Saudi Journal of Gastroenterology
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Table of Contents   
LETTER TO EDITOR  
Year : 2015  |  Volume : 21  |  Issue : 4  |  Page : 260-261
Ribavirin-free treatment may soon be a reality


Department of Medicine, Multi-Organ Transplant Unit, Western University, London, Ontario, Canada; Department of Medicine, Division of Gastroenterology, King Saud University, Riyadh, Saudi Arabia

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Date of Web Publication29-Jul-2015
 

How to cite this article:
Al-Judaibi B. Ribavirin-free treatment may soon be a reality. Saudi J Gastroenterol 2015;21:260-1

How to cite this URL:
Al-Judaibi B. Ribavirin-free treatment may soon be a reality. Saudi J Gastroenterol [serial online] 2015 [cited 2019 Aug 18];21:260-1. Available from: http://www.saudijgastro.com/text.asp?2015/21/4/260/161633


Sir,

I read with great interest the recent SASLT statement on the direct-acting antiviral agents (DAA) for the treatment of hepatitis C virus (HCV) infection that was published in this journal.[1] The panel of experts stated that all DAAs listed in their table are equally efficacious for the management of HCV patients. However, some of these regimens have different sustained virological response (SVR) rates among different genotypes.

The panel of experts recommended sofosbuvir and ledipasvir in combination with ribavirin (RBV) for 12 weeks in naïve cirrhotic patients or for 24 weeks among null responder cirrhotics. This combination has been evaluated in HCV genotype (GT) 1 cirrhotic patients in ION-1 and ION-2 studies.[2] Treatment-naïve or treatment-experienced patients with cirrhosis were randomly assigned to 12 or 24 weeks of sofosbuvir/ledipasvir with or without RBV. Among treatment-experienced cirrhotic patients, SVR rate after 24 weeks of therapy was higher than the SVR rate after 12 weeks of therapy (100% vs. 86%), without a clear benefit of the use of RBV. However, in a subsequent larger study (SIRIUS) in treatment-experienced cirrhotic GT1 patients,[3] participants were randomized to 24 weeks of sofosbuvir/ledipasvir or 12 weeks with the addition of RBV. The SVR rates were similar in both groups. Therefore, the 12-week regimen with RBV can be used as an alternative option to 24 weeks of sofosbuvir/ledipasvir in treatment-experienced GT1 patients.

Another recommendation was sofosbuvir and simeprevir for 12 weeks in combination with RBV. In the COSMOS study, treatment-naïve or treatment-experienced cirrhotic HCV GT1 patients received this combination with or without RBV for 12 or 24 weeks.[4] The SVR rate ranged from 79 to 100%, without a clear benefit of the extended therapy or the use of RBV. Therefore, RBV has not been recommended with this combination. Likewise, this combination might be very effective in managing patients with HCV GT4. However, there is a lack of data to support the use of this combination in these patients. On the other hand, the combination of sofosbuvir and RBV was evaluated among treatment-naïve or treatment-experienced cirrhotics with GT4. Patients were randomly assigned to 12 or 24 weeks of therapy. Indeed, cirrhotics benefited from prolonged therapy; the SVR rate was 67% in the group treated for 12 weeks compared to 100% in the group treated for 24 weeks. However, the SVR rate was lower in treatment-experienced cirrhotic patients: 60% in the 12-week treatment group and 67% in the 24-week treatment group.[5] Also, the 12-week regimen of sofosbuvir/ledipasvir has been evaluated in GT4 patients. The SVR rate was 95% based on 21 patients (38% treatment-experienced; 40% with cirrhosis). Due to the small sample size, more studies are required to validate this combination among cirrhotic HCV GT4 patients.

Next, the panel of experts recommended paritaprevir, ritonavir, ombitasvir, dasabuvir, and RBV for 12 weeks (F3, GT4) or 24 weeks (GT4, cirrhosis). This regimen has been evaluated in treatment-naïve and treatment-experienced non-cirrhotics with HCV GT4.[6] Therefore, future studies are required to assess the safety and efficacy of this regimen among cirrhotics with GT4.

The expert panel also recommended daclatasvir and sofosbuvir in combination with RBV for 12 weeks for treatment-naïve or for 24 weeks for treatment-experienced cirrhotics. This regimen has been evaluated in treatment-naïve and treatment-experienced HCV GT1 patients.[7] Cirrhotic patients were excluded from the study. The SVR rate was 98% in both groups, without clear benefit of the use of RBV.

In the ALLY-3 study, treatment-naïve or treatment-experienced patients with HCV GT3 received 12-week regimen of daclatasvir and sofosbuvir, and 19 (19%) patients in the treatment-naïve group and 13 (25%) patients in the treatment-experienced group had cirrhosis. The SVR rate was higher in non-cirrhotics compared to cirrhotics (96% vs 63%). In this study, the addition of RBV or the extension of duration of therapy was not explored. Therefore, a larger sample size with a longer duration of treatment is required in cirrhotic GT3 patients.

Finally, the expert panel failed to mention that sofosbuvir and RBV is a therapeutic option, especially in prioritized patients with HCV GT2. In the VALENCE study, treatment-naïve or treatment-experienced GT2 patients received 12-week regimen of sofosbuvir and RBV. The SVR rate ranged from 97 to 100% in the treatment-naïve patients. However, the SVR rate was lower in treatment-experienced cirrhotics (88%).[8]

In conclusion, the new DDAs are very effective and well tolerable even in patients with advanced liver disease. Multiple IFN-free regimens are available, including regimens for difficult-to-treat patients, with an excellent SVR rate. However, access to these therapies is quite limited by cost, although market competition will eventually drive down the costs.



 
   References Top

1.
Alghamdi AA, Alqutub A, Abaalkhail F, Sanai FM, Alghamdi H, Altraif I, et al. SASLT position statement on the direct-acting antiviral agents for the treatment of hepatitis C virus infection. Saudi J Gastroenterol 2015;21:60-3.  Back to cited text no. 1
[PUBMED]  Medknow Journal  
2.
Afdhal N, Reddy KR, Nelson DR, Lawitz E, Gordon SC, Schiff E, et al.; ION-2 Investigators. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med 2014;370:1483-93.  Back to cited text no. 2
    
3.
Bourlière M, Bronowicki JP, de Ledinghen V, Hézode C, Zoulim F, Mathurin P, et al. Ledipasvir-sofosbuvir with or without ribavirin to treat patients with HCV genotype 1 infection and cirrhosis non-responsive to previous protease-inhibitor therapy: A randomised, double-blind, phase 2 trial (SIRIUS). Lancet Infect Dis 2015;15:397-404.  Back to cited text no. 3
    
4.
Lawitz E, Sulkowski MS, Ghalib R, Rodriguez-Torres M, Younossi ZM, Corregidor A, et al. Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: The COSMOS randomised study. Lancet 2014;384:1756-65.  Back to cited text no. 4
    
5.
Doss W, Shiha G, Hassany M, Soliman R, Fouad R, Khairy M, et al. Sofosbuvir Plus ribavirin for treating Egyptian patients with hepatitis C genotype 4. J Hepatol 2015. [Epub ahead of print].  Back to cited text no. 5
    
6.
Pol S, Reddy KR, Hezode C, Hassanein T, Marcellin P, Berenguer M, et al. Interferon-free Regimens of Ombitasvir and ABT-450/r with or without Ribavirin in Patients with HCV Genotype 4 Infection: PEARL-I Study Results. 65th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). Vol. 60. Boston, MA: American Association for the Study of Liver Diseases (AASLD); 2014. p. 1129A.  Back to cited text no. 6
    
7.
Sulkowski MS, Gardiner DF, Rodriguez-Torres M, Reddy KR, Hassanein T, Jacobson I, et al.; AI444040 Study Group. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med 2014;370:211-21.  Back to cited text no. 7
    
8.
Zeuzem S, Dusheiko GM, Salupere R, Mangia A, Flisiak R, Hyland RH, et al.; VALENCE Investigators. Sofosbuvir and ribavirin in HCV genotypes 2 and 3. N Engl J Med 2014;370:1993-2001.  Back to cited text no. 8
    

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Correspondence Address:
Bandar Al-Judaibi
Department of Medicine, Multi-Organ Transplant Unit, Western University, London, Ontario, Canada; Department of Medicine, Division of Gastroenterology, King Saud University, Riyadh, Saudi Arabia

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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1319-3767.161633

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