Mechanisms and consequences of COVID-19 associated liver injury: What can we affirm?

Table 1 Different studies that evaluates liver enzymes according to disease severity and treatment protocol

	n	Disease severity, n (%)	Death, n (%)	Complications, n (%)	Treatment (%), Antiviral therapy; Antibiotic therapy; Antimalarial	Treatment (Drugs)
Xie et al[12]	79	Moderate: 51 (64.5%), Severe: 28 (2.5%)	0	NR	NR	NR
Huang et al[5]	41	Non-severe: 28 (68.3%), Severe: 13 (31.7%)	6 (15%)	Acute respiratory distress: 12 (29%); Acute cardiac injury: 5 (12%); Acute kidney injury: 3 (7%); Secondary infection: 4 (10%); Shock: 3 (7%)	All patients: AV (93%); AB (100%) Non-ICU care: AV (93%); AB (100%) ICU care: AV (92%); AB (100%)	Antiviral: Oseltamivir Antibiotic: NR
Guan et al[6]	1099	Non severe: 926 (84.3%), Severe: 173 (15.7%)	15 (1.4%)	Acute respiratory distress: 37 (3.4%); Acute kidney injury: 6 (0.5%); Septic Shock: 12 (1.1%); Disseminated intravascular coagulation: 1 (0.1); Rhabdomyolysis: 2 (0.2)	All patients: AV (35.8%); AB (58%) Non-severe: AV (33.8%); AB (53.8%) Severe: AV (46.2%); AB (80.3%)	Antiviral: Oseltamivir Antibiotic: NR
Zhang et al[13]	115	Non severe: 84 (73%), Severe: 31 (27%)	1 (0.9%)	NR	NR	NR
Cao et al[31]	128	Non severe: 107 (83.6%), Severe: 21 (16.4%)	0%	NR	NR	NR
Chen et al[9]	99	Non severe: 76 (77%), Severe (ICU): 23 (23%)	11 (11%)	Acute respiratory injury: 8 (8%); Acute kidney injury: 3 (3%); Septic Shock: 4 (4%); Ventilator-associated pneumonia: 1 (1%)	All patients: AV (76%), AB (71%)	Antiviral: Oseltamivir, ganciclovir, lopinavir/ritonavir Antibiotic: Cephalosporins, quinolones, carbapenems, tigecycline, linezolid
Richardson et al[18]	5700	Non severe: 4414 (77.4%), Severe (ICU): 1286 (22.6%)	553/2634 (21%)	Acute kidney injury: 1370 (24%); Acute Hepatic injury 89 (1.6%)	NR	NR
Zhang et al[10]	221	Non severe: 166 (75%), Severe: 55 (25%)	12 (5.4%)	Acute respiratory injury: 48 (21.7%); Acute kidney injury: 10 (4.5%); Acute cardiac injury: 17 (7.6%); Arrhythmia: 24 (11%); Shock: 15 (6.8)	All patients: AV (88.7%) Non-severe: AV (88%), Severe: AV (90.9%)	Antiviral: NR Antibiotic: NR
Bhatraju et al[11]	24	Severe: 24 (100%)	12 (50%)	Shock: 17 (71%)	All patients: AV (29.2%)	Antiviral: Remdesivir
Zhou et al[8]	191	General: 72 (38%), Severe: 66 (35%); Critical: 53 (28%)	54 (28%)	Sepsis: 112 (59%); Respiratory failure: 103 (54%); Heart failure: 44 (23%); Septic shock: 38 (20%); acute cardiac injury: 33 (17%); Acute kidney injury: 28 (15%); Secondary infection: 28 (15%)	All patients: AV (21%), AB (95%) Survivors: AV (21%), AB (93%)Non-survivors: AV (22%), AB (98%)	Antiviral: Lopinavir/ritonavir Antibiotic: NR
Pan et al[15]	204	NR (total)	36 (17.6%)	NR	All patients: AV (90.2%), AB (64.7%)	Antiviral: Lopinavir/ritonavir Antibiotic: NR
Wang et al[7]	138	Non severe: 102 (74%), Severe (ICU): 36 (26%)	6 (4.3%)	Respiratory failure: 27 (19.6%); Arrhythmia: 23 (16.7%); Shock: 12 (8.7%); Acute cardiac injury: 10 (7.2%); Acute Kidney injury: 5 (3.6%)	All patients: AV (89.9%); AB (100%) Non-ICU care: AV (88.2%); ICU care: AV (94.4%)	Antiviral: Oseltamivir Antibiotic: Moxifloxacin, ceftriaxone, azithromycin
Fu et al[16]	350	Common: 211 (60.3%), Severe: 88 (25.2%); Critical ill: 51 (14.5%)	34 (9.8%)	NR	NR	NR
Chen et al[17]	113	NR	113 (41%)	Type I respiratory failure: 18/67 (27%), Sepsis: 179 (65%), Acute cardiac injury: 89/203 (44%), Heart failure: 43/176 (24%), Acute kidney injury: 29 (11%)	All patients: AV (86%); AB (91%); Recovered: AV (91%); AB (89%) Deaths: AV (79%); AB (93%)	Antiviral: Oseltamivir, arbidol, lopinavir/ritonavir Antibiotic: Moxifloxacin, cefoperazone, or azithromycin

NR: Not report; ICU: Intensive care unit; AV: Antiviral therapy; AB: Antibiotic therapy; AM: Antimalarial.

Table 2 Frequency and serum levels of hepatic enzymes abnormalities in different studies

	AST abnormalities %1	Serum levelsAST U/L1	ALT abnormalities %	Serum levelsALT U/L1	Total bilirubinabnormalities %	Serum levels, Total bilirubin mol/L1
Xie et al[12]	35.4%	2All patients: 30 (20-50); Moderate: 28 (22-48); Severe: 35 (22-55)	31.6%	2All patients: 34 (18-67); Moderate: 28 (21-43.5); Severe: 36.5 (17.5-71.5)	5.1%	2All patients: 13.6 (8.8-17.6); Moderate: 13.9 (8.9-18.7); Severe: 12.7 (8.1-15.4)
Huang et al[5]	2All patients: 37%, Non-ICU: 25%; ICU: 6%	2All patients: 34 (26-48); Non-ICU: 34 (24-40.5); ICU: 44 (30-70)	NR	2All patients: 32 (21-50); Non-ICU care: 27 (19.5-40); ICU care: 49 (29-115)	NR	2All patients: 11.7 (9.5-13.9); Non-ICU care: 10.8 (9.4-12.3); ICU care: 49 (11.9-32.9)
Guan et al[6]	All patients: 22.2%; Non-severe: 18.2%; Severe: 39.4%; ICU/IMV/Death: 50%	NR	All patients: 21.3%; Non-severe: 19.8%; Severe: 28.1%; ICU/IMV/Death: 40.8%	NR	All patients: 10.5%; Non-severe: 9.9%; Severe: 13.3%; ICU/IMV/Death: 20.8%	NR
Zhang et al[13]	17%	2All patients: 28.3 ± 15.6; ULN ≤ 50 U/L: 85%; 50-150 U/L: 15%; > 150: none	11%	2All patients: 25.71 ± 21.8; ULN: ≤ 50 U/L: 90.4%; 50-150 U/L: 8.7%; > 150: 0.9%	6.96%	2All patients: 11.31 ± 5.8; ULN: ≤ 21 μmol/L: 94%; 21-31.5 μmol/L: 6%
Cao et al[31]	NR	All patients: 30.63 ± 18.85; Non-severe: 27.98 ± 25.8; Severe: 44.13 ± 36.26	NR	All patients: 31.35 ± 20.36; Non-severe: 28.89 ± 31.83; Severe: 43.87 ± 47.8	NR	NR
Chen N et al[9]	35%	All patients: 34 (26-48)	28%	All patients: 39 (21-55)	18%	All patients: 15.1 ± 7.6
Richardson et al[10]	58.4%	All patients: 46 (31-71)	39%	All patients: 33 (21-55)	NR	NR
Zhang et al[10]	NR	All patients: 29 (22-49); Non-severe: 27 (20-38); Severe: 51 (29-78)	NR	All patients: 23 (16-39); Non-severe: 22 (14-33); Severe: 32 (22-57)	NR	All patients: 10 (8-14.2); Non-severe: 9.6 (7.9-13.8); Severe: 11.4 (8.6-17.4)
Bhatraju et al[11]	41%	NR	32%	NR	NR	0.6 (0.5-0.7)
Zhou et al[8]	NR	NR	All patients: 31% Survivor: 24%; Non-survivor: 48%	All patients: 30 (17-46); Survivor: 27 (15-40); Non-survivor: 40 (24-51)	NR	NR
Pan et al[15]	NR	All patients: 35.6 ± 59.6	NR	All patients: 35.8 ± 48.5	NR	All patients: 13.3 ± 10.2
Wang et al[7]	NR	All patients: 31 (24-51); Non-ICU: 29 (21-38); ICU: 52 (30-70)	NR	All patients: 24 (16-40); Non-ICU: 23 (15-36); ICU: 35 (19-57)	NR	All patients: 9.8 (8.4-14.1); Non-ICU: 9.3 (8.2-12.8); ICU: 11.55 (9.6-18.6)
Fu et al[16]	NR	Common: 16 (20-35); Severe: 29 (23-54); Critical ill: 49 (35-80)	NR	Common: 22 (14-35); Severe: 23 (15-36); Critical ill: 33 (19-61)	NR	2Common: 10.4 (7.5-14.7) Severe: 10.9 (8.0-16.2); Critical ill: 12.6 (10.5-17)
Chen et al[17]	All patients: 31%; Deaths: 52%; Recovered: 16%	All patients: 16 (22-46); Recovered: 25 (20-33.3); Deaths: 45 (31-67)	All patients: 22%; Deaths: 27%; Recovered: 19%	All patients: 23 (15-38); Recovered: 20 (14.2-32); Deaths: 28 (18-57)	NR	All patients: 9.6 (6.7-13.5); Recovered: 8.4 (5.8-11.2); Deaths: 12.6 (9.4-16.7)

¹Data is mean ± SD or median.

²Values on admission. ALT: Alanine transaminase; AST: Aspartate transaminase; NR: Not report; ICU: Intensive care unit; IMV: Invasive mechanical ventilation; ULN: Upper limit of normal.