|Year : 2014 | Volume
| Issue : 5 | Page : 490-492
Supervised conventional interferon α2a in combination with ribavirin therapy is the preferred alternative for treatment of chronic hepatitis C
Harmeet Singh Rehan1, Seema Manak1, Madhur Yadav2
1 Department of Pharmacology, Lady Hardinge Medical College and Shrimati Sucheta Kriplani Hospital, New Delhi, India
2 Department of Medicine, Lady Hardinge Medical College and Shrimati Sucheta Kriplani Hospital, New Delhi, India
|Date of Submission||11-Feb-2014|
|Date of Decision||22-Jul-2014|
|Date of Acceptance||10-Aug-2014|
|Date of Web Publication||11-Sep-2014|
Harmeet Singh Rehan
Department of Pharmacology, Lady Hardinge Medical College and Shrimati Sucheta Kriplani Hospital, New Delhi
Source of Support: CCRUM, Department of AYUSH, Ministry of Health
and Family Welfare, Govt. of India., Conflict of Interest: None
Objective: To document the significant sustained virological response with supervised conventional interferon α and ribavirin therapy in hepatitis C virus (HCV)-infected patients, this study was planned.
Materials and Methods: Sixty chronic hepatitis C naive patients were included in this study. Complete blood counts, prothrombin time, ALT, AST, and qualitative HCV RNA were done. Conventional interferon (INF) α2a, 3MIU, S.C and ribavirin 1000 mg PO was given as supervised therapy for 24 weeks in genotype 3 and 48 weeks in genotype 1 and 4 HCV patients. Qualitative HCV RNA was repeated at 12 weeks, 24 weeks for HCV infections with genotype 1, 2, 3 and 4, at 48 weeks for genotype 1 and 4, and thereafter 6 months after completion of treatment. End virological and sustained virological responses were observed.
Results: Out of 60 patients, 55 completed the study. Five patients were lost to follow-up. Overall SVR was seen in 47 patients (85.4%) and 4 patients had relapses.
Conclusion: Significant sustained virological response rates were seen in patients with supervised conventional INF α2a and ribavirin therapy.
Keywords: Conventional interferon, hepatitis C, ribavirin, supervised
|How to cite this article:|
Rehan HS, Manak S, Yadav M. Supervised conventional interferon α2a in combination with ribavirin therapy is the preferred alternative for treatment of chronic hepatitis C
. Indian J Pharmacol 2014;46:490-2
|How to cite this URL:|
Rehan HS, Manak S, Yadav M. Supervised conventional interferon α2a in combination with ribavirin therapy is the preferred alternative for treatment of chronic hepatitis C
. Indian J Pharmacol [serial online] 2014 [cited 2020 Jan 27];46:490-2. Available from: http://www.ijp-online.com/text.asp?2014/46/5/490/140578
| » Introduction|| |
In India, hepatitis C virus (HCV) genotype 3 is the leading cause of hepatitis C, which spreads through blood transfusion, intravenous drug use and use of unsterilized equipments. HCV infection leads to acute hepatitis in 15% of the patients, whereas rest of the patients develops chronic hepatitis, which further progresses to fibrosis, cirrhosis, hepatic malignancy, and liver failure.
The goal of the anti-HCV treatment is to achieve an early and sustained virological response (SVR), prevent the progress of disease and the development of its associated complications. In 2002, National Institute of Health Consensus Guideline for the treatment of HCV infection recommended the weekly injection of pegylated interferon (INF α) in combination with daily oral ribavirin (RBV) which is reported to have better efficacy in terms of achieving SVR, safety profile and convenient to administer than the combination of the thrice weekly conventional INF α2a injection and oral RBV. Convenience of once a week administration of pegylated INF may improve adherence to the treatment.
Diseases which are likely to be deteriorated and/or spread due to non adherence of the treatment have always been an issue of serious concern. To overcome non adherence of the treatment, directly observed therapy short term (DOTs) is a well-practiced strategy to improve the compliance. DOTs have shown overwhelming response in the management of tuberculosis and leprosy. Routine practice of DOTs may improve the outcomes of therapy and minimize/reduce the life-threatening complications. Retrospective analysis of literature encompassing the treatment of HCV infection in Germany, revealed that supervised anti- HCV treatment with INFα2a and RBV improved the efficacy of antiviral therapy, in regular visitors than irregular visitors, due to better compliance. 
In India, the cost of single pegylated INF α injection is almost six times that of the cost of conventional INF α2a injection, which may be one of the limiting factors for the patients to complete their course of treatment especially in poor-resource settings. Considering the importance of early and complete treatment of HCV infection to achieve early and SVR, affordability and adherence to the treatment, it is meaningful to consider directly observed conventional thrice a week interferon α therapy. Therefore, this work was planned to study the effect of combination of thrice a week conventional interferon α2a and ribavirin on early and SVR and to compare these outcomes with that of pegylated interferon base therapy as reported in the literature.
| » Materials and Methods|| |
An open label, prospective study was conducted on interferon naive HCV-RNA positive with any genotype patients of either sex with age between 18-60 years. Patients above 60 years or less than 18 years, those with decompensated liver disease, creatinine levels above 150 μmol/L, hemoglobin levels below 10 gm/dl, white blood cell count below 3 × 10 9 /L; or platelet count below 1 × 10 11 /L, those with a history of varices, ascites, and/or encephalopathy were excluded from the study.
Study protocol was approved by Institutional Ethics Committee. After taking the informed consent, 60 enrolled patients were treated with conventional INF α2a (3 MIU, subcutaneously, thrice weekly) and RBV (1000 mg, PO, daily, in two divided doses). Injection of conventional INF α2a was administered thrice weekly as supervised therapy in the hospital along with the morning dose of RBV (200 mg, 2 tablets) by one of the investigators. Patients were advised to take the remaining doses of ribavirin themselves unsupervised at home. Importance of adherence was explained to all the patients. Compliance to ribavirin tablets was assessed by counting remaining medicines and inspecting empty rappers at every visit.
Duration of treatment for HCV infection with genotype 1 and 4 was 48 weeks and with genotype 2 and 3 was 24 weeks. After completion of treatment all the patients were followed for a period of 24 weeks.
To assess the primary outcome, HCV RNA levels were repeated at 12 weeks, 24 weeks for HCV infections with genotype 1, 2, 3 and 4, at 48 weeks for genotype 1 and 4, and thereafter 6 months after completion of treatment. Early virological response (EVR) was considered complete (cEVR) when HCV RNA was undetectable in the blood at 12 weeks of treatment and was considered partial when HCV RNA drops by more than 2 logs (100 times) from the baseline level by week 12 (pEVR). End of treatment response (EOTR) was defined when HCV RNA undetectable in the blood at the end of treatment and in SVR, HCV RNA were undetectable after six months of treatment. All these parameters were estimated.
| » Results|| |
Of the total 60 patients of chronic hepatitis C (CHC) enrolled, only 55 patients completed the study and follow-up. Five patients were lost to the follow-up due to their personal reasons. HCV genotype 3 was found to be the most common genotype (72.7%) followed by genotype 1 (18.1%) and genotype 4 (9%). Overall
complete EVR (cEVR) that is including all genotype patients was achieved in 48 (87.2%) of HCV patients. cEVR was 60% in genotype 1; 95% in genotype 3 and 80% in genotype 4 of HCV patients. Partial EVR was achieved in 1 (1.8%) of HCV patient with genotype 1.
Overall EOTR was obtained in 51 (92.7%) of HCV patients. EOTR was 80%, 95% and 100% respectively in genotype 1, genotype 3 and genotype 4 patients. Two patients each with genotype 1 and 3 were non-responders.
Overall 47 (85.4%) patients showed SVR, where as SVR in genotype 1, genotype 3 and genotype 4 patients was 70%, 87.5%, and 100% respectively. Three patients with genotype 3 (7.5%) and one with genotype 1 (10%) experienced a relapse during the follow-up that is after the end of the treatment. [Table 1] All the patients had 100% compliance to the supervised injection of conventional INF. With ribavirin compliance was seen in 86% patients and rest of the patients averagely missed 5 doses every month.
|Table 1: HCV patients showing distribution of genotype, complete early virological response, partial early virological response, end of treatment response and sustained virological response, relapse and non responders|
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| » Discussion|| |
In the recent past, therapy of HCV infection has evolved from conventional INF α2a alone to combination therapy with ribavirin. Monotherapy of HCV infection with genotype 2 and 3 and 1 and 4 with conventional INF-α for 24-48 weeks treatment could achieve SVR in only 20-25% of patients , where as combination of conventional INF-α with ribavirin has been demonstrated to be more efficacious than monotherapy with INF α. , Introduction of pegylated INF α has further enhanced the efficacy, tolerability and reduction in disease-related complications over conventional INF. 
Results of the present study showed an overall SVR in 85.4% of the HCV patients treated with directly observed conventional INF α with RBV combination therapy. Several other studies of non-observed conventional INF α and RBV combination have reported an overall SVR varying between 71% and 87% at the end of 24 weeks treatment. , On the contrary, use of pegylated INF α and ribavirin combination reported overall SVR ranging between 54-56%, , which was lower than that observed in our study with supervised conventional INF α2a and RBV therapy. This difference in overall SVR could be due to the reason that majority of the HCV patients in their studies had genotype 1, whereas in our study majority of the patients had HCV genotype 3 infection. [Table 1] HCV genotype 2 and 3 is known to respond better to the antiviral therapy than genotype 1 and 4.  In our study, observed conventional antiviral therapy in genotype 3 HCV patients exhibited the SVR in 87.5% of the patients, which was superior to the non-observed conventional INF α and RBV-based therapy (SVR, 75%) for genotype 2 and 3 patients.  Even the SVR in this study was found better than non-observed pegylated INF α and ribavirin treatment for HCV genotypes 1 and 4, and 2 and 3 patients (SVR ranging between 50-85%). , On the contrary, in a cohort type of case series study, unsupervised pegylated INF and RBV (SVR, 90.19%) was found superior to conventional INFα and RBV (SVR, 72.93%) regimen in HCV genotype 2 and 3 patients,  which was inferior to our study. Outcomes of present study were either superior and/or comparable to the pegylated INF and RBV combination studies available in
the literature. Such effect of conventional INF and RBV therapy was probably due to the administration of treatment under supervision and free of cost. The counseling of the patients on the importance of treatment and compliance, done at every visit, probably also improved the outcome of conventional INF and RBV combination therapy. The benefits of directly observed therapy and adherence to anti HCV treatment have been associated to achieve better viral response and lesser dropouts. , Though few studies advocated marginally better efficacy and convenience of weekly administered pegylated INF, , it is associated with high cost, which may be one of the limiting factors for adherence to treatment. Michael et al. have concluded in the systemic review that high cost of treatment directly decreases the adherence to therapy thereby affecting the outcome of the therapy.  On the other hand, low cost of conventional INF is an affordable alternative to the more expensive pegylated INF therapy for developing countries. ,
To conclude, pegylated INF with ribavirin is the recommended treatment for HCV infection. Pegylated INF is more expensive than the conventional INF, which makes it unaffordable to the HCV patients with poor socio-economic status. As a result, the underlying condition is left untreated with development of life-threatening complications. Hence supervised conventional INF thrice a week with ribavirin may be considered to prevent long-term mortality due to HCV infection.
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