Liver injury in patients with COVID-19 in comparison to patients with the pandemic influenza A (H1N1) 2009: a population-based study

Elevated liver tests in patients with COVID-19 are widely reported. Population-based studies utilizing a validated analysis of drug-induced liver injury (DILI), with a control group of other viral illnesses and follow-up are largely lacking. All hospitalized patients in Iceland with SARS-CoV-2 in 2020 and pandemic influenza A (H1N1) in 2009 were included in this retrospective, population-based study. Liver tests were compared between the two groups and the correlation to inflammatory markers and persistence of alanine aminotransferase (ALT) elevations were assessed. Potential DILI cases were reviewed using the Roussel Uclaf Causality Assessment Method (RUCAM). 225 SARS-CoV-2-positive and 73 influenza A (H1N1)-positive patients were included. Liver test values were similar between the groups, except for aspartate aminotransferase (AST) which was significantly lower in COVID-19, with a mean difference of 26 U/L (95%CI 4.2-47). Ferritin elevation was positively correlated with ALT, AST and alkaline phosphatase. No patient had persistently elevated ALT in COVID-19 and none had a probable DILI. Only 3 patients had a possible DILI according to the RUCAM. Elevated liver enzymes are not specific for COVID-19. Hyperferritinemia was associated with elevated liver tests. DILI was very rare in COVID-19 and an unlikely cause of elevated liver enzymes in COVID-19. Abnormal liver tests are nonpersistent and generally not clinically important in these patients.

新型冠状病毒（SARS-CoV-2）感染患者出现肝指标升高的情况已有广泛报道。然而，目前仍缺乏采用经过验证的药物性肝损伤（drug-induced liver injury，DILI）分析方法、设置其他病毒性疾病对照并开展随访的人群队列研究。本回顾性人群队列研究纳入了2020年冰岛所有因感染SARS-CoV-2住院的患者，以及2009年因甲型H1N1大流行性流感住院的患者。研究对比了两组患者的肝指标水平，并评估了肝指标与炎症标志物的相关性，以及丙氨酸氨基转移酶（alanine aminotransferase，ALT）升高的持续情况。潜在DILI病例采用吕塞耳乌克拉夫因果评估法（Roussel Uclaf Causality Assessment Method，RUCAM）进行回顾审查。本研究共纳入225例SARS-CoV-2阳性患者与73例甲型H1N1阳性患者。两组患者的肝指标水平总体相近，仅天冬氨酸氨基转移酶（aspartate aminotransferase，AST）存在显著差异：新冠感染组的AST水平显著更低，平均差值为26 U/L（95%置信区间4.2~47）。铁蛋白升高与ALT、AST及碱性磷酸酶水平呈正相关。新冠感染组中无患者出现持续性ALT升高，亦无确诊为很可能的DILI病例；仅3例患者经RUCAM评估为可能的DILI病例。研究结果显示，肝酶升高并非新冠病毒感染的特异性表现。高铁蛋白血症与肝指标升高存在关联。新冠感染相关的DILI极为罕见，并非新冠患者肝酶升高的常见诱因。本研究中，异常肝指标多为一过性，且通常不具有临床重要性。