Ishay Yuval, Kolben Yotam, Kessler Asa, Ilan Yaron
Department of Medicine, Faculty of Medicine, Hadassah Medical Center, Hebrew University, Jerusalem, Israel.
Am J Physiol Gastrointest Liver Physiol. 2021 Oct 1;321(4):G400-G412. doi: 10.1152/ajpgi.00186.2021. Epub 2021 Aug 4.
Hepatic encephalopathy (HE) is a common, incapacitating complication of cirrhosis that affects many patients with cirrhosis. Although several therapies have proven effective in the treatment and prevention of this condition, several patients continue to suffer from covert disease or episodes of relapse. The circadian rhythm has been demonstrated to be pivotal for many body functions, including those of the liver. Here, we explore the impact of circadian rhythm-dependent signaling on the liver and discuss the evidence of its impact on liver pathology and metabolism. We describe the various pathways through which circadian influences are mediated. Finally, we introduce a novel method for improving patient response to drugs aimed at treating HE by utilizing the circadian rhythm. A digital system that introduces a customization-based technique for improving the response to therapies is presented as a hypothetical approach for improving the effectiveness of current medications used for the treatment of recurrent and persistent hepatic encephalopathy.
肝性脑病(HE)是肝硬化常见的、使人丧失能力的并发症,影响许多肝硬化患者。尽管几种疗法已被证明对这种疾病的治疗和预防有效,但仍有一些患者持续患有隐匿性疾病或复发。昼夜节律已被证明对包括肝脏功能在内的许多身体功能至关重要。在这里,我们探讨昼夜节律依赖性信号传导对肝脏的影响,并讨论其对肝脏病理和代谢影响的证据。我们描述了昼夜节律影响所介导的各种途径。最后,我们介绍一种通过利用昼夜节律来提高患者对治疗HE药物反应的新方法。一种引入基于定制技术以改善治疗反应的数字系统被作为一种假设方法提出,以提高目前用于治疗复发性和持续性肝性脑病药物的有效性。