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Drug-induced hepatitis associated with anticytoplasmic organelle autoantibodies

Authors

  • Professor Jean-Claude Homberg,

    Corresponding author
    1. Laboratoire Central d-Immunologie et d-Hématologie, Laboratoire de Pharmacologie, Clinique Hépatogastroentörologique and Service d-Hépatogastroentérologie, Hǒpital Saint-Antoine, Paris 12, France; Service d-Hépatogastroentérologie, Hǒpital Jean Verdier, Bondy, France; Service d-Hépatologie, Hǒpital Universitaire, Paris 14, France; and Service d-Hépatologie, Hǒpital Beaujon, Clichy, France
    • Hǒpital Saint-Antoine, 184, rue du Faubourg Saint-Antoine, 75571 Paris Cedex 12, France
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  • Nielsen Abuaf,

    1. Laboratoire Central d-Immunologie et d-Hématologie, Laboratoire de Pharmacologie, Clinique Hépatogastroentörologique and Service d-Hépatogastroentérologie, Hǒpital Saint-Antoine, Paris 12, France; Service d-Hépatogastroentérologie, Hǒpital Jean Verdier, Bondy, France; Service d-Hépatologie, Hǒpital Universitaire, Paris 14, France; and Service d-Hépatologie, Hǒpital Beaujon, Clichy, France
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  • Samir Helmy-Khalil,

    1. Laboratoire Central d-Immunologie et d-Hématologie, Laboratoire de Pharmacologie, Clinique Hépatogastroentörologique and Service d-Hépatogastroentérologie, Hǒpital Saint-Antoine, Paris 12, France; Service d-Hépatogastroentérologie, Hǒpital Jean Verdier, Bondy, France; Service d-Hépatologie, Hǒpital Universitaire, Paris 14, France; and Service d-Hépatologie, Hǒpital Beaujon, Clichy, France
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    • Drs. Helmy-Khalil (Department of Immunology and Metabolism, Faculty of Medicine, Alexandria, Egypt) and S. Islam (Department of Medicine of Dacca Medical College, Dacca, Bangladesh) are both recepients of a French government scholarship.

  • Michel Biour,

    1. Laboratoire Central d-Immunologie et d-Hématologie, Laboratoire de Pharmacologie, Clinique Hépatogastroentörologique and Service d-Hépatogastroentérologie, Hǒpital Saint-Antoine, Paris 12, France; Service d-Hépatogastroentérologie, Hǒpital Jean Verdier, Bondy, France; Service d-Hépatologie, Hǒpital Universitaire, Paris 14, France; and Service d-Hépatologie, Hǒpital Beaujon, Clichy, France
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  • Raoul Poupon,

    1. Laboratoire Central d-Immunologie et d-Hématologie, Laboratoire de Pharmacologie, Clinique Hépatogastroentörologique and Service d-Hépatogastroentérologie, Hǒpital Saint-Antoine, Paris 12, France; Service d-Hépatogastroentérologie, Hǒpital Jean Verdier, Bondy, France; Service d-Hépatologie, Hǒpital Universitaire, Paris 14, France; and Service d-Hépatologie, Hǒpital Beaujon, Clichy, France
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  • Shamsul Islam,

    1. Laboratoire Central d-Immunologie et d-Hématologie, Laboratoire de Pharmacologie, Clinique Hépatogastroentörologique and Service d-Hépatogastroentérologie, Hǒpital Saint-Antoine, Paris 12, France; Service d-Hépatogastroentérologie, Hǒpital Jean Verdier, Bondy, France; Service d-Hépatologie, Hǒpital Universitaire, Paris 14, France; and Service d-Hépatologie, Hǒpital Beaujon, Clichy, France
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    • Drs. Helmy-Khalil (Department of Immunology and Metabolism, Faculty of Medicine, Alexandria, Egypt) and S. Islam (Department of Medicine of Dacca Medical College, Dacca, Bangladesh) are both recepients of a French government scholarship.

  • François Darnis,

    1. Laboratoire Central d-Immunologie et d-Hématologie, Laboratoire de Pharmacologie, Clinique Hépatogastroentörologique and Service d-Hépatogastroentérologie, Hǒpital Saint-Antoine, Paris 12, France; Service d-Hépatogastroentérologie, Hǒpital Jean Verdier, Bondy, France; Service d-Hépatologie, Hǒpital Universitaire, Paris 14, France; and Service d-Hépatologie, Hǒpital Beaujon, Clichy, France
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  • Victor Georges Levy,

    1. Laboratoire Central d-Immunologie et d-Hématologie, Laboratoire de Pharmacologie, Clinique Hépatogastroentörologique and Service d-Hépatogastroentérologie, Hǒpital Saint-Antoine, Paris 12, France; Service d-Hépatogastroentérologie, Hǒpital Jean Verdier, Bondy, France; Service d-Hépatologie, Hǒpital Universitaire, Paris 14, France; and Service d-Hépatologie, Hǒpital Beaujon, Clichy, France
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  • Pierre Opolon,

    1. Laboratoire Central d-Immunologie et d-Hématologie, Laboratoire de Pharmacologie, Clinique Hépatogastroentörologique and Service d-Hépatogastroentérologie, Hǒpital Saint-Antoine, Paris 12, France; Service d-Hépatogastroentérologie, Hǒpital Jean Verdier, Bondy, France; Service d-Hépatologie, Hǒpital Universitaire, Paris 14, France; and Service d-Hépatologie, Hǒpital Beaujon, Clichy, France
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  • Michel Beaugrand,

    1. Laboratoire Central d-Immunologie et d-Hématologie, Laboratoire de Pharmacologie, Clinique Hépatogastroentörologique and Service d-Hépatogastroentérologie, Hǒpital Saint-Antoine, Paris 12, France; Service d-Hépatogastroentérologie, Hǒpital Jean Verdier, Bondy, France; Service d-Hépatologie, Hǒpital Universitaire, Paris 14, France; and Service d-Hépatologie, Hǒpital Beaujon, Clichy, France
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  • Jacques Toulet,

    1. Laboratoire Central d-Immunologie et d-Hématologie, Laboratoire de Pharmacologie, Clinique Hépatogastroentörologique and Service d-Hépatogastroentérologie, Hǒpital Saint-Antoine, Paris 12, France; Service d-Hépatogastroentérologie, Hǒpital Jean Verdier, Bondy, France; Service d-Hépatologie, Hǒpital Universitaire, Paris 14, France; and Service d-Hépatologie, Hǒpital Beaujon, Clichy, France
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  • Gaby Danan,

    1. Laboratoire Central d-Immunologie et d-Hématologie, Laboratoire de Pharmacologie, Clinique Hépatogastroentörologique and Service d-Hépatogastroentérologie, Hǒpital Saint-Antoine, Paris 12, France; Service d-Hépatogastroentérologie, Hǒpital Jean Verdier, Bondy, France; Service d-Hépatologie, Hǒpital Universitaire, Paris 14, France; and Service d-Hépatologie, Hǒpital Beaujon, Clichy, France
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  • Jean-Pierre Benhamou

    1. Laboratoire Central d-Immunologie et d-Hématologie, Laboratoire de Pharmacologie, Clinique Hépatogastroentörologique and Service d-Hépatogastroentérologie, Hǒpital Saint-Antoine, Paris 12, France; Service d-Hépatogastroentérologie, Hǒpital Jean Verdier, Bondy, France; Service d-Hépatologie, Hǒpital Universitaire, Paris 14, France; and Service d-Hépatologie, Hǒpital Beaujon, Clichy, France
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Abstract

A study from five hepatology units documenting 157 cases of drug-induced hepatitis and a second study from a laboratory of immunology which tested more than 100,000 sera permitted us to establish the frequency of antiorganelle antibodies and their diagnostic value in drug-induced hepatitis. In drug-induced hepatitis caused by a heterogenous group of drugs consisting of ajmaline, aminopterine, isaxonine, isoniazid, perhexiline, phenylbutazone and troleandromycine, antiorganelle antibodies were absent or rare. In drug-induced hepatitis caused by another heterogenous group of drugs, including clometacin, fenofibrate, oxyphenisatin and papaverine, antismooth muscle, antinucleus and antimitochondria antibodies were found in isolation or in different combinations in 70% of cases. From the presence of antismooth muscle antibodies in sera, we could trace 30 cases of clometacin-induced hepatitis. The third group included drug-induced hepatitis with special antibody:iproniazid-induced hepatitis with antimitochondrial antibody 6 and tienilic acid (ticrynafen)-induced hepatitis with antiliver/kidney microsome antibody 2 (anti-LKM2). These two antibodies are rare in routine sera and were absent in patients who received the drug and had no liver damage. From the presence of corresponding antibodies, we detected six cases of iproniazid-induced hepatitis and 67 cases of tienilic acid-induced hepatitis. Antiorganelle antibodies found in high titers disappeared in 2 to 24 months following withdrawal of the offending drug. The fourth group was represented by halothane-induced hepatitis; antiliver/kidney microsome antibody 1 was weak and infrequent. Similarities between drug-induced hepatitis of the second group and lupoïd hepatitis suggest that drugs may reveal this spontaneous disorder. The specific antibody found in iproniazid and tienilic acid-induced hepatitis may suggest the site where the drug attaches in vivo. Immunoallergic hypersensitivity seems to be the mechanism involved in halothane-induced hepatitis; autoimmune phenomenon may play a role in liver damage caused by tienilic acid.

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