The effect of chronic viral hepatitis on prognostic value of inflammatory biomarkers in hepatocellular carcinoma

• Main Authors: Cortlandt M. Sellers, Johannes Uhlig, Johannes M. Ludwig, Jeffrey S. Pollak, Tamar H. Taddei, Stacey M. Stein, Joseph K. Lim, Hyun S. Kim
• Format: Article
• Language: English
• Published: Wiley 2021-08-01
• Series: Cancer Medicine
• Subjects: hepatitis C; carcinoma; hepatocellular; inflammation; neutrophils; lymphocytes
• Online Access: https://doi.org/10.1002/cam4.3573

Abstract Background Inflammation and the immune system significantly impact the development, progression, and treatment response of hepatocellular carcinoma (HCC). This retrospective study investigated the neutrophil‐to‐lymphocyte ratio (NLR) as a prognostic biomarker in Western patients with HCC in the setting of chronic viral hepatitis. Methods Patients diagnosed with HCC from 2005 to 2016 were selected from a tertiary care institution. NLR was calculated within 30 days prior to treatment and dichotomized at the median. Kaplan–Meier overall survival (OS) curves and Cox hazard proportional models were utilized. Tumor and liver reserve parameters were included in multivariable analyses (MVA). Results A total of 581 patients met inclusion criteria (median age 61.0 yr; 78.3% male; 66.3% Caucasian) with median OS = 34.9 mo. 371 patients (63.9%) had viral hepatitis, of which 350 had hepatitis C (94.3%). The low‐NLR group (<median NLR = 2.45) demonstrated higher median OS of 45.6 mo versus the high‐NLR group (median OS 23.9 mo, p < 0.0001). Log‐transformed NLR was associated with decreased OS, after multivariable adjustment for confounders (hazard ratio [HR] = 1.34, p = 0.0033). Viral hepatitis was identified as an NLR effect modifier: in nonviral hepatitis (n = 210), low NLR was associated with higher median OS versus high NLR (56.7 mo vs. 17.6 mo, p < 0.0001). This was decreased in viral hepatitis (n = 371) (low vs. high NLR: 41.9 mo vs. 35.2 mo, p = 0.0109). Further, the interaction term between hepatitis and log‐transformed NLR was significant (p = 0.0274) on MVA. Conclusions Lower baseline NLR was associated with increased overall survival in HCC. Viral hepatitis serves as an effect modifier of NLR, attenuating its prognostic relevance in this hepatitis C‐predominant population.