ASSOCIATION OF RESPONSE TO COMBINED INTERFERON ALPHA- 2b AND RIBAVIRIN THERAPY IN PATIENTS OF CHRONIC HEPATITIS C WITH SERUM ALANINE AMINOTRANSFERASE LEVELS AND SEVERITY OF THE DISEASE ON LIVER BIOPSY
AbstractBackground: Raised serum alanine aminotransferase (serum ALT) levels indicate active liver diseasewhile liver biopsy has been considered the ‘gold standard’ for assessing the severity of disease inpatients of chronic Hepatitis C. The response of these patients to standard treatment regimen ofinterferon (INF)-alpha- 2b and ribavirin for 24 weeks have been studied. Objective: The objective ofthis study was to evaluate the association of response to combined INF alpha-2b and ribavirin therapyin patients of chronic hepatitis C with serum ALT levels and severity of the disease on liver biopsy.Methods: This quasi experimental study was conducted in Department of Physiology at Army MedicalCollege and Military Hospital, Rawalpindi from January 2006 to February 2007. One hundred andseven diagnosed non cirrhotic chronic hepatitis C patients were studied. Prior to the commencement oftreatment, qualitative assay of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) was done byPolymerase chain reaction (PCR). Knodell Histopathological Index (HPI) was determined on liverbiopsy. The standard treatment of INF-alpha-2b, 3 million units 3 times a week subcutaneous, andRibavirin 800–1200 mg per day was given for 24 weeks. Serum ALT levels were determined beforethe start of treatment and later at weeks 12 and 24. Qualitative assay of HCV RNA was done by PCRat the end of treatment to determine the response to treatment. Statistical analysis was done on SPSS 15.Results: Out of 107 patients of chronic hepatitis C, 92 (69 males, 23 females) patients (84%) respondedto INF-alpha-2b and ribavirin therapy and revealed negative qualitative assay of HCV RNA by PCR atthe end of 24 weeks of treatment while serum ALT levels were normal in 88% of patients at 12 weeksand in 97% at the end of 24 weeks of treatment. Knodell HPI revealed mild, moderate and severedisease in 47.7%, 39.9% and 13.1% of patients respectively. No association was established betweenresponse to treatment and severity of the disease on liver biopsy (p<0.11) and serum ALT levels(p=0.09). Conclusion: Response to Interferon alpha-2b and ribavirin therapy in patients of chronichepatitis C is not associated with the levels of serum ALT and the severity of the illness graded on liverbiopsy.Keywords: Chronic hepatitis C, interferon, liver biopsy, serum alanine aminotransferase
World Health Organization. Hepatitis C. Fact Sheet No. 164,
Revised October 2000.
Gul A, Iqbal F. Prevalence of Hepatitis C in patients on
maintenance hemodialysis. J Coll Physicians Surg Pak
Khan TS, Rizvi F, Rashid A. Hepatitis C seropositivity among
chronic liver disease patients in Hazara, Pakistan. J Ayub Med
Muhammad N, Jan MA. Frequency of hepatitis C in Buner,
NWFP. J Coll Physicians Surg Pak 2005;15:11–4.
Giannini E, Risso D, Botta F. Validity and clinical utility of the
aspartate aminotranferase-alanine aminotranferase ratio in
assessing severity and prognosis in patients with chronic
hepatitis C virus related chronic liver disease. Arch Intern Med
Hajeer A, Ali H, Ziad M, Al Knawy A, Bandar A. Laboratory
diagnosis of hepatitis C virus infection. A change to common
practice. Saudi Med J 2004;25:827–9.
Dienstag JL. The role of liver biopsy in chronic hepatitis C.
Hepatology 2002;36(suppl 1):152–60.
National Institute of Health. Consensus Development
Conference Statement: Management of Hepatitis C
Mann MP, Wedermayer H, Cornberg M. Treating viral hepatitis
C: efficacy, side effects, and complications. Gut 2006;55:1350–9.
Herrine SK, Rossi S, Navarro VJ. Management of patients with
chronic hepatitis C infection. Clin Exp Med 2006;6:20–6.
Strader DB, Wright T, Thomas DL. Diagnosis, management
and treatment of hepatitis C. Hepatology 2004;39:1147–71.
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–
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.
Sarwar S, Butt AK, Khan AA, Alam A, Ahmad I, Dilshad A,
et al. Serum alanine aminotranferase level and response to
Interferon-Ribavirin combination therapy in patients with
Chronic Hepatitis C. J Coll Physicians Surg Pak 2006;16:460–3.
Makiyama A, Itoh Y, Yasui K, Mori K, Okita M, Nakayama M,
et al. First phase viral kinetic parameters and prediction of
response to interferon alpha-2b/Ribavirin combination therapy
in patients with chronic hepatitis C. Hepatol Res 2006:94-9.
Lloyd AR, Jagger E, Post JJ, Crooks LA, Rawlinson WD, Hahn
YS, et al. Host and viral factors in the immunopathogenesis of
primary hepatitis C virus infection. Immunology and Cell
Batool Q, Qureshi S. Declining sustained virological response in
Hepatitis C. J Coll Physicians Surg Pak 2006:16;187–91.
Davis GL, Wong JB, McHutchison JG, Mann MP, Harvey J,
Albreecht J, et al. Early virologic response to treatment with
peginterferon alfa-2b plus Ribavirin in patients with chronic
hepatitis C. Hepatology 2003;38:645–52.
Yu ML, Chuang WL, Dai CY, Lee LP, Hsieh MY, Lin ZY, et
al. Different viral kinetics between hepatitis C virus genotype 1
and 2 as on-treatment predictors of response to a 24-week
course of high-dose interferon-alpha plus Ribavirin combination
therapy. Transl Res 2006;148:120–7.
Akhtar F, Mushtaq S, Luqman M, Jamal S, Mamoon N,
Rehman Z, et al. Histological Prognostic Markers in Interferon
treated chronic Hepatitis C Patients.J Coll Physicians Surg Pak
Rubbia-Brandt L, Leandro G, Spahr L, Giostra E, Quadri E,
Male PJ, et al. Liver steatosis in chronic hepatitis C: a
morphological sign suggesting infection with HCV genotype 3.