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©The Author(s) 2018.
World J Transplant. Aug 9, 2018; 8(4): 84-96
Published online Aug 9, 2018. doi: 10.5500/wjt.v8.i4.84
Published online Aug 9, 2018. doi: 10.5500/wjt.v8.i4.84
Table 1 The four classes of direct acting antivirals agents
The four classes of DAAs | Mechanism of action | Drugs (targeted genotypes in brackets) |
NS3/4A PIs (PIs) | Block a viral enzyme (protease) that enables the HCV to survive and replicate in host cells | Glecaprevir (1-6) Paritaprevir (1, 4) Voxilaprevir (1-6) Grazoprevir (1, 3, 4) |
Nucleoside and nucleotide NS5B polymerase inhibitors | Target the HCV to stop it from making copies of itself in the liver. So doing block the virus from multiplying | Sofosbuvir (1-4) |
NS5A inhibitors | Block a virus protein, NS5A, that HCV needs to reproduce and for various stages of infection | Ombitasvir (1, 4) Pibrentasvir (1-6) Daclatasvir (3) Elbasvir (1, 4) Ledipasvir (1) Ombitasvir (1) Velpatasvir (1-6) |
Non-nucleoside NS5B polymerase inhibitors | Stop HCV from reproducing by inserting themselves into the virus so that other pieces of the HCV cannot attach to it | Dasabuvir (1) |
Table 2 Available, approved direct acting antiviral-based regimens for treating hepatitis C virus in treatment-naive patients
Genotype 1a | Genotype 4 |
Ledipasvir + sofosbuvir Paritaprevir + ritonavir + ombitasvir + dasabuvir Sofosbuvir+ simeprevir ± ribavirin | Ledipasvir + sofosbuvir Paritaprevir + ritonavir + ombitasvir + dasabuvir + ribavirin Sofosbuvir + ribavirin + pegIFN Sofosbuvir + simeprevir + ribavirin |
Genotype 1b | Genotype 5 |
Ledipasvir + sofosbuvir Paritaprevir + ritonavir + ombitasvir + dasabuvir Sofosbuvir + simeprevir | Sofosbuvir + ribavirin PegIFN + ribavirin |
Genotype 2 | Genotype 6 |
Sofosbuvir + ribavirin | Ledipasvir + sofosbuvir Sofosbuvir + ribavirin + pegIFN |
Genotype 3 | Pangenotype |
Sofosbuvir + ribavirin Sofosbuvir + ribavirin + pegIFN | Glecaprevir + pibrentasvir Sofosbuvir + velatapasvir |
Table 3 Recommended regimens for kidney transplant patients
Recommended | Duration | Rating |
Recommended regimens listed by evidence level and alphabetically for treatment-naive and experienced kidney transplant patients with genotype 1 or 4 infection, with or without compensated cirrhosis | ||
Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg) | 12 wk | I, A1 |
IIa, C2 | ||
Daily fixed dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) | 12 wk | I, A |
Recommended and alternative regimens for treatment-naïve and experienced kidney transplant patients with genotype 2, 3, 4, 5 or 6 infection, with or without compensated cirrhosis | ||
Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg) | 12 wk | I, A3 |
IIa, C4 | ||
Alternative | ||
Daily daclatasvir (60 mg) plus sofosbuvir (400 mg) plus low initial dose of ribavirin (600 mg; increased as tolerated) | 12 wk | II, A |
Table 4 Main literature studies with direct acting antiviral therapy in patients with chronic hepatitis C and renal dysfunction
Ref. | Title | Journal | Year |
[62] | Efficacy of direct-acting antiviral combination for patients with HCV genotype 1 infection and severe renal impairment or end-stage renal disease | Gastroenterology | 2016 |
[63] | Glecaprevir and Pibrentasvir in patients with HCV and severe renal impairment | N Engl J Med | 2017 |
[64] | Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with HCV genotype 1 infection and stage 4-5 chronic kidney disease (the C-SURFER study): A combination phase 3 study | Lancet | 2015 |
[65] | Elbasvir plus grazoprevir in patients with HCV infection and stage 4-5 chronic kidney disease: clinical, virological, and health-related quality-of-life outcomes from a phase 3, multicentre, randomized, double-blind, placebo-controlled trial | Lancet Gastroenterol Hepatol | 2017 |
[70] | Use of sofosbuvir-based direct-acting antiviral therapy for HCV infection in patients with severe renal insufficiency | Infect Dis | 2015 |
[71] | Safety, efficacy and tolerability of half-dose sofosbuvir plus simeprevir in treatment of hepatitis C in patients with end stage renal disease | J Hepatol | 2015 |
[72] | Sofosbuvir and simeprevir in hepatitis C genotype 1-patients with end-stage renal disease on haemodialysis or GFR < 30 mL/min | Liver Int | 2016 |
[74] | Use of direct-acting agents for HCV-positive kidney transplant candidates and kidney transplant recipients | Transpl Int | 2016 |
[75] | Safety and efficacy of sofosbuvir-containing regimens in hepatitis C-infected patients with impaired renal function | Liver Int | 2016 |
Table 5 American Association for the Study of Liver Diseases Recommendation for treating hepatitis C virus in patients with renal impairment
Recommended | Rating | Genotype | Duration |
Recommendations for patients with CKD stage 1, 2 or 3 | |||
No dose adjustment is required when using (1) Daclatasvir (60 mg) (2) Daily fixed-dose combination of elbasvir (50 mg)/grazopevir (100 mg) (3) Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg) (4) Fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) (5) Fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) (6) Simeprevir (150 mg) (7) Fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg)/voxilaprevir (100 mg) (8) Sofosbuvir (400 mg) | I, A | ||
Recommendations for patients with CKD stage 4 or 5 (eGFR < 30 mL/min or ESRD | |||
Daily fixed-dose combination of elbasvir (50 mg)/grazoprevir (100 mg) | I, B | 1a, 1b, 4 | 12 wk |
Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg) | I, B | 1, 2, 3, 4, 5, 6 | 8 to 16 wk |
Table 6 European Association for the Study of the Liver Recommendations for treating hepatitis C virus in patients with reduced or absent renal function
Hemodialysis patients, particularly those who are suitable candidates for renal transplantation, should be considered for antiviral therapy (B1) |
Hemodialysis patients should receive an IFN-free, if possible ribavirin-free regimen, for 12 wk in patients without cirrhosis, for 24 wk in patients with cirrhosis (B1) |
Simeprevir, daclatasvir, and the combination of ritonavir-boosted paritaprevir, ombitasvir and dasabuvir are cleared by hepatic metabolism and can be used in patients with severe renal disease (A1) |
Sofosbuvir should not be administered to patients with an eGFR < 30 mL/min per 1.73 m2 or with end-stage renal disease until more data is available (B2) |
- Citation: Salvadori M, Tsalouchos A. Hepatitis C and renal transplantation in era of new antiviral agents. World J Transplant 2018; 8(4): 84-96
- URL: https://www.wjgnet.com/2220-3230/full/v8/i4/84.htm
- DOI: https://dx.doi.org/10.5500/wjt.v8.i4.84