Background: To evaluate the safety and effectiveness of locally produced pegylated interferon-a2a in treatment-naïve patients with chronic hepatitis C.Methods: All treatment-naïve patients diagnosed with chronic hepatitis C who referred to two university based outpatient clinics in Tehran from December 2007 to May 2008 were enrolled. Exclusion criteria included the presence of a debilitating disease, decompensated cirrhosis, or refusal to participate in the study. Patients were treated with 180 mg pegylated interferon-a2a (Pegaferon) weekly and 800-1200 mg ribavirin daily for 24 or 48 weeks depending on genotype and weight. Viral and biochemical response and adverse drug reactions were recorded.Results: A total of 108 patients were enrolled; 63 with genotype 1 and 45 with genotypes 2 and 3. The mean age of the patients was 39 years (range: 19-65). Ninety-seven patients completed the study and 76 achieved sustained viral response. The sustained viral response among patients completing the study was 67% for genotype 1 and 95% for genotypes 2 and 3. Adverse events were well tolerated and none led to discontinuation of treatment, however dose adjustment was necessitated in 16 patients. The most common adverse events were fatigue (73.5%), poor appetite (66.2%), and feverishness (57.4%). The mean hemoglobin drop was 2.9 g/dL.Conclusions: Locally produced PEG-IFN in Iran is safe and effective in treatment-naïve chronic hepatitis C. Clinical Trials. gov identifier: NCT01137383

Background: Hepatitis C virus (HCV) infection is the most common transfusion transmitted disease in poly-transfused patients worldwide. In this study we aimed to evaluate the effects of pegylated interferon alfa-2a (PEG-IFN A-2a) in reducing serum ALT and eradicating serum hepatitis C virus (HCV) RNA in HCV infected polytransfused thalassemic patients.Materials and Methods: A cohort of 51 HCV-RNA positive thalassemic patients was enrolled to our study and received 180 mg PEG-IFN A-2a once-weekly for 48 weeks. The primary end point was sustained virological response (SVR). The secondary outcome was normalization of ALT. Patient safety was assured by monthly, and if needed, weekly laboratory assessment and visits.Results: Of 52 patients, 42 participants completed the treatment schedule. A sustained virological response (SVR) was attained in 22/51 (43%) cases. Among non-responders or relapsers to previous HCV antiviral therapy, 9/27 (33%) attained an SVR. Five patients died during treatment and 3 subjects discontinued the therapy because of adverse effects. Adverse events were generally mild, and laboratory abnormalities were rare.Conclusion: A course of 48-week PEG-IFN A-2a monotherapy is effective in eradicating HCV-RNA during treatment. But about one third of thalassemic patients would relapse within 6 months of treatment schedule completion, in whom combination therapy is needed.

Background: Despite significant advances in the treatment of chronic hepatitis C in the past decades, factors which can affect response rates to combination therapy; peginterferon and ribavirin, are still under study and reaching sustained virological response (SVR) is affected by several different factors.Objectives: To investigate predictor factors contributing to SVR in Iranian patients.Patients and Methods: The present non-randomized, clinical trial was conducted on 100 patients referred to the Tehran Hepatitis Center in 2009-2011. The patients were administered combined peginterferon a-2a-ribavirin treatment, based on the standard protocol of the Iranian Ministry of Health. At the end of the treatment, the SVR rate and predictors were evaluated.Results: The mean age of the patients was 42 and 78% were male. Genotype 1a was the most common (70%) and 55% of patients were treatment naive. The outcomes showed that 12%, 16% and 22% patients were; non-responders, breakthroughs and relapsers, respectively, while 50% of the patients reached SVR. Patients reaching SVR were aged 40 years or lower, they were less likely to have been a non-responder in prior treatments, more likely to have a non-1a genotype and a higher number had an HCV RNA of less than 600 000 IU/ml. The multivariate analysis showed that an age of 40 or lower (OR=3.74, CI95%=1.52-9.22), a non-1a genotype (OR=3.71, CI 95%=1.40-9.81) and an HCV RNA less than 600 000 IU/ml (OR=2.52, CI 95%=1.03-6.15) may be useful SVR predictors.Conclusions: The findings of the present study showed that half of the patients reached SVR through combined peginterferon a-2a and ribavirin treatment, the majority of whom had genotype 3a and a minority had genotype 1a. In addition, an age of 40 or lower, non-1a genotype and a viral load less than 600 000 IU/ml were strong SVR predictors

Background: Most thalassemic patients with chronic hepatitis C virus (HCV) infection do not respond to therapy with pegylated interferon (Peg-IFN) plus ribavirin (RBV) due to hepatic siderosis and RBV dose reduction caused by RBV-induced anemia.Objectives: In the present study, we recruited HCV genotype 1-infected thalassemic patients who had relapsed after a 48-week treatment with Peg-IFN plus RBV in order to evaluate the efficacy of a 72-week regimen of Peg-IFN plus RBV.Patients and Methods: In this retrospective study, 23 thalassemic patients with HCV genotype 1 infection who had prior relapse after treatment with Peg-IFN and RBV for 48 weeks were consecutively enrolled in this study for evaluation of the efficacy of a 72-week treatment regimen.Results: For the 21 included cases, mean age was 29.7 years; 81% were men and 28.6% had cirrhosis. At the end of the treatment, nine (42.9%) patients had an undetectable level of HCV RNA in their sera. However, six months after treatment completion four of these patients relapsed and a sustained virological response (SVR) was found in five (23.8%) patients. Undetectable HCV RNA level at week 4 (P=0.03) and undetectable HCV RNA level at week 12 (P<0.01) were found to be predictors of SVR. There was an average 47.9% increase in blood transfusion during therapy and treatment was discontinued for 12 (57.1%) patients prematurely.Conclusions: The present study suggests that thalassemic patients with chronic hepatitis C genotype 1 infection who did not achieve SVR after a course of therapy with Peg-IFN and RBV may benefit from being retreated with a 72-week regimen.

Background: Treatment guidelines contraindicate ribavirin for treatment of hepatitis C virus (HCV) infection in thalassemia major patients. nevertheless, the current evidence suggests that ribavirin might be tolerated by these patients.Objectives: Despite this evidence, low dose ribavirin combination therapy has not been compared with peginterferon monotherapy in these patients so far.Patients and Methods: Two hundred eighty thalassemia patients with detectable HCVRnA PCR ( ³ 50 IU/mL) and liver histology consistent with chronic HCV infection were selfassigned to receive peginterferon alfa-2a (n = 81) monotherapy or its combination therapy with ribavirin, 600-800 mg QD, according to hemoglobin levels (n = 199). Treatment experienced patients were eligible for this study.Results: Sustained virological response (SVR) was significantly higher in patients who received ribavirin (51 % vs. 38 % P = 0.02). In multivariate regression, oR of ribavirin for prediction of SVR was 2.2 (95 % CI 1.24-3.91). The SVR was significantly higher in the ribavirin group in subgroups of patients with more than 24 years of age, elevated ALT, ferritin < 2006 ng/ mL, previous treatment failure, genotype 1, positive history of splenectomy, fibrosis score of 0-4 HAI and viral load < 600,000 IU/mL. Treatment discontinuations due to the safety concerns were comparable between the treatment groups (6.5 and 8 %). Furthermore, transfusion intervals were almost halved in patients who received low dose ribavirin.Conclusions: According to the present study, adult thalassemia patients with HCV infection can be treated successfully with low dose ribavirin. Hence, we strongly advise combination therapy in thalassemia patients with aforementioned clinical characteristics. Moreover, ribavirin does not seem to be beneficial in thalassemia patients below 18 years of age.

Background: The prevalence of hepatitis C in Iran is 1% and 18% in general population and thalassemia patients respectively. The cost effectiveness analysis of adding Ribavirin to Peginterferon alfa-2a (PEG IFN alfa-2a) as a combination treatment strategy of chronic hepatitis C in thalassemia patients in comparison with monotherapy could help clinicians and policy makers to provide the best treatment for the patients.Objectives: In this study we aimed to assess whether adding Ribavirin to PEG IFN alfa-2a is a cost effective strategy in different genotypes and different subgroups of 280 patients with chronic hepatitis C infection from the perspective of society in Iranian setting.Patients and Methods: A cost effectiveness analysis including all costs and outcomes of treatments for chronic hepatitis C infected thalassemia major patients was conducted. We constructed a decision tree of treatment course in which a hypothetical cohort of 100 patients received “PEG IFN alfa-2a” or “Peg IFN alfa-2a plus Ribavirin.” The cost analysis was based on cost data for 2008 and we used 9300 Iranian Rials (IR Rial) as exchange rate declared by the Iranian Central Bank on that time to calculating costs by US Dollar (USD). To evaluate whether a strategy is cost effective, one time and three times of GDP per capita were used as threshold based on recommendation of the World Health Organization.Results: The Incremental Cost Effectiveness Ratio (ICER) for combination therapy in genotype-1 and genotypes non-1 subgroups was 2,673 and 19,211 US dollars (USD) per one Sustain Virological Response (SVR), respectively. In low viral load and high viral load subgroups, the ICER was 5,233 and 14,976 USD per SVR, respectively. The calculated ICER for combination therapy in subgroup of patients with previously resistant to monotherapy was 13,006 USD per SVR. Combination therapy in previously resistant patients to combination therapy was a dominant strategy.Conclusions: Adding low dose of Ribavirin to PEG IFN alfa-2a for treatment of chronic hepatitis C patients with genotype-1 was “highly cost effective” and in patients with low viral load and in previous monotherapy resistant patients was “cost effective.”

Background: HCV virus (HCV) is a significant global problem with wide-ranging socio-economic impacts. Because of the high morbidity and mortality associated with end-stage liver disease, cirrhosis, and hepatocellular carcinoma (HCC), the economic burden of HCV infection is substantial.Objectives: This study aimed to estimate the direct medical care costs of chronic HCV infection. Patients and Methods: For this cross-sectional study, 365 courses of HCV treatment were extracted from medical records of 284 patients being referred to Tehran HCV clinic, a clinical clinic of Baqiyatallah Research Center for Gastroenterology and Liver diseases, from 2005 to 2010. All the patients had been diagnosed with HCV. Direct medical care costs for each course of HCV treatment have been calculated based on Purchasing Power Parity Dollar (PPP$).Results: Average direct medical costs for the courses treated with conventional interferon plus ribavirin (INF-RBV) were 4,403 PPP$, and 20,010 PPP$ for peg-interferon plus ribavirin (PEG-RBV) courses. There was an increase of the direct costs in both courses of treatment to achieve Sustain Viral Response (SVR). The costs amounted to 10,072 PPP$ in (INF-RBV) treatment and 34,035 PPP$ in (PEG-RBV). The significant difference between the costs of these two courses of treatment is attributable to high cost of Peg-interferon. This indicates that the medication costs are the dominant costs.Conclusions: According to the results, total direct medical costs for HCV patients in Iran exceeded 12 billion PPP$ in (INF-RBV) treatment and 55 billion PPP$ in (PEG-RBV).