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Meta-Analysis
. 2014 Mar;109(3):325-34.
doi: 10.1038/ajg.2013.476. Epub 2014 Jan 21.

The effect of PNPLA3 on fibrosis progression and development of hepatocellular carcinoma: a meta-analysis

Amit G Singal  1 , Hema Manjunath  2 , Adam C Yopp  3 , Muhammad S Beg  2 , Jorge A Marrero  1 , Purva Gopal  4 , Akbar K Waljee  5
Affiliations
Meta-Analysis

The effect of PNPLA3 on fibrosis progression and development of hepatocellular carcinoma: a meta-analysis

Amit G Singal et al. Am J Gastroenterol. 2014 Mar.

Abstract

Objectives: The PNPLA3 rs738409 single-nucleotide polymorphism is known to promote nonalcoholic steatohepatitis (NASH), but its association with fibrosis severity and hepatocellular carcinoma (HCC) risk is less well-defined. The objectives of this study were to determine the association between PNPLA3 and liver fibrosis severity, HCC risk, and HCC prognosis among patients with liver disease.

Methods: We performed a systematic literature review using the Medline, PubMed, Scopus, and Embase databases through May 2013 and a manual search of national meeting abstracts from 2010 to 2012. Two investigators independently extracted data on patient populations, study methods, and results using standardized forms. Pooled odds ratios (ORs), according to PNPLA3 genotype, were calculated using the DerSimonian and Laird method for a random effects model.

Results: Among 24 studies, with 9,915 patients, PNPLA3 was associated with fibrosis severity (OR 1.32, 95% confidence interval (CI) 1.20-1.45), with a consistent increased risk across liver disease etiologies. Among nine studies, with 2,937 patients, PNPLA3 was associated with increased risk of HCC in patients with cirrhosis (OR 1.40, 95% CI 1.12-1.75). On subgroup analysis, increased risk of HCC was demonstrated in patients with NASH or alcohol-related cirrhosis (OR 1.67, 95% CI 1.27-2.21) but not in those with other etiologies of cirrhosis (OR 1.33, 95% CI 0.96-1.82). Three studies, with 463 patients, do not support an association between PNPLA3 and HCC prognosis but are limited by heterogeneous outcome measures. For all outcomes, most studies were conducted in homogenous Caucasian populations, and studies among racially diverse cohorts are needed.

Conclusions: PNPLA3 is associated with an increased risk of advanced fibrosis among patients with a variety of liver diseases and is an independent risk factor for HCC among patients with nonalcoholic steatohepatitis or alcohol-related cirrhosis.

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Conflict of interest statement

CONFLICT OF INTEREST

Guarantor of the article: Amit G. Singal, MD, MS.

Specific author contributions: Amit G. Singal was involved in study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, and study supervision. Hema Manjunath was involved in acquisition of data and critical revision of the manuscript for important intellectual content. Adam C. Yopp was involved in critical revision of the manuscript for important intellectual content. Jorge A. Marrero was involved in critical revision of the manuscript for important intellectual content. Purva Gopal was involved in critical revision of the manuscript for important intellectual content. Akbar K. Waljee was involved in analysis and interpretation of data and critical revision of the manuscript for important intellectual content.

Potential competing interests: The content is solely the responsibility of the authors and does not necessarily represent the official views of UT-STAR, the University of Texas Southwestern Medical Center and its affiliated academic and health care centers, the National Center for Advancing Translational Sciences, the Veterans Affairs, or the National Institutes of Health. The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Map of literature search and selection process.
Figure 2
Figure 2
Association between PNPLA3 rs738409 single-nucleotide polymorphism (SNP) and advanced fibrosis.
Figure 3
Figure 3
Association between PNPLA3 rs738409 single-nucleotide polymorphism (SNP) and development of hepatocellular carcinoma.
See this image and copyright information in PMC

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