Response rates of standard interferon therapy in chronic HCV patients of Khyber Pakhtunkhwa (KPK)
© Ahmad et al; licensee BioMed Central Ltd. 2012
Received: 11 August 2011
Accepted: 14 January 2012
Published: 14 January 2012
Interferon based therapy is used to eradicate the Hepatitis C Virus from the bodies of the infected individuals. HCV is highly prevalent in Khyber Pakhtunkhwa (KPK) that is why it is important to determine the response of standard interferon based therapy in Chronic HCV patients of the region.
A total of 174 patients were selected for interferon based therapy. The patients were selected from four different regions of KPK. After confirmation of active HCV infection by Real Time PCR, standard interferon with ribavirn was given to patients for 6 months. After completion of therapy, end of treatment virologic response (ETR) was calculated.
Out of total 174 patients, 130 (74.71%) showed ETR and 44 (25.28%) did not show ETR. In district Bunir, out of 52 patients, 36 (69.23%) showed ETR and 16 (30.79%) did not show ETR. In district Mardan, out of the total 74 patients, 66 (89.18%) were negative for HCV RNA and 8 (10.81%) were resistant to therapy. In Peshawar, out of 22, 16 (60%) were negative and 6 (40%) were positive for HCV RNA at the end of 6 months therapy. In the Federally Administered Tribal Area (FATA), out of 18 only 10 (55.5%) were negative and 8 (44.45%) were positive for active HCV infection.
It is concluded that the response of antiviral therapy against HCV infection in chronic HCV patients of KPK province is 74.71%. The high response rate may be due to the prevalence of IFN-responsive HCV genotypes (2 and 3) in KPK.
KeywordsEnd of treatment virologic response Interferon Ribavirin KPK (Khyberpakhtunkhwa) Hepatitis C ALT (Alanin Aminotransferase)
The hepatitis C virus (HCV), a major public health problem and the leading cause of chronic liver disease has affected an estimated 180 million people worldwide [1, 2]. The HCV genome is single-stranded, positive-sense RNA, approximately 9600 bp long and encodes a single polyprotein. HCV infection has reached epidemic proportions and annually more than one million new cases of infection are reported world wide. It is believed that HCV infection is more than that of hepatitis B virus infection (HBV) . Besides this HCV is the leading cause of liver transplantation and organ shortage is the major associated problem. The introduction of effective therapy for the prevention of such life threatening infection is the ultimate goal. It is especially more important in underdeveloped countries, where HCV infection rate is more and most of the patients have financial problems for its treatment.
Eradication of the virus is the primitive goal of hepatitis C treatment that is sustained virologic response (SVR) which is defined as absence of HCV RNA in serum after 6 months of treatment completion and is evidenced by sensitive molecular tests, Polymerase Chain Reaction (PCR). It has been observed over the past decades that there is great improvement in the SVR rates when treatment strategies have been shifted from interferon monotherapy to combination interferon plus ribavirin [4, 5].
Hepatitis C therapy started with a small trial of recombinant human interferon Alfa almost 25 years ago . Interferon was selected because of its broad activities against the viruses and it was thought that it might also be active against still-undiscovered agent of non-A, non-B hepatitis. No doubt, interferon was found very active against HCV and resultant effects were decrease in the level of serum alanin aminotransferase (ALT). So far HCV was not discovered, the effects of interferon were not understood but the result of using interferon was the reduction in HCV RNA level, which led to a sustained absence of virus in a proportion of patients . Ribavirin a nucleoside analogue, known to have activity against several flaviviruses had strong effects in lowering the level of aminotransferase and histologic characteristics of the liver but had little effects on serum HCV RNA levels . Moreover when ribavirin was combined with interferon then it has increased sustained virologic response rate . Interferon and ribavirin when given in combination for 48 weeks then sustained virologic response rates was 40-50% which is two to three times more than that obtained with interferon alone . Interferon alpha (IFN-α) along with ribavirin has been widely used as a standard treatment option for patients with chronic HCV infection all over the world . Pegylated interferon with Ribavirin has better response rate as compared to standard interferon .
In Pakistan the general concept is the use of standard interferon therapy. This is partly due to economic reasons and Pakistan Society of Gastroenterology and GI Endoscopy also favours the use of SdIF in genotype-3 . Government of Pakistan is also providing only SdIF via a special Prime Minister's initiative programme against hepatitis, thus PgIF is out of reach for the majority of the patients.
Response rates of standard interferon in chronic HCV patients have never been investigated in KPK. The study had focused on the efficacy of standard interferon therapy as administered in the case of chronic HCV patients in Khyber Pakhtunkhwa province of Pakistan.
To evaluate the response of standard interferon combination therapy against chronic HCV infection, we selected four different regions of KPK province. The regions were districts Bunir, Peshawar, Mardan and FATA region. Through coordination with practioners and lab workers, samples were collected from the suspected patients. After initial screening with ICT and Elisa, PCR test was performed for each patient sample according to the instructions of the manufacturers (Roboscreen, Germany). Among the confirmed anti-HCV patients, only 174 patients whose PCR was positive, were selected for interferon therapy keeping in mind the exclusive therapy criteria that is, age of the selected personals (18-55 years), no co-infection associated, ALT level higher than normal, platelets and Hb levels within the accepted range, and stage of cirrhosis. We selected 52 patients from Bunir, 22 from Peshawar, 74 patients from Mardan and 18 from FATA regions.
PCR positive patients were given standard interferon combination therapy i.e. interferon alpha 2a (3MIU thrice a week) plus Ribavirin (1000-1200 mg/day) continuously for 6 months with repeated testing of ALT level and HCV RNA during and after the interferon therapy.
Region wise distribution of positive HCV RNA samples and their respective ETR
Hepatitis C Virus infection is spreading rapidly. HCV prevalence is nearly 200 million people world wide and every year infects 3-4 million more people . The seroprevalence of Hepatitis C virus in different parts of Pakistan, reported in the last 5 years, is from 2.2%-13.5%. The highest seroprevalence of hepatitis C has been reported from Lahore (13.5%)  Jasmshoro (9%) and Mardan (9%) [15, 16].
Pakistan is a developing country and the literacy rate is also low, due to which lack of information regarding the pathogenecity, routes of transmission and the proper procedures of diagnosis and treatment are rarely followed. Therefore HCV infection has become an economic burden on the people of Pakistan and especially in KPK.
In this study we determined the End of Treatment Response (ETR), defined as the absence of HCV RNA at the end of 6 months IFN therapy, in chronic HCV patients. The average calculated ETR was 74.71% and resistance calculated was 25.28%. Different regions of KPK province had different ETR rates; like ETR was very high in district Mardan followed by district Bunir and lower in district Peshawar and FATA regions [Figure 1].
The average response rate of IFN combination therapy with ribavirin in chronic HCV patients of KPK population was 74.71% [Table 1]. Although KPK have different population groups which may vary regarding response to IFN based therapy. Instead, the response rate was similar to other studies conducted internationally [17–19] as well as locally [20, 21], when treated with IFN and ribavirin combination therapy.
In district Mardan prevalence of HCV infection has been recorded as 9% . The high ETR rate in district Mardan might be due to the high prevalence of HCV genotypes 2 and 3 and might be due to high literacy rate, as by adopting proper procedures for diagnosis and treatment, the efficacy rate might be increased as compared to those who have no or little knowledge.
In district Bunir HCV prevalence has also been shown to be 5% . As this district is less developed and is considered as an economically poor district, through the prime minister's control programme for Hepatitis, HCV patients have been treated and ETR rate was comparatively higher than that of Peshawar and FATA regions [Table 1].
In district Peshawar the response rate was low as compared to districts Mardan and Bunir. Low response rate might be attributed to migration of people from Afghanistan, from FATA and other associated regions due to the Floods and regional conflicts. Low response rate in this district may be due to prevalence of resistance types common in other regions.
In FATA regions, the lowest response was found which again could be attributed to the prevalence of resistant HCV genotypes that may have resulted due to the influx of people from the Gulf and Central Asian Countries.
The above discussion shows that antiviral therapy against HCV infection in chronic HCV patients of KPK province is 74.71%. The high response rate may be due to the prevalence of genotypes 2 and 3.
The authors are thankful to the University of Peshawar, Peshawar, Khyber Pakhtunkhwa, Pakistan for funding the research work. Graduate study committee and Board of Advance Study and Research, of University of Peshawar, for approval of this study.
- Williams R: Global challenges in liver disease. Hepatology. 2006, 44: 521-526. 10.1002/hep.21347.PubMedView ArticleGoogle Scholar
- World Health Organization Hepatitis C: 1999, [http://www.who.int/immunization/topics/hepatitis_c/en/]
- Cooreman MP, Schoondermark-Van de Ven EM: Hepatitis C virus. Biological and clinical consequences of genetic heterogeneity. Scand J Gastroenterol Suppl. 1996, 218: 106-115.PubMedView ArticleGoogle Scholar
- McHutchison JG, Gordon SC, Schiff ER, Shiffman ML, Lee WM, Rustgi VK: Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med. 1998, 339: 1485-1492. 10.1056/NEJM199811193392101.PubMedView ArticleGoogle Scholar
- Poynard T, Marcellin P, Lee SS, Niederau C, Minuk GS, Ideo Gl: Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT). Lancet. 1998, 352: 1426-1432. 10.1016/S0140-6736(98)07124-4.PubMedView ArticleGoogle Scholar
- Hoofnagle JH, Mullen KD, Jones DB: Treatment of chronic non-A, non-B hepatitis with recombinant human alpha interferon: a preliminary report. N Engl J Med. 1986, 315: 1575-1578. 10.1056/NEJM198612183152503.PubMedView ArticleGoogle Scholar
- Hoofnagle JH, Seeff LB: Peg-interferon and ribavirin for chronic hepatitis C. N Engl J Med. 2006, 355: 2444-2451. 10.1056/NEJMct061675.PubMedView ArticleGoogle Scholar
- Di Bisceglie AM, Conjeevaram HS, Fried MW: Ribavirin as therapy for chronic hepatitis C: A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1995, 123: 897-903.PubMedView ArticleGoogle Scholar
- McHutchison JG, Gordon SC, Schiff ER: Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. N Engl J Med. 1998, 339: 1485-1492. 10.1056/NEJM199811193392101.PubMedView ArticleGoogle Scholar
- Ghanay MG, Strader DB, Thomas DL, Seeff LB: Diagnosis, management and Treatment of hepatitis C: An update. Hepatology. 2009, 49: 1335-1374. 10.1002/hep.22759.View ArticleGoogle Scholar
- Fried MW, Shiffman ML, Reddy KR: Peg-interferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002, 347: 975-982. 10.1056/NEJMoa020047.PubMedView ArticleGoogle Scholar
- Hamid S, Umar M, Alam A, Siddiqui A, Qureshi H, Butt J: PSG consensus statement on management of hepatitis C virus infection-2003. J Pak Med Assoc. 2004, 54: 146-150.PubMedGoogle Scholar
- Yvan H, Mary EK, Gregory JD, Joseph FP, Gregory L, Geoffrey D, Hiromi I, Peter G, Michael K, Patrick M, Leonard BS, Philippe B, Christopher N, Claudia S, Pascal Z, Gary C, Robert V, Alfredo A, Zuhair SH, Stephen H, Daniel L: Global Burden of Disease (GBD) for hepatitis C. J Clin Pharmacol. 2004, 44: 20-29.View ArticleGoogle Scholar
- Amin J, Yousf H, Mumtaz A, Iqbal M, Ahmed R, Adhami SZ: Prevalence of Hepatitis B surface antigen and Anti Hepatitis C virus. Professional Med J. 2004, 11 (3): 334-337.Google Scholar
- Almani SA, Memon AS, Qureshi AF, Memon NM: Hepatitis viral status in Sindh. Professional Med J. 2002, 9 (1): 36-43.Google Scholar
- Khan MSA, Khalid M, Ayub N, Javed M: Seroprevalence and risk factors of Hepatitis C virus (HCV) in Mardan: N.W.F.P. Rawal Med. 2004, 29: 57-60.Google Scholar
- Mann MP, Wedermayer H, Cornberg M: Treating viral hepatitis C: efficacy, side effects, and complications. Gut. 2006, 55: 1350-1359. 10.1136/gut.2005.076646.View ArticleGoogle Scholar
- Herrine SK, Rossi S, Navarro VJ: Management of patients with chronic hepatitis C infection. Clin Exp Med. 2006, 6: 20-26. 10.1007/s10238-006-0089-4.PubMedView ArticleGoogle Scholar
- Strader DB, Wright T, Thomas DL: Diagnosis, management and treatment of hepatitis C. Hepatology. 2004, 39: 1147-1171. 10.1002/hep.20119.PubMedView ArticleGoogle Scholar
- Wazir MS, Majid AS, Solangi GA, Zuberi BF: Role of interferon and interferon plus Ribavirin in the management of chronic hepatitis C. J Coll Physicians Surg Pak. 2002, 12: 609-612.Google Scholar
- Farooqi JI, Farooqi RJ: Efficacy of conventional Interferon alpha-2b plus Ribavirin combination in the treatment of Chronic Hepatitis C naïve patients. Rawal Med J. 2005, 30: 9-11.Google Scholar
- Muhammad N, Jan A: Frequency of hepatitis C in Bunir: NWFP. J Coll Physicians Surg Pak. 2005, 15: 11-14.PubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.