Correspondence

Lack of Sustained Efficacy of Interferon in Patients with Chronic Hepatitis C

N Engl J Med 1996; 334:1479-1480May 30, 1996

Article

To the Editor:

The hepatitis C virus (HCV) has been shown to cause progressive and chronic liver damage.1 Interferon therapy apparently eradicates HCV in 20 to 30 percent of patients, but the follow-up in published studies is generally short (6 to 18 months) and never exceeds 3 to 5 years.2-4

We followed for 92 to 99 months (mean, 93) 13 patients (9 men and 4 women; mean age, 35 years; range, 21 to 54) who had received 3 million units of recombinant interferon alfa-2a (Roferon r-A, Roche) or interferon alfa-2b (Intron A, Schering-Plough) three times per week for 6 months (group 1), and for 73 to 80 months (mean, 76) we followed 16 patients (12 men and 4 women; mean age, 33 years; range, 23 to 50) who had received 6 million units of one of these drugs three times per week for 6 months, followed by 3 million units three times per week for an additional 6 months (group 2). None of these patients were positive for hepatitis B surface antigen or antibody to the human immunodeficiency virus; none were alcoholics or drug abusers. All the patients (12 with post-transfusion hepatitis and 17 with sporadic hepatitis C) had had abnormal alanine aminotransferase values for over one year. Liver biopsy was performed in each patient during the six months before therapy. Cirrhosis was not present in any; 23 patients had chronic active hepatitis, 4 chronic persistent hepatitis, and 2 chronic lobular hepatitis.

All 29 patients had responses to interferon alfa. Their alanine aminotransferase levels returned to normal during treatment and remained so until one year after the end of therapy. At that time, their serum was negative for HCV RNA by the polymerase chain reaction, and liver biopsy showed improvement (mean Knodell score for histologic activity5 before treatment, 8.8; one year after the end of therapy, 4.5). The results of the long-term follow-up are shown in Table 1Table 1Long-Term Follow-up of 29 Patients with Chronic Hepatitis C Treated with Two Regimens of Interferon Alfa..

Six years after interferon therapy, two of the four patients in group 2 with normal alanine aminotransferase values had liver biopsies that showed chronic active hepatitis. The other two patients in this group had minimal lesions on liver biopsy. The liver biopsy of the only patient, in group 1, who had a normal alanine aminotransferase value after seven years of follow-up showed chronic active hepatitis with cirrhosis.

Thus, in a prolonged follow-up of 29 patients with chronic hepatitis C infections who were treated with recombinant interferon alfa at total doses ranging from 216 million to 648 million units, only 2 had sustained improvement. In all 29 patients, the virus had apparently cleared and the histologic features of the liver had improved after a one-year follow-up.

Our findings indicate that at the doses used, interferon has little, if any, long-term efficacy in patients with chronic hepatitis C.

Sandro Vento, M.D.
Ercole Concia, M.D.
Teresa Ferraro, M.D.
University of Verona, 37124 Verona, Italy

5 References

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Citing Articles (7)

Citing Articles

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   Martin-Walter Welker, Stefan Zeuzem. (2009) Occult hepatitis C: How convincing are the current data?. Hepatology 49:2, 665-675
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   Ivanko Bojic, Ljubisa Dokic, Svetlana Minic. (2006) Treatment options for chronic hepatitis C virus infection. Medicinski pregled 59:11-12, 560-566
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   Calogero Camma, Marco Giunta, Giovanbattista Pinzello, Alberto Morabito, Paolo Verderio, Luigi Pagliaro. (1999) Chronic hepatitis C and interferon alpha: conventional and cumulative meta-analyses of randomized controlled trials. The American Journal of Gastroenterology 94:3, 581-595
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   Alberto Larghi, Alessandro Tagger, Andrea Crosignani, Maria Lisa Ribero, Savino Bruno, Giuseppe Portera, Pier Maria Battezzati, Marco Maggioni, Michele Fasola, Massimo Zuin, Mauro Podda. (1998) Clinical significance of hepatic HCV RNA in patients with chronic hepatitis C demonstrating long-term sustained response to interferon-alpha therapy. Journal of Medical Virology 55:1, 7-11
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5. 5

   Stephen D.H.P. Malnick, Hemda Schmilovitz-Weiss. (1997) Editorial: Interferon Therapy for Chronic HCV Hepatitis: Trick or Treat?. Journal of Clinical Gastroenterology 25:1, 310-313
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   Greg A. Knoll, Martha R. Tankersley, Jeannette Y. Lee, Bruce A. Julian, John J. Curtis. (1997) The impact of renal transplantation on survival in hepatitis C-positive end-stage renal disease patients. American Journal of Kidney Diseases 29:4, 608-614
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7. 7

   Peter J Scheuer, Kris Krawczynski, Amar P Dhillon. (1997) Histopathology and detection of hepatitis C virus in liver. Springer Seminars in Immunopathology 19:1, 27-45
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