Introduction
Interferon supersensitive group
Some viral and host factors are related to supersensitivity to the interferon-based therapy
#1 Consensus statements and recommendation on interferon supersensitive group
Is interferon still needed in DAA affordable countries?
ALL-oral treatment for HCV GT-1 infection
Ledipasvir and sofosbuvir
Treatment-naïve HCV GT-1 patients
Treatment-experienced HCV GT-1 patients
Paritaprevir/ritonavir and ombitasvir
Companies (regimen) [references] | Drug targets | Ribavirin | Duration of treatment (weeks) | SVR (%) | ||
---|---|---|---|---|---|---|
NS3/4A protease | NS5A | NS5B | ||||
– | Ledipasvir (90 mg daily) | Sofosbuvir (400 mg daily) | ± | 12 | 93–100 | |
Abbvie (2D) [57] | Paritaprevir (150 mg daily)/ritonavir (100 mg daily) | Ombitasvir (25 mg daily) | – | ± | 12 | 89–100 |
Paritaprevir (150 mg daily)/ritonavir (100 mg daily) | Ombitasvir (25 mg daily) | Dasabuvir (500 mg daily) | ± | 12 | 90–100 | |
Asunaprevir (200 mg daily) | Daclatasvir (60 mg daily) | – | – | 24 | 81–91 | |
Bristol-Myers Squibb (3D) [64] | Asunaprevir (200 mg daily) | Daclatasvir (60 mg daily) | BMS-791325 (75 or 150 mg daily) | – | 12 or 24 | 89–94 |
MSD [65] | Grazoprevir (MK-5172) (100 mg daily) | Elbasvir (MK-8742) (50 mg daily) | – | – | 12 | 90–100 |
Paritaprevir/ritonavir, ombitasvir and dasabuvir
Asunaprevir and daclatasvir
Asunaprevir, daclatasvir and BMS-791325
Grazoprevir (MK-5172) and elbasvir (MK-8742)
Future perspectives of chronic HCV GT-1 patients in Asian countries
#2 Consensus Statements and Recommendation on all-oral treatment for HCV GT-1 infection
All-oral treatment for HCV GT-2 and GT-3 infection
HCV GT-2
Companies (regimen) [references] | Drug targets | Ribavirin | Duration of treatment (weeks) | SVR (%) | |
---|---|---|---|---|---|
NS5A | NS5B | ||||
Sofosbuvir (400 mg daily) | + | 12 | 88–100 | ||
Bristol-Myers Squibb [73] | Daclatasvir (60 mg daily) | Sofosbuvir (400 mg daily) | ± | 24 | 96 |
Gilead Sciences [74] | Ledipasvir (90 mg daily) | Sofosbuvir (400 mg daily) | – | 12 | 96 |
Gilead Sciences [75] | Velpatasvir (GS-5816) (25 or 100 mg) | Sofosbuvir (400 mg daily) | – | 12 | 25 mg: 91 100 mg: 100 |
HCV GT-3
Companies (regimen) [references] | Drug targets | Ribavirin | Duration of treatment (weeks) | SVR (%) | |
---|---|---|---|---|---|
NS5A | NS5B | ||||
Sofosbuvir (400 mg daily) | + | 12 or 24 | 12 weeks Non-cirrhotic: 61–68 F4: 21–34 24 weeks Non-cirrhotic: 94 F4: 92 | ||
Bristol-Myers Squibb [76] | Daclatasvir (60 mg daily) | Sofosbuvir (400 mg daily) | – | 12 | Non-cirrhotic: 97 F4: 58 |
Companies (regimen) [references] | Drug targets | Ribavirin | Duration of treatment (weeks) | SVR (%) | |
---|---|---|---|---|---|
NS5A | NS5B | ||||
Sofosbuvir (400 mg daily) | + | 16 or 24 | 16 weeks Non-cirrhotic: 63 F4: 61 24 weeks Non-cirrhotic: 87 F4: 60 |
#3 Consensus statements and recommendation on all-oral treatment for HCV GT-2 and GT-3 infection
PAN-oral therapy for HCV GT-4, GT-5 and GT-6 infection
Current clinical data with registered agents
Genotype | Company | Regimen | Non-cirrhotic (LSM < 14.7 kPa) | Cirrhotic (LSM ≥ 14.7 kPa) |
---|---|---|---|---|
SVR12 (%)/number of treated patients | ||||
GT-4 | AbbVie | Ombitasvir plus paritaprevir, 12 weeks | 91 % (41/44, treatment-naïve) [81] | No data available |
Ombitasvir plus paritaprevir plus RBV, 12 weeks | 100 % (42/42, treatment-naïve or experienced) [81] | No data yet (study is on-going) | ||
Gilead | Ledipasvir and sofosbuvir (Harvoni™), 12 Weeks | 95 % [19/20, treatment-naïve (62 %) or experienced (38 %)] [80] | No data available | |
Sofosbuvir plus velpatasvir | 100 % (116/116, Sofosbuvir plus velpatasvir 12 weeks) [ASTRAL-1 study] [86] | 83 % (75/90, GT1-6, Sofosbuvir plus velpatasvir 12 weeks) [ASTRAL-4 study] [86] 94 % (82/87, GT1-6, Sofosbuvir plus velpatasvir plus ribavirin (RBV) 12 weeks) [ASTRAL-4 study] [86] 86 % (77/90, GT1-6, Sofosbuvir plus velpatasvir 24 weeks) [ASTRAL-4 study] [86] | ||
MSD | Grazoprevir plus elbasvir | 100 % (18/18) [253] | ||
GT-5 | Gilead | Sofosbuvir plus velpatasvir | 97 % (34/35, Sofosbuvir plus velpatasvir 12 weeks) [ASTRAL-1 study] [86] | 83 % (75/90, GT1-6, Sofosbuvir plus Velpatasvir 12 weeks) [ASTRAL-4 study] [86] 94 % (82/87, GT1-6, Sofosbuvir plus Velpatasvir plus RBV 12 weeks) [ASTRAL-4 study] [86] 86 % (77/90, GT1-6, Sofosbuvir plus Velpatasvir 24 weeks) [ASTRAL-4 study] [86] |
GT-6 | Gilead | Ledipasvir and sofosbuvir (Harvoni™) | 96 % [24/25, treatment-naïve: 23 (92 %); experienced:2 (8 %); Cirrhosis: (8 %)] [80] | |
Sofosbuvir plus velpatasvir | 100 % (41/41, Sofosbuvir plus velpatasvir 12 weeks) [ASTRAL-1 study] [86] | 83 % (75/90, GT1-6, Sofosbuvir plus velpatasvir 12 weeks) [ASTRAL-4 study] [86] 94 % (82/87, GT1-6, Sofosbuvir plus velpatasvir + RBV 12 weeks) [ASTRAL-4 study] [86] 86 % (77/90, GT1-6, Sofosbuvir plus velpatasvir 24 weeks) [ASTRAL-4 study] [86] |
Emerging clinical study
#4 Consensus statements and recommendation on all-oral treatment for HCV GT-4 infection
#5 Consensus statements and recommendation on all-oral treatment for HCV GT-5 and GT-6 infection
Generic licensing of all-orals in Pakistan
New DAA in Egypt: the licensing scenario
-
Other approved treatment options for HCV GT-4 as, LEDIPASVIR/SOFOSBUVIR “Harvoni”, Daklatasvir and Viekirax [92] will soon be available.
-
The National Committee for Control of Viral Hepatitis (NCCVH), finalized the regulations for using these new brands. This current phase of the national program to treat HCV in Egypt was preceded by a state announcement that has been spread in all Egyptian media, starting from September 2014, requesting all Egyptian patients known to have HCV with advanced liver disease to register on the website, www.nccvh.org.e.g.
-
Electronic replies to patients were used to fix individual appointment dates and referred to a center where each patient has to be assessed for legibility to use the new treatment protocols.
-
By September 18 2014, 180,000 Egyptians have registered on the website, with 10 % of those registered living outside Egypt. By March 2015, 850,000 patients in total were already registered and processed through the website.
-
Thirty-four governmental centers are currently participating in the project. The number is increasing monthly to cover all governorates.
-
The first doses were distributed starting October 20 2014 and 25,000 patients had been treated by March 2015. It is planned that more than 250,000 patients yearly would receive the new treatment protocols. The same rules will be applied for all patients regardless of the source of payment, and there will be no place for patients’ preferences in deciding the treatment regimen.
-
Treatment in its first phase included only cases with F2, F3, F4, or compensated cirrhosis, excluding cases with decompensation or with HCC patients except after successful radical curative intervention (4 months after resection or successful local ablation) evident by triphasic CT.
-
The presence of large risky esophageal varices, required prophylactic management before being treatment-eligible.
-
Age limits for treatment eligibility fixed to be above 18 years and below 70 years for all patients while body mass index (BMI) will be accepted up to 35.
-
For special population groups; priority for treatment will be offered for post-liver transplantation, post-kidney transplantation patients and combined HCV/HBV infection regardless of the fibrosis stage. Other groups such as pediatric age groups and kidney disease patients will be reviewed following the availability of sufficient data. Patients with documented extra-hepatic manifestations will be prioritized for treatment according to the same guidelines.
-
Treatment-experienced patients should only start 6 months after cessation of the previous therapy.
-
No differentiation in treatment priority will be established based on the previous treatment experience.
-
Sofosbuvir (nucleotide polymerase inhibitor) was introduced in the national treatment program through 2 treatment options:
-
The increasing number of reports that treatment with the new DAAs are well tolerated and efficacious in patients with decompensated cirrhosis and, more importantly, markers of hepatic and synthetic function improved during the short-term follow-up [94, 95], will be reviewed. The inclusion of these cases in the national program will be considered during the next phases of the national treatment program.
-
In the new era of the DAAs, in addition to increased treatment efficacy with SVR more than 90 %, by increasing cases detection and reducing new infections, according to a mathematical modeling, the government strategy is to achieve <2 % prevalence by 2025 and >90 % drop in prevalence by 2030 (near-total HCV elimination) [96].
Results
Treatment responders (n = 798) | Treatment non-responders (n = 9) |
p value | |
---|---|---|---|
Gender | |||
Male | 548 | 5 | 0.47 |
Female | 250 | 4 | |
Age (mean ± SD) | 53 ± 8 | 57 ± 6 | 0.16 |
Treatment status | |||
Naïve | 540 | 3 | 0.07* |
Experienced | 258 | 6 | |
Baseline laboratory values (mean ± SD) | |||
Hemoglobin | 13.4 ± 1.7 | 13.3 ± 1.6 | 0.82 |
WBCs | 5.8 ± 4 | 5.1 ± 2 | 0.66 |
Platelets | 129 ± 66 | 133 ± 92 | 0.88 |
Albumin | 3.8 ± 0.7 | 3.8 ± 0.8 | 0.87 |
Viremia (log10) | 5.5 ± 1 | 5.5 ± 0.7 | 0.98 |
Fibrosis assessment | |||
FIB-4 median (IQR) | 4.34 (4.2) | 6.6 (4.5) | 0.23 |
Fibrosis grading (n = 257) F2/F3/F4 | 2/171/84 | 1/2/0 | <0.01* |
Child score | |||
Non cirrhotic/A/B | 535/226/37 | 3/4/2 | 0.08/0.46 |
Regimen type | |||
Dual | 452 | 6 | 0.79 |
Triple (Roch/MSD) | 346(198/148) | 3(2/1) | 0.36 |
Abdominal U/S | |||
Liver cirrhosis | 482 | 5 | 0.96 |
Ascites | 17 | 0 | 0.47 |
Sponsorship | |||
Governmental | 715 | 5 |
#6 Consensus statements and recommendation on generic licensing of all-orals in Egypt
Generic licensing of all-orals in Indonesia
DAA in Indonesia
#7 Consensus statements and recommendation on generic licensing of all-orals in Indonesia
HCV infection in patients with hepatic decompensation, liver transplant candidates and recipients
#8 Consensus statements and recommendation on decompensated liver disease
#9 Consensus statements and recommendation on awaiting liver transplant
#10 Consensus statements and recommendation on following liver transplant
SVR for renal failure and co-infection with HBV/HIV
SVR for HCV infection in patients with renal failure
#11 Consensus statements and recommendation on HCV and CKD
SVR for HCV co-infection with HIV
#12 Consensus statements and recommendation on HCV and HIV co-infection
SVR for HCV co-infection with HBV
#13 Consensus statements and recommendation on HCV and HBV co-infection
Grading | TN/TE-PR
| TE-NS3/4A inhibitor
| TE-NS5A inhibitor
| |||
---|---|---|---|---|---|---|
Non-cirrhosis/cirrhosis | Non-cirrhosis/cirrhosis | Non-cirrhosis | Cirrhosis | |||
(A) GT-1 | ||||||
A1 | SOF/LDV for 12 weeks | SOF/LDV for 12 weeks | ||||
(GT-1b) PrOD for 12 weeks | ||||||
(GT-1b) GZR/EBR for 12 weeks | ||||||
A2 | (GT-1b and RAV Check) ASN/DCV for 24 weeks | |||||
C1 | Wait | RAV check |
Grading | TN | TE-PR
| ||
---|---|---|---|---|
Non-cirrhosis | Cirrhosis | Non-cirrhosis | Cirrhosis | |
(B) GT-2 | ||||
A1 | SOF/RBV for 12 weeks | SOF/RBV for 12 weeks | SOF/RBV for 12 weeks | SOF/RBV for 12 weeks |
A1 | SOF/RBV for 16-24 weeks | |||
B1 (for RBV-intolerant) | SOF/DCV for 24 weeks SOF/LDV for 12 weeks SOF/VEL for 12 weeks | SOF/DCV for 24 weeks SOF/LDV for 12 weeks SOF/VEL for 12 weeks | SOF/DCV for 24 weeks SOF/LDV for 12 weeks SOF/VEL for 12 weeks | SOF/DCV for 24 weeks SOF/LDV for 12 weeks SOF/VEL for 12 weeks |
Grading | TN | TE-PR
| ||
---|---|---|---|---|
Non-cirrhosis | Cirrhosis | Non-cirrhosis | Cirrhosis | |
(C) GT-3 | ||||
A1 | SOF/RBV for 24 weeks | SOF/RBV for 24 weeks | SOF/RBV for 24 weeks | SOF/RBV for 24 weeks |
A2 | SOF/DCV for 12 weeks | SOF/DCV ± RBV for 24 weeks | SOF/DCV for 12 weeks | |
B2 | SOF/RBV for 16 weeks | SOF/DCV/RBV for 24 weeks |
Grading | Non-cirrhosis | Cirrhosis |
---|---|---|
(D) GT-4 | ||
A1 | SOF/LDV for 12 weeks SOF/VEL for 12 weeks | SOF/LDV for 24 weeks |
B1 | PrO/RBV for 12 weeks | PrO/RBV for 24 weeks SOF/VEL for 24 weeks |
B2 | SOF/DCV/RBV for 12 weeks SOF/DCV for 24 weeks | |
(E) GT-5/GT-6 | ||
A1 | SOF/VEL for 12 weeks | |
B1 | SOF/LDV for 12 weeks | SOF/DCV for 12 or 24 weeks |
B1 | SOF/LDV for 12 weeks | SOF/LDV for 12 or 24 weeks |
B1 | SOF/VEL for 12 weeks |