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1
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Pogorelova M, Sungur CM. Chylous ascites as an initial presentation of lupus nephritis. BMJ Case Rep 2025; 18:e264415. [PMID: 40107757 DOI: 10.1136/bcr-2024-264415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/22/2025] Open
Abstract
We report the case of a man in his 50s who presented with pleural and pericardial effusions, chylous ascites, lymphadenopathy, weight loss and fatigue. Extensive evaluation ruled out malignancy, infection and many autoimmune conditions, but test results were positive for antinuclear antibodies and anti-double-stranded DNA antibodies. A kidney biopsy showed evidence of lupus nephritis (class 5). He ultimately was diagnosed with systemic lupus erythematosus and lupus nephritis. The patient began immunosuppressive treatment, and the manifestations started to resolve. Recognition of systemic lupus erythematosus as the cause of chylous ascites was essential for identifying effective therapy.
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2
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Weinberg S, Amarnani A, Jolly M. Gastrointestinal and hepatic manifestations. DUBOIS' LUPUS ERYTHEMATOSUS AND RELATED SYNDROMES 2025:505-520. [DOI: 10.1016/b978-0-323-93232-5.00045-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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SORRENTINO MC, a nome del GdS-AI SIPMeL, CARBONE T, CINQUANTA L, ALESSIO MG, INFANTINO M, DELEONARDI G, TREVISAN MT, PORCELLI B, TERZUOLI L, PLATZGUMMER S, BRUSCA I, ANTICO A, TAMPOIA M, PESCE G, VILLALTA D, BIZZARO N. Linee guida SIPMeL per la determinazione degli autoanticorpi nella diagnosi delle malattie autoimmuni del fegato. LA RIVISTA ITALIANA DELLA MEDICINA DI LABORATORIO 2024; 20. [DOI: 10.23736/s1825-859x.24.00226-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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4
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Bellamy CO, Burt AD. Liver in Systemic Disease. MACSWEEN'S PATHOLOGY OF THE LIVER 2024:1039-1095. [DOI: 10.1016/b978-0-7020-8228-3.00015-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Weltzsch JP, Ziegler A, Lohse A. [Autoimmune hepatitis : From autoantibodies to cirrhosis]. INNERE MEDIZIN (HEIDELBERG, GERMANY) 2023:10.1007/s00108-023-01519-9. [PMID: 37306752 DOI: 10.1007/s00108-023-01519-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Accepted: 04/12/2023] [Indexed: 06/13/2023]
Abstract
Autoimmune Hepatitis (AIH) is an immune-mediated liver disease of unknown origin. Its clinical presentation is heterogeneous and ranges from asymptomatic courses over several years to acute forms with acute liver failure. Accordingly, the diagnosis is only made at the stage of cirrhosis in about one third of affected individuals. Early diagnosis and a consistent, adequate, individualized, immunosuppressive therapy are crucial for the prognosis, which is excellent when treated properly. AIH is rare in the general population and can be easily overlooked due to its variable clinical picture and sometimes difficult diagnosis. AIH should be considered as a differential diagnosis in any unclear acute or chronic hepatopathy. The therapy initially consists of remission induction and subsequently maintenance therapy with (often lifelong) immunosuppressants.
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Affiliation(s)
- Jan Philipp Weltzsch
- I. Med. Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Deutschland.
| | - Annerose Ziegler
- I. Med. Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Deutschland
| | - Ansgar Lohse
- I. Med. Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Deutschland
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6
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Dalekos GN, Gatselis NK. Autoimmune serology testing in clinical practice: An updated roadmap for the diagnosis of autoimmune hepatitis. Eur J Intern Med 2023; 108:9-17. [PMID: 36400668 DOI: 10.1016/j.ejim.2022.11.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Revised: 11/04/2022] [Accepted: 11/06/2022] [Indexed: 11/18/2022]
Abstract
Diagnosis of autoimmune hepatitis (AIH) is in most cases challenging for clinicians as there is not a single specific laboratory or histological marker to diagnose or exclude the presence of the disease. The clinical spectrum of AIH varies from completely asymptomatic to acute-severe or even rarely fulminant hepatic failure, while everybody can be affected irrespective of age, gender, and ethnicity. The old revised and the newer simplified diagnostic scores have been established by the International Autoimmune Hepatitis Group (IAIHG) in 1999 and 2008, respectively, which are based on several clinical, laboratory and histological parameters. Additionally, a thorough differential diagnosis from other diseases mimicking AIH is absolutely indicated. In this context, autoantibodies detection in patients with suspected AIH is mandatory -even though not pathognomonic- not only for AIH diagnosis but furthermore, for AIH classification (AIH-type 1 and AIH-type 2). Although autoimmune serology can be supportive of AIH diagnosis in ≥95% of cases if testing has been performed according to the IAIHG guidelines, this is not the case under real-life circumstances in routine clinical laboratories. Clinicians should be careful both for the importance of the required testing and how to interpret the results and therefore, they should communicate and discuss with the laboratory personnel to achieve the maximum benefit for the patient. Herein, a detailed and updated review of the diagnostic work-up for AIH diagnosis under real-life conditions is given to minimize the underestimation and misdiagnosis of AIH which can result in progression of the disease and unfavourable outcomes.
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Affiliation(s)
- George N Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa, Greece.
| | - Nikolaos K Gatselis
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa, Greece
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7
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Cancado ELR, Goldbaum-Crescente J, Terrabuio DRB. HLA-related genetic susceptibility in autoimmune hepatitis according to autoantibody profile. Front Immunol 2022; 13:1032591. [PMID: 36311739 PMCID: PMC9606223 DOI: 10.3389/fimmu.2022.1032591] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 09/26/2022] [Indexed: 11/13/2022] Open
Abstract
Although the prevalence of autoimmune hepatitis in first-degree relatives is small, the relationship between genetic markers, especially human leucocyte antigens (HLA), and susceptibility to this disease, has been studied for over three decades. The genetic susceptibility to AIH is believed to be different in the two subtypes of the disease, AIH type 1 and AIH type 2. Type 1 AIH has anti-smooth muscle and anti-nuclear antibodies as its main markers, while those of type 2 AIH are the anti-liver/kidney microsome type 1 and anti-liver cytosol type 1 antibodies. The anti-soluble liver antigen/liver-pancreas antibodies, which, in addition to being present in both subtypes, mark an important number of patients without serological markers. Therefore, a third type of disease is questionable. The vast majority of immunogenetic studies compare the differences between the two main types and make no difference between which antibodies are present to define the subtype. This review seeks to analyze what was most important published in the AIH in this context, trying to relate the HLA alleles according to the AIH marker autoantibodies.
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Affiliation(s)
- Eduardo Luiz Rachid Cancado
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
- Instituto de Medicina Tropical da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
- *Correspondence: Eduardo Luiz Rachid Cancado,
| | - Juliana Goldbaum-Crescente
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
- Instituto de Medicina Tropical da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
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Challenges and opportunities in achieving effective regulatory T cell therapy in autoimmune liver disease. Semin Immunopathol 2022; 44:461-474. [PMID: 35641679 PMCID: PMC9256571 DOI: 10.1007/s00281-022-00940-w] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 04/15/2022] [Indexed: 12/29/2022]
Abstract
Autoimmune liver diseases (AILD) include autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). These immune-mediated liver diseases involve a break down in peripheral self-tolerance with largely unknown aetiology. Regulatory T cells (Treg) are crucial in maintaining immunological tolerance. Hence, Treg immunotherapy is an attractive therapeutic option in AILD. Currently, AILD do not have a curative treatment option and patients take life-long immunosuppression or bile acids to control hepatic or biliary inflammation. Clinical investigations using good manufacturing practice (GMP) Treg in autoimmune liver disease have thus far demonstrated that Treg therapy is safe and that Treg migrate to inflamed liver tissue. For Treg immunotherapy to achieve efficacy in AILD, Treg must be retained within the liver and maintain their suppressive phenotype to dampen ongoing immune responses to hepatocytes and biliary epithelium. Therefore, therapeutic Treg subsets should be selected for tissue residency markers and maximal functionality. Optimisation of dosing regime and understanding longevity of Treg in vivo are critical to successful Treg therapy. It is also essential to consider combination therapy options to complement infused Treg, for instance low-dose interleukin-2 (IL-2) to support pre-existing and infused Treg survival and suppressive function. Understanding the hepatic microenvironment in both early- and late-stage AILD presents significant opportunity to better tailor Treg therapy in different patient groups. Modification of a hostile microenvironment to a more favourable one either prior to or during Treg therapy could enhance the efficacy and longevity of infused GMP-Treg. Applying recent technology to discovery of autoantigen responses in AILD, T cell receptor (TCR) sequencing and use of chimeric antigen receptor (CAR) technology represents the next frontier for disease-specific CAR-Treg therapies. Consideration of all these aspects in future trials and discovery research would position GMP Treg immunotherapy as a viable personalised-medicine treatment option for effective control of autoimmune liver diseases.
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The Interaction of Anti-DNA Antibodies with DNA: Evidence for Unconventional Binding Mechanisms. Int J Mol Sci 2022; 23:ijms23095227. [PMID: 35563617 PMCID: PMC9105193 DOI: 10.3390/ijms23095227] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 04/28/2022] [Accepted: 04/30/2022] [Indexed: 12/04/2022] Open
Abstract
Antibodies to DNA (anti-DNA) are the serological hallmark of systemic lupus erythematosus, a prototypic autoimmune disease. These antibodies bind to conserved sites on single-stranded and double-stranded DNA and display variable region somatic mutations consistent with antigen selection. Nevertheless, the interaction of anti-DNA with DNA has unconventional features. Anti-DNA antibodies bind by a mechanism called monogamous bivalency, in which stable interaction requires contact of both Fab sites with determinants on the same extended DNA molecule; the size of this DNA can be hundreds to thousands of bases, especially in solid phase assays. This binding also requires the presence of the Fc portion of IgG, a binding mechanism known as Fc-dependent monogamous bivalency. As shown by the effects of ionic strength in association and dissociation assays, anti-DNA binding is primarily electrostatic. Like anti-DNA autoantibodies, anti-DNA antibodies that bind specifically to non-conserved sites on bacterial DNA, a type of anti-DNA found in otherwise healthy individuals, also interact by monogamous bivalency. The unconventional features of anti-DNA antibodies may reflect the highly charged and polymeric nature of DNA and the need for molecular rearrangements to facilitate monogamous bivalency; the Fc portion contributes to binding in an as yet unknown way.
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Cockx M, Van Hoovels L, De Langhe E, Lenaerts J, Thevissen K, Persy B, Bonroy C, Vercammen M, Bossuyt X. Laboratory evaluation of anti-dsDNA antibodies. Clin Chim Acta 2022; 528:34-43. [PMID: 35016875 DOI: 10.1016/j.cca.2021.12.029] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 12/24/2021] [Accepted: 12/28/2021] [Indexed: 11/19/2022]
Abstract
Antibodies to dsDNA are an important laboratory parameter for diagnosis, monitoring and classification of systemic lupus erythematosus (SLE). In clinical laboratories, several techniques are used to detect and quantify anti-dsDNA antibodies. Each technique has its advantages and disadvantages regarding sensitivity, specificity, avidity and assay procedure. Assays differ with respect to the antigen source (native versus synthetic versus molecular biological) used and the way the antigen is presented (e.g. in solution, covalently linked to a solid phase,…). Consequently, correlation between assays can be poor and standardization of anti-dsDNA antibody tests is challenging. We here provide an overview of the currently available anti-dsDNA tests frequently used in clinical laboratories [Crithidiae luciliae immunofluorescence test (CLIFT), Enzyme linked immune sorbent assay (ELISA), fluoroenzyme immunoassay (FEIA), chemiluminescence (CIA), multiplexed bead-based assays and Farr-RIA] and their performance characteristics. From this literature study, we concluded that performance characteristics differ between assays. Often, a combination of techniques is necessary for the best result interpretation.
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Affiliation(s)
- Maaike Cockx
- Department of Microbiology, Immunology and Transplantation, University of Leuven, Leuven, Belgium
| | - Lieve Van Hoovels
- Department of Microbiology, Immunology and Transplantation, University of Leuven, Leuven, Belgium; Department of Laboratory Medicine, OLV Hospital, Aalst, Belgium
| | - Ellen De Langhe
- Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium; Department of Development and Regeneration, University of Leuven, Leuven, Belgium
| | - Jan Lenaerts
- Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium; Reumainstituut and Jessa Hospital, Hasselt, Belgium
| | | | - Ben Persy
- Department of Laboratory Medicine, Ziekenhuis Oost-Limburg, Genk, Belgium
| | - Carolien Bonroy
- Department of Diagnostic Sciences, Ghent University Hospitals, Ghent, Belgium; Department of Laboratory Medicine, Ghent University Hospitals, Ghent, Belgium
| | | | - Xavier Bossuyt
- Department of Microbiology, Immunology and Transplantation, University of Leuven, Leuven, Belgium; Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium.
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Pisetsky DS, Lipsky PE. Reply to: Diagnostic role of anti-dsDNA antibodies: do not forget autoimmune hepatitis. Nat Rev Rheumatol 2021; 17:245. [PMID: 33462416 DOI: 10.1038/s41584-021-00574-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Affiliation(s)
- David S Pisetsky
- Department of Medicine and Immunology, Duke University Medical Center and Medical Research Service, VA Medical Center, Durham, NC, USA.
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12
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Praharaj DL, Mallick B, Nath P, Panigrahi SC, Padhan P, Sahu N. Unusual Presentation of Systemic Lupus Erythematosus in a Young Male: A Case Report. J Clin Exp Hepatol 2021; 11:264-269. [PMID: 33746453 PMCID: PMC7953008 DOI: 10.1016/j.jceh.2020.05.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Accepted: 05/28/2020] [Indexed: 12/12/2022] Open
Abstract
Hepatic involvement in systemic lupus erythematosus (SLE) is common but described infrequently. Liver is usually never the primary organ to be affected in lupus. Again hepatic involvement probably does not carry much prognostic importance though it may correlate with lupus activity. We here report a case of 21-year-old man with no prior comorbidity or addiction who presented to us with acute hepatic illness with jaundice. He also had malar rash and arthralgia. Viral markers were negative. Antinuclear antibody and anti-double-stranded DNA (dsDNA) were strongly positive. Liver biopsy was consistent with autoimmune hepatitis, whereas skin biopsy was suggestive of SLE. He had a brisk and complete recovery with prompt use of immunosuppressive agents (corticosteroids and azathioprine). Cyclophosphamide was started latter in view of lupus nephritis. This is probably the fourth reported case of SLE presenting as acute hepatic illness with jaundice.
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Key Words
- ACR, American College of Rheumatology
- AIH, Autoimmune Hepatitis
- ALP, Alkaline Phosphatase
- ALT, Alanine Transaminase
- ANA, Antinuclear Antibody
- AST, Aspartate Transaminase
- DILI, Drug-induced Liver Injury
- HAV, Hepatitis A Virus
- HEV, Hepatitis E Virus
- MRCP, Magnetic Resonance Cholangiopancreatography
- PBC, Primary Biliary Cholangitis
- PSC, Primary Sclerosing Cholangitis
- SLE, Systemic Lupus Erythematosus
- TLC, Total Leucocyte Count
- acute hepatitis
- ds DNA, Double-stranded DNA
- immunosuppressive agents
- lupus hepatitis
- lupus nephritis
- systemic lupus erythematous
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Affiliation(s)
- Dibya L. Praharaj
- Department of Gastroenterology and Hepatology, Kalinga Insitute of Medical Science, Bhubaneswar, Odisha, India,Address for correspondence: Dibya L Praharaj, Assistant Professor, Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Science, Bhubaneswar, India.
| | - Bipadabhanjan Mallick
- Department of Gastroenterology and Hepatology, Kalinga Insitute of Medical Science, Bhubaneswar, Odisha, India
| | - Preetam Nath
- Department of Gastroenterology and Hepatology, Kalinga Insitute of Medical Science, Bhubaneswar, Odisha, India
| | - Sarat C. Panigrahi
- Department of Gastroenterology and Hepatology, Kalinga Insitute of Medical Science, Bhubaneswar, Odisha, India
| | - Prasanta Padhan
- Department of Rheumatology, Kalinga Insitute of Medical Science, Bhubaneswar, Odisha, India
| | - Nageswar Sahu
- Department of Pathology, Kalinga Institute of Medical Science, Bhubaneswar, Odisha, India
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Abstract
Liver involvement in rheumatic diseases may occur as a primary liver disease, primary rheumatic disease with hepatic manifestations or antirheumatic drug-induced liver disease. The aim of our article is to underline the importance of monitoring and control of the level of aminotransferases and cholestatic enzymes in rheumatic disorders. Some of the rheumatic diseases with constantly elevated liver enzymes need to be investigated in consideration of concomitant primary autoimmune liver disease (such as autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis) or drug hepatotoxicity. Also, we should be aware of hepatitis B reactivation or hepatitis C flare when immunosuppressants are used.
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Wei Q, Jiang Y, Xie J, Yang M, Zhang Y, Wu Z, Chen S, Liao Z, Lin Z, Gu J. Investigation and analysis of HEp 2 indirect immunofluorescence titers and patterns in various liver diseases. Clin Rheumatol 2020; 39:2425-2432. [PMID: 32103375 DOI: 10.1007/s10067-020-04950-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Revised: 12/30/2019] [Accepted: 01/16/2020] [Indexed: 11/29/2022]
Abstract
INTRODUCTION Antinuclear antibody (ANA) testing using indirect immunofluorescence assay (IIFA) is a common and economical method which contributes to detect systemic autoimmune diseases (SARD) and autoimmune liver diseases (AILD). The primary aim of our study was to investigate ANA positivity and their patterns in multiple liver diseases, including primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH), hepatitis B virus infection (HBV), hepatitis C virus infection (HCV), and hepatic carcinoma (HCC). Besides, we also compared the ANA titers and patterns in patients with liver disease, SARD, and healthy controls (HC). METHODS A total of 2537 patients with SARD, 137 PBC cases, 57 AIH cases, 3420 HBV cases, 769 HCV cases, 268 HCC cases, and 1073 HC were retrospectively assessed. The titers and patterns of ANA were detected with the IIFA method. RESULTS ANA positivity rate was considerably discernible between these diseases, which is 90.1% in SARD, 93.4% in PBC, 49.1% in AIH, 19.1% in HBV, 13.9% in HCV, and 23.5% in HCC. Moreover, only 4.9% of HCC cases, 2.5% of HBV patients, and 1.6% of HCV patients had an ANA titer ≥ 1:320. The mixed pattern which composed of at least two patterns majorly lied in PBC. AC-15 and AC-21 was frequently related to liver diseases; the former pattern was more frequently found in AIH (84.2%) and PBC (8.8%), and the latter pattern was easily seen in PBC (62.2%) and HCC (22.6%). The positive rate of ANA in HC was 12.2%, and its major pattern was AC-2. CONCLUSIONS There are differences in ANA positivity among patients with SARD and various liver diseases. Some mixed patterns may provide important evidence for the diagnosis of PBC. Clinicians should pay attention to ANA patterns and titer during the interpretation of this test. Key Points • Defining the clinical relevance of antinuclear antibody (ANA) using indirect immunofluorescence assay in the context of diseases can be an important tool for the clinician in the diagnostic work-up of patients with liver diseases. • The mixed pattern of ANA is majorly found in primary biliary cirrhosis (PBC). ANA patterns including AC-15 and AC-21 are frequently related to liver diseases. AC-15 is more often found in autoimmune hepatitis (AIH) (84.2%) and PBC (8.8%), and AC-21 is easily found in PBC (62.2%, and hepatic carcinoma (HCC) (22.6%). • ANA positivity can be seen in 19.1% of hepatitis B virus infection (HBV) cases, 13.9% of hepatitis C virus infection (HCV) cases, and 23.5% of HCC cases. Only 2.5% of HBV patients, 1.6% of HCV patients, and 4.9% of HCC cases have an ANA titer ≥ 1:320.
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Affiliation(s)
- Qiujing Wei
- Department of Rheumatology, the Third Affiliated Hospital of Sun Yat-sen University, Guangdong Province, Guangzhou, China
| | - Yutong Jiang
- Department of Rheumatology, the Third Affiliated Hospital of Sun Yat-sen University, Guangdong Province, Guangzhou, China
| | - Jiewen Xie
- Department of Rheumatology, the Third Affiliated Hospital of Sun Yat-sen University, Guangdong Province, Guangzhou, China
| | - Mingcan Yang
- Department of Rheumatology, the Third Affiliated Hospital of Sun Yat-sen University, Guangdong Province, Guangzhou, China
| | - Yanli Zhang
- Department of Rheumatology, the Third Affiliated Hospital of Sun Yat-sen University, Guangdong Province, Guangzhou, China
| | - Zhongming Wu
- Department of Rheumatology, the Third Affiliated Hospital of Sun Yat-sen University, Guangdong Province, Guangzhou, China
| | - Shuhong Chen
- Department of Rheumatology, the Third Affiliated Hospital of Sun Yat-sen University, Guangdong Province, Guangzhou, China
| | - Zetao Liao
- Department of Rheumatology, the Third Affiliated Hospital of Sun Yat-sen University, Guangdong Province, Guangzhou, China
| | - Zhiming Lin
- Department of Rheumatology, the Third Affiliated Hospital of Sun Yat-sen University, Guangdong Province, Guangzhou, China
| | - Jieruo Gu
- Department of Rheumatology, the Third Affiliated Hospital of Sun Yat-sen University, Guangdong Province, Guangzhou, China.
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Fine RL, Manfredo Vieira S, Gilmore MS, Kriegel MA. Mechanisms and consequences of gut commensal translocation in chronic diseases. Gut Microbes 2019; 11:217-230. [PMID: 31306081 PMCID: PMC7053960 DOI: 10.1080/19490976.2019.1629236] [Citation(s) in RCA: 73] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
Humans and other mammalian hosts have evolved mechanisms to control the bacteria colonizing their mucosal barriers to prevent invasion. While the breach of barriers by bacteria typically leads to overt infection, increasing evidence supports a role for translocation of commensal bacteria across an impaired gut barrier to extraintestinal sites in the pathogenesis of autoimmune and other chronic, non-infectious diseases. Whether gut commensal translocation is a cause or consequence of the disease is incompletely defined. Here we discuss factors that lead to translocation of live bacteria across the gut barrier. We expand upon our recently published demonstration that translocation of the gut pathobiont Enterococcus gallinarum can induce autoimmunity in susceptible hosts and postulate on the role of Enterococcus species as instigators of chronic, non-infectious diseases.
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Affiliation(s)
- Rebecca L. Fine
- Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA,Department of Medicine, Yale School of Medicine, New Haven, CT, USA
| | | | - Michael S. Gilmore
- Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA,Department of Microbiology, Harvard Medical School, Boston, MA, USA
| | - Martin A. Kriegel
- Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA,Department of Medicine, Yale School of Medicine, New Haven, CT, USA,CONTACT Martin A. Kriegel Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA
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16
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Zipprich A. Rheumatologie und Hepatologie: Diagnostik und Therapie von
autoimmunen Lebererkrankungen. AKTUEL RHEUMATOL 2019. [DOI: 10.1055/a-0885-9314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
ZusammenfassungUnter autoimmunen Lebererkrankungen werden im klassischen Sinne 3 verschiedene
Entitäten, die Autoimmune Hepatitis (AIH), die Primär biliäre Cholangitis (PBC)
und die Primär sklerosierende Cholangitis (PSC) verstanden. Der nachfolgende
Übersichtartikel fokusiert auf die Diagnostik und die Therapie dieser 3
autoimmunen Lebererkrankungen und gibt eine Übersicht zu möglichen zusätzlich
assoziierten Autoimmunerkrankungen.
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Schranz M, Lucà MG, D’Antiga L, Fagiuoli S. The Liver in Systemic Illness. PEDIATRIC HEPATOLOGY AND LIVER TRANSPLANTATION 2019:361-396. [DOI: 10.1007/978-3-319-96400-3_22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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18
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Terziroli Beretta-Piccoli B, Mieli-Vergani G, Vergani D. The clinical usage and definition of autoantibodies in immune-mediated liver disease: A comprehensive overview. J Autoimmun 2018; 95:144-158. [DOI: 10.1016/j.jaut.2018.10.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Revised: 10/09/2018] [Accepted: 10/11/2018] [Indexed: 02/06/2023]
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Sebode M, Weiler-Normann C, Liwinski T, Schramm C. Autoantibodies in Autoimmune Liver Disease-Clinical and Diagnostic Relevance. Front Immunol 2018; 9:609. [PMID: 29636752 PMCID: PMC5880919 DOI: 10.3389/fimmu.2018.00609] [Citation(s) in RCA: 81] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Accepted: 03/12/2018] [Indexed: 12/12/2022] Open
Abstract
Testing for liver-related autoantibodies should be included in the workup of patients with hepatitis or cholestasis of unknown origin. Although most of these autoantibodies are not disease specific, their determination is a prerequisite to diagnose autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC), and they are components of the diagnostic scoring system in these diseases. In primary sclerosing cholangitis (PSC), on the other hand, autoantibodies are frequently present but play a minor role in establishing the diagnosis. In PSC, however, data on antibodies suggest a link between disease pathogenesis and the intestinal microbiota. This review will focus on practical aspects of antibody testing in the three major autoimmune liver diseases AIH, PBC, and PSC.
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Affiliation(s)
- Marcial Sebode
- 1st Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Christina Weiler-Normann
- 1st Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.,Martin Zeitz Centre for Rare Diseases, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Timur Liwinski
- 1st Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Christoph Schramm
- 1st Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.,Martin Zeitz Centre for Rare Diseases, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
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20
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Rekvig OP. Systemic Lupus Erythematosus: Definitions, Contexts, Conflicts, Enigmas. Front Immunol 2018; 9:387. [PMID: 29545801 PMCID: PMC5839091 DOI: 10.3389/fimmu.2018.00387] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2017] [Accepted: 02/12/2018] [Indexed: 12/15/2022] Open
Abstract
Systemic lupus erythematosus (SLE) is an inadequately defined syndrome. Etiology and pathogenesis remain largely unknown. SLE is on the other hand a seminal syndrome that has challenged immunologists, biologists, genetics, and clinicians to solve its nature. The syndrome is characterized by multiple, etiologically unlinked manifestations. Unexpectedly, they seem to occur in different stochastically linked clusters, although single gene defects may promote a smaller spectrum of symptoms/criteria typical for SLE. There is no known inner coherence of parameters (criteria) making up the disease. These parameters are, nevertheless, implemented in The American College of Rheumatology (ACR) and The Systemic Lupus Collaborating Clinics (SLICC) criteria to classify SLE. Still, SLE is an abstraction since the ACR or SLICC criteria allow us to define hundreds of different clinical SLE phenotypes. This is a major point of the present discussion and uses "The anti-dsDNA antibody" as an example related to the problematic search for biomarkers for SLE. The following discussion will show how problematic this is: the disease is defined through non-coherent classification criteria, its complexity is recognized and accepted, its pathogenesis is plural and poorly understood. Therapy is focused on dominant symptoms or organ manifestations, and not on the syndrome itself. From basic scientific evidences, we can add substantial amount of data that are not sufficiently considered in clinical medicine, which may change the paradigms linked to what "The Anti-DNA antibody" is-and is not-in context of the imperfectly defined syndrome SLE.
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Affiliation(s)
- Ole Petter Rekvig
- Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway
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21
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Selmi C, Generali E, Gershwin ME. Rheumatic Manifestations in Autoimmune Liver Disease. Rheum Dis Clin North Am 2018; 44:65-87. [PMID: 29149928 DOI: 10.1016/j.rdc.2017.09.008] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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22
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23
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Dyggve H, Meri S, Spillmann T, Jarva H, Speeti M. Antihistone Autoantibodies in Dobermans With Hepatitis. J Vet Intern Med 2017; 31:1717-1723. [PMID: 28963850 PMCID: PMC5697184 DOI: 10.1111/jvim.14838] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2017] [Revised: 06/25/2017] [Accepted: 08/21/2017] [Indexed: 12/16/2022] Open
Abstract
Background Immune system involvement is suggested as an underlying cause for Doberman hepatitis (DH) based on female predisposition, lymphocyte infiltration, abnormal hepatocyte expression of major histocompatibility complex class II antigens, and homozygosity for dog leukocyte antigen DRB1*00601. Objective To measure serum antinuclear antibodies (ANA) and serum antihistone antibodies (AHA) in Dobermans with hepatitis. To determine whether increased serum ANA or serum AHA could be used to support the diagnosis of Doberman hepatitis (DH). Animals Privately owned 25 subclinically and 13 clinically affected DH Dobermans and 17 healthy control Dobermans. Methods Case–control study. Indirect immunofluorescence (IIF) microscopy and line blot tests were employed for the ANA pilot studies and an enzyme‐linked immunosorbent assay (ELISA) assay for detection of IgG AHA. Results Indirect immunofluorescence revealed ANA‐positive cases, and line blot showed AHA reactivity. In ELISA, importantly increased concentrations of AHA were found in 92% (23/25) of dogs in the subclinical stage and 84.6% (11 of 13) of dogs in the clinical stage of DH compared with no control dogs (0/17) (P < 0.0005). The mean AHA absorbance values of the blood samples obtained from the 25 subclinical DH dogs (1.36 ± 0.60, mean ± SD) and the 13 clinically affected dogs (1.46 ± 0.49) were significantly higher than in 17 control dogs (0.51 ± 0.18; P < 0.0001). Conclusions and Clinical Importance As the presence of AHA indicates autoimmune activity, our results favor an autoimmune background as one cause for DH. Antihistone antibody could represent a novel means for screening Dobermans with increased serum alanine transaminase concentrations and suspicion of DH.
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Affiliation(s)
- H Dyggve
- Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.,Department of Bacteriology and Immunology and Immunobiology Research Program, University of Helsinki and HUSLAB, Helsinki, Finland
| | - S Meri
- Department of Bacteriology and Immunology and Immunobiology Research Program, University of Helsinki and HUSLAB, Helsinki, Finland
| | - T Spillmann
- Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland
| | - H Jarva
- Department of Bacteriology and Immunology and Immunobiology Research Program, University of Helsinki and HUSLAB, Helsinki, Finland
| | - M Speeti
- Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland
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24
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Global Disparities and Their Implications in the Occurrence and Outcome of Autoimmune Hepatitis. Dig Dis Sci 2017; 62:2277-2292. [PMID: 28710658 DOI: 10.1007/s10620-017-4675-y] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2017] [Accepted: 07/06/2017] [Indexed: 02/07/2023]
Abstract
Autoimmune hepatitis has a variable occurrence, clinical phenotype, and outcome, and the factors contributing to this variability are uncertain. The goals of this review are to examine the global disparities in the occurrence and outcome of autoimmune hepatitis, suggest bases for these disparities, and encourage investigations that extend beyond single-center experiences. Disparities in the incidence and prevalence of autoimmune hepatitis in different age groups, genders, ethnicities, and geographical regions suggest that factors other than genetic predisposition are involved. Age- and gender-related antigen exposures from the external (infections, toxins, and medications) and internal (intestinal microbiome) environment may affect the incidence of the disease, and the timeliness and nature of treatment may influence its prevalence. The increasing incidence of autoimmune hepatitis in Spain, Denmark, and the Netherlands suggests that a new etiological trigger has been introduced or that the susceptible population has changed. Variations in mortality between Western and Asian-Pacific countries may result from differences in disease detection or management, and variations in gender predilection, peak age of onset, frequency of concurrent immune diseases, and serological profile may reflect gender-biased and age-related antigen exposures and genetic predispositions. Global collaborations, population-based epidemiological studies that identify case clustering, and controlled interview-based surveys are mechanisms by which to understand these disparities and improve management. In conclusion, autoimmune hepatitis has a rising incidence in some countries and variable occurrence, phenotype, and outcome between countries and subgroups within countries. These disparities suggest that unrecognized population-based environmental, infectious, or socioeconomic factors are affecting its character.
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25
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Mitra S, Minz RW. Autoantibodies in Autoimmune Liver Diseases-Methods of Detection and Interpretation: An Update for the Reporting Pathologist. Int J Surg Pathol 2016; 24:576-85. [PMID: 27388199 DOI: 10.1177/1066896916657643] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Autoimmune liver disease (AILD) is a type of chronic liver disease with autoimmune etiology. The diagnosis of the disease is multipronged and detection of autoantibodies in AILDs is an important diagnostic tool and it also helps in the classification of the disease. There are multiple autoantibodies that are detected in AILDs but none is diagnostic. Moreover, these autoantibodies are detected in many other pathological and nonpathological conditions. So the significance of seropositivity for these autoantibodies should be known by both the pathologists as well as the clinicians. In addition, there is prognostic significance associated with some of the antibodies and they also sometimes help in the disease monitoring. The whole array of antibodies detected in AILDs is discussed in detail in this review along with their clinical significance and interpretation.
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Affiliation(s)
- Suvradeep Mitra
- PGIMER (Post-Graduate Institute of Medical Education and Research), Chandigarh, India
| | - Ranjana Walker Minz
- PGIMER (Post-Graduate Institute of Medical Education and Research), Chandigarh, India
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26
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Clinical Characteristics of Concomitant Systemic Lupus Erythematosus and Primary Biliary Cirrhosis: A Literature Review. J Immunol Res 2015; 2015:713728. [PMID: 26090497 PMCID: PMC4452083 DOI: 10.1155/2015/713728] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2014] [Accepted: 01/17/2015] [Indexed: 12/14/2022] Open
Abstract
Although autoimmune diseases often coexist, concomitant cases of systemic lupus erythematosus (SLE) and primary biliary cirrhosis (PBC) are uncommon. In this review paper, 34 cases of SLE with concomitant PBC found in English and Japanese scientific literature and Japanese proceedings were reviewed and summarized, including cases with liver dysfunction complicated by SLE. Of the 34 reported concomitant cases of SLE and PBC, 97.1% (33/34) were females, and PBC was diagnosed initially in 69.0% (20/29), except for five cases in which both SLE and PBC were simultaneously diagnosed. Sjögren's syndrome was the most common autoimmune disease complicating concomitant SLE and PBC (23.5%, 8/34). Five deaths have been reported: two elderly patients died of liver failure because of the worsening of PBC, and another two patients died from pulmonary infection associated with SLE pharmacotherapy. It is uncertain whether concomitant cases occur by chance or share a common immunological or genetic basis.
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27
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Abstract
Historically, liver biopsy has been used to determine the etiology of liver disease, the degree of inflammation, the stage of liver fibrosis, and the response to treatments. In the last decade, the advent of noninvasive tests has improved the diagnosis and management of autoimmune liver diseases. For example, serum markers can identify hepatic inflammation, whereas ultrasound and MRI can diagnose liver fibrosis. Physicians now have a much larger repertoire of diagnostic tests to assess the liver parenchyma compared with liver biopsy alone. In some rare cases, noninvasive tests may provide an alternative to liver biopsy. In general, however, these noninvasive tests complement liver biopsy and provide quick, accurate, and reliable adjunctive data.
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28
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Ferucci ED, Choromanski TL, Hurlburt KJ, Livingston S, Plotnik J, Manns MP, McMahon BJ, James JA. Autoimmune hepatitis in the Alaska Native population: autoantibody profile and HLA associations. Liver Int 2014; 34:1241-9. [PMID: 24939565 DOI: 10.1111/liv.12372] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2013] [Accepted: 10/27/2013] [Indexed: 01/03/2023]
Abstract
BACKGROUND & AIMS The Alaska Native population is one of few populations in the world with a high prevalence of autoimmune hepatitis. The objective of this study was to determine the frequency and HLA and clinical associations of autoantibodies in Alaska Native people with autoimmune hepatitis. METHODS Alaska Native individuals with autoimmune hepatitis were recruited in clinics conducted statewide. Sera were tested for the presence of autoantibodies described in either autoimmune hepatitis or rheumatic disease. Associations between autoantibodies and HLA alleles and clinical features were assessed. RESULTS Seventy-one patients were included. At the study visit, 34 patients (47.9%) had antibodies to double-stranded DNA by immunofluorescence; 27 (38.0%) had anti-neutrophil cytoplasmic antibodies; and 11 (15.5%) had anti-Ro antibodies. Only one person had antibodies against soluble liver antigen, and in that person, anti-Ro was absent. Associations were found between autoantibodies and HLA alleles, including positive associations between HLA DR3 and anti-double-stranded DNA antibodies and between HLA DR14 and antineutrophil cytoplasmic antibodies. There was no association between autoantibodies and clinical outcomes. CONCLUSIONS As in other populations, the prevalence of anti-double-stranded DNA antibodies and antineutrophil cytoplasmic antibodies is high in Alaska Native people with autoimmune hepatitis. In contrast to data from other populations, there is a lower prevalence of anti-soluble liver antigen and a lack of association between anti-Ro and anti-soluble liver antigen. In addition, the HLA profile and associations with autoantibodies are unique. No clear prognostic implications of autoantibodies have emerged in this population.
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Affiliation(s)
- Elizabeth D Ferucci
- Division of Community Health Services, Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, AK, USA
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29
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Bessone F, Poles N, Roma MG. Challenge of liver disease in systemic lupus erythematosus: Clues for diagnosis and hints for pathogenesis. World J Hepatol 2014; 6:394-409. [PMID: 25018850 PMCID: PMC4081614 DOI: 10.4254/wjh.v6.i6.394] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2014] [Revised: 03/08/2014] [Accepted: 05/14/2014] [Indexed: 02/06/2023] Open
Abstract
Systemic lupus erythematosus (SLE) encompass a broad spectrum of liver diseases. We propose here to classify them as follows: (1) immunological comorbilities (overlap syndromes); (2) non-immunological comorbilities associated to SLE; and (3) a putative liver damage induced by SLE itself, referred to as "lupus hepatitis". In the first group, liver injury can be ascribed to overlapping hepatopathies triggered by autoimmune mechanisms other than SLE occurring with higher incidence in the context of lupus (e.g., autoimmune hepatitis, primary biliary cirrhosis). The second group includes non-autoimmune liver diseases, such as esteatosis, hepatitis C, hypercoagulation state-related liver lesions, hyperplasic parenchymal and vascular lesions, porphyria cutanea tarda, and drug-induced hepatotoxicity. Finally, the data in the literature to support the existence of a hepatic disease produced by SLE itself, or the occurrence of a SLE-associated prone condition that increases susceptibility to acquire other liver diseases, is critically discussed. The pathological mechanisms underlying each of these liver disorders are also reviewed. Despite the high heterogeneity in the literature regarding the prevalence of SLE-associated liver diseases and, in most cases, lack of histopathological evidence or clinical studies large enough to support their existence, it is becoming increasingly apparent that liver is an important target of SLE. Consequently, biochemical liver tests should be routinely carried out in SLE patients to discard liver disorders, particularly in those patients chronically exposed to potentially hepatotoxic drugs. Diagnosing liver disease in SLE patients is always challenging, and the systematization of the current information carried out in this review is expected to be of help both to attain a better understanding of pathogenesis and to build an appropriate work-up for diagnosis.
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Affiliation(s)
- Fernando Bessone
- Fernando Bessone, Natalia Poles, Gastroenterology and Hepatology Department, University of Rosario School of Medicine, Rosario 2000, Argentina
| | - Natalia Poles
- Fernando Bessone, Natalia Poles, Gastroenterology and Hepatology Department, University of Rosario School of Medicine, Rosario 2000, Argentina
| | - Marcelo G Roma
- Fernando Bessone, Natalia Poles, Gastroenterology and Hepatology Department, University of Rosario School of Medicine, Rosario 2000, Argentina
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30
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Abstract
The liver is the largest organ in the body and is generally regarded by nonimmunologists as having little or no lymphoid function. However, such is far from accurate. This review highlights the importance of the liver as a lymphoid organ. Firstly, we discuss experimental data surrounding the role of liver as a lymphoid organ. The liver facilitates tolerance rather than immunoreactivity, which protects the host from antigenic overload of dietary components and drugs derived from the gut and it is instrumental to fetal immune tolerance. Loss of liver tolerance leads to autoaggressive phenomena, which if not controlled by regulatory lymphoid populations, may lead to the induction of autoimmune liver diseases. Liver-related lymphoid subpopulations also act as critical antigen-presenting cells. The study of the immunological properties of liver and delineation of the microenvironment of the intrahepatic milieu in normal and diseased livers provides a platform to understand the hierarchy of a series of detrimental events that lead to immune-mediated destruction of the liver and the rejection of liver allografts. The majority of emphasis within this review will be on the normal mononuclear cell composition of the liver. However, within this context, we will discuss selected, but not all, immune-mediated liver disease and attempt to place these data in the context of human autoimmunity.
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Affiliation(s)
- Dimitrios P Bogdanos
- Institute of Liver Studies, Transplantation Immunology and Mucosal Biology, King's College London School of Medicine at King's College Hospital, London, UK
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31
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Liberal R, Mieli-Vergani G, Vergani D. Clinical significance of autoantibodies in autoimmune hepatitis. J Autoimmun 2013; 46:17-24. [DOI: 10.1016/j.jaut.2013.08.001] [Citation(s) in RCA: 68] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2013] [Accepted: 08/04/2013] [Indexed: 01/14/2023]
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32
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Tang J, Lu J, Yan HP. Diagnostic and predictive significance of autoantibody profiles in autoimmune liver disease. Shijie Huaren Xiaohua Zazhi 2013; 21:2544-2550. [DOI: 10.11569/wcjd.v21.i25.2544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Autoimmune liver disease (AILD) is a chronic inflammatory disease presumably induced by a disorder of immune homeostasis within the liver, which can lead to damage to or loss of the hepatic parenchyma or bile duct epithelia. Indirect immunofluorescence and antibody specificity assays are important tools for the diagnosis of AILD. Over the last decade, there have been an increasing number of newly characterized target antigens for autoantibodies in AILD. Autoantibodies, as biomarkers, are used not only for disease diagnosis, but also for monitoring disease activity and progression and predicting prognosis and treatment responses.
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33
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Ferri Liu PM, de Miranda DM, Fagundes EDT, Ferreira AR, Simões e Silva AC. Autoimmune hepatitis in childhood: the role of genetic and immune factors. World J Gastroenterol 2013; 19:4455-4463. [PMID: 23901220 PMCID: PMC3725369 DOI: 10.3748/wjg.v19.i28.4455] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2013] [Revised: 06/05/2013] [Accepted: 06/08/2013] [Indexed: 02/06/2023] Open
Abstract
Autoimmune hepatitis (AIH) is a rare chronic inflammatory disease of the liver, which affects a group of patients who lost their immunological tolerance to antigens of the liver. It is clinically characterized by hypergammaglobulinemia, elevated liver enzymes, presence of autoantibodies and histological changes. Although being rare in children, it represents a serious cause of chronic hepatic disease that can lead to cirrhosis and hepatic failure. Clinical findings, exclusion of more common liver disorders and the detection of antibodies antinuclear antibodies, smooth muscle antibodies and anti-LKM1 are usually enough for diagnosis on clinical practice. The pathogenic mechanisms that lead to AIH remain obscure, but some research findings suggest the participation of immunologic and genetic factors. It is not yet knew the triggering factor or factors that stimulate inflammatory response. Several mechanisms proposed partially explain the immunologic findings of AIH. The knowledge of immune factors evolved might result in better markers of prognosis and response to treatment. In this review, we aim to evaluate the findings of research about genetic and immune markers and their perspectives of application in clinical practice especially in pediatric population.
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34
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[Inflammatory diseases with liver and joint involvement. A differential diagnostic challenge]. Internist (Berl) 2013; 54:441-8. [PMID: 23455625 DOI: 10.1007/s00108-012-3191-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Elevated levels of liver enzymes in patients with rheumatic symptoms require a comprehensive differential diagnostic thought process. On the one hand there can be hepatic involvement of primarily rheumatological diseases but this is quite rare. Drug-induced liver injury by antirheumatic medication is more frequent. On the other hand arthralgia can be a sign of primary hepatopathy whereby hemochromatosis and autoimmune hepatitis (AIH) are typical examples. Furthermore, some liver diseases are associated with rheumatological diseases, such as primary biliary cirrhosis (PBC) and chronic hepatitis C infection (HCV). Only an exact diagnosis will lead to specific treatment which will improve the symptoms and course of disease.
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35
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Himoto T, Nishioka M. Autoantibodies in liver disease: important clues for the diagnosis, disease activity and prognosis. AUTOIMMUNITY HIGHLIGHTS 2013; 4:39-53. [PMID: 26000142 PMCID: PMC4389052 DOI: 10.1007/s13317-013-0046-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/27/2012] [Accepted: 01/18/2013] [Indexed: 12/18/2022]
Abstract
It has been well established that numerous kinds of autoantibodies have been detected in liver disease. Some kinds of autoantibodies may be helpful in the diagnosis of autoimmune liver diseases including autoimmune hepatitis, primary biliary cirrhosis or primary sclerosing cholangitis. However, these autoantibodies are present even in sera of patients with viral hepatitis, drug-induced hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease and hepatocelluar carcinoma as well as in sera of patients with autoimmune liver diseases. Other kinds of autoantibodies are recognized as predictive hallmarks for disease activity or prognosis in liver diseases. On the other hand, treatment with interferon initiates the production of several types of autoantibodies in patients with chronic hepatitis C virus infection. Some of autoantibodies induced by interferon may postulate the treatment outcome in those patients. Recent studies also revealed the close correlation between oxidative stress and the production of autoantibodies in liver diseases. This article primarily reviews the recent advances of autoantibodies in the liver diseases and discusses the clinical significance of these autoantibodies.
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Affiliation(s)
- Takashi Himoto
- Department of Integrated Medicine, Kagawa University School of Medicine, Kagawa, 761-0793 Japan ; Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kagawa, 761-0793 Japan
| | - Mikio Nishioka
- Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kagawa, 761-0793 Japan
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36
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Fallatah HI, Akbar HO. Autoimmune hepatitis as a unique form of an autoimmune liver disease: immunological aspects and clinical overview. Autoimmune Dis 2012; 2012:312817. [PMID: 23304455 PMCID: PMC3530748 DOI: 10.1155/2012/312817] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2012] [Revised: 09/09/2012] [Accepted: 10/12/2012] [Indexed: 12/11/2022] Open
Abstract
Autoimmune hepatitis (AIH) is a unique form of immune-mediated disease that attacks the liver through a variety of immune mechanisms. The outcomes of AIH are either acute liver disease, which can be fatal, or, more commonly, chronic progressive liver disease, which can lead to decompensated liver cirrhosis if left untreated. AIH has characteristic immunological, and pathological, features that are important for the establishment of the diagnosis. More importantly, most patients with AIH have a favorable response to treatment with prednisolone and azathioprine, although some patients with refractory AIH or more aggressive disease require more potent immune-suppressant agents, such as cyclosporine or Mycophenolate Mofetil. In this paper, we discuss the immunological, pathological and clinical features of AIH, as well as the standard and alternative treatments for AIH.
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Affiliation(s)
- Hind I. Fallatah
- Medical Department, Arab Board and Saudi Board of Internal Medicine, MACP, King Abdul Aziz University Hospital, P.O. Box 9714, Jeddah 21423, Saudi Arabia
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37
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Freire M, Villaverde I, Gonzalez-Carrero J, Rivera A, Sopena B. Autoimmune hepatitis and hepatic arteritis. Rheumatology (Oxford) 2012; 51:2106-7. [DOI: 10.1093/rheumatology/kes070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
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Johanet C, Beleoken E, Ballot E. Autoantibodies in autoimmune hepatitis: antinuclear antibodies (ANA). Clin Res Hepatol Gastroenterol 2012; 36:394-6. [PMID: 22481089 DOI: 10.1016/j.clinre.2012.02.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2012] [Accepted: 02/07/2012] [Indexed: 02/04/2023]
Affiliation(s)
- Catherine Johanet
- Unité d'immunologie, CHU Saint-Antoine, AP-HP, 75571 Paris cedex 12, France.
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Clinical significance of autoantibodies to p53 protein in patients with autoimmune liver diseases. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2012; 26:125-9. [PMID: 22408762 DOI: 10.1155/2012/890698] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Autoantibodies to p53 (anti-p53) are rarely present in the sera of patients with autoimmune diseases or the sera of patients with malignancies. OBJECTIVE To examine the prevalence of anti-p53 in patients with autoimmune liver disease including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), AIH⁄PBC overlap syndrome (AIH⁄PBC OS) and primary sclerosing cholangitis (PSC), and to determine the clinical significance of anti-p53 in autoimmune liver diseases. METHODS Forty patients with AIH, 41 patients with PBC, eight patients with AIH⁄PBC OS and five patients with PSC were enrolled. Anti-p53 and antibodies to double-stranded DNA (anti-ds-DNA) were analyzed using commercially available ELISA kits. Demographic, laboratory and histological data were compared between the AIH groups seropositive and seronegative for anti-p53. RESULTS Six of 40 (15.0%) patients with AIH and four of eight (50.0%) patients with AIH⁄PBC OS were positive for anti-p53. One of 41 (2.4%) patients with PBC was also positive for anti-p53, but all five patients with PSC were negative, indicating a significantly higher prevalence of anti-p53 in patients with AIH or AIH⁄PBC OS compared with patients with PBC. None of the AIH patients positive for anti-p53 progressed to hepatic failure or relapsed after immunosuppressive treatment. Titres of anti-ds-DNA in patients with AIH and AIH⁄PBC OS significantly correlated with titres of anti-p53 (r=0.511; P=0.0213). CONCLUSION The emergence of anti-p53 is likely to be useful for discriminating AIH or AIH⁄PBC OS from PBC and helpful for predicting favourable prognoses in patients with AIH. DNA damage may trigger the production of anti-p53 in patients with AIH or AIH⁄PBC OS.
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40
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Dhir V. Biomarkers in systemic lupus erythematosus: Do they make the mark? INDIAN JOURNAL OF RHEUMATOLOGY 2012. [DOI: 10.1016/s0973-3698(12)60004-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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Abstract
Autoimmune hepatitis has a variable clinical phenotype, and the absence of conventional autoantibodies does not preclude its diagnosis or need for treatment. The goals of this review are to describe the frequency and nature of autoantibody-negative autoimmune hepatitis, indicate its outcome after corticosteroid treatment, and increase awareness of the diagnosis in patients with unexplained acute and chronic hepatitis. The frequency of presumed autoantibody-negative autoimmune hepatitis in patients with acute and acute severe presentations is ≤7%, and its frequency in patients with chronic presentations is 1-34%. Patients with acute presentations can have normal serum γ-globulin levels, centrilobular zone 3 necrosis, and low pre-treatment international diagnostic scores. Liver tissue examination is essential for the diagnosis, and hepatic steatosis can be a co-morbid feature. The comprehensive international scoring system can support but never override the clinical diagnosis pre-treatment, and non-standard serological markers should be sought if the clinical diagnosis is uncertain or the diagnostic score is low. A 3-month treatment trial with corticosteroids should be considered in all patients, regardless of the serological findings, and improvements have occurred in 67-87% of cases. Autoantibody-negative autoimmune hepatitis may be associated with an autoantibody outside the conventional battery; it may have a signature autoantibody that is still undiscovered, or its characteristic autoantibodies may have been suppressed or have a delayed expression. The pathogenic mechanisms are presumed to be identical to those of classical disease. Autoantibody-negative autoimmune hepatitis is an infrequent but treatable disease that must be considered in unexplained acute and chronic hepatitis.
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Affiliation(s)
- Albert J Czaja
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street S.W., Rochester, MN 55905, USA.
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Efe C, Purnak T, Ozaslan E, Ozbalkan Z, Karaaslan Y, Altiparmak E, Muratori P, Wahlin S. Autoimmune liver disease in patients with systemic lupus erythematosus: a retrospective analysis of 147 cases. Scand J Gastroenterol 2011; 46:732-737. [PMID: 21348808 DOI: 10.3109/00365521.2011.558114] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE We aimed to investigate the characteristics of autoimmune liver disease (AILD) developed in patients with systemic lupus erythematosus (SLE), including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and the AIH/PBC overlap syndrome. We also evaluated the accuracy of diagnostic criteria and scoring systems for AILD in SLE. METHODS A retrospective analysis of patients attending the rheumatology and gastroenterology clinics in Ankara, Turkey, between 1999 and 2010. SLE patients with elevated liver enzymes were investigated for liver diseases. RESULTS A total of 147 SLE patients were identified and 36 of them had liver enzyme abnormalities. AILD was diagnosed in 4.7% of all SLE patients, in 19.4% of those with elevated liver enzymes. Of patients with liver enzyme abnormalities, 72.3% fulfilled the criteria for AIH proposed by the International Autoimmune Hepatitis Group (IAIHG), whereas 66.7% had AIH by using the simplified criteria. Yet, only 13.8% of these patients had liver biopsy findings consistent with AIH. Patients with AILD were treated with conventional therapy including ursodeoxycholic acid, prednisolone, azathioprine or combinations of these. Treatment failure and subsequent advanced liver disease developed in one patient. CONCLUSIONS AILD may occur during the course of SLE. Due to biochemical similarities between AIH and SLE, AIH could be considered very probable by using both IAIHG scoring system and simplified criteria. For definitive diagnosis of AIH, liver biopsy should be performed in all SLE patients with chronic enzyme abnormalities. The response to therapy is favorable in these patients, and early diagnosis is important for preventing advanced liver disease.
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MESH Headings
- Adult
- Antibodies, Antinuclear/analysis
- Azathioprine/therapeutic use
- Biopsy
- Enzyme-Linked Immunosorbent Assay
- Female
- Hepatitis, Autoimmune/complications
- Hepatitis, Autoimmune/diagnosis
- Hepatitis, Autoimmune/drug therapy
- Humans
- Hydroxychloroquine/therapeutic use
- Immunoblotting
- Immunoglobulin G/analysis
- Liver Cirrhosis, Biliary/complications
- Liver Cirrhosis, Biliary/diagnosis
- Liver Cirrhosis, Biliary/drug therapy
- Lupus Erythematosus, Systemic/complications
- Lupus Erythematosus, Systemic/diagnosis
- Lupus Erythematosus, Systemic/drug therapy
- Middle Aged
- Prednisolone/therapeutic use
- Prevalence
- Retrospective Studies
- Syndrome
- Treatment Outcome
- Ursodeoxycholic Acid/therapeutic use
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Affiliation(s)
- Cumali Efe
- Department of Internal Medicine, Ankara Numune Research and Education Hospital, Ankara, Turkey.
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Autoimmune hepatitis: a review of current diagnosis and treatment. HEPATITIS RESEARCH AND TREATMENT 2011; 2011:390916. [PMID: 21760995 PMCID: PMC3132488 DOI: 10.1155/2011/390916] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/13/2010] [Revised: 02/15/2011] [Accepted: 03/03/2011] [Indexed: 12/20/2022]
Abstract
Autoimmune hepatitis (AIH) is a chronic inflammatory disorder characterized by periportal inflammation, elevated immunoglobulins, autoantibodies, and a dramatic response to immunosuppression. An environmental agent is hypothesized to trigger an immune-mediated attack directed against liver antigens in genetically predisposed individuals. A plethora of clinical presentations can be seen ranging from chronic indolent disease to fulminant hepatic failure, and diagnosis requires exclusion of other causes of liver disease. Corticosteroid therapy must be instituted early and modified in an individualized fashion. Treatment decisions are often complicated by the diverse clinical manifestations, uncertainty about natural history, evolving ideas about treatment end points, and a multitude of alternative immunosuppressive agents. Achieving normal liver tests and tissue is the ideal treatment end point, but needs to be weighed against the risk of side effects. Decompensated patients may benefit from early liver transplantation. Long-term prognosis is excellent with early and aggressive initiation of therapy. Our paper discusses AIH, giving a detailed overview of its clinical presentation, risk factors, immunopathogenesis, up-to-date diagnostic criteria, current updates in therapy with a brief discussion of AIH in pregnancy, and long-term implications for cirrhosis and hepatocellular carcinoma in AIH patients.
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Tovoli F, De Giorgio R, Caio G, Grasso V, Frisoni C, Serra M, Caputo C, Stanghellini V, Bolondi L, Corinaldesi R, Volta U. Autoimmune Hepatitis and Celiac Disease: Case Report Showing an Entero-Hepatic Link. Case Rep Gastroenterol 2010; 4:469-475. [PMID: 21103207 PMCID: PMC2988861 DOI: 10.1159/000321992] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Celiac disease is an autoimmune disorder primarily targeting the small bowel, although extraintestinal extensions have been reported. The autoimmune processes can affect the liver with manifestations such as primary biliary cirrhosis and autoimmune hepatitis. We describe a 61-year-old woman with celiac disease and an increased levels of aminotransferases. The persistence of increased levels of aminotransferases after 1 year of gluten-free diet and the positivity for an anti-nuclear and anti-double-strand DNA antibodies led to a misdiagnosis of systemic lupus erythematosus-related hepatitis. Based on these findings the patient was placed on steroids, which after a few months were stopped because of the onset of diabetes mellitus. Soon after steroid withdrawal, the patient had a marked increase in aminotransferases and γ-globulins, and a liver biopsy revealed chronic active hepatitis. A course of three months of steroids and azathioprine normalized both biochemical and clinical parameters. Currently the patient is symptom-free and doing well. In conclusion, a hypertransaminasemia persisting after a gluten-free diet should be interpreted as a sign of coexisting autoimmune liver disease. Any autoantibody positivity (in this case to ANA and anti-dsDNA) should be carefully considered in order to avoid misdiagnosis delaying appropriate clinical management.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Umberto Volta
- Department of Clinical Medicine and Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, Università Alma Mater Studiorum di Bologna, Bologna, Italy
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45
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Czaja AJ. Autoantibodies as prognostic markers in autoimmune liver disease. Dig Dis Sci 2010; 55:2144-61. [PMID: 20464491 DOI: 10.1007/s10620-010-1268-4] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2010] [Accepted: 04/23/2010] [Indexed: 01/25/2023]
Abstract
Certain autoantibodies in autoimmune liver disease have prognostic implications that are under-utilized and under-developed. The goals of this review are to indicate progress in characterizing the autoantibodies with prognostic connotations and to indicate the feasibility and importance of discovering other markers. Prime source and review articles in English were selected by a Medline search through 2010. Antibodies to soluble liver antigen, actin, liver cytosol type 1, asialoglycoprotein receptor, chromatin, cyclic citrullinated peptide, and uridine glucuronosyltransferases have been associated with the occurrence, severity, and progression of autoimmune hepatitis, and antibodies to Sp100, gp210, and centromere have had similar implications in primary biliary cirrhosis. Antibodies to soluble liver antigen have shown the most promise in autoimmune hepatitis as they have been associated with severe histological changes, long durations of treatment, relapse after drug withdrawal, and high frequency of liver failure. Antibodies to the nuclear rim pore protein, gp210, have shown the most promise in primary biliary cirrhosis as they have been associated with severe interface hepatitis, lobular inflammation, and progression to liver failure. The major limitations of the autoantibodies have been their lack of standardized assays, low negative predictabilities, and fluctuating levels. Performance parameters will improve as critical pathogenic pathways, comprehensive testing batteries, and standardized assays through international exchange workshops are developed. Progress has been made in identifying the serological markers of prognosis in autoimmune liver disease, and they promise to reflect critical disease mechanisms and enhance patient management.
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Affiliation(s)
- Albert J Czaja
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
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46
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Czaja AJ. The role of autoantibodies as diagnostic markers of autoimmune hepatitis. Expert Rev Clin Immunol 2010; 2:33-48. [PMID: 20477086 DOI: 10.1586/1744666x.2.1.33] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Autoantibody testing is the first step towards the diagnosis of autoimmune hepatitis, and it is essential in the evaluation of acute and chronic hepatitis of undetermined cause and allograft dysfunction following liver transplantation. A standard diagnostic repertoire has been promulgated, and other autoantibodies are emerging that may have prognostic value. Supplemental autoantibodies may prove useful in assessing patients who lack the standard markers or who are distinctive among those with conventional markers. Serologic testing will improve as assays are standardized by serum exchange workshops, core diagnostic batteries are codified and promulgated, and markers emerge that are tightly associated with pathogenic mechanisms, and closely reflect disease activity and outcome.
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Affiliation(s)
- Albert J Czaja
- Mayo Clinic, Mayo Clinic, 200 First Street S.W., Rochester, MN 55905, USA.
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Muratori P, Granito A, Quarneti C, Ferri S, Menichella R, Cassani F, Pappas G, Bianchi FB, Lenzi M, Muratori L. Autoimmune hepatitis in Italy: the Bologna experience. J Hepatol 2009; 50:1210-1218. [PMID: 19395113 DOI: 10.1016/j.jhep.2009.01.020] [Citation(s) in RCA: 88] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2008] [Revised: 12/13/2008] [Accepted: 01/12/2009] [Indexed: 12/14/2022]
Abstract
BACKGROUND/AIMS Autoimmune hepatitis affects mainly women. It is subdivided into type 1 and type 2 according to the autoantibody profile and without immunosuppression usually evolves to cirrhosis and end-stage liver failure. METHODS We evaluated clinical, biochemical, immunological and genetic features and treatment response of 163 consecutive Italian patients with autoimmune hepatitis. RESULTS At diagnosis, type 1 autoimmune hepatitis showed more inflamed liver histology and more pronounced cholestasis, whereas type 2 was more common in children. Male and female patients shared similar clinical, biochemical and immunological features. Of 89 patients with 5-year follow-up or longer, 23 patients irrespective of presenting clinical, biochemical and immunological features achieved complete remission (normal transaminases and gammaglobulin levels) which was maintained with minimal steroid dosage; attempt at treatment withdrawal led to disease exacerbation. Complete responders had more often HLA DRB1*0401 (p = 0.011) and their risk of disease progression was lower (p < 0.0001). CONCLUSIONS Type 1 and type 2 autoimmune hepatitis is one and the same disease. Autoimmune hepatitis has similar features in male and female patients. HLA DRB1*0401 positive patients are more likely to achieve complete remission. Continuous low-dose steroids are necessary to maintain remission, significantly reducing the risk of disease progression.
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Affiliation(s)
- Paolo Muratori
- Department of Clinical Medicine, Alma Mater Studiorum, University of Bologna, Policlinico Sant'Orsola-Malpighi, Via Massarenti, 9, 40138 Bologna, Italy
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Servais G, Karmali R, Guillaume MP, Badot V, Duchateau J, Corazza F. Anti DNA antibodies are not restricted to a specific pattern of fluorescence on HEp2 cells. Clin Chem Lab Med 2009; 47:543-9. [DOI: 10.1515/cclm.2009.122] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Bogdanos DP, Invernizzi P, Mackay IR, Vergani D. Autoimmune liver serology: Current diagnostic and clinical challenges. World J Gastroenterol 2008; 14:3374-87. [PMID: 18528935 PMCID: PMC2716592 DOI: 10.3748/wjg.14.3374] [Citation(s) in RCA: 145] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Liver-related autoantibodies are crucial for the correct diagnosis and classification of autoimmune liver diseases (AiLD), namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2), primary biliary cirrhosis (PBC), and the sclerosing cholangitis variants in adults and children. AIH-1 is specified by anti-nuclear antibody (ANA) and smooth muscle antibody (SMA). AIH-2 is specified by antibody to liver kidney microsomal antigen type-1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1). SMA, ANA and anti-LKM antibodies can be present in de-novo AIH following liver transplantation. PBC is specified by antimitochondrial antibodies (AMA) reacting with enzymes of the 2-oxo-acid dehydrogenase complexes (chiefly pyruvate dehydrogenase complex E2 subunit) and disease-specific ANA mainly reacting with nuclear pore gp210 and nuclear body sp100. Sclerosing cholangitis presents as at least two variants, first the classical primary sclerosing cholangitis (PSC) mostly affecting adult men wherein the only (and non-specific) reactivity is an atypical perinuclear antineutrophil cytoplasmic antibody (p-ANCA), also termed perinuclear anti-neutrophil nuclear antibodies (p-ANNA) and second the childhood disease called autoimmune sclerosing cholangitis (ASC) with serological features resembling those of type 1 AIH. Liver diagnostic serology is a fast-expanding area of investigation as new purified and recombinant autoantigens, and automated technologies such as ELISAs and bead assays, become available to complement (or even compete with) traditional immunofluorescence procedures. We survey for the first time global trends in quality assurance impacting as it does on (1) manufacturers/purveyors of kits and reagents, (2) diagnostic service laboratories that fulfill clinicians’ requirements, and (3) the end-user, the physician providing patient care, who must properly interpret test results in the overall clinical context.
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50
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Antimitochondrial antibodies and other antibodies in primary biliary cirrhosis: diagnostic and prognostic value. Clin Liver Dis 2008; 12:261-76; vii. [PMID: 18456179 DOI: 10.1016/j.cld.2008.02.009] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Antimitochondrial antibodies (AMA) are the serologic cornerstone in the diagnosis of primary biliary cirrhosis (PBC), even if they are not detectable in a proportion of patients, notwithstanding the most sensitive and sophisticated technologies used. To fill in the serologic gap in AMA-negative PBC, there is sound evidence to consider antinuclear antibody (ANA) patterns, such as anti-multiple nuclear dots and anti-membranous/rim-like, as PBC-specific surrogate hallmarks of the disease, and their detection can be considered virtually diagnostic. Furthermore, particular ANA specificities, such as anti-gp210, anti-p62, anticentromere antibodies, and anti-dsDNA, may provide additional diagnostic and prognostic information.
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