Hepatitis c virus and chronic kidney disease

Figures & data

Table 1. Pharmacokinetic data of new direct-acting antiviral treatment in HCV patients and significant drug Interactions [76,81,83].

Drug - HCV targets	Metabolism	Elimination	Adjustment if GFR <30 ml/min/1.73 m2 or HD	Interaction with immunosuppressive medications	Important drug interactions
Sofosbuvir - NS5B	Mainly Renal oxidative metabolism and dephosphorylation	Urine (80%) Feces (15%)	No adjustment needed	No significant interaction	c-i with amiodarone Safe with antiretrovirals
Simeprevir - NS3/4A protease (co-formulation with sofosbuvir)	Hepatic	Biliary (91%) Urine (<1%)	No adjustment needed	Decreased Tacrolimus lvl, Increased CsA lvl Alters Sirolimus lvl	Significant interaction with triazole antifungals, digoxin, antiarrhythmics & anticonvulsants
Daclatasvir - NS5A replication Complex (co-formulation with sofosbuvir)	Hepatic	Feces (88%) Urine (7%	No adjustment needed	Not Clinically relevant	C-i with dexamethasone, St. John wart, rifampin, phenytoin and carbamazepine
Ledipasvir - NS5A (co-formulation with sofosbuvir)	Hepatic	Feces (>80%) Urine (<1%)	No adjustment needed	No change in levels of CsA, Tacrol and sirolimus	Use in caution with digoxin and dabigatran Not recommended with rosuvastatin
Velpatasvir - NS5A (co-formulation with sofosbuvir)	Hepatic	fecal 94% urine 0.4%	No adjustment needed	No significant interaction	Not recommended with efavirenz, etravirine and nevirapine.
Paritaprevir/ritonavir/ ombitasvir/ dasabuvir NS3/4A protease/ HIV protease/NS5A polymerase	Hepatic	Feces (>86%) Urine (2–11%)	No, if GFR 15–30 ml/min/1.73 m2 Caution for ESRD or HD	Reduce dose of Tacrolimus Decrease dose of CsA to 1/5^th Increase lvl of Sirolimus and everolimus (monitor)	Not recommended in Child B,C Cirrhosis
Grazoprevir/elbasvir NS3/4A protease/ NS5A	Hepatic (CYP3A)	Feces (>90%)	No adjustment needed	Increase tacrolimus level Increase lvl of Sirolimus and everolimus (monitor) Do not use with CsA	Not recommended with boosted protease inhibitors, some azole antifungal
Glecaprevir/Pibrentasvir NS3/4A protease/NS5A polymerase	Hepatic (CYP3A)	Feces (>90%)	No adjustment needed	Not recommended with CsA > 100 mg/day	c-i with atazanavir-containing HIV regimens

Protease inhibitor drugs (simeprevir, paritaprevir, grazoprevir, voxilaprevir) containing regimen are not recommended in Child B/C cirrhosis.

CsA: cyclosporin.

Tacrol: tacrolimus.

Lvl: level.

C-i: contra indication.

Table 2. Therapeutic options for treating hepatitis C virus infection [9,81,83].

CKD stage	HCV genotype	DAA regimens
Stages 1-3 (eGFR, 31-90 mL/min)	All (1-6)	Sofosbuvir + velpatasvir (8–12 weeks) or Sofosbuvir + velpatasvir + voxilaprevir (8 weeks for patients without cirrhosis; 12 weeks for patients with cirrhosis) or Glecaprevir + pibrentasvir(8 weeks for patients without cirrhosis; 12 weeks for patients with cirrhosis) or Sofosbuvir + Daclatasvir (12 weeks with dose escalating ribavirin)^a or Sofosbuvir + Ledipasvir (12 weeks)^b or Grazoprevir + elbasvir (8–12 weeks)^c
Stage 4 or 5 (eGFR, <30 mL/min or hemodialysis)	• 1a, 1b, 4 • All (1-6)	Elbasvir/grazoprevir Glecaprevir/pibrentasvir Sofosbuvir containing regimens since November 2019[83]

a: For genotype 1–4, Extend treatment duration to 24 weeks if ribavirin ineligible.

b: For genotype 1,4,5,6.

c: Approved for genotype 1a,1b, and 4.

The choice of therapy for HCV and duration of treatment depends on genotype, presence or absence of cirrhosis, and tolerability to ribavirin.

Protease inhibitor drugs (simeprevir, paritaprevir, grazoprevir, voxilaprevir) containing regimen are not recommended in Child B/C cirrhosis.

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