populations.