Diagnosis and Management of Autoimmune Hepatitis

This guideline has been approved by the American Association for the Study of Liver Diseases (AASLD) and represents the position of the Association. Clinical practice guidelines are defined as “systematically developed statements to assist practitioner and patient decisions about appropriate heath care for specific clinical circumstances.”1 (All references are available in the Supporting Information.) These guidelines on autoimmune hepatitis provide a data-supported approach to the diagnosis and management of this disease. They are based on the following: (1) formal review and analysis of the recently-published world literature on the topic [Medline search]; (2) American College of Physicians Manual for Assessing Health Practices and Designing Practice Guidelines;2 (3) guideline policies, including the AASLD Policy on the Development and Use of Practice Guidelines and the American Gastroenterological Association Policy Statement on Guidelines;3 and (4) the experience of the authors in the specified topic. These recommendations, intended for use by physicians, suggest preferred approaches to the diagnostic, therapeutic and preventive aspects of care. They are intended to be flexible, in contrast to standards of care, which are inflexible policies to be followed in every case. Specific recommendations are based on relevant published information. To more fully characterize the quality of evidence supporting the recommendations, the Practice Guidelines Committee of the AASLD requires a class (reflecting benefit versus risk) and level (assessing strength or certainty) of evidence to be assigned and reported with each recommendation.4 The grading system applied to the recommendations has been adapted from the American College of Cardiology and the American Heart Association Practice Guidelines, and it is given below (Table 1). AASLD, American Association for the Study of Liver Diseases; AIH, autoimmune hepatitis; ALT, alanine aminotransferase; ANA, antinuclear antibody; AST, aspartate aminotransferase; CYP1A2, cytochrome P450 1A2; HCV, hepatitis C virus; IBD, inflammatory bowel disease; IgG, immunoglobulin G; LKM-1, liver/kidney microsome type 1; PBC, primary biliary cirrhosis; PSC, primary sclerosing cholangitis; SMA, smooth muscle antibodies. Autoimmune hepatitis (AIH) is a generally unresolving inflammation of the liver of unknown cause. A working model for its pathogenesis postulates that environmental triggers, a failure of immune tolerance mechanisms, and a genetic predisposition collaborate to induce a T cell–mediated immune attack upon liver antigens, leading to a progressive necroinflammatory and fibrotic process in the liver.5,6 Onset is frequently insidious with nonspecific symptoms such as fatigue, jaundice, nausea, abdominal pain, and arthralgias at presentation,7 but the clinical spectrum is wide, ranging from an asymptomatic presentation8,9 to an acute severe disease.10,11 The diagnosis is based on histologic abnormalities, characteristic clinical and laboratory findings, abnormal levels of serum globulins, and the presence of one or more characteristic autoantibodies.12-16 Women are affected more frequently than men (sex ratio, 3.6:1).17-19 and the disease is seen in all ethnic groups20-34 and at all ages.21,35-44 There are no robust epidemiological data on AIH in the United States. In Norway and Sweden, the mean incidence is 1 to 2 per 100,000 persons per year, and its point prevalence is 11 to 17 per 100,000 persons per year.45,46 A similar incidence and prevalence can be assumed for the Caucasian population of North America. Data on the natural progression of untreated disease are derived principally from experiences published prior to the widespread use of immunosuppressive agents for AIH and before the detection of the hepatitis C virus (HCV).47-54 These studies showed that as many as 40% of patients with untreated severe disease died within 6 months of diagnosis,47,49 and that survivors frequently developed cirrhosis, esophageal varices and subsequent hemorrhage.47,49,50,55 An acute onset of illness is common (∼40%),56-63 and an acute severe presentation, characterized by within of clinical is that or in with laboratory findings, and These studies to the of immunosuppressive as the in and an autoimmune pathogenesis of the disease. studies before the of be in studies and one can that of patients with Liver has as an for the and the patient and The for AIH and a system by an in and in (Table The clinical for the diagnosis are to or or AIH in the of The system developed as a by which to the of in clinical (Table and can be applied in by the The is in the and a can be before and (Table A of or or a of or AIH at A of has a of a of and of A of of has a of a of and a of A the of the system in with A system has been to clinical and is based on the presence and level of by serum immunoglobulin or and the of (Table In the system with and in the diagnosis of AIH, but it has to be in The diagnosis of AIH requires the presence of characteristic clinical and laboratory and the of that hepatitis and (Table The clinical an of and the use of to be The laboratory of the levels of serum alanine or aspartate or IgG, and and AIH can be asymptomatic in of patients are men and serum levels at than findings, including the of cirrhosis, are similar asymptomatic patients and as many as of asymptomatic patients the of asymptomatic patients be followed by an to for in disease In the level be a of biliary primary sclerosing than the which can be to in the the the presence or of in with The of AIH be including antinuclear smooth muscle to liver/kidney microsome type 1 and type 1 (Table be to disease and 1 and autoimmune liver that AIH primary biliary and Liver at is to the diagnosis and to the In acute of liver from of hepatitis is the and is is specific for AIH, and the of in the the and be The generally the In all but the is with or is and liver of this to hepatitis in The on the of the disease. to patients with an insidious patients with acute severe failure more and and but and The of the is by a and characterized by about the the and with a inflammatory and patients of AIH and such as PSC, PBC, or autoimmune a histologic such as or the presence of one of In the system can be to assist in diagnosis (Table The of or suggest or such as liver hepatitis or a and diagnosis of AIH by the system to the of serum of and of to or that liver There is no to and and histologic generally the the are a diagnosis can be by the presence of such as or liver ANA, SMA, and the for the diagnosis of AIH (Table In North American of patients with AIH ANA, SMA, or and are more in AIH patients and are by or They are in the United are by but be with this can be by to cytochrome the of are specific to and can the of the the diagnosis of AIH, the of the in the or in with disease clinical and In are of disease and can be to on an of is in in of for and SMA, and for are is in in the diagnosis of AIH, liver is by clinical The for is on of and This the detection of ANA, SMA, and but the presence of of an clinical such as to liver type 1 and to liver microsome type of the presence of the is with to and 1 (Table that be in patients the are and specific for and inflammatory bowel disease are frequently in patients with and can be the (Table with evidence that the of is within the this a more be (Table and as in AIH, to the and to a These are to as or is a (Table has been are in patients with AIH are for ANA, SMA, and but are more in with the are are specific for the diagnosis of autoimmune liver and detection patients with more severe disease and are available for The and in AIH are in an for the use of in the diagnosis of The use of in the diagnosis of in the of acute or hepatitis of cause. 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