Non-invasive fibrosis scoring systems can predict future metabolic complications and overall mortality in non-alcoholic fatty liver disease (NAFLD)

Figures & data

Figure 1. Flow chart for patients’ inclusion.

Table 1. Patients’ characteristics at baseline and follow-up.

	NAFLD (n = 144)
	Mean ± SD, N (%)	Median (IQR)	Missing (N)
Sex F/M	61 (42.4)/83 (57.6)	n/a	0
Age (years)^a	53.2 ± 13.4	54.4 (43.0–63.3)	0
Follow-up time (years)	18.8 ± 9.2	17.7 (12.1–25.7)	0
Age at death (years)	75.6 ± 9.4	75.5 (70.6–82.9)	0
BMI (kg/m^b)^a	28.0 ± 4.6	27.7 (24.9–30.7)	12
ALT (U/L)^a	79.1 ± 64.5	56.5 (36.6–101.8)	0
AST (U/L)^a	51.9 ± 41.8	41.2 (29.4–64.6)	0
Total bilirubin (µmol/L)^a	17.4 ± 13.8	14.0 (10.0–20.0)	5
Platelets (×10^9/L)^a	210.8 ± 77.0	207.0 (158.5–258.5)	3
Albumin (g/L)^a	41.0 ± 5.9	42.0 (38.8–45.0)	10
Creatinine (µmol/L)^a	86.2 ± 18.5	84.0 (75.0–98.9)	6
Diabetes Mellitus at baseline^b	32 (22.2)	n/a	0
Diabetes Mellitus at follow-up^b	77 (53.5)	n/a	5
Hypertension at baseline^c	66 (45.8)	n/a	0
Hypertension at follow-up^c	95 (66.0)	n/a	4
Obesity at baseline^d	106 (73.6)	n/a	5
Obesity at follow-up^d	76 (52.8)	n/a	25
Cardiovascular disease at baseline^e	17 (11.8)	n/a	1
Cardiovascular disease at follow-up^e	77 (53.5)	n/a	6
Chronic kidney disease at baseline^f	18 (12.5)	n/a	6
Chronic kidney disease at follow-up^f	47 (32.6)	n/a	19
Steatosis grade
1	58 (40.3)	n/a	0
2	44 (30.6)
3	42 (29.2)
Fibrosis stage
0	92 (63.9)	n/a	0
1	17 (11.8)
2	9 (6.3)
3	10 (6.9)
4	16 (11.1)
Cirrhosis at follow-up	24 (16.7)	n/a	0
HCC at follow-up	8 (5.6)	n/a	0
FIB-4-index	2.0 ± 1.9	1.3 (0.8–2.3)	3
NAFLD fibrosis score	−1.4 ± 1.8	−1.57 (−2.7 to −0.4)	20
APRI	0.7 ± 0.6	0.5 (0.3–0.8)	3
BARD	1.5 ± 1.3	1.0 (0.0–2.0)	13

^aAt baseline; ^bAccording to medical files; ^cBlood pressure ≥140/90 mm Hg or antihypertensive drugs; ^dBody Mass Index ≥ 25 kg/m²; ^eMyocardial infarction, angina pectoris or ischaemic stroke; ^fCKD-EPI equation; eGFR < 60 mL/min/1.73 m².

HCC: hepatocellular cancer; IQR: interquartile range.

Figure 2. Mean values of non-invasive fibrosis scores according to fibrosis stage, p < .001 for FIB-4, NFS and APRI, and p = .001 for BARD.

Table 2. Area under the ROC curve for non-invasive scoring systems in predicting outcomes (AUROC ± SE (95% CI)).

	FIB-4	NFS	APRI	BARD
Overall mortality	0.82 ± 0.04	0.82 ± 0.04	0.59 ± 0.05	0.75 ± 0.04
	(0.75–0.90)	(0.74–0.90)	(0.50–0.68)	(0.66–0.83)
	p < .001	p < .001	p = .070	p < .001
Liver-related events	0.81 ± 0.06	0.77 ± 0.06	0.82 ± 0.05	0.61 ± 0.08
	(0.69–0.93)	(0.64–0.89)	(0.72–0.92)	(0.50–0.75)
	p < .001	p < .001	p < .001	p < .151
Diabetes mellitus at follow-up	0.55 ± 0.05	0.61 ± 0.05	0.63 ± 0.05	0.57 ± 0.05
	(0.45–0.65)	(0.51–0.72)	(0.54–0.73)	(0.47–0.67)
	p = .288	p = .031	p = .006	p = .173
Cardiovascular disease at follow-up	0.74 ± 0.05	0.76 ± 0.05	0.53 ± 0.05	0.69 ± 0.05
	(0.65–0.83)	(0.67–0.85)	(0.43–0.63)	(0.60–0.79)
	p < .001	p < .001	p = .505	p < .001
Chronic kidney disease at follow-up	0.64 ± 0.05	0.63 ± 0.06	0.56 ± 0.06	0.64 ± 0.05
	(0.54–0.74)	(0.52–0.74)	(0.45–0.66)	(0.54–0.74)
	p = .009	p = .025	p = .316	p = .013

Bold values indicates a significant p-value <.05.

Table 3. Multivariate-adjusted Hazard Ratios (HR) for metabolic complications at follow-up according to risk categories in fibrosis scoring systems (HR (95% CI), p-value).

Score	CVD	Diabetes mellitus	CKD
FIB-4^a
Low	1.0	1.0	1.0
Intermediate	2.67 (1.40–5.09),p = .003	2.14 (1.11–4.14),p = .024	4.77 (1.95–11.64),p = .001
High	6.52 (3.07–13.86),p < .001	4.18 (1.96–8.92),p < .001	7.25 (2.51–20.94),p < .001
NFS^b
Low	1.0	1.0	1.0
Intermediate	4.39 (2.39–8.07),p < .001	2.20 (1.17–4.14),p = .015	3.31 (1.41–7.74),p = .006
High	16.88 (5.68–50.23),p < .001	20.74 (6.90–62.38),p < .001	31.38 (7.92–124.38),p < .001
APRI^c
Low	1.0	1.0	1.0
Intermediate	1.05 (0.60–1.82),p = .872	1.54 (0.90–2.66),p = .118	1.49 (0.71–3.11),p = .288
High	3.21 (1.40–7.37),p = .006	2.70 (1.16–6.28),p = .021	4.31 (1.46–12.69),p = .008
BARD^d
Low	1.0	1.0	1.0
Intermediate	1.32 (0.67–2.57),p = .423	0.91 (0.48–1.73),p = .770	1.32 (0.58–3.02),p = .512
High	1.92 (0.98–3.77),p = .057	1.91 (0.98–3.72),p = .056	1.89 (0.77–4.65),p = .165

^aAdjusted for sex, BMI > 25, CVD, diabetes mellitus, hypertension, fibrosis stage.

^bAdjusted for sex, CVD, hypertension, fibrosis stage.

^cAdjusted for age, sex, BMI > 25, CVD, diabetes mellitus, hypertension, fibrosis stage.

^dAdjusted for age, sex, CVD, hypertension, fibrosis stage.

CKD: chronic kidney disease; CVD: cardiovascular disease.

Bold values indicates a significant p-value <.05.

Table 4. Multivariate-adjusted Hazard Ratios (HR) for overall mortality and liver-related events according to risk categories in fibrosis scoring systems (HR (95% CI), p-value).

Score	Overall mortality	Liver-related events
FIB-4^a
Low	1.0	1.0
Intermediate	3.09 (1.66–5.73),p < .001	0.48 (0.07–3.38),p = .464
High	6.46 (3.17–13.15),p < .001	5.88 (1.25–27.80),p = .025
NFS^b
Low	1.0	1.0
Intermediate	3.13 (1.77–5.54),p < .001	2.38 (0.49–11.49).p = .282
High	11.61 (4.54–29.71),p < .001	12.72 (1.67–97.00),p = .014
APRI^c
Low	1.0	1.0
Intermediate	1.17 (0.70–1.98),p = .55	2.57 (0.47–15.20),p = .297
High	2.75 (1.24–6.12),p = .01	9.36 (1.34–65.31),p = .024
BARD^d
Low	1.0	1.0
Intermediate	1.09 (0.59–0.98),p = .80	0.80 (0.23–2.75),p = .718
High	1.82 (0.98–3.39),p = .06	0.67 (0.16–2.74),p = .574

^aAdjusted for sex, BMI > 25, CVD, diabetes mellitus, hypertension, fibrosis stage.

^bAdjusted for sex, CVD, hypertension, fibrosis stage.

^cAdjusted for age, sex, BMI >25, CVD, diabetes mellitus, hypertension, fibrosis stage.

^dAdjusted for age, sex, CVD, hypertension, fibrosis stage.

CVD: cardiovascular disease.

Bold values indicates a significant p-value <.05.