Following the identification of the hepatitis C virus (HCV) in 1989 (1.Choo Q-L Kuo G Weiner AJ Overby LR Bradley DW Houghton M Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome.Science. 1989; 244: 359-362Crossref PubMed Scopus (6209) Google Scholar), there was considerable uncertainty about criteria for diagnosis of the liver disorder which was then known as autoimmune chronic active hepatitis. In 1992, a panel of 27 physicians and pathologists with a particular interest in the syndrome was therefore convened at a meeting in Brighton, UK, to review the diagnostic criteria. That panel became the International Autoimmune Hepatitis Group (IAIHG), which shortly thereafter expanded to 40 members from 17 countries. The Group met againinChicago in 1993 and in Copenhagen in 1994, acted as the advisory panel on autoimmune hepatitis (AIH) at the International Workshop on Terminology of Chronic Hepatitis at the World Congresses of Gastroenterology in Los Angeles in 1994 (2.Ludwig J McFarlane IG Rakela J Demetris AJ Wanless IR Chairs Panel Terminology of chronic hepatitis, hepatic allograft rejection, and nodular lesions of the liver: summary of recommendations developed by an international working party.Am J Gastroenterol. 1994; 89: S177-S181PubMed Google Scholar, 3.Ludwig J McFarlane IG Rakela J Terminology of Chronic Hepatitis: International Working Party.Am J Gastroenterol. 1995; 90 (Chairs Panel): 181-189PubMed Google Scholar), and has since continued to monitor developments that impact on the diagnosis of the condition and to foster collaborative research.The consensus report of the initial meeting in Brighton (4.Johnson PJ McFarlane IG Meeting Report: International Autoimmune Hepatitis Group.Hepatology. 1993; 18: 998-1005Crossref PubMed Scopus (1059) Google Scholar) included a descriptive set of criteria which it was recommended could be used for diagnosis in routine clinical practice to classify patients as having either “definite” or “probable” autoimmune hepatitis (AIH). Additionally, a diagnostic scoring system was devised to provide an objective method for selection of relatively homogeneous groups of patients for research purposes. It was acknowledged in that report (4.Johnson PJ McFarlane IG Meeting Report: International Autoimmune Hepatitis Group.Hepatology. 1993; 18: 998-1005Crossref PubMed Scopus (1059) Google Scholar) that these recommendations would require validation by prospective evaluation. In the intervening years, both the descriptive criteria and the scoring system have been widely used by many investigators and there is now sufficient published information to allow for a comprehensive review in relation to progress that has been made in understanding the clinical expression of this disease, although the pathogenesis remains obscure. During 1998, the IAIHG undertook a detailed review by correspondence between members and at a meeting of the Group in Chicago on 9th November 1998 during the 49th annual conference of the American Association for the Study of Liver Diseases. We report here the outcome of these deliberations.Review of Diagnostic CriteriaThe descriptive criteria appear to have stood the test of time and require at most only minor modifications (see below) to bring them into line with recent developments in diagnostic modalities for liver disease generally. The review has, however, revealed that the scoring system requires some adjustments to improve specificity and simplify its use.There are six published studies in which the scoring system has been applied to sufficient numbers of patients to allow for meaningful evaluation (5.Czaja AJ Carpenter HA Validation of scoring system for diagnosis of autoimmune hepatitis.Dig Dis Sci. 1996; 41: 305-314Crossref PubMed Scopus (118) Google Scholar, 6.Bianchi FB Cassani F Lenzi M Ballardini G Muratori L Giostra F et al.Impact of International Autoimmune Hepatitis Group scoring system in definition of autoimmune hepatitis. An Italian experience.Dig Dis Sci. 1996; 41: 166-171Crossref PubMed Scopus (38) Google Scholar, 7.Toda G Zeniya M Watanabe F Imawari M Kiyosawa K Nishioka M et al.the Japanese National Study Group of Autoimmune HepatitisPresent status of autoimmune hepatitis in Japan - correlating the characteristics with international criteria in an area with a high rate of HCV infection.J Hepatol. 1997; 26: 1207-1212Abstract Full Text PDF PubMed Scopus (195) Google Scholar, 8.Miyakawa H Kitazawa E Abe K Kawaguchi N Fuzikawa H Kikuchi K et al.Chronic hepatitis C associated with anti-liver/kidney microsome-1 antibody is not a subgroup of autoimmune hepatitis.J Gastroenterol. 1997; 32: 769-776Crossref PubMed Scopus (28) Google Scholar, 9.Dickson RC Gaffey MJ Ishitani MB Roarty TP Driscoll CJ Caldwell SH The international autoimmune hepatitis score in chronic hepatitis C.J Viral Hep. 1997; 4: 121-128PubMed Google Scholar, 10.Boberg KM Fausa O Haaland T Holter E Mellbye OJ Spurkland A et al.Features of autoimmune hepatitis in primary sclerosing cholangitis: an evaluation of 114 primary sclerosing cholangitis patients according to a scoring system for the diagnosis of autoimmune hepatitis.Hepatology. 1996; 23: 1369-1376Crossref PubMed Google Scholar). Three of these (5.Czaja AJ Carpenter HA Validation of scoring system for diagnosis of autoimmune hepatitis.Dig Dis Sci. 1996; 41: 305-314Crossref PubMed Scopus (118) Google Scholar, 6.Bianchi FB Cassani F Lenzi M Ballardini G Muratori L Giostra F et al.Impact of International Autoimmune Hepatitis Group scoring system in definition of autoimmune hepatitis. An Italian experience.Dig Dis Sci. 1996; 41: 166-171Crossref PubMed Scopus (38) Google Scholar, 7.Toda G Zeniya M Watanabe F Imawari M Kiyosawa K Nishioka M et al.the Japanese National Study Group of Autoimmune HepatitisPresent status of autoimmune hepatitis in Japan - correlating the characteristics with international criteria in an area with a high rate of HCV infection.J Hepatol. 1997; 26: 1207-1212Abstract Full Text PDF PubMed Scopus (195) Google Scholar) included a total of nearly 600 patients with AIH diagnosed by different criteria in different countries (Table 1). In a study of patients attending the Mayo Clinic, Czaja & Carpenter (5.Czaja AJ Carpenter HA Validation of scoring system for diagnosis of autoimmune hepatitis.Dig Dis Sci. 1996; 41: 305-314Crossref PubMed Scopus (118) Google Scholar) employed the“conventional” clinical criteria (11.Czaja AJ Natural history, clinical features, and treatment of autoimmune hepatitis.Semin Liver Dis. 1984; 4: 1-12Crossref PubMed Scopus (163) Google Scholar) that were in use prior to publication of the “Brighton report”(4.Johnson PJ McFarlane IG Meeting Report: International Autoimmune Hepatitis Group.Hepatology. 1993; 18: 998-1005Crossref PubMed Scopus (1059) Google Scholar), Bianchi et al. (6.Bianchi FB Cassani F Lenzi M Ballardini G Muratori L Giostra F et al.Impact of International Autoimmune Hepatitis Group scoring system in definition of autoimmune hepatitis. An Italian experience.Dig Dis Sci. 1996; 41: 166-171Crossref PubMed Scopus (38) Google Scholar) applied the IAIHG descriptive criteria to Italian patients, and in the study on Japanese patients by Toda et al. (7.Toda G Zeniya M Watanabe F Imawari M Kiyosawa K Nishioka M et al.the Japanese National Study Group of Autoimmune HepatitisPresent status of autoimmune hepatitis in Japan - correlating the characteristics with international criteria in an area with a high rate of HCV infection.J Hepatol. 1997; 26: 1207-1212Abstract Full Text PDF PubMed Scopus (195) Google Scholar) AIH was diagnosed according to the Japanese Ministry of Health & Welfare criteria (7.Toda G Zeniya M Watanabe F Imawari M Kiyosawa K Nishioka M et al.the Japanese National Study Group of Autoimmune HepatitisPresent status of autoimmune hepatitis in Japan - correlating the characteristics with international criteria in an area with a high rate of HCV infection.J Hepatol. 1997; 26: 1207-1212Abstract Full Text PDF PubMed Scopus (195) Google Scholar) which specify seropositivity for antinuclear antibodies (ANA). All three studies agreed that the scoring system has a very high degree of sensitivity, ranging from 97% to 100%, for diagnosis of AIH (Table 1).TABLE 1Analysis of sensitivity of scoring system for diagnosis of autoimmune hepatitisStudyDiagnostic criterianPercent scoring asOverall diagnostic sensitivityDefinite AIHProbable AIHCzaja & Carpenter (5)“Conventional”11981.5%18.5%100%Bianchi et al. (6)IAIHG descriptive4568.8%31.1%99.9%Toda et al. (7)Japanese43454.8%42.5%97.3%Total=598AIH=autoimmine hepatitis. IAIHG=International Autoimmune Hepatitis Group. Open table in a new tab In five of these six studies (5.Czaja AJ Carpenter HA Validation of scoring system for diagnosis of autoimmune hepatitis.Dig Dis Sci. 1996; 41: 305-314Crossref PubMed Scopus (118) Google Scholar, 6.Bianchi FB Cassani F Lenzi M Ballardini G Muratori L Giostra F et al.Impact of International Autoimmune Hepatitis Group scoring system in definition of autoimmune hepatitis. An Italian experience.Dig Dis Sci. 1996; 41: 166-171Crossref PubMed Scopus (38) Google Scholar, 7.Toda G Zeniya M Watanabe F Imawari M Kiyosawa K Nishioka M et al.the Japanese National Study Group of Autoimmune HepatitisPresent status of autoimmune hepatitis in Japan - correlating the characteristics with international criteria in an area with a high rate of HCV infection.J Hepatol. 1997; 26: 1207-1212Abstract Full Text PDF PubMed Scopus (195) Google Scholar, 8.Miyakawa H Kitazawa E Abe K Kawaguchi N Fuzikawa H Kikuchi K et al.Chronic hepatitis C associated with anti-liver/kidney microsome-1 antibody is not a subgroup of autoimmune hepatitis.J Gastroenterol. 1997; 32: 769-776Crossref PubMed Scopus (28) Google Scholar, 9.Dickson RC Gaffey MJ Ishitani MB Roarty TP Driscoll CJ Caldwell SH The international autoimmune hepatitis score in chronic hepatitis C.J Viral Hep. 1997; 4: 121-128PubMed Google Scholar) the scoring system was also applied to a total of 242 patients with chronic hepatitis C who presented with features suggestive of AIH, including ANA, smooth muscle (SMA) or type 1 liver-kidney microsomal (anti-LKM-1) autoantibodies (Table 2). Additionally, Czaja & Carpenter (5.Czaja AJ Carpenter HA Validation of scoring system for diagnosis of autoimmune hepatitis.Dig Dis Sci. 1996; 41: 305-314Crossref PubMed Scopus (118) Google Scholar) and Boberg et al. (10.Boberg KM Fausa O Haaland T Holter E Mellbye OJ Spurkland A et al.Features of autoimmune hepatitis in primary sclerosing cholangitis: an evaluation of 114 primary sclerosing cholangitis patients according to a scoring system for the diagnosis of autoimmune hepatitis.Hepatology. 1996; 23: 1369-1376Crossref PubMed Google Scholar) tested the specificity of the system for excluding AIH in a total of 143 patients with primary sclerosing cholangitis (PSC) and other biliary disorders (Table 3). Specificity for exclusion of definite AIH in these 385 cases ranged from 96% to 100%. However, a variable proportion (between 8% and 52%) of patients achieved scores within the range stipulated for a diagnosis of probable AIH, reducing the overall specificity to between 45% and 92%. Similar findings have been reported from studies on smaller numbers of patients (12.Nishioka M Morshed SA Recent progress in autoimmune liver disease.in: Husband AJ Advances in Mucosal Immunology, vol. 1. University of Sydney Press, Sydney1997: 425-437Google Scholar). In the majority of these cases the aggregate scores were borderline, i.e. only one or two points above the cut-off (10 points) for diagnosis of probable AIH. It was noted that indices which contributed mainly to inappropriate upgrading of scores to within the“probable” range included positive scoring for autoantibodies, mild to moderate elevations in serum immunoglobulins, low ratios of alkaline phosphatase (ALP) to aspartate (AST) or alanine (ALT) aminotransferases, concurrent immunological disorders and relevant HLA markers, together with inadequate weighting against histological evidence of biliary disease (5.Czaja AJ Carpenter HA Validation of scoring system for diagnosis of autoimmune hepatitis.Dig Dis Sci. 1996; 41: 305-314Crossref PubMed Scopus (118) Google Scholar, 6.Bianchi FB Cassani F Lenzi M Ballardini G Muratori L Giostra F et al.Impact of International Autoimmune Hepatitis Group scoring system in definition of autoimmune hepatitis. An Italian experience.Dig Dis Sci. 1996; 41: 166-171Crossref PubMed Scopus (38) Google Scholar, 7.Toda G Zeniya M Watanabe F Imawari M Kiyosawa K Nishioka M et al.the Japanese National Study Group of Autoimmune HepatitisPresent status of autoimmune hepatitis in Japan - correlating the characteristics with international criteria in an area with a high rate of HCV infection.J Hepatol. 1997; 26: 1207-1212Abstract Full Text PDF PubMed Scopus (195) Google Scholar, 8.Miyakawa H Kitazawa E Abe K Kawaguchi N Fuzikawa H Kikuchi K et al.Chronic hepatitis C associated with anti-liver/kidney microsome-1 antibody is not a subgroup of autoimmune hepatitis.J Gastroenterol. 1997; 32: 769-776Crossref PubMed Scopus (28) Google Scholar, 9.Dickson RC Gaffey MJ Ishitani MB Roarty TP Driscoll CJ Caldwell SH The international autoimmune hepatitis score in chronic hepatitis C.J Viral Hep. 1997; 4: 121-128PubMed Google Scholar, 10.Boberg KM Fausa O Haaland T Holter E Mellbye OJ Spurkland A et al.Features of autoimmune hepatitis in primary sclerosing cholangitis: an evaluation of 114 primary sclerosing cholangitis patients according to a scoring system for the diagnosis of autoimmune hepatitis.Hepatology. 1996; 23: 1369-1376Crossref PubMed Google Scholar).TABLE 2Specificity of scoring system for excluding autoimmune hepatitis in patients with chronic hepatitis C presenting with autoimmune featuresStudynPercent scoring asOverall diagnostic specificityDefinite AIHProbable AIHCzaja & Carpenter (5)60023.3%76.7%Bianchi et al. (6)65012.3%87.7%Toda et al. (7)62033.9%66.1%Miyakawa et al. (8)2508.0%92.0%Dickson et al. (9)30013.3%86.7%Total=242AIH=autoimmune hepatitis. Open table in a new tab TABLE 3Specificity of scoring system for excluding autoimmune hepatitis in patients with biliary disordersStudyPatient groupnPercent scoring asOverall diagnostic specificityDefinite AIHProbable AIHCzaja & Carpenter (5)PBCPSC293.4%51.7%44.8%AICBoberg et al. (10)PSC1141.8%33.3%64.9%Total=143AIH=autoimmune hepatitis. PBC=primary biliary cirrhosis. PSC=primary sclerosing cholangitis. AIC=autoimmune cholangitis (patients with features of AIH and cholestatic biochemical profiles and/or histological or cholangiographic evidence of biliary disease). Open table in a new tab From the data provided for the 983 patients in the six main reports cited above (5.Czaja AJ Carpenter HA Validation of scoring system for diagnosis of autoimmune hepatitis.Dig Dis Sci. 1996; 41: 305-314Crossref PubMed Scopus (118) Google Scholar, 6.Bianchi FB Cassani F Lenzi M Ballardini G Muratori L Giostra F et al.Impact of International Autoimmune Hepatitis Group scoring system in definition of autoimmune hepatitis. An Italian experience.Dig Dis Sci. 1996; 41: 166-171Crossref PubMed Scopus (38) Google Scholar, 7.Toda G Zeniya M Watanabe F Imawari M Kiyosawa K Nishioka M et al.the Japanese National Study Group of Autoimmune HepatitisPresent status of autoimmune hepatitis in Japan - correlating the characteristics with international criteria in an area with a high rate of HCV infection.J Hepatol. 1997; 26: 1207-1212Abstract Full Text PDF PubMed Scopus (195) Google Scholar, 8.Miyakawa H Kitazawa E Abe K Kawaguchi N Fuzikawa H Kikuchi K et al.Chronic hepatitis C associated with anti-liver/kidney microsome-1 antibody is not a subgroup of autoimmune hepatitis.J Gastroenterol. 1997; 32: 769-776Crossref PubMed Scopus (28) Google Scholar, 9.Dickson RC Gaffey MJ Ishitani MB Roarty TP Driscoll CJ Caldwell SH The international autoimmune hepatitis score in chronic hepatitis C.J Viral Hep. 1997; 4: 121-128PubMed Google Scholar, 10.Boberg KM Fausa O Haaland T Holter E Mellbye OJ Spurkland A et al.Features of autoimmune hepatitis in primary sclerosing cholangitis: an evaluation of 114 primary sclerosing cholangitis patients according to a scoring system for the diagnosis of autoimmune hepatitis.Hepatology. 1996; 23: 1369-1376Crossref PubMed Google Scholar), it is calculated that the overall diagnostic accuracy of the scoring system (i.e. the number of patients correctly diagnosed as having or not having definite or probable AIH as a percentage of the total number of patients studied) is 89.8%. This should be considered to be a minimal value because the calculation is based on the presumption that none of the patients with chronic hepatitis C or biliary disorders also had concomitant AIH (which is unknown).Considerations for Revision of Diagnostic CriteriaPresenting clinical and serum biochemical featuresThe present review has reaffirmed that there are no particular signs, symptoms or liver test abnormalities that are of sufficient specificity to be considered part of the diagnostic criteria (4.Johnson PJ McFarlane IG Meeting Report: International Autoimmune Hepatitis Group.Hepatology. 1993; 18: 998-1005Crossref PubMed Scopus (1059) Google Scholar). Onset is usually insidious, with fatigue, fluctuating jaundice and arthralgia as typical features, but a substantial proportion of patients either have no obvious signs or symptoms of liver disease or have an (occasionally severe) acute presentation (13.Herzog D Rasquin-Weber AM Debray D Alvarez F Subfulminant hepatic failure in autoimmune hepatitis type 1: an unusual form of presentation.J Hepatol. 1997; 27: 578-582Abstract Full Text PDF PubMed Scopus (51) Google Scholar, 14.Parker DR Kingham JGC Type 1 autoimmune hepatitis is primarily a disease of later life.Q J Med. 1997; 90: 289-296Crossref Scopus (56) Google Scholar, 15.Gordon SC Diagnostic criteria, clinical manifestations and natural history of autoimmune hepatitis.in: Krawitt EL Wiesner RH Nishioka M Autoimmune Liver Diseases. 2nd ed. Elsevier, Amsterdam1998: 343-360Google Scholar). There is often a history of other autoimmune disorders in the patient or first-degree relatives. The disease predominates among women, the archetypal patient being a young female with endocrine abnormalities, but it also affects males and it can present at almost any age. Distribution of age at onset was thought to be bimodal, with peaks around puberty and between the fourth and sixth decades of life (16.McFarlane IG The relationship between autoimmune markers and different clinical syndromes in autoimmune hepatitis.Gut. 1998; 42: 599-602Crossref PubMed Scopus (76) Google Scholar), but it has been suggested that this impression probably relates to patterns of patient referral to specialist centres (14.Parker DR Kingham JGC Type 1 autoimmune hepatitis is primarily a disease of later life.Q J Med. 1997; 90: 289-296Crossref Scopus (56) Google Scholar). In Japan, and in general gastroenterology practices elsewhere, the large majority of patients present between 50 and 70 years of age (7.Toda G Zeniya M Watanabe F Imawari M Kiyosawa K Nishioka M et al.the Japanese National Study Group of Autoimmune HepatitisPresent status of autoimmune hepatitis in Japan - correlating the characteristics with international criteria in an area with a high rate of HCV infection.J Hepatol. 1997; 26: 1207-1212Abstract Full Text PDF PubMed Scopus (195) Google Scholar, 14.Parker DR Kingham JGC Type 1 autoimmune hepatitis is primarily a disease of later life.Q J Med. 1997; 90: 289-296Crossref Scopus (56) Google Scholar).It is reaffirmed that hypergammaglobulinaemia with selective elevation of serum IgG is characteristic of AIH (4.Johnson PJ McFarlane IG Meeting Report: International Autoimmune Hepatitis Group.Hepatology. 1993; 18: 998-1005Crossref PubMed Scopus (1059) Google Scholar). Other serum biochemical abnormalities show a predominantly hepatitic pattern, but bilirubin concentrations and aminotransferase activities may range from just above the upper normal limits to more than 50 times these levels (4.Johnson PJ McFarlane IG Meeting Report: International Autoimmune Hepatitis Group.Hepatology. 1993; 18: 998-1005Crossref PubMed Scopus (1059) Google Scholar), with usually normal or only moderately elevated ALP, and do not reliably reflect severity of the disease. In keeping with the fluctuating nature of the condition, these biochemical indices may even spontaneously normalise despite histological evidence of continuing activity (15.Gordon SC Diagnostic criteria, clinical manifestations and natural history of autoimmune hepatitis.in: Krawitt EL Wiesner RH Nishioka M Autoimmune Liver Diseases. 2nd ed. Elsevier, Amsterdam1998: 343-360Google Scholar).Review of the scoring system has revealed that adjustments to the scoring for ALP:AST(or ALT) ratio are necessary. During initial development of the system it was found that this parameter was essential to exclude PBC, and the ratio specified (3.0) achieved this without excluding the small proportion of AIH patients who present with cholestatic features. In retrospect, insufficient consideration was given to PSC, in which ALP activities are often only moderately raised and mild to moderate elevations of serum aminotransferase activities are frequently seen (10.Boberg KM Fausa O Haaland T Holter E Mellbye OJ Spurkland A et al.Features of autoimmune hepatitis in primary sclerosing cholangitis: an evaluation of 114 primary sclerosing cholangitis patients according to a scoring system for the diagnosis of autoimmune hepatitis.Hepatology. 1996; 23: 1369-1376Crossref PubMed Google Scholar). In such cases the ALP:AST (or ALT) ratio falls below the cut-off that was set for negative weighting and this was a major contributory factor to the high proportion of patients with biliary diseases who achieved scores suggesting a diagnosis of“probable” AIH in the studies of Czaja & Carpenter (5.Czaja AJ Carpenter HA Validation of scoring system for diagnosis of autoimmune hepatitis.Dig Dis Sci. 1996; 41: 305-314Crossref PubMed Scopus (118) Google Scholar) and Boberg et al. (10.Boberg KM Fausa O Haaland T Holter E Mellbye OJ Spurkland A et al.Features of autoimmune hepatitis in primary sclerosing cholangitis: an evaluation of 114 primary sclerosing cholangitis patients according to a scoring system for the diagnosis of autoimmune hepatitis.Hepatology. 1996; 23: 1369-1376Crossref PubMed Google Scholar).HistologyIt is reaffirmed that: (a) there are no morphological features that are pathognomonic of AIH, but the characteristic histological picture is that of an interface (periportal or periseptal) hepatitis with a predominantly lymphoplasmacytic necroinflammatory infiltrate, with or without lobular (intra-acinar) involvement and portal-portal or central-portal bridging necrosis, often with the formation of liver cell rosettes and nodular regeneration (even in the early stages) in severe cases; and (b) patients in whom these features are seen together with clear evidence of bile duct damage or welldefined granulomas (see also“Overlapping syndromes” below) should not be regarded as having AIH (4.Johnson PJ McFarlane IG Meeting Report: International Autoimmune Hepatitis Group.Hepatology. 1993; 18: 998-1005Crossref PubMed Scopus (1059) Google Scholar). Other features such as lymphoid aggregates, steatosis, siderosis, cuprinosis, and bile ductule proliferation (which may occur to some degree in AIH, even in the absence of cirrhosis), are considered not to have the required specificity to exclude AIH, except where such features (and particularly combinations thereof) are sufficiently prominent to raise doubts about the diagnosis. Additionally, it is noted that the biochemical and immunological features of AIH can be seen in other disorders such as systemic lupus erythematosus in the absence of any significant liver involvement (17.Kooy A de Heide LJM Engelkens HJH Mulder AH van Hagen M Schalm SW How to diagnose autoimmune hepatitis in systemic lupus erythematosus.Hepatology. 1996; 23: 937-938Crossref Google Scholar). It is therefore reiterated that a diagnosis of definite AIH should not be made without liver histology - and consultation with a hepatopathologist is strongly recommended (4.Johnson PJ McFarlane IG Meeting Report: International Autoimmune Hepatitis Group.Hepatology. 1993; 18: 998-1005Crossref PubMed Scopus (1059) Google Scholar).AutoantibodiesIt is reaffirmed that about 70–80% of AIH patients present with significant titres (1:40 or greater) of ANA or SMA (or both) and overall about 3–4% (mainly young females) have anti-LKM-1 (sometimes at titres <1:40), while up to 20% have none of these antibodies (4.Johnson PJ McFarlane IG Meeting Report: International Autoimmune Hepatitis Group.Hepatology. 1993; 18: 998-1005Crossref PubMed Scopus (1059) Google Scholar). In the context of liver disease, perinuclear staining antineutrophil cytoplasmic antibodies (pANCA) were previously thought to be particularly associated with PSC (18.Snook JA Chapman RW Fleming K Jewell DP Anti-neutrophil nuclear antibody in ulcerative colitis, Crohn's disease and primary sclerosing cholangitis.Clin Exp Immunol. 1989; 76: 30-33PubMed Google Scholar, 19.Seibold F Weber P Klein R Berg PA Wiedmann KH Clinical significance of antibodies against neutrophils in patients with inflammatory bowel disease and primary sclerosing cholangitis.Gut. 1992; 33: 657-662Crossref PubMed Scopus (194) Google Scholar), but several recent studies have documented high titres of pANCA (detected by immunofluorescence on ethanol fixed neutrophils) in the sera of up to 90% of patients with AIH (20.Hardarson S La Brecque DR Mitros FA Neil GA Goeken JA Antineutrophil cytoplasmic antibody in inflammatory bowel and hepatobiliary diseases: high prevalence in ulcerative colitis, primary sclerosing cholangitis, and autoimmune hepatitis.Clin Microbiol Immunol. 1993; 99: 277-281Google Scholar, 21.Mulder AHL Horst G Haagsma EB Limburg PC Kleibeuker JH Kallenberg CGM Prevalence and characterization of neutrophil cytoplasmic antibodies in autoimmune liver disease.Hepatology. 1993; 17: 411-417Crossref PubMed Scopus (212) Google Scholar, 22.Vidrich A Lee J James E Cobb L Targan S Segregation of pANCA antigenic recognition by Dnase treatment of neutrophils: ulcerative colitis, type 1 autoimmune hepatitis and primary sclerosing cholangitis.J Clin Immunol. 1995; 15: 293-299Crossref PubMed Scopus (99) Google Scholar, 23.Targan SR Landers C Vidrich A Czaja AJ High-titer antineutrophil cytoplasmic antibodies in type-1 autoimmune hepatitis.Gastroenterology. 1995; 108: 1159-1166Abstract Full Text PDF PubMed Scopus (178) Google Scholar, 24.Zauli D Ghetti S Grassi A Descovich C Cassani F Ballardini G et al.Anti-neutrophil cytoplasmic antibodies in type 1 and 2 autoimmune hepatitis.Hepatology. 1997; 25: 1105-1107Crossref PubMed Scopus (123) Google Scholar). 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RG Landes, Austin, Texas1996: 24-44Google Scholar, 30.Stoffel MP Csernok E Herzberg C Johnston T Carroll SF Gross WL Anti-neutrophil cytoplasmic (ANCA) directed against bactericidal/permeability increasing protein (BPI): a new seromarker for inflammatory bowel disease and associated disorders.Clin Exp Immunol. 1996; 104: 54-59Crossref PubMed Scopus (120) Google Scholar, 31.Zauli D Cassani F Bianchi FB Cytoskeletal antigens.in: McFarlane IG Williams R Molecular Basis of Autoimmune Hepatitis. RG Landes, Austin, Texas1996: 45-58Google Scholar, 32.Manns MP Cytoplasmic antigens.in: McFarlane IG Williams R Molecular Basis of Autoimmune Hepatitis. RG Landes, Austin, Texas1996: 59-74Google Scholar, 33.Terjung B Herzog V Worman HJ Gestmann I Bauer C Sauerbruch T et al.Atypical antineutrophil cytoplasmic antibodies with perinuclear fluorescence in chronic inflammatory bowel diseases and hepatobiliary disorders colocalize with nuclear lamina proteins.Hepatology. 1998; 28: 332-340Crossref PubMed Scopus (80) Google Scholar). However, (a) sub-specificities of some antibodies (e.g. ANA) seem to have limited clinical implications in AIH (34.Czaja AJ Cassani F Cataleta M Valentini P Bianchi FB Antinuclear antibodies and patterns of nuclear immunofluorescence in type 1 autoimmune hepatitis.Dig Dis Sci. 1997; 42: 1688-1696Crossref PubMed Scopus (87) Google Scholar, 35.Chen M Shirai M Czaja A
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