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

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.

Keywords: carcinoma; hepatitis C; hepatocellular; inflammation; lymphocytes; neutrophils.

FIGURE 1

Correlation between log‐transformed inflammatory biomarkers. (A) Platelet‐to‐lymphocyte ratio by neutrophil‐to‐lymphocyte ratio (Spearman ρ = 0.62). (B) Systemic immune‐inflammatory index by neutrophil‐to‐lymphocyte ratio (Spearman ρ = 0.74) (C) Systemic immune‐inflammatory index by platelet‐to‐lymphocyte ratio (Spearman ρ = 0.85)

FIGURE 2

Kaplan–Meier curves of survival from diagnosis of HCC by NLR group. (A) Entire cohort (log‐rank test, p < 0.0001). (B) Nonviral hepatitis (log‐rank test, p < 0.0001). (C) Viral hepatitis (Wilcoxon test, p = 0.0109)