Hepatitis, autoimmune chronic active

Autoimmune active chronic hepatitis a corticosteroid improves wellbeing, liver function and histology prednisolone will benefit some 80% and should be continued in the long term, as most patients relapse if the drug is withdrawn. 

Diseases in which the body produces antibodies against its own components. Among the diseases which are thought to have an autoimmune basis are primary myxoedema, thyrotoxicosis, pernicious anaemia, Addison s disease, Goodpasture s syndrome, myasthenia gravis, some haemolytic anaemias, primary biliary cirrhosis, active chronic hepatitis, ulcerative colitis, Sjogren s syndrome, rheumatoid arthritis and systemic lupus erythematosus. See separate entries for some of these diseases. 

It is indicated in renal transplantation, severe active rheumatoid arthritis unresponsive to other therapy, certain autoimmune diseases, chronic active hepatitis, idiopathic thrombocytopenic purpura and acquired haemolytic anaemia. 

Rerson, J.L., McHutchison, J.G., Fong, T., Redeker, A.G. A case of cyclosporine-sensitive, steroid-resistant autoimmune chronic active hepatitis. J. Clin. Gastroent. 1993 17 317-320 Rratt, D.S., Flavin, D.R., Kaplan, M.M. The successful treatment of autoimmune hepatitis with 6-mercaptopurine after failure with azathioprine. Gastroenterology 1996 110 271-274 Rahaman, SM., Chira, R, Koff, R.S. Idiopathic autoimmune chronic hepatitis triggered by hepatitis A. Amer. J. Gastroent. 1994 89 106-108... 

In 25 children with chronic hepatitis C, pretreatment positivity for liver/kidney microsomal type 1 (LKM-1) antibodies was associated with more frequent treatment-limiting increases in serum alanine transaminase activity (256). Withdrawal of interferon alfa-2b because of hypertransaminasemia was required in three of four LKM-1 positive children compared with two of the 21 LKM-1 negative children. Although none developed features of autoimmune hepatitis, careful surveillance of hepatic function is recommended in LKM-l-positive patients. 

Corticosteroids. Corticosteroids are immunosuppressant drugs which have had beneficial effects in autoimmune chronic active hepatitis. They were investigated for the treatment of ehronic aetive hepatitis B (183-185), resulting in increased HBV replication, membrane expression of viral antigen, and delayed HBeAg seroconversion (132, 186). Stopping steroid treatment usually leads to a rebound in hepatic disease activity but may be followed by termination of viral replication within a few months (187). Thus, despite the decrease in transaminase activity, corticosteroids have little role in the treatment of chronic hepatitis B. However, corticosteroids may be useful for pretreatment of certain patients prior to interferon therapy (188) or for enhaneing the efficacy of interferon or adenine arabinoside (ARA-A) treatment by prior steroid withdrawal in patients with mild inflammatory activity (189). 

Hematologic diseases autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, pernicous anemia Kidney disease Goodpasture syndrom, lipoid nephroses, minimal change glomerulonephritis Diseases of the gastrointestinal tract autoimmune chronic active hepatitis, autoimmune atrophic gastritis, Crohn s disease, ulcerative colitis... 

Scully, L.J., Clarke, D., and Barr, R.J., Diclofenac induced hepatitis. 3 cases with features of autoimmune chronic active hepatitis, Dig. Dis. Sci., 38, 744, 1993. 

Several types of immunosuppression have also been tried. Azathioprine alone was found to have no effect on PBC [82], but additional benificial effects were found in combination with ursodeoxychohc add and corticosteroids [78]. Cyclosporin showed some success, espe-dally in corticosteroid-resistant autoimmune hepatitis [83], but its use is generally considerably hmited by severe side-effects. Corticosteroids were effective in the management of several types of autoimmune chronic active hepatitis [84,85] and in the management of acute al-cohohc hepatitis [86]. Their use, however, has to be brief hi order to minimize side-effects. In the treatment of PBC, corticosteroids alone were found to be toxic and had only limited efficacy [77]. 

Immunosuppressive therapy is utilized in chronic severe asthma, where cyclosporine is often effective and sirolimus is another alternative. Omalizumab (anti-IgE antibody) has recently been approved for the treatment of severe asthma (see previous section). Tacrolimus is currently under clinical investigation for the management of autoimmune chronic active hepatitis and of multiple sclerosis, where IFN-3 has a definitive role. 

Preziati D, La Rosa L, Covini G, Marcelli R, Rescalli S, Persani L, Del Ninno E, Meroni PL, Colombo M, Beck-Peccoz P. Autoimmunity and thyroid function in patients with chronic active hepatitis treated with recombinant interferon alpha-2a. Eur J Endocrinol 1995 132(5) 587-93. 

To a varying extent, ANA are detectable in chronic active hepatitis (CAH), in mixed forms of CAH/PBC and particularly in lupoid hepatitis (autoimmune hepatitis type I) (in 80-100%) as well as in oxyphenisatin-in-duced CAH. Clinically relevant titres start at a serum dilution of 1 80. Level of the titre, pattern of fluorescence and in particular interaction with the complement system are relevant for the pathogenic valence of ANA. The determination of ANA and SMA is indicated when autoimmune hepatitis is in question. 

Fig. 5.12 Antibodies against smooth muscles (SMA) in autoimmune chronic active hepatitis...

Manns, M., Kyriatsoulis, A., Gerken, G., Staritz, M., Meyer zum Bii-schenfelde, K.-H. Characterisation of a new subgroup of autoimmune chronic active hepatitis by autoantibodies against a soluble liver antigen. Lancet 1987/1 292- 294... 

Hashimoto, E., Lindor, K.D., Homburger, HA., Dickson, E.R., Czaja, A.J., Wiesner, R.H., Ludwig, J. Immunohistochemical characterization of hepatic lymphocytes in primary biliary cirrhosis in comparison with primary sclerosing cholangitis and autoimmune chronic active hepatitis. Mayo Clin. Proc. 1993 68 1049-1055... 

Ben-Ari, Z., Dhillon, A.R, Sherlock, S. Autoimmune cholangiopathy Part of the spectrum of autoimmune chronic active hepatitis. Hepatology 1993 18 10-15... 

Minnk, G.Y., Sutherland, L.R., Pappas, S.C., Kelley, J.K., Martin, S.E. Autoimmunic chronic active hepatitis (lupoid hepatitis) and primary sclerosing cholangitis in two young adult females. Can. J. Gastroenterol. 1988 2 22-27... 

Simultaneous occurrence of primary sclerosing cholangitis and autoimmune chronic active hepatitis in a patient with ulcerative colitis. Dig. Dis. Sci. 1992 37 1606-1611... 

Autoimmune hepatitis has no distinctive histology. The picture presented resembles that of chronic active hepatitis portal and periportal infiltration from some plasma cells as well as a high number of lymphocytes are in evidence, (s. figs. 33.1, 33.2) The lymphocytes are mainly of the T-cell type, whereby the ratio of subtypes CD4 CD8 is about 1 1. The lymphocytes demonstrate emperipolesis (= capable of infiltrating and surrounding other cells), (s. fig. 21.11) Hepatocytes often show... 

Czaja, A.J., Wang, K.K., Shiels, M.T., Katzmann, J.H. Oral pulse prednisone therapy after relapse of severe autoimmune chronic active hepatitis. J. Hepatol. 1993 17 180-186... 

Danielsson, A., Prytz, H. Oral budesonide for treatment of autoimmune chronic active hepatitis. Aliment. Pharmacol. Ther. 1994 8 ... 

Donaldson, P.T., Doherty, D.G., Hayllar, KJM., McFarlane, I.G., Johnson, P.J., WilUams, R. Susceptibility to autoimmune chronic active hepatitis human leukocyte antigens DR4 and A1-B8-DR3 are independent risk factors. Hepatology 1991 13 701—706... 

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