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Autoimmune hepatitis is a disease in which the body’s own immune system attacks the liver and causes it to become inflamed.
• Before a diagnosis of autoimmune hepatitis can be made, it is important to exclude other causes: toxic (alcohol, drugs)
• metabolic diseases (Wilson’s disease, haemochromatosis, A1-antitrypsin deﬁciency), hepatitis and HCV. viral causes, although there is a complex link between autoimmune
.Predominantly a disease of younger women (90% of patients are female).
• May present with acute hepatitis, jaundice, profound malaise and fatigue, and amenorrhoea in women (?autoimmune).
• May be marked extra-hepatic features: vitiligo and alopecia, thyroid disease, pernicious anaemia, type I diabetes mellitus, autoimmune haemolytic anaemia and ITP, rheumatoid arthritis, ulcerative colitis, glomerulonephritis, cryptogenic ﬁbrosing alveolitis, and coeliac disease.
• There is a strong association with HLA-B1, B8, DR3, DR4.
Major features are piecemeal necrosis of hepatocytes in the periportal region.
• There is an inﬁltrate of CD4+ T cells and B cells.
• Later stages of the disease show typical cirrhosis.
• LFTs show markedly elevated transaminases.
• Prothrombin time may be prolonged in late disease.
• Markers of hepatitis virus infection are absent.
• Polyclonal hypergammaglobulinaemia (mainly IgG and IgA).
• Antibodies to HCV or HCV PCR+ = exclusion criteria for autoimmune hepatitis!
• addition to the LKM antibodies.
Type 2b hepatitis is associated with antibodies to hepatitis C in
• Autoantibodies to nuclear components, dsDNA, smooth muscle (anti- actin), LKM antibodies, and liver membranes can be detected.
• Low-titre AMA may also be detected.
The pattern of antibodies present has led to a classiﬁcation scheme for autoimmune hepatitis.
• Autoimmune hepatitis type 1 (AIH-1) is ANA+, smooth muscle antibody (SMA)+, P-ANCA+, and soluble liver antigen (SLA) antibody+. In AIH-1, 50% are ANA
• +/SMA+, 15% are ANA+ only, and 35% are SMA+ only.
• + only. 8% of AIH-1 are SLA
• to therapy; 90% female.
Typically occurs in adults, has a better prognosis, and responds well.
• Previously known as lupoid hepatitis. High frequency of extrahepatic features.
• Autoimmune hepatitis type 2a (AIH-2a) is typically liver–kidney microsomal (LKM-1, LKM-3) antibody+ and liver cytosol (LC-1) antibody+.
• + only. 43% of AIH-2 are LC-1 with poor response to therapy.
AIH-2a is seen in children (50% of cases) and has a worse prognosis
• Hypergammaglobulinaemia is less marked; IgA is usually low. Associated with thyroid and gastric parietal cell autoimmunity.
• Autoimmune hepatitis type 2b (AIH-2b).
• No female predominance; occurs in over-40s; milder disease. HCV-associated; HCV-RNA positive, antibodies to HCV positive.
• No extra-hepatic features.
• LKM-1 positive (NB: HCV antigen cross-reactive with P450 (IID6)
• Autoimmune hepatitis type 3 (AIH-3) is ANA–, LKM–, SLA+. SMA and AMA are seen less commonly.
• that of type 1.Most patients are women (90%) and have a similar presentation to
• Autoimmune hepatitis type 4 (AIH-4).
• with antibodies to M2 antigen. Overlap syndrome of autoimmune hepatitis and PBC; AMA positive
• There are cases of biopsy-proven but serologically negative hepatitis.
• Tests for both SLA and LC-1 should be performed.
• LKM-1 antibodies recognize the cytochrome P450IID6 and are associated with types 2a and 2b autoimmune chronic active hepatitis.
• Liver–kidney microsomal antibodies may be found in autoimmune hepatitis and recognize different hepatic cytochrome enzymes.
✅LKM-1: cytochrome P450 (IID6). associated with types 2a and 2b autoimmune hepatitis. Antibodies to LKM-1 may be triggered by HCV and HSV as both have proteins sharing homology with P450 (IID6). France only.
✅LKM-2: cytochrome P450 (IIC9). Drug-induced, tienilic acid, in antibod