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©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
PNPLA3 polymorphism increases risk for and severity of chronic hepatitis C liver disease
Habeeb Salameh, Maen Masadeh, Muhannad Al Hanayneh, Vincent Petros, Matthew Maslonka, Arjun Nanda, Ashwani K Singal
Habeeb Salameh, Muhannad Al Hanayneh, Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Texas Medical Branch, Galveston, TX 77555, United States
Maen Masadeh, Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Iowa, Iowa City, IA 52242, United States
Vincent Petros, Matthew Maslonka, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, United States
Arjun Nanda, Ashwani K Singal, Division of Gastroenterology and Hepatology, University of Alabama, Birmingham, AL 35294, United States
Author contributions: Salameh H study design, data collection and interpretation, drafting and editing manuscript; Masadeh M literature review, data extraction and study quality assessment; Al Hanayneh M and Maslonka M literature review, data extraction and study quality assessment; Petros V literature review, drafting and editing the manuscript; Nanda A drafting and editing the manuscript; Singal AK study design, data analysis and interpretation, and manuscript editing; all the authors approved the final version of the manuscript.
Conflict-of-interest statement: The authors deny any conflict of interest.
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: Habeeb Salameh, MD, CMQ, Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, United States. habeeb.salameh@yahoo.com
Telephone: +1-409-7721501 Fax: +1-409-7724789
Received: June 28, 2016
Peer-review started: June 28, 2016
First decision: August 10, 2016
Revised: September 9, 2016
Accepted: October 17, 2016
Article in press: October 18, 2016
Published online: December 18, 2016
AIM
To examine the association of PNPLA3 polymorphisms in chronic hepatitis C patients and development of liver disease spectrum.
METHODS
Literature was searched systematically from PubMed/MEDLINE, EMBASE, and Cochrane search engines for full-length articles written in English that examined PNPLA3 polymorphism in chronic hepatitis C (CHC) patients. Studies evaluating the association of PNPLA3 polymorphism spectrum (fatty liver, steatohepatitis, cirrhosis, and hepatocellular carcinoma) of CHC were included. Pooled data are reported as OR with 95%CI. Our study endpoint was the risk of the entire liver disease spectrum including: Steatosis/fatty liver, cirrhosis, and hepatocellular carcinoma in CHC patients with PNPLA3 polymorphisms.
RESULTS
Of 380 studies identified, a total of 53 studies were included for full-text review. Nineteen on chronic hepatitis C were eligible for analysis. Pooled ORs for rs738409 GG compared to CC and CG among patients with fatty liver was 2.214 (95%CI: 1.719-2.853). ORs among advanced fibrosis/cirrhosis were 1.762 (95%CI: 1.258-2.468). Similar odds ratios among hepatocellular carcinoma patients were 2.002 (95%CI: 1.519-2.639). Pooled ORs for rs738409 GG and CG compared to CC among patients with fatty liver were 1.750 (95%CI: 1.542-1.986). Pooled ORs for advanced fibrosis/cirrhosis patients were 1.613 (95%CI: 1.211-2.147). All analyses were homogenous and without publication bias except one. The associations were maintained after adjusting for publication bias and heterogeneity.
CONCLUSION
PNPLA3 polymorphisms have strong association with increased risk and severity of the liver disease spectrum in CHC patients.
Core tip:PNPLA3 polymorphisms (rs738409 CG and GG) are associated with increased risk of steatosis, advanced fibrosis, cirrhosis, and hepatocellular carcinoma in chronic hepatitis C patients.
