Inflammatory markers in intrahepatic cholangiocarcinoma: Effects of advanced liver disease

BACKGROUND: To investigate the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) as prognostic biomarkers in intrahepatic cholangiocarcinoma (ICC) with a focus on viral hepatitis and liver status. METHODS: In this retrospective cohort study, patients from the institutional cancer registry with ICC from 2005 to 2016 were stratified by treatment group. Baseline inflammatory markers were dichotomized at the median. Overall survival (OS) was assessed via Kaplan-Meier curves and Cox proportional hazard models. Multiple patient, liver, and tumor factors were included in the multivariable analysis (MVA). RESULTS: About 131 patients (median age 65 years, 52% male, 76% Caucasian) had a median OS of 13.0 months. Resection/interventional oncology with/without systemic therapy had improved survival vs systemic therapy alone in Child-Pugh A patients (P < 0.01). In Child-Pugh B/C patients, this survival difference became nonsignificant (P = 0.22). Increased NLR and SII were associated with decreased survival (P < 0.01), while dichotomized PLR was not (P = 0.3). On MVA, increased NLR remained an independent prognostic factor (HR 1.6, P < 0.05). In Child-Pugh class A (n = 94), low-NLR had higher OS vs high-NLR (25.4 vs 12.2 months, P < 0.01). In Child-Pugh class B/C (n = 28), NLR did not have a significant effect on median OS (low- vs high-NLR: 6.7 vs 2.9 months, P = 0.2). Child-Pugh class acted as an effect modifier on MVA for NLR (P = 0.0124). CONCLUSIONS: The NLR has a stronger impact as a prognostic marker in ICC over the PLR and SII. This survival effect is decreased in advanced liver disease.