Prognostic Value of the C-Reactive Protein-Albumin-Lymphocyte Index in Hepatobiliary and Pancreatic Cancers: A Systematic Review and Meta-Analysis.

BACKGROUND: The C-reactive protein-albumin-lymphocyte (CALLY) index integrates systemic inflammation, nutritional status, and immune competence, but evidence in hepatobiliary and pancreatic (HBP) malignancies remains uncertain. We evaluated its association with survival outcomes. METHODS: A systematic search of PubMed, Embase, Scopus, and Web of Science was performed from inception to 9 September 2026. Observational studies involving adults with hepatobiliary and pancreatic malignancies were eligible if they evaluated pretreatment CALLY and reported HRs for survival outcomes. Random-effects were used to pool HRs for overall survival (OS) and recurrence-free/disease-free survival (RFS/DFS). Risk of bias was assessed using the Newcastle-Ottawa Scale, and certainty of evidence was evaluated using GRADE. RESULTS: Sixteen studies (17 cohorts; 3,833 participants) were included. High CALLY was associated with better OS across 17 cohorts (HR 0.50, 95% CI 0.44-0.58; I²=35.3%) and better RFS/DFS across eight cohorts (HR 0.60, 95% CI 0.49-0.73; I²=55.0%). Cancer-specific OS estimates favored high CALLY in hepatocellular carcinoma (HR 0.58), cholangiocarcinoma (CCA)/biliary tract cancer (HR 0.47), and pancreatic cancer (HR 0.46). Exploratory anatomical stratification of CCA reduced heterogeneity from 56.5% overall to 11.0% in intrahepatic CCA and 0% in mixed CCA/biliary cohorts. Leave-one-out analyses identified no influential cohort. Funnel-plot asymmetry suggested small-study effects for OS. Evidence certainty was moderate for both outcomes. CONCLUSION: High pretreatment CALLY was associated with favorable survival across HBP malignancies. Predominantly retrospective evidence, heterogeneous clinical settings, variable cutoffs, and possible small-study effects preclude routine clinical use. Prospective multicenter validation using standardized thresholds is required.