Effect of Prolongation of Combined Treatment in HCV-4 Infection
Yehia El Shazly1, Salwa El Hadad2, Wafaa Kamal1, Mohamed Abdel Moghny1, Reham Al Swaff1 and Mohamed Hassan Fouad1
Internal medicine1 and pathology 2 Departments, Ain Shams University, Cairo, Egypt
Abstract: Background and aim: The recommended treatment for patients infected with hepatitis C virus (HCV) genotypes 1 and 4 is pegylated interferon plus ribavirin 1000 or 1200 mg/day for 48 weeks .Efforts to optimize and improve therapeutic outcomes are ongoing. Rapid virologic response (RVR) after 4 weeks of treatment and early virologic response (EVR) after 12 weeks of treatment play an important role in customization of therapy. In RVR patients who received 24 weeks of combined treatment but did not achieve SVR, the effect of prolongation of combined treatment on sustained virological response rate was not evaluated.The current study was to determine the effect of prolongation of combined treatment with pegylated interferon alfa-2a plus ribavirin to 48 weeks on increasing sustained virological response rate in patients infected with hepatitis C virus (genotype 4) who achieve rapid virological response. Study design and methods This study was conducted on 300 patients with chronic HCV genotype 4 infections who received combined treatment with peginterferon alfa-2a plus ribavirin. All patients were treatment naïve and older than 18 years with mean age of 42.15±9.5.Those patients who achieved RVR were randomly selected for 24 or 48 weeks of therapy. All patients received a combination of pegylated interferon α 2a 180ucg SC injection weekly plus ribavirin 800 – 1200 mg/day (dose adjusted according to body weight). All patients were adherent to treatment (all were compliant and did not develop any adverse effect that mandates either stoppage of treatment or reduction of the dose of either or both drugs),adherence to Treatment is defined as taking 80 % of each drug for at least 80 % of the duration of therapy .All patients were subjected to History taking, thorough clinical examination including funds examination, laboratory investigations including: fasting and post prandial blood glucose level, liver function tests, Alpha fetoprotein ,prothrombin time and INR, renal function tests, complete blood count, free T3,free T4, TSH, ANA, HIV and hepatitis C virus antibody using ELISA technique, HBsAg , HBs Ab, HBc Ab, HBeAg and HBe Ab.HCV RNA (PCR) in serum, both quantitative and qualitative and also HCV genotyping using INNO-LIPA HCVII test ,Qualitative HCV RNA PCR was done for all patients at week 4 of combined treatment to assess RVR.For those who achieved RVR,Qualitative HCV RNA PCR was done at week 24 for group A patients’ and week 48 for group B patients’ to assess end of treatment response (ETR).For those who achieved ETR, Qualitative HCV RNA PCR was done 24 weeks after stoppage of treatment to assess SVR, Abdominal ultrasonography, Liver biopsy was done for 17 patients only (as the rest of the participants denied such an invasive procedure).The biopsy specimen was fixed in 10% formalin then transferred to the pathology department. METAVIR scoring system was used to assess the histological lesions, Fibroscan was done for the rest of the patients. The operator who performed the liver stiffness measurement was unaware of neither the clinical nor the laboratory data of the patients. Results were expressed in kilopascals (kPa). The values used to correlate elastometry with METAVIR scoring system were as follows: 0-2.9 kPa for F0, 3-5.9 for F1, 6-8.9 for F2, 9-16.9 for F3 and 17-75 for F4[8 ] .This study was approved by the local ethical committee of Ain Shams University Hospitals and a written consent was obtained from each individual before participation in the study. Results: 57 patients who achieved RVR(19%) (Out of 300 patients who received treatment for chronic hepatitis C genotype 4) were included. All patients were treatment naïve and older than 18 years with mean age of 42.15±9.5. They were randomly assigned into two groups. Group A: 29 patients (22 males and 7 females) received combined treatment for 24 weeks with mean age 42.2.±9.2Group B: 28 patients (24 males and 4 females) received combined treatment for 48 weeks with mean age 42.1.±9.8.The differences between the two studied groups as regards the demographic data were insignificant; also there were insignificant differences between the two studied groups as regards pretreatment level of HCV viraemia, stages of fibrosis .The current study revealed an insignificant difference between the two studied groups as regards SVR and also statistically insignificant differences in SVR rates between rapid responders with different levels of viraemia whether treated for 24 or 48 weeks. There was a statistically insignificant difference in SVR rate between patients with F1 or F2 stages of fibrosis whether treated for 24 or 48 weeks, the same finding was observed among patients with F3 - F4 stages of fibrosis , however, the correlation between fibrosis stage and SVR was significant in both studied groups. Conclusion; Prolongation of standard combined treatment to 48 weeks does not influence SVR in HCV genotype 4 patients who achieve RVR while shortening of standard combined treatment to 24 weeks seems to be possible to all rapid responders without compromising their chance for achieving SVR.
[Yehia El Shazly, Salwa El Hadad, Wafaa Kamal, Mohamed Abdel Moghny, Reham Al Swaff, and Mohamed Hassan Fouad. Effect of Prolongation of Combined Treatment in HCV-4 Infection. J Am Sci2013;9(3):284-292]. (ISSN: 1545-1003). http://www.jofamericanscience.org. 39
Keywords: prolonged combined treatment, HCV-4 infection. Full Text 39