Characteristics and Mechanism of Liver Injury in 2019 Coronavirus Disease

Li, Jie; Fan, Jian-Gao

Abnormal liver enzymes in patients with COVID-19 was first reported by Chen et al. 2 Among 99 cases with COVID-19 from Wuhan, 43 cases (43.4%) had increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactic dehydrogenase. Most of them had mild elevation of aminotransferase, and only one case had very high levels of aminotransferases (ALT of 7590 U/L and AST of 1445 U/L). However, no case was reported with the features of obvious intrahepatic cholestasis or liver failure. Holshue et al. 12 reported the first Chinese case of COVID-19 confirmed in the USA with detailed information of liver function tests. The patient was admitted to hospital on day 4 of illness and progressed to pneumonia on day 9 of illness, and his serum levels of ALT increased from 68 to 203 U/L and AST increased from 37 to 89 U/L. In another report, among 12 severe patients with COVID-19 from Shenzhen, only 1 had abnormal liver enzymes (ALT of 107 U/L and AST of 62 U/L). 13 In 62 patients with COVID-19 from Zhejiang, 16.1% patients had elevation of AST ($40 U/L) and the mean ALT level was 22 U/L. 14 Among 305 patients with COVID-19 from Wuhan, 39.1% (119/304) cases had elevation of ALT, AST, or bilirubin at admission. Of them, 24 cases had increased ALT ($80 U/L) and 19 had increased AST ($80 U/L), while only 6 had increased bilirubin level. 15 Recently, increasing evidence has highlighted the close relationship of abnormal liver biochemistries with severity of COVID-19. In the cohort of 1099 patients with COVID-19 from mainland China, 39.4% had AST >40 U/L and 28.1% had ALT >40 U/L, and most of them occurred in severe and critical cases. 9 The mean levels of serum ALT, AST, and bilirubin in severe or critical cases were significantly higher than those in control cases in another multicenter retrospective study including 32 patients. 16 Serum levels of ALT and AST in severe to critical cases were significantly higher than those in mild to moderate cases among 265 patients with COVID-19 from Shanghai. 17 Similarly, patients admitted to the ICU were more likely to have high levels of serum ALT, AST, and total bilirubin. 18,19 In 52 critically ill patients with multiple organ damage, 35 (67%) had ARDS, 15 (29%) had acute kidney injury, 15 (29%) had liver injury, and 12 (23%) had cardiac injury. 20 Among 298 patients with COVID-19 from Shenzhen, the percentage of liver injury in the severe group was substantially higher than that in the non-severe group. 21 However, significant differences of serum levels of ALT, AST and total bilirubin between patients with and without ARDS were not found in a small sample cohort study from Wuhan. 22 In addition, abnormal liver function test in cases of COVID-19 is often transient and often simultaneously combined with increased enzymes from muscle and heart; these laboratory changes can return to normal without liver-related morbidity and mortality.