1] Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA [2] Harold C. Simmons Cancer Center, UT Southwestern Medical Center, Dallas, Texas, USA.
Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA.
Am J Gastroenterol. 2014 Mar;109(3):325-34. doi: 10.1038/ajg.2013.476. Epub 2014 Jan 21.
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.
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.
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.
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.
已知 PNPLA3 rs738409 单核苷酸多态性可促进非酒精性脂肪性肝炎（NASH），但其与纤维化严重程度和肝细胞癌（HCC）风险的关系尚未明确。本研究旨在确定 PNPLA3 与肝病患者的肝纤维化严重程度、HCC 风险和 HCC 预后之间的关系。
我们通过 Medline、PubMed、Scopus 和 Embase 数据库进行了系统文献回顾，检索时间截至 2013 年 5 月，并对 2010 年至 2012 年全国会议摘要进行了手工检索。两名研究人员使用标准化表格独立提取患者人群、研究方法和结果的数据。采用随机效应模型的 DerSimonian 和 Laird 方法计算按 PNPLA3 基因型分组的汇总比值比（OR）。
在 24 项研究中，有 9915 例患者，PNPLA3 与纤维化严重程度相关（OR 1.32，95%置信区间（CI）1.20-1.45），在各种肝病病因中均存在一致的风险增加。在 9 项研究中，有 2937 例患者，PNPLA3 与肝硬化患者 HCC 风险增加相关（OR 1.40，95%CI 1.12-1.75）。亚组分析显示，在 NASH 或酒精性肝硬化患者中，HCC 风险增加（OR 1.67，95%CI 1.27-2.21），但在其他病因的肝硬化患者中，风险无增加（OR 1.33，95%CI 0.96-1.82）。3 项研究（463 例患者）不支持 PNPLA3 与 HCC 预后之间的关联，但受异质性结局测量的限制。对于所有结局，大多数研究在同质的白种人群中进行，需要在种族多样化的队列中开展研究。
PNPLA3 与多种肝病患者的晚期纤维化风险增加相关，是 NASH 或酒精性肝硬化患者 HCC 的独立危险因素。
