Autoimmune Hepatitis Workup
- Author: David C Wolf, MD, FACP, FACG, AGAF, FAASLD; Chief Editor: BS Anand, MD more...
Clinicians must consider the diagnosis of autoimmune hepatitis in any patient who has acute hepatitis or acute liver failure (defined by the new onset of coagulopathy). In addition to aminotransferase levels and other liver function studies, the workup of such patients should include the following assays:
Serum antinuclear antibody (ANA)
Anti–smooth muscle antibody (ASMA)
Liver-kidney microsomal type 1 (LKM-1) antibody
Serum protein electrophoresis (SPEP)
Urgent liver biopsy, transjugular if appropriate, may help to confirm the clinical suspicion of autoimmune hepatitis.
Laboratory findings in autoimmune hepatitis include the following:
Elevated serum aminotransferase levels (1.5-50 times reference values)
Elevated serum immunoglobulin levels, primarily immunoglobulin G (IgG)
Seropositive results for ANAs, SMAs, or LKM-1 or anti–liver cytosol 1 (anti-LC1) antibodies
In 50% of patients, abnormal results on liver function tests include decreased albumin levels and prolonged prothrombin time.
In August 2012, the Centers for Disease Control and Prevention (CDC) expanded their existing, risk-based testing guidelines to recommend a 1-time blood test for hepatitis C virus (HCV) infection in baby boomers—the generation born between 1945 and 1965, who account for approximately three fourths of all chronic HCV infections in the United States—without prior ascertainment of HCV risk (see Recommendations for the Identification of Chronic Hepatitis C Virus Infection Among Persons Born During 1945–1965). One-time HCV testing in this population could identify nearly 808,600 additional people with chronic infection. All individuals identified with HCV should be screened and/or managed for alcohol abuse, followed by referral to preventative and/or treatment services, as appropriate.
Autoimmune hepatitis is characterized by positive findings on autoantibody tests, as follows:
AIH-1 - ASMA and ANA
AIH-2 - Anti–LKM-1 antibody
AIH-3 - Antibodies to soluble liver antigen (anti-SLA)
SMAs are present in 90-100% of patients with autoimmune hepatitis type 1 (AIH-1). ANAs are present in 10% of patients with AIH-1 and in association with SMAs in 40-60% of patients with AIH-1. Titers range from 1:100-500,000. SMAs occur in low titers in healthy children and patients with viral hepatitis and other diseases that do not affect the liver.
LKM-1 antibodies are present in 40-45% of patients with AIH-2 and are associated with anti-LC1 antibodies in 50% of patients. Anti-LC1 antibodies occur alone in 30% of patients with AIH-2; these antibodies recognize formiminotransferase cyclodeaminase, a liver-specific 58kD metabolic enzyme. Anti-asialoglycoprotein receptor antibodies occur more often in patients with AIH-1 and may serve as a marker of inflammatory activity.
Other autoantibodies may be evident. Atypical perinuclear antineutrophil cytoplasmic antibodies (pANCA) are frequently present. Czaja et al have shown that patients with autoimmune hepatitis who have positive test results for actin antibody are younger, more commonly test positive for human leukocyte antigen (HLA)–DR3, and required transplantation more frequently than patients with ANAs who test negative for actin antibody.
Serum Proteins and Immunoglobulins
An IgG-predominant polyclonal hypergammaglobulinemia is a common finding in patients with untreated autoimmune hepatitis. Gamma globulin values typically range from 3-4 g/dL and frequently are as high as 5-6 g/dL. Cases of hyperviscosity syndrome secondary to high IgG levels are reported. Autoimmune hepatitis is an unlikely diagnosis in patients who have acute hepatitis without hypergammaglobulinemia.
The gamma globulin or the IgG level may be followed on a regular basis as a marker of disease responsiveness to therapy.
Patients with AIH-2 commonly have partial immunoglobulin A (IgA) deficiency.
Serum aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) are elevated in 100% of patients at initial presentation, with average values of 200-300 U/L. Aminotransferase values correlate poorly with the degree of hepatic necrosis; however, values in the thousands may indicate acute hepatitis or a severe flare of preexisting disease.
Continued elevation of the aminotransferases in the face of ongoing therapy is a reliable marker for ongoing inflammatory activity in the liver. Normalization of the aminotransferase levels during therapy is an encouraging sign, but active liver inflammation is present in more than 50% of patients with normalized liver chemistries. Indeed, biochemical remission may precede true histologic remission by 3-6 months.
Typically, patients are treated for at least 1 year after documentation of normal liver chemistries. Liver biopsy is recommended by some experts to confirm that the patient is in histologic remission. Drug withdrawal may be attempted at this time (see Treatment).
Worsening of aminotransferase levels in a patient undergoing treatment or in a patient who is in remission may signal a resurgence of disease activity.
Other liver chemistries
Serum bilirubin and alkaline phosphatase values are mildly to moderately increased in 80-90% of patients. A sharp increase in the alkaline phosphatase values during the course of autoimmune disease might reflect the development of PSC or the onset of hepatocellular carcinoma as a complication of cirrhosis.
Hypoalbuminemia and prolongation of prothrombin time are markers of severe hepatic synthetic dysfunction, which may be observed in active disease or decompensated cirrhosis.
Complete Blood Count and Other Blood Studies
Other hematologic abnormalities may include the following:
Coombs-positive hemolytic anemia
Elevated erythrocyte sedimentation rate
Eosinophilia is uncommon, but counts ranging from 9% to 48% are described. Autoimmune hepatitis has even been described as the sole presenting feature of idiopathic hypereosinophilic syndrome.
Hepatic Imaging Studies
Imaging studies, in general, are not helpful in reaching a definitive diagnosis of autoimmune hepatitis; however, the presence of heterogeneous hepatic echotexture on abdominal ultrasound or abnormal contrast enhancement on abdominal CT imaging may suggest the presence of active inflammation or necrosis.
The appearance of an irregular nodular liver may confirm the presence of cirrhosis. Furthermore, these imaging studies may be used to rule out the presence of hepatocellular carcinoma, a potential complication of autoimmune hepatitis–induced cirrhosis.
When alkaline phosphatase levels are 7-8 times reference values or gamma glutamyl transferase levels are 2-3 times reference values, a patient with autoimmune hepatitis and ulcerative colitis may require endoscopic retrograde cholangiopancreatography (ERCP) to rule out coexisting primary sclerosing cholangitis (PSC).
Liver biopsy is the most important diagnostic procedure in patients with autoimmune hepatitis. This procedure can be performed percutaneously, with or without ultrasound guidance, or by the transjugular route. The latter is preferred if the patient has coagulopathy or severe thrombocytopenia. A transjugular liver biopsy also may be preferable if ascites is present or if the liver is small, shrunken, and difficult to reach percutaneously.
Liver biopsy routinely is performed in the outpatient setting to investigate abnormal liver chemistries. Liver biopsy should be performed as early as possible in patients with acute hepatitis who are thought to have autoimmune hepatitis. Confirmation of the diagnosis enables initiation of treatment at an early stage in the disease process.
The role of biopsy in patients presenting with well-established cirrhosis secondary to autoimmune hepatitis is less clear. As an example, the initiation of treatment in a patient with cirrhosis, normal aminotransferase levels, and a minimally elevated gamma globulin level is not expected to influence the disease outcome.
Histopathologic findings on liver biopsy specimens are crucial to determining the diagnosis of autoimmune hepatitis and the disease's severity. Liver biopsy findings can help to differentiate autoimmune hepatitis from chronic hepatitis C virus (HCV) infection, alcohol-induced hepatitis, drug-induced liver disease, primary biliary cirrhosis, and PSC.
Autoimmune hepatitis is characterized by a portal mononuclear cell infiltrate that invades the limiting plate surrounding the portal triad and permeates the surrounding lobule (ie, periportal infiltrate) and beyond. A plasma cell infiltrate sometimes occurs, which, in the past, led to use of the term plasma cell hepatitis.
Biopsies may show evidence for interface hepatitis (ie, piecemeal necrosis), bridging necrosis, and fibrosis. Interface hepatitis essentially spares the biliary tree but may involve most of the lobule. Lobular collapse, best identified by reticulin staining, is a common finding.
Interface hepatitis does not predict a progressive disease course. By contrast, a strong likelihood exists that cirrhosis will develop when bridging necrosis is present. The presence or absence of cirrhosis on liver biopsy is an important determinant of the patient's prognosis.
Fibrosis is present in most patients with autoimmune hepatitis. Without effective therapy, fibrosis starts to connect the portal and central areas, which ultimately leads to cirrhosis.
In 1999, the International Autoimmune Hepatitis Group established a scoring system that is particularly helpful in establishing the diagnosis of autoimmune hepatitis in problematic cases.[44, 45]
Histopathologic findings in patients with autoimmune hepatitis are characteristic but nonspecific; autoimmune hepatitis has findings in common with chronic viral hepatitis, drug-associated chronic hepatitis, and several other chronic liver disorders. Multinucleated giant hepatocytes are found in 10-20% of biopsy specimens; their occurrence after the neonatal period may suggest a diagnosis of autoimmune hepatitis.
Tucker et al indicate that the presence of characteristic hyaline droplets in the cytoplasm of Kupffer cells on routine hematoxylin and eosin (H&E) from biopsy specimens in pediatric patients with autoimmune hepatitis may provide a useful diagnostic clue to distinguish this disease from other forms of chronic hepatitis.
Oettinger R, Brunnberg A, Gerner P, Wintermeyer P, Jenke A, Wirth S. Clinical features and biochemical data of Caucasian children at diagnosis of autoimmune hepatitis. J Autoimmun. 2005 Feb. 24(1):79-84. [Medline].
Strassburg CP, Manns MP. Treatment of autoimmune hepatitis. Semin Liver Dis. 2009 Aug. 29(3):273-85. [Medline].
Centers for Disease Control and Prevention. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. MMWR Recomm Rep. 2012 Aug 17. 61:1-32. [Medline]. [Full Text].
Waldenstrom J. The diagnostic importance of ACTH. Acta Endocrinol (Copenh). 1950. 5(3):235-42. [Medline].
Kunkel HG, Ahrens EH, Eisenmenger WJ. Extreme hypergammaglobulinemia in young women with liver disease of unknown etiology. J Clin Invest. 1950. 30:654.
Bearn AG, Kunkel HG, Slater RJ. The problems of chronic liver disease in young women. Am J Med. 1956. 21:3-15.
Joske RA, King WE. The L.E.-cell phenomenon in active chronic viral hepatitis. Lancet. 1955 Sep 3. 269(6888):477-80. [Medline].
Cowling DC, Mackay IR, Taft LI. Lupoid hepatitis. Lancet. 1956 Dec 29. 271(6957):1323-6. [Medline].
Johnson PJ, McFarlane IG. Meeting report: International Autoimmune Hepatitis Group. Hepatology. 1993 Oct. 18(4):998-1005. [Medline].
Scully LJ, Toze C, Sengar DP, et al. Early-onset autoimmune hepatitis is associated with a C4A gene deletion. Gastroenterology. 1993 May. 104(5):1478-84. [Medline].
Czaja AJ, Carpenter HA, Santrach PJ, et al. Genetic predispositions for the immunological features of chronic active hepatitis. Hepatology. 1993 Oct. 18(4):816-22. [Medline].
Longhi MS, Ma Y, Mieli-Vergani G, Vergani D. Aetiopathogenesis of autoimmune hepatitis. J Autoimmun. 2009 Sep 17. [Medline].
Vento S, Cainelli F. Is there a role for viruses in triggering autoimmune hepatitis?. Autoimmun Rev. 2004 Jan. 3(1):61-9. [Medline].
Wen L, Peakman M, Lobo-Yeo A, McFarlane BM, Mowat AP, Mieli-Vergani G, et al. T-cell-directed hepatocyte damage in autoimmune chronic active hepatitis. Lancet. 1990 Dec 22-29. 336(8730):1527-30. [Medline].
Umemura T, Ota M. Genetic factors affect the etiology, clinical characteristics and outcome of autoimmune hepatitis. Clin J Gastroenterol. 2015 Dec. 8 (6):360-6. [Medline].
Wang Q, Yang F, Miao Q, Krawitt EL, Gershwin ME, Ma X. The clinical phenotypes of autoimmune hepatitis: A comprehensive review. J Autoimmun. 2015 Nov 21. [Medline].
Czaja AJ. Diagnosis and management of autoimmune hepatitis. Clin Liver Dis. 2015 Feb. 19 (1):57-79. [Medline].
Pathmakanthan S, Kay EW, Murray FE. Autoimmune chronic active hepatitis associated with the presence of antiphospholipid antibodies. Eur J Gastroenterol Hepatol. 1998 Feb. 10(2):155-7. [Medline].
Czaja AJ. Autoimmune hepatitis. Sleisenger and Fordtran's Gastrointestinal and Liver Disease. 6th ed. Philadelphia, Pa: WB Saunders Company; 1998. 1265-1274.
Ramakrishna J, Johnson AR, Banner BF. Long-term minocycline use for acne in healthy adolescents can cause severe autoimmune hepatitis. J Clin Gastroenterol. 2009 Sep. 43(8):787-90. [Medline].
Adar T, Mizrahi M, Pappo O, Scheiman-Elazary A, Shibolet O. Adalimumab-induced autoimmune hepatitis. J Clin Gastroenterol. 2010 Jan. 44(1):e20-2. [Medline].
Fairhurst DA,Sheehan-Dre R. Autoimmune hepatitis associated with infliximab in a patient with palmoplanter pustular psoriasis. Clin Exp Dermatol. 2009/04. 34(3):421-2.
Liu ZX, Kaplowitz N. Immune-mediated drug-induced liver disease. Clin Liver Dis. 2002 Aug. 6(3):755-74. [Medline].
Casswall TH, Németh A, Nilsson I, Wadström T, Nilsson HO. Helicobacter species DNA in liver and gastric tissues in children and adolescents with chronic liver disease. Scand J Gastroenterol. 2010. 45(2):160-7. [Medline].
Michitaka K, Nishiguchi S, Aoyagi Y, Hiasa Y, Tokumoto Y, Onji M. Etiology of liver cirrhosis in Japan: a nationwide survey. J Gastroenterol. 2009 Sep 30. [Medline].
Seki T, Kiyosawa K, Inoko H, et al. Association of autoimmune hepatitis with HLA-Bw54 and DR4 in Japanese patients. Hepatology. 1990 Dec. 12(6):1300-4. [Medline].
Boberg KM. Prevalence and epidemiology of autoimmune hepatitis. Clin Liver Dis. 2002 Aug. 6(3):635-47. [Medline].
Czaja AJ. Special clinical challenges in autoimmune hepatitis: the elderly, males, pregnancy, mild disease, fulminant onset, and nonwhite patients. Semin Liver Dis. 2009 Aug. 29(3):315-30. [Medline].
McFarlane IG, Heneghan MA. Autoimmunity and the female liver. Hepatol Res. 2004 Apr. 28(4):171-176. [Medline].
Mieli-Vergani G, Vergani D. Autoimmune hepatitis in children: what is different from adult AIH?. Semin Liver Dis. 2009 Aug. 29(3):297-306. [Medline].
Haider AS, Kaye G, Thomson A. Autoimmune hepatitis in a demographically isolated area of Australia. Intern Med J. 2009 Aug 27. [Medline].
Czaja AJ, Carpenter HA. Distinctive clinical phenotype and treatment outcome of type 1 autoimmune hepatitis in the elderly. Hepatology. 2006 Mar. 43(3):532-8. [Medline].
Kirk AP, Jain S, Pocock S, et al. Late results of the Royal Free Hospital prospective controlled trial of prednisolone therapy in hepatitis B surface antigen negative chronic active hepatitis. Gut. 1980 Jan. 21(1):78-83. [Medline].
Ferreira AR, Roquete ML, Toppa NH, de Castro LP, Fagundes ED, Penna FJ. Effect of treatment of hepatic histopathology in children and adolescents with autoimmune hepatitis. J Pediatr Gastroenterol Nutr. 2008 Jan. 46(1):65-70. [Medline].
Greene MT, Whitington PF. Outcomes in pediatric autoimmune hepatitis. Curr Gastroenterol Rep. 2009 Jun. 11(3):248-51. [Medline].
Gleeson D, Heneghan MA. British Society of Gastroenterology (BSG) guidelines for management of autoimmune hepatitis. Gut. 2011 Jul 13. [Medline].
Gregorio GV, Portmann B, Reid F, Donaldson PT, Doherty DG, McCartney M, et al. Autoimmune hepatitis in childhood: a 20-year experience. Hepatology. 1997 Mar. 25(3):541-7. [Medline].
Caprai S, Vajro P, Ventura A, et al. Autoimmune liver disease associated with celiac disease in childhood: a multicenter study. Clin Gastroenterol Hepatol. 2008 Jul. 6(7):803-6. [Medline].
Czaja AJ. Autoimmune hepatitis and viral infection. Gastroenterol Clin North Am. 1994 Sep. 23(3):547-66. [Medline].
Floreani A, Rizzotto ER, Ferrara F, et al. Clinical course and outcome of autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome. Am J Gastroenterol. 2005 Jul. 100(7):1516-22. [Medline].
Czaja AJ, Cassani F, Cataleta M, Valentini P, Bianchi FB. Frequency and significance of antibodies to actin in type 1 autoimmune hepatitis. Hepatology. 1996 Nov. 24(5):1068-73. [Medline].
Czaja AJ, Carpenter HA. Sensitivity, specificity, and predictability of biopsy interpretations in chronic hepatitis. Gastroenterology. 1993 Dec. 105(6):1824-32. [Medline].
Alvarez F, Berg PA, Bianchi FB, et al. International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol. 1999 Nov. 31(5):929-38. [Medline].
Wiegard C, Schramm C, Lohse AW. Scoring systems for the diagnosis of autoimmune hepatitis: past, present, and future. Semin Liver Dis. 2009 Aug. 29(3):254-61. [Medline].
Tucker SM, Jonas MM, Perez-Atayde AR. Hyaline droplets in Kupffer cells: a novel diagnostic clue for autoimmune hepatitis. Am J Surg Pathol. 2015 Jun. 39 (6):772-8. [Medline].
Lichtenstein GR. Use of laboratory testing to guide 6-mercaptopurine/azathioprine therapy. Gastroenterology. 2004 Nov. 127(5):1558-64. [Medline].
Muratori P, Lalanne C, Barbato E, et al. Features and progression of asymptomatic autoimmune hepatitis in Italy. Clin Gastroenterol Hepatol. 2016 Jan. 14 (1):139-46. [Medline].
[Guideline] Manns MP, Czaja AJ, Gorham JD, Krawitt EL, Mieli-Vergani G, Vergani D, et al. Diagnosis and management of autoimmune hepatitis. Hepatology. 2010 Jun. 51(6):2193-213. [Medline].
Manns MP, Woynarowski M, Kreisel W, Lurie Y, Rust C, Zuckerman E, et al. Budesonide induces remission more effectively than prednisone in a controlled trial of patients with autoimmune hepatitis. Gastroenterology. 2010 Oct. 139(4):1198-206. [Medline].
Alvarez F, Ciocca M, Cañero-Velasco C, Ramonet M, de Davila MT, Cuarterolo M, et al. Short-term cyclosporine induces a remission of autoimmune hepatitis in children. J Hepatol. 1999 Feb. 30(2):222-7. [Medline].
Sciveres M, Caprai S, Palla G, Ughi C, Maggiore G. Effectiveness and safety of ciclosporin as therapy for autoimmune diseases of the liver in children and adolescents. Aliment Pharmacol Ther. 2004 Jan 15. 19(2):209-17. [Medline].
Fernandes NF, Redeker AG, Vierling JM, et al. Cyclosporine therapy in patients with steroid resistant autoimmune hepatitis. Am J Gastroenterol. 1999 Jan. 94(1):241-8. [Medline].
Aqel BA, Machicao V, Rosser B, et al. Efficacy of tacrolimus in the treatment of steroid refractory autoimmune hepatitis. J Clin Gastroenterol. 2004 Oct. 38(9):805-9. [Medline].
Van Thiel DH, Wright H, Carroll P, et al. Tacrolimus: a potential new treatment for autoimmune chronic active hepatitis: results of an open-label preliminary trial. Am J Gastroenterol. 1995 May. 90(5):771-6. [Medline].
Than NN, Wiegard C, Weiler-Normann C, et al. Long-term follow-up of patients with difficult to treat type 1 autoimmune hepatitis on tacrolimus therapy. Scand J Gastroenterol. 2016 Mar. 51 (3):329-36. [Medline].
Devlin SM, Swain MG, Urbanski SJ, et al. Mycophenolate mofetil for the treatment of autoimmune hepatitis in patients refractory to standard therapy. Can J Gastroenterol. 2004 May. 18(5):321-6. [Medline].
Inductivo-Yu I, Adams A, Gish RG, et al. Mycophenolate mofetil in autoimmune hepatitis patients not responsive or intolerant to standard immunosuppressive therapy. Clin Gastroenterol Hepatol. 2007 Jul. 5(7):799-802. [Medline].
Richardson PD, James PD, Ryder SD. Mycophenolate mofetil for maintenance of remission in autoimmune hepatitis in patients resistant to or intolerant of azathioprine. J Hepatol. 2000 Sep. 33(3):371-5. [Medline].
Wolf DC, Bojito L, Facciuto M, Lebovics E. Mycophenolate mofetil for autoimmune hepatitis: a single practice experience. Dig Dis Sci. 2009 Nov. 54(11):2519-22. [Medline].
Aw MM, Dhawan A, Samyn M, Bargiota A, Mieli-Vergani G. Mycophenolate mofetil as rescue treatment for autoimmune liver disease in children: a 5-year follow-up. J Hepatol. 2009 Jul. 51(1):156-60. [Medline].
Czaja AJ, Lindor KD. Failure of budesonide in a pilot study of treatment-dependent autoimmune hepatitis. Gastroenterology. 2000 Nov. 119(5):1312-6. [Medline].
Zandieh I, Krygier D, Wong V, Howard J, Worobetz L, Minuk G, et al. The use of budesonide in the treatment of autoimmune hepatitis in Canada. Can J Gastroenterol. 2008 Apr. 22(4):388-92. [Medline]. [Full Text].
Osterman MT, Kundu R, Lichtenstein GR, et al. Association of 6-thioguanine nucleotide levels and inflammatory bowel disease activity: a meta-analysis. Gastroenterology. 2006 Apr. 130(4):1047-53. [Medline].
Johnson PJ, McFarlane IG, Williams R. Azathioprine for long-term maintenance of remission in autoimmune hepatitis. N Engl J Med. 1995 Oct 12. 333(15):958-63. [Medline].
Faisal N, Renner EL. Recurrence of autoimmune liver diseases after liver transplantation. World J Hepatol. 2015 Dec 18. 7 (29):2896-905. [Medline].
Tripathi D, Neuberger J. Autoimmune hepatitis and liver transplantation: indications, results, and management of recurrent disease. Semin Liver Dis. 2009 Aug. 29(3):286-96. [Medline].
Reich DJ, Fiel I, Guarrera JV, et al. Liver transplantation for autoimmune hepatitis. Hepatology. 2000 Oct. 32(4 Pt 1):693-700. [Medline].
Duclos-Vallee JC, Sebagh M, Rifai K, et al. A 10 year follow up study of patients transplanted for autoimmune hepatitis: histological recurrence precedes clinical and biochemical recurrence. Gut. 2003 Jun. 52(6):893-7. [Medline].
Montano-Loza AJ, Mason AL, Ma M, Bastiampillai RJ, Bain VG, Tandon P. Risk factors for recurrence of autoimmune hepatitis after liver transplantation. Liver Transpl. 2009 Sep 29. 15(10):1254-1261. [Medline].
Chazouillères O, Wendum D, Serfaty L, et al. Long term outcome and response to therapy of primary biliary cirrhosis-autoimmune hepatitis overlap syndrome. J Hepatol. 2006 Feb. 44(2):400-6. [Medline].
Douglas D. Budesonide Helpful in Pediatric Autoimmune HepatitisMedscape. July 10, 2013. Available at http://www.medscape.com/viewarticle/807623. Accessed: July 22, 2013.
Woynarowski M, Nemeth A, Baruch Y, Koletzko S, Melter M, Rodeck B, et al. Budesonide versus Prednisone with Azathioprine for the Treatment of Autoimmune Hepatitis in Children and Adolescents. J Pediatr. 2013 Jun 27. [Medline].
|Clinical Features||Type 1||Type 2||Type 3|
Synthetic core motif peptides 254-271
|Soluble liver-kidney antigen
Cytokeratins 8 and 18
|Age||10 y-elderly||Pediatric (2-14 y)
Rare in adults
|Adults (30-50 y)|
|Concurrent immune disease (%)||41||34||58|
|Gamma globulin elevation||+++||+||++|
|HLA association||B8, DR3, DR4||B14, Dr3, C4AQO||Uncertain|
|Progression to cirrhosis (%)||45||82||75|
|Serum AST 10-fold or more greater than the upper limit of normal||Symptoms (eg, fatigue, arthralgia, jaundice)|
|Serum AST 5-fold or more greater than the upper limit of normal and gamma-globulin level 2-fold or more greater than normal||Serum AST and/or gamma-globulin less than absolute criteria|
|Bridging necrosis or multiacinar necrosis on
|AST = aspartate aminotransferase.|
|Prednisone only (mg/d)||Combination|
|Prednisone (mg/d)||Azathioprine (mg/d)|
|Reasons for Preference||Cytopenia
Thiopurine methyltransferase deficiency
Short course (6 mo or less)
|Initial Regimen||Maintenance Regimen||End Point|
|Prednisone, 1-2 mg/kg/d (up to 60 mg/d), for 2 weeks, either alone or in combination with azathioprine, 1-2 mg/kg/d||a. Prednisone taper over 6-8 weeks to 0.1-0.2 mg/kg daily or 5 mg daily
b. Azathioprine at constant dose if added initially
c. Continue daily prednisone dose with or without azathioprine or switch to alternate day prednisone dose adjusted to response with or without azathioprine
|a. Normal liver tests for 1-2 years during treatment
b. No flare during entire interval
c. Liver biopsy examination discloses no inflammation