Neutrophil‐lymphocyte ratio in relation to risk of hepatocellular carcinoma in patients with non‐alcoholic fatty liver disease

Abstract

Background Blood neutrophil to lymphocyte ratio (NLR) or lymphocyte count may be important markers for immune function. Previous work has shown higher NLR was associated with higher risk of hepatitis B‐related hepatocellular carcinoma (HCC). However, studies in non‐alcoholic fatty liver disease (NAFLD) patients are lacking. Methods Utilizing the University of Pittsburgh Medical Center (UPMC) electronic health records, we created a retrospective cohort of 27,834 patients diagnosed with NAFLD from 2004 to 2018 with complete NLR data. After an average 5.5 years of follow‐up, 203 patients developed HCC. Cox proportional hazard regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of HCC incidence associated with different levels of NLR and lymphocyte count. Results Compared with the lowest tertile of NLR (<1.97), the highest tertile of NLR (≥3.09) was statistically significantly associated with a 43% higher risk of HCC incidence (HR = 1.43, 95% CI: 1.01–2.03, p trend = 0.031) after adjustment for age, sex, race, body mass index, smoking status, history of type 2 diabetes, hyperlipidemia, hypertension, and fibrosis‐4 score category. Conversely the highest tertile of lymphocyte count (≥2.15 K/ul) was significantly associated with a 36% lower risk of HCC (HR = 0.64, 95% CI: 0.43–0.94, p trend = 0.028) compared to the lowest tertile (<1.55 K/ul). There was no association between neutrophil count and HCC risk. Conclusions Higher NLR and lower lymphocyte count are associated with significantly higher risk of HCC among NAFLD patients. These findings warrant further investigation of immune response and surveillance in association with HCC development in NAFLD patients.

Distinct Morphological and Molecular Profiles of NAFLD and NAFLD-associated HCC Revealed by Immunohistochemistry and MicroRNA Analysis

“…The NLR, frequently used to assess inflammatory disorders, measures the absolute quantity of neutrophils in lymphocytes [30]. Our findings are in concordance with the evidence from a recent study by Thomas et al [31], who showed that patients with NAFLD with higher NLR counts have a greater chance of developing HCC.…”

Development of a nomogram to predict the risk of hepatocellular carcinoma in patients with hepatitis B-related cirrhosis on antivirals

“…The pathogenesis of HCC is closely related to immune status and inflammatory response ( 36 ). Our and other studies have reported that a higher NLR and lower lymphocyte count are associated with a significantly higher risk of HCC in patients with hepatitis-B related cirrhosis and non-alcoholic fatty liver disease ( 37 , 38 ). The immune system plays an important role in immune surveillance and controls tumor growth effects ( 39 ).…”

Non-invasive biomarkers prognostic of decompensation events in NASH cirrhosis: a systematic literature review

“…In the current review, one study was found linking NLR and absolute lymphocyte count to the prediction of HCC. NLR ≥ 3.09 predicted HCC development (HR: 1.43 (95% CI: 1.01–2.03), Table 2 ), whereas an absolute lymphocyte count ≥ 2.15 predicted lower HCC incidence (HR: 0.64 (95% CI: 0.43–0.94), Table 2 ) over 5.5 years follow-up [ 70 ]. Importantly, the authors of the study note that the NLR and lymphocyte count-associated risk of HCC development was independent of advanced fibrosis, as patients with mild fibrosis had the same risk to develop HCC as those with advanced fibrosis, provided their NLR and absolute lymphocyte count values were higher than the designated threshold.…”

“…Importantly, the authors of the study note that the NLR and lymphocyte count-associated risk of HCC development was independent of advanced fibrosis, as patients with mild fibrosis had the same risk to develop HCC as those with advanced fibrosis, provided their NLR and absolute lymphocyte count values were higher than the designated threshold. For this reason, the authors recommend using NLR and absolute lymphocyte counts as early markers of HCC rather than biomarkers for unidentified cirrhosis [ 70 ]. NRL and absolute lymphocyte count represent potentially interesting treatment monitoring biomarkers, as they reflect changes in immune cell dynamics that can be fluctuating according to the intensity of the immune response itself.…”