Wellcome Centre for Cell-Matrix Research, Faculty of Biology, Medicine & Health, Manchester Academic Health Science Centre, University of Manchester, Oxford Road M13 9PT, Manchester, UK.
Division of Diabetes, Endocrinology and Gastroenterology, Faculty of Biology, Medicine & Health, Manchester Academic Health Science Centre, University of Manchester, Oxford Road, Manchester, UK.
Curr Diab Rep. 2021 Feb 5;21(3):8. doi: 10.1007/s11892-021-01377-5.
Non-alcoholic fatty liver disease (NAFLD) is a major and increasing health burden, with the potential to overwhelm hepatology services. However, only a minority of patients develop advanced liver disease. The challenge is early identification of patients at risk of progression. This review aims to summarize current knowledge on the genetic predisposition to NAFLD, and its implications for prognostication and risk stratification.
PNPLA3-I148M is the most robustly associated genetic variant with NAFLD. Recently, variants in TM6SF2, MBOAT7, GCKR and HSD17B13 have also been implicated. NAFLD is a complex disease, and any one genetic variant alone is insufficient for risk stratification, but combining multiple genetic variants with other parameters is a promising strategy. It is anticipated that, in the near future, analysis of data from large-scale prospective cohorts will reveal NAFLD subtypes and enable the development of prognostic models. This will facilitate risk stratification of patients, enabling optimisation of resources to effectively manage the NAFLD epidemic.
非酒精性脂肪性肝病(NAFLD)是一个主要且日益加重的健康负担,有可能使肝脏病学服务不堪重负。然而,只有少数患者发展为晚期肝病。挑战在于早期识别有进展风险的患者。本文旨在总结导致 NAFLD 的遗传易感性及其对预后和风险分层的影响。
PNPLA3-I148M 是与 NAFLD 相关性最强的遗传变异。最近,TM6SF2、MBOAT7、GCKR 和 HSD17B13 的变异也与之相关。NAFLD 是一种复杂的疾病,任何单一的遗传变异都不足以进行风险分层,但将多个遗传变异与其他参数相结合是一种很有前途的策略。预计在不久的将来,对大型前瞻性队列数据的分析将揭示 NAFLD 亚型,并能够开发预后模型。这将有助于对患者进行风险分层,从而优化资源以有效管理 NAFLD 流行。