Observational Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2016; 22(21): 5096-5103
Published online Jun 7, 2016. doi: 10.3748/wjg.v22.i21.5096
Serum adipokines might predict liver histology findings in non-alcoholic fatty liver disease
Raika Jamali, Mohsen Razavizade, Abbas Arj, Mohammad Hossein Aarabi
Raika Jamali, Research Development Center, Sina Hospital, Tehran 15614, Iran
Raika Jamali, Digestive Disease Research Institute, Tehran University of Medical sciences, Tehran 15614, Iran
Mohsen Razavizade, Abbas Arj, Department of Internal Medicine, Shahid Beheshti Hospital, Kashan University of Medical Sciences, Kashan 87137, Iran
Mohammad Hossein Aarabi, Research Center for Biochemistry and Nutrition in Metabolic Disease, Faculty of Medicine, Kashan University of Medical Sciences, Kashan 87137, Iran
Author contributions: Jamali R and Aarabi MH proposed the idea and designed the research; Jamali R, Arj A and Razavizade M diagnosed NAFLD and enrolled patients; Jamali R, Arj A, Aarabi MH and Razavizade M collected the data; Jamali R performed the statistical analysis and interpreted the data; Jamali R and Aarabi MH wrote the draft; all authors read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved by the Kashan University of Medical Sciences Institutional Review Board.
Informed consent statement: All study participants, or their legal guardians, provided informed written consent before study enrollment.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Mohammad Hossein Aarabi, PhD, Professor, Research Center for Biochemistry and Nutrition in Metabolic Disease, Faculty of Medicine, Kashan University of Medical Sciences, 15th Khordad Square, Abazar Street, Kashan 87137, Iran. aarabi_mh@kaums.ac.ir
Telephone: +98-31-55443026 Fax: +98-31-55546112
Received: January 5, 2016
Peer-review started: January 5, 2016
First decision: February 18, 2016
Revised: February 25, 2016
Accepted: March 18, 2016
Article in press: March 18, 2016
Published online: June 7, 2016
Processing time: 146 Days and 13.1 Hours
Abstract

AIM: To assess significance of serum adipokines to determine the histological severity of non-alcoholic fatty liver disease.

METHODS: Patients with persistent elevation in serum aminotransferase levels and well-defined characteristics of fatty liver at ultrasound were enrolled. Individuals with a history of alcohol consumption, hepatotoxic medication, viral hepatitis or known liver disease were excluded. Liver biopsy was performed to confirm non-alcoholic liver disease (NAFLD). The degrees of liver steatosis, lobular inflammation and fibrosis were determined based on the non-alcoholic fatty liver activity score (NAS) by a single expert pathologist. Patients with a NAS of five or higher were considered to have steatohepatitis. Those with a NAS of two or lower were defined as simple fatty liver. Binary logistic regression was used to determine the independent association of adipokines with histological findings. Receiver operating characteristic (ROC) analysis was employed to determine cut-off values of serum adipokines to discriminate the grades of liver steatosis, lobular inflammation and fibrosis.

RESULTS: Fifty-four participants aged 37.02 ± 9.82 were enrolled in the study. Higher serum levels of visfatin, IL-8, TNF-α levels were associated independently with steatosis grade of more than 33% [β = 1.08 (95%CI: 1.03-1.14), 1.04 (95%CI: 1.008-1.07), 1.04 (95%CI: 1.004-1.08), P < 0.05]. Elevated serum IL-6 and IL-8 levels were associated independently with advanced lobular inflammation [β = 1.4 (95%CI: 1.09-1.8), 1.07 (95%CI: 1.003-1.15), P < 0.05]. Similarly, higher TNF-α, resistin, and hepcidin levels were associated independently with advanced fibrosis stage [β = 1.06 (95%CI: 1.002-1.12), 19.86 (95%CI: 2.79-141.19), 560.72 (95%CI: 5.98-5255.33), P < 0.05]. Serum IL-8 and TNF-α values were associated independently with the NAS score, considering a NAS score of 5 as the reference value [β = 1.05 (95%CI: 1.01-1.1), 1.13 (95%CI: 1.04-1.22), P < 0.05].

CONCLUSION: Certain adipokines may determine the severity of NAFLD histology accurately.

Keywords: Non-alcoholic fatty liver disease; Adipokine; Histology; Adiponectin; Visfatin; Resistin; Hepcidin; Interleukin; Tumor necrosis factor

Core tip: Considering the drawbacks of current assays, it seemed reasonable to find appropriate serum biomarkers to define the extent of liver damage in non-alcoholic liver disease (NAFLD). We investigated several key adipokines together with metabolic profiles and liver function tests, providing an advantage over previous studies. We concluded that serum visfatin, IL-8, TNF-α levels were associated with liver steatosis degree; serum IL-6 and IL-8 concentrations correlated with lobular inflammation grade; and TNF-α, resistin, and hepcidin levels correlated with fibrosis stage. The study suggested that certain adipokines might have better accuracy than currently used serum biomarkers to determine NAFLD histology.