Review
Copyright ©The Author(s) 2023.
World J Gastroenterol. Apr 28, 2023; 29(16): 2397-2432
Published online Apr 28, 2023. doi: 10.3748/wjg.v29.i16.2397
Table 1 Liver function tests and factors associated significantly with clinical outcomes in COVID-19
Author/yr
Type of study (n of patients)
Factor
Outcome - statistical significance (severity/mechanical ventilation/ICU/mortality)
Krishnan et al[321], 2022, United StatesRetrospective (n = 3830)TBIL1
2–5 × ULNMortality risk significantly increased 6-fold (P < 0.001)
> 5 × ULNMortality risk increased 7.86-fold (P = 0.005)
AST1
2–5 × ULNAll-cause mortality HR, 1.49; P < 0.001
> 5 × ULNAll-cause mortality HR, 2.19; P = 0.005
ALP1
1–2 × ULNAll-cause mortality risk increased 1.42-fold (P = 0.009)
> 2–5 × ULNAll-cause mortality risk increased 1.81-fold (P = 0.032)
Inflammatory markers
CRPaHR, 1.04 associated with mortality (P = 0.001)
FerritinaHR, 1.0 associated with mortality (P = 0.001)
IL-6aHR, 1.0 associated with mortality (P = 0.001)
neutrophil countaHR, 1.0 associated with mortality (P = 0.008)
D-DimeraHR, 1.03 associated with mortality (P = 0.004)
LDHaHR, 1.0 associated with mortality (P < 0.001)
AST, ALT, TBILSignificantly increased for those who received MV (P < 0.0001)
Kodavoor et al[180], 2022, IndiaRetrospective (n = 708)AST1aOR 1.007, per 1 IU/L increase for SD
AST1aHR 1.002 per 1 IU/L increase for mortality
Sensitivity/specificity90.6%/67% to predict mortality
PPV/NPV17.5%/95.73% to predict mortality
Albumin1aOR 0.217 per 1 g/dL increase for SD
aHR 0.396 per 1 g/dL increase for mortality
Lombardi et al[230], 2022, ItalyRetrospective (n = 382)Transaminases1
> 2 × ULNOR 2.6, 95%CI: 1.3–6.7 for SD
FIB-4 score < 1.451(OR 0.4; P = 0.04) protective factor for mortality
Hartl et al[326], 2022, AustriaRetrospective (n = 900)AST1aHR: 1.47; P = 0.043 for mortality
TBIL1aHR: 2.20; P = 0.009 for mortality
Siddiqui et al[229], 2022, United StatesRetrospective (n = 1935)Abnormal LFTs
Liver injury defined as: (AST/ALT > 3 × ULN or ALP/TBIL > 2 × ULN)RR, 4.26; P < 0.0001 risk for mortality
Mild elevated enzymesRR, 5.52; P < 0.0001 for ICU admission
(Levels lower than LI)RR, 11.01; P < 0.0001 for MV
RR, 2.16; P < 0.0001 for mortality
RR, 2.48; P < 0.0001 ICU admission
CirrhoticsRR, 3.76; P < 0.0001 for MV
RR, 2.19; P = 0.0022 for mortality
Cai et al[20], 2020, ChinaRetrospective (n = 417)Hepatocellular LIOR, 2.73; P = 0.02 for severe disease
Mixed LIOR, 4.44; P < 0.001 for severe disease
LI1aOR, 9.04; P < 0.001 for severe disease
Huang et al[191], 2020, ChinaRetrospective (n = 675)AST1 3-fold ULNaOR, 19.27; P < 0.0001 for mortality
aOR, 116.72; P < 0.0001 for MV
Lei et al[192], 2020, ChinaRetrospective (n = 5771)AST1 40-120 U/LaOR, 4.81; P < 0.001 for all-cause mortality
AST1 > 120 U/LaOR, 14.87; P < 0.001 for all-cause mortality
Ding et al[22], 2020, ChinaRetrospective (n = 2073)Abnormal AST1aHR, 1.39; P = 0.027 for mortality
Abnormal DBIL1aHR, 1.66; P = 0.001 for mortality
LI during hospitalization1aHR, 4.63; P < 0.001 for in-hospital mortality
LI at admission1aHR 1.87; P = 0.003 for in-hospital mortality
Mixed LI1aHR, 4.77; P < 0.001 for in-hospital mortality
Cholestatic LI1aHR, 3.99; P = 0.008 for in-hospital mortality
Phipps et al[23], 2020, United StatesRetrospective (n = 3381)Ferritin1OR, 2.40; P < 0.001 for SLI
IL-61OR, 1.45; P = 0.009 for SLI
Peak ALT1OR, 1.14; P = 0.044 for mortality
Older age1OR, 1.07; P < 0.001 for mortality
DM1OR, 1.30; P = 0.045 for mortality
Medetalibeyoglu et al[221], 2020, TurkeyRetrospective (n = 554)AST/ALT > 1AUC = 0.713, P = 0.001 marker of mortality risk
AUC = 0.636, P = 0.001 for ICU admission
Chen et al[199], 2020, ChinaRetrospective (n = 502)Grade of Liver damage1aHR, 1.377; P = 0.049 risk factor for mortality
Mishra et al[200], 2021, United StatesRetrospective (n = 348)AST1 (1 unit increase) IU/L Peak AST1 (1 unit increase)OR, 1.011; P = 0.006 for mortality
Peak ALT1 (1 unit increase)OR, 1.007; P < 0.001 for mortality
TBIL1 (1 unit increase) mg/dLOR, 1.005; P = 0.003 for mortality
Alb1 (1 unit increase) g/dLOR, 1.997; P = 0.04
Male1OR, 0.5; P = 0.01
BMI > 40 kg/m2OR, 1.94; P = 0.001
LI1OR, 2.17; P = 0.003
OR, 1.79; P = 0.008
Chew et al[190], 2021, United StatesRetrospective (n = 834)Ischemic disease state1OR, 2.4; P = 0.001 for mortality
Hypecoagulable1OR, 1.7; P = 0.02 for mortality
Hyperinflammatory1OR, 1.9; P = 0.02 for mortality
Ponziani et al[327], 2021, ItalyRetrospective (n = 515)ALP1 peak valueaOR, 1.007; P = 0.005 for mortality
CRP1aOR, 1.007; P = 0.008 for mortality
Piano et al[246], 2020, ItalyRetrospective (n = 565)Abnormal LFTs1OR, 3.53; P < 0.001 for ICU admission/death
Yip et al[287], 2021, ChinaRetrospective (n = 1040)ALT/AST1 ≥ 2 × ULNaOR, 7.92; P < 0.001 for ICU/MV/death
Marjot et al[237], 2021, multinationalRetrospective (n = 785)Age1OR, 1.02; P = 0.011 for mortality
Cirrhotics CTP-A1OR, 1.90; P = 0.040 for mortality
Cirrhotics CTP-B1OR, 4.14; P < 0.001 for mortality
Cirrhotics CTP-C1OR, 9.32; P < 0.001 for mortality
ArLD1OR, 1.79; P = 0.040 for mortality
Lee et al[328], 2020, South KoreaRetrospective (n = 1005)Age1aHR = 4.96; P < 0.001 for mortality
Liver cirrhosis1aHR = 2.86; P = 0.042 fro mortality
DM1aHR = 2.29; P < 0.001 for mortality
COPD1aHR = 4.52; P = 0.001 for mortality
Singh et al[236], 2020, United StatesRetrospective (n = 2780)CLD1RR, 2.8; P < 0.001 risk of mortality
propensity matchingRR, 3.0; P = 0.001 risk of mortality
Cirrhotics1RR, 4.6; P < 0.001 risk of mortality
Hashemi et al[232], 2020, United StatesRetrospective (n = 363)CLD1aOR 1.77; P = 0.04 for ICU admission
aOR, 2.08; P = 0.0092 for IMV
Cirrhotics1aOR, 12.5; P = 0.009 mortality risk
Sarin et al[235], 2020, AsianRetrospective (n = 228 CLD)Cirrhotics1
AST/ALT > 1.4HR = 1.4; P = 0.02 for mortality
ObesityOR = 8.1; P = 0.002 for LI
DecompensatedOR = 2.5; P = 0.05 for mortality
CTP score > 8HR = 19.2; P < 0.001 for mortality
DM in CLD non-cirrhoticsOR = 2.1; P = 0.01 for LI
Wang et al[51], 2020, ChinaRetrospective (n = 657)Male gender1OR, 2.038; P < 0.001 for LI
hsCRP ≥ 10 mg/LOR, 1.733; p = 0.014 for LI
NLR ≥ 5OR, 2.154; P < 0.001 for LI
Zhang et al[183], 2020, ChinaRetrospective (n = 218)Male1OR, 6.203; P < 0.001 risk for LI
Neutrophil percentage1OR, 1.004; P = 0.003 risk for LI
CRP1P < 0.001 in LI patients
D-dimer1OR, 1.486; P < 0.001 risk for LI
Shauly-Aharonov et al[329], 2021, IsraelRetrospective (n = 37121)AgeOR = 1.1 for every year increase; P < 0.001) risk for severity
Male genderOR = 1.34; P = 0.012 risk for severity
BMIOR = 1.02 for 1 kg/m2 increase; P = 0.025 risk for severity
Kovalic et al[208], 2020, United StatesMeta-analysis (n = 24299)CLD1Pooled OR, 1.48; P = 0.001 for severity
Pooled OR, 1.78; P = 0.02 for mortality
Kulkarni et al[6], 2020, IndiaMeta-analysis Multinational (n = 20874)Increased LFTsOR, 3.46; P < 0.001 for mortality
OR, 2.87; P < 0.001 for severe disease
Sharma et al[207], 2021, United StatesMeta-analysis (n = 12882)AST1Pooled OR, 2.98; P < 0.00001 for poor outcomes
ALT1Pooled OR, 1.73; P < 0.0001 for poor outcomes
Del Zompo et al[323], 2020, ItalyMeta-analysis (n = 20724)ALT1OR 1.54, 95%CI: 1.17-2.03 for severity
ALT1OR 1.48, 95%CI: 1.12-1.96 for mortality
AST1OR 3.17, 95%CI: 2.10-4.77 for severity
AST1OR 4.39, 95%CI: 2.68-7.18 for mortality
TBIL1OR 2.32, 95%CI: 1.18-4.58 for severity
TBIL1OR 7.75, 95%CI: 2.28-26.40 for mortality