Abstract:
The current pandemic has markedly shifted the focus of the global research and development ecosystem toward infectious agents such as SARS-CoV-2, the causative agent for COVID-19. A case in point is the chronic liver disease associated with hepatitis B virus (HBV) infection that continues to be a leading cause of severe liver disease and death globally. The burden of HBV infection is highest in the World Health Organization designated western Pacific and Africa regions. Tenofovir disoproxil fumarate (TDF) is a nucleoside analogue used in treatment of HBV infection but carries a potential for kidney toxicity. TDF is not metabolized by the cytochrome P450 enzymes and, therefore, its clearance in the proximal tubule of the renal nephron is controlled mostly by membrane transport proteins. Clinical pharmacogenomics of TDF with a focus on drug transporters, discussed in this perspective article, offers a timely example where resource-limited countries and regions of the world with high prevalence of HBV can strengthen the collective efforts to fight both COVID-19 and liver diseases impacting public health. We argue that precision/personalized medicine is invaluable to guide this line of research inquiry. In all, our experience in Ghana tells us that it is important not to forget the burden of chronic diseases while advancing research on infectious diseases such as COVID-19. For the long game with COVID-19, we need to address the public health burden of infectious agents and chronic diseases in tandem.
摘要:
当前的大流行已将全球研发生态系统的重点明显转向传染性病原体,如SARS-CoV-2,即COVID-19的病原体。一个典型的例子是与乙型肝炎病毒(HBV)感染相关的慢性肝病,这仍然是全球严重肝病和死亡的主要原因。在世界卫生组织指定的西太平洋和非洲地区,HBV感染的负担最高。富马酸替诺福韦酯(TDF)是用于治疗HBV感染的核苷类似物,但具有潜在的肾毒性。TDF不被细胞色素P450酶代谢,因此,它在肾肾单位近端小管中的清除主要由膜转运蛋白控制。以药物转运体为重点的TDF临床药物基因组学,在这篇透视文章中讨论的,提供了一个及时的例子,其中资源有限的国家和世界上HBV高流行的地区可以加强集体努力,以对抗COVID-19和影响公共卫生的肝病。我们认为,精准/个性化医疗对于指导这一研究探索是非常宝贵的。总之,我们在加纳的经验告诉我们,重要的是在推进COVID-19等传染病研究的同时,不要忘记慢性病的负担。对于与COVID-19的长期博弈,我们需要同时解决传染病和慢性病的公共卫生负担。