Prognostic non-invasive biomarkers for all-cause mortality in non-alcoholic fatty liver disease: A systematic review and meta-analysis

Table 2 Meta-analysis of non-invasive scoring systems and all-cause mortality and cardiovascular-related mortality

Comparison categories1	No. studies	Studies included	Heterogeneity: I2 (P value for Q)2	Pooled HR (95%CI)	P value for overall effect (pHR)
All-cause mortality
NFS high vs low	4	Le et al[18], 2019; Kim et al[29], 2013; Hagstrom et al[30], 2019; Angulo et al[31], 2013	75.7%(0.006)	3.07 (1.62 – 5.83)	0.001
NFS Int. vs low	4	Le et al[18], 2019; Kim et al[29], 2013; Hagstrom et al[30], 2019; Angulo et al[31], 2013	81.5%(0.001)	1.91 (1.18 – 3.09)	0.008
FIB-4 high vs low	3	Kim et al[29], 2013; Hagstrom et al[30], 2019; Angulo et al[31], 2013	73.0%(0.025)	3.06 (1.54 – 6.07)	0.001
FIB-4 Int. vs low	3	Kim et al[29], 2013; Hagstrom et al[30], 2019; Angulo et al[31], 2013	0.0%(0.396)	1.60 (1.33 – 1.91)	< 0.001
APRI high vs low	3	Kim et al[29], 2013; Hagstrom et al[30], 2019; Angulo et al[31], 2013	0.0%(0.589)	1.90 (1.32 – 2.73)	0.001
APRI Int. vs low	3	Kim et al[29], 2013; Hagstrom et al[30], 2019; Angulo et al[31], 2013	0.0%(0.411)	0.98 (0.76 – 1.26)	0.887
BARD high vs low	2	Hagstrom et al[30], 2019; Angulo et al[31], 2013	45.1%(0.177)3	2.87 (1.27 – 6.46)	0.011
BARD Int. vs low	2	Hagstrom et al[30], 2019; Angulo et al[31], 2013	0.0%(0.862)	1.64 (1.21 – 2.23)	0.001
Cardiovascular mortality
NFS high vs low	2	Le et al[18], 2019; Kim et al[29], 2013	0.0%(0.317)	3.09 (1.78 – 5.34)	< 0.001
NFS Int. vs low	2	Le et al[18], 2019; Kim et al[29], 2013	0.0%(0.759)	2.12 (1.41 – 3.17)	< 0.001

¹For Non-alcoholic fatty liver disease fibrosis score, cut-off values were “low” < -1.455 (reference group), “intermediate” -1.455 – 0.676, and “high” > 0.676. For fibrosis-4 index, cut-off values were “low” < 1.30 (reference group), “intermediate” 1.30-2.67, and “high” > 2.67. For AST to platelet ratio index, “low” < 0.5 (reference group), “intermediate” 0.5-1.5, and “high” > 1.5. For BARD, “low” 0-1 (reference group), “intermediate” 2-3, and “high” 4.

²Where the heterogeneity is statistically significant the results of the random effects analysis (DerSimonian-Laird method) are shown. Where heterogeneity is not a concern the results of the fixed effects analysis (inverse variance method) are shown. The P value is for the Cochran’s Q statistic.

³For the analysis of BARD high vs low the results of the random effects analysis are shown as the I² value suggests moderate heterogeneity is present, however note the low number (n = 2) of studies included.

NAFLD: Non-alcoholic fatty liver disease; NFS: NAFLD fibrosis score; FIB-4: Fibrosis-4 index; APRI: AST to platelet ratio index; BARD score: BMI ≥ 28 kg/m² (1 point), AST/ALT ratio ≥ 0.8 (2 points), and diabetes mellitus (1 point).