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.