Plasma interleukin-17 and alpha-fetoprotein combination effectively predicts imminent hepatocellular carcinoma occurrence in liver cirrhotic patients

Kung-Hao Liang,Yang-Hsiang Lin,Rong-Nan Chien,Tong-Hung Wang,Chau-Ting Yeh,Wey-Ran Lin,Ya-Hui Huang,Chih-Lang Lin,Tsung-Hui Hu,Yu-De Chu,Ming-Wei Lai

doi:10.1186/s12876-021-01761-1

Abstract

BackgroundPredicting imminent hepatocellular carcinoma (HCC) in liver cirrhotic patients is an unmet medical need. We aimed to investigate circulatory biomarkers and their optimum combinations in a prospective study.MethodsWe investigated plasma interleukin 17 (IL-17) concentrations, quantified using enzyme-linked immunosorbent assay (ELISA), for the prediction of HCC in a large cohort of 404 HCC-naïve liver cirrhotic patients regularly followed after recruitment. Additionally, IL-17 in surgically resected tumor tissues were evaluated using immunohistochemistry staining.ResultsIL-17 was detected in HCC tissues. The IL-17 concentrations in the peripheral blood do not have correlation with an extensive list of 31 common demographic, metabolic and liver function variables in the cohort of liver cirrhotic patients. Furthermore, patients stratified by IL-17 and alpha-fetoprotein (AFP) showed distinctive cumulative incidence of HCC. Imminent HCC, defined here as HCC occurrence within 1 year, can be predicted by IL-17 alone with an area under the receiver operating characteristic curve [AUC] of 0.762 (P = 0.002). An multivariate analysis showed that age, hepatitis C viral infection, AFP and IL-17 were four independent factors associated with imminent HCC (adjusted P = 0.03, 0.041, 0.024 and 0.008 respectively). An explicit risk score (R) combining the concentrations of two plasma biomarkers, AFP and IL-17, achieved a high AUC of 0.933 (95% confidence interval 0.893–0.972, P < 0.001) in predicting imminent HCC, with 100% sensitivity and 79.9% specificity at the optimum cutoff. The score is defined as: {text{R}} = (2.6914)*{text{IL-17}} + (0.3909)*{text{AFP}} - (0.80812875)*{text{IL-17}}^{2} + (0.10288876884)*{text{IL-17}}^{2} *{text{AFP}}.ConclusionsThe circulatory IL-17 concentration is a predictor of subsequent HCC occurrence in liver cirrhotic patients. The combination of AFP and IL-17 is highly effective in predicting imminent HCC within 1 year.

Highlights

Predicting imminent hepatocellular carcinoma (HCC) in liver cirrhotic patients is an unmet medical need
Noninvasive scores such as fibrosis-4 (FIB-4), Aspartate aminotrans‐ ferase (AST) to Platelet Ratio Index (APRI) and gamma-glutamyl transpeptidase-to-platelet ratio have been developed to estimate the severity of fibrosis [3, 4]
IL‐17 and AFP are present in HCC tissues We first evaluated whether interleukin 17 (IL-17) and AFP can be found in the tumor tissues of patients in Taiwan

Summary

Introduction

Predicting imminent hepatocellular carcinoma (HCC) in liver cirrhotic patients is an unmet medical need. Knowing exactly when HCC will occur is highly pertinent to the clinical care of cirrhotic patients. Noninvasive scores such as fibrosis-4 (FIB-4), AST to Platelet Ratio Index (APRI) and gamma-glutamyl transpeptidase-to-platelet ratio have been developed to estimate the severity of fibrosis [3, 4]. These scores were subsequently used for the prediction of HCC [5,6,7,8,9,10,11], based on the rationale that the severity of fibrosis correlates with HCC risks. The organic anion transporter peptides (OATP) 1B1 and 1B3 has been shown to be indicative of HCC recurrence after liver transplanation [14]

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