Nationwide cohort study suggests that nucleos(t)ide analogue therapy decreases dialysis risk in Taiwanese chronic kidney disease patients acquiring hepatitis B virus infection

Table 1 Baseline characteristics and renal outcome of the untreated hepatitis B virus-infected and hepatitis B virus-uninfected chronic kidney disease patients (n = 103002), 1997-2012

Variable	Overall CKD patients (n = 103002)			Propensity score-matched CKD patients (n = 14580)
	Untreated (n = 2916)	Uninfected (n = 100086)	P value	Untreated (n = 2916)	Uninfected (n = 11664)	P value
Sex			< 0.0001			0.45
Men	1713 (58.7)	51592 (51.6)		1713 (58.7)	6762 (58.0)
Women	1203 (41.3)	48494 (48.4)		1203 (41.3)	4902 (42.0)
Age (yr, mean ± SD)	48.1 ± 14.4	56.3 ± 17.4	< 0.0001	48.1 ± 14.4	47.7 ± 15.9	0.21
Comorbidity
Diabetes	749 (25.7)	33023 (33.0)	< 0.0001	749 (25.7)	3049 (26.1)	0.62
Hypertension	884 (30.3)	45139 (45.1)	< 0.0001	884 (30.3)	3420 (29.3)	0.29
Coronary heart disease	316 (10.8)	18668 (18.7)	< 0.0001	316 (10.8)	1152 (9.9)	0.12
Hyperlipidemia	695 (23.8)	29595 (29.6)	< 0.0001	695 (23.8)	2851 (24.4)	0.49
Cirrhosis	139 (4.8)	1528 (1.5)	< 0.0001	139 (4.8)	472 (4.1)	0.08
Urbanization level			0.0003			0.47
Urban	892 (30.6)	27951 (27.9)		892 (30.6)	3595 (30.8)
Suburban	1351 (46.3)	46163 (46.1)		1351 (46.3)	5498 (47.2)
Rural	673 (23.1)	25972 (26.0)		673 (23.1)	2571 (22.0)
Enrolee category			< 0.0001			0.011
1 + 2	1122 (38.5)	29935 (29.9)		1122 (38.5)	4680 (40.1)
3	1278 (43.8)	47825 (47.8)		1278 (43.8)	4760 (40.8)
4	516 (17.7)	22326 (22.3)		516 (17.7)	2224 (19.1)
No. of medical visits (mean ± SD)	26.1 ± 20.8	29.0 ± 22.8	< 0.0001	26.1 ± 20.8	25.7 ± 22.5	0.31
Charlson comorbidity index score (mean ± SD)	1.6 ± 1.9	1.9 ± 2.3	< 0.0001	1.6 ± 1.9	1.5 ± 2.1	0.06
Propensity score (mean ± SD)	0.4 ± 0.2	0.3 ± 0.2	< 0.0001	0.4 ± 0.2	0.4 ± 0.2	1.00
End-stage renal disease
Follow-up year (mean ± SD)	8.9 ± 3.9	6.9 ± 4.5	< 0.0001	8.9 ± 3.9	7.4 ± 4.5	< 0.0001
Total follow-up (person-year)	26098	689592	< 0.0001	26098	86780	< 0.0001
Event	197 (6.8)	4076 (4.1)	< 0.0001	197 (6.8)	414 (3.6)	< 0.0001

Categorical variables are given as n (%); continuous variable given as mean ± SD. CKD: Chronic kidney disease.

Table 2 Baseline characteristics and renal outcome of the treated and untreated hepatitis B virus-infected chronic kidney disease patients (n = 3358), 1997-2012

Variable	Overall HBV patients (n = 3358)			Propensity score-matched HBV patients (n = 1768)
	Treated (n = 442)	Untreated (n = 2916)	P value	Treated (n = 442)	Untreated (n = 1326)	P value
Sex			< 0.0001			0.76
Men	319 (72.2)	1713 (58.7)		319 (72.2)	967 (72.9)
Women	123 (27.8)	1203 (41.3)		123 (27.8)	359 (27.1)
Age (yr, mean ± SD)	51.0 ± 13.9	48.1 ± 14.4	< 0.0001	51.0 ± 13.9	51.6 ± 14.7	0.49
Interval to start nucleos(t)ide analogue therapy (yr, mean ± SD)	1.2 ± 1.9	-		1.2 ± 1.9	-
Nucleos(t)ide analogue therapy duration (yr, mean ± SD)	0.8 ± 0.8	-		0.8 ± 0.8	-
Comorbidity
Diabetes	141 (31.9)	749 (25.7)	0.006	141 (31.9)	424 (32.0)	0.98
Hypertension	150 (33.9)	884 (30.3)	0.12	150 (33.9)	457 (34.5)	0.84
Coronary heart disease	59 (13.4)	316 (10.8)	0.12	59 (13.4)	198 (14.9)	0.41
Hyperlipidemia	108 (24.4)	695 (23.8)	0.78	108 (24.4)	334 (25.2)	0.75
Cirrhosis	59 (13.4)	139 (4.8)	< 0.0001	59 (13.4)	135 (10.2)	0.07
Urbanization level			0.45			0.88
Urban	129 (29.2)	892 (30.6)		129 (29.2)	381 (28.7)
Suburban	199 (45.0)	1351 (46.3)		199 (45.0)	615 (46.4)
Rural	114 (25.8)	673 (23.1)		114 (25.8)	330 (24.9)
Enrolee category			0.32			0.61
1 + 2	161 (36.4)	1122 (38.5)		161 (36.4)	460 (34.7)
3	190 (43.0)	1278 (43.8)		190 (43.0)	606 (45.7)
4	91 (20.6)	516 (17.7)		91 (20.6)	260 (19.6)
No. of medical visits (mean ± SD)	26.5 ± 18.2	26.1 ± 20.8	0.75	26.5 ± 18.2	26.3 ± 19.3	0.90
Charlson comorbidity index score (mean ± SD)	1.9 ± 2.1	1.6 ± 1.9	< 0.0001	1.9 ± 2.1	1.9 ± 2.2	0.79
Propensity score (mean ± SD)	1.6 ± 0.7	1.3 ± 0.6	< 0.0001	1.6 ± 0.7	1.5 ± 0.7	0.51
End-stage renal disease
Follow-up year (mean ± SD)	7.6 ± 4.3	8.9 ± 3.9	< 0.0001	7.6 ± 4.3	8.5 ± 4.0	< 0.0001
Total follow-up (person-year)	3359	26101	< 0.0001	3359	22478	< 0.0001
Event	5 (1.1)	197 (6.8)	< 0.0001	5 (1.1)	108 (8.1)	< 0.0001

Categorical variables are given as n (%); continuous variable given as mean ± SD. HBV: Hepatitis B virus.

Table 3 Hazard ratios for end-stage renal disease in the untreated hepatitis B virus-infected and hepatitis B virus-uninfected chronic kidney disease patients, with adjustment for competing mortality

Variable	Overall CKD patients (n = 103002)				Propensity score-matched CKD patients (n = 14580)
	Crude		Adjusted1		Crude		Adjusted1
	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
CKD patients
Uninfected	1.00 (Reference)		1.00 (Reference)		1.00 (Reference)		1.00 (Reference)
Untreated	1.39 (1.20-1.60)	< 0.0001	1.69 (1.47-1.96)	< 0.0001	1.64 (1.38-1.94)	< 0.0001	1.67 (1.40-1.98)	< 0.0001
Sex (Men/Women)	0.94 (0.88-0.99)	0.028	1.38 (1.25-1.51)	< 0.0001	1.24 (1.05-1.46)	0.011	1.65 (1.26-2.16)	0.0003
Age (per year)	1.01 (1.01-1.01)	< 0.0001	0.96 (0.96-0.97)	< 0.0001	1.03 (1.02-1.03)	< 0.0001	0.98 (0.96-0.98)	0.012
Comorbidity (Yes/No)
Diabetes	2.49 (2.35-2.65)	< 0.0001	1.96 (1.83-2.10)	< 0.0001	2.55 (2.18-2.99)	< 0.0001	1.96 (1.63-2.35)	< 0.0001
Hypertension	2.85 (2.67-3.03)	< 0.0001	2.08 (1.88-2.29)	< 0.0001	3.59 (3.06-4.20)	< 0.0001	2.51 (1.95-3.22)	< 0.0001
Coronary heart disease	1.26 (1.17-1.35)	< 0.0001	0.86 (0.80-1.05)	0.37	1.25 (0.98-1.60)	0.08	0.93 (0.74-1.15)	0.49
Hyperlipidemia	1.16 (1.08-1.24)	< 0.0001	1.01 (0.93-1.08)	0.90	1.07 (0.89-1.30)	0.48	0.84 (0.68-1.03)	0.09
Cirrhosis	0.81 (0.62-1.05)	0.11	8.34 (5.72-12.17)	< 0.0001	0.73 (0.46-1.15)	0.17	4.36 (1.56-12.17)	0.005
Urbanization level
Urban	1.00 (Reference)		1.00 (Reference)		1.00 (Reference)		1.00 (Reference)
Suburban	1.01 (0.95-1.08)	0.69	0.93 (0.87-1.00)	0.06	1.10 (0.94-1.28)	0.26	0.99 (0.81-1.19)	0.87
Rural	1.03 (0.97-1.11)	0.35	0.84 (0.77-1.03)	0.07	0.99 (0.82-1.20)	0.94	0.80 (0.63-1.01)	0.06
Enrolee category
1 + 2	1.00 (Reference)		1.00 (Reference)		1.00 (Reference)		1.00 (Reference)
3	1.28 (1.21-1.36)	< 0.0001	1.34 (1.23-1.47)	< 0.0001	1.36 (1.16-1.60)	0.0001	1.44 (1.15-1.79)	0.001
4	1.26 (1.18-1.35)	< 0.0001	1.34 (1.21-1.49)	< 0.0001	1.52 (1.27-1.82)	< 0.0001	1.55 (1.21-1.98)	0.0006

¹Adjusted for all covariates (age per year, sex, comorbidities, urbanization level, enrolee category, number of medical visits, Charlson comorbidity index score, and propensity score) and competing mortality. CKD: Chronic kidney disease.

Table 4 Hazard ratios for end-stage renal disease in the untreated hepatitis B virus-infected and hepatitis B virus-treated chronic kidney disease patients, with adjustment for competing mortality

Variable	Overall HBV patients (n = 3358)				Propensity score-matched HBV patients (n = 1768)
	Crude		Adjusted1		Crude		Adjusted1
	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
HBV cohort
Untreated	1.00 (Reference)		1.00 (Reference)		1.00 (Reference)		1.00 (Reference)
Treated	0.17 (0.07-0.41)	< 0.0001	0.15 (0.06-0.36)	< 0.0001	0.14 (0.06-0.34)	< 0.0001	0.13 (0.05-0.31)	< 0.0001
Sex (Men/Women)	1.12 (0.84-1.49)	0.43	0.91 (0.46-1.79)	0.78	0.87 (0.58-1.30)	0.49	0.63 (0.24-1.63)	0.34
Age (per year)	1.02 (1.01-1.02)	0.0002	1.00 (0.98-1.02)	0.86	1.01 (1.00-1.02)	0.20	0.99 (0.96-1.01)	0.34
Comorbidity (Yes/No)
Diabetes	2.01 (1.52-2.67)	< 0.0001	1.92 (1.33-2.77)	0.0005	1.89 (1.31-2.74)	0.0007	1.77 (1.08-2.91)	0.024
Hypertension	3.09 (2.35-4.06)	< 0.0001	3.90 (2.66-5.72)	< 0.0001	2.59 (1.79-3.74)	< 0.0001	3.52 (2.09-5.95)	< 0.0001
Coronary heart disease	0.85 (0.53-1.36)	0.49	0.51 (0.31-0.84)	0.008	0.93 (0.54-1.60)	0.80	0.59 (0.32-1.09)	0.09
Hyperlipidemia	1.12 (0.81-1.54)	0.51	0.84 (0.58-1.20)	0.33	1.23 (0.81-1.86)	0.33	0.98 (0.61-1.56)	0.91
Cirrhosis	0.57 (0.27-1.22)	0.15	0.35 (0.05-2.61)	0.30	0.53 (0.25-1.14)	0.10	0.30 (0.03-3.32)	0.33
Urbanization level
Urban	1.00 (Reference)		1.00 (Reference)		1.00 (Reference)		1.00 (Reference)
Suburban	1.18 (0.90-1.56)	0.24	1.18 (0.85-1.65)	0.33	1.27 (0.88-1.84)	0.20	1.06 (0.68-1.64)	0.80
Rural	1.03 (0.75-1.43)	0.85	1.09 (0.73-1.64)	0.68	0.79 (0.50-1.23)	0.30	0.91 (0.52-1.59)	0.73
Enrolee category
1 + 2	1.00 (Reference)		1.00 (Reference)		1.00 (Reference)		1.00 (Reference)
3	0.96 (0.73-1.27)	0.78	1.05 (0.74-1.50)	0.78	0.79 (0.54-1.14)	0.21	0.99 (0.60-1.62)	0.97
4	1.57 (1.14-2.16)	0.006	1.60 (1.06-2.40)	0.024	1.78 (1.19-2.67)	0.005	1.89 (1.10-3.26)	0.022

¹Adjusted for all covariates (age per year, sex, comorbidities, urbanization level, enrolee category, number of medical visits, Charlson comorbidity index score, and propensity score). HBV: Hepatitis B virus.

Table 5 Sensitivity analysis in the propensity-matched chronic kidney disease patients (n = 14580) n (%)

Model 1: CKD patients without diabetes at baseline (n =10782)
	Uninfected cohort ( = 8615)	Untreated cohort (n = 2167)
No. of ESRD	222 (2.58)	118 (5.45)
Adjusted HR (95%CI)1	1.00 (reference)	1.82 (1.45-2.28)
Model 2: CKD patients without cirrhosis at baseline (n = 13969)
	Uninfected cohort (n = 11192)	Untreated cohort (n = 2777)
No. of ESRD	401 (3.58)	191 (6.88)
Adjusted HR (95%CI)1	1.00 (reference)	1.67 (1.40-1.99)
Model 3: CKD patients without diabetes and cirrhosis at baseline (n = 10420)
	Uninfected cohort (n = 8327)	Untreated cohort (n = 2093)
No. of ESRD	218 (2.62)	116 (5.54)
Adjusted HR (95%CI)1	1.00 (reference)	1.81 (1.44-2.27)

¹Adjusted for all covariates (age per year, sex, comorbidities, urbanization level, enrolee category, number of medical visits, Charlson comorbidity index score, and propensity score) and competing mortality. ESRD: End-stage renal disease; CKD: Chronic kidney disease.