Diagnostic accuracy of routine liver function tests to identify patients with significant and advanced alcohol-related liver fibrosis

Figures & data

Table 1. Patient characteristics (n = 225).

	Median (p25–p75)
Gender, male (%)	169 (75%)
Age, years	56 (51–64)
Body mass index, kg/m^2	27 (23–31)
Abstinence, yes (%)	109 (48%)
Alanine transaminase, U/L	39 (21–47)
Alkaline phosphatase, U/L	105 (71–121)
Aspartate aminotransferase, U/L	48 (25–52)
Albumin, g/L	40 (39–44)
Bilirubin, µmol/L	12 (7–14)
Gamma glutamyltransferase, U/L	203 (38–215)
Platelets, U/L	236 (189–293)
Cholesterol, total mmol/L	5.0 (4.3–6.0)
Sodium, mmol/L	139 (138–141)
INR	1.0 (0.9–1.1)
APRI score	0.7 (0.2–0.7)
FIB-4	2.5 (1.0–2.8)
Forns index	5.5 (4.0–6.8)
Fibro test	0.35 (0.11–0.58)
ELF test	9.7 (8.7–10.5)
Transient elastography, kPa	14.5 (5.1–11.8)
Kleiner fibrosis stage (0–1/2/3/4)	113/63/16/33

INR: international normalized ratio; APRI score: AST to platelet ratio index, FIB-4: fibrosis-4 score; ELF test: enhanced liver fibrosis test. All data rounded to one decimal.

Figure 1. Diagnostic performance of the routine liver function tests and non-invasive markers shown in receiver operating characteristics curves. AUROC: area under receiver operating curves; ALT: alanine transaminase; AST: aspartate aminotransferase; GGT: gamma glutamyltransferase; INR: international normalized ratio; APRI: aspartate to platelet ratio index; FIB-4: fibrosis-4 score; ELF test: enhanced liver fibrosis test.

Figure 2. Results of doctors, laboratory tests, and indirect and direct fibrosis markers as diagnostic test for significant fibrosis shown in four forest plots. N = 210, since 15 patients were not biopsied due to change in protocol, because of data showing NPV of 100% when TE below 6 kPa. TP: true positive; FP: false positive; FN: false negative; TN: true negative; ALT: alanine transaminase (cut-off: 45 as ULN for female, 70 as ULN for male); AST: aspartate aminotransferase (cut-off: 45 as ULN for female, 100 as ULN for male); GGT: gamma glutamyltransferase (cut-off: 75 as ULN for female, 115 as ULN for male); INR: international normalized ratio (cut-off: 1.1 as ULN for both female and male); APRI: aspartate to platelet ratio index (cut-off: 0.7 as ULN for both female and male); FIB-4: fibrosis-4 score (cut-off: 3.25 as ULN for both female and male); ELF test: enhanced liver fibrosis test; (cut-off: 7.7 ULN for significant fibrosis for both female and male).

Figure 3. Results of doctors, laboratory tests, and indirect and direct fibrosis markers as diagnostic test for significant fibrosis shown in four forest plots. N = 225. TP: true positive; FP: false positive; FN: false negative; TN: true negative; ALT: alanine transaminase (cut-off: 45 as ULN for female, 70 as ULN for male); AST: aspartate aminotransferase (cut-off: 45 as ULN for female, 100 as ULN for male); GGT: gamma glutamyltransferase (cut-off: 75 as ULN for female, 115 as ULN for male); INR: international normalized ratio (cut-off: 1.1 as ULN for both female and male); APRI: aspartate to platelet ratio index (cut-off: 1.0 as ULN for both female and male); FIB-4: fibrosis-4 score (cut-off: 3.25 as ULN for both female and male); ELF test: enhanced liver fibrosis test; (cut-off: 10.5 ULN for advanced fibrosis for both female and male).

Table 2. Diagnostic accuracy of the nine doctors.

	Significant fibrosis (≥F2)			Severe fibrosis (≥F3)
	Sensitivity	Specificity	Correctly classified (TP + TN)	Sensitivity	Specificity	Correctly classified (TP + TN)
Family doctor 1	93% (86–97)	12% [7–20]	55% (104 + 12)	61% (46–75)	75% (68–81)	72% (30 + 132)
Family doctor 2	60% (50–69)	69% (59–78)	64% (67 + 67)	45% (31–60)	95% (91–98)	84% (22 + 168)
Family doctor 3	58% (46–69)	56% (43–68)	57% (45 + 35)	25% (12–42)	94% (88–98)	48% (9 + 99)
Family doctor 4	76% (65–85)	79% (67–89)	77% (59 + 50)	69% (52–84)	85% (76–91)	51% (25 + 89)
Family doctor 5	72% (61–81)	75% (62–85)	73% (56 + 47)	64% (46–79)	75% (66–83)	45% (23 + 79)
Hepatologist 1	66% (57–75)	74% (65–83)	70% (74 + 73)	51% (36–66)	92% (87–96)	83 % (25 + 162)
Hepatologist 2	47% (38–57)	91% (83–96)	68% (53 + 89)	63% (48–77)	93% (88–96)	87% (31 + 164)
Hepatologist 3	22% (13–33)	86% (75–93)	50% (17 + 54)	64% (46–79)	90% (82–95)	83% (23 + 94)
Hepatologist 4	69% (58–79)	67% (54–78)	68% (54 + 42)	58% (41–75)	88% (80–93)	80% (21 + 92)

95% confidence intervals in parenthesis for sensitivity and specificity. Actual numbers in parenthesis for the correctly classified. TP: true positives; TN: true negatives.