Autoimmune liver disease

Current Opinion in Gastroenterology

Volumn 25, Issue 3, 2009, Pages 215-222

  Czaja, Albert J ^a  

^a MAYO CLINIC   (United States)

Author keywords

Diagnostic features; Pathogenic mechanisms; Therapeutic options

Indexed keywords

ARGINASE; AUTOANTIGEN; AZATHIOPRINE; BIOLOGICAL MARKER; BUDESONIDE; CYTOKERATIN 18; CYTOKERATIN 8; F ACTIN; F ACTIN ANTIBODY; HEAT SHOCK PROTEIN; HEPATITIS A VACCINE; HEPATITIS B VACCINE; MERCAPTOPURINE; MITOCHONDRION ANTIBODY; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; PHOSPHOGLYCERATE MUTASE; PHOSPHOGLYCERATE MUTASE B; PREDNISOLONE; UNCLASSIFIED DRUG; VALOSIN CONTAINING PROTEIN;

ADOPTIVE TRANSFER; AUTOIMMUNE HEPATITIS; BONE MARROW TOXICITY; CD4+ CD25+ T LYMPHOCYTE; DRUG CLEARANCE; DRUG DOSE REDUCTION; DRUG RECEPTOR BINDING; ELASTOGRAPHY; GENETIC SUSCEPTIBILITY; HEPATITIS A; HEPATITIS A VIRUS; HEPATITIS B; HEPATITIS B VIRUS; HUMAN; IMMUNOPATHOGENESIS; LIVER FIBROSIS; LIVER TOXICITY; LIVER TRANSPLANTATION; LOW DRUG DOSE; MESENCHYMAL STEM CELL TRANSPLANTATION; NONHUMAN; PHENOTYPE; PROGNOSIS; REVIEW; SALVAGE THERAPY; SCORING SYSTEM; SENSITIVITY AND SPECIFICITY; SEX DIFFERENCE; SUPERINFECTION; UNSPECIFIED SIDE EFFECT; VACCINATION;

ANIMALS; AUTOANTIBODIES; DIAGNOSIS, DIFFERENTIAL; HEPATITIS, AUTOIMMUNE; HUMANS; IMMUNOSUPPRESSIVE AGENTS; LIVER TRANSPLANTATION; MESENCHYMAL STEM CELL TRANSPLANTATION; PROGNOSIS;

EID: 67651107335     PISSN: 02671379     EISSN: None     Source Type: Journal    
DOI: 10.1097/MOG.0b013e328324ed06     Document Type: Review

References (68)

1. Luxon BA. Diagnosis and treatment of autoimmune hepatitis. Gastroenterol Clin N Am 2008; 37:461-478.
2. Bogdanos DP, Invernizzi P, Mackay IR, Vergani D. Autoimmune liver serology: current diagnostic and clinical challenges. World J Gastroenterol 2008; 14:3374-3387.
3. Herkel J, Lohse AW. Significance of autoantibodies [editorial]. Hepatology 2008; 47:786-788. This editorial is a very erudite discussion of the nature and significance of autoantibodies detected by proteomic analyses of serum, emphasizing the nondisease-specific nature of the serological findings, the ubiquitous nature of the implicated antigens, and the need to revise current hypotheses of autoimmunity to accommodate the likelihood that aggressive clones of lymphocytes with limited epitope specificity actually drive the disease after their selection from a lymphocyte population that has similar antigenic reactivity.
4. Zen Y, Notsumata K, Tanaka N, Nakanuma Y. Hepatic centrilobular zonal necrosis with positive antinuclear antibody: a unique subtype or early disease of autoimmune hepatitis? Hum Pathol 2007; 38:1669-1675.
5. Miyake Y, Iwasaki Y, Terada R, et al. Clinical features of Japanese type 1 autoimmune hepatitis patients with zone III necrosis. Hepatol Res 2007; 37:801-805. (Pubitemid 47308221)
6. Rust C, Beuers U. Overlap syndromes among autoimmune liver diseases. World J Gastroenterol 2008; 14:3368-3373.
7. Al-Chalabi T, Portmann BC, Bernal W, et al. Autoimmune hepatitis overlap syndromes: an evaluation of treatment response, long-term outcome and survival. Aliment Pharmacol Ther 2008; 28:209-220. (Pubitemid 351861961)
8. Vergani D, Mieli-Vergani G. Autoimmune hepatitis and PSC connection. Clin Liver Dis 2008; 12:187-202.
9. Vergani D, Mieli-Vergani G. Aetiopathogenesis of autoimmune hepatitis. World J Gastroenterol 2008; 14:3306-3312.
10. Verma S, Torbenson M, Thuluvath PJ. The impact of ethnicity on the natural history of autoimmune hepatitis. Hepatology 2007; 46:1828-1835. The association between ethnicity and disease behavior is explored, and the possible impact of genetic predisposition, indigenous etiological agents, and socioeconomical issues on the natural history of the disease is discussed.
11. Flores YN, Yee HF Jr, Leng M, et al. Risk factors for chronic liver disease in Blacks, Mexican Americans, and Whites in the United States: results from NHANES IV, 1999-2004. Am J Gastroenterol 2008; 103:2231-2238.
12. Larsen FS. Treatment of patients with severe autoimmune hepatitis. Minerva Gastroenterol Dietol 2008; 54:57-63.
13. Hennes EM, Zeniya M, Czaja AJ, et al. Simplified diagnostic criteria for autoimmune hepatitis. Hepatology 2008; 48:169-176. A simplified scoring system is proposed for the diagnosis of autoimmune hepatitis based on four clinical components (autoantibody titer, serum IgG level, histological features, and viral markers) and validated in different ethnic groups and liver diseases.
14. Czaja AJ. Performance parameters of the diagnostic scoring systems for autoimmune hepatitis. Hepatology 2008; 48:1540-1548. The performance parameters of the original revised and simplified scoring systems of the IAIHG are compared, and the systems are shown to have excellent performance parameters and to be complementary, with the original revised system most useful in evaluating patients with few or atypical features of autoimmune hepatitis and the simplified scoring system most useful in excluding the diagnosis in patients with confusing concurrent immune features.
15. Iwai M, Jo M, Ishii M, et al. Comparison of clinical features and liver histology in acute and chronic autoimmune hepatitis. Hepatol Res 2008; 38:784-789. (Pubitemid 352015629)
16. Al-Chalabi T, Underhill JA, Portmann BC, et al. Impact of gender on the long-term outcome and survival of patients with autoimmune hepatitis. J Hepatol 2008; 48:140-147. (Pubitemid 350191991)
17. O'Brien C, Joshi S, Feld JJ, et al. Long-term follow-up of antimitochondrial antibody-positive autoimmune hepatitis. Hepatology 2008; 48:550-556.
18. Montano-Loza AJ, Carpenter HA, Czaja AJ. Frequency, behavior and prognostic implications of antimitochondrial antibodies in type 1 autoimmune hepatitis. J Clin Gastroenterol 2008; 42:1047-1053. This comprehensive analysis of 130 patients with autoimmune hepatitis demonstrates that the behavior of AMAs is not associated with changes in clinical phenotype or outcome of the disease, being present in 13% at presentation, developing later in 5%, and disappearing in 3% during 141±33 months of observation.
19. Mishima S, Omagari K, Ohba K, et al. Clinical implications of antimitochondrial antibodies in type 1 autoimmune hepatitis: a longitudinal study. Hepatogastroenterology 2008; 55:221-227.
20. Leung PSC, Rossaro L, Davis PA, et al. Antimitochondrial antibodies in acute liver failure: implications for primary biliary cirrhosis. Hepatology 2007; 46:1436-1442. AMAs developed in 41% of 69 patients with acute liver failure and could rapidly disappear during follow-up, suggesting a transient modification of mitochondrial antigens, possibly because of reactive oxygen species, and raising the possibility that severe liver inflammation could generate transient seropositivity.
21. Bittencourt PL, Farias AQ, Porta G, et al. Frequency of concurrent autoimmune disorders in patients with autoimmune hepatitis: effect of age, gender, and genetic background. J Clin Gastroenterol 2008; 42:300-305. (Pubitemid 351301497)
22. Czaja AJ. Clinical features, differential diagnosis and treatment of autoimmune hepatitis in the elderly. Drugs Aging 2008; 25:219-239. This is an important review of autoimmune hepatitis in the elderly because the disease may be underdiagnosed and undertreated in these patients, resulting in high frequencies of cirrhosis at presentation, misinterpretation of the significance of concurrent rheumatic conditions, and deferred treatment despite an excellent outcome and tolerance of therapy.
23. Caprai S, Vajro P, Ventura A, et al. Autoimmune liver disease associated with celiac disease in childhood: a multicenter study. Clin Gastroenterol Hepatol 2008; 6:803-806.
24. Cosnes J, Cellier C, Viola S, et al. Incidence of autoimmune diseases in celiac disease: protective effect of the gluten-free diet. Clin Gastroenterol Hepatol 2008; 6:753-758.
25. Abdalian R, Dhar P, Jhaveri K, et al. Prevalence of sclerosing cholangitis in adults with autoimmune hepatitis: evaluating the role of routine magnetic resonance imaging. Hepatology 2008; 47:949-957. This important study suggests that routine assessment of the biliary tract by MRI may be justified as 10% of adult patients with autoimmune hepatitis had biliary changes, which were not suspected by clinical features such as male gender, concurrent IBD, or a cholestatic syndrome.
26. Aubert V, Pisler IG, Spertini F. Improved diagnoses of autoimmune hepatitis using an antiactin ELISA. Clin Lab Anal 2008; 22:340-345.
27. Lu F, Xia Q, Ma Y, et al. Serum proteomic-based analysis for the identification of a potential serological marker for autoimmune hepatitis. Biochem Biophys Res Commun 2008; 367:284-290.
28. Tahiri F, Le Naour F, Huguet S, et al. Identification of plasma membrane autoantigens in autoimmune hepatitis type 1 using a proteomics tool. Hepatology 2008; 47:937-948. This important study uses proteomic tools to implicate liver arginase, cytokeratins, HSPs, and valosin-containing protein as antigenic targets expressed on the hepatocyte plasma membrane of patients with autoimmune hepatitis.
29. Werner M, Prytz H, Ohlsson B, et al. Epidemiology and the initial presentation of autoimmune hepatitis in Sweden: a nationwide study. Scand J Gastroenterol 2008; 43:1232-1240.
30. Kim WR, Flamm SL, Di Bisceglie AM, Bodenheimer HC Jr. Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease. Hepatology 2008; 47:1363-1370.
31. Lee TH, Kim WR, Benson JT, et al. Serum aminotransferase activity and mortality risk in a United States community. Hepatology 2008; 47:880-887.
32. Al-Chalabi T, Underhill JA, Portmann BC, et al. Effects of serum aspartate aminotransferase levels in patients with autoimmune hepatitis influence disease course and outcome. Clin Gastroenterol Hepatol 2008; 6:1389-1395.
33. Czaja AJ. Features and consequences of untreated type 1 autoimmune hepatitis. Liver Int 2009 [Epub ahead of print].
34. Nguyen GC, Thuluvath PJ. Racial disparity in liver disease: biological, cultural, or socioeconomic factors. Hepatology 2008; 47:1058-1066. This excellent analysis of the factors contributing to racial disparities in the occurrence and outcome of liver disease provides an essential understanding of the factors that must be interpreted before concluding a biological basis for a disease manifestation in an ethnic group.
35. Twaddell WS, Lefkowitch J, Berk PD. Evolution from primary biliary cirrhosis to primary biliary cirrhosis/autoimmune hepatitis overlap syndrome. Semin Liver Dis 2008; 28:128-134. (Pubitemid 351326539)
36. Czaja AJ. Genetic factors associated with the occurrence, clinical phenotype and outcome of autoimmune hepatitis. Clin Gastroenterol Hepatol 2008; 6:379-388. This comprehensive update of the genetic factors associated with the development and behavior of autoimmune hepatitis indicates the diversity of genetic factors within and outside the MHC that can affect susceptibility and individualize the expression of the disease in different geographical regions.
37. del Pilar Fortes M, Machado IV, Gil G, et al. Genetic contribution of major histocompatibility complex class II region to type 1 autoimmune hepatitis susceptibility in Venezuela. Liver Int 2007; 27:1409-1416. (Pubitemid 350142256)
38. Czaja AJ, Carpenter HA, Moore SB. HLA DRB1*13 as a risk factor for type 1 autoimmune hepatitis in North American patients. Dig Dis Sci 2008; 53:522-528.
39. Lim YS, Oh HB, Choi SE, et al. Susceptibility to type 1 autoimmune hepatitis is associated with shared amino acid sequences at positions 70-74 of the HLADRB1 molecule. J Hepatol 2008; 48:133-139. This important analysis not only clarifies the genetic risk factors for autoimmune hepatitis in Korea by implicating DRB1*0405 and DQB1*0401, but it also connects with the North American and northern European experiences by extending the susceptibility motif in the polypeptide chain of the antigen-binding groove to include the amino acid sequence QRRAA at positions DRβ70-74.
40. Huang HC, Wu JC, Huang YS, et al. Genetic distinctions and clinical characteristics of type 1 autoimmune hepatitis in Taiwan. Hepatogastroenterology 2008; 55:605-608. (Pubitemid 351741511)
41. Umemura T, Ota M, Yoshizawa K, et al. Association of cytotoxic T-lymphocyte antigen 4 gene polymorphisms with type 1 autoimmune hepatitis in Japanese. Hepatol Res 2008; 38:689-695. (Pubitemid 351784982)
42. Juran BD, Atkinson EJ, Schlict EM, et al. Primary biliary cirrhosis is associated with a genetic variant in the 3′ flanking region of the CTLA4 gene. Gastroenterology 2008; 135:1200-1206.
43. Romanque P, Stickel F, Dufour J-F. Disproportionally high results of transient elastography in patients with autoimmune hepatitis [letter to editor]. Liver Int 2008; 28:1177-1178.
44. Miyake Y, Iwasaki Y, Terada R, et al. A model for estimating cirrhosis in patients with type 1 autoimmune hepatitis. Hepatol Res 2008; 38:658-663. (Pubitemid 351784978)
45. Van Leeuwen DJ, Balabaud C, Crawford JM, et al. A clinical and histopathologic perspective on evolving noninvasive and invasive alternatives for liver biopsy. Clin Gastroenterol Hepatol 2008; 6:491-496. (Pubitemid 351609453)
46. Tabak F, Ozdemir F, Tabak O, et al. Autoimmune hepatitis induced by the prolonged hepatitis A virus infection. Ann Hepatol 2008; 7:177-179. (Pubitemid 351845533)
47. Bowen DG. Of mice and molecular mimicry: modeling autoimmune hepatitis. Hepatology 2008; 48:1013-1015.
48. Mattner J, Savage PB, Leung P, et al. Liver autoimmunity triggered by microbial activation of natural killer cells. Cell Host Microbe 2008; 15:304-315. (Pubitemid 351637431)
49. Holdener M, Hintermann E, Bayer M, et al. Breaking tolerance to the natural human liver autoantigen cytochrome P450 2D6 by virus infection. J Exp Med 2008; 205:1409-1422. A mice model of autoimmune liver disease is developed using a liver-trophic adenovirus that expresses the human cytochrome CYP2D6, and it extends hypotheses invoking a microbial trigger for the disease.
50. Hirschfield GM, Heathcote J. T regulatory cells and autoimmune liver disease [editorial]. Liver Int 2008; 28:155-157. (Pubitemid 351201029)
51. + T cells were necessary for the massive necrosis.
52. Longhi MS, Meda F, Wang P, et al. Expansion and de novo generation of potentially therapeutic regulatory T cells in patients with autoimmune hepatitis. Hepatology 2008; 47:581-591. This study prepares the way for using the adoptive transfer of T regulatory cells in the treatment of autoimmune hepatitis by demonstrating that the T regulatory cell population can be expanded or freshly generated in cell cultures exposed to anti-CD3/anti-CD28 T-cell expander and high doses of IL-2.
53. Yang GX, Lian ZX, Chuang YH, et al. Adoptive transfer of CD8+ T cells from transforming growth factor beta receptor type II (dominant negative form) induces autoimmune cholangitis in mice. Hepatology 2008; 47:1974-1982.
54. Xu XD, Ueta H, Zhou S, et al. Trafficking of recirculating lymphocytes in the rat liver: rapid transmigration into the portal area and then to the hepatic lymph. Liver Int 2008; 28:319-330. (Pubitemid 351279579)
55. Sprengers D, Sille FC, Derkow K, et al. Critical role for CD1d-restricted invariant NKT cells in stimulating intrahepatic CD8 T-cell responses to liver antigen. Gastroenterology 2008; 134:2132-2143. (Pubitemid 351783251)
56. Kawashima H, Kato N, Ioi H, et al. mRNA expression of T-helper 1, T-helper 2 cytokines in autoimmune hepatitis in childhood. Pediatr Int 2008; 50:284-286.
57. Czaja AJ. Safety issues in the management of autoimmune hepatitis. Expert Opin Drug Saf 2008; 7:319-333. This comprehensive review details the frequency, nature, and mechanisms of the toxicities associated with the drugs used to treat autoimmune hepatitis, and it outlines preemptive strategies that might decrease their frequency.
58. Hlivko JT, Shiffman ML, Stravitz RT, et al. A single center review of the use of mycophenolate mofetil in the treatment of autoimmune hepatitis. Clin Gastroenterol Hepatol 2008; 6:1036-1040.
59. Manns MP, Bahr MJ, Woynarowski M, et al. Budesonide 3mg TID is superior to prednisolone in combination with azathioprine in the treatment of autoimmune hepatitis [abstract]. J Hepatol 2008; 48 (Suppl 2):S369. This important study demonstrates the superior efficacy and safety of budesonide, 3mg thrice daily, in combination with azathioprine, 1-2 mg/kg daily, in achieving biochemical remission after 6 months as compared with a prednisone-based regimen.
60. Kuo TK, Hung SP, Chuang CH, et al. Stem cell therapy for liver disease: parameters governing the success of using bone marrow mesenchymal stem cells. Gastroenterology 2008; 134:2111-2121. The transplantation of bone marrow-derived mesenchymal stem cells is a potentially powerful weapon against liver failure as the cells engraft on the damaged liver, differentiate into functional hepatocytes, and rescue mice gavaged with carbon tetrachloride.
61. Seo S, Toutounjian R, Conrad A, et al. Favorable outcomes of autoimmune hepatitis in a community clinic setting. J Gastroenterol Hepatol 2008; 23:1410-1414.
62. Luth S, Herkel J, Kanzler S, et al. Serologic markers compared with liver biopsy for monitoring disease activity in autoimmune hepatitis. J Clin Gastroenterol 2008; 42:926-930.
63. Worns MA, Teufel A, Kanzler S, et al. Incidence of HAV and HBV infections and vaccination rates in patients with autoimmune liver diseases. Am J Gastroenterol 2008; 103:138-146. This practice reminder indicates that susceptibility to infections with the HAV and HBV is high in autoimmune liver disease and that the frequency of vaccination is low, thereby imperiling these patients with viral superinfection and increased mortality.
64. Yeoman AD, Al-Chalabi T, Karani JB, et al. Evaluation of risk factors in the development of hepatocellular carcinoma in autoimmune hepatitis: implications for follow-up and screening. Hepatology 2008; 48:863-870.
65. Montano-Loza AJ, Carpenter HA, Czaja AJ. Predictive factors for hepatocellular carcinoma in type 1 autoimmune hepatitis. Am J Gastroenterol 2008; 103:1944-1951. This study identifies the independent risk factors for hepatocellular carcinoma in patients with autoimmune hepatitis who undergo hepatic ultrasonography and serum alpha-fetoprotein determinations at 6-12-month intervals, and it suggests that this high-risk composite phenotype can focus on the screening strategy.
66. Campsen J, Zimmermann MA, Trotter JF, et al. Liver transplantation for autoimmune hepatitis and the success of aggressive corticosteroid withdrawal. Liver Transpl 2008; 14:1281-1286. This investigation documents a 5-year survival after liver transplantation of 91% in patients with autoimmune hepatitis, and it demonstrates that corticosteroids can be withdrawn in 50% of these patients without affecting the frequency of recurrent disease.
67. Demetris AJ, Sebagh M. Plasma cell hepatitis in liver allografts: variant of rejection or autoimmune hepatitis? [Editorial]. Liver Transpl 2008; 14:750-755. This is an erudite review of the causes of plasma cell infiltration of the liver allograft and the difficulties in distinguishing it from rejection or de-novo autoimmune hepatitis.
68. Fiel MI, Agarwal K, Stanca C, et al. Posttransplant plasma cell hepatitis (de novo autoimmune hepatitis) is a variant of rejection and may lead to a negative outcome in patients with hepatitis C virus. Liver Transpl 2008; 14:861-871. (Pubitemid 351895516)