Economic burden of hepatitis B infection among patients with diabetes

Figures & data

Figure 1. Patient Attrition. ^aAt least 2 medical claims for diabetes at least 30 d apart (250.xx); OR at least 1 medical claim for diabetes and at least 1 pharmacy claim for a diabetes medication (GPI 27xx or 39100016x). ^bHepatitis B identified by ICD-9-CM codes 070.2x or 070.3x. ^cHepatitis C identified by ICD-9-CM codes 070.44, 070.54, 070.70, 070.71, 070.41, 070.51, or V02.62.

Table 1. Baseline Patient Clinical Characteristics Included in Propensity Score by Matched Status.^a

Clinical Characteristics	Prior to matching (N=918,488)			Matched cohort (N=6,180)
	Diabetes without HBV (n = 917,248)	Diabetes with HBV (n = 1,240)	p-value^b	Diabetes without HBV (n = 4,944)	Diabetes with HBV (n = 1,236)	p-value^b
Age (on index date), mean, median (SD)	56.6, 57.0 (14.33)	54.0, 54.0 (11.36)	<0.0001	54.1, 55.0 (14.15)	54.0, 54.0 (11.36)	0.8164
Gender, n (%)
Female	430,681 (47.0)	433 (34.9)	<0.0001	1,742 (35.2)	432 (35.0)	0.8521
Geographic region of healthplan, n (%)			<0.0001			0.9218
Northeast	177,957 (19.4)	290 (23.4)		1,113 (22.5)	290 (23.5)
Midwest	292,693 (31.9)	164 (13.2)		651 (13.2)	164 (13.3)
South	252,570 (27.5)	197 (15.9)		776 (15.7)	196 (15.9)
West	147,377 (16.1)	557 (44.9)		2,261 (45.7)	554 (44.8)
Unknown	46,651 (5.1)	32 (2.6)		143 (2.9)	32 (2.6)
Index year, n (%)			<0.0001			0.9608
2007	407,886 (44.5)	405 (32.7)		1,599 (32.3)	405 (32.8)
2008	120,931 (13.2)	183 (14.8)		696 (14.1)	183 (14.8)
2009	106,874 (11.7)	179 (14.4)		760 (15.4)	178 (14.4)
2010	87,960 (9.6)	164 (13.2)		664 (13.4)	164 (13.3)
2011	92,531 (10.1)	169 (13.6)		678 (13.7)	167 (13.5)
2012	79,581 (8.7)	121 (9.8)		461 (9.3)	120 (9.7)
2013	21,485 (2.3)	19 (1.5)		86 (1.7)	19 (1.5)
Length of pre-index eligibility (months), mean, median (SD)	19.6, 13.3 (13.56)	25.8, 18.5 (16.60)	<0.0001	25.8, 14.5 (19.43)	25.7, 18.4 (16.54)	0.8379
Presence of diabetes during pre-index period, n (%)	624,248 (68.1)	860 (69.4)	0.3272	3,368 (68.1)	857 (69.3)	0.4119
Severity of diabetes^c, n (%)
aDCSI score, mean, median (SD)	0.9, 0.0 (1.52)	1.1, 0.0 (1.91)	<0.0001	1.2, 0.0 (1.77)	1.1, 0.0 (1.90)	0.6690
Mild (aDCSI=0)	558,858 (60.9)	747 (60.2)		2,812 (56.9)	745 (60.3)
Moderate (aDCSI=1-4)	321,362 (35.0)	398 (32.1)		1,823 (36.9)	398 (32.2)
1	132,771 (41.3)	148 (37.2)		589 (32.3)	148 (37.2)
2	109,483 (34.1)	141 (35.4)		704 (38.6)	141 (35.4)
3	45,218 (14.1)	49 (12.3)		280 (15.4)	49 (12.3)
4	33,890 (10.5)	60 (15.1)		250 (13.7)	60 (15.1)
Severe (aDCSI=5-13)	37,028 (4.0)	95 (7.7)		309 (6.3)	93 (7.5)
Comorbidities, n (%)
HIV	1,233 (0.1)	36 (2.9)	<0.0001	100 (2.0)	33 (2.7)	0.1608
Hypertension	572,813 (62.4)	677 (54.6)	<0.0001	2,701 (54.6)	674 (54.5)	0.9491
Hyperlipidemia	544,942 (59.4)	693 (55.9)	0.0116	2,791 (56.5)	691 (55.9)	0.7292
Coronary artery disease	155,949 (17.0)	210 (16.9)	0.9504	829 (16.8)	209 (16.9)	0.9052
Congestive heart failure	50,751 (5.5)	105 (8.5)	<0.0001	391 (7.9)	103 (8.3)	0.6224
Peripheral vascular disease	41,409 (4.5)	47 (3.8)	0.2196	180 (3.6)	47 (3.8)	0.7868
Cerebrovascular disease	62,410 (6.8)	79 (6.4)	0.5450	343 (6.9)	79 (6.4)	0.4960
Dementia	4,212 (0.5)	5 (0.4)	0.7708	23 (0.5)	5 (0.4)	0.7763
Chronic obstructive pulmonary disease	125,224 (13.7)	134 (10.8)	0.0035	547 (11.1)	134 (10.8)	0.8232
Rheumatological disease	17,222 (1.9)	28 (2.3)	0.3240	126 (2.5)	28 (2.3)	0.5678
Peptic ulcer disease	8,616 (0.9)	35 (2.8)	<0.0001	132 (2.7)	35 (2.8)	0.7537
Hemiplegia or paraplegia	3,236 (0.4)	5 (0.4)	0.7647	26 (0.5)	5 (0.4)	0.5891
Moderate or severe renal disease	43,704 (4.8)	170 (13.7)	<0.0001	702 (14.2)	168 (13.6)	0.5833
Malignancy	58,841 (6.4)	104 (8.4)	0.0046	445 (9.0)	104 (8.4)	0.5168
Metastatic solid tumor	5,972 (0.7)	17 (1.4)	0.0017	83 (1.7)	17 (1.4)	0.4496
AIDS	1,233 (0.1)	36 (2.9)	<0.0001	100 (2.0)	33 (2.7)	0.1608
Other liver disease	33,379 (3.6)	367 (29.6)	<0.0001	1,485 (30.0)	363 (29.4)	0.6466
Healthcare utilization in pre-index period^d, mean, median (SD)
Inpatient hospitalizations	0.2, 0.0 (0.70)	0.3, 0.0 (0.87)	0.0744	0.3, 0.0 (0.83)	0.3, 0.0 (0.86)	0.4500
Office visits	7.6, 6.0 (7.78)	8.0, 5.0 (8.47)	0.1379	8.0, 6.0 (8.06)	8.0, 5.0 (8.45)	0.9863

aDCSI=adapted Diabetes Comorbidity Severity Index; HBV=hepatitis B virus; SD=standard deviation

^a Baseline period includes the 12 months pre-index for each patient

^b p-value calculated using t-test for continuous variables and χ² test for categorical variables, comparing diabetes without hepatitis B to all diabetes with hepatitis B.

^c Severity of diabetes as calculated by the adapted Diabetes Comorbidity Severity Index (aDCSI)

^d Reported for healthcare utilization in the pre-index period where it is not related to hepatitis B or its related complications (ie, cirrhosis, decompensated cirrhosis, liver cancer, fulminant hepatic failure, or liver transplant)

Table 2. Multivariate Analysis of Annualized Healthcare Utilization^a.^a

Place of Service	Diabetes without HBV (n=4,944)	Diabetes with HBV (n=1,236)	95% CI p-value^b	Diabetes without HBV Adjusted Mean^c,d^c, d(95% CI)	Diabetes with HBV Adjusted Mean^c,d^c, d(95% CI)	IRR^c(95% CI) p-value^b
Inpatient hospitalizations
Patients with ≥1 hospitalization, n (%)	1,879 (38.0)	454 (36.7)	0.84–1.09 0.5205
Number of hospitalizations among all patients, mean, median (SD)	0.4, 0.0 (0.87)	0.5, 0.0 (1.24)		0.4 (0.4–0.5)	0.6 (0.5–0.7)	1.41 (1.26–1.58) <0.0001
Number of hospitalizations among patients with ≥1 hospitalization, mean, median (SD)	1.0, 0.6 (1.19)	1.4, 0.8 (1.71)		1.0 (1.0–1.1)	1.5 (1.3–1.6)	1.43 (1.29–1.58) <0.0001
LOS among all patients, mean, median (SD)	2.2, 0.0 (7.80)	3.6, 0.0 (13.14)		2.5 (2.2–2.7)	4.0 (3.4–4.7)	1.61 (1.36–1.90) <0.0001
LOS among patients with ≥1 hospitalization, mean, median (SD)	5.7, 1.6 (11.83)	9.7, 2.7 (20.29)		5.9 (5.4–6.4)	9.8 (8.6–11.3)	1.67 (1.45–1.92) <0.0001
ED visits
Patients with ≥1 visit, n (%)	1,900 (38.4)	404 (32.7)	0.69–0.90 0.0003
Number of visits among all patients, mean (SD)	0.3, 0.0 (1.15)	0.2, 0.0 (0.57)		0.3 (0.3–0.4)	0.3 (0.2–0.3)	0.84 (0.74–0.96) 0.0124
Number of visits among patients ≥1 visit, mean (SD)	0.8, 0.5 (1.76)	0.8, 0.5 (0.77)		0.8 (0.8–0.9)	0.8 (0.7–0.9)	0.98 (0.86–1.12) 0.7478
Office visits
All office visits
Patients with ≥1 visit, n (%)	4,911 (99.3)	1,234 (99.8)	0.95–17.67 0.0579
Number of visits  among all patients,  mean (SD)	9.1, 6.7 (7.96)	10.0, 7.5 (8.42)		9.8 (9.6–10.1)	10.9 (10.4–11.4)	1.11 (1.06–1.16) <0.0001
Number of visits  among patients with ≥1  visit, mean (SD)	9.1, 6.8 (7.95)	10.0, 7.6 (8.42)		9.9 (9.6–10.2)	10.9 (10.4–11.6)	1.10 (1.05–1.15) <0.0001
Visits to a gastroenterologist
Patients with ≥1 visit, n (%)	935 (18.9)	615 (49.8)	3.72–4.88 <0.0001
Number of visits  among all patients, mean (SD)	0.2, 0.0 (0.61)	0.8, 0.0 (1.31)		0.2 (0.2–0.2)	0.8 (0.7–0.9)	4.73 (4.20–5.33) <0.0001
Number of visits  among patients with ≥1  visit, mean (SD)	0.9, 0.5 (1.15)	1.6, 1.1 (1.49)		0.9 (0.8–1.0)	1.6 (1.5–1.8)	1.80 (1.62–1.99) <0.0001
Visits to an infectious disease specialist
Patients with ≥1 visit, n (%)	137 (2.8)	61 (4.9)	1.31–2.45 0.0003
Number of visits among  all patients, mean (SD)	0.0, 0.0 (0.35)	0.1, 0.0 (0.53)		0.0 (0.0–0.1)	0.1 (0.1–0.1)	2.13 (1.44–3.15) 0.0001
Number of visits among  patients with ≥1 visit, mean (SD)	1.4, 0.8 (1.53)	1.7, 1.0 (1.70)		1.4 (1.2–1.8)	1.7 (1.3–2.2)	1.18 (0.89–1.57) 0.2527
Outpatient services^e
Patients with ≥1 visit, n (%)	4,887 (98.8)	1,232 (99.7)	1.26–9.63 0.0159
Number of visits among all patients, mean (SD)	17.7, 9.3 (30.61)	30.5, 11.3 (53.88)		20.4 (19.5–21.3)	34.2 (32.0–36.5)	1.68 (1.57–1.79) <0.0001
Number of visits among patients with ≥1 visit, mean (SD)	17.9, 9.4 (30.73)	30.6, 11.4 (53.94)		20.6 (19.7–21.5)	34.2 (32.0–36.5)	1.66 (1.56–1.78) <0.0001
Skilled nursing facility services
Patients with ≥1 visit, n (%)	561 (11.3)	140 (11.3)	0.83–1.24 0.8606
Pharmacy prescriptions
Patients with ≥1 pharmacy claim, n (%)	4,703 (95.1)	1,179 (95.4)	0.80–1.53 0.5326
Number of pharmacy claims among all patients, mean (SD)	47.4, 38.5 (39.72)	41.5, 30.4 (39.76)		58.9 (56.7–61.2)	51.2 (48.2–54.3)	0.87 (0.82–0.92) <0.0001
Number of pharmacy claims among patients with ≥1 pharmacy claim, mean (SD)	49.9, 41.1 (39.21)	43.6, 32.4 (39.62)		60.2 (58.3–62.2)	52.2 (49.6–55.0)	0.87 (0.82–0.91) <0.0001
Number of unique medication classes among all patients, mean (SD)	6.8, 5.5 (5.42)	6.9, 5.0 (6.26)		7.7 (7.5–7.9)	7.7 (7.3–8.0)	1.00 (0.95–1.05) 0.9474
Number of unique medication classes among patients with ≥1 pharmacy claim, mean (SD)	7.2, 5.8 (5.35)	7.2, 5.2 (6.26)		7.9 (7.7–8.1)	7.8 (7.5–8.2)	1.00 (0.97–1.04) 0.8197

CI=confidence interval; ED=emergency department; HBV=hepatitis B virus; IRR=incidence rate ratio; LOS=length of stay; OR=odds ratio; SD=standard deviation

^a Healthcare utilization was measured from the index date to the end of patients' follow up in the study and was annualized

^b p-value was calculated using multivariate regression (ie, negative binomial regression for count variables and logistic regression for dichotomous variables) comparing patients with diabetes with HBV to patients with diabetes without HBV

^c Patients with diabetes without HBV used as referent. Multivariate model adjusted for baseline insulin use and use of antidiabetic agents associated with hepatotoxicity

^d Comparison of patients with diabetes and HBV to patients with diabetes without HBV; patients with diabetes without HBV used as referent

^e Other outpatient services included, for example, laboratory procedures, etc.

Table 3. Multivariate Analysis of Annualized Costs^a.^a

Costs	Diabetes without HBV (n=4,944)	Diabetes with HBV (n=1,236)	DifferenceMean^b (%)	Diabetes without HBV Adjusted Mean^c,d^b, c(95% CI)	Diabetes with HBV Adjusted Mean^c,d^b, c (95% CI)	Incidence rate ratio^c	95% CI	p-value^d
Inpatient hospitalizations
All patients, mean, median (SD)	$7,604, $0 ($29,952)	$13,412, $0 ($59,513)	$5,808 (76.4)	$8,089 ($7,274–$8,994)	$14,097 ($11,877–$16,729)	1.74	1.47–2.06	<0.0001
Patients with ≥1 hospitalization, mean, median (SD)	$20,007, $7,266 ($45,968)	$36,514, $10,243 ($93,865)	$16,507 (82.5)	$19,341 ($17,860–$20,946)	$34,704 ($30,236–$39,831)	1.79	1.56–2.06	<0.0001
ED visits
All patients, mean, median (SD)	$457, $0 ($1,423)	$365, $0 ($1,066)	−$92 (−20.1)	$504 ($461–$552)	$405 ($352–$466)	0.80	0.70–0.92	0.0020
Patients with ≥1 visit, mean, median (SD)	$1,189, $590 ($2,097)	$1,117, $642 ($1,626)	−$72 (−6.1)	$1,230 ($1,149–$1,315)	$1,157 ($1,029–$1,301)	0.94	0.84–1.06	0.3175
Office visits
All patients, mean, median (SD)	$1,340, $791 ($3,427)	$1,451, $894 ($2,519)	$111 (8.3)	$1,421 ($1,367–$1,478)	$1,539 ($1,448–$1,636)	1.08	1.02–1.15	0.0106
Patients with ≥1 visit, mean, median (SD)	$1,349, $801 ($3,436)	$1,453, $896 ($2,520)	$104 (7.7)	$1,432 ($1,379–$1,488)	$1,543 ($1,454–$1,637)	1.08	1.02–1.14	0.0140
Visits to a gastroenterologist
All patients, mean,  median (SD)	$20, $0 ($78)	$89, $0 ($162)	$69 (345.0)	$21 ($19–$22)	$88 ($79–$99)	4.27	3.82–4.78	<0.0001
Patients with ≥1  visit, mean,  median (SD)	$107, $59 ($152)	$179, $127 ($191)	$72 (67.3)	$108 ($100–$117)	$181 ($166–$198)	1.68	1.53–1.84	<0.0001
Visits to an infectious disease specialist
All patients, mean,  median (SD)	$5, $0 ($48)	$11, $0 ($82)	$6 (120.0)	$6 ($6–$7)	$14 ($13–$16)	2.23	2.01–2.46	<0.0001
Patients with ≥1 visit,  mean, median (SD)	$167, $81 ($239)	$228, $130 ($300)	$61 (36.5)	$174 ($141–$215)	$240 ($179–$322)	1.38	1.02–1.86	0.0370
Outpatient services^e
All patients, mean, median (SD)	$6,238, $1,826 ($18,909)	$12,621, $2,286 ($35,678)	$6,383 (102.3)	$7,361 ($6,939–$7,807)	$14,400 ($13,137–$15,785)	1.96	1.78–2.14	<0.0001
Patients with ≥1 visit, mean, median (SD)	$6,311, $1,849 ($19,007)	$12,662, $2,293 ($35,728)	$6,351 (100.6)	$7,434 ($7,015–$7,878)	$14,423 ($13,179–$15,785)	1.94	1.77–2.12	<0.0001
Skilled nursing facility services
All patients, mean, median (SD)	$310, $0 ($2,399)	$435, $0 ($3,006)	$125 (40.3)	$304 ($275–$336)	$481 ($408–$567)	1.58	1.35–1.86	<0.0001
Patients with ≥1 visit, mean, median (SD)	$2,730, $606 ($6,646)	$3,841, $632 ($8,191)	$1,111 (40.7)	$2,290 ($1,966–$2,666)	$3,406 ($2,599–$4,464)	1.49	1.12–1.98	0.0061
Pharmacy prescriptions
All patients, mean, median (SD)	$3,918, $2,060 ($6,725)	$6,072, $2,672 ($9,624)	$2,154 (55.0)	$5,114 ($4,844–$5,400)	$8,029 ($7,369–$8,748)	1.57	1.44–1.71	<0.0001
Patients with ≥1 pharmacy claim, mean, median (SD)	$4,119, $2,270 ($6,835)	$6,365, $2,946 ($9,758)	$2,246 (54.5)	$5,233 ($4,989–$5,489)	$8,181 ($7,580–$8,831)	1.56	1.45–1.69	<0.0001
Total medical costs,^f mean, median (SD)	$15,948, $4,145 ($42,226)	$28,284, $4,471 ($78,485)	$12,336 (77.4)	$17,765 ($16,788–$18,802)	$30,968 ($28,311–$33,874)	1.74	1.59–1.91	<0.0001
Total costs,^g mean, median (SD)	$19,867, $7,373 ($44,010)	$34,356, $10,160 ($80,378)	$14,489 (72.9)	$23,038 ($21,921–$24,212)	$39,435 ($36,454–$42,655)	1.71	1.58–1.85	<0.0001

CI=confidence interval; ED=emergency department; HBV=hepatitis B virus; SD=standard deviation

^a All-cause costs calculated as sum of plan-paid and patient-paid costs and were adjusted to 2014 Consumer Price Index information provided by the Bureau of Labor & Statistics. Costs were measured from index date to the end of patients' follow up in the study and were annualized

^b Comparison between patients with diabetes with HBV to patients with diabetes without HBV; patients with diabetes without HBV used as referent

^c Multivariate model adjusted for baseline insulin use and use of antidiabetic agents associated with hepatotoxicity

^d p-value calculated using multivariate regression (ie, logistic regression with gamma transformation for cost variables) comparing patients with diabetes with HBV to patients with diabetes without HBV

^e Other outpatient services included, for example, laboratory procedures, etc.

^f Sum of inpatient, ED, office visit, and other outpatient visit costs

^g Sum of total medical and pharmacy costs