Autoimmune hepatitis chronic

Autoimmune hepatitis Chronic viral hepatitis Non-alcoholic steatohepatitis (NASH)... 

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]. 

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. 

Chronic Hepatitis B Chronic Hepatitis C Autoimmune Hepatitis Wilson s Disease... 

Osteoporosis is also common in those on long-term corticosteroid therapy (for example patients with autoimmune hepatitis or coexisting inflammatory bowel disease). Patients with chronic liver disease may also have other risk factors for osteoporosis related to their disease state. These include vitamin D deficiency, excessive alcohol consumption, poor diet, physical inactivity and low body mass index. Oestrogen deficiency in the postmenopausal stage further increases the risk. 

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prednisolone will benefit some 80% and should be continued in the long term, as most patients relapse if the drug is withdrawn. 

Fig. 5.10 Antinuclear antibodies (ANA) with homogeneous fluorescence pattern, here in chronic autoimmune hepatitis...

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. 

In acute and chronic HCV infections, various antibodies such as ANA, SMA, LKM-1, anti-GOR, etc. (s. pp 118-121, 679) (up to 65% of cases) as well as a positive rheiunatoid factor (approx. 20% of cases) were detected. The differentiation between genuine autoimmune hepatitis and HCV infection with autoimmune phenomena is of paramount chnical significance. 

The pathogenesis of NASH is multifactorial, i.e. in the presence of steatosis, it is attributed to the additional (even combined) influence of different noxae (e.g. oxygen deficiency, endotoxins, medicaments, chemicals, iron, biotoxometabolites). There should be no laboratory findings pointing to alcohol abuse chronic hepatitis B and C as well as autoimmune hepatitis (75) must also be ruled out. 

The cause of autoimmune hepatitis (AIH) is unknown. Autoimmune reactions lead to a chronic (rarely acute) inflammatory process (periportal piecemeal necrosis, infiltration of portal zones). AIH is frequently associated with autoimmune diseases of other organs. It occurs predominantly among women, particularly in younger years. Hypergammaglobulinaemia is invariably in evidence. Various autoantibodies to components of the liver parenchyma are found. The presence and specificity of these antibodies, together with the respective clinical symptoms, facilitate differentiation between the various subtypes of AIH. Diagnosis is substantiated by the response to immunosuppressive therapy. If left untreated, AIH progresses rapidly with transition to cirrhosis and/or liver failure. If treated adequately, the course taken by the disease is favourable. 

In chronic hepatitis B, 5-10% of cases display ANA and/or SMA. Due to the subtle differentiation achieved with HBV markers, it is possible to classify each individual case reliably. Prognosis and therapy are determined by chronic hepatitis B. Interferon therapy can trigger or exacerbate autoimmune hepatitis. (13, 66, 74, 78)... 

Occasionally, forms of autoantibody-negative chronic hepatitis are found with no detectable cause. They resemble autoimmune hepatitis in every respect and respond well to corticosteroid therapy. This special group (10-15%) possibly comprises cases of autoimmune hepatitis for which no immunoserologic markers are known as yet. In numerous cases of cryptogenic chronic hepatitis, AIH type 3 can be detected due to evidence of high-titric LP/LSA. 

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... 

If cholestasis is not present, the additional application of ursodeoxycholic acid (UDCA) is worth considering because of its pharmacological properties and lack of side effects or interactions. Initial results on the treatment of chronic hepatitis with UDCA were reported by F. IcHiDA (1961), T. Nakahara et al. (1975) and K. Miyaji (1976). (s. p. 705) In 1988 our study group also noted obvious and permanent effects of UDCA on the course of disease in terms of clinical and laboratory indices in severe acute viral hepatitis B. (s. p. 437) Such observations were confirmed by A. Jorge in 1993. Owing to the multiple mechanisms of action of UDCA, in particular its immunomodulatory effect, adjuvant therapeutic efficacy can be anticipated in autoimmune hepatitis, as reported by P. Janowitz et al. in 1996. In autoimmune-associated chronic hepatitis C, UDCA proved to be a successful therapeutic agent (K. Nakamura et al., 1999). 

Cianciara, J., Laskus, T. Development of transient autoimmune hepatitis during interferon treatment of chronic hepatitis B. Dig. Dis. Sci. 1995 40 1842-1844... 

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... 

Sekl, T., Klyosawa, K., Inoko, H., Ota, M. Association of autoimmune hepatitis with HLA-Bw54 and DR4. Hepatology 1990 12 1300—1304 Sherman, K.E., Narkewicz, M., Pinto, P.C. Cyclosporine in the management of corticosteroid-resistant type I autoimmune chronic active hepatitis. J. Hepatol. 1994 21 1040—1047... 

Lobular inflammation Whereas lobular, diffusely distributed inflammation is more evident, in acute hepatitis portal and periportal inflammation predominates in chronic hepatitis and lobular hepatitis is less pronounced. Generally, it consists of separate small clusters of mononuclear cells. Scattered necrotic hepatocytes (= acidophilic / Councilman bodies) are found the hepatocellular nuclei are in disarray (= anisonucleosis) there is swelling of the hepatocytes, and mitoses are present. Marked lobular hepatitis in conjunction with considerable portal and periportal inflammation is typical of flares of chronic viral hepatitis or autoimmune hepatitis. In addition to single-cell necroses, there are confluent necroses, which affect entire lobules. Bridging necroses link portal tracts with other portal tracts or with terminal venules, (l)... 

Steatosis is uncommon in chronic hepatitis however, in chronic hepatitis C, steatosis is found in about 70% of cases (especially in genotype 3). Generally it is mild and non-zonal. Cholestasis is rare in chronic hepatitis, but more frequent in autoimmune hepatitis. 

Cassani, F., Catdeta, M., Valentinl, R, Muratori, R, Giostra, F., Fran-cesconi, R., Muratori, L., Leuzi, M., Bianchi, G., Zauli, D., Bianchi, F.B. Serum autoantibodies in chronic hepatitis C comparison with autoimmune hepatitis and impact on the disease profde. Hepatology 1997 26 561-566... 

Chronic autoimmune hepatitis If untreated, AIH (especially type 2) develops almost inevitably into cirrhosis the condition is further aggravated by the presence of multilobular necrosis and bridging necrosis. In bridging necrosis, development of cirrhosis is more rapid between the portal fields and the central vein than between the portal fields themselves, (s. p. 683) (s. fig. 33.4)... 

Rheumatic diseases can also cause direct or indirect liver damage. A common denominator is the frequent occurrence of HLA type B8. There is frequently a close association between rheumatic diseases or collagenoses and chronic viral hepatitis (B, C), autoimmune hepatitis, primary biliary cholangitis as well as cirrhosis. 

De novo induction rather than exacerbation of autoimmune hepatitis is still possible, as indicated by anecdotal reports in patients with cancer or chronic viral hepatitis (SED-13, 1094) (SEDA-22, 402). Such a very rare event is in keeping with the usual absence of autoantibody specific for autoimmune hver disease after interferon alfa treatment. 

Positive serological markers of autoimmune hepatitis before treatment in patients with concomitant chronic hepatitis C are sometimes associated with further exacerbation of an underlying autoimmune liver disease during interferon alfa treatment. Of three patients with raised antimitochondrial antibodies (over 1 160), only the two patients with M2 (with or without M4 or M8) subtypes had biochemical exacerbation of cholestasis and an unfavorable response to interferon alfa (255). Although very few patients were investigated, determination of antibodies against submitochondrial particles may help to identify patients who are likely to have no benefit and even exacerbation of liver disease with interferon alfa. 

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. 

Two studies have provided insights into the incidence and risk factors of the immune-mediated comphcations of interferon alfa in patients with chronic myeloid leukemia. In the first study, 13 of 46 patients had autoimmune manifestations consisting of a combination of autoimmune thyroiditis in four, a direct antiglobulin test without hemolysis in eight, cryoagglutinins in one, Raynaud s phenomenon in two, and chronic autoimmune hepatitis in one (343). Overall, six patients had chnically symptomatic manifestations after a median of 15 months of treatment. In the second study, there were autoimmune diseases in seven of 76 patients after a median of 19 months of treatment, including hypothyroidism in one, immune-mediated hemolysis in two, systemic lupus erythematosus in two, Raynaud s phenomenon in one, and mixed connective tissue disease in one (344). In... 

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