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Acute hepatitis C virus infection: to treat or not to treat?

2004; Elsevier BV; Volume: 126; Issue: 4 Linguagem: Inglês

10.1053/j.gastro.2004.02.041

1528-0012

Elmar Jaeckel, Heiner Wedemeyer, Johannes Wiegand, Michael P. Manns,

Hepatitis B Virus Studies

We read with great interest the editorial by Gordon1Gordon S.C. New insights into acute hepatitis C.Gastroenterology. 2003; 125: 253-256Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar on the paper of Gerlach et al.2Gerlach J.T. Diepolder H.M. Zachoval R. Gruener N.H. Jung M.C. Ulsenheimer A. Schraut W.W. Schirren C.A. Waechtler M. Backmund M. Pape G.R. Acute hepatitis C high rate of both spontaneous and treatment-induced viral clearance.Gastroenterology. 2003; 125: 80-88Abstract Full Text Full Text PDF PubMed Scopus (505) Google Scholar and would like to provide our comments. The results of Gerlach et al. that delayed start of therapy in patients with acute HCV infection with a high probability of developing chronic infection leading to a sustained treatment response in 81% of cases is very interesting.2Gerlach J.T. Diepolder H.M. Zachoval R. Gruener N.H. Jung M.C. Ulsenheimer A. Schraut W.W. Schirren C.A. Waechtler M. Backmund M. Pape G.R. Acute hepatitis C high rate of both spontaneous and treatment-induced viral clearance.Gastroenterology. 2003; 125: 80-88Abstract Full Text Full Text PDF PubMed Scopus (505) Google Scholar Yet their study population, as well as their treatment protocol (dosage, duration, combination with ribavirin) was very heterogeneous. The patients were acquired in the setting of a tertiary referral center and do therefore not represent the typical patients seen in private practice. One of the clues in making the decision about therapy of acute HCV infection is the natural course of the disease. Although Gerlach et al. are reporting a chronicity rate of 66%,2Gerlach J.T. Diepolder H.M. Zachoval R. Gruener N.H. Jung M.C. Ulsenheimer A. Schraut W.W. Schirren C.A. Waechtler M. Backmund M. Pape G.R. Acute hepatitis C high rate of both spontaneous and treatment-induced viral clearance.Gastroenterology. 2003; 125: 80-88Abstract Full Text Full Text PDF PubMed Scopus (505) Google Scholar most recent studies evaluating the natural disease course still report about the development of chronic HCV infection in 70%–84% of patients.3Santantonio T. Sinisi E. Guastadisegni A. Casalino C. Mazzola M. Gentile A. Leandro G. Pastore G. Natural course of acute hepatitis C a long-term prospective study.Dig Liver Dis. 2003; 35: 104-113Abstract Full Text Full Text PDF PubMed Scopus (98) Google Scholar, 4Parana R. Vitvitski L. Andrade Z. Trepo C. Cotrim H. Bertillon P. Silva F. Silva I, L. deOliveira I.R. Lyra L. Acute sporadic non-A, non-B hepatitis in northeastern Brazil etiology and natural history.Hepatology. 1999; 30: 289-293Crossref PubMed Scopus (36) Google Scholar, 5Orland J.R. Wright T.L. Cooper S. Acute hepatitis C.Hepatology. 2001; 33: 321-327Crossref PubMed Scopus (187) Google Scholar We think that the distinction between symptomatic and asymptomatic acute HCV infection can be very subjective and might therefore not be very helpful in the clinical setting. Likewise we should rather compare time from expected exposure until start of therapy instead time from symptoms until therapy whenever possible. In our recently published study, the period from exposure to therapy was 89 days.6Jaeckel E. Cornberg M. Wedemeyer H. Santantonio T. Mayer J. Zankel M. Pastore G. Dietrich M. Trautwein C. Manns M.P. Treatment of acute hepatitis C with interferon alfa-2b.N Engl J Med. 2001; 345: 1452-1457Crossref PubMed Scopus (760) Google Scholar Therefore, the patients treated in our study were most likely not patients who would have cleared the virus spontaneously.7Hofer H. Watkins-Riedel T. Janata O. Penner E. Holzmann H. Steindl-Munda P. Gangl A. Ferenci P. Spontaneous viral clearance in patients with acute hepatitis C can be predicted by repeated measurements of serum viral load.Hepatology. 2003; 37: 60-64Crossref PubMed Scopus (184) Google Scholar All patients in our study had hepatitis (ALT elevations); patients with mere positive HCV-RNA without elevations of liver function tests were not included and not treated.6Jaeckel E. Cornberg M. Wedemeyer H. Santantonio T. Mayer J. Zankel M. Pastore G. Dietrich M. Trautwein C. Manns M.P. Treatment of acute hepatitis C with interferon alfa-2b.N Engl J Med. 2001; 345: 1452-1457Crossref PubMed Scopus (760) Google Scholar We deem the “suboptimal therapy” as cited by Gordon1Gordon S.C. New insights into acute hepatitis C.Gastroenterology. 2003; 125: 253-256Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar from our study still the gold standard until prospective trials show a more effective form of therapy. Furthermore, we recently demonstrated the durability of the sustained response in our patient cohort.8Wiegand J. Tillmann H.L. Jaeckel E. Cornberg M. Dietrich M. Hinrichsen H. Fritsch W.P. Kroger J. Aslan N. Kubitschke A. Manns M.P. Wedemeyer H. Immunological, virological and clinical long-term follow-up after interferon therapy of acute hepatitis C infection.J Hepatol. 2003; 8 (abstr. 623): 181Abstract Full Text PDF Google Scholar We want especially emphasize that so far there is no need and no data to support the inclusion of ribavirin in the treatment of acute HCV infection. We should rather test other treatment regimens with less side effects, lower costs and shorter durations than combination therapy. In this respect we recently presented data from another nationwide, prospective study conducted in Germany during the AASLD meeting in Boston showing that monotherapy with pegylated interferon alfa-2b for 6 month once a week was equally effective in the therapy of acute HCV infection as our initial protocol.9Wiegand J. Boecher W. Buggisch P. Zeuzem S. Gelbmann C.M. Cornberg M. Jaeckel E. Wedemeyer H. Manns M.P. 24 weeks of monotherapy with pegylated interferon alfa-2b in patients with acute hepatitis C.Hepatology. 2003; 38: 227AGoogle Scholar The recommendation of Gordon to wait up to 6 months before initiating therapy is until now not supported by published data.1Gordon S.C. New insights into acute hepatitis C.Gastroenterology. 2003; 125: 253-256Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar Furthermore, treatment of the 66%–85% of patients developing a chronic course of their disease, would mean to treat these patients in most cases for 12 months with combination therapy instead of interferon monotherapy for 6 months. This would results in higher cost, more side effects, and potentially lower sustained response rates. However, we agree that it will be of importance to find out if we can delay the initiation of therapy in patients to prevent treatment of patients with a self-limited course of the disease. As there are no validated markers of a self-limited disease we initiated another nationwide study in Germany starting in January 2004 comparing the a “wait and see” strategy with immediate pegylated IFN monotherapy in a prospective, randomized study sponsored by the German network of excellence for viral hepatitis (Hep-Net; www.kompetenznetz-hepatitis.de),10Manns M.P. Meyer S. Wedemeyer H. The German network of excellence for viral hepatitis (Hep-Net).Hepatology. 2003; 38: 543-544Crossref PubMed Scopus (30) Google Scholar which enabled us to recruit 40–60 patients with acute HCV infection per year, a number not yet met by any other trial. To meet the justified criticism with current trials, this study will be prospectively randomized and aims to enroll larger numbers of patients. We will have to await the results of these trials before definitive recommendations regarding a delayed initiation of therapy can be made. Until then we think that there is abundant data of prospective trials demonstrating the benefit of early monotherapy with IFN alfa-2b. There seems to be no need for the combination therapy with ribavirin.