Date of Award

January 2019

Document Type


Degree Name

Medical Doctor (MD)



First Advisor

Hyun S. Kim


Inflammatory Markers as Predictors in Primary Liver Cancers with Emphasis on Chronic Viral Hepatitis

Cortlandt M. Sellers and Hyun S. Kim. Section of Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale University, Yale School of Medicine, New Haven, CT, USA.

Inflammation and the immune system significantly impact the development, progression, and treatment response of primary liver cancers (PLC), namely hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). This retrospective study investigated the peripheral blood neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index (SII) as prognostic biomarkers in patients with PLC in the setting of advanced liver disease and chronic viral hepatitis. Patients diagnosed with HCC or ICC from 2005 to 2016 were selected from the cancer registry of a single tertiary care institution. Baseline NLR was calculated within 30 days prior to treatment and was dichotomized at the median. Kaplan-Meier overall survival (OS) curves and Cox hazard proportional models were performed. Tumor and liver reserve parameters were included and analyzed in multivariable analyses (MVA). 581 HCC patients and 109 ICC patients met inclusion criteria. In both forms of PLC, the low-NLR group demonstrated higher median overall survival vs. the high-NLR group (p<0.01). Log-transformed NLR was also associated with decreased OS, after multivariable adjustment for confounders (p<0.05). In HCC, viral hepatitis was identified as a NLR effect modifier (interaction term p<0.05) on MVA. In ICC, advanced liver disease acted as an effect modifier for the NLR (p<0.05). Lower baseline neutrophil-to-lymphocyte ratio is associated with increased overall survival in HCC and ICC and has more utility than the PLR or the SII as a prognostic marker. The impact of the NLR is decreased by chronic viral hepatitis in HCC and advanced liver disease in ICC.


This thesis is restricted to Yale network users only. It will be made publicly available on 07/15/2021