Review
Copyright ©The Author(s) 2021.
World J Gastroenterol. Mar 21, 2021; 27(11): 1006-1021
Published online Mar 21, 2021. doi: 10.3748/wjg.v27.i11.1006
Table 1 Efficacy of interferon-free regimens in genotype 3 patients in clinical trials
Ref.
Phase
Number of GT3 participants
Regimen
Treatment duration
SVR
Noncirrhotics
Cirrhotics
Treatment-naive (%)
Treatment-experienced (%)
Treatment-naive (%)
Treatment-experienced (%)
Lawitz et al[40], FISSION3173SOF + RBV12 wk61-34-
Jacobson et al[64], POSITRON398SOF + RBV12 wk68-21-
Jacobson et al[64], FUSION3127SOF + RBV12 wk-37-19
16 wk-63-61
Foster et al[58], BOSON3363SOF + RBV16 wk83765747
24 wk90828277
Zeuzem et al[65], VALENCE3250SOF + RBV24 wk95879262
Nelson et al[69], ALLY-33152SOF + DCV12 wk97945869
Leroy et al[70], ALLY-3+350SOF + DCV + RBV12 wk10010050 (1/2)93
16 wk10010010086
Poordad et al[71], ALLY-3C378SOF + DCV + RBV24 wk--9379
Esteban et al[81], NCT027815582204SOF/VEL12 wk--91
SOF/VE + RBV12 wk--96
Foster et al[80], ASTRAL-33552SOF + RBV24 wk90737158
SOF/VEL12 wk98939189
Bourlière et al[102], POLARIS-1378SOF/VEL+ VOX12 wk-1001-931
Jacobson et al[103], POLARIS-23181SOF/VEL12 wk97--
SOF/VEL+ VOX8 wk99--
Jacobson et al[103], POLARIS-33219SOF/VEL12 wk--9991
SOF/VEL+ VOX8 wk--9697
Bourlière et al[102], POLARIS-43106SOF/VEL12 wk-852-85%2
SOF/VEL+ VOX12 wk-962-962
Gane et al[114], LEPTON241SOF/VEL+ VOX6 wk--83-
8 wk-100100
Gane et al[115], NCT02378961274SOF/VEL+ VOX6 wk100---
8 wk--94-
12 wk-100-94
Zeuzem et al[92], ENDURANCE-33505GLE/PIB8 wk95---
12 wk95---
SOF + DCV12 wk97---
Kwo et al[93], SURVEYOR-II (part 2)353GLE/PIB8 wk97---
12 wk-92--
Wyles et al[94], SURVEYOR-II (part 3)3131GLE/PIB12 wk-9198-
16 wk-95-96
Brown et al[90], EXPEDITION-83124GLE/PIB8 wk--98-
Wyles et al[104], MAGELLAN-3314GEL/PIB+ SOF + RBV16 wk-100-100
Gane et al[105], ELECTRON-22101SOF/LDV12 wk64---
SOF/LDV + RBV12 wk10089-73
Pawlotsky et al[106], VITAL-12181ALV24 wk76---
ALV + RBV24 wk93---
Lawitz et al[109], NAVIGATOR221OBV/PTV/r12 wk40---
OBV/PTV/r + RBV12 wk9---
Shafran et al[110], QUARTZ II-III251OBV/PTV/r + SOF12 wk98---
OBV/PTV/r + SOF + RBV12 wk91-100-
Gane et al[107], C-WORTHY (part D)241GZR/EBR + RBV12 wk45---
18 wk57---
Lawitz et al[111], C-SWIFT241GZR/EBR + SOF8 wk93---
12 wk100-91-
Foster et al[112], C-ISLE2100GZR/EBR + SOF8 wk--91-
12 wk--961003
16 wk---94
Lawitz et al[113], C-CREST-1 and -22337GZR + EBR + UPR ± RBV8 wk95
12 wk97
16 wk96
Lawitz et al[108], C-BREEZE-2261RZR + UPR12 wk8068
1NS5A-inhibitor-experienced.
2No detailed information on the response rate in patients with and without liver cirrhosis.
3Recommended by American Association for the Study of Liver Diseases/Infectious Diseases Society of America as an alternative option for pegylated interferon + ribavirin-experienced patients with compensated liver cirrhosis. SVR: Sustained virologic response; GT: Genotype; SOF: Sofosbuvir; RVB: Ribavirin; DCV: Daclatasvir; VEL: Velpatasvir; VOX: Voxilaprevir; GLE: Glecaprevir; PIB: Pibrentasvir; LDV: Ledipasvir; ALV: Alisporivir; OBV: Ombitasvir; PTV/r: Paritaprevir boosted by ritonavir; GZR: Grazoprevir; EBR: Elbasvir; UPR: Uprifosbuvir; RBV: Ribavirin; RZR: Ruzasvir.
Table 2 European Association for the Study of the Liver and American Association for the Study of Liver Diseases/Infectious Diseases Society of America current recommendations on the treatment of genotype 3-infected patients
Recommendations
Genotype/subtype
Cirrhosis status
Prior treatment experience
SOF/VEL
GLE/PIB
SOF/VEL/VOX
GZR/EBR + SOF
European Association for the Study of the Liver[78]GT3No cirrhosisTreatment-naïve12 wk8 wk--
Treatment-experienced12 wk--
Compensated cirrhosisTreatment-naïve12 wk with RBV18-12 wk212 wk-
Treatment-experienced16 wk-
Decompensated cirrhosisTreatment-naïve and experienced12 wk with RBV or 24 wk---
GT3, subtype b, g or any other subtype naturally harbouring one or several NS5A RASs3No cirrhosisTreatment-naïveUnknownUnknown12 wk-
Treatment-experienced-
Compensated cirrhosisTreatment-naïve-
Treatment-experienced-
AASLD/IDSA (Ghany et al[79])GT3No cirrhosisTreatment-naïve12 wk8 wk--
Treatment-experienced12 wk16 wk412 wk4-
SOF + RBV ± PEGIFN-experienced-16 wk12 wk-
DAA-experienced5--12 wk, + RBV for NS5A failures-
Compensated cirrhosisTreatment-naïve12 wk, + RBV for 12 wk48 wk12 wk4-
PEGIFN + RBV-experienced+ RBV for 12 wk416 wk12 wk12 wk4
SOF + RBV ± PEGIFN-experienced-16 wk12 wk-
DAA-experienced5--12 wk, + RBV for NS5A failures-
Decompensated cirrhosisTreatment-naïve and experienced12 wk with RBV or 24 wk---
1If resistance testing is performed, only patients with the nonstructural protein 5A Y93H resistance-associated substitutions at baseline should be treated with sofosbuvir/velpatasvir plus ribavirin or with sofosbuvir/velpatasvir/voxilaprevir, whereas patients without the Y93H resistance-associated substitutions should be treated with sofosbuvir/velpatasvir alone.
2In treatment-naïve patients infected with genotype 3 with compensated (Child-Pugh A) cirrhosis, treatment with glecaprevir/pibrentasvir can be shortened to 8 wk, but more data are needed to consolidate this recommendation.
3As determined by sequence analysis of the nonstructural protein 5A region by means of population sequencing or deep sequencing (cutoff 15%).
4Alternative regimen.
5Including nonstructural protein 5A inhibitors except glecaprevir/pibrentasvir failures. NS5A: Nonstructural protein 5A; SOF: Sofosbuvir; VEL: Velpatasvir; GLE: Glecaprevir; PIB: Pibrentasvir; VOX: Voxilaprevir; GZR: Grazoprevir; EBR: Elbasvir; EASL: European Association for the Study of the Liver; GT: Genotype; RBV: Ribavirin; PEGIFN: Pegylated interferon; DAA: Direct-acting antivirals; AASLD/IDSA: American Association for the Study of Liver Diseases/Infectious Diseases Society of America.