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AASLD PRACTICE GUIDELINES Diagnosis and Management of Autoimmune Hepatitis

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AASLD PRACTICE GUIDELINES Diagnosis and Management of Autoimmune Hepatitis AASLD PRACTICE GUIDELINES Diagnosis and Management of Autoimmune Hepatitis Michael P. Manns,1 Albert J. Czaja,2 James D. Gorham,3 Edward L. Krawitt,4 Giorgina Mieli-Vergani,5 Diego Vergani,6 and John M. Vierling7 This guideline has been approved by the American ment on Guidelines;3 and (4) the experience of the Association for the Study of Liver Diseases (AASLD) authors in the specified topic. and represents the position of the Association. These recommendations, intended for use by physi- cians, suggest preferred approaches to the diagnostic, 1. Preamble therapeutic and preventive aspects of care. They are intended to be flexible, in contrast to standards of Clinical practice guidelines are defined as ‘‘systemati- care, which are inflexible policies to be followed in ev- cally developed statements to assist practitioner and ery case. Specific recommendations are based on rele- patient decisions about appropriate heath care for spe- vant published information. To more fully characterize 1 cific clinical circumstances.’’ These guidelines on the quality of evidence supporting the recommenda- autoimmune hepatitis provide a data-supported tions, the Practice Guidelines Committee of the approach to the diagnosis and management of this dis- AASLD requires a class (reflecting benefit versus risk) ease. They are based on the following: (1) formal and level (assessing strength or certainty) of evidence review and analysis of the recently-published world lit- to be assigned and reported with each recommenda- erature on the topic [Medline search]; (2) American tion.4 The grading system applied to the recommenda- College of Physicians Manual for Assessing Health tions has been adapted from the American College of 2 Practices and Designing Practice Guidelines; (3) Cardiology and the American Heart Association Prac- guideline policies, including the AASLD Policy on the tice Guidelines, and it is given below (Table 1). Development and Use of Practice Guidelines and the American Gastroenterological Association Policy State- 2. Introduction Autoimmune hepatitis (AIH) is a generally unresolv- All AASLD Practice Guidelines are updated annually. If you are viewing a ing inflammation of the liver of unknown cause. A Practice Guideline that is more than 12 months old, please visit www.aasld.org for an update in the material. working model for its pathogenesis postulates that Abbreviations: AASLD, American Association for the Study of Liver environmental triggers, a failure of immune tolerance Diseases; AIH, autoimmune hepatitis; ALT, alanine aminotransferase; ANA, mechanisms, and a genetic predisposition collaborate antinuclear antibody; AST, aspartate aminotransferase; CYP1A2, cytochrome P450 1A2; HCV, hepatitis C virus; IBD, inflammatory bowel disease; IgG, to induce a T cell–mediated immune attack upon liver immunoglobulin G; LKM-1, liver/kidney microsome type 1; PBC, primary antigens, leading to a progressive necroinflammatory biliary cirrhosis; PSC, primary sclerosing cholangitis; SMA, smooth muscle and fibrotic process in the liver.5,6 Onset is frequently antibodies. insidious with nonspecific symptoms such as fatigue, From the 1Medical School of Hannover, Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Germany; 2Mayo Clinic College of jaundice, nausea, abdominal pain, and arthralgias at Medicine, Division of Gastroenterology and Hepatology, Rochester, MN; presentation,7 but the clinical spectrum is wide, rang- 3Dartmouth Medical School, Department of Pathology, Lebanon, NH; 8,9 4 ing from an asymptomatic presentation to an acute University of Vermont College of Medicine, Department of Medicine, Given 10,11 Building, Burlington, VT; 5Pediatric Liver Centre and 6Institute of Liver Studies, severe disease. The diagnosis is based on histologic King’s College London School of Medicine at King’s College Hospital, Denmark abnormalities, characteristic clinical and laboratory Hill, London, UK; and 7Baylor Liver Health, Baylor College of Medicine, findings, abnormal levels of serum globulins, and the Houston, TX. Received January 22, 2010; accepted January 25, 2010. presence of one or more characteristic autoantibod- 12-16 Address reprint requests to: Michael P. Manns, M.D., Department of ies. Women are affected more frequently than Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, men (sex ratio, 3.6:1).17-19 and the disease is seen in Carl-Neuberg-Straße 1, D-30625 Hannover, Germany. E-mail: manns. all ethnic groups20-34 and at all ages.21,35-44 There are [email protected]; fax: þ49 511 532-4896. Copyright VC 2010 by the American Association for the Study of Liver Diseases. no robust epidemiological data on AIH in the United Published online in Wiley InterScience (www.interscience.wiley.com). States. In Norway and Sweden, the mean incidence is DOI 10.1002/hep.23584 1 to 2 per 100,000 persons per year, and its point Potential conflict of interest: Michael Manns has received research support, lecture fees and took part in clinical trials for Falk Pharma GmbH, Freiburg, prevalence is 11 to 17 per 100,000 persons per 45,46 Germany, and Roche Pharma, Basel, Switzerland. year. A similar incidence and prevalence can be 1 2 MANNS ET AL. HEPATOLOGY, June 2010 Table 1. Description of Grading System Used to Assign Class 3. Diagnosis: Criteria and Methods and Level of Evidence The diagnostic criteria for AIH and a diagnostic Classification Description scoring system were codified by an international panel Class I Conditions for which there is evidence and/or general in 199375 and revised in 199913 (Table 2). The clinical agreement that a given diagnostic evaluation, procedure or treatment is beneficial, useful, and effective criteria for the diagnosis are sufficient to make or Class II Conditions for which there is conflicting evidence and/or exclude definite or probable AIH in the majority of a divergence of opinion about the usefulness/efficacy patients. The revised original scoring system was devel- of a diagnostic evaluation, procedure or treatment Class IIa Weight of evidence/opinion is in favor of usefulness/efficacy oped as a research tool by which to ensure the compa- Class IIb Usefulness/efficacy is less well established by rability of study populations in clinical trials (Table evidence/opinion 3),13 and can also be applied in diagnostically challeng- Class III Conditions for which there is evidence and/or general ing cases not readily captured by the descriptive crite- agreement that a diagnostic evaluation/procedure/treatment 13 is not useful/effective and in some cases may be harmful ria. The treatment response is graded in the revised Level of Evidence Description original scoring system, and a score can be rendered 13 Level A Data derived from multiple randomized clinical trials both before and after treatment (Table 3). A pretreat- or meta analyses ment score of 10 points or higher, or a posttreatment Level B Data derived from a single randomized trial, or score of 12 points or higher, indicate ‘‘probable’’ AIH nonrandomized studies at presentation. A pretreatment score of 10 points has a Level C Only consensus opinion of experts, case studies, or standard of care sensitivity of 100%, a specificity of 73%, and diagnos- tic accuracy of 67%.76 A pretreatment score of 15 points, indicative of ‘‘definite AIH’’ has a sensitivity of 95%, a specificity of 97%, and a diagnostic accuracy of 94%.76 A retrospective study supports the usefulness of assumed for the Caucasian population of North 77 America. the revised original system in children with AIH. A simplified scoring system has been proposed Data on the natural progression of untreated disease 78 are derived principally from experiences published recently to ease clinical application and is based on prior to the widespread use of immunosuppressive the presence and level of autoantibody expression by agents for AIH and before the detection of the hepati- indirect immunofluorescence, serum immunoglobulin tis C virus (HCV).47-54 These studies showed that as G (IgG) concentration, compatible or typical histologi- cal features, and the absence of viral markers (Table many as 40% of patients with untreated severe disease 78 died within 6 months of diagnosis,47,49 and that survi- 3). In three recent retrospective studies, the simpli- vors frequently developed cirrhosis, esophageal varices fied scoring system performed with high sensitivity 47,49,50,55 and specificity in the diagnosis of AIH, but it has yet and subsequent hemorrhage. An acute onset 76,79,80 of illness is common (40%),56-63 and an acute severe to be validated in prospective studies. presentation, characterized by hepatic encephalopathy within 8 weeks of clinical symptoms, is sometimes 3.1. Clinical, Laboratory, and Histological seen.10,11,58,64-68 Assessment Three randomized, controlled treatment trials estab- The diagnosis of AIH requires the presence of charac- lished that prednisone alone or in combination with teristic clinical and laboratory features, and the exclu- azathioprine improved symptoms, laboratory tests, his- sion of other conditions that cause chronic hepatitis and tological findings, and immediate survival.48-50 These cirrhosis (Table 2).13 The clinical assessment should studies led to the acceptance of immunosuppressive include an evaluation of alcohol consumption and the regimens as the standard in treatment, and supported use of drugs known to be hepatotoxic. The laboratory an autoimmune pathogenesis of the disease. However, assessment should include determinations of the levels these studies
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