Factors influencing subclinical atherosclerosis in patients with biopsy-proven nonalcoholic fatty liver disease.

Taeang Arai,Norio Itokawa,Tomomi Okubo,Ai Iwashita,Keiko Kaneko,Akihito Tsubota,Etsuko Iio,Katsuhiko Iwakiri,Yasuhito Tanaka,Tomohide Tanabe,Masanori Atsukawa,Chiaki Kawamoto,Mai Koeda,Tadamichi Kawano,Chisa Kondo,Naoya Emoto,Tsutomu Hatori,Korenobu Hayama,Yūji Yoshida

doi:10.1371/journal.pone.0224184

Abstract

Although the presence of nonalcoholic fatty liver disease (NAFLD) is known to be related to subclinical atherosclerosis, the relationship between the severity of NAFLD and subclinical atherosclerosis is not clear. This study aimed to clarify the factors related to subclinical arteriosclerosis, including the histopathological severity of the disease and PNPLA3 gene polymorphisms, in NAFLD patients. We measured brachial-ankle pulse wave velocity (baPWV) as an index of arterial stiffness in 153 biopsy-proven NAFLD patients. The baPWV values were significantly higher in the advanced fibrosis group than in the less advanced group (median, 1679 cm/s vs 1489 cm/s; p = 5.49×10-4). Multiple logistic regression analysis revealed that older age (≥55 years) (p = 8.57×10-3; OR = 3.03), hypertension (p = 1.05×10-3; OR = 3.46), and advanced fibrosis (p = 9.22×10-3; OR = 2.94) were independently linked to baPWV ≥1600 cm/s. NAFLD patients were categorized into low-risk group (number of risk factors = 0), intermediate-risk group (= 1), and high-risk group (≥2) based on their risk factors, including older age, hypertension, and biopsy-confirmed advanced fibrosis. The prevalence of baPWV ≥1600 cm/s was 7.1% (3/42) in the low-risk group, 30.8% (12/39) in the intermediate-risk group, and 63.9% (46/72) in the high-risk group. Non-invasive liver fibrosis markers and scores, including the FIB-4 index, NAFLD fibrosis score, hyaluronic acid, Wisteria floribunda agglutinin positive Mac-2-binding protein, and type IV collagen 7s, were feasible substitutes for invasive liver biopsy. Older age, hypertension, and advanced fibrosis are independently related to arterial stiffness, and a combination of these three factors may predict risk of arteriosclerosis in NAFLD patients.

Highlights

Nonalcoholic fatty liver disease (NAFLD) is a major chronic liver disease, with a worldwide prevalence of approximately 25% [1, 2]
The patatin-like phospholipase domain containing 3 gene (PNPLA3) rs738409 was genotyped in 142 patients, and the distribution of the PNPLA3 polymorphisms was as follows: CC, GC, and GG genotypes were found in 40.1% (57/142), 40.1% (57/142), and 19.7% (28/142) of patients, respectively
We clarified that older age, hypertension, and advanced liver fibrosis were independently associated with arterial stiffness in Japanese biopsy-proven NAFLD patients

Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD) is a major chronic liver disease, with a worldwide prevalence of approximately 25% [1, 2]. The disease is associated with the risk of progression to liver cirrhosis and hepatocellular carcinoma in some patients [3, 4]. The prognosis of NAFLD patients depends on the advancement of liver fibrosis [5,6,7] and is less favorable than that of healthy individuals. NAFLD is a multifactorial disease mutually associated with metabolic syndrome [9]. The presence of NAFLD is associated with subclinical atherosclerosis, independent from conventional metabolic risk factors [10,11,12]. The association between the advancement liver fibrosis and subclinical atherosclerosis remains controversial. A few studies have investigated the association between histological severity and subclinical atherosclerosis in biopsy-diagnosed NAFLD patients [13,14,15]

Objectives

Methods

Results

Conclusion