Genomic medicine for liver disease.
Genomic medicine for liver disease.
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DOI：
10.1002/hep.32364
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发表时间：
2022-09
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影响因子：
--
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中科院分区：
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肝病是一种全球健康负担，包括超过1.2亿的终末期肝病病例，全世界每年有超过200万人死亡。[1，2]尽管病毒性肝炎的诊断和治疗取得了显著进展，[3]肝病的患病率及其相关发病率和死亡率仍在继续上升。[2]不同的肝病病因对全球疾病负担的贡献可能很难确定。这在一定程度上是因为大多数慢性肝病(CLD)的自然病史会合并成肝硬变[4]，在这个阶段，不同的肝病病因通常在活检、实验室发现或体检上是无法区分的。[5]另一方面，肝病的早期阶段通常在临床上是沉默的，因此一直没有被发现。1965年以前，大约50%的肝硬变病例被认为是不明原因的，被指定为隐源性。[5]随着1965年和分别发现了乙肝病毒和丙型肝炎病毒，以及在过去20年中人们认识到非酒精性脂肪肝和非酒精性脂肪肝是肝硬变的驱动因素，随着我们对患者发生慢性肝病的了解的扩大，隐源性肝硬变的诊断已经减少。2003年，人类基因组计划的完成以及下一代测序(NGS)技术的重大进展导致了人类基因组研究的前所未有的进步，改变了生物医学研究和临床医学的格局。由此产生的基因组医学学科，被定义为利用患者的基因组信息来指导他们的临床护理，[8]已经导致了肿瘤学和儿科临床实践的范式转变。截至2021年11月，PubMed共检索到16,899篇以“基因组医学”为主题的出版物，通过PubMed以“基因组医学”和“肝脏”或“肝病学”检索的出版物有747篇，其中一半以上的稿件发表于最近3年，突显了基因组医学作为一门学科的指数级增长。目前，随着基因组学越来越多地融入临床治疗，我们对肝病的分子理解不断完善，更多原因不明的肝病病例正在得到解决。在这里，我们回顾了遗传学和基因组学在肝病中的过去和现在，从基因发现到临床诊断，然后展望了未来(图1)。我们提供了一个基于病例的讨论，以说明扩大基因组分析在肝病中应用的未得到满足的医学需求，培训该领域下一代肝病专家的重要性，以及人类基因组学改变我们对罕见和常见形式的儿童和成人CLD的理解和治疗的潜力。
Liver disease is a global health burden, encompassing over 120 million cases of end-stage liver disease and accounting for over 2 million deaths annually worldwide.[1, 2] Despite notable advances in the diagnosis and treatment of viral hepatitis,[3] the prevalence of liver disease and its related morbidity and mortality continues to rise.[2] The contribution of different causes of liver disease to overall global disease burden can be difficult to ascertain. This is in part because the natural history of most chronic liver diseases (CLDs) coalesces into cirrhosis,[4] and frequently at this stage, different etiologies of liver disease are indistinguishable on biopsy, laboratory findings, or physical examination.[5] On the other hand, earlier stages of liver disease are often clinically silent and therefore remain undetected. Before 1965, approximately 50% of all cirrhosis cases were considered of unknown cause, designated as cryptogenic.[5] With the discoveries of hepatitis B and C viruses in 1965 and 1989, respectively, and the recognition of NAFLD and NASH as drivers of cirrhosis within the last two decades,[6, 7] cryptogenic cirrhosis diagnoses have been curtailed as our understanding of why patients develop CLD expands. In 2003, the completion of the Human Genome Project combined with major advances in next generation sequencing (NGS) technologies led to unprecedented progress in human genomics research, which has changed the landscape of biomedical research and clinical medicine. The resultant emerging discipline of genomic medicine, defined as the utilization of a patient’s genomic information in guiding their clinical care,[8] has already led to paradigm shifts in oncology and pediatrics clinical practice. As of November 2021, there were 16,899 publications queried through PubMed with “genomic medicine” and 747 publications queried through PubMed with “genomic medicine” and either “liver” or “hepatology,” with over half these manuscripts published in the last 3 years, highlighting the exponential growth of genomic medicine as a discipline. Presently, with increasing integration of genomics into clinical care, our molecular understanding of liver disease continues to be refined, and more cases of unexplained liver disease are now being solved. Here, we review the past and the present of genetics and genomics in liver disease from gene discovery to clinical diagnosis, followed by a perspective into the future (Figure 1). We provide a case-based discussion to illustrate the unmet medical need to expand the application of genomic analysis in hepatology, the importance of training the next generation of hepatologists in this field, and the potential of human genomics to revolutionize our understanding and treatment of both rare and common forms of pediatric and adult CLD.
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影响因子：
64.8
作者：
Green ED;Gunter C;Biesecker LG;Di Francesco V;Easter CL;Feingold EA;Felsenfeld AL;Kaufman DJ;Ostrander EA;Pavan WJ;Phillippy AM;Wise AL;Dayal JG;Kish BJ;Mandich A;Wellington CR;Wetterstrand KA;Bates SA;Leja D;Vasquez S;Gahl WA;Graham BJ;Kastner DL;Liu P;Rodriguez LL;Solomon BD;Bonham VL;Brody LC;Hutter CM;Manolio TA
通讯作者：
Manolio TA
影响因子：
30.8
作者：
BULL, PC;THOMAS, GR;COX, DW
通讯作者：
COX, DW
影响因子：
7.7
作者：
Bird, Jeremy G.;Basu, Urmimala;Nickels, Bryce E.
通讯作者：
Nickels, Bryce E.
影响因子：
25.7
作者：
Asrani, Sumeet K.;Devarbhavi, Harshad;Kamath, Patrick S.
通讯作者：
Kamath, Patrick S.
DOI：
10.1097/00042737-200409000-00008
发表时间：
2004-09-01
影响因子：
2.1
作者：
Gleeson, F;Ryan, E;Crowe, J
通讯作者：
Crowe, J