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Intravenous Immunoglobulin Plus Interferon-α in Autoimmune Hepatitis C

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Abstract

Background: Hepatitis C virus (HCV) may be associated with a variety of autoimmune phenomena causing a therapeutic dilemma for treatment with interferon-α (IFNα), which stimulates autoimmune symptoms, or with corticosteroids, which may lead to an increasing of viral load. To evaluate the possible role of intravenous immunoglobulins (IVIg) in the response of patients treated with IFNα, we administered IVIg plus IFNα and compared the results with a group of patients treated with IFNα alone.

Methods: Forty-two patients affected by chronic hepatitis C with probable autoimmune disease were eligible for this open-label, randomised study. All patients tested positively for anti-nuclear antibodies, anti-smooth muscle antibodies, anti-liver/kidney microsomal antibodies and anti-mitochondrial antibodies. Patients were randomly assigned to one of two groups: group A received IVIg at a dosage of 400 mg/kg each day for 5 days, and then 3 MUI of leucocyte IFNα three times a week, while group B received physiological solution followed by the administration of leucocyte IFNα three times a week at the same dosage for 6 months.

Complete biochemical response was defined as a sustained normalisation of alanine aminotransferase levels, and complete virological response was defined as complete clearance of virus throughout the entire 6-month follow-up period. Immunological response was measured in terms of Autoimmune Hepatitis (AIH) score, while histological response was based on a reduction in histological activity index (HAI) score.

Results: Compared with patients receiving IFNα alone, a higher percentage of patients who received IFNα plus IVIg showed complete virological and histological responses (p = 0.04). More patients in the combination therapy group achieved biochemical and immunological responses, although the differences between the groups were not statistically significant at all time points.

Conclusions: Exogenously added Ig might modulate the immune network at various points. We propose that the immunomodulating action of IVIg acts synergistically with IFNα, achieving a better response to IFN treatment in patients with chronic HCV associated with autoimmunity. Data obtained from this preliminary study indicate a positive prospective for the clinical use of gamma globulins in patients with a high probability of autoimmune disorders associated with HCV infection.

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Acknowledgements

No sources of funding were used to assist in the preparation of this study. The authors have no conflicts of interest that are directly relevant to the content of this study.

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Authors and Affiliations

  1. Institute of Internal Medicine and Geriatrics, University of Catania, Via Messina, 829-95126, Catania, Italy

    Mariano Malaguarnera, Nicoletta Guccione, Massimo Motto & Ignazio Di Fazio

  2. Department of Pharmacology, Gynecology and Obstetrics, Pediatrics, University of Sassari and Institute of Population Genetic National Research Council, Alghero, Italy

    Salvatore Musumeci

  3. Institute of Internal Medicine, University of Catania, Catania, Italy

    Alfio Brogna

Authors
  1. Mariano Malaguarnera
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  2. Nicoletta Guccione
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  3. Salvatore Musumeci
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  4. Alfio Brogna
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  5. Massimo Motto
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  6. Ignazio Di Fazio
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Correspondence to Mariano Malaguarnera.

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Malaguarnera, M., Guccione, N., Musumeci, S. et al. Intravenous Immunoglobulin Plus Interferon-α in Autoimmune Hepatitis C. BioDrugs 18, 63–70 (2004). https://doi.org/10.2165/00063030-200418010-00006

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