INTERFERON-RIBAVIRIN TREATMENT IN CHRONIC HEPATITIS C– THE LESS TALKED ABOUT ASPECTS

Authors

  • Shahid Raza Khalid
  • Anwaar A Khan
  • Altaf Alam
  • Altaf Alam
  • Nasir Hassan Lak
  • Arshad Kamal Butt
  • Farzana Shafqat
  • Aftab Alvi
  • Irfan Ahmed
  • Shahid Sarwar
  • Amir Niazi

Abstract

Background: Combination therapy with interferon and ribavirin has become the standard of carein the treatment of Chronic Hepatitis C (CHC) infected patients. Treatment response, however, isnot 100% and is accompanied with side effects faced by the patient as well as observed inhaematologic indices. Studies are focusing on daily or high-dose induction therapy withinterferon, the titration of interferon dosing to initial viral load, higher doses of interferonthroughout treatment, and adjustment of interferon dosing to the viral responses. The safety andefficacy of these approaches have not been sufficiently established. Objectives were to see theresponse of 2 different dosage regimens, effects and side effects and to assess the efficacy and sideeffects of 2 treatment regimens of Interferon and Ribavirin in CHC. Methods: A total of 32patients with CHC at Department of Gastroenterology and Hepatology, Shaikh ZayedPostgraduate Medical Institute Lahore from June 2001 to February 2003 were included in thestudy and were divided into two groups for treatment. Group A (14 patients) received 5 MU ofinjection Interferon alpha 2 b S/C daily for 2 weeks followed by 3 MU thrice weekly for the next22 weeks. Group B (18 patients) received injection interferon alpha 2 b 3 MU S/C thrice weeklyfor 24 weeks. Ribavirin therapy was started at 1200 mg daily in 3 divided doses and later modifiedaccording to side effects. Patients were evaluated at 2, 4, 8, 12, 16, 20 and 24 weeks during thetherapy and then 24 weeks after the completion of treatment. Results: Out of 32 adult patientsincluded in the study, 18 were males and 14 females. Haemoglobin was more than 12 gm/dl infemales and more than 13 gm/dl in males, WBC count was more than 3.0109/L and Platelet countwas more than 100109/L. Twenty patients completed 6 months combination treatment, 16reported with their end of treatment HCV RNA PCR results, 8 from each group. Twelve patientswere lost to follow up. End of treatment response (ETR) in group A was 88% and 62.5% in groupB. Sustained virological response in group-A was 5/8 (62.5%) and 4/5 (50%) in group-B. Thefrequency and severity of flu like symptoms like fever, body aches, skin rash, hair loss, cough andpsychiatric symptoms were more in group A than in group B. There was no significant differencein the 2 groups for haematologic side effects. Conclusions: Treatment with 5 MU interferon dailyfor initial two weeks followed by 3 MU thrice weekly for 22 weeks is more effective than 3 MUthrice weekly for 24 weeks but with more side effects.Keywords: Hepatitis, Chronic Hepatitis C, Interferon, Ribavirin, Therapy, Side effects

References

WHO. Global surveillance and control of hepatitis C. Report of

WHO consultation organized in collaboration with the Viral

Hepatitis Prevention Board, Antwerp, Belgium. J Viral Hept

;6:35–47.

Amin J, Yousaf H, Mumtaz A, Iqbal M, Ahmed R, Zaman S, et

al. Prevalence of hepatitis B surface antigen and anti hepatitis C

virus. Professional Med J 2004;11:334–7.

Mahmood MA, Khawar S, Anjum AH, Ahmed SM, Rafiq S,

Nazir I, et al. Prevalence of hepatitis B, C and HIV infection in

blood donors of Multan region. Ann KE Med Coll

;10(4):459–61.

Strader DB, Wright T, Thomas DL, Seeff LB. Diagnosis,

management, and treatment of hepatitis C. AASLD practice

guide lines. 2004 Available at: http://www.natap.org/

/pdf/AASLD_Prac._Guide_Hep_C.pdf

Peine, CJ, Albracht, JK, Rizel, JP, Gershwin E, Ansari M, Aftab

A. et al. A comparison of standard and induction interferon

therapy with and without initial ribavirin in treatment of naïve

patients with chronic hepatitis C. Hepatology 2000;32:364A.

Carithers, RL, Manns, MP, Pemillow, RP, Dickson R, Jorgensen

R, Petz JL. et al. Multicenter, randomized, controlled trial

comparing high dose daily induction interferon plus ribavirin

versus standard interferon alfa-2 B plus ribavirin. Hepatology

;32:317A.

Poynard T, Bedossa P, Chevallier M, Mathurin P, Lemonnier C,

Trepo C, et al. A Comparison of three alfa-2b interferon

regimens for the long term-treatment of chronic non-A, non-B

hepatitis. N Engl J Med 1995;332:1457–62.

J Ayub Med Coll Abbottabad 2009;21(2)

http://www.ayubmed.edu.pk/JAMC/PAST/21-2/Shahid.pdf

Shindo M, Aria K, Sokawa Y, Okuno T. Hepatic hepatitis C

virus RNA as a predictor of long- term response to interferon

alpha therapy. Ann Intern Med1995;122:586–91.

Afdhal, NH, Brand, M, Epstein, A, Massimo R, Colombo P,

Borzio M. et al. Randomized controlled trial of interferon-A

(Interon A) 5 MU daily plus ribavirin 1000 mg daily versus

interferon-A (Interon A) 3 MU TIW plus ribavirin 1000 mg daily

in patients with HCV who have never received precious therapy.

Hepatology 2000;32:363A.

Marcellin P, Boyer N, Gervais A, Martinot M, Pouteau M,

Castelnau C, et al. Long-term histologic improvement and loss of

detectable intrahepatic HCV RNA in patients with chronic

hepatitis C and sustained response to interferon-alpha therapy.

Ann Intern Med 1997;127:875–81.

McHutchison JG, Gordon SC, Schiff ER, Shiffman ML, Lee

WM, Rustgi VK, et al. Interferon alfa-2b alone or in combination

with ribavirin as initial treatment for chronic hepatitis C. N Engl J

Med 1998;339:1485–92.

Poynard T, Marcellin P, Lee SS, Niederau C, Minuk GS, Ideo G,

et al. Randomized trial of interferon alfa-2b plus ribavirin for 48

weeks or for 24 weeks versus interferon alfa-2b plus placebo for

weeks for treatment of chronic infection with hepatitis C virus.

Lancet 1998;352:1426–32.

Poynar T, Leroy V, Cohard M, Thevenot T, Mathurin P, Opolon

P, et al. Meta-analysis of interferon randomized trials in the

treatment of viral hepatitis C: effects of dose and duration.

Hepatology 1996;24:778–89.

Davis GL, Balart LA, Schiff ER, Lindsay K, Bodenheimer HC

Jr, Perrillo RP, et al. Treatment of chronic hepatitis C with

recombinant interferon alpha. A multicenter randomized,

controlled trial. Hepatitis interventional therapy group. N Engl J

Med 1989;321:1501–6.

Lertora JJ, Rege AB, Lacour JT, Ferencz N, George WJ,

VanDyke RB, et al. Pharmacokinetics and long-term tolerance to

ribavirin in asymptomatic patients infected with human

immunodeficiency virus. Clin Pharmacol Ther 1991;50:442–9.

Page T, Connor JD. The metabolism of ribavirin in erythrocytes

and nucleated cells. Int J Biochem 1990;22:379–83.

Schalm SW, Hansen BE, Chemello L, Bellobuono A, Brouwer

JT, Weiland O, et al. Ribavirin enhances the efficacy but not the

adverse effects of interferon in chronic hepatitis C. A metaanalysis of individual patients data from European centers. J

Hepatol 1997; 26:961–6.

Dusheiko G Side effects of alpha interferon in chronic hepatitis

C. Hepatology 1997;26(suppl 1):112S–121S.

Levenson JL, Fallon HJ. Flouxitine treatment of depression

caused by interferon-alpha. Am J Gastroenterol 1993;88:761–1.

Valentine AD, Meyers CA, Kling MA, Richelson E, Hauser P.

Mood and cognitive side of interferon-a therapy. Semin Oncol

;25(Suppl 1):39–47.

Meyers CA, Scheibel RS, Forman AD. Persistent neurotoxicity

of systemically administered interferon-alpha. Neurology

;41:672–6.

Wiranowska M, Wilson TC, Thompson K, Prockop LD.

Cerebral interferon entry in mice after entry in mice after osmotic

alteration of blood-brain barrier. J Interferon Res 1989;9:353–6.

Published

2009-06-01

Most read articles by the same author(s)