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©The Author(s) 2015.
World J Hepatol. Jun 28, 2015; 7(12): 1606-1616
Published online Jun 28, 2015. doi: 10.4254/wjh.v7.i12.1606
Published online Jun 28, 2015. doi: 10.4254/wjh.v7.i12.1606
Table 1 Direct acting antivirals commenced on patients with decompensated cirrhosis or recipients after liver transplantation
Approved protease inhibitors | |
Boceprevir | NS3-4A serine protease inhibitors |
Telaprevir | Second-wave NS3/4A protease inhibitor |
Simeprevir | |
Approved NS5A inhibitors | |
Daclatasvir | NS5A inhibitor |
Approved NS5B RNA-dependent RNA polymerase nucleotide inhibitor | |
Sofosbuvir | NS5B RNA-dependent RNA polymerase nucleotide inhibitor |
Newer DAAs evaluated in combination regimens without Peg-IFN | |
Ledipasvir (formerly GS-5885) | NS5A inhibitor |
ABT-450 | NS3/4A protease inhibitor |
Ombitasvir (formerly ABT-267) | NS5A inhibitor |
Dasabuvir (formerly ABT-333) | Non-nucleoside NS5B polymerase inhibitor |
Table 2 Doses of antivirals in liver transplant candidates and recipients
Peg-IFN-α 2a | 180 μg/wk, subcutaneous | Renal adjustment |
Peg-IFN-α 2b | Weight-based 1.5 μg/kg per week, subcutaneous | No CNI adjustment |
Ribavirin | Weight-based, 1000 mg in patients < 75 kg, 1200 mg in patients ≥ 75 kg, orally twice a day | |
Boceprevir | 800 mg orally three times a day | No renal adjustment |
Telaprevir | 1125 mg orally twice a day | CNI adjustment |
Sofosbuvir | 400 mg daily, orally | |
Daclatasvir | 60 mg daily, orally | No renal adjustment1 |
Simeprevir | 150 mg daily, orally | No CNI adjustment2 |
Table 3 Treatment of liver transplant candidates with hepatitis C[6]
Cirrhosis CP A, all HCV genotypes | ||
Sofosbuvir + RBV until LT | Peg-IFN + RBV + sofosbuvir for 12 wk | RBV + sofosbuvir + daclatasvir for 12 wk |
Cirrhosis CP B and C, all HCV genotypes | ||
Sofosbuvir + RBV until LT | IFN contraindicated | RBV + sofosbuvir + daclatasvir for 12 wk |
Table 4 Major studies of interferon-free regimens for treatment of hepatitis C virus positive liver transplant candidates reported in 2014
Ref. | n | CP score | Antiviral scheme | Virological response |
Curry et al[37] | 61 | ≤ 7 | SOF + RBV for 48 wk or until LT | 69% (12 wk after LT) |
Gane et al[39] | 20 | 7-9 | SOF ± RBV + ledipasvir for 12 wk | 89% (SVR 4 wk) |
Flamm et al[40] | 108 | Decompensated cirrhosis (range: 7-12) | SOF + RBV + ledipasvir for 12 or 24 wk | 87% and 89%, respectively (SVR 12 wk) |
Afdhal et al[38] | 50 | 5-10 | SOF + RBV for 48 wk | 100% CP class A |
93% CP class B at 24 wk under treatment |
Table 5 Treatment of hepatitis C virus recurrence post liver transplant
IFN-free: Sofosbuvir + RBV (HCV genotype 2 for 12-24 wk); sofosbuvir + daclatasvir ± RBV (HCV genotypes 1, 3-6 for 12-24 wk); sofosbuvir + simeprevir ± RBV (HCV genotypes 1, 4 for 12 -24 wk) | ||
In case of restriction applying first generation DAAs | ||
Fibrosis metavir stage 3-4 | Genotype 2/3 | Genotype 1 |
Genotype 1a | Fibrosis metavir stage 2 | |
IL-28B polymorphism | Predictors of poor response | |
Fibrosing cholestatic hepatitis | Peg-IFN plus RBV | Peg-IFN plus RBV plus boceprevir or telaprevir |
Non responders to previous treatments | Monitor closely Hb, WBC, PLTs CNI levels, renal function | |
Consider | ||
Administration of blood transfusions, EPO, CSGF | ||
Decrease of RBV dose | ||
Renal dose adjustment | ||
Decrease of CNI dose |
Table 6 Major studies tested the efficacy of first generation direct antiviral agents combined with peg-interferon and ribavirin in liver transplant recipients
Ref. | Year of publication | No. of patients | Sustained virological response |
Coilly et al[73] | 2013 | 37 | 50% (20% for telaprevir and 71% for boceprevir) |
Pungpapong et al[74] | 2013 | 60 | 56% (67% for telaprevir and 45% for boceprevir) |
Werner et al[75] | 2012 | 9 | 89% |
Stravitz et al[76] | 2013 | 122 | 28% |
Ann Brown et al[77] | 2013 | 46 | 60% |
Faisal et al[78] | 2014 | 76 | 59.5% |
Werner et al[79] | 2014 | 14 | 50% |
Table 7 Major studies of sofosbuvir with other novel direct antiviral agents with or without ribavirin for treatment of hepatitis C virus positive liver transplant recipients reported in 2014
Ref. | n | Patient characteristics | Antiviral scheme | Virological response | SVR | Duration (wk) |
Pungpapong et al[85] | 55 | Fibrosis 3-4 (29%) | SOF + simeprevir ± RBV | 98% (EOT) | 91% | 12 |
Decompensated cirrhosis (4%) | ||||||
Cholestatic recurrence (15%) | ||||||
Leroy et al[87] (CUPILT) | 21 | Fibrosing cholestatic hepatitis | SOF + daclatasvir ± RBV (n = 13) | 95% HCV RNA < 15 IU/mL | - | 24 |
SOF + RBV (n = 6) | 81% were not detectable (at week 12 under treatment) | |||||
Conti et al[86] | 55 | Fibrosis 3-4 (33%) | SOF + daclatasvir | 85% (at week 8 under treatment) | - | 24 |
Fibrosing cholestatic hepatitis (7%) | ||||||
Kwo et al[89] (CORAL I) | 34 | Fibrosis 0-2 | Paritaprevir + ritonavir + ombitasvir + dasabuvir + RBV | 100% (EOT) | 97% | 24 |
Reddy et al[88] | 223 | Fibrosis 0-3, CP A-C | SOF + ledipasvir + RBV | - | 96%-98% (CP A: 9% CP B: 83%-85% CP C: 60%-67%) | 12-24 |
Table 8 Major drug-drug interactions of the newer direct acting antivirals for hepatitis C
DAA | Co-administration should be avoided |
Sofosbuvir | P-glycoprotein inducers |
Anticonvulsants: Carbamazepine, oxcarbazepine, phenobarbital, phenytoin; antimycobacterials: Rifampin, rifabutin, rifapentin; St. John's wort; HIV drugs: Tipranavir/ritonavir | |
Simeprevir | Inhibitors or inducers of CYP3A4 |
Antifungals: Fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole; Antibiotics: Clarithromycin, erythromycin, telithromycin; Dexamethasone; Cicapride; HIV drugs: Cobicistat, efavirenz, delavirdine, etravirine, nevirapine, ritonavir and any HIV protease inhibitor | |
P-glycoprotein inducers | |
Daclatasvir | Strong inducers of CYP3A4 and/or P-glycoprotein |
e.g., phenytoin, carbamazepine, oxcarbazepine, phenobarbital, rifampicin, rifabutin, rifapentine, dexamethasone, St. John's wort; HIV drugs: darunavir, lopinavir, etravirine | |
Sofosbuvir/ledipasvir | P-glycoprotein inducers, rosuvastatin, simeprevir |
- Citation: Pipili C, Cholongitas E. Treatment of chronic hepatitis C in liver transplant candidates and recipients: Where do we stand? World J Hepatol 2015; 7(12): 1606-1616
- URL: https://www.wjgnet.com/1948-5182/full/v7/i12/1606.htm
- DOI: https://dx.doi.org/10.4254/wjh.v7.i12.1606