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.
Dr Amit Singal and colleagues from Texas, USA determined the association between PNPLA3 and liver fibrosis severity, HCC risk, and HCC prognosis among patients with liver disease.
The team performed a systematic literature review using the Medline, PubMed, Scopus, and Embase databases through 2013, and a manual search of national meeting abstracts from 2010 to 2012.
There were 2 investigators independently extracted data on patient populations, study methods, and results using standardized forms.
|PNPLA3 was associated with increased risk of HCC in patients with cirrhosis|
|American Journal of Gastroenterology|
Pooled odds ratios (ORs), according to PNPLA3 genotype, were calculated using the DerSimonian and Laird method for a random effects model.
The team found that among 24 studies, with 9,915 patients, PNPLA3 was associated with fibrosis severity, with a consistent increased risk across liver disease etiologies.
The researchers observed that among 9 studies, with 2,937 patients, PNPLA3 was associated with increased risk of HCC in patients with cirrhosis.
On subgroup analysis, increased risk of HCC was demonstrated in patients with NASH or alcohol-related cirrhosis but not in those with other etiologies of cirrhosis.
The team identified 3 studies, with 463 patients, that 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.
Dr Singal's team comments, "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."