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01-01-2011 | International Forum

Clinical significance of immunoglobulin G4-associated autoimmune hepatitis

Authors: Takeji Umemura, Yoh Zen, Hideaki Hamano, Satoru Joshita, Tetsuya Ichijo, Kaname Yoshizawa, Kendo Kiyosawa, Masao Ota, Shigeyuki Kawa, Yasuni Nakanuma, Eiji Tanaka

Published in: Journal of Gastroenterology | Special Issue 1/2011

Abstract

Background

Immunoglobulin (Ig) G4-associated autoimmune hepatitis (AIH) is a recently identified and possibly new disease entity. However, the epidemiology and clinical features of IgG4-associated AIH remain uncertain. The aim of this study was to determine the prevalence and the clinical, serological, and histological characteristics of IgG4-associated AIH.

Methods

We examined the clinical features, serum IgG4 concentration, liver biopsy histology, and IgG4-bearing plasma cell infiltration of 60 patients with type 1 AIH and 22 patients with autoimmune pancreatitis.

Results

High serum IgG4 concentration (≥135 mg/dL) and IgG4-bearing plasma cell infiltration in the liver (≥10/high-power fields [HPFs]) were found in 2 of the 60 (3.3%) patients with type 1 AIH. These patients had high serum levels of IgE, giant cell change, and rosette formation in the liver. Although corticosteroid therapy reduced the serum IgG4 concentration and normalized liver enzymes and histology, one patient developed IgG4-related sclerosing cholangitis after 5 years of follow-up.

Conclusions

Because IgG4-associated AIH was found in over 3% of Japanese patients with type 1 AIH in our cohort, further studies are needed on this possible new disease entity and its impact on the diagnostic guidelines of AIH.

Krawitt EL. Autoimmune hepatitis. N Engl J Med. 2006;354:54–66.CrossRefPubMed

Manns MP, Vogel A. Autoimmune hepatitis, from mechanisms to therapy. Hepatology. 2006;43:S132–44.CrossRefPubMed

Vergani D, Longhi MS, Bogdanos DP, Ma Y, Mieli-Vergani G. Autoimmune hepatitis. Semin Immunopathol. 2009;31:421–35.CrossRefPubMed

Alvarez F, Berg PA, Bianchi FB, Bianchi L, Burroughs AK, Cancado EL, et al. International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol. 1999;31:929–38.CrossRefPubMed

Umemura T, Zen Y, Hamano H, Ichijo T, Kawa S, Nakanuma Y, et al. IgG4 associated autoimmune hepatitis: a differential diagnosis for classical autoimmune hepatitis. Gut. 2007;56:1471–2.CrossRefPubMed

Hamano H, Kawa S, Horiuchi A, Unno H, Furuya N, Akamatsu T, et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med. 2001;344:732–8.CrossRefPubMed

Hamano H, Kawa S, Ochi Y, Unno H, Shiba N, Wajiki M, et al. Hydronephrosis associated with retroperitoneal fibrosis and sclerosing pancreatitis. Lancet. 2002;359:1403–4.CrossRefPubMed

Umemura T, Zen Y, Hamano H, Kawa S, Nakanuma Y, Kiyosawa K. Immunoglobin G4-hepatopathy: association of immunoglobin G4-bearing plasma cells in liver with autoimmune pancreatitis. Hepatology. 2007;46:463–71.CrossRefPubMed

Zen Y, Harada K, Sasaki M, Sato Y, Tsuneyama K, Haratake J, et al. IgG4-related sclerosing cholangitis with and without hepatic inflammatory pseudotumor, and sclerosing pancreatitis-associated sclerosing cholangitis: do they belong to a spectrum of sclerosing pancreatitis? Am J Surg Pathol. 2004;28:1193–203.CrossRefPubMed

10.

Ghazale A, Chari ST, Zhang L, Smyrk TC, Takahashi N, Levy MJ, et al. Immunoglobulin G4-associated cholangitis: clinical profile and response to therapy. Gastroenterology. 2008;134:706–15.PubMed

11.

Chung H, Watanabe T, Kudo M, Maenishi O, Wakatsuki Y, Chiba T. Identification and characterization of IgG4-associated autoimmune hepatitis. Liver Int. 2010;30(2):222–31.CrossRefPubMed

12.

Okazaki K, Kawa S, Kamisawa T, Naruse S, Tanaka S, Nishimori I, et al. Clinical diagnostic criteria of autoimmune pancreatitis: revised proposal. J Gastroenterol. 2006;41:626–31.CrossRefPubMed

13.

Umemura T, Wang RY, Schechterly C, Shih JW, Kiyosawa K, Alter HJ. Quantitative analysis of anti-hepatitis C virus antibody-secreting B cells in patients with chronic hepatitis C. Hepatology. 2006;43:91–9.CrossRefPubMed

14.

Ota M, Seki T, Nomura N, Sugimura K, Mizuki N, Fukushima H, et al. Modified PCR-RFLP method for HLA-DPB1 and -DQA1 genotyping. Tissue Antigens. 1991;38:60–71.CrossRefPubMed

15.

Ota M, Seki T, Fukushima H, Tsuji K, Inoko H. HLA-DRB1 genotyping by modified PCR-RFLP method combined with group-specific primers. Tissue Antigens. 1992;39:187–202.CrossRefPubMed

16.

Umemura T, Zen Y, Nakanuma Y, Kiyosawa K. Another cause of autoimmune hepatitis. Hepatology. 2010;52:389–90.CrossRefPubMed

17.

Koyabu M, Uchida K, Miyoshi H, Sakaguchi Y, Fukui T, Ikeda H, et al. Analysis of regulatory T cells and IgG4-positive plasma cells among patients of IgG4-related sclerosing cholangitis and autoimmune liver diseases. J Gastroenterol. 2010;45(7):732–41.CrossRefPubMed

18.

Chari ST, Smyrk TC, Levy MJ, Topazian MD, Takahashi N, Zhang L, et al. Diagnosis of autoimmune pancreatitis: the Mayo Clinic experience. Clin Gastroenterol Hepatol. 2006;4:1010–6.CrossRefPubMed

19.

McNair AN, Moloney M, Portmann BC, Williams R, McFarlane IG. Autoimmune hepatitis overlapping with primary sclerosing cholangitis in five cases. Am J Gastroenterol. 1998;93:777–84.CrossRefPubMed

20.

Gohlke F, Lohse AW, Dienes HP, Lohr H, Marker-Hermann E, Gerken G, et al. Evidence for an overlap syndrome of autoimmune hepatitis and primary sclerosing cholangitis. J Hepatol. 1996;24:699–705.CrossRefPubMed

21.

Abdo AA, Bain VG, Kichian K, Lee SS. Evolution of autoimmune hepatitis to primary sclerosing cholangitis: a sequential syndrome. Hepatology. 2002;36:1393–9.PubMed

22.

van Buuren HR, van Hoogstraten HJE, Terkivatan T, Schalm SW, Vleggaar FP. High prevalence of autoimmune hepatitis among patients with primary sclerosing cholangitis. J Hepatol. 2000;33:543–8.CrossRefPubMed

23.

Kaya M, Angulo P, Lindor KD. Overlap of autoimmune hepatitis and primary sclerosing cholangitis: an evaluation of a modified scoring system. J Hepatol. 2000;33:537–42.CrossRefPubMed

24.

Gregorio GV, Portmann B, Karani J, Harrison P, Donaldson PT, Vergani D, et al. Autoimmune hepatitis/sclerosing cholangitis overlap syndrome in childhood: a 16-year prospective study. Hepatology. 2001;33:544–53.CrossRefPubMed

25.

Jeannin P, Lecoanet S, Delneste Y, Gauchat JF, Bonnefoy JY. IgE versus IgG4 production can be differentially regulated by IL-10. J Immunol. 1998;160:3555–61.PubMed

26.

Meiler F, Klunker S, Zimmermann M, Akdis CA, Akdis M. Distinct regulation of IgE, IgG4 and IgA by T regulatory cells and toll-like receptors. Allergy. 2008;63:1455–63.CrossRefPubMed

27.

Zen Y, Fujii T, Harada K, Kawano M, Yamada K, Takahira M, et al. Th2 and regulatory immune reactions are increased in immunoglobin G4-related sclerosing pancreatitis and cholangitis. Hepatology. 2007;45:1538–46.CrossRefPubMed

28.

Seki T, Ota M, Furuta S, Fukushima H, Kondo T, Hino K, et al. HLA class II molecules and autoimmune hepatitis susceptibility in Japanese patients. Gastroenterology. 1992;103:1041–7.PubMed

29.

Kawa S, Ota M, Yoshizawa K, Horiuchi A, Hamano H, Ochi Y, et al. HLA DRB10405-DQB10401 haplotype is associated with autoimmune pancreatitis in the Japanese population. Gastroenterology. 2002;122:1264–9.CrossRefPubMed

30.

Umemura T, Ota M, Yoshizawa K, Katsuyama Y, Ichijo T, Tanaka E, et al. Association of cytotoxic T-lymphocyte antigen 4 gene polymorphisms with type 1 autoimmune hepatitis in Japanese. Hepatol Res. 2008;38:689–95.CrossRefPubMed

31.

Umemura T, Ota M, Hamano H, Katsuyama Y, Muraki T, Arakura N, et al. Association of autoimmune pancreatitis with cytotoxic T-lymphocyte antigen 4 gene polymorphisms in Japanese patients. Am J Gastroenterol. 2008;103:588–94.CrossRefPubMed

32.

Umemura T, Ota M, Yoshizawa K, Katsuyama Y, Ichijo T, Tanaka E, et al. Lack of association between FCRL3 and FcgammaRII polymorphisms in Japanese type 1 autoimmune hepatitis. Clin Immunol. 2007;122:338–42.CrossRefPubMed

33.

Umemura T, Ota M, Hamano H, Katsuyama Y, Kiyosawa K, Kawa S. Genetic association of Fc receptor-like 3 polymorphisms with autoimmune pancreatitis in Japanese patients. Gut. 2006;55:1367–8.CrossRefPubMed

Title: Clinical significance of immunoglobulin G4-associated autoimmune hepatitis
Authors: Takeji Umemura
Yoh Zen
Hideaki Hamano
Satoru Joshita
Tetsuya Ichijo
Kaname Yoshizawa
Kendo Kiyosawa
Masao Ota
Shigeyuki Kawa
Yasuni Nakanuma
Eiji Tanaka
Publication date: 01-01-2011
Publisher: Springer Japan
Published in: Journal of Gastroenterology / Issue Special Issue 1/2011
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI: https://doi.org/10.1007/s00535-010-0323-4

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