Hepatocellular carcinoma development in diabetic patients: a nationwide survey in Japan

Ryosuke Tateishi ,Takeshi Matsumura ,Masato Kasuga ,Eiichi Araki ,Goshi Shiota ,Takayoshi Sasako ,Naoto Kubota ,Etsuko Hashimoto ,Hirotaka Watada ,Kazuhiko Koike ,Kazuyoshi Kon ,Takeshi Okanoue ,Hiroshi Inoue ,Kosuke Kashiwabara ,Koji Uchino ,Toshihide Shima ,Hideo Tanaka ,Yutaka Matsuyama ,Hitoshi Shimano ,Makiko Taniai ,Naoto Fujiwara ,Takafumi Senokuchi ,Sumio Watanabe ,Takumi Kawaguchi ,Kohjiro Ueki ,Shuichi Kaneko ,Lucid Study Investigators

doi:10.1007/s00535-020-01754-z

Abstract

BackgroundAlthough type 2 diabetes mellitus (T2DM) is a known risk factor for hepatocellular carcinoma (HCC) development, the annual incidence in diabetes patients is far below the threshold of efficient surveillance. This study aimed to elucidate the risk factors for HCC in diabetic patients and to determine the best criteria to identify surveillance candidates.MethodsThe study included 239 patients with T2DM who were diagnosed with non-viral HCC between 2010 and 2015, with ≥ 5 years of follow-up at diabetes clinics of 81 teaching hospitals in Japan before HCC diagnosis, and 3277 non-HCC T2DM patients from a prospective cohort study, as controls. Clinical data at the time of and 5 years before HCC diagnosis were collected.ResultsThe mean patient age at HCC diagnosis was approximately 73 years, and 80% of the patients were male. The proportion of patients with insulin use increased, whereas the body mass index (BMI), proportion of patients with fatty liver, fasting glucose levels, and hemoglobin A1c (HbA1c) levels decreased significantly in 5 years. In the cohort study, 18 patients developed HCC during the mean follow-up period of 4.7 years with an annual incidence of 0.11%. Multivariate logistic regression analyses showed that the FIB-4 index was an outstanding predictor of HCC development along with male sex, presence of hypertension, lower HbA1c and albumin levels, and higher BMI and gamma-glutamyl transpeptidase levels. Receiver-operating characteristic analyses showed that a FIB-4 cut-off value of 3.61 could help identify high-risk patients, with a corresponding annual HCC incidence rate of 1.1%.ConclusionA simple calculation of the FIB-4 index in diabetes clinics can be the first step toward surveillance of HCC with a non-viral etiology.

Highlights

Liver cancer is the seventh most common cancer and the fourth most common cause of death [1]
Multivariate logistic regression analyses showed that the FIB-4 index was an outstanding predictor of hepatocellular carcinoma (HCC) development along with male sex, presence of hypertension, lower HbA1c and albumin levels, and higher body mass index (BMI) and gamma-glutamyl transpeptidase levels
A simple calculation of the FIB-4 index in diabetes clinics can be the first step toward surveillance of HCC with a non-viral etiology

Summary

Introduction

Liver cancer is the seventh most common cancer and the fourth most common cause of death [1]. Growing evidence suggests that obesity and diabetes increase various cancer risks [5,6,7,8,9], and the liver is one of the organs upon which obesity and obesity-associated conditions have the largest impact [5, 8, 10, 11]. Obesity and diabetes represent the largest risk factors for liver cancer development in the United States [12], and the increase in the incidence of HCC was the highest among all types of cancers between 2003 and 2012 [13]. 2 diabetes mellitus (T2DM) is a known risk factor for hepatocellular carcinoma (HCC) development, the annual incidence in diabetes patients is far below the threshold of efficient surveillance. This study aimed to elucidate the risk factors for HCC in diabetic patients and to determine the best criteria to identify surveillance candidates.

Objectives

Methods

Results

Conclusion