Hepatitis: Homberg JC

Alvarez F, Berg PA, Bianchi FB, Bianchi L, Burroughs AK, Cancado EL, Chapman RW, Cooksley WG, Czaja AJ, Desmet VJ, Donaldson PT, Eddleston AL, Fainboim L, Heathcote J, Homberg JC, Hoofnagle JH, Kakumu S, Krawitt EL, Mackay IR, MacSween RN, Maddrey WC, Manns MP, McFarlane IG, Meyer zum Büschenfelde KH, Zeniya M. · Institute of Liver Studies, King's College Hospital, London, UK. · J Hepatol. · Pubmed #10580593 No free full text.

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Homberg JC. · Laboratoire Central d'Immunologie et d'Hématologie, Hôpital Saint-Antoine, Paris. · Presse Med. · Pubmed #10228484 No free full text.

Abstract: AUTOANTIBODY PRODUCTION: The production of autoantibodies can only occur if immune tolerance is circumvented. Thus drug-induced autoimmune hemolytic anemia requires that the drug have an effect on both autoantigens and on the immune system. AN EXAMPLE, METHYLDOPA: Methyldopa is a hypotensive agent which induces major production of anti-Rh IgG anti-erythrocyte autoantibodies, anti-nuclear antibodies and anti-actin antibodies. These autoantibodies generally appear 6 months after treatment onset and are observed in 20% of treated patients. Hemolysis is however exceptional and is only clinically or biologically perceptible in 1 to 2% of the patients who become immunized. Induced lupus has been reported as have been several dozen cases of drug-induced hepatitis with anti-actin autoantibodies. DRUGS INDUCING HEMOLYTIC ANEMIA: Besides methyldopa, other drugs known to induce hemolytic anemia include levodopa used for Parkinson's disease, mefenamic acid, a nonsteroidal antiinflammatory drug, interferon-alpha, used in chronic viral hepatitis, cyclosporin used for the prevention of graft rejection and the treatment of certain autoimmune diseases, and fludarabin, used in chronic lymphoid leukemia. THERAPEUTIC STRATEGY: If there is no clinical or biological expression, the drug can be continued, excepting fludarabin where regular controls are needed. If hemolytic anemia is patent, the drug must be discontinued, transfusion and corticosteroid therapy should be envisaged.

Cattan P, Berney T, Conti F, Calmus Y, Homberg JC, Houssin D, Soubrane O. · Service de Chirurgie, Hôpital Cochin, 27 rue du Faubourg Saint-Jacques, 75679 Paris Cedex 14, France. · Transpl Int. · Pubmed #11875611 No free full text.

Abstract: The relevance of autoimmune hepatitis (AIH) classification for clinical purposes is controversial. We analyzed the outcome after orthotopic liver transplantation (OLT) of nine type I and seven type II AIH patients. Type II patients had a significantly higher incidence of cirrhosis at the time of diagnosis, more resistance to steroid therapy, and a higher Child-Pugh score at the time of OLT. OLT was performed in emergency in three type II patients and electively in all type I patients. Four type II and one type I patients died in the postoperative period. There was no difference regarding the incidence of post-OLT infection and rejection between the two types. No recurrence of AIH was observed. The 6-year actuarial survival rates for type I and type II patients were 76% and 43%, respectively. Type II AIH patients who have a poor response to medical therapy should be considered for OLT with a shortened delay.

Ballot E, Homberg JC, Johanet C. · Laboratoire d'Immunologie, Hôpital Saint Antoine, Paris, France. · J Hepatol. · Pubmed #10952238 No free full text.

Abstract: BACKGROUND/AIMS: Auto-immune hepatitis patients are divided into two well-defined subgroups on the basis of immunoserological markers, i.e. anti-actin cable and/or anti-nuclear antibodies for the auto-immune hepatitis type 1, anti-liver/kidney microsome type 1 and/or anti-liver cytosol type 1 for the autoimmune hepatitis type 2. Controversial antibodies to a soluble liver antigen have been proposed as a diagnostic marker for the putative auto-immune hepatitis type 3. The aim was to investigate the implication of anti-soluble liver antigen antibodies in the diagnosis of auto-immune hepatitis and their ability to define auto-immune hepatitis type 3. METHODS: Sera from 483 patients with hepatic and non-hepatic diseases, and 102 sera from blood donors were analyzed by an inhibition capture enzyme-linked immunosorbent assay. RESULTS: Anti-soluble liver antigen antibodies were found in 13 of the 106 (12%) auto-immune hepatitis type 1 patients and 10 of the 49 (20%) cryptogenic hepatitis patients tested. In contrast, they were not detected in auto-immune hepatitis type 2 (n=54), primary sclerosing cholangitis (n=37), primary biliary cirrhosis (n=52), hepatitis C virus infection (n=105), alcoholic hepatitis (n=25), various non-hepatic autoimmune disorders (n=55) and in healthy blood donors (n=102). The clinical and biological features of antisoluble liver antigen-seropositive patients were similar to those of auto-immune hepatitis type 1 and did not distinguish a subgroup of auto-immune hepatitis. CONCLUSION: The data support the concept that antisoluble liver antigen-positive cryptogenic hepatitis is similar to auto-immune hepatitis type 1. Anti-soluble liver antigen antibodies can be considered as an additional and specific auto-immune hepatitis type 1 diagnostic marker.

Lapierre P, Hajoui O, Homberg JC, Alvarez F. · Service de Gastroentérologie et Nutrition, Hôpital Sainte-Justine, Montréal, Québec, Canada. · Gastroenterology. · Pubmed #10029623 No free full text.

Abstract: BACKGROUND & AIMS: Anti-liver cytosol type 1 autoantibodies have been reported in association with anti-liver-kidney microsome type 1 autoantibodies in 30% of patients with autoimmune hepatitis type II. In 10% of cases, anti-liver cytosol type 1 antibodies are the only liver-related circulating autoantibodies. The liver cytosol antigen is a liver-specific 62-kilodalton protein present in the cell as an oligomer of approximately 240 kilodaltons. The aim of this study was to identify the antigen recognized by anti-liver cytosol antibody. METHODS: To identify the liver cytosol antigen, an anti-liver cytosol type 1-positive serum was used for the screening of a complementary DNA library from HepG2 cells. Double immunodiffusion method was used to show the identity between the cytosolic and the cloned protein. RESULTS: The sequence of two isolated clones showed 85.2% homology with the formiminotransferase cyclodeaminase (FTCD) enzyme from pig liver. Antibodies purified by affinity with the recombinant protein and sera from mice immunized with FTCD recognized a 62-kilodalton human cytosolic protein when tested by immunoblot. The identity of precipitation lines was found between the cytosolic antigen and FTCD. CONCLUSIONS: This enzyme is a liver-specific antigen recognized by the sera of patients with autoimmune hepatitis.