Minireviews
Copyright ©The Author(s) 2017.
World J Hepatol. Feb 8, 2017; 9(4): 180-190
Published online Feb 8, 2017. doi: 10.4254/wjh.v9.i4.180
Table 1 Main characteristics of the approved direct acting antivirals that are currently used for the treatment of hepatitis C
DAA (commercial name), doseCategoryDose adjustment in renal impairmentAntiviral activityCNIs co-administration
Sofosbuvir (Sovaldi®), tablet 400 mg, once dailyNucleotide analogue NS5B polymerase inhibitorContraindicated in patients with GFR < 30 mL/minGenotypes 1-6No change
High genetic barrier
Simeprevir (Olysio®), tablet 150 mg, once daily with foodNS3/4A protease inhibitorNo change in renal impairmentGenotypes 1,4Contraindicated with cyclosporine
Low genetic barrier
Daclatasvir (Daklinza®), tablet 60 mg, once dailyNS5A inhibitorNo change in renal impairmentGenotypes 1, 2, 3, 4No change
Low genetic barrier
Ledipasvir/sofosbuvir/(Harvoni®), tablet 90/400 mg, once dailyNS5A inhibitor + nucleotide analogue NS5B polymerase inhibitorContraindicated in patients with GFR < 30 mL/minGenotypes 1, 4, 5, 6No change
High genetic barrier
Ombitasvir/paritaprevir/ritonavir (Viekirax®), tablet 12.5/75/50 mg, two once daily with foodNS5A inhibitor + NS3/4A protease inhibitor boosted by ritonavir boostedNo change in renal dysfunctionGenotypes 1, 4Cyclosporine: 20% of pretreatment total daily dose; tacrolimus: 0.2 mg/72 h or 0.5 mg once weekly
Genetic barrier depending on HCV genotype
Dasabuvir (Exviera®), tablet 250 mg, every 12 hNon-nucleos(t)ide analogue NS5B polymerase inhibitorNo change in renal dysfunctionGenotype 1
Low genetic barrier
Elbasvir/Grazoprevir (Zepatier®), tablet 100/50 mg, once dailyNS5A inhibitor + NS3/4A inhibitorNo change in renal dysfunctionGenotypes 1,4Co-administration increases tacrolimus concentrations
Velpatasvir/sofosbuvir/(Epclusa®), tablet 100/400 mg, once dailyNS5A inhibitor + nucleotide analogue NS5B polymerase inhibitorContraindicated in patients with GFR < 30 mL/minGenotypes 1-6No change
High genetic barrier
Table 2 Studies of interferon free regimens for treatment of hepatitis C virus patients with severe renal disease or under hemodialysis
Ref.Patients, nPatient characteristicsRegimen: Patients number (dose of sofosbuvir)Sustained virological response at 12 wk, n/NAdverse events, n
Pockros et al[25]20GT1: 20 patients (1a: 13)3D ± RBV: 2018/20 (EOT-VR: 20/20)Death from drug unrelated cause (cardiac arrest at 14 d after the end of therapy): 1
Gomez et al[26]33GT1: 29 (1a: 6)3D ± RBV: 3331/31Serious adverse events: 5 (all unrelated to study drugs)
Age: 57 yr
Basu et al[27]36GT1: 36 (1a: 23)3D ± RBV: 3634/36No serious adverse event
Roth et al[28]122GT1: 122 patientsElbasvir/grazoprevir: 122115/122Serious adverse events: 16
Czul et al[29]28GT1: 26 (1a: 16)SOF + SMV: 2621/25Encephalopathy: 1
Age: 58 yrSOF + RBV: 2 (200 mg/eod-400 mg/d)Uncontrolled diarrhea: 1
Beinhardt et al[30]15GT1: 11 patientsSOF + DCV: 91/1 (EOT-VR: 5/5)Pancytopenia at week 7: 1 (change SOF from every 24 h to every 48 h)
Age: 52 yrSOF + SMV: 5
SMV + DCV: 1 (400 mg/d)
Dumortier et al[31]50GT1: 28 patientsSOF + RBV: 724/26 (EOT-VR: 50/50)No serious adverse event
Age: 60 yrSOF + RBV + PEG-IFN: 2
SOF + DCV ± RBV: 30
SOF + SMV ± RBV: 11
Gane et al[32]10GT1: 9 (1a: 7)SOF + RBV: 10 (200 mg/d)4/10Serious adverse events: 2 (diabetic acidosis, angina)
Age: 62 yr
Nazario et al[33]40GT1: 26 (1a: 26)SOF + LDV: 929/29Drug discontinuation: 1 (unknown reason)
Age: 57 yrSOF + DCV: 2
SOF + SMV: 29 (400 mg/d)
Baliellas et al[34]21 (10 on hemodialysis)GT1: 20 patients (1a: 2)SMV + DCV: 1217/19No serious adverse event
Age: 57 yrSMV + DCV + RBV: 9
Moreno et al[35]42GT1: 25 (1a: 8)SOF + RBV: 532/42Drug discontinuation: 11
Age: 54 yrLDV/SOF: 8
SOF + DCV: 14
SOF + SMV: 3
SMV + DCV: 12
Saxena et al[36]19GT1: 16 (1a: 8)SOF + SMV + RBV: 2SOF + SMV + RBV: 2/2Therapy discontinuation: 1
SOF + SMV: 11SOF + SMV: 8/10Serious adverse events: 3
SOF + RBV: 5SOF + RBV: 4/4
SOF + RBV + PEG-IFN: 1 (400 mg/d)SOF + RBV + PEG: 1/1
Martin et al[37]10GT1: 8 patientsSOF + RBV: 10 (400 mg/d)6/10Acute respiratory failure - drug discontinuation: 1, hematemesis: 1
Age: 58 yr
Table 3 Studies of interferon-free regimens for treatment of hepatitis C virus positive kidney transplant recipients
Ref.Patients, nPatient characteristicsRegimen: Patients numberSustained virological response at 12 wk, n/NAdverse events, n
Huard et al[39]17GT1: 16 patients (1a: 5) Age: 65 yrSOF + RBV: 17 (400 mg/d)1/6Therapy discontinuation: 4 (3 due to pruritus, myalgia, anemia, 1 unclarified) Anemia: 8
Lin et al[40]15GT1: 14 (1a: 10) Age: 55.8 yrSOF + SMV ± RBV: 12 (SOF + SMV: 9)13/15No serious adverse events under therapy (1 died by massive hemorrhage 4 wk after therapy) Proteinuria: 2
SOF + RBV: 2 SOF + LDV: 1Bradycardia under amiodarone (pacemaker placement): 1
Bhamidimarri et al[41]14GT1: 14 (1a: 12)SOF + LDV: 1313/14No serious adverse events
Age: 54 yr(in 9 plus RBV)Therapy discontinuation: 1
SOF + SMV: 1Anemia: 7
Hussein et al[42]3GT4: 3SOF + RBV3/3No serious adverse events
(400 mg/d)
Sawinski et al[43]20GT1: 17 (1a: 7)SOF + SMV: 920/20No serious adverse events
Age: 57 yrSOF/LDV: 7
SOF + RBV: 3
SOF + DCV: 1
(400 mg/d)
Moreno et al[44]12GT1: 11 (1a: 4)SOF + SMV: 111/12Therapy discontinuation: 1
Age: 53 yrSOF/LDV: 8
SOF + DCV: 3
(400 mg/d)
El-Halawany et al[45]11GT1: 10 (1a: 10)SOF + SMV: 210/11No serious adverse events
Age: 57.6 yrSOF/LDV: 8
SOF + RBV: 1
Londono et al[46]74GT1: 61 (1a: 6)SOF/LDV ± RBV: 3745/46Rejection episodes: 3
Age: 54 yrSOF + DCV ± RBV: 15
SOF + SMV ± RBV: 6
SMV + DCV ± RBV: 7
SOF + RBV: 4
3 “D” or 2 “D”: 5
Colombo et al[47]114GT1: 104SOF/LDV112/114Therapy discontinuation: 1
Serious adverse events: 12
Reddy et al[48]50SOF/LDV ± RBV: 4210/10Rejection episode: 1
SOF + DCV ± RBV: 1
3 “D”: 7
Table 4 Recommended regimens from the American Association for the Study of Liver Diseases and European Association for the Study of the Liver for patients with chronic hepatitis C and severe renal impairment (glomerular filtration rate < 30 mL/min) who need urgent hepatitis C virus therapy and renal transplantation is not an immediate option
HCV genotypeAASLD recommended regimenEASL recommended regimen3
1Elbasvir/grazoprevir for 12 wk (for 1a or 1b) or ombitasvir/paritaprevir/ritonavir plus dasabuvir1 (for 1b) for 12 wkElbasvir/grazoprevir or ombitasvir/paritaprevir plus dasabuvir (for 1a or 1b), for 12 wk (plus RBV 200 mg/d for 1a if the haemoglobin level is > 10 g/dL at baseline)
2, 3, 5 or 6Pegylated interferon-alfa plus dose-adjusted ribavirin (200 mg daily)2Sofosbuvir/velpatasvir or sofosbuvir plus daclatasvir (plus ribavirin if the haemoglobin level is > 10 g/dL at baseline for genotype 3) for 12 wk (or for 24 wk without ribavirin for genotype 3)4
4Elbasvir/grazoprevir for 12 wkElbasvir/grazoprevir for 12 wk or ombitasvir/paritaprevir plus dasabuvir plus ribavirin (if the haemoglobin level is > 10 g/dL at baseline) for 12 wk