INTERFERON BASED THERAPY OF CHRONIC HEPATITIS C PATIENTS. A CASE STUDY OF KHYBER PAKHTUNKHWA.

Abstract

Hepatitis C is the inflammation of the Liver caused by Hepatitis C virus (HCV), the leading cause of the liver cirrhosis and hepatocellular carcinoma. About 3% of the people have been affected by HCV world wide and in Pakistan being an underdeveloped country; an estimated 10 million people have Hepatitis C infection (WHO). As hepatitis C infection is asymptomatic and due to untimely diagnosis it leads to severe liver diseases and anuualy a lot of affected individuals lose their lives. In order to cure the infection Food and Drug Agency (FDA) has approved the use of Interferon (IFN) as the treatment remedy. In Pakistan National Institute of Health (NIH) has also given the recommendation for the use of IFN as the therapeutic agent In KhyberPakhtunKhwa (KPK) mostly conventional IFN and Ribavirin combination therapy is considered due to the prevalence of responsive genotypes 2 and 3. Earlier no study has been conducted to sort out IFN response among chronic HCV patients in different districts of KPK province, therefore we attempted to find out response of conventional IFN combination therapy at districts level in KPK. Samples were collected from chronic HCV patients referred by clinician/laboratories of different regions of KPK. The samples were analyzed for screening by ICT (Immunochromatographic Technique) and ELISA (Enzyme Linked Immunosorbant Asaay) followed by confirmation through polymerase chain reaction (PCR). We have also done genotyping for some of the chronic HCV patients. PCR confirmed positive patients were given IFN and Ribavirin combination therapy keeping in mind the therapy exclusion criteria. The dose of IFN and Ribavirin was 3 Million Units thrice a week and 800-1200mg daily depending on the age of the patients, respectively. This therapy was continued for six months with repeated testing of ALT (Alanin Transaminase) and CBC (Complete Blood Count), during and after therapy. At the end of six months of therapy, PCR test was done for all course completed patients. Active HCV infection was present in 66.6% among 3075 anti-HCV positive patients while 33.3% anti-HCV positive patients were negative for HCV RNA. Rate of active iiHCV infection was comparatively more in districts Bunir (72%), Dir (70 %) and in Mardan (69%). While lower in districts Swabi (66%), Peshawar (64%) and Kohat (59%). HCV genotype analysis in chronic HCV patients of KPK revealed that the most abundant genotypes/subtypes among the patients analyzed were 2a followed by subtype 3a. Other common genotypes included the untypable type of the virus and genotype 3b. Response of IFN and Ribavirn combination therapy in the 1st trial among 174 PCR positive patients was 74.71% and the resistance was 25.28%. Among different districts, high end of treatment response (ETR) was shown by district Mardan patients population (89.18%), followed by Bunir (69.23%). While low response was present in case of district Peshawar (60%) and Federally Administered Triable Area (FATA) (55.55%). In the second trial of IFN therapy, out of total (341) selected patients for standard IFN- based therapy 81% showed ETR and 19% did not show response. Among the districts high ETR was shown by district Swabi (92%), followed by district Kohat (80%). Comparatively low response was present in case of district Bunir (71%). In genotype specific response of IFN based therapy, out of total 51 selected patients. Responsive genotypes among these were 2a followed by 3a. Response rate among different HCV genotypes were as, 2a HCV genotypes had high (77.72%) ETR, followed by 3a genotypes (72.22%). Comparatively low response was present in case of 3b and 1b genotypes (66.66%) and (33.33%) respectively. While untypable genotypes showed no response. Our results revealed that response of combination IFN therapy is good in some of the districts patients’ population. High ETR rate in these districts may be attributed to prevalence of responsive HCV genotypes 2 and 3. In case of non responsive genotypes some new effective remedies should be discovered. While untypable genotypes should be sequenced so as to adopt some new therapeutic agents against them.