Precision Medicine - Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden; Clinical Medicine and Hepatology Unit, Department of Internal Medicine and Geriatrics, Campus Bio-Medico University, Rome, Italy.
Curr Opin Pharmacol. 2021 Dec;61:6-11. doi: 10.1016/j.coph.2021.08.014. Epub 2021 Sep 17.
Nonalcoholic fatty liver disease is the leading cause of chronic liver disease. Genetic predisposition, lifestyle, and metabolic comorbidities concur to nonalcoholic fatty liver disease development and progression to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. Improvement in risk stratification and development of effective therapies for nonalcoholic steatohepatitis are key unmet clinical needs. Knowledge emerging from genomics could meet this need. A polygenic risk score (PRS) is calculated by summing the number of trait-associated alleles carried by an individual, which can be weighted by their effect size on the trait and captures the individual's genetic risk to develop a disease. In this review, we focalize on the potential use of PRSs for disease detection at an early stage and stratification of the risk of progression to severe forms. PRSs may represent robust instruments to implement targeted prevention programs, hepatocellular carcinoma surveillance in at-risk individuals, and to develop precision medicine therapeutic approaches.
非酒精性脂肪性肝病是慢性肝病的主要病因。遗传易感性、生活方式和代谢合并症共同导致非酒精性脂肪性肝病的发生和发展，进而导致非酒精性脂肪性肝炎、肝硬化和肝细胞癌。改善风险分层和开发有效的非酒精性脂肪性肝炎治疗方法是未满足的关键临床需求。来自基因组学的知识可以满足这一需求。多基因风险评分 (PRS) 通过将个体携带的与特征相关的等位基因数量相加来计算，这些等位基因可以根据它们对特征的影响大小进行加权，并捕获个体患疾病的遗传风险。在这篇综述中，我们重点关注 PRS 在早期疾病检测和严重形式进展风险分层中的潜在用途。PRS 可能是实施靶向预防计划、对高危个体进行肝细胞癌监测以及开发精准医学治疗方法的有力工具。
