Two Studies Find Benefit in Treating HCV During Acute Infection

There were two interesting poster abstracts at DDW 2001 addressing the unusual patient group--patients with acute HCV infection. They are unusual because they are hard to find. Therefore, treating this patient group has not been studied much. Just as in HIV its hard to identify patients with acute infection. It 's not until years later, in general, that patients get tested and find out they have HIV or HCV. In the Jaeckel study below, at the end of the 24-week treatment period, 97% of treated patients were virologic responders, whereas only 30% of untreated patients spontaneously cleared virus. I think that the sustained response at the end of the 24-week follow-up period in the treated group was 70%. This was using the standard interferon without ribavirin, so using pegylated interferon with ribavirin ought to yield better results. Although, Jaeckel suggests interferon monotherapy is adequate I suppose because of the high response rates he saw. In the Chone study (n=14), at the end of treatment 71% (n=10) were responders (HCV-RNA negative and normal liver enzymes). 60% of the responders had an average follow-up of 17 months & all were sustained responders. The studies concluded treatment during acute infection can prevent chronic infection in a high percentage of patients and unexpected side effects do not appear to occur.

EARLY TREATMENT OF ACUTE HEPATITIS C INFECTION WITH MONOTHERAPY INTERFERON ALFA IS EFFECTIVE TO PREVENT DEVELOPMENT OF CHRONIC HEPATITIS
     Laurence Chone, Jean-Pierre Bronowicki, Helene Barraud, Jerome Watelet, Herve Hudziak, Patrice Wolff, Marc-Andre Bigard, CHU Nancy-Brabois, Nancy France

Acute hepatitis C is often asymptomatic but has a great propensity to become chronic. Available data seem to indicate that Interferon may reduce the rate of chronicity. From 1990 until October 2000, 1605 patients with hepatitis C infection were sent in our unit because of HCV infection. Among them, 18 (1.1%) had symptomatic acute HCV hepatitis. Acute infection was defined as a period of less than 4 months after time of infection. The mean age of patients was 24.5 years and 50% were female. Fifteen patients (83%) were infected by intravenous drug abuse, one (6%) patient after tattooing and in 2 patients (11%) the mode remained unclear. Mean viral load at inclusion was 234 600 UI/ml (Cobas Amplicor HCV Monitor 2.0). Eleven (61%) patients were icteric with a mean bilirubin of 145 mg/L. Mean ALT was 1080 UI/L (range 172-2120). Fourteen patients (77%) were treated with 3 MU Interferon alfa s.c. tiw for 6 months. One patient became spontaneously HCV-RNA negative before treatment and four months after contamination. Three patients were lost of view. Therapy was initiated medium time of 51 days after acute infection. Among treated patients, 57% were HCV-RNA negative with normal transaminases after one month. All patients HCV-RNA positive after 8 weeks of treatment remained non-responders during the treatment. At the end of the treatment, 10 patients (71%) were responders (HCV-RNA negative and normal transaminases). Among the responder patients, 60% had a mean follow up period of 17 months, and all of them had sustained response. The others started intravenous drug abuse again and were lost of sight. Conclusions: Early therapy of acute HCV infection with interferon alfa prevents development of chronic infection in 71% of patients. Response became soon (after one month in most of cases) and was sustained in all patients who accepted follow up. But to keep in view this patients, often active intravenous drug users, is the great challenge.

TREATMENT OF ACUTE HEPATITIS C INFECTION WITH INTERFERON-ALFA 2B MONOTHERAPY PREVENTS DEVELOPMENT OF CHRONIC HCV INFECTION
     Elmar Jaeckel, Markus Cornberg, Medicine Hochschule Hannover, Hannover Germany; Teresa Santantonio, Clin Malattie Infettive, Bari Italy; Julika Mayer, Heiner Wedemeyer, Medicine Hochschule Hannover, Hannover Germany; Myrga Zankel, Essex Pharma, Munich Germany; Christian Trautwein, Medicine Hochschule Hannover, Hannover Germany; Guiseppe Pastore, Clin Malattie Infettive, Bari Italy; Michael P. Manns, Medicine Hochschule Hannover, Hannover Germany

Background: Animal models of infections with non-cytopathic RNA viruses as well as recent success in treating acute HIV-infection support the importance of early control of viral replication for preventing or controlling chronic infection. As the incidence of new HCV infections is decreasing, few patients are seen at one institution thereby preventing larger clinical trials.

Aim / methods: Therefore in 1998 we initiated a national prospective treatment trial in Germany. Over 7000 information brochures were distributed to hospitals and private practices. From March 1998 until October 2000, 43 patients with acute HCV infections were included into the study by 24 different centers. All patients were treated within 4 month after infection with 5 Mio. IU interferon-alfa-2b (IFN) s.c. daily for 4 weeks, followed by 5 Mio. U IFN tiw for 20 further weeks (group A). Therapy was initiated medium time of 89 days after acute infection and 34 patients have completed the follow-up of 6 month after end of therapy. 40 patients with acute HCV-infection seen at the University of Bari between 1995 and 2000, who did not receive therapy, were taken as control (group B).

Results: Mean age of the patients was 36 / 40 (group A / B) years and 58 / 42% were female. 16 / 60% were infected by medical procedures, 33 / 8% by needle-stick injury, 19 / 18% by intravenous drug abuse which was not ongoing at the time of therapy, 23 / 8% had sexual contact with HCV-infected partners and in 9 / 8% the mode of infection remained unclear. 53 / 63% of patients were infected with HCV-genotype I, 7 / 28% with genotype II, 19 / 8% with genotype and 0 / 5% with genotype IV. Mean ALT was 891 / 1563 U/l. HCV-RNA was undetectable in 97% of patients in group A vs. 30% in group B after 24 weeks (p>0.000001). One patient in group A subsequently cleared the virus after an hepatitis flare. 74% of patients in group A were already HCV-RNA negative at week 2. At the end of follow-up no patient in group A had signs of chronic HCV-infection while 70% of patients in group B developed chronic HCV-infection (p<0.000001). Therapy was well tolerated and profile of side effects was comparable to IFN-monotherapy-trials for chronic HCV infections.

Conclusions: 1) Early therapy of acute HCV infection with interferon-alfa-2b prevents development of chronic infection in all patients treated. 2) If IFN-monotherapy is initiated early, combination therapy is unnecessary. 3) Without early treatment acute HCV-infection becomes chronic in the majority of patients.