Higher Accumulation of Visceral Adipose Tissue Is an Independent Risk Factor for Hepatocellular Carcinoma among Viral Hepatitis Patients with Non-Cirrhotic Livers.

Kenji Imai,Yohei Shirakami,Toshihide Maeda,Koji Takai,Takao Miwa,Tatsunori Hanai,Masahito Shimizu,Atsushi Suetsugu

doi:10.3390/cancers13235980

Abstract

Simple SummaryHepatocellular carcinoma (HCC) occurring in non-cirrhotic livers is often overlooked in clinical practice because the present HCC surveillance strategies usually focus only on patients with cirrhotic livers. This study aimed to determine the risk factors for HCC among viral hepatitis patients with non-cirrhotic livers. The findings of this study could be very useful in detecting HCC at an early stage, especially in patients with viral hepatitis who may not have developed extensive cirrhosis.This study aimed to determine the risk factors for hepatocellular carcinoma in non-cirrhotic livers among viral hepatitis patients. A total of 333 HCC cases, including 69 hepatitis B virus (HBV)-related and 264 hepatitis C virus (HCV)-related, were divided into cirrhotic (Fibrosis-4 [FIB-4] index > 3.25) and non-cirrhotic groups (FIB-4 index ≤ 3.25). The clinical characteristics of the two groups were compared. The independent risk factors for the development of HCC were analyzed using logistic regression analysis. The patients with HBV-related HCC were significantly younger, had better Child-Pugh scores, lower FIB-4 index and Mac-2 binding protein glycosylated isomers (M2BPGi) levels, more progressive cancer stage, and higher alpha-fetoprotein (AFP) levels than those with HCV-related HCC. Diabetes mellitus and hypertension were less common in patients with HBV-related HCC. The non-cirrhotic group with HBV-related HCC had a higher visceral adipose tissue index (VATI), better Child-Pugh score, and higher hemoglobin A1c (HbA1c), whereas the one with HCV-related HCC had a higher proportion of men, higher VATI, better Child-Pugh score, higher HbA1c, and a higher prevalence of hypertension, than the corresponding cirrhotic groups. Logistic regression analyses demonstrated that age, male sex, VATI, HbA1c, the presence of hypertension, and HBV etiology were independent risk factors for HCC in a non-cirrhotic liver. A high accumulation of VAT is a risk factor for HCC in patients with non-cirrhotic livers.

Highlights

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide; more than half a million people are diagnosed with HCC annually [1]
Typical HCC was diagnosed based on lesions that were visualized as high-attenuation areas in the arterial phase, and low-attenuation areas in the portal/equilibrium phase of dynamic computed tomography (CT) or magnetic resonance imaging (MRI) compared to the surrounding liver parenchyma
In case of hepatitis C virus (HCV)-related HCC (Table 3), the non-cirrhotic group had a higher proportion of men, higher visceral adipose tissue index (VATI) (40.5 cm2/m2 vs. 33.7 cm2/m2, p = 0.015), better Child-Pugh score (5/6/7/8/9/10/11/12: 51/8/4/0/0/0/0/0 vs. 88/58/34/15/2/3/1/0, p < 0.011), higher hemoglobin A1c (HbA1c) (6.2 vs. 5.8%, p = 0.006), and a higher prevalence of hypertension (37/26 vs. 77/124, p = 0.005)

Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide; more than half a million people are diagnosed with HCC annually [1]. 20% of the cases of nonalcoholic fatty liver disease (NAFLD), hepatic manifestations of obesity, and metabolic syndromes present as nonalcoholic steatohepatitis with a risk of progression to cirrhosis and HCC [5]. Regardless of these etiologies, cirrhosis precedes the diagnosis of HCC in most individuals, but cirrhosis is not always a prerequisite of HCC development [5]. According to the guidelines of the American Association for the Study of Liver Diseases, the European Association for the Study of the Liver, and the Japan Society of Hepatology (JSH) [6,7,8], cirrhosis patients are considered at a high risk for developing HCC, and frequent HCC surveillance is recommended for these patients. To screen for HCC, including the cases originating in non-cirrhotic livers, the risk factors for HCC in a non-cirrhotic liver should be determined

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