Outcome of patients with HCC and liver dysfunction under immunotherapy: a systematic review and meta-analysis

BACKGROUND AIMS: Immunotherapy-based regimes have changed the management of hepatocellular carcinoma (HCC). However, evidence of efficacy in patients with impaired liver function is unknown. This systematic review and meta-analysis assesses survival of HCC patients and liver dysfunction treated with immunotherapy-based regimens.

METHODS: Systematic review and meta-analysis of original articles or abstracts reporting survival (OS) of HCC patients treated with immunotherapy according to liver function between 2017-2022. OS according to Restricted Mean Survival Time (RMST) and median OS, and hazard ratio (HR) of Child-Pugh B or B/C versus Child-Pugh A were assessed while considering the line of treatment.

RESULTS: Of 2.218 articles considered, 15 articles recruiting 2.311 patients were included. Of these, 639 (27.7%) were Child-Pugh B and 34 (1.5%) C. RMST was 8.36 (95%CI, 6.15-10.57; I2=93%) months, estimated from 8 studies. The HR was reported in 8 studies for survival between Child-Pugh B versus Child-Pugh A and metanalysis disclosed a 1.65 HR (95% CI 1.45-1.84, I2=0% heterogeneity P=0.45). Treatment line data were available for 47% of the patients and three studies included patients treated with atezolizumab-bevacizumab in first line.

CONCLUSIONS: The high heterogeneity across studies reflects the incapacity of the current evidence to support the indication of immunotherapy in HCC patients with relevant liver dysfunction. It is mandatory to report complementary information to Child-Pugh classification such as prior liver decompensation, use of concomitant medication to control ascites, or signs of clinically significant portal hypertension to allow better patient stratification in future studies.