Zhang Rongzhi, Wang Qiang, Yang Jianshe
The Second Clinical Medical College of Lanzhou University, Lanzhou, Gansu, China.
Gansu Medical College, Pingliang, Gansu, China.
J Clin Transl Hepatol. 2022 Aug 28;10(4):748-756. doi: 10.14218/JCTH.2021.00368. Epub 2022 Jan 4.
Liver injury is an important complication that may arise in patients suffering from coronavirus disease 2019 (COVID-19) and is accompanied by a transient increase of transaminases and/or other liver enzymes. Liver function test (LFT) abnormalities generally disappear when the COVID-19 resolves or hepatotoxic drugs are discontinued. The LFT abnormalities are associated with drug-induced liver injury (DILI), due to the overuse of antimalarials, antivirals, and antimicrobials. Studies have reported varying levels of these liver injuries in COVID-19 patients; however, most involve elevated serum aminotransferases. Hepatic dysfunction is significantly high in patients with severe illness and has poor outcome. Normally, the liver is involved in the metabolism of many drugs, including nucleoside analogs and protease inhibitors, which are currently repurposed to treat COVID-19. In addition to the manifestation of COVID-19, drugs implemented in its treatment may aggravate liver injuries. Thus, DILI should be considered especially in those COVID-19 patients with underlying liver disease. It was unclear whether the elevated liver enzymes have originated from the underlying disease or DILI in this population. Furthermore, it is difficult to establish a direct relationship between a specific drug and liver injury. Another possible effect of liver damage may due to inflammatory cytokine storm in severe COVID-19. Liver injury can change metabolism, excretion, dosing, and expected concentrations of the drugs, which may make it difficult to achieve a therapeutic dose of the drug or increase the risk of adverse effects. These repurposed drugs have shown limited efficacy against the virus and the disease itself; however, they still pose risk of adverse effects. Careful and close monitoring of LFTs in COVID-19 patients can provide early diagnosis of liver injury, and the risk of DILI could be reduced. Also, drug interactions in liver-transplanted patients should always be kept in mind for certain immunosuppressive therapies and their known signs of DILI. Altogether, abnormal LFTs should not be regarded as a contraindication to use COVID-19 experimental therapies if needed under emergent status.
肝损伤是2019冠状病毒病（COVID-19）患者可能出现的一种重要并发症，伴有转氨酶和/或其他肝酶的短暂升高。当COVID-19缓解或停用肝毒性药物时，肝功能检查（LFT）异常通常会消失。LFT异常与药物性肝损伤（DILI）有关，这是由于过度使用抗疟疾药物、抗病毒药物和抗菌药物所致。研究报告了COVID-19患者中这些肝损伤的不同程度；然而，大多数涉及血清转氨酶升高。重症患者的肝功能障碍显著高发，且预后不良。正常情况下，肝脏参与许多药物的代谢，包括核苷类似物和蛋白酶抑制剂，目前这些药物被重新用于治疗COVID-19。除了COVID-19的表现外，其治疗中使用的药物可能会加重肝损伤。因此，对于那些患有基础肝病的COVID-19患者，尤其应考虑DILI。在这一人群中，尚不清楚肝酶升高是源于基础疾病还是DILI。此外，很难确定特定药物与肝损伤之间的直接关系。肝损伤的另一个可能原因可能是重症COVID-19中的炎症细胞因子风暴。肝损伤会改变药物的代谢、排泄、剂量和预期浓度，这可能会使达到药物治疗剂量变得困难或增加不良反应的风险。这些重新利用的药物对病毒和疾病本身的疗效有限；然而，它们仍然存在不良反应的风险。对COVID-19患者进行仔细和密切的LFT监测可以早期诊断肝损伤，并降低DILI的风险。此外，对于某些免疫抑制治疗及其已知的DILI迹象，肝移植患者的药物相互作用应始终牢记在心。总之，如果在紧急情况下需要，LFT异常不应被视为使用COVID-19实验性疗法的禁忌证。
