Liver injury in COVID-19: The hepatic aspect of the respiratory syndrome — what we know so far

Table 1 Summary of the pattern of liver injury reported in coronavirus disease 2019 in various studies

Ref.	Number of patients	Pattern of liver injury	Pre-existing liver diseases	Comments	Place of study
Richardson et al[3]	5700	Elevated AST: 58.4%; elevated ALT: 39%	Cirrhosis: 0.4%; chronic hepatitis B: 0.1%; chronic hepatitis C: 0.1%		Northwell Health System, New York, United States
Huang et al[4]	41	15(31%)	1 (2%)	Elevated AST observed in 62% of patients in ICU compared with only 25% of patients not in ICU	Wuhan, China
Wang et al[5]	138	Mild elevation of AST and ALT	4 (2.9%)	-	Wuhan, China
Guan et al[12]	1099	Elevated AST: 22.2%; elevated ALT: 21.3%; elevated total bilirubin: 10.5%	23 (2.3%)	AST elevated in 18.2% of non-severe disease but in 39.4% of severe disease; ALT elevated in 19.8% with non-severe disease and 28.1% of severe disease	552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China
Shi et al[16]	81	Transaminitis in 43 (53.1%)	7 (8.6%)	Patients with subclinical infection had lower AST	Wuhan, China
Fan et al[25]	148	Abnormal LFT in 50.7%; elevated ALT in 18.2%; elevated AST in 21.6%		Higher proportion (56.1%) with liver injury received lopinavir/ ritonavir than those without liver injury (25%)	Shanghai Public health Clinical Centre, China
Chen et al[35]	99	43(43%); elevated AST: 35%; elevated ALT: 28%; elevated total bilirubin: 98%		One patient had severe liver injury with ALT 7590U/L	Wuhan, China
Cai et al[36]	417	During hospitalisation, rise in liver enzymes > 3 times of upper limit seen; elevated ALT: 49 (23.4%); elevated AST: 31 (14.8%); elevated total bilirubin: 24 (11.5%); elevated GGT: 51 (24.4%)		318 (76.3%) had abnormal liver biochemistries and 90 (21.5%) had liver injury during hospitalization; 91 (21.8%) developed severe disease and 326 (78.2%) had mild disease during hospitalization; use of lopinavir/ritonavir increased the odds of liver injury by 7-fold	Shenzhen, China
Tabata et al[40]	104	Elevated AST: 17.3%; elevated ALT: 16.3%	-	-	Diamond Princess Cruise, Japan
Huang et al[41]	36	Elevated ALT: 13.33%; elevated AST: 58.06%; elevated Total bilirubin: 12.90%		All fatal cases only	Wuhan, China
Zhang et al[42]	82	Liver dysfunction in 64 (78%)	2 (2.4%)	All fatal cases only	Wuhan, China
Yang et al[43]	52	15 (29%)		No difference in incidence of liver injury between survivors and non-survivors	Wuhan, China
Cao et al[44]	128			Transaminitis present only in severe disease	Xiangyang, China
Xu et al[45]	62	Elevated AST in only 16.1%	7 (11.0%)	No patient had elevated ALT while a sixth had elevated AST	Zhejiang Province, China
Cai et al[46]	298	44 (14.8%)	8 (2.7%)	Transaminitis 4 times commoner in severe disease (36.2%) compared to mild disease (9.6%)	Shenzhen, China
Kujawski et al[47]	12	Elevated AST: 58.3%; elevated ALT: 58.3%	8.3% had HBV and 8.3% had fatty liver disease		Center of Disease Control California, Illinois, Arizona, Massachusetts,Washington, Wisconsin, United States
Arentz et al[48]	21	Median AST: 273 (range 14-4432); median ALT: 108 (range 11-1414)	4.8% had cirrhosis of liver		Kirkland, Washington, United States
Jin et al[49]	651	Liver injury seen in 13 out of 74 with GI symptoms vs 51 out of 577 without GI symptoms		Rate of increased AST, but not ALT, was significantly higher in patients with GI symptoms than in those without GI symptoms	Zhejiang Province, China
Qi et al[50]	267	Elevated AST: 7.2%; elevated ALT: 7.5%; elevated bilirubin: 2.2%		Elevated AST seen in 9 out of 217 patients with non-severe disease and 10 out of 50 patients with severe disease.Elevated ALT seen in 10 out of 217 patients with non-severe disease and 10 out of 50 patients with severe disease.Elevated bilirubin in 3 out of 217 patients with non-severe disease and 3 out of 50 patients with severe disease	Chongqing, China
Omrani-Nava et al[51]	93	Elevated AST: 29.2%; elevated ALT: 30.3%; elevated ALP: 17%; elevated total bilirubin: 10.2%; elevated direct bilirubin: 45.8%		Risk of being transferred to the intensive care unit strongly associated with the elevated levels of AST and direct bilirubin	Sari, Amol, Mazandaran Province, Iran
Mao et al[52]	214	Median AST 26 (8-8191); median ALT 26 (5-1933)		Liver enzymes were significantly higher in severe cases compared to non-severe cases	Wuhan, China
Xu et al[53]	45	Elevated AST/ALT: 37.8%; median Bilirubin: 0.91 (IQR 0.61-1.3)
Tian et al[54]	24	Elevated AST: 8.33 %; elevated ALT: 4.17 %	4.17 % had cirrhosis		Shandong, China
Chen et al[55]	291	Elevated AST: 15.1%; elevated ALT: 10.3%; elevated bilirubin: 9.3%	5.2% chronic liver disease	Elevated AST in 5 out of 29 cases in mild illness, 23 out of 212 cases in moderate illness and 16 out of 50 cases in critically ill. Elevated ALT in 4 out of 29 in mild illness, 16 out of 212 cases in moderately ill and 10 out of 50 cases in critically ill. Elevated bilirubin in 4 out of 29 cases in mild illness, 17 out of 212 in moderately ill and 6 out of 50 in critically ill	Hunan Province, China
Wang et al[56]	18	Elevated AST or ALT in 25%			Zhengzhou, Henan Province, China
Yan et al[57]	168	Elevated AST: 17.3%; elevated ALT: 8.0%		Elevated AST seen in 7 out of 75 patients with non-severe disease and 11 out of 29 patients with severe disease; Elevated ALT seen in 5 out of 81patients with severe disease and 4 out of 31 patients with severe disease	Hainan, China
Lin et al[58]	95	Elevated AST: 4.2%; elevated ALT: 5.3%			Zhuhai, Guangdong Province, China
Zhao et al[59]	77	Elevated AST: 26.0%; elevated ALT: 33.8%		Elevated AST seen in 11 out of 57 non severe patients and 9 out of 20 severe patients; Elevated ALT seen in 17 out of 57 patients with non-severe disease and 9 out of 20 patients with severe disease	Beijing, China
Chen et al[60]	274	Elevated AST: 30.7%; elevated ALT: 21.9%; median bilirubin: 0.6 (IQR 0.4-0.8)	4 % were HbsAg positive		Wuhan, China
Rubin et al[61]	54	Elevated AST: 42.59%; elevated ALT: 40.7%	1.8 % were HBV infected	AST: mean/SD-73.4 ± 61.8 (females); 45.1 ± 19.5 (males) ALT: mean/SD- 69.6 ± 65.2 (females); 43.9 ± 25.8 (males)	Stanford University School of Medicine, California
Cholankeril et al[62]	116	Deranged LFT in 26 out of 65 cases (40%). Higher levels of AST compared to ALT. Median bilirubin- 0.4 (IQR 0.3-0.7)	2.6% chronic liver disease	22 of the 26 patientswith liver enzyme elevations had normal baseline liver enzymes	Stanford University HospitalsCalifornia, United States
Yao et al[63]	40	Elevated AST: 40%; elevated ALT: 52.5% Elevated Bilirubin: 25%		Out of 22 critical cases, 17 had hepatic dysfunction. Out of 18 noncritical cases, 5 had hepatic dysfunction	Xi’an, Shaanxi Province, China
Zhao et al[64]	75	Elevated AST: 18.7%; elevated ALT: 20%; elevated Bilirubin: 16%	5.3 % had chronic liver disease		Hefei, Anhui Province, China
Ai et al[65]	102	Elevated AST: 25.5%; elevated ALT: 19.6%			Xiangyang, China
Ma et al[66]	81	Deranged AST/ALT: 38.2%			Wuhan, China
Xu et al[67]	355	Elevated AST: 28.7%; elevated ALT: 25.6%; elevated Total bilirubin: 18.6%			Wuhan, China
Shi et al[68]	416	Median AST: 30 (IQR 22-43); median ALT: 28 (IQR 18-46)	1% had HBV infection		Wuhan, China
Luo et al[69]	1141	Among 183 patients, median AST: 65.8 ± 12.7, median ALT: 66.4 ± 13.2			Wuhan, China
Qi et al[70]	21	Elevated AST: 38.1%; elevated ALT: 23.8%; elevated GGT: 23.8%	All patients	Most common etiology of chronic liver disease was chronic hepatitis B infection	16 designated hospitals in China

AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; GGT: Gamma glutamyl transpeptidase; IQR: Interquartile range; HBV: Hepatitis B virus; LEF: Liver function tests; GI: Gastrointestinal; ICU: Intensive care unit; SD: Standard deviation.