Immune Checkpoint Inhibitor Outcomes Across Child-Pugh A, B, and C Hepatocellular Carcinoma: A Real-World Integrated Health-System Cohort.
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BACKGROUND: Pivotal first-line immune checkpoint inhibitor (ICI) trials in advanced hepatocellular carcinoma (HCC) largely restricted enrollment to patients with Child-Pugh A liver function, leaving outcomes in patients with more advanced hepatic dysfunction poorly defined. We evaluated survival, tumor response, and early mortality across Child-Pugh A, B, and C classes in a real-world integrated health-system cohort. METHODS: We identified 264 consecutive patients with HCC who received first-line ICI-based systemic therapy at the University of Pittsburgh Medical Center between September 2015 and November 2024, with follow-up through December 2025. Child-Pugh class was re-adjudicated at ICI initiation. The primary endpoint was overall survival. Secondary endpoints included progression-free survival, objective response rate, disease control rate, and 90-day mortality. RESULTS: The cohort included 113 patients with Child-Pugh A, 124 with Child-Pugh B, and 27 with Child-Pugh C liver function. Median overall survival was 25.0 months, 13.3 months, and 4.2 months, respectively. Ninety-day mortality was 5.4%, 16.3%, and 40.7%, while objective response rate was 25.5%, 17.0%, and 5.6%. In multivariable Cox regression, Child-Pugh B and C remained independently associated with mortality compared with Child-Pugh A. Among patients who survived at least 90 days, disease control in Child-Pugh C was 38.5%, approaching that observed in Child-Pugh A. CONCLUSIONS: In this real-world HCC cohort, worsening Child-Pugh class was associated with progressively shorter survival and higher early mortality after first-line ICI therapy. Although outcomes in Child-Pugh C were poor overall, a subset of patients experienced durable survival or disease control. These findings support careful individualized treatment consideration rather than automatic exclusion of selected Child-Pugh C patients from ICI-based therapy.