Hepatitis C in hemodialysis patients

Table 1 Histological features in hepatitis C virus infected hemodialysis patients

Ref.	Study design/country	No. of patients	Control group	Histological features	Milderhistology in HD as conclusion
Barril[50]	Multicenter observational/ Spain	n = 218 HD pts	None	70% chronic hepatitis 3% steatosis 15% cirrhosis	(+/-)
		Rebiopsy after 7 yr (n = 181)		74% stable disease 11% progression
Trevizoli et al[48]	Case-control study/Brasil	n = 36 aHCV(+) HD pts	n = 37 aHCV(+) with normal renal function	HD pts vs control group: Hepatic fibrosis 47.2% vs 73% (P < 0.025) Inflammatory activity 27.7% vs 59.5 % (P = 0.003)	(++)
Mysorekar et al[51]	Observational/ India	n = 45 aHCV(+) HD pts	None	67% (n = 30/45) mild inflammatory activity+mild fibrosis (stage 0, 1, 2)	(+/-)
Sterling et al[31]	Prospective case-contrrol study/United States	n = 50 aHCV(+) HD pts (transplant candidates)	Two A.Normal renal function, normal ALT (n = 43) B.Normal renal function, ↑ALT (n = 43)	Advanced liver disease (bridging fibrosis/cirrhosis) in 22% of HD pts vs 12% in group A (NS) and 48% in group B (P < 0.001) Mild hepatic inflammation in 62% of HD pts (score1-3) vs 36% in control groups A and B (P < 0.0001)	(++)
Cotler et al[30]	Case-control study/United States	n = 46 aHCV(+) HD pts	n = 46 aHCV (+) with normal renal function	HD pts vs control group: Less inflammatory activity (P < 0.001) Less bridging fibrosis/cirrhosis (13% vs 30%, P = 0.043)	(++)
Aslinia et al[49]	Cross sectional/United States	n = 156 aHCV(+) HD pts	n = 138 aHCV(+) with normal renal function	HD pts vs control group: Less necroinflammation (P < 0.05) Less fibrosis (P < 0.0001)	(++)
Becker et al[19]	Brasil	n = 216 aHCV(+) HD pts	None	77% absence of septal fibrosis (F0, F1) 12% F2 7% F3	(+)
Sakellariou et al[18]	Comparative analysis/Greece	n = 61 aHCV(+) HD pts	n = 326 non-HD, aHCV(+) pts	4% cirrhosis HD pts vs control group: Milder stage (P = 0.033) Lower grade (periportal activity, portal inflammation, lobular activity) (P < 0.001) Lower frequency of: Lymphoid aggregates (10.2% vs 50%, P < 0.001) Bile duct lesions (1.7% vs 22.1%, P < 0.001) Less extent of steatosis in HD pts (P = 0.022)	(++)

HD: Hemodialysis; HCV: Hepatitis C virus; ALT: Aminotransferase.

Table 2 Hepatitis C virus-associated mortality in hemodialysis patients: National surveys

National survey	Ref.	No. of HD patients	Outcome	Relative risk
Australia New Zealand Dialysis and Transplant Registry	Scott et al[62]	23046 (10-yr follow up)	Independent and significant association between a HCV(+) and all-cause mortality	HR = 1.25 (95%CI: 1.07-1.46, P = 0.004)
National or regional dialysis registries of 10 Asia-Pacific countries/areas (Australia, New Zealand, Japan, China, Taiwan, Korea, Thailand, Hong-Kong, Malaysia, India)	Johnson et al[63]	173788	Data available for Australia, New Zealand and Japan	HR = 1.25 (95%CI: 1.07-1.46, P = 0.004)
Dialysis Outcomes and Practice Patterns Study (DOPPS) from the United States (in three continents: Europe, Japan, United States)	Goodkin et al[64]	206134	a HCV(+) is an independent predictor of all-cause mortality	RR = 1.17 (P < 0.0159)
The Japanese cohort	Japanese Society of Dialysis[65]	76201	a HCV(+) is an independent predictor of all-cause mortality	RR = 1.37 (95%CI: 1.15-1.62, P = 0.003)

HD: Hemodialysis; HCV: Hepatitis C virus.

Table 3 Meta-analyses of trials with convetional and pegylated interferon-α in hepatitis C virus infected hemodialysis patients

Conventional IFN/Peg IFNtherapy	Ref.	No. of patients	Dose	Duration	SVR (%)	Withdrawal rate (%)
Two metaanalysis studies (IFN-α)	Fabrizi et al[73]	269	1.5-6.0 MU/d to 3 times per week	24-48 wk	37	17
IFN-α	Russo et al[74]	213	3.0-5.0 MU/d to 3 times per week	24-48 wk	33	30
Two head-to-head comparisons (IFN-αvs PegIFN-α)	Fabrizi et al[75]	645	1.0-6.0 MU/d to 3 times per week (n = 529)	8-48 wk	39	19
			135-180 μg/wk (a-2a) or 0.5-1.0 μg/kg per week (a-2b) (n = 116)	48 wk	31	27
IFN-αvs PegIFNα + ribavirin	Gordon et al[76]	546	1.0-6.0 MU/d to 3 times per week (n = 459)	16-48 wk	41	26
			135-180 μg/wk (a-2a) or 0.5-1.0 μg/kg per week (a-2b) (n = 87)	24-48 wk	37	28
PegIFN-α	Fabrizi et al[77]	254	135-180 μg/wk (a-2a) or 0.5-1.1 μg/kg per week (a-2b)	24-48 wk	33	23

HD: Hemodialysis; HCV: Hepatitis C virus; IFN-α: Interferon-α; PegIFN-α: Pegylated interferon-α; RBV: Ribavirin.

Table 4 Studies with combined Ribavirin plus Interferon-α therapy in hepatitis C virus infected hemodialysis patients

Combinationtherapy	Ref.	No. of patients	Dose	Duration	SVR (%)	Withdrawal rate (%)
IFN-α + RBV	Mousa et al[78]	20	3 MU (IFN) + 200 mg (RBV) 3 times per week	24 wk (n = 9)	67	0
			3 MU (IFN) + 200 mg (RBV) 3 times per week	48 wk (n = 11)	36	0
PegIFN-α + RBV	Rendina et al[79]	35	135 μg/wk (Peg-IFN-a-2a) + 200 mg/qd (RBV)	48 wk (gtp 1)	97	14
				24 wk (non-gtp 1)
PegIFN-α + RBV	Carriero et al[80]	14	135 μg/wk (Peg-IFN-a-2a) + 200 mg/qd(RBV)	48 wk	29	71
PegIFN-α + RBV	Hakim et al[81]	15	135 μg/wk (Peg-IFN-a-2a) + 200 mg/wk to 3 times per week (RBV)	48 wk	7	33
PegIFN-α + RBV	Liu et al[82]	35	135 μg/wk (Peg-IFN-a-2a) + 200 mg/qd (RBV)	48 wk (gtp 1)
				24 wk (non-gtp 1)	60	17

IFN-α: Interferon-α; PegIFN-α: Pegylated interferon-α; RBV: Ribavirin.