Observational Study
Copyright ©The Author(s) 2024.
World J Hepatol. Feb 27, 2024; 16(2): 251-263
Published online Feb 27, 2024. doi: 10.4254/wjh.v16.i2.251
Table 1 Clinical parameter baseline data for training cohort, validation cohorts and prospective confirmatory cohorts
Variable1
DifG3BP1 in training cohort
Validation cohorts
Overall
T1 (< 0)
T2 (0-1)
T3 (> 1)
P value2
Patients (n)2448312041514
Age (yr), mean ± SD51.9 ± 13.253.20 ± 12.0850.91 ± 14.0752.10 ± 13.100.47754.35 ± 15.6
Men, n (%)204 (83.6)68 (81.9)99 (82.5)37 (90.2)0.45426 (82.8)
AFP, mean ± SD108.93 ± 170.1268.65 ± 119.17124.85 ± 180.26143.86 ± 211.320.024106.94 ± 114.56
WBC, mean ± SD7.19 ± 3.548.28 ± 4.266.61 ± 2.976.70 ± 3.000.0027.43 ± 3.65
N%, mean ± SD69.38 ± 11.8572.79 ± 10.6067.33 ± 12.3968.50 ± 11.350.00471.34 ± 12.38
SAA, mean ± SD9.33 ± 14.1010.27 ± 13.579.61 ± 15.096.63 ± 11.990.3859.56 ± 13.87
CRP, mean ± SD14.03 ± 20.3117.94 ± 23.6412.09 ± 17.9311.78 ± 18.840.09613.67 ± 18.48
PCT, mean ± SD0.62 ± 0.750.76 ± 0.920.55 ± 0.680.56 ± 0.540.130.65 ± 0.71
ALB (g/L), mean ± SD31.23 ± 4.0030.99 ± 3.5331.36 ± 4.4331.31 ± 3.610.79932.56 ± 4.15
PTA (%), mean ± SD43.69 ± 20.0137.24 ± 15.9046.35 ± 21.9948.97 ± 18.400.00142.17 ± 21.03
PT, mean ± SD20.56 ± 6.2123.13 ± 7.0919.41 ± 5.4118.74 ± 4.85< 0.00119.15 ± 6.12
INR, mean ± SD1.83 ± 0.592.07 ± 0.701.72 ± 0.481.67 ± 0.47< 0.0011.87 ± 0.61
ALT, mean ± SD276.93 ± 546.24185.54 ± 266.86332.65 ± 701.28298.85 ± 420.080.162295.13 ± 537.87
TBIL, mean ± SD322.21 ± 131.10353.56 ± 150.78303.54 ± 122.07313.37 ± 101.510.024317.81 ± 145.11
AST, mean ± SD247.66 ± 468.92179.95 ± 188.58292.26 ± 623.86254.20 ± 299.160.244238.98 ± 464.17
LDH, mean ± SD273.07 ± 82.84302.18 ± 70.80250.64 ± 84.55279.78 ± 82.64< 0.001286.46 ± 86.78
GFR, mean ± SD101.69 ± 25.0597.36 ± 27.28104.94 ± 24.51100.96 ± 20.710.104102.54 ± 26.33
PLT, mean ± SD111.18 ± 67.1996.40 ± 66.11118.06 ± 64.91120.95 ± 72.380.046106.54 ± 71.77
Family history of liver disease, n (%)336 (14.75)14 (16.9)17 (14.2)5 (12.2)0.76378 (15.2)
Treatment method = PE + DPMAS (%)20 (8.20)7 (8.6)6 (7.3)7 (8.6)0.93846 (8.9)
LOS time (months), mean ± SD35.55 (20.63)34.36 (19.78)36.51 (22.33)35.75 (19.84)0.79735.78 (21.34)
Diabetes, n (%)33 (13.52)11 (13.6)8 (9.8)14 (17.3)0.37369
ALF, n (%)53 (21.72)14 (26.41)29 (54.72)10 (18.87)111 (21.60)
ACLF, n (%)191 (78.28)69 (36.13)91 (47.64)31 (16.23)403 (78.40)
1Continuous variables are expressed as mean ± SD or median, categorical variables are expressed as n (%).
2Comparing the covariates across the 3 categories of the difference of G3BP1 between the level of discharge and admission.
3The family history included hepatitis B, liver cirrhosis, and liver cancer.
ACLF: Acute-on-chronic liver failure; AFP: Alpha-fetoprotein; ALB: Albumin; ALF: Acute liver failure; ALT: Alanine aminotransferase; AST: Aspartate transaminase; CRP: C-reactive protein; DifG3BP1: Difference of G3BP1 between the level of discharge and admission; DPMAS: Dual plasma molecular adsorption system; GFR: Glomeruar filtration rate; INR: International normalized ratio; LDH: Lactate dehydrogenase; N%: Neutrophil percent; PCT: Procalcitonin; PE: Plasma exchange; PLT: Platelet; PTA: Prothrombin activity; PT: Prothrombin time; SAA: Serum amyloid A protein; TBIL: Total bilirubin; WBC: White blood cell. T1 group: The group patients with the changed value of difference of G3BP1 between the level of discharge and admission discharge and admission (difG3BP1) was less than 0; T2 group: The group patients with the changed value of difG3BP1 was more than 0 and less than 1; T3 group: The group patients with the changed value of difG3BP1 was more than 1.
Table 2 Multivariable Cox regression analyses of difference of G3BP1 between the level of discharge and admission discharge and admission for predicting the risk for progression in training cohort
G3BP1 cut points
Progression (%)1
Unadjusted HR (95%CI)
P value
Model 13
Adjusted HR (95%CI) P value
Total cohort (n = 244)
    T1 + T2 G3BP1 (n = 161)≥ 014 (8.7)1.0 (Reference)1.0 (Reference)
    T3 G3BP1 (n = 83)< 064 (77.1)11.70 (6.50-21.04)< 0.0019.23 (5.08-16.75)< 0.001
Subgroup with MELD2 high risk (n = 154)
    T2 + T3 G3BP1 (n = 94)≥ 013 (13.8)1.0 (Reference)1.0 (Reference)
    T1 G3BP1 (n = 60)< 053 (88.3)8.01 (4.33-14.81)< 0.0015.71 (3.04-10.74)< 0.001
Subgroup with MELD low-medium risk (n = 90)
    T2 + T3 G3BP1 (n = 67)≥ 01 (1.5)1.0 (Reference)1.0 (Reference)
    T1 G3BP1 (n = 23)< 011 (47.8)39.46 (5.05-308.3)< 0.00123.80 (2.96-191.3)< 0.001
1The progression was death or liver transplantation.
2Model for end-stage liver disease score = 3.78 × ln [total bilirubin (μmol/L)/17.1] + 11.2 × ln (international normalized ratio) + 9.57 × ln [creatinine (μmol/L)/88.4] + 6.43. The higher the score, the worse the prognosis. The score of low risk is ≤ 14 points, the score of medium risk is 15-18 points, and the score of high risk is > 18 points.
3Model 1 adjusts the linear variables lactate dehydrogenase, alpha-fetoprotein.
HR: Hazard ratio; MELD: Model for end-stage liver disease.
Table 3 Multivariable Cox regression analyses of biomarkers for predicting the risk for progression in training cohort
Biomarker
G3BP1 cut points
Progression (%)
Unadjusted HR (95%CI)
P value
Model 11
Adjusted HR (95%CI) P value
IL-1β (pg/mL)
    T1 IL-1β (n = 122)≤ 168.015 (12.3)1.0 (Reference)1.0 (Reference)
    T2 IL-1β (n = 122)> 168.058 (47.5)5.38 (3.03-9.54)< 0.014.27 (2.37-7.67)< 0.01
IL-18 (pg/mL)
    T1 IL-18 (n = 122)≤ 13.42538 (31.1)1.0 (Reference)1.0 (Reference)
    T2 IL-18 (n = 122)> 13.42535 (28.7)0.94 (0.59-1.49)0.780.95 (0.59-1.52)0.83
TNF-α (pg/mL)
    T1 TNF-α (n = 122)≤ 5.46546 (37.7)1.0 (Reference)1.0 (Reference)
    T2 TNF-α (n = 122)> 5.46527 (22.1)0.50 (0.31-0.80)< 0.010.55 (0.34-0.90)0.02
1Model 1 adjusts the linear variables lactate dehydrogenase, alpha-fetoprotein.
HR: Hazard ratio; IL: Interlenkin; TNF-α: Tumor necrosis factor-α.
Table 4 Performance of biomarkers and/or clinical data for predicting risk for progression in training and validation cohorts
BiomarkersC statistic (95%CI)1
Training cohort (n = 244)
Validation cohort (n = 514)2
Univariable models of biomarkers
    G3BP10.75 (0.68-0.81)0.75 (0.71-0.78)
    IL-1β0.68 (0.63-0.74)
    IL-180.54 (0.48-0.63)
    TNF-α0.57 (0.50-0.64)
Clinical models
    Clinical data0.78 (0.72-0.84)0.71 (0.66-0.76)
Models containing clinical data and biomarkers
    Clinical data + G3BP10.84 (0.77-0.89)0.80 (0.76-0.84)
    Clinical data + IL-1β0.80 (0.75-0.85)
    Clinical data + IL-180.78 (0.72-0.84)
    Clinical data + TNF-α0.78 (0.72-0.84)
Model containing clinical data and multiple biomarkers
    Clinical data + G3BP1 + IL-1β + IL-18 + TNF-α30.84 (0.79-0.90)
1Expressed as Harrell’s C-index, continuous biomarkers were used in the model.
2Due to limited sample availability of the validation cohort, only G3BP1 assay was performed for participants from the cohort.
3Comprising lactate dehydrogenase, alpha-fetoprotein.
HR: Hazard ratio; IL: Interlenkin; TNF-α: Tumor necrosis factor-α.