Cost-effectiveness of enhanced liver fibrosis test to assess liver fibrosis in chronic hepatitis C virus and alcoholic liver disease patients

Table 1 Test strategies

Strategy	First test result		Confirmation test result
	Negative	Positive	Negative	Positive
Single biopsy	No action	Treatment + annual screening for HCC and DC if F = 4	No confirmation test is performed
Annual ELF/LSM	Annual ELF	LSM	Annual ELF	Treatment + annual screening for HCC and DC if F = 4
Annual ELF	Annual ELF	Treatment + annual screening for HCC and DC if F = 4	No confirmation test is performed

ELF: Enhanced liver fibrosis test; LSM: Liver stiffness measurement; HCC: Hepatocellular carcinoma; DC: Decompensated cirrhosis.

Table 2 Transition probabilities, accuracy of tests, and other parameters

		Baseline	Range	PSA distribution1	Source
Annual transition probabilities in HCV (%)
From	To
F0-F1	F2-F3	2.5	2.0-3.1	β (2.5; 0.4)	[27]
F2-F3	F4	3.7	2.5-5.3	β (3.7; 0.7)	[27]
F4	DC	3.9	3.1-5.0	β (3.9; 0.5)	[29]
F4	HCC	3.7	3.2-4.2	β (3.7; 0.25)	[30]
DC	HCC	6.8	-	-	[31]
DC/HCC	LTX	2	1-21	U (1; 21)	[12,32]
DC	Death	12.7	-	-	[31]
HCC	Death	43	-	-	[29]
LTX	Death	19	18-20	-	[33]
Post-LTX	Death	4.6	-	-	[33]
Response rate to treatment in HCV (%)
F0-F3		100.0	98.0-100	β (99.4; 0.6)	[17]
F4		97.0	84.2-99.9	β (97.0; 2.9)	[17]
Annual transition probabilities in ALD (%)
From	To
F0-F1	F2-F3	2.0	1.1-3.2	β (2; 0.5)	[22]
F0-F1 (abstainers)	F2-F3	0.01	-	-	[22]
F2-F3	F4	20	7-33	U (7; 33)	[22]
F2-F3 (abstainers)	F0-F1	26	10-50	U (10; 50)	[34]
F4	DC	23	18-29	β (23; 2.75)	[23]
F4	HCC	1.7	1.2-2.2	β (1.7; 0.25)	[30]
DC	HCC	2.15	-	-	[24]
DC/HCC	LTX	2	1-21	U (1; 21)	[12,32]
DC	Death	17.5	16-19	β (17.5; 0.75)	[24]
HCC	Death	43	-	-	Assumed as for HCV
LTX	Death	19	18-20	-	[33]
Post-LTX	Death	4.6	-	-	[33]
Abstinence rate following therapy (%)
If diagnosed F2-F3		27	14-43	β (27; 7)	[35]
If diagnosed F4		66	46-82	β (66; 9)	[35]
Probability of relapse before 12 mo (%)
F2-F3		45	17-77	β (45; 15)	[35]
F4		58	33-88	β (58; 14)	[35]
Test accuracy for F ≥ 2 (%)
ELF Sensitivity		90	85-93	β (90; 1.9)	[26]
ELF Specificity		52	43-61	β (52; 4.6)	[26]
LSM Sensitivity (HCV)		79	75-83	β (79; 2.0)	[15]
LSM Specificity (HCV)		89	84-93	β (89; 2.0)	[15]
LSM Sensitivity (ALD)		81	70-88	β (81; 4.5)	[15]
LSM Specificity (ALD)		92	76-98	β (92; 5.5)	[15]
Biopsy Sensitivity		90	85-95	U (85; 95)	Based on [25]
Biopsy Specificity		90	85-95	U (85; 95)	Based on [25]
Test accuracy for F = 4 (%)
ELF Sensitivity		90	84-94	-	[26]
ELF Specificity		53	46-59	-	[26]
LSM Sensitivity (HCV)		84	72-91	-	[15]
LSM Specificity (HCV)		77	50-92	-	[15]
LSM Sensitivity (ALD)		86	76-92	-	[15]
LSM Specificity (ALD)		83	74-89	-	[15]
Biopsy Sensitivity		90	85-95	U (85; 95)	Based on [25]
Biopsy Specificity		90	85-95	U (85; 95)	Based on [25]
Other Parameters
Relative risk of mortality for drinkers		2.0	1.0-4.0	U (1.0; 4.0)	Assumption
Relative risk of DC for F4 abstainers		0.33	0.33-1.0	U (0.33; 1.0)	Based on [36]
Relative risk of HCC for F4 abstainers		0.33	0.33-1.0	U (0.33; 1.0)	Based on [36]
Cohort’s initial age (years)		40	30-50	γ (40; 10)	Assumption
Prevalence of LF (F ≥ 2) (%)		53	40-66	U (40; 66)	Assumption
Prevalence of cirrhosis (F = 4) (%)		20	14-27	U (14; 27)	Assumption
Death probability related to biopsy (%)		0.09	0.06-0.12	β (0.09; 0.01)	[28]
Prob. of nonfatal adverse event related to Biopsy (%)		0.72	-	-	[28]

¹PSA: Probabilistic sensitivity analysis; In beta (β) and gamma (γ) distributions, parameters correspond to mean and SD; In uniform (U) distributions, parameters correspond to minimum and maximum values. F0-F1: No fibrosis or mild fibrosis; F2-F3: Moderate or severe fibrosis; F4: Cirrhosis. ELF: Enhanced liver fibrosis test; LSM: Liver stiffness measurement; LF: Liver fibrosis; DC: Decompensated cirrhosis; HCC: Hepatocellular carcinoma; LTX: Liver transplantation.

Table 3 Diagnostic accuracy, health outcomes and costs in hepatitis C virus patients

Diagnostic accuracy (%)1		Biopsy	ELF/LSM	ELF
Liver fibrosis (F ≥ 2)
TP		47.7	37.7	47.7
FN		5.3	15.3	5.3
TN		42.3	44.5	24.4
FP		4.7	2.5	22.6
Cirrhosis (F4)
TP		18.1	15.2	18.1
FN		2.0	4.9	2.0
TN		71.9	71.2	42.3
FP		8.0	8.6	37.5
Frequency of events (%)	No testing	Single	Annual	Annual
		Biopsy	ELF/LSM	ELF
Compensated cirrhosis (new cases)	40.4	16.8	0.9	0.2
Decompensated cirrhosis	24.7	7.0	0.3	0.1
Hepatocellular carcinoma	25.6	7.2	0.3	0.1
Fibrosis-related death	47.9	13.5	0.6	0.2
QALYs, costs and ICER	No testing	Single	Annual	Annual
		Biopsy	ELF/LSM	ELF
QALYs	12.36	15.27	16.33	16.75
Cost per patient (€)	24 353	43 447	57 691	60 443
ICER relative to “no testing”		6 561	8 397	8 221
ICER relative to biopsy			13 438	11 484

¹Percentage of cases detected on first test. Initial prevalence: liver fibrosis = 53%; cirrhosis = 20%. TP: True positives; FN: False negatives; TN: True negatives; FP: False positives; QALY: Quality-adjusted life year; ICER: Incremental cost-effectiveness ratio (€ per QALY); ELF: Enhanced liver fibrosis test; LSM: Liver stiffness measurement.

Table 4 Diagnostic accuracy, health outcomes and costs in alcoholic liver disease patients

Diagnostic accuracy (%)1		Biopsy	ELF/LSM	ELF
Liver fibrosis (F ≥ 2)
TP		47.7	38.6	47.7
FN		5.3	14.4	5.3
TN		42.3	45.2	24.4
FP		4.7	1.8	22.6
Cirrhosis (F4)
TP		18.1	15.6	18.1
FN		2.0	4.5	2.0
TN		71.9	73.5	42.3
FP		8.0	6.4	37.5
Frequency of events (%)	No testing	Single	Annual	Annual
		Biopsy	ELF/LSM	ELF
Compensated cirrhosis (new cases)	51.8	49.7	39.0	27.8
Decompensated cirrhosis	64.7	61.4	38.7	30.2
Hepatocellular carcinoma	10.2	9.8	7.3	5.8
Fibrosis-related death	68.8	66.5	54.8	44.4
QALYs, costs and ICER	No testing	Single	Annual	Annual
		Biopsy	ELF/LSM	ELF
QALYs	9.2	9.55	10.88	11.94
Cost per patient (€)	13 985	14 209	14 581	14 661
ICER relative to “no testing”		640	355	247
ICER relative to biopsy			280	189

¹Percentage of cases detected on first test. Initial prevalence: liver fibrosis = 53%; cirrhosis = 20%. TP: True positives, FN: False negatives; TN: True negatives; FP: False positives; QALY: Quality-adjusted life year; ICER: Incremental cost-effectiveness ratio (€ per QALY); ELF: Enhanced liver fibrosis test; LSM: Liver stiffness measurement.