Review
Copyright ©The Author(s) 2016.
World J Gastroenterol. Nov 7, 2016; 22(41): 9044-9056
Published online Nov 7, 2016. doi: 10.3748/wjg.v22.i41.9044
Table 1 Currently approved1 direct-acting antivirals combination regimens for hepatitis C virus associated cirrhosis
Drug classNameCombination DAA partnerGenotypeRibavirinTherapy duration (wk)Approved cirrhosis class (CPT)
NS3/4A protease inhibitorsSimeprevirSofosbuvir1, 4No12A
ParitaprevirIn fixed combination with ritonavir and ombitasvir1, 4No/Yes12-24A
GrazoprevirIn fixed combination with elbasvir1, 4No/Yes12-16A
NS5A inhibitorsDaclatasvirSofosbuvir1, 3, 4No/Yes12-24A, B, C
LedipasvirIn fixed combination with sofosbuvir1, 3, 4, 5, 6No/Yes12-24A, B, C2
OmbitasvirIn fixed combination with paritaprevir and ritonavir1, 4No/Yes12-24A
ElbasvirIn fixed combination with grazoprevir1, 4No/Yes12-16A
VelpatasvirIn fixed combination with sofosbuvir1, 2, 3, 4, 5, 6No/Yes12A, B, C
NS5B non-nucleoside analog polymerase inhibitorsDasabuvirOmbitasvir/paritaprevir/ritonavir1No/Yes12-24A
NS5B nucleoside analog polymerase inhibitorsSofosbuvirDaclatasvir1, 2, 3, 4, 5, 63No/Yes12-24A, B, C
Simeprevir
Ledipasvir in fixed combination
Velpatasvir in fixed combination
1Approved by EMA and/or FDA by October 2016. Approval details may differ with respect to region, genotype, and combination partner;
2Genotype 3, only CPT A;
3Different approvals for SOF/RBV, and SOF/LDV. Adapted from[96]. CPT: Child-Pugh-Turcotte; DAA: Direct-acting antivirals; EMA: European Medicines Agency; FDA: Food and Drug Administration; LDV: Ledipasvir; RBV: Ribavirin; SOF: Sofosbuvir.
Table 2 Efficacy of direct-acting antivirals based, (peg)-interferon-free antiviral therapy in patients with hepatitis C virus-associated (de-) compensated cirrhosis in controlled, prospective trials
Ref.Therapy regimenTreatment duration (wk)Genotypen (all)n (cirrhotic patients)n (MELD > 16)SVR12 % (all patients)
Abergel et al[17]LDV/SOF125419Not specified39/41 (95%)
Afdhal et al[53] (ION-1)LDV/SOF ± RBV12-241865136Not specified849/865 (98%)
Afdhal et al[54] (ION-2)LDV/SOF ± RBV12-24144088Not specified427/440 (97%)
Bouliere et al[18] (SIRIUS)LDV/SOF ± RBV12-241155155Not specified149/154 (97%)
Charlton et al[19] (SOLAR-1)LDV/SOF/RBV12-241, 43371082789/108 (82%)1
Curry et al[20] (ASTRAL-4)VEL/SOF ± RBV12-241, 2, 3, 4, 626726713234/267 (88%)
Curry et al[21]SOF/RBVUp to 481, 2, 3, 46161None30/43 (70%)
Feld et al[22] (ASTRAL-1)VEL/SOF121, 2, 4, 5, 67412142Not specified618/624 (99%)3
Feld et al[23] (TURQUOISE-III)OBV/PTV/r + DSV121b6060Not specified60/60 (100%)
Forns et al[24] (C-SALVAGE)Grazoprevir/Elbasvir/RBV1217934Not specified76/79 (96%)
Foster et al[25] (ASTRAL-2/-3)VEL/SOF vs SOF/RBV122, 3818201Not specified742/818 (91%)
Foster et al[68] (BOSON)SOF/RBV ± IFN12-242, 3592219Not specified494/592 (83%)
Kumada et al[26] (GIFT-1)OBV/PTV/r121b36342Not specified346/363 (95%)
Lawitz et al[27] (OPTIMIST-2)SMV/SOF121103103Not specified86/103 (83%)
Lawitz et al[28] (C-WORTHY)Grazoprevir/Elbasvir ± RBV12-181253170Not specified240/253 (95%)
Lawitz et al[29] (PEARL-I)OBV/PTV/r + DSV12-24118199Not specified172/181 (95%)
Leroy et al[30] (ALLY-3+)DCV/SOF/RBV12-1635050Not specified45/50 (90%)
Manns et al[31] (SOLAR-2)LDV/SOF/RBV121, 4328160441121/140 (86%)
Mizokami et al[32]LDV/SOF ± RBV12134176Not specified338/341 (99%)
Nelson et al[33] (ALLY-3)DCV/SOF12315232Not specified135/152 (89%)
Omata et al[34]SOF/RBV12215317Not specified148/153 (97%)
Poordad et al[35] (TURQUOISE-II)OBV/PTV/r + DSV/RBV12-241380380Not specified5356/380 (94%)
Poordad et al[36] (ALLY-1)DCV/SOF/RBV121, 2, 3, 4, 6113660Not specified (CPT C 16)100/113 (89%)7
Poordad et al[37] (QUARTZ-I)OBV/PTV/r + DSV + SOF + RBV12-241227Not specified14/15 (93%)8
Wyles et al[38]LDV/SOF/RBV1215114Not specified50/51 (98%)
Zeuzem et al[39] (VALENCE)SOF/RBV12-242, 341990Not specified302/334 (90%)9
Zeuzem et al[40] (C-EDGE)Grazoprevir/elbasvir121, 4, 642192Not specified299/316 (95%)10
1Only pretransplant cohort;
2116 patients received placebo;
3SVR in patients with compensated cirrhosis 99%;
4Patients with CPT class B or C cirrhosis pre- and posttranplant, additionally CPT class A patients posttransplant participated in this trial, the number was not specified;
5Only patients with CPT class A cirrhosis included;
6Only patients who had undetectable HCV-RNA at transplant were included in efficacy analysis;
783% in the advanced cirrhosis cohort;
8Not all patients completed follow up until conference;
985 patients received placebo;
10105 patients had deferred therapy. CPT: Child-Pugh-Turcotte; DAA: Direct-acting antivirals; DCV: Daclatasvir; DSV: Dasabuvir; LDV: Ledipasvir; RBV: Ribavirin; SMV: Simeprevir; SOF: Sofosbuvir; PTV/r: Paritaprevir/ritonavir; VEL: Velpatasvir; SVR12: Sustained virologic response 12 wk after end of treatment.
Table 3 Efficacy of direct-acting antivirals based, (peg-)-interferon-free antiviral therapy in patients with hepatitis C virus liver graft infection in controlled, prospective trials
Ref.Therapy regimeTreatment duration (wk)Genotype1nSVR12
Charlton et al[19] (SOLAR-1)1LDV/RBV + RBV12-241, 42292214/229 (93%)
1Charlton et al[82]SOF + RBV241, 3, 44028/40 (70%)
Kwo et al[84] (CORAL-1)DSV/OMV/PTV/r + RBV2413433/34 (97%)
Manns et al[31,72] (SOLAR-2)LDV/SOF +RBV12 or 241, 41683146/151 (97%)
Poordad et al[36] (ALLY-1)1DCV/SOF + RBV121, 2, 3, 4, 6453250/53 (94%)
Reddy et al[83]SOF/LDV + RBV12-241, 4223120/129 (93%)5
1Mainly patients with genotype 1;
2The complete study included patients prior and after liver transplantation;
3Preliminary results with regard to publication status or completed SVR12 (SVR not available in all patients enrolled into the study);
4Only one patient had GT 2, 4 or 6;
5Interims SVR4 results. LDV: Ledipasvir; RBV: Ribavirin; SMV: Simeprevir; SOF: Sofosbuvir; OMV: Ombitasvir; PTV/r: Paritaprevir/ritonavir; SVR12: Sustained virologic response 12 wk after end of treatment.