Anti-hepatitis C virus therapy in chronic kidney disease patients improves long-term renal and patient survivals

Table 1 Baseline characteristics of the three study cohorts, 1997-2012, n = 6266

Variables	Propensity score-matched CKD patients
	Treated(n = 482)	Untreated(n = 1928)	Uninfected(n = 3856)	P1 value
Sex				0.38
Men	253 (52.5)	979 (50.8)	2032 (52.7)
Women	229 (47.5)	949 (49.2)	1824 (47.3)
Age in yr	58.5 ± 10.5	58.5 ± 13.7	58.4 ± 14.1	0.96
Interferon-based therapy duration in yr	0.5 ± 0.8	-	-
Comorbidity
Diabetes	228 (47.3)	878 (45.5)	1727 (44.8)	0.55
Hypertension	290 (60.2)	1150 (59.6)	2315 (60.0)	0.95
Coronary heart disease	182 (37.8)	746 (38.7)	1519 (39.4)	0.73
Hyperlipidemia	239 (49.6)	961 (49.8)	1938 (50.3)	0.93
Cirrhosis	120 (24.9)	446 (23.1)	892 (23.1)	0.68
ACEI/ARB use	14 (2.9)	37 (1.9)	66 (1.7)	0.19
Enrollee category				< 0.0001
1	152 (31.5)	546 (28.3)	1332 (34.5)
2	10 (2.1)	30 (1.6)	61 (1.6)
3	255 (52.9)	968 (50.2)	1622 (42.1)
4	65 (13.5)	384 (19.9)	841 (21.8)
Number of medical visits	38.6 ± 25.6	34.4 ± 26.7	30.0 ± 25.0	< 0.0001
Charlson comorbidity index score	4.2 ± 2.7	3.5 ± 2.6	3.2 ± 2.7	< 0.0001

Data are presented as n (%).

¹For comparison among three cohorts. Categorical variables given as number (percentage); continuous variable, as mean ± SD. CKD: Chronic kidney disease; ACEI/ARB: Angiotensin converting enzyme inhibitor/angiotensin receptor blocker.

Table 2 Outcomes between treated, untreated, and uninfected cohorts, n = 6266

	Treated cohort (n = 482)	Untreated cohort (n = 1928)	Uninfected cohort (n = 3856)	P value
End-stage renal disease
Events number (%)	5 (1.0)	134 (7.0)	188 (4.9)	< 0.0001
Competing mortality (%)	58 (12.0)	573 (29.7)	775 (20.1)	< 0.0001
Cumulative incidence (%)	2.4 (95%CI: 0.9-5.2)	11.7 (95%CI: 8.0-16.1)	8.2 (95%CI: 6.2-10.5)	0.0032
Overall mortality
Events number (%)	61 (12.7)	648 (33.6)	861 (22.3)	< 0.0001
Cumulative incidence (%)	41.4 (95%CI: 8.1-54.1)	58.0 (95%CI: 51.5-63.9)	37.8 (95%CI: 34.4-41.3)	< 0.0001

Table 3 Crude and adjusted hazard ratios for end-stage renal disease

Variable	Crude			Adjusted1
	HR	95%CI	P value	HR	95%CI	P value
CKD patients
Uninfected	1.00	Reference		1.00	Reference
Treated	0.31	0.13-0.77	0.011	0.34	0.14-0.84	0.019
Untreated	1.25	1.00-1.56	0.046	1.28	1.03-1.60	0.029
Sex, men/women	1.11	0.89-1.38	0.35	1.23	0.99-1.55	0.07
Age, per year	1.01	1.00-1.01	0.15	0.99	0.98-0.99	0.006
Comorbidity, yes/no
Diabetes	2.87	2.28-3.61	< 0.001	3.06	2.37-3.95	< 0.001
Hypertension	3.08	2.37-4.01	< 0.001	3.51	2.57-4.79	< 0.001
Coronary heart disease	1.28	1.02-1.59	0.031	0.92	0.72-1.16	0.46
Hyperlipidemia	1.29	1.04-1.60	0.023	0.85	0.68-1.07	0.16
Cirrhosis	0.62	0.46-0.83	0.001	0.61	0.44-0.84	0.003
ACEI/ARB, yes/no	1.38	0.65-2.92	0.40	0.96	0.46-2.04	0.92
Enrollee category
1	1.00	Reference		1.00	Reference
2	0.68	0.21-2.14)	0.50	0.56	0.17-1.80	0.33
3	1.26	0.97-1.64	0.08	1.24	0.95-1.63	0.11
4	1.47	1.09-1.99	0.012	1.40	1.03-1.92	0.03
Number of medical visits	1.00	1.00-1.01	0.36	1.00	0.99-1.00	0.41
Charlson comorbidity index score	1.01	00.98-1.04	0.46	0.93	0.89-0.98	0.008

¹Adjusted for all covariates (age per year, sex, comorbidity, ACEI/ARB, enrollee category, number of medical visits, and Charlson comorbidity index score) and competing mortality. CKD: Chronic kidney disease; ACEI/ARB: Angiotensin converting enzyme inhibitor/angiotensin receptor blocker; CI: Confidence interval.

Table 4 Sensitivity analysis of adjusted hazard ratios for end-stage renal disease and death between the untreated and uninfected chronic kidney disease patients as well as between the treated and untreated chronic kidney disease patients

	Adjusted HR for ESRD1			Adjusted HR for death2
	HR	95%CI	P value	HR	95%CI	P value
Propensity score-matched CKD patients
Uninfected cohort (n = 3856)	1.00	Reference		1.00	Reference
Untreated HCV-infected cohort (n = 1928)	1.28	1.03-1.61	0.028	1.31	1.18-1.45	< 0.001
Propensity score-matched CKD patients
Untreated HCV-infected cohort (n = 1928)	1.00	Reference		1.00	Reference
Treated HCV-infected cohort (n = 482)	0.28	0.11-0.71	0.007	0.71	0.54-0.92	0.011

¹Adjusted for all covariates (age per year, sex, comorbidity, ACEI/ARB, enrollee category, number of medical visits, and Charlson comorbidity index score) and competing mortality;

²Adjusted for all covariates (age per year, sex, comorbidity, ACEI/ARB, enrollee category, number of medical visits, and Charlson comorbidity index score). CKD: Chronic kidney disease; CI: Confidence interval; ACEI/ARB: Angiotensin converting enzyme inhibitor/angiotensin receptor blocker; ESRD: End-stage renal disease; HCV: Hepatitis C virus.

Table 5 The effect of the duration of interferon-based therapy for hepatitis C virus infection on the risk of end-stage renal disease and death

	IBT duration	ESRD events (%)	Adjusted HR1 (95%CI)	P value	Death events (%)	Adjusted HR2 (95%CI)	P value
Propensity score-matched HCV-infected CKD patients (n = 2410)	No (n = 1928)	134 (7.0)	1.00 (reference)		648 (33.6)	1.00 (reference)
	< 4 mo (n = 126)	3 (2.4)	0.79 (0.24-2.63)	0.70	23 (18.3)	1.18 (0.78-1.81)	0.44
	≥ 4 mo (n = 356)	2 (0.6)	0.14 (0.03-0.58)	0.007	38 (10.7)	0.57 (0.41-0.79)	0.001

¹Adjusted for all covariates (age per year, sex, comorbidity, ACEI/ARB, enrollee category, number of medical visits, and Charlson comorbidity index score) and competing mortality; ²Adjusted for all covariates (age per year, sex, comorbidity, ACEI/ARB, enrollee category, number of medical visits, and Charlson comorbidity index score). CKD: Chronic kidney disease; CI: Confidence interval; ACEI/ARB: Angiotensin converting enzyme inhibitor/angiotensin receptor blocker; ESRD: End-stage renal disease; HCV: Hepatitis C virus.