Prognostic value of a simplified score based on routine parameters in patients with hepatocellular carcinoma treated...

The systemic treatment landscape for advanced hepatocellular carcinoma (HCC) has evolved from tyrosine kinase inhibitors, such as sorafenib (SOR), to immune checkpoint inhibitor-based combinations (IO). Despite these advances, there is a lack of simple, objective tools to stratify patient prognosis in clinical practice. While several laboratory parameters are known to correlate with outcomes, their combined utility across treatment types remains unclear. We aimed to evaluate the prognostic value of commonly available biomarkers and to develop a simplified score applicable to both SOR- and IO-treated patients.

This retrospective cohort study analyzed patients with advanced or intermediate-stage HCC treated with first-line systemic therapy at a single center in Brazil from 2009 to 2024. Patients were stratified into a SOR cohort and an IO cohort. Baseline variables included demographics and biochemical markers. We assessed the association between survival and three baseline biomarkers: alpha-fetoprotein (AFP), albumin-bilirubin (ALBI) grade, and neutrophil-to-lymphocyte ratio (NLR). A prognostic score was developed in the SOR cohort by assigning one point to each adverse factor: AFP ≥200 ng/mL, ALBI grade 2-3, and NLR ≥3. Overall survival (OS) was estimated by the Kaplan-Meier method and compared using the log-rank test. Hazard ratios (HRs) were derived from Cox regression models.

The study included 440 patients in the SOR cohort and 32 in the IO cohort. In the SOR cohort. Most patients in both cohorts were Child-Pugh A, PS 0-1 and hepatitis C was the predominant etiology. AFP ≥200 ng/mL (P<0.001), ALBI 2-3 (P<0.001), and NLR ≥3 (P<0.001) were independently associated with worse OS. Median OS in the SOR cohort was 17.4 months for patients with 0-1 points, 7.9 months for 2 points, and 4.2 months for 3 points (P<0.001). The score remained prognostic in the IO cohort, where patients with 0-1 vs. 2-3 points had significantly different OS (HR 2.2; 95% CI: 1.1-4.9; P=0.04).

This simplified prognostic score, based on three routine laboratory parameters, stratifies survival outcomes in HCC patients receiving either sorafenib or immunotherapy. While further validation is needed in larger and more diverse populations, this tool may support individualized clinical counseling and risk-adapted trial design.