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SMJ // Article

Original Article

Daily Interferon Monotherapy for Chronic Hepatitis C in Patients with Normal or Near-normal Serum Alanine Transaminase Levels: A Comparison of Two Protocols

Authors: Dasarathy Srinivas, MD, Haresh Mani, MD, Charles C. Crumpler, MD, David H. Van Thiel, MD

Abstract

Objectives: Up to 30% of the 5 million patients with chronic hepatitis C in the United States have normal serum alanine transaminase (ALT) levels. These individuals have not been treated aggressively, and reported response rates have been low. No study has targeted patients treated in a community practice setting.


Methods: Consecutive patients with chronic hepatitis C with normal or near-normal serum ALT levels seen over a 2-year period in a community gastroenterology-hepatology practice were randomly assigned to receive either 3 MU or 6 MU daily interferon (IFN)-α-2a monotherapy for 12 months.


Results: Sixteen patients (8 in each treatment arm) qualified for study. End-of-treatment response was 87.5% with 6 MU IFN daily and 75% with 3 MU IFN daily, whereas sustained virologic response was 62.5% and 50%, respectively. Genotype 1 patients had an improved outcome with the higher 6 MU dose.


Conclusions: Daily IFN monotherapy achieves high response rates in patients with chronic hepatitis C with normal or near-normal ALT. Present-day pegylated interferon regimes can be expected to be as effective.


Key Points


* Six MU interferon-α-2a daily is more efficacious than 3 MU daily.


* Genotype 1 infections respond when higher doses of interferon are used.


* No differences in side effects were observed as a function of dose.

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References

1.Bacon BR. Treatment of patients with hepatitis C and normal serum aminotransferase levels.Hepatology 2002;36:S179–S184.
 
2.Barnes E, Webster G, Whalley S, Dusheiko G. Predictors of a favorable response to alpha interferon therapy for hepatitis C. Clin Liver Dis 1999;3:775–791.
 
3.Shakil AO, Conry-Cantelina C, Alter HJ, et al. Volunteer blood donors with antibody to hepatitis C virus: clinical, biochemical, virologic and histologic features. Ann Intern Med 1995;123:330–337.
 
4.Russo MW, Brown RS. Should patients with chronic hepatitis C who have normal ALT levels be treated? Curr Gastroenterol Rep 2001;3:49–53.
 
5.Marcellin P, Martinot M, Boyer N, Levy S. Treatment of hepatitis C patients with normal aminotransferases levels. Clin Liver Dis 1999;3:843–853.
 
6.Tassopoulos NC, Vafiadis I, Tsantoulas D, et al. IFN-alpha2b monotherapy in patients with chronic hepatitis C and persistently normal or near normal aminotransferase activity: a randomized, controlled study. J Interferon Cytokine Res 2002;22:365–369.
 
7.Van Thiel DH, Colantoni A, De Maria N. Treatment of HCV positive individuals with normal serum ALT levels. Hepatogastroenterology 1998;45:321–324.
 
8.National Institute of Health Consensus Development Conference Statement. Management of Hepatitis C-2002. June 10 to 12, 2002.
 
9.Srinivas D, Mani H, Crumpler C, Van Thiel DH. Daily interferon therapy for chronic hepatitis C: a report of a community practice experience. Hepatogastroenterology 2002;49:1053–1057.
 
10.Di Bisceglie AM. Chronic hepatitis C viral infection in patients with normal serum alanine aminotransferases. Am J Med 1999;107:53S–55S.
 
11.Voronkova NV, Blokhina NP, Kelli EI, et al. [Prospects for interferon therapy in chronic hepatitis C with normal transaminase levels]. Ter Arkh 2002;74:12–15.
 
12.Rossini A, Ravaggi A, Biasi L, et al. Virological response to interferon treatment in hepatitis C virus carriers with normal aminotransferase levels and chronic hepatitis. Hepatology 1997;26:1012–1017.
 
13.Silverman AL, Piquette DL, Filipiak CL, et al. Alfa interferon treatment of hepatitis C virus RNA-positive patients with normal or near-normal alanine aminotransferase levels. Am J Gastroenterol1997;92:1793–1795.
 
14.Sangiovanni A, Morales R, Spinzi G, et al. Interferon alfa treatment of HCV RNA carriers with persistently normal transaminase levels: a pilot randomized controlled study. Hepatology 1998;27:853–856.
 
15.Serfaty L, Chazouillières O, Pawlotsky JM, et al. Interferon alpha therapy in patients with chronic hepatitis C and persistently normal aminotransferase activity. Gastroenterology 1996;110:291–295.
 
16.Gholson CF, Faypot D, Taylor B, et al. Chronic hepatitis C virus (HCV) infection and persistently normal aminotransferases: a preliminary report of alfa interferon (IFN) resistance (Abstract 1097).Hepatology 1996;24:401A.
 
17.Hasan F, Asker H, Al-Khalid J, et al. Interferon-alpha in combination with ribavirin for the treatment of chronic hepatitis C in patients with persistently normal aminotransferase levels. Digestion 2002;65:127–130.
 
18.Sakugawa H, Nakasone H, Nakayoshi T, et al. Alanine aminotransferase (ALT) levels in a normal population and interferon therapy in chronic hepatitis C patients with normal ALT.Hepatogastroenterology 2003;50:165–169.
 
19.Poynard T, Leroy V, Cohard M, et al. Meta-analysis of interferon randomized trials in the treatment of hepatitis C: effects of dose and duration. Hepatology 1996;24:778–787.
 
20.Lee SS, Sherman M. Pilot study of interferon-alpha and ribavirin treatment in patients with chronic hepatitis C and normal transaminase values. J Viral Hepat 2001;8:202–205.
 
21.Orito E, Mizokami M, Suzuki K, et al. Loss of serum HCV RNA at week 4 of interferon alpha therapy is associated with more favourable long term response in patients with chronic hepatitis C. J Med Virol1995;46:109–115.
 
22.Shindo M, Arai K, Sokawa Y, et al. The virological and histological states of anti-hepatitis C virus positive subjects with normal liver biochemical values. Hepatology 1995;22:418–425.
 
23.Silini E, Bono F, Cividini A, et al. Differential distribution of hepatitis C virus genotypes in patients with and without liver function abnormalities. Hepatology 1995;21:285–290.
 
24.Pradat P. Predictive value of ALT levels for histologic findings in chronic hepatitis C: a European collaborative study. Hepatology 2002;36:973–977.
 
25.Healey CJ, Chapmann RWG, Fleming KA. Liver histology in hepatitis C infection: a comparison between patients with persistently normal or abnormal transaminases. Gut 1995;37:274–278.