Cost-effectiveness analysis of population-based screening of hepatocellular carcinoma: Comparing ultrasonography with two-stage screening

Table 1 Base-case estimates and ranges used in sensitivity analysis

Variables	Base-case		Distribution of probabilistic sensitivity analysis		Ref.
Natural history and prognosis, per year
Prevalence of cirrhosis	1.77%		Β (1069, 59257)		[23]
Annual transition rates
HCC incidence (1/yr)	NC	Cirrhosis	NC	Cirrhosis
30-39 yr	0.00012	0.0024	Gamma (0.06, 510)	Gamma (0.23, 96)	[2,10,23]
40-49 yr	0.00036	0.0070	Gamma (0.33, 1190)	Gamma (1.2, 220)
50-59 yr	0.00100	0.0200	Gamma (3.07, 3614)	Gamma (10, 632)
60-69 yr	0.00210	0.0410	Gamma (19, 8928)	Gamma (67, 1640)
70-79 yr	0.00430	0.0820	Gamma (79, 18280)	Gamma (269, 3280)
PHCC to CHCC (Non-cirrhosis)	0.376 (0.157- 0.595)		Gamma (11.3, 30.1)		[10,15]
PHCC to CHCC (Cirrhosis )	0.637 (0.21-1.06)		Gamma (8.7, 13.6)
CHCC to HCC death	1.05 (0.93-1.18)		Gamma (1.14, 1.09)
Age-specific mortality rate of cirrhosis
30-39 yr	0.0046		Gamma (0.2, 49.4)		[2,16-19]
40-49 yr	0.0086		Gamma (0.8, 92.3)
50-59 yr	0.0170		Gamma (3.1, 182.4)
60-69 yr	0.0380		Gamma (15.5, 407.7)
70-79 yr	0.0980		Gamma (103, 1051.5)
Survival rate of surveillance-detected PHCC (%)	75		Gamma (11.2, 15.8)		[15]
First-stage 5 markers screening characteristics
Attendance rate (%)	60		Β (23654, 18733)		[9,13,24]
Sensitivity to Cirrhosis (%)	80		Β (62, 15)		[20]
Sensitivity to HCC	95		Β (50, 1)		[13]
Specificity to HCC	70		Β (9493, 4282)		[13]
Second-stage ultrasonography screening characteristics
Compliance rate of ultrasonography (%)	80		Β (16394, 3212)		[9,13,24]
Sensitivity to cirrhosis (%)	75		Β (11, 3)		[21]
Sensitivity to HCC (%)	83		Β (48, 10)		[9,12,22]
Specificity to HCC (%)	97		Β (20137, 637)		[9,12,22]
Direct cost (USD)
Biochemical test
HBsAg	4.7				BNHI
HCVAb	7.4				BNHI
GOT	1.5				BNHI
GPT	1.5				BNHI
AFP	5.9				BNHI
Ultrasonography	26				BNHI
Confirmation (USD)
Triple-phase abdominal CT	148				BNHI
Ultrasonic guidance for biopsy	38.3				BNHI
Liver puncture	36				BNHI
Specimen examinations of pathology	51.2				BNHI
Treatment (USD)
Initial cost of HCC treatment	4892		Lognormal (8.28, 0.53)		NTUH
Continuing cost of HCC treatment	4266		Lognormal (8.18, 0.46)		NTUH
Incurable-cancer care (average)	5691		Lognormal (8.36, 0.81)		NTUH
Indirect cost (USD)
Screening time (h)	0.5				[10,26]
Person accompanied for screening	0				[10,26]
Time spent for ultrasonography	4				[10,26]
Confirmation time (h)	8				NTUH, [26]
Person accompanied for confirmation	1				NTUH, [26]
Inpatient hospitalization (d)	15				NTUH
Inpatient recovered at home (d)	15				[26]
Person accompanied for inpatient care	1.69				[26]
Outpatient time per visit (h)	4				[26]
Outpatient visit per year	9.7				NTUH
Patient accompanied for outpatient visit	0.77				[26]
Inpatient of terminal care (d)	30				NTUH
Person accompanied for terminal care	1				[26]
Average work per month (h)	184				DGBAS
Production value per hour (USD)	7.6				DGBAS
Discount rate (%)	3

NC: Non-cirrhosis; HCC: Hepatocellular carcinoma; PHCC: Preclinical hepatocellular carcinoma; CHCC: Clinical hepatocellular carcinoma; CT: Computed tomography; GNP: Gross national product; BNHI: Bureau of the National Health Insurance; NTUH: National Taiwan University Hospital; DGBAS: Directorate General of Budget, Accounting and Statistics.

Table 2 Simulated results for screening strategies to prevent hepatocellular carcinoma

Outcome	No intervention	Two-stage screening	Mass screening using ultrasonography
Cost per individual screened, USD	2755	3389	3359
Life-year gain1 (yr)	20.4798	20.4926	20.4950
Comparing with ICER
No screening as reference	-	49733	39825
Two-stage screening as reference	-	-	Dominant2

¹Screening starting age was 40 years old, screening interval was 1 year;

²More effective and less costly than reference strategy. ICER: Incremental cost-effectiveness ratio.