Hepatitis C and kidney disease: An overview and approach to management

Table 1 Summary of recommendations on hepatitis C virus therapy in various stages of renal impairment according to guidelines

CKD stage	KDIGO 2008	APASL 2012	EASL 2014	AASLD/IDSA/IAS-USA 2014
Stage 1 and 2 Stage 1 = GFR ≥ 90 mL/min per 1.73 m2 Stage 2 = GFR 60-89 mL/min per 1.73 m2	PegIFN and ribavirin Dose of ribavirin to be titrated to patient’s tolerance	PegIFN and ribavirin		PegIFN and ribavirin/sofosbuvir/simeprevir Dose of: (1) PegIFN 2a is 180 μg/wk (2) PegIFN 2b is 1.5 μg/kg per week (3) Ribavirin is 1000 mg or 1200 mg if body weight < 75 kg or ≥ 75 kg (4) Sofosbuvir is 400 mg daily (5) Simeprevir is 150 mg daily
Stage 3, 4 and 5 Stage 3 = GFR 30-59 mL/min per 1.73 m2 Stage 4 = GFR 15-29 mL/min per 1.73 m2 Stage 5 = GFR < 15 mL/min per 1.73 m2	PegIFN Dose of PegIFN to be adjusted to renal function	PegIFN and ribavirin Dose of: (1) PegIFN 2a is 135 μg/wk (2) PegIFN 2b is 1 μg/kg per week (3) Ribavirin is 200-800 mg/d		For GFR = 30-50 mL/min per 1.73 m2 PegIFN and ribavirin/sofosbuvir/simeprevir Dose of: (1) PegIFN 2a is 180 μg/wk (2) PegIFN 2b is 1 μg/kg per week or 25% reduction (3) Ribavirin is alternating doses 200 and 400 mg every other day (4) Sofosbuvir is 400 mg daily (5) Simeprevir is 150 mg daily For GFR < 30 mL/min per 1.73 m2 PegIFN and ribavirin/simeprevir Dose of: (1) PegIFN 2a is 135 μg/wk (2) PegIFN 2b is 1 μg/kg per week or 50% reduction (3) Ribavirin is 200 mg daily (4) Simeprevir is 150 mg daily
Stage 5D GFR < 15 mL/min per 1.73 m2 on maintenance hemodialysis	Conventional IFN Dose to be adjusted to a GFR < 15 mL/min per 1.73 m2	Conventional IFN or PegIFN and markedly reduced dose of ribavirin Dose of: (1) PegIFN 2a is 135 μg/wk (2) PegIFN 2b is 1 μg/kg per week	IFN free and if possible ribavirin free but no safety and efficacy data	PegIFN or conventional IFN and ribavirin Dose of: (1) PegIFN 2a is 135 μg/wk (2) PegIFN 2b is 1 μg/kg per week (3) Conventional IFN is 3 mU 3 x/wk (4) Ribavirin is 200 mg/d

CKD: Chronic kidney disease; KDIGO: Kidney Disease Improving Global Outcome; APASL: Asian Pacific Association for the Study of the Liver; EASL: European Association for the Study of the Liver; AASLD: American Association for the Study of Liver Disease; IDSA: Infectious Disease Society of America; IAS-USA: International Antiviral Society-United States of America; PegIFN: Pegylated interferon; IFN: Interferon; GFR: Glomerular filtration rate; KDIGO 2008: Patients with genotypes 1 or 4 is for 48 wk of therapy if an early virological response (EVR) is obtained at 12 wk (> 2 log fall in viral titer). Genotype 2 or 3 is for 24 wk[9]. APASL 2012: Patients with genotypes 1 is for 48 wk treatment if achieve a complete EVR at week 12, if achieved rapid virological response (HCV RNA undetectable) at week 4 and HCV RNA at baseline is < 400000 IU/mL for shorten treatment to 24 wk and if not achieve an EVR at week 12, but show a significant reduction in HCV RNA levels (partial EVR) and negativity of HCV RNA at week 24 (late virological response, LVR), treatment may be continued up to 72 wk. For Genotype 2 or 3 is 24 wk treatment[26]. EASL 2014: Regimens for patients with genotype 1 are 12 wk of sofosbuvir/ribavirin/PegIFN or 12 wk of sofosbuvir/simeprevir/ribavirin or 24 wk of sofosbuvir/ribavirin. For genotype 2 is 12 wk of sofosbuvir/ribavirin. For genotype 3 are 24 wk of sofosbuvir/ribavirin or 12 wk of sofosbuvir/ribavirin/PegIFN. For genotype 4 are 12 wk of sofosbuvir/ribavirin/PegIFN or 24 wk of sofosbuvir/ribavirin or 24 wk PegIFN/ribavirin/simeprevir for first 12 wk. For genotype 5 or 6 are 12 wk of sofosbuvir/ribavirin/PegIFN or 24 wk of sofosbuvir/ribavirin[55]. AASLD/IDSA/IAS-USA 2014: Regimens for patients with genotype 1 are 12 wk of sofosbuvir/ribavirin/PegIFN or 12 wk of sofosbuvir/ribavirin/simeprevir or 24 wk of PegIFN/ ribavirin/simeprevir for first 12 wk or 24 wk of sofosbuvir/ribavirin or 24 wk of sofosbuvir/simeprevir. For genotype 2 is 12 wk of sofosbuvir/ribavirin. For genotype 3 are 24 wk of sofosbuvir/ribavirin or 12 wk of sofosbuvir/ribavirin/PegIFN. For genotype 4 are 12 wk of sofosbuvir/ribavirin/PegIFN or 24 wk of sofosbuvir/ribavirin or 24-48 wk of PegIFN/ ribavirin/sofosbuvir for first 12 wk. For genotype 5 or 6 are 12 wk of sofosbuvir/ribavirin/PegIFN or 48 wk of PegIFN/ribavirin[132].

Table 2 Summary of systematic reviews on hepatitis C virus treatment in patients with renal disease

HCV and renal condition/ref. and year	No. of trials/patients	Types and duration of treatment	SVR	Notes
Glomerulonephritis
Fabrizi et al[90] (2013)	Trials = 10	Combination of PegIFN plus ribavirin	52%	Dropout rate = 15%
		6 mo to more than 12 mo
	Patients = 300	Conventional IFN plus ribavirin	32%
		6 mo to more than 12 mo
Acute Hepatitis C
Fabrizi et al[116] (2012)	Trials = 8	Conventional or PegIFN	58%	Dropout rate = 9%
	Patients = 173	3 mo to 12 mo		Genotype 1 = 49%
Hemodialysis
Fabrizi et al[117] (2008)	Trials = 28	Conventional IFN or PegIFN	31%-39%	Dropout rate = 19%-27%
	Patients = 645
Fabrizi et al[118] (2010)	Trials = 16	PegIFN	33%-38%	Dropout rate = 23%
	Patients = 254	24-48 wk
Fabrizi et al[122] (2011)	Trials = 10	Conventional interferon + ribavirin or Peg-IFN + ribavirin	56%	Dropout rate = 25%
	Patients = 151	24-48 wk		Genotype 1 = 58.3%
Renal transplant
Wei et al[128] (2014)	Trials = 12	Conventional IFN monotherapy or Conventional IFN plus ribavirin or PegIFN + ribavirin	26.6% PegIFN base = 40.6%	Dropout rate = 21.1%
	Patients = 140	3.5 to 33 mo	Conventional IFN base = 20.9%	Graft rejection rates = 4%

HCV: Hepatitis C virus; SVR: Sustained viral response; IFN: Interferon; PegIFN: Pegylated interferon.