COVID-19-related liver injury: Focus on genetic and drug-induced perspectives.

Deepak Parchwani, Amit D Sonagra, Sagar Dholariya, Anita Motiani, Ragini Singh
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Abstract

Background: Empirical use of potentially hepatotoxic drugs in the management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is considered as one of the major etiopathogenetic factors for liver injury. Recent evidence has shown that an underlying genetic factor may also occur. Hence, it is important to understand the host genetics and iatrogenic-based mechanisms for liver dysfunction to make timely remedial measures.

Aim: To investigate drug-induced and genetic perspectives for the development of coronavirus disease 2019 (COVID-19)-related liver injury.

Methods: Reference Citation Analysis, PubMed, Google Scholar and China National Knowledge Infrastructure were searched by employing the relevant MeSH keywords and pertaining data of the duration, site and type of study, sample size with any subgroups and drug-induced liver injury outcome. Genetic aspects were extracted from the most current pertinent publications.

Results: In all studies, the hepatic specific aminotransferase and other biochemical indices were more than their prescribed upper normal limit in COVID-19 patients and were found to be significantly related with the gravity of disease, hospital stay, number of COVID-19 treatment drugs and worse clinical outcomes. In addition, membrane bound O-acyltransferase domain containing 7 rs641738, rs11385942 G>GA at chromosome 3 gene cluster and rs657152 C>A at ABO blood locus was significantly associated with severity of livery injury in admitted SARS-CoV-2 patients.

Conclusion: Hepatic dysfunction in SARS-CoV-2 infection could be the result of individual drugs or due to drug-drug interactions and may be in a subset of patients with a genetic propensity. Thus, serial estimation of hepatic indices in hospitalized SARS-CoV-2 patients should be done to make timely corrective actions for iatrogenic causes to avoid clinical deterioration. Additional molecular and translational research is warranted in this regard.

Abstract Image

covid -19相关肝损伤:关注遗传和药物诱导的观点
背景:在严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)感染的治疗中经经验使用潜在肝毒性药物被认为是肝损伤的主要致病因素之一。最近的证据表明,潜在的遗传因素也可能发生。因此,了解肝功能障碍的宿主遗传学和医源性机制对及时采取治疗措施具有重要意义。目的:探讨2019冠状病毒病(COVID-19)相关肝损伤的药物诱导和遗传机制。方法:采用文献引用分析、PubMed、Google Scholar和中国国家知识基础设施检索相关MeSH关键词和研究持续时间、研究地点和研究类型、各亚组样本量和药物性肝损伤结局的相关数据。遗传方面是从最新的相关出版物中提取的。结果:在所有研究中,COVID-19患者的肝脏特异性转氨酶等生化指标均高于规定的正常上限,并与病情严重程度、住院时间、COVID-19治疗药物数量及较差的临床结局显著相关。此外,膜结合o -酰转移酶结构域在3号染色体上含有7个rs641738、rs11385942 G>GA基因簇和ABO血位点含有rs657152 C>A基因簇与入院的SARS-CoV-2患者肝脏损伤的严重程度显著相关。结论:SARS-CoV-2感染的肝功能障碍可能是个体药物或药物相互作用的结果,可能存在于具有遗传倾向的患者亚群中。因此,应对住院SARS-CoV-2患者的肝脏指标进行系列评估,及时对医源性原因采取纠正措施,避免临床恶化。在这方面需要进一步的分子和翻译研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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