EARLY PREDICTABILITY OF VIROLOGICAL RESPONSE IN PATIENTS OF CHRONIC HEPATITIS-C WITH GENOTYPE-3, TREATED WITH PEGYLATED INTERFERON AND RIBAVIRIN
AbstractBackground: This study was conducted to assess the early predictability of virological response in chronic hepatitis-C patients (Genotype-3), treated with pegylated interferon alpha-2a and ribavirin with an objective of determining predictive values of Rapid Virological Response (RVR) and Early Virological Response (ETR) on Sustained Virological Response (SVR). Method: This cross sectional study was conducted in January 2014, at Holy Family Hospital, Rawalpindi by inclusion of 582 patients of chronic hepatitis being treated with Pegylated Interferon α 2b and ribavirin. Based on Polymerase Chain Reaction (PCR) for HCV RNA Qualitative on 4th, 12th and 24th week of treatment regimen, RVR, EVR and End treatment Response (ETR) was assessed respectively whereas 24th week post treatment PCR concluded as SVR. Effect of treatment was determined as proportions for responses in total and then compared for treatment naïve, responders and relapsers to previous conventional therapy using Chi square test. Positive and Negative Predictive Values were also calculated. Results: Qualitative PCR for HCV revealed that 281 (69.2%) achieved RVR where 60.3% attained SVR. PPV and NPV of RVR in study population were 67.41% and 44.45% respectively and 66.29% and 57.14% respectively for EVR. Statistically significant differences in RVR, EVR and ETR were observed in patients based on conventional treatment response. Conclusion: Attainment of RVR is a prospect to categorize patients appropriate for abridged treatment and this study supported the evidence that failure to achieve EVR was congruent with failure to achieve SVR.Keywords: Hepatitis-C Virus, Rapid Virologic Response, Early Virologic Response, Positive Predictive Value, Negative Predictive Value, Pegylated Interferon, Ribavirin, conventional Interferon treatment naive, relapsers, non-repsonders
Martinot-Peignoux M, Maylin S, Moucari R, Ripault MP, Boyer N, Cardoso AC, et al. Virological response at 4 weeks to predict outcome of hepatitis C treatment with pegylated interferon and ribavirin. AntivirTher 2009;14(4):501–11.
Roger C, Susan C, Benjamin KSC and C Byron. Drug Class Review: Pegylated Interferon for Chronic Hepatitis C Infection. Final Report Drug Class Reviews Portland (OR): Oregon Health & Science University; May 2007.
Ward RP, Kugelmas M. Using Pegylated Interferon and Ribavirin to Treat Patients with Chronic Hepatitis C. Am Fam Physician 2005;72(4):655–62.
Yu ML, Dai CY, Huang JF, Chiu CF, Yang YH, Hou NJ, et al . Rapid Virological
Response and Treatment Duration for Chronic Hepatitis C Genotype 1 Patients: A Randomized
Trial, Hepatology. 2008;47(6):1884–93.
Yu JW, Wang GQ, Sun LJ, Li XG, Li SC. Predictive value of rapid virological response and early virological response on sustained virological response in HCV patients treated with pegylated interferon alpha-2a and ribavirin. J Gastroenterol Hepatol 2007;22(6):832–6.
Andriulli A, Mangia A, Iacobellis A, Ippolito A, Leandro G, Zeuzem S. Meta-analysis: the outcome of anti-viral therapy in HCV genotype 2 and genotype 3 infected patients with chronic hepatitis. Aliment Pharmacol Ther 2008;28(4):397–404.
Mandokhel SK, Rehman A, Khan MS. Interferon alpha 2b in combination with ribavirin as a treatment for chronic hepatitis C. Pak J Med Health Sci 2011;5(1):168–71.
Rumi MG, Aghemo A, D'Ambrosio R, Ronchi G, Del Ninno E, Gallus S et al. Lack of rapid virological response predicts interferon-alpha 2b/ribavirin therapy failure in HCV genotype 2 patients: a single-centre study. Antivir Ther 2007;12:1033–0.
Aghemo A, Rumi MG, Soffredini R, D'Ambrosio R, Ronchi G, Del Ninno E, et al. Impaired response to interferon-alpha2b plus ribavirin in cirrhotic patients with genotype 3a hepatitis C virus infection. Antivir Ther 2006;11:797–802.
von Wagner M, Huber M, Berg T, Hinrichsen H, Rasenack J, Heintges T et al. Peginterferon-α-2a (40KD) and ribavirin for 16 or 24 weeks in patients with genotype 2 or 3 chronic hepatitis C. Gastroenterology 2005;129(2):522–7.
Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P et al.Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004;140:346–55.
Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R et al. Peginterferon alpha-2b plus ribavirin compared with interferon alpha-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001;358:958–65.
Zeuzem S, Hultcrantz R, Bourliere M, Goeser T, Marcellin P, Sanchez-Tapias J et al. Peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C in previously untreated patients infected with HCV genotypes 2 or 3. J Hepatol 2004;40:993–9.
Mangia A, Santoro R, Minerva N, Ricci GL, Carretta V, Persico M, et al. Peginterferon Alfa-2b and Ribavirin for 12 vs. 24 Weeks in HCV Genotype 2 or 3. N Engl J Med 2005;352:2609–17.
15. Dalgard O, Bjøro K, Hellum KB, Myrvang B, Ritland S, Skaug K, et al. Treatment with pegylated interferon and ribavirin in HCV infection with genotype 2 or 3 for 14 weeks: a pilot study. Hepatology 2005;40:1260–5.
Fred P and Chrispin K. Predictability of Response: Positive and Negative Predictive Values of Rapid and Early Virologic Responses to Peginterferon alfa-2b and Ribavirin in the Treatment of Chronic Hepatitis C. presented at 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) Boston, MA. November 2-6, 2007.
Davis GL, Wong JB, McHutchison JG, Manns MP, Harvey J, Albrecht J. Early virologic response to treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C. Hepatology 2003;38(3):645–52
Kamal SM, El Kamary SS, Shardell MD, Hashem M, Ahmed IN, Muhammadi M, et al.Pegylated interferon alpha-2b plus ribavirin in patients with genotype 4 chronic hepatitis C: The role of rapid and early virologic response..Hepatology 2007; 46(6):1732–40.
Hasan F, Asker H, Al-Khaldi J, Siddique I, Al-Ajmi M, Owaid S, et al. Peginterferon alfa-2b plus ribavirin for the treatment of chronic hepatitis C genotype 4. Am J Gastroenterol 2004;99(9):1733–7