A randomized controlled trial of a 12‐month course of recombinant human interferon‐α in chronic delta (type D) hepatitis: A multicenter Italian study
ABSTRACT To determine whether long-term therapy with recombinant interferon- can improve the course of chronic delta hepatitis, 61 Italian patients with this disease were randomly assigned to receive either interferon--2b three times a week (5 MU/m2 for 4 mo and then 3 MU/m2 for another 8 mo) or no treatment. At the end of the 12-mo study, all patients were followed-up for 12 additional months. Normalization or decrease of more than 50% from baseline of serum ALT levels occurred in 42% of treated patients the fourth month of therapy, 26% the twelfth month and 3% the twenty-fourth month vs. 7%, 7% and 0%, respectively, in the control group. However, relapses occurred in 7 of 8 (87.5%) responders 1 to 10 mo (mean = 3.5 mo) after cessation of therapy.Liver biopsies were carried out at baseline and during the twelfth month of treatment. Histological improvement, mostly caused by decrease of portal inflammation, was observed in 57% of treated and 36% of untreated patients. Measures of antiviral activity (serum hepatitis delta virus RNA and intrahepatic hepatitis delta antigen) showed similar levels in treated and control patients. In treated patients the percentage of patients who were negative for HDV RNA never exceeded that of baseline.Although interferon- in the dosage given in this study had no antiviral effect on patients with chronic hepatitis D, it reduced hepatic inflammation as measured by ALT levels. Whether a longer duration or reinstitution of interferon- therapy would achieve longterm control of ALT levels and prevent chronic liver damage is not known. (HEPATOLOGY 1991;13:1052–1056.)
- Gastroenterologie Clinique Et Biologique - GASTROEN CLIN BIOL. 01/2005; 29(4):384-387.
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ABSTRACT: Chronic coinfection with the hepatitis B (HBV) and hepatitis δ (HDV) viruses is known to cause severe liver disease, but the importance of coinfection with hepatitis C virus (HCV) and HBV has not been well documented. In the present study, the clinical and pathological severity of liver disease among patients with hepatitis resulting from multiple viruses was examined and an open trial of the efficacy of interferon-α2b (IFN-α) treatment was conducted. Nineteen patients with chronic HBV and HCV infection and 17 with HBV, HCV and HDV infection were studied: 12 in each group underwent liver biopsy. For each coinfected patient, two patients infected with HCV alone were selected as controls, and these were matched for age and risk factor and were estimated to have been infected for a similar duration. Coinfection with HBV and HCV or HBV, HCV and HDV was associated with more severe liver disease than HCV alone (P < 0.01); total Scheer score, portal and lobular inflammation and fibrosis were all worse in coinfected subjects. Eight patients with chronic HBV and HCV were treated with recombinant IFN-α2b [3 million units (MU), thrice weekly for 6 months]. Liver function tests normalized in two patients and one lost hepatitis B surface antigen (HBsAg). Seven patients with hepatitis B, C and δ coinfection were treated with the same regimen and only one normalized serum alanine aminotransferase (ALT) during (and after) treatment. It is concluded that coinfection with multiple hepatitis viruses is associated with histologically more severe liver disease than HCV alone. Short-and long-term responses to doses of IFN-α that are used to treat HCV are infrequent, but further studies are required to determine whether higher-dose IFN-α may benefit patients with combined hepatitis virus infections.Journal of Viral Hepatitis 12/2007; 2(1):39 - 45. · 3.08 Impact Factor
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ABSTRACT: Background: Chronic hepatitis delta virus (HDV) is a severe and rapidly progressive liver disease for which no therapy has been proved to be effective.Objective: The aim of this study was to investigate the efficacy and tolerability of long-term therapy with a combination of recombinant interferon (IFN)-alfa and lamivudine.Methods: In this single-center, prospective, open-label, uncontrolled study, patients aged 18 to 60 years with chronic HDV were eligible. Patients were treated with a combination of 10 million units of IFN-alfa-2b subcutaneously 3 times weekly and lamivudine 100 mg once daily for 12 months. The primary outcome measures were biochemical and histologic response at the end of treatment and at least 12 months thereafter.Results: Twelve patients (10 men, 2 women; mean age, 33.9 years [range, 19–49 years]) were enrolled (6 treatment-naive patients, 6 previously treated patients). Normalization or decrease of >50% from baseline in serum alanine aminotransferase (ALT) level occurred in 8 (66.7%) of 12 patients at month 12 of treatment. Of the 12 patients, 10 (83.3%) completed the trial; 1 (8.3%) was withdrawn because of severe leukopenia and 1 (8.3%) was lost to follow-up. Relapses occurred in 5 of 8 (63.3%) initial responders shortly after the cessation of therapy. In 3 (25%) patients whose ALT levels became normal at the end of the therapy, the complete biochemical responses persisted for up to 3 years (mean, 31 months). The treatment was associated with a marked improvement in histologic activity.Conclusions: In this study, combination therapy with IFN-alfa and lamivudine was well tolerated and reduced hepatic inflammation was found. Further controlled trials are needed to show possible beneficial effects of this model of therapy and to determine the optimal dose and duration of therapy for chronic HDV.Current Therapeutic Research 01/2002; 63(11):736-747. · 0.45 Impact Factor