Liver injury in COVID-19: Clinical features, potential mechanisms, risk factors and clinical treatments

Table 1 Criteria, grading, and incidence of abnormal liver function or injury

Ref.	Sample size	Study type	Criteria and grading of ALF or injury	Comments
Salık et al[5]	533	Retrospective study	Liver biochemical parameters: ALT, AST, and TBiL > ULN. Liver injury: ALT and/or AST > 3 ULN, and/or TBiL > 3 ULN	NA
Cai et al[6]	417	Retrospective, single-center study	ALF: > ULN. Liver injury: ALT and/or AST > 3 ULN, ALP, GGT, and/or TBiL > 2 ULN	76.3% had ALF and 21.5% had liver injury during hospitalization
Fan et al[8]	148	Retrospective, single-center study	Increased levels of ALT, AST, GGT, ALP, and total bilirubin	37.2% had ALF at hospital admission
Kulkarni et al[9]	20874	Meta-analysis	ELC: AST or ALT > ULN. SLI: Any elevation of enzymes > ULN and bilirubin over 2 ULN	ELC: 23.1% at initial presentation. 24.4% developed ELC during the illness
Xu et al[10]	1003	Retrospective cohort study	Mild liver injury: 1-2 ULN. Moderate liver injury: 2-5 ULN. Significant liver injury: > 5 ULN	Most patients with abnormal liver function parameters had mild elevations (1-2 ULN) at admission and peak hospitalization
Hundt et al[13]	1827	Retrospective observational cohort study	ELC: AST, ALT, ALP, TBiL, albumin: > ULN	ELC at pre-hospitalization (AST 25.9%, ALT 38.0%, ALP 56.8%, and TBiL 44.4%). Admission (AST 66.9%, ALT 41.6%, ALP 13.5%, and TBiL 4.3%). Peak hospitalization (AST 83.4%, ALT 61.6%, ALP 22.7%, and TBiL 16.1%)
Balderramo et al[14]	298	Multicenter study	ALEx2: The elevation of at least one of the following: TBil, ALT, AST, GGT, or ALP > 2 ULN	During admission, 29.2% out of 298 patients presented ALEx2
Phipps et al[19]	6913	Retrospective cohort study	Mild: ALT 1-2 ULN. Moderate: ALT between 2-5 ULN. Severe: ALT > 5 ULN	Among patients who tested positive, 45% had mild, 21% moderate, and 6.4% SLI
Wang et al[21]	156	Retrospective, 2-centers study	Elevated aminotransferases	41.0% patients with elevated aminotransferases
Liu et al[22]	245	Retrospective, single-center study	Mild liver dysfunction: AST ≥ ULN. Moderate liver dysfunction: AST ≥ ULN combined with any parameter being greater than the ULN values of ALT, GGT, and TBiL. Severe liver dysfunction: AST ≥ ULN combined with ALT ≥ 3 ULN and/or GGT, TBiL ≥ 2 ULN	43.7% experienced mild liver dysfunction, 40.4% experienced moderate liver dysfunction, and 20.4% experienced severe liver dysfunction
Chaibi et al[23]	281	Retrospective cohort study	ALF: AST, ALT, GGT, ALP or TBil > ULN	36.3 % had liver dysfunctions. Only a minority of patients (6.4%) had perturbations above 5 times the ULN
Shousha et al[24]	547	Multicenter cohort study	Liver injury: Transaminase > 3 ULN	26% and 32% of patients had elevated ALT and AST, respectively. 4.91 and 3.70%patients, respectively, had AST or ALT elevation > 3 ULN

ALEx2: Abnormal liver enzymes over twice the upper limit of normal; ALF: Abnormal liver function; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ELC: Elevated liver chemistries; DBiL: Direct bilirubin; GGT: Gamma-glutamyl transferase; NA: Not available; TBil: Total bilirubin; ULN: Upper limit of normal.