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Igg4 Associated Autoimmune Hepatitis: a Differential Diagnosis for Classical Autoimmune Hepatitis [2]

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Igg4 Associated Autoimmune Hepatitis: a Differential Diagnosis for Classical Autoimmune Hepatitis [2] View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Kanazawa University Repository for Academic Resources IgG4 associated autoimmune hepatitis: A differential diagnosis for classical autoimmune hepatitis [2] 著者 Umemura Takeji, Zen Yoh, Hamano Hiroaki, Ichijo Tetsuya, Kawa Shigeyuki K. H., Nakanuma Yasuni, Kiyosawa K. journal or Gut publication title volume 56 number 10 page range 1471-1472 year 2007-10-01 URL http://hdl.handle.net/2297/19724 doi: 10.1136/gut.2007.122283 Downloaded from gut.bmj.com on 26 November 2009 IgG4 associated autoimmune hepatitis: a differential diagnosis for classical autoimmune hepatitis T Umemura, Y Zen, H Hamano, T Ichijo, S Kawa, Y Nakanuma and K Kiyosawa Gut 2007;56;1471-1472; originally published online 15 May 2007; doi:10.1136/gut.2007.122283 Updated information and services can be found at: http://gut.bmj.com/cgi/content/full/56/10/1471 These include: References This article cites 3 articles, 1 of which can be accessed free at: http://gut.bmj.com/cgi/content/full/56/10/1471#BIBL 1 online articles that cite this article can be accessed at: http://gut.bmj.com/cgi/content/full/56/10/1471#otherarticles Email alerting Receive free email alerts when new articles cite this article - sign up in the box at service the top right corner of the article Notes To order reprints of this article go to: http://journals.bmj.com/cgi/reprintform To subscribe to Gut go to: http://journals.bmj.com/subscriptions/ Downloaded from gut.bmj.com on 26 November 2009 PostScript 1471 hepatitis C liver disease. N Engl J Med 1999;341:22–6. 3 Fukuda R, Ishimura N, Niigaki M, et al. Serologically silent hepatitis B virus coinfection in patients with hepatitis C virus-associated chronic liver disease: clinical and virological significance. J Med Virol 1999;58:201–7. 4 Munoz SJ. Use of hepatitis B core antibody-positive donors for liver transplantation. Liver Transpl 2002;8:S82–7. 5 Rizzetto M. Transmission of hepatitis B infection from hepatitis B core antibody-positive livers: background and prevention. Liver Transpl 2001;7:518–20. 6 Persico M, De Marino F, Di Giacomo Russo G, et al. Efficacy of lamivudine to prevent hepatitis reactivation in hepatitis B virus-infected patients treated for non-Hodgkin lymphoma. Blood 2002;99:724–5. 7 Lau JYN, Lai CL, Lin HJ, et al. Fatal reactivation of chronic hepatitis B infection following withdrawal of chemotherapy in lymphoma patients. Q J Med 1989;73:911–17. 8 Liang RHS, Lok ASF, Lai CL, et al. Hepatitis B infection in patients with lymphoma. Hematol Oncol 1990;8:261–70. 9 Hui CK, Cheung WW, Zhang HY, et al. Kinetics and risk of de novo hepatitis B infection in HBsAg- negative patients undergoing cytotoxic chemotherapy. Gastroenterology 2006;131:59–68. IgG4 associated autoimmune hepatitis: a differential diagnosis Figure 1 Pathological findings of the second liver biopsy. (A) Portal tracts are enlarged with severe inflammatory cell infiltration. Interface hepatitis is also observed (H&E, 6200). (B) Hepatocytes show for classical autoimmune hepatitis rosette formation (H&E, 6400). (C) Syncytial multinucleated giant cell change of hepatocytes is Autoimmune pancreatitis is characterised by observed (H&E, 6400). (D) Immunostaining for IgG4 reveals abundant IgG4 bearing plasma cells in a raised serum levels of IgG4 and IgG4-bearing portal tract (IgG4 immunostaining, 6400). plasma cells in the inflammatory tissue.1 Similar pathology can also occur in the larger bile ducts, resembling sclerosing cholangitis.2 hepatitis, lobular hepatitis, rosette formation, 557 mg/dl pretreatment (reference range ,135 We report a patient with hepatitis and chronic syncytial multinucleated giant cell change, and mg/dl), 226 mg/dl after one month, and 44 mg/ cholecystitis, raised IgG4 level, and IgG4- marked plasma cell infiltration (fig 1, panels A to dl after one year. Serum aspartate aminotrans- bearing plasma cells in the liver and gall C). Biliary features, such as cholangitis and ferase and alanine aminotransferase were 94 bladder wall, but no evident pancreatic disease. periductal fibrosis, were not evident. and 278 IU/l after one month, 31 and 73 IU/l In January 2003, a cholecystectomy was Immunostaining of liver tissue showed abun- after two months, and 22 and 25 IU/l after one undertaken on a 54 year old woman for chronic dance of plasma cells with strong immunohis- year, respectively. cholecystitis. The extracted gall bladder tochemical reactivity to IgG4 (fig 1D). The Raised serum IgG4 concentration and IgG4- showed lymphoplasmacytic infiltration and International Autoimmune Hepatitis Group bearing plasma cell infiltrates have a high subserosal fibrosis. A liver biopsy was done (IAIHG) disease score was 18, identifying sensitivity and specificity for the diagnosis of definite autoimmune hepatitis3 (table 1). autoimmune pancreatitis1 and associated dis- because of abnormal liver function tests and 2 showed severe lobular hepatitis with mild Treatment was successful with prednisolone 40 eases, including sclerosing cholangitis. In the portal inflammation. Plasma cell infiltration mg daily for four weeks, tapered by 5 mg weekly present case, the clinical and histological was observed in the portal tracts and parench- to 5 mg daily. Serum IgG4 concentrations were criteria for definite autoimmune hepatitis were yma, though fibrosis was not significant. IgG4 met and, additionally, both biopsies showed bearing plasma cell infiltration was found both hepatitis with abundant IgG4-bearing plasma in the liver and the gall bladder wall. After six Table 1 Autoimmune hepatitis cells in the liver and gallbladder. months, liver function was still abnormal: score using IAIHG scoring system We previously studied 17 patients with aspartate aminotransferase, 234 IU/l (reference classic autoimmune hepatitis. Both serum range, 12 to 37); alanine aminotransferase, Variable/feature Score IgG4 and IgG4-bearing plasma cells were 487 IU/l (7 to 45); alkaline phosphatase, completely absent in the liver of 13, and a Female sex: female +2 478 IU/l (124 to 367); c-glutamyl transpepti- minor increase in only one index was seen in ALP:AST ratio: 0.2 (,1.5) +2 4 dase, 581 IU/l (6 to 30); total bilirubin, four. Thus we can identify a new disease Serum IgG above normal: 1.4 g/dl +1 entity—IgG4 associated autoimmune hepati- 46.2 mmol/l (5 to 20); IgG, 2403 mg/dl (870 to (1.0 to 1.5) 1700). The antinuclear antibody titre (1:80 on tis—which can be differentiated from other ANA: 1:80 +2 recognised types. Our present case implies that rodent tissue) was abnormal, and tests for AMA positive: negative 0 autoantibodies to smooth muscle, double IgG4 related inflammatory processes can occur Hepatitis viral markers: negative +3 in the hepatic parenchyma in the same way as stranded DNA, and mitochondria were nega- + Drug history: negative 1 in the pancreatobiliary system, and such cases tive. Infection with hepatitis viruses A, B, and Average alcohol intake: ,25 g/ +2 may resemble autoimmune hepatitis both C, cytomegalovirus, and Epstein-Barr virus was day clinically and pathologically. As such, detection excluded. HLA DRB1 alleles were *1302 and Liver histology: *1501. Interface hepatitis +3 of IgG4 and assessment of liver histology using She denied taking medicines or herbal Predominantly lymphoplasmacytic +1 IgG4 immunostaining may be useful for remedies. infiltrate differentiating IgG4 related diseases from Ultrasonography, abdominal computed Rosetting of liver cells +1 definite autoimmune hepatitis. Further studies tomography, endoscopic retrograde cholangio- Total +18 are needed on this possible new disease entity graphy, and magnetic resonance cholangio- and its impact on the diagnostic guidelines for pancreatography showed no abnormalities in ALP, alkaline phosphatase; AMA, anti- autoimmune hepatitis. the extrahepatic bile ducts or pancreas. A mitochondrial antibodies; ANA, antinuclear antibody; AST, aspartate aminotransferase; second liver biopsy, which was done six IAIHG, International Autoimmune Hepatitis Acknowledgements months after the first, showed changes asso- Group. This work was supported in part by a research on ciated with autoimmune hepatitis, interface Measures for Intractable Diseases of the Pancreas, www.gutjnl.com Downloaded from gut.bmj.com on 26 November 2009 1472 PostScript Health and Labour Sciences Research Grants, sometimes used to screen patients. A fourfold HIDA scanning, cross sectional imaging, endo- Japanese Ministry of Health, Labour and Welfare. increase in either serum amylase or lipase and scopic retrograde cholangiopancreatography, We are indebted to Taeko Yamamoto for her technical reproduction of pain after intramuscular injec- and exclusion of luminal pathology. All assistance and to Dr Eishi Hara of Iida Hospital, tion of 10 mg morphine (to induce sphincteric patients had significant debilitating upper Japan, for his clinical assistance. spasm) and 1 mg prostigmine (to stimulate abdominal pain requiring regular strong pancreatic exocrine secretions) is considered a analgesia and had a poor quality of life. T Umemura positive test.23 However, the enzymatic Patients were Milwaukee class I or II and had Department of Internal Medicine, Division of Hepatology and Gastroenterology, Shinshu University School of changes may also occur in healthy subjects microscopic stenosis/fibrosis, but biliary mano- Medicine, Matsumoto, Japan and in patients with irritable bowel syn- metry was not done routinely. We excluded drome,34bringing the clinical value of the test from the
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