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1
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Haghollahi S, Wood RM, Ould Ismail AA, Ren B, Afzal MZ. Anastrozole-induced autoimmune hepatitis: a rare case report and literature review. Oxf Med Case Reports 2025; 2025:omaf062. [PMID: 40443853 PMCID: PMC12118058 DOI: 10.1093/omcr/omaf062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 01/15/2025] [Accepted: 03/26/2025] [Indexed: 06/02/2025] Open
Abstract
BACKGROUND Anastrozole, an aromatase inhibitor (AI), has been used extensively for the treatment of estrogen receptor-positive breast cancer. Autoimmune hepatitis (AIH) is an extremely rare but serious complication of anastrozole treatment. CASE DESCRIPTION We present the case of an 81-year-old female who presented with significantly elevated liver function test (LFTs) results 8 months after the initiation of anastrozole for early-stage breast cancer. Serological and liver biopsy findings were consistent with AIH. Discontinuation of anastrozole, along with a short course of steroids, resulted in rapid clinical improvement and normalization of both LFTs and autoantibodies. CONCLUSION Clinicians should be aware of drug-induced AIH as a rare but life-threatening complication of anastrozole and potentially other aromatase inhibitors.
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Affiliation(s)
- Shahab Haghollahi
- Department of Medicine, Dartmouth-Hitchcock Medical Center at Dartmouth Geisel School of Medicine, Hanover, NH 03756, United States
| | - Rebecca M Wood
- Department of Medicine, Dartmouth-Hitchcock Medical Center at Dartmouth Geisel School of Medicine, Hanover, NH 03756, United States
| | - Abdol Aziz Ould Ismail
- Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center at Dartmouth Geisel School of Medicine, Hanover, NH 03756, United States
| | - Bing Ren
- Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center at Dartmouth Geisel School of Medicine, Hanover, NH 03756, United States
| | - Muhammad Z Afzal
- Department of Hematology and Oncology, Dartmouth Hitchcock Cancer Center at Dartmouth Geisel School of Medicine, Hanover, NH 03756, United States
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2
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Guedes LR, Cançado GGL, Santos BC, Jacomassi LDS, Nardelli MJ, Osório FMF, Faria LC, Couto CA. Clinical, biochemical and histological features related to treatment response and prognosis in autoimmune hepatitis. Ann Hepatol 2024; 29:101497. [PMID: 38460715 DOI: 10.1016/j.aohep.2024.101497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 11/19/2023] [Accepted: 01/02/2024] [Indexed: 03/11/2024]
Abstract
INTRODUCTION AND OBJECTIVES Autoimmune hepatitis (AIH) is a rare disease with a complex and not fully understood pathogenesis. Prognostic factors that might influence treatment response, relapse rates, and transplant-free survival are not well established. This study investigates clinical and biochemical markers associated with response to immunosuppression in patients with AIH. MATERIALS AND METHODS This retrospective cohort study included 102 patients with AIH treated with immunosuppressants and followed at the Federal University of Minas Gerais, Brazil, from 1990 to 2018. Pretreatment data such as clinical profiles, laboratory, and histological exams were analyzed regarding biochemical response at one year, histological remission, relapse, and death/transplantation rates. RESULTS Cirrhosis was present in 59 % of cases at diagnosis. One-year biochemical remission was observed in 55.7 % of the patients and was found to be a protective factor for liver transplant. Overall survival was 89 %. Patients with ascites at disease onset showed a higher aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) ratio and elevated Model of end-stage liver disease (MELD) score. The presence of ascites was significantly associated with a 20-fold increase in mortality rate. CONCLUSIONS AIH has a severe clinical phenotype in Brazilians, with high rates of cirrhosis and low remission rates. Early diagnosis and treatment are essential for achieving remission and reducing complications. The presence of ascites is significantly associated with mortality, emphasizing the importance of monitoring and prompt intervention. This study also stresses the need for further research on AIH in Latin America.
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Affiliation(s)
- Ludmila Resende Guedes
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Hospital Mater Dei, Belo Horizonte, Minas Gerais, Brazil.
| | - Guilherme Grossi Lopes Cançado
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Hospital da Polícia Militar de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Bruno Campos Santos
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Luma Dos Santos Jacomassi
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Mateus Jorge Nardelli
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Fernanda Maria Farage Osório
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Luciana Costa Faria
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Cláudia Alves Couto
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
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Abstract
Autoimmune hepatitis (AIH) is a chronic immunologic disorder in which the immune system targets the liver. The disease has a genetic basis and this accounts for the epidemiologic variation observed in serologic testing and clinical presentation across different populations. The incidence of AIH increases with age into the 70s and seems to be increasing in prevalence. Most patients test positive for antinuclear antibody, ASMA, or anti-LKM but about 20% of patients do not have these serologic markers. At clinical presentation, patients may be asymptomatic, symptomatic, have acute liver failure, or decompensated cirrhosis.
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Affiliation(s)
- Mitchell L Shiffman
- Bon Secours Liver Institute of Richmond, Bon Secours Mercy Health, 5855 Bremo Road, Suite 509, Richmond, VA 23226, USA; Bon Secours Liver Institute of Hampton Roads, Bon Secours Mercy Health, 12720 Mc Manus Boulevard, Suite 313, Newport News, VA, 23602, USA.
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4
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Toniutto P, Zorzi M, D'Alì L, Cussigh A, Cmet S, Bitetto D, Fornasiere E, Fumolo E, Di Loreto C, Falleti E. Baseline Predictors of the Long-Term Insufficient Biochemical Response in Patients with Autoimmune Hepatitis: A Single Center Experience. J Clin Med 2023; 12:jcm12083008. [PMID: 37109344 PMCID: PMC10142659 DOI: 10.3390/jcm12083008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 04/12/2023] [Accepted: 04/19/2023] [Indexed: 04/29/2023] Open
Abstract
The treatment response criteria in autoimmune hepatitis (AIH) have been recently updated. This study aimed to assess treatment responses in 39 (16 males) patients with AIH confirmed by histology. Prednisone added to azathioprine or mycophenolate was the most frequent first-line treatment. Serum alanine aminotransferase (ALT) levels were periodically checked for a median of 45 months. Eight (20.5%) patients presented 4 weeks non-response (NR). Baseline lower multiples of ALT above the upper normal limit (UNL) (p = 0.005), Ishak liver fibrosis score > 3 (p = 0.029), and less frequent confluent necrosis > 2 (p < 0.001) were independent predictors of NR. 24 (61.5%) patients achieved complete biochemical response (CBR) at six months. Ishak liver fibrosis score ≤ 3 (p < 0.001), lobular eosinophilic infiltrate (p < 0.001), and ≥50% decrease in serum ALT levels at week 4 (p < 0.001) were independent predictors of CBR. In addition, the GLUCRE score, derived from the multiplication of serum creatinine (mg/dL) and glucose (mg/dL) levels, were identified. A baseline GLUCRE value > 100 strongly predicted CBR failure (p = 0.003) at a follow-up greater than 12 months. In conclusion, the absence of cirrhosis and a ≥50% UNL decrease in serum ALT levels were independent predictors for CBR. A baseline GLUCRE score may help identify patients maintaining longer CBR.
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Affiliation(s)
- Pierluigi Toniutto
- Hepatology and Liver Transplantation Unit, Department of Specialized Medicine, Udine University Hospital, 33100 Udine, Italy
| | - Michela Zorzi
- Hepatology and Liver Transplantation Unit, Department of Specialized Medicine, Udine University Hospital, 33100 Udine, Italy
| | - Lorenzo D'Alì
- Department of Medicine, Institute of Pathological Anatomy, Udine University Hospital, 33100 Udine, Italy
| | - Annarosa Cussigh
- Clinical Pathology, Udine University Hospital, 33100 Udine, Italy
| | - Sara Cmet
- Clinical Pathology, Udine University Hospital, 33100 Udine, Italy
| | - Davide Bitetto
- Hepatology and Liver Transplantation Unit, Department of Specialized Medicine, Udine University Hospital, 33100 Udine, Italy
| | - Ezio Fornasiere
- Hepatology and Liver Transplantation Unit, Department of Specialized Medicine, Udine University Hospital, 33100 Udine, Italy
| | - Elisa Fumolo
- Hepatology and Liver Transplantation Unit, Department of Specialized Medicine, Udine University Hospital, 33100 Udine, Italy
| | - Carla Di Loreto
- Department of Medicine, Institute of Pathological Anatomy, Udine University Hospital, 33100 Udine, Italy
| | - Edmondo Falleti
- Hepatology and Liver Transplantation Unit, Department of Specialized Medicine, Udine University Hospital, 33100 Udine, Italy
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5
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Zhang X, Jain D. The many faces and pathologic diagnostic challenges of autoimmune hepatitis. Hum Pathol 2023; 132:114-125. [PMID: 35753409 DOI: 10.1016/j.humpath.2022.06.019] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 06/16/2022] [Accepted: 06/17/2022] [Indexed: 02/07/2023]
Abstract
Autoimmune hepatitis (AIH) is an immune-mediated chronic inflammatory liver disease, characterized by hypergammaglobulinemia, the presence of specific autoantibodies, and typical abnormalities in liver histology. Prompt diagnosis and initiation of immunosuppressive treatment are necessary for both chronic and acute onset AIH to prevent progression to end-stage liver disease or fatal liver failure. However, the diagnosis of AIH is challenging mainly because of its heterogeneous clinical, serological and pathological features. Although portal lymphoplasmacytosis and interface hepatitis are the most typical histological features of AIH, many other histological features can be observed in AIH, including emperipolesis, hepatocyte rosettes, and Kupffer cell hyaline globules. Recent studies have questioned emperipolesis and hepatocyte rosette formation as typical features of AIH, and atypical clinical and histological presentations have also been recognized. This led an international working group to propose the modified AIH diagnostic criteria. However, it is well recognized that there are no pathognomonic characteristics that can be used to diagnose AIH and careful clinicopathological correlation is required to arrive at the correct diagnosis. The aim of this review is to summarize the histological features of AIH, its varied histopathologic spectrum, recent updates and major differential diagnoses in routine clinical practice.
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Affiliation(s)
- Xuchen Zhang
- Department of Pathology, Yale School of Medicine, New Haven, CT, 06520, United States.
| | - Dhanpat Jain
- Department of Pathology, Yale School of Medicine, New Haven, CT, 06520, United States.
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6
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Khedr MA, Salem TA, Boghdadi GM, Elharoun AS, El-Shahaway AA, Atallah HR, Sira MM. Seronegative autoimmune hepatitis in children : A real diagnostic challenge. Wien Klin Wochenschr 2022; 134:195-201. [PMID: 34283299 DOI: 10.1007/s00508-021-01907-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 06/11/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIM Classical autoimmune hepatitis (AIH) is characterized by the presence of conventional autoantibodies (anti-smooth muscle, antinuclear and anti-liver-kidney-microsomal antibodies). The absence of such autoantibodies in some patients does not preclude AIH diagnosis or the need for its treatment. This group of patients was termed seronegative AIH. Whether non-conventional autoantibodies can identify this group of patients is still elusive. We aimed to study the prevalence of seronegativity of conventional autoantibodies and the occurrence of non-conventional autoantibodies in children with AIH. METHODS In this study, 55 children with AIH were investigated for non-conventional autoantibodies (anti-neutrophil cytoplasmic antibodies, antibodies to soluble liver antigen, anti-tissue transglutaminase and antiplatelet antibodies). All the patients received immunosuppressive therapy and were assessed for treatment response. RESULTS Of the patients 44 had classical AIH (type 1, 70.09%, type 2, 9.09%) and 20% were seronegative. The four studied non-conventional autoantibodies occurred in four patients, one for each. All non-conventional autoantibodies were exclusively associated with type 1 AIH. The clinical profile, ultrasonographic findings, liver biochemistry and histopathological findings were comparable in the classical and seronegative AIH. The majority of patients with classical (72.7%) and seronegative (54.5%) AIH were treatment responders. CONCLUSION Seronegative AIH represents a substantial percentage of pediatric patients diagnosed with AIH. They were even negative for non-conventional autoantibodies. Furthermore, apart from autoantibodies, seronegative AIH is almost indistinguishable from the classical AIH and the majority of patients were treatment responders. This favorable response to immunosuppression deserves sustainable efforts for considering such a diagnosis and start therapy to halt disease progression is worthwhile.
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Affiliation(s)
- Mohammed A Khedr
- Department of Pediatric Hepatology, Gastroenterology and Nutrition, National Liver Institute, Menoufia University, 32511, Shebin El-koom, Menoufia, Egypt
| | - Tahany A Salem
- Department of Pediatric Hepatology, Gastroenterology and Nutrition, National Liver Institute, Menoufia University, 32511, Shebin El-koom, Menoufia, Egypt.
| | - Ghada M Boghdadi
- Department of Immunology Research Laboratories, Microbiology and Immunology, Faculty of Medicine, Zagazig University, 44519, El-Sharkiya, Egypt
| | - Ahmed S Elharoun
- Department of Microbiology and Immunology, Faculty of Medicine, Menoufia University, Shebin El-koom, Menoufia, Egypt
| | - Allia A El-Shahaway
- Department of Immunology Research Laboratories, Microbiology and Immunology, Faculty of Medicine, Zagazig University, 44519, El-Sharkiya, Egypt
| | - Hany R Atallah
- Department of Pediatrics, Ahmed Maher Teaching Hospital, Ministry of Health, Cairo, Egypt
| | - Mostafa M Sira
- Department of Pediatric Hepatology, Gastroenterology and Nutrition, National Liver Institute, Menoufia University, 32511, Shebin El-koom, Menoufia, Egypt
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7
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Kemme S, Mack CL. Pediatric Autoimmune Liver Diseases: Autoimmune Hepatitis and Primary Sclerosing Cholangitis. Pediatr Clin North Am 2021; 68:1293-1307. [PMID: 34736590 DOI: 10.1016/j.pcl.2021.07.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
In chronic hepatitis, a broad differential diagnosis should be considered to accurately identify the cause(s) of liver injury. Autoimmune liver diseases (autoimmune hepatitis, primary sclerosing cholangitis, overlap syndrome) can occur in the setting of limited symptoms; therefore, a high index of suspicion and appropriate diagnostic workup should be performed. Most children with autoimmune hepatitis achieve sustained remission with medical therapy; however, there are no equivalent therapies for primary sclerosing cholangitis that impact the progression of disease. Research should include biomarker studies to predict histologic remission in autoimmune hepatitis and mechanistic studies to define future treatment targets for primary sclerosing cholangitis.
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Affiliation(s)
- Sarah Kemme
- Section of Gastroenterology, Hepatology, and Nutrition, Digestive Health Institute, University of Colorado Denver School of Medicine and Children's Hospital Colorado, 13123 East 16th Avenue, Mailstop B290, Aurora, CO 80045, USA.
| | - Cara L Mack
- Section of Gastroenterology, Hepatology, and Nutrition, Digestive Health Institute, University of Colorado Denver School of Medicine and Children's Hospital Colorado, 13123 East 16th Avenue, Mailstop B290, Aurora, CO 80045, USA
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8
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Rahim MN, Miquel R, Heneghan MA. Approach to the patient with acute severe autoimmune hepatitis. JHEP Rep 2020; 2:100149. [PMID: 32995712 PMCID: PMC7509236 DOI: 10.1016/j.jhepr.2020.100149] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Revised: 07/09/2020] [Accepted: 07/15/2020] [Indexed: 12/11/2022] Open
Abstract
Autoimmune hepatitis is associated with varied clinical presentations and natural history, as well as somewhat unpredictable treatment responses. Understanding how to stratify patients who require further escalation of therapy will help clinicians manage these patients. The presentation of acute severe autoimmune hepatitis (AS-AIH) is relatively uncommon, although its prevalence is potentially greater than currently perceived. Previous studies consist of small retrospective single-centre series and are not directly comparable due to the diversity of presentations, disease definitions and non-standardised treatment regimens. We define AS-AIH as those who present acutely with AIH and are icteric with an international normalised ratio ≥1.5 and no evidence of hepatic encephalopathy. Those with hepatic encephalopathy should be defined as having AS-AIH with acute liver failure. In this review, we provide a structured practical approach for diagnosing and managing this unique group of patients.
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Key Words
- ACLF, acute-on-chronic liver failure
- AIH, autoimmune hepatitis
- ALF, acute liver failure
- ALI, acute liver injury
- ALT, alanine aminotransferase
- ANA, anti-nuclear antibody
- AS-AIH, acute severe autoimmune hepatitis
- ASMA, anti-smooth muscle antibody
- AST, aspartate aminotransferase
- AUROC, analysis of area under the receiver operator characteristic curve
- Acute liver failure
- Acute severe presentation
- Autoimmune hepatitis
- CT, computed tomography
- Corticosteroids
- DILI, drug-induced liver injury
- EBV, Epstein-Barr virus
- HE, hepatic encephalopathy
- HLA, human leukocyte antigen
- IAIHG, International Autoimmune Hepatitis Group
- INR, international normalised ratio
- LT, liver transplantation
- Liver transplantation
- MELD, model for end-stage liver disease
- MELD-Na, model for end-stage liver disease-sodium
- MHN, massive hepatic necrosis
- NAC, N-acetylcysteine
- PT, prothrombin time
- UKELD, United Kingdom end-stage liver disease
- USALF, United States Acute Liver Failure
- anti-LC-1, anti-liver cytosol-1
- anti-LKM, anti-liver kidney microsomal
- anti-SLA/LP, anti-soluble liver antigen/liver pancreas
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Affiliation(s)
- Mussarat N. Rahim
- Institute of Liver Studies, King's College Hospital, London, SE5 9RS, UK
| | - Rosa Miquel
- Liver Histopathology Laboratory, King's College Hospital, London, SE5 9RS, UK
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9
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Mack CL, Adams D, Assis DN, Kerkar N, Manns MP, Mayo MJ, Vierling JM, Alsawas M, Murad MH, Czaja AJ. Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases. Hepatology 2020; 72:671-722. [PMID: 31863477 DOI: 10.1002/hep.31065] [Citation(s) in RCA: 548] [Impact Index Per Article: 109.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Accepted: 11/25/2019] [Indexed: 02/06/2023]
Affiliation(s)
- Cara L Mack
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
| | - David Adams
- Centre for Liver Research, University of Birmingham, Birmingham, UK
| | - David N Assis
- Department of Internal Medicine, Yale School of Medicine, New Haven, CT
| | - Nanda Kerkar
- Golisano Children's Hospital at Strong, University of Rochester Medical Center, New York, NY
| | - Michael P Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Marlyn J Mayo
- Division of Digestive and Liver Diseases, University of Texas SW Medical Center, Dallas, TX
| | - John M Vierling
- Medicine and Surgery, Baylor College of Medicine, Houston, TX
| | | | - Mohammad H Murad
- Mayo Knowledge and Encounter Research Unit, Mayo Clinic College of Medicine, Rochester, MN
| | - Albert J Czaja
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN
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10
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Aljumah AA, Al Jarallah B, Albenmousa A, Al Khathlan A, Al Zanbagi A, Al Quaiz M, Al-Judaibi B, Nabrawi K, Al Hamoudi W, Alghamdi M, Fallatah H. The Saudi association for the study of liver diseases and transplantation clinical practice guidelines for management of autoimmune hepatitis. Saudi J Gastroenterol 2018; 24:S1-S20. [PMID: 30264737 PMCID: PMC6305081 DOI: 10.4103/sjg.sjg_159_18] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Affiliation(s)
- Abdulrahman A. Aljumah
- Division of Hepatology, Hepatobiliary Sciences and Organ Transplant Center, King Abdulaziz Medical City and King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Badr Al Jarallah
- Department of Medicine, Division of Gastroenterology, Al Qassim University, Al Qassim, Saudi Arabia
| | - Ali Albenmousa
- Department of Gastroenterology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Abdullah Al Khathlan
- Department of Medicine, Division of Gastroenterology, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Adnan Al Zanbagi
- Department of Medicine, Division of Gastroenterology, King Abdullah Medical City, Makkah, Saudi Arabia
| | - Mohammed Al Quaiz
- Department of Medicine, Section of Gastroenterology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Bandar Al-Judaibi
- Department of Medicine, University of Rochester, Rochester City, New York State, USA
| | - Khalid Nabrawi
- Department of Internal Medicine, Aseer Central Hospital, Abha, Saudi Arabia
| | - Waleed Al Hamoudi
- Department of Medicine, Division of Gastroenterology, King Saud University, Riyadh, Saudi Arabia
| | - Mohammed Alghamdi
- Department of Internal Medicine, King Fahad Military Medical City, Dhahran, Saudi Arabia
| | - Hind Fallatah
- Department of Medicine, Division of Gastroenterology and Hepatology, King Abdulaziz University, Jeddah, Saudi Arabia
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11
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Clinical features of autoimmune hepatitis with acute presentation: a Japanese nationwide survey. J Gastroenterol 2018; 53:1079-1088. [PMID: 29476251 DOI: 10.1007/s00535-018-1444-4] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Accepted: 02/15/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Autoimmune hepatitis (AIH) is characterized by progressive inflammation and necrosis of hepatocytes and eventually leads to a variety of phenotypes, including acute liver dysfunction, chronic progressive liver disease, and fulminant hepatic failure. Although the precise mechanisms of AIH are unknown, environmental factors may trigger disease onset in genetically predisposed individuals. Patients with the recently established entity of AIH with acute presentation often display atypical clinical features that mimic those of acute hepatitis forms even though AIH is categorized as a chronic liver disease. The aim of this study was to identify the precise clinical features of AIH with acute presentation. METHODS Eighty-six AIH patients with acute presentation were retrospectively enrolled from facilities across Japan and analyzed for clinical features, histopathological findings, and disease outcomes. RESULTS Seventy-five patients were female and 11 were male. Patient age ranged from adolescent to over 80 years old, with a median age of 55 years. Median alanine transaminase (ALT) was 776 U/L and median immunoglobulin G (IgG) was 1671 mg/dL. There were no significant differences between genders in terms of ALT (P = 0.27) or IgG (P = 0.51). The number of patients without and with histopathological fibrosis was 29 and 57, respectively. The patients with fibrosis were significantly older than those without (P = 0.015), but no other differences in clinical or histopathological findings were observed. Moreover, antinuclear antibody (ANA)-positive (defined as × 40, N = 63) and -negative (N = 23) patients showed no significant differences in clinical or histopathological findings or disease outcomes. Twenty-five patients experienced disease relapse and two patients died during the study period. ALP ≥ 500 U/L [odds ratio (OR) 3.20; 95% confidence interval (CI) 1.12-9.10; P < 0.030] and GGT ≥ 200 U/L (OR 2.98; 95% CI 1.01-8.77; P = 0.047) were identified as independent risk factors of disease relapse. CONCLUSIONS AIH with acute presentation is a newly recognized disease entity for which diagnostic hallmarks, such as ALT, fibrosis, and ANA, are needed. Further investigation is also required on the mechanisms of this disorder. Clinicians should be mindful of disease relapse during patient care.
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12
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Czaja AJ. Emerging therapeutic biomarkers of autoimmune hepatitis and their impact on current and future management. Expert Rev Gastroenterol Hepatol 2018. [PMID: 29540068 DOI: 10.1080/17474124.2018.1453356] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Autoimmune hepatitis lacks a quantifiable biomarker that is close to its pathogenic mechanisms and that accurately reflects inflammatory activity, correlates with treatment response, and ensures inactive disease before treatment withdrawal. Areas covered: Micro-ribonucleic acids, programmed death-1 protein and its ligands, macrophage migration inhibitory factor, soluble CD163, B cell activating factor, and metabolite patterns in blood were considered the leading candidates as therapeutic biomarkers after search of PubMed from August 1981 to August 2017 using the search words 'biomarkers of autoimmune hepatitis'. Expert commentary: Each of the candidate biomarkers is close to the putative pathogenic mechanisms of autoimmune hepatitis, and each has attributes that support its potential role as a surrogate marker of inflammatory activity that can be monitored during treatment. Future studies must demonstrate the superiority of each biomarker to conventional indices of inflammatory activity and validate their correlation with treatment response and outcome. A reliable therapeutic biomarker would facilitate the individualization of current management algorithms, ensure that pathogenic mechanisms were disrupted or eliminated prior to treatment withdrawal, and reduce the frequency of relapse or unnecessary protracted therapy. The biomarker might also prove to be a target of next-generation therapies.
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Affiliation(s)
- Albert J Czaja
- a Division of Gastroenterology and Hepatology , Mayo Clinic College of Medicine and Science , Rochester , MN , USA
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13
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Abstract
GOALS The aim of this study was to analyze the natural history and treatment outcomes of autoimmune hepatitis (AIH) variants presenting with severe-AIH. BACKGROUND Severe acute presentation is an uncommon manifestation of AIH, and it remains poorly characterized. MATERIALS AND METHODS We included 101 patients with AIH from January 2011 to December 2015. Patients were classified as seropositive-AIH and seronegative-AIH. Patients with acute liver failure, acute-on-chronic liver failure, and severe acute hepatitis were defined as severe-AIH patients. Patient characteristics and treatment outcomes with follow-up until 12 months were analyzed between the different groups. RESULTS Out of 101 cases, 24 (23.76%) had severe AIH. Of them 9 (37.5%) had severe acute hepatitis, 3 (12.5%) had acute liver failure, and 12 (50%) had acute-on-chronic liver failure. Seronegative-AIH patients presented with severe-AIH significantly more frequently compared with seropositive-AIH patients (50% vs. 20.27%, P=0.022). Severe-AIH had 50% complete responders, 25% partial responders, and 25% treatment failures. Jaundice (88.88% vs. 68.7%, P=0.048), encephalopathy (55.55% vs. 6.66%, P=0.014), and higher international normalized ratio values (2.17±0.60 vs. 1.82±0.14, P=0.038) were factors associated with nonresponse rather than the presence or absence of autoantibodies in severe-AIH. The hazard ratio for predicting remission in the non-severe AIH group as compared with the severe-AIH group was 1.502, which was statistically not significant (95% CI, 0.799-2.827; P=0.205). CONCLUSION Approximately 24% of patients with AIH have severe-AIH. Conventional autoantibodies are often absent in severe-AIH; however, it does not alter the outcome. Immunosuppressants should be given expediently in patients with severe-AIH.
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Than NN, Ching DKS, Hodson J, McDowell P, Mann J, Gupta R, Salazar E, Ngu JH, Oo YH. Difference in clinical presentation, immunology profile and treatment response of type 1 autoimmune hepatitis between United Kingdom and Singapore patients. Hepatol Int 2016; 10:673-9. [PMID: 27101826 PMCID: PMC4939157 DOI: 10.1007/s12072-016-9727-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2015] [Accepted: 03/21/2016] [Indexed: 01/10/2023]
Abstract
Background Autoimmune hepatitis (AIH) is an immune-mediated liver disease of unknown etiology. Increasing incidence of AIH in Asian patients has been reported. However, the phenotypic difference of Asian patients in Europe and Asia has still not been explored. Aim To evaluate the clinical presentation, biochemical and immunological profiles, treatment response and survival outcome of type 1 AIH from two tertiary liver transplant centres (United Kingdom and Singapore). Method Patients who fulfilled the simplified diagnostic scoring criteria of AIH were included in the study. Patients with overlap syndrome were excluded. Results Totals of 40 Asian patients and 159 Caucasian patients from the University Hospital of Birmingham National Health Service Foundation Trust, UK, were compared with 57 Asian patients from Singapore General Hospital, Singapore. Asian patients from Singapore present significantly much later (median 55 vs. 32 years, p < 0.001), had higher MELD (p < 0.001) with lower albumin (p < 0.001) and higher bilirubin (p < 0.001) and lower ASMA positivity (p < 0.001) at diagnosis compared to UK Asian. Jaundice at presentation was much higher in Singapore Asian patients compared to UK Asian (53 vs. 30 %) but cirrhosis at diagnosis was more common in UK patients. Associated autoimmune conditions were less commonly seen in Singapore Asians. Comparing between UK cohorts, Asian patients present at younger age and have higher IgG level compared to Caucasian. Overall, 5-year transplant-free survival in all three cohorts was similar (p = 0.846). Conclusion We demonstrate that AIH patients from Singapore present at older age with jaundice and have a low positivity of SMA. Despite these differences, transplant-free survival is similar in the two groups.
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Affiliation(s)
- Nwe Ni Than
- Centre for Liver Research and NIHR Biomedical Research Unit in Liver Diseases, Institute of Immunology and Immunotherapy, University of Birmingham, Vincent Drive, Edgbaston, Birmingham, B15 2TT, UK.,Liver and Hepatobiliary Unit, Queen Elizabeth Hospital, Birmingham, UK
| | - Doreen Koay Siew Ching
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore, Singapore
| | - James Hodson
- Institute of Translational Medicine, Queen Elizabeth Hospital, Birmingham, UK
| | - Patrick McDowell
- Centre for Liver Research and NIHR Biomedical Research Unit in Liver Diseases, Institute of Immunology and Immunotherapy, University of Birmingham, Vincent Drive, Edgbaston, Birmingham, B15 2TT, UK
| | | | - Ravi Gupta
- Liver and Hepatobiliary Unit, Queen Elizabeth Hospital, Birmingham, UK
| | - Ennaliza Salazar
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore, Singapore
| | - Jing Hieng Ngu
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore, Singapore
| | - Ye Htun Oo
- Centre for Liver Research and NIHR Biomedical Research Unit in Liver Diseases, Institute of Immunology and Immunotherapy, University of Birmingham, Vincent Drive, Edgbaston, Birmingham, B15 2TT, UK. .,Liver and Hepatobiliary Unit, Queen Elizabeth Hospital, Birmingham, UK.
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Czaja AJ. Diagnosis and Management of Autoimmune Hepatitis: Current Status and Future Directions. Gut Liver 2016; 10:177-203. [PMID: 26934884 PMCID: PMC4780448 DOI: 10.5009/gnl15352] [Citation(s) in RCA: 101] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2015] [Accepted: 11/04/2015] [Indexed: 02/06/2023] Open
Abstract
Autoimmune hepatitis is characterized by autoantibodies, hypergammaglobulinemia, and interface hepatitis on histological examination. The features lack diagnostic specificity, and other diseases that may resemble autoimmune hepatitis must be excluded. The clinical presentation may be acute, acute severe (fulminant), or asymptomatic; conventional autoantibodies may be absent; centrilobular necrosis and bile duct changes may be present; and the disease may occur after liver transplantation or with features that suggest overlapping disorders. The diagnostic criteria have been codified, and diagnostic scoring systems can support clinical judgment. Nonstandard autoantibodies, including antibodies to actin, α-actinin, soluble liver antigen, perinuclear antineutrophil antigen, asialoglycoprotein receptor, and liver cytosol type 1, are tools that can support the diagnosis, especially in patients with atypical features. Prednisone or prednisolone in combination with azathioprine is the preferred treatment, and strategies using these medications in various doses can ameliorate treatment failure, incomplete response, drug intolerance, and relapse after drug withdrawal. Budesonide, mycophenolate mofetil, and calcineurin inhibitors can be considered in selected patients as frontline or salvage therapies. Molecular (recombinant proteins and monoclonal antibodies), cellular (adoptive transfer and antigenic manipulation), and pharmacological (antioxidants, antifibrotics, and antiapoptotic agents) interventions constitute future directions in management. The evolving knowledge of the pathogenic pathways and the advances in technology promise new management algorithms.
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Affiliation(s)
- Albert J. Czaja
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN,
USA
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16
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Muratori P, Lalanne C, Barbato E, Fabbri A, Cassani F, Lenzi M, Muratori L. Features and Progression of Asymptomatic Autoimmune Hepatitis in Italy. Clin Gastroenterol Hepatol 2016; 14:139-146. [PMID: 26192146 DOI: 10.1016/j.cgh.2015.07.017] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2015] [Revised: 06/23/2015] [Accepted: 07/09/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Patients with autoimmune hepatitis (AIH) can present with symptoms ranging from those that are insidious and nonspecific to acute hepatitis with jaundice. However, some patients have no symptoms at diagnosis and are identified incidentally. We investigated disease progression and outcomes of these 2 groups of patients. METHODS We performed a retrospective study to compare clinical, immunologic, and histologic features and outcomes of patients with asymptomatic vs. symptomatic AIH. We analyzed data collected from 305 patients (90 asymptomatic and 215 with symptoms), diagnosed with AIH from 1994 and 2013, at the Center for the Study and Treatment of the Autoimmune Diseases of the Liver and Biliary System in Bologna, Italy. RESULTS At diagnosis, patients with asymptomatic AIH had significantly lower mean levels of alanine aminotransferase (7.0- ± 8.0-fold the upper limit of normal) than patients with symptomatic disease (23.0- ± 18.0-fold the upper limit of normal; P < .001), and lower mean levels of bilirubin (1.4 ± 1.4 mg/dL vs. 8.6 ± 10.4 mg/dL; P < .001). Asymptomatic patients also had significantly lower histologic grades (7.0 ± 2.5) than symptomatic patients (9.0 ± 2.9; P < .001). However, larger proportions of asymptomatic patients had anti-liver/kidney microsomal antibodies type 1 (26.8% vs. 13.1%; P < .006), and associated autoimmune thyroid (26.7% vs. 12.6%; P = .003) or skin (8.9% vs. 2.3%; P = .010) disorders. Age at onset, sex, response to therapy, disease progression, genetic factors, and other autoantibody markers did not differ between patients with asymptomatic vs. symptomatic disease. CONCLUSIONS Patients with asymptomatic vs. symptomatic AIH have similar courses of disease progression and responses to immunosuppressive agents, and therefore should receive the same treatment. Patients affected by thyroid or dermatologic autoimmune disorders are at increased risk of developing subclinical liver disease, and should be assessed routinely for AIH.
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Affiliation(s)
- Paolo Muratori
- Centro per lo Studio e la Cura delle Malattie Autoimmuni del Fegato e delle Vie Biliari, Policlinico di Sant'Orsola, Bologna, Italy; Dipartimento di Scienze Mediche e Chirurgiche, Alma Mater Studiorum-Università di Bologna, Bologna, Italy
| | - Claudine Lalanne
- Centro per lo Studio e la Cura delle Malattie Autoimmuni del Fegato e delle Vie Biliari, Policlinico di Sant'Orsola, Bologna, Italy; Dipartimento di Scienze Mediche e Chirurgiche, Alma Mater Studiorum-Università di Bologna, Bologna, Italy
| | - Erica Barbato
- Centro per lo Studio e la Cura delle Malattie Autoimmuni del Fegato e delle Vie Biliari, Policlinico di Sant'Orsola, Bologna, Italy; Dipartimento di Scienze Mediche e Chirurgiche, Alma Mater Studiorum-Università di Bologna, Bologna, Italy
| | - Angela Fabbri
- Centro per lo Studio e la Cura delle Malattie Autoimmuni del Fegato e delle Vie Biliari, Policlinico di Sant'Orsola, Bologna, Italy; Dipartimento di Scienze Mediche e Chirurgiche, Alma Mater Studiorum-Università di Bologna, Bologna, Italy
| | - Fabio Cassani
- Centro per lo Studio e la Cura delle Malattie Autoimmuni del Fegato e delle Vie Biliari, Policlinico di Sant'Orsola, Bologna, Italy; Policlinico di Sant'Orsola, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Marco Lenzi
- Centro per lo Studio e la Cura delle Malattie Autoimmuni del Fegato e delle Vie Biliari, Policlinico di Sant'Orsola, Bologna, Italy; Dipartimento di Scienze Mediche e Chirurgiche, Alma Mater Studiorum-Università di Bologna, Bologna, Italy
| | - Luigi Muratori
- Centro per lo Studio e la Cura delle Malattie Autoimmuni del Fegato e delle Vie Biliari, Policlinico di Sant'Orsola, Bologna, Italy; Dipartimento di Scienze Mediche e Chirurgiche, Alma Mater Studiorum-Università di Bologna, Bologna, Italy.
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17
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Abdel-Ghaffar TY, Sira MM, Sira AM, Salem TA, El-Sharawy AA, El Naghi S. Serological markers of autoimmunity in children with hepatitis A: relation to acute and fulminant presentation. Eur J Gastroenterol Hepatol 2015; 27:1161-1169. [PMID: 26062080 DOI: 10.1097/meg.0000000000000413] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Hepatitis A virus (HAV) infection tends to be a self-limiting disease without serious sequelae, but fulminant hepatitis, with a high mortality, develops in 0.1-0.2% of the cases. Sometimes, HAV infection precipitates autoimmune hepatitis (AIH). We aimed to assess the frequency and clinical significance of serologic markers of autoimmunity during hepatitis A infection with an acute or fulminant presentation compared with those in AIH. METHODS The study included 126 children: 46 with HAV infection (33 with acute and 13 with fulminant presentation), 53 with AIH, and 27 healthy controls. In all, we measured autoantibodies titer (antinuclear antibody, antismooth muscle antibody, and liver kidney microsomal antibody-1) and serum gammaglobulins. RESULTS Autoantibodies were detected in the majority of HAV (63.1%) and AIH (79.2%) groups, but in none of the controls. Gammaglobulins were significantly higher in the HAV group (1.93±0.57 g/dl) than in the controls (1.32±0.29 g/dl), but lower than that in the AIH group (2.93±1.2 g/dl) (P<0.0001 for all). In the HAV group, gammaglobulins were significantly higher in those with fulminant (2.21±0.46 g/dl) than in those with acute presentation (1.82±0.57 g/dl) (P=0.019), but comparable with that in AIH (P=0.095). Gammaglobulins correlated significantly with disease severity in both HAV and AIH groups. CONCLUSION Hypergammaglobulinemia and a high occurrence of autoantibodies are encountered in HAV infection. This may support the immunological basis of its pathogenesis. Moreover, the higher gammaglobulins in fulminant HAV, with an insignificant difference from that in AIH, suggest that a more aggressive immunological reaction is related to this presentation.
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Affiliation(s)
- Tawhida Y Abdel-Ghaffar
- aYassin Abdel-Ghaffar Charity Center for Liver Disease and Research bDepartment of Pediatrics, Faculty of Medicine, Ain Shams University cPediatric Department, National Hepatology and Tropical Medicine Research Institute, Cairo Departments of dPediatric Hepatology eClinical Pathology, National Liver Institute, Menofiya University, Menofiya, Egypt
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18
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Muratori P, Lalanne C, Fabbri A, Cassani F, Lenzi M, Muratori L. Type 1 and type 2 autoimmune hepatitis in adults share the same clinical phenotype. Aliment Pharmacol Ther 2015; 41:1281-1287. [PMID: 25898847 DOI: 10.1111/apt.13210] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2015] [Revised: 02/24/2015] [Accepted: 03/31/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND Autoimmune hepatitis (AIH) is historically classified into type 1 and type 2 on the basis of the autoantibody profile, anti-nuclear and/or anti-smooth muscle antibodies being the serological markers of type 1 AIH, whereas anti-liver/kidney microsomal antibody type 1 and/or anti-liver cytosol antibody type 1 characterise type 2 AIH. AIM To evaluate whether such a distinction is justified on the basis of different expression of the disease in adults. METHODS Twenty-six adult patients with type 2 AIH and 52 age- and sex-matched patients with type 1 AIH, representative of the entire cohort of adults with type 1 AIH, were compared at onset and during follow-up. RESULTS At diagnosis, median age was 26 years (range 17-53), female sex 86%, acute presentation 43%, severe liver histology 54%, cirrhosis 14%, complete response to treatment 52%, progression of the disease 17%, and median disease duration 72 months (range 12-280). HLA-DRB1*0301 was present in 26%, HLA-DRB1*0401 in 23% and HLA-DRB1*0701 in 25%. Clinical presentation, biochemical parameters, severe liver histology, genetic profile, response rate and progression of the disease were identical between type 1 and type 2 AIH. CONCLUSION There is not enough clinical, biochemical, histological or genetic reason to subdivide adults with autoimmune hepatitis into type 1 and type 2 on the basis of the autoantibody profile, and the term 'autoimmune hepatitis' without qualification should be preferred.
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Affiliation(s)
- P Muratori
- Centro per lo Studio e la Cura delle Malattie Autoimmuni del Fegato e delle Vie Biliari, Bologna, Italy
- Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Alma Mater Studiorum - Università di Bologna, Bologna, Italy
| | - C Lalanne
- Centro per lo Studio e la Cura delle Malattie Autoimmuni del Fegato e delle Vie Biliari, Bologna, Italy
- Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Alma Mater Studiorum - Università di Bologna, Bologna, Italy
| | - A Fabbri
- Centro per lo Studio e la Cura delle Malattie Autoimmuni del Fegato e delle Vie Biliari, Bologna, Italy
- Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Alma Mater Studiorum - Università di Bologna, Bologna, Italy
| | - F Cassani
- Centro per lo Studio e la Cura delle Malattie Autoimmuni del Fegato e delle Vie Biliari, Bologna, Italy
- Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola-Malpighi, via Massarenti 9, Bologna 40138, Bologna, Italy
| | - M Lenzi
- Centro per lo Studio e la Cura delle Malattie Autoimmuni del Fegato e delle Vie Biliari, Bologna, Italy
- Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Alma Mater Studiorum - Università di Bologna, Bologna, Italy
| | - L Muratori
- Centro per lo Studio e la Cura delle Malattie Autoimmuni del Fegato e delle Vie Biliari, Bologna, Italy
- Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Alma Mater Studiorum - Università di Bologna, Bologna, Italy
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Schotte H, Willeke P, Schmalhorst J, Schlüter B. Diagnostic Performance of an Anti-Actin Autoantibody Binding Enzyme Immunodot Blot in Autoimmune Hepatitis Type 1. J Clin Lab Anal 2014; 30:123-9. [PMID: 25425293 DOI: 10.1002/jcla.21825] [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] [Received: 06/01/2014] [Accepted: 10/22/2014] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND A serologic hallmark of autoimmune hepatitis (AIH) type 1 are anti-smooth muscle autoantibodies (ASMA) with specificity for filamentous actin (F-actin; AAA (anti-actin antibodies)), traditionally detected by indirect immunofluorescence (IFT) using rat liver, kidney, and stomach tissue sections as substrates. However, IFT is a subjective method requiring an experienced investigator. Therefore, a more objective technique for the detection of AAA may be a helpful diagnostic tool. METHODS In a retrospective study with cross-sectional design, we evaluated AAA detected by an enzyme immunodot blot (IDB; Liver5 IgG BlueDot, D-tek, Mons, Belgium). Serum samples of patients with AIH type 1 (n = 47) and specified controls (n = 142) were included. For comparison, standard IFT was applied to rat LKS (liver, kidney, stomach) triple tissue sections. RESULTS IDB readings were done by two independent investigators (92% concordance). The diagnostic sensitivity of the AAA-IDB was 70%, compared to 51% of AAA-IFT (n.s.). The diagnostic specificity of AAA-IDB was significantly lower compared to AAA-IFT (76% vs. 94%; P < 0.0005). Correspondingly, the positive predictive value (49% vs. 75%; P < 0.05) and positive likelihood ratio (2.9 vs. 8.5) differed significantly. Neither prescreening for ANA or ASMA, nor the exclusion of infectious hepatopathies resulted in a significantly better diagnostic performance of the IDB. CONCLUSION Compared to standard IFT, testing for AAA via IDB did not result in a significantly better diagnostic performance for AIH type 1. A blot with higher antigen binding specificity may be more functional.
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Affiliation(s)
| | - Peter Willeke
- Medizinische Klinik und Poliklinik D, Universitätsklinikum Münster, Germany
| | | | - Bernhard Schlüter
- Centrum für Laboratoriumsmedizin, Universitätsklinikum Münster, Germany
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Nares-Cisneros J, Jaramillo-Rodríguez Y. Hepatitis autoinmune en niños: evolución de 20 casos del norte de México. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2014; 79:238-43. [DOI: 10.1016/j.rgmx.2014.08.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/18/2014] [Revised: 08/10/2014] [Accepted: 08/13/2014] [Indexed: 12/11/2022]
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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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Nares-Cisneros J, Jaramillo-Rodríguez Y. Autoimmune hepatitis in children: Progression of 20 cases in northern Mexico. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2014. [DOI: 10.1016/j.rgmxen.2014.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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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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Kobayashi M, Kakuda Y, Harada K, Sato Y, Sasaki M, Ikeda H, Terada M, Mukai M, Kaneko S, Nakanuma Y. Clinicopathological study of primary biliary cirrhosis with interface hepatitis compared to autoimmune hepatitis. World J Gastroenterol 2014; 20:3597-3608. [PMID: 24707143 PMCID: PMC3974527 DOI: 10.3748/wjg.v20.i13.3597] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2013] [Revised: 07/16/2013] [Accepted: 08/20/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate histological and immunohistochemical differences in hepatitis between autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) with AIH features.
METHODS: Liver needle biopsies of 41 PBC with AIH features and 43 AIH patients were examined. The activity of periportal and lobular inflammation was scored 0 (none or minimal activity) to 4 (severe), and the degree of hepatitic rosette formation and emperipolesis was semiquantatively scored 0-3. The infiltration of mononuclear cells positive for CD20, CD38, CD3, CD4, and CD8 and positive for immunoglobulins (IgG, IgM, and IgA) at the periportal areas (interface hepatitis) and in the hepatic lobules (lobular hepatitis) were semiquantitatively scored in immunostained liver sections (score 0-6). Serum aspartate aminotransferase (AST), immunoglobulins, and autoantibodies at the time of liver biopsy were correlated with the histological and immunohistochemical scores of individual lesions.
RESULTS: Lobular hepatitis, hepatitic rosette formation, and emperipolesis were more extensive and frequent in AIH than in PBC. CD3+, CD4+, and CD8+ cell infiltration scores were higher in the hepatic lobules and at the interface in AIH but were also found in PBC. The degree of mononuclear cell infiltration correlated well with the degree of interface and lobular hepatitis in PBC, but to a lesser degree in AIH. CD20+ cells were mainly found in the portal tracts and, occasionally, at the interface in both diseases. Elevated AST correlated well with the hepatocyte necroinflammation and mononuclear cell infiltration, specifically CD38+ cells in PBC. No correlation existed between autoantibodies and inflammatory cell infiltration in PBC or AIH. While most AIH cases were IgG-predominant at the interface, PBC cases were divided into IgM-predominant, IgM/IgG-equal, and IgG-predominant types, with the latter sharing several features with AIH.
CONCLUSION: These results suggest that the hepatocellular injuries associated with interface and lobular hepatitis in AIH and PBC with interface hepatitis may not be identical.
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Couto CA, Bittencourt PL, Porta G, Abrantes-Lemos CP, Carrilho FJ, Guardia BD, Cançado ELR. Antismooth muscle and antiactin antibodies are indirect markers of histological and biochemical activity of autoimmune hepatitis. Hepatology 2014; 59:592-600. [PMID: 23929663 DOI: 10.1002/hep.26666] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2013] [Accepted: 07/29/2013] [Indexed: 12/18/2022]
Abstract
UNLABELLED Reactivity and titers of autoantibodies vary during the course of autoimmune hepatitis (AIH), and some autoantibodies have been associated with disease activity and adverse outcomes after treatment. The aim of this study was to assess the autoantibody behavior in AIH and its significance as predictors of biochemical and histological remission. A total of 117 patients with AIH (mean age 18.6 [4-69] years) were evaluated and tested for autoantibodies at disease onset and successively (mean 3.2 [2-6] times) after a mean follow-up evaluation of 70 [20-185] months. Antismooth muscle (ASMA), antiliver kidney microsome type 1 (anti-LKM1), antiliver cytosol type 1 (anti-LC1), antimitochondrial, antinuclear (ANA), and antiactin antibodies (AAA) were determined at disease onset and 379 other times during the follow-up evaluation through indirect immunofluorescence in rodent tissues, HEp-2 cells, and human fibroblasts. Anti-SLA/LP were assessed 45 times in the follow-up evaluation of 19 patients using enzyme-linked immunosorbent assay (ELISA). Upon admission, AIH types 1 and 2 were observed in 95 and 17 patients, respectively. Five subjects had AIH with anti-SLA/LP as the sole markers. Patients initially negative for AAA did not develop these antibodies thereafter. ANA were detected de novo in six and three subjects with AIH types 1 and 2, respectively. After treatment, only ASMA (>1:80) and AAA (>1:40) were significantly associated with biochemical (76.9% and 79.8%) and histological features (100% and 100%) of disease activity (P < 0.001). CONCLUSION With the exception of ANA, the autoantibody profile does not markedly vary in the course of AIH. The persistence of high titers of ASMA and/or AAA in patients with AIH is associated with disease activity.
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Affiliation(s)
- Claudia A Couto
- Universidade Federal de Minas Gerais, Department of Internal Medicine, School of Medicine, Belo Horizonte, Minas Gerais, Brazil; Universidade Federal de Minas Gerais, University Hospital, Alfa Institute of Gastroenterology, Belo Horizonte, Minas Gerais, Brazil
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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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Hagymási K, Tulassay Z. [Review of overlap syndromes in autoimmune liver diseases. Diagnostic and therapeutic difficulties]. Orv Hetil 2013; 154:923-929. [PMID: 23752047 DOI: 10.1556/oh.2013.29640] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Overlap syndromes are biochemical, serological, histological and radiological overlaps across the classic autoimmune liver diseases in the presence of autoimmun hepatitis and primary biliary cirrhosis or primary sclerosing cholangitis. The exact prevalence of the disease is not known, but it may vary between 5% and 20%. Because it has no generally accepted diagnostic criteria, clinical signs, biochemical, serological, radiological and histological findings are evaluated together. Treatment depends on the predominant feature of the overlap syndrome; ursodeoxycholic acid and/or immunsuppressive (corticosteroid) treatment are used, based on observations from retrospective, non-randomized studies.
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Affiliation(s)
- Krisztina Hagymási
- Semmelweis Egyetem, Általános Orvostudományi Kar, II. Belgyógyászati Klinika, Budapest.
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Abstract
Autoimmune hepatitis is a chronic necroinflammatory disease of unknown etiology that is characterized by increased aminotransferases, serum autoantibodies, increased immunoglobulin G levels, and histological interface hepatitis. The disease does not have a pathognomonic clinical, laboratory, or histological feature; diagnosis depends on a combination of clinical and pathologic criteria which also form the basis for a weighted scoring system to aid diagnosis. Liver biopsy is an essential part of the diagnostic criteria and is also crucial to the management of the disease. This review focuses on the diagnosis, microscopic features, differential diagnosis and overlap syndromes of autoimmune hepatitis.
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Affiliation(s)
- Cristina D Cole
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 350 West 11th Street, Indianapolis, IN 46202, USA
| | - Romil Saxena
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 350 West 11th Street, Indianapolis, IN 46202, USA.
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Tachecí I, Květina J, Kuneš M, Pavlík M, Kopáčová M, Černý V, Rejchrt S, Edakkanambeth Varayil J, Bureš J. The effect of general anaesthesia on gastric myoelectric activity in experimental pigs. BMC Gastroenterol 2013; 13:48. [PMID: 23496859 PMCID: PMC3607881 DOI: 10.1186/1471-230x-13-48] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2012] [Accepted: 02/26/2013] [Indexed: 11/10/2022] Open
Abstract
Background Surface electrogastrography (EGG) is a non-invasive method for clinical assessment of gastric myoelectrical activity. Different forms of general anaesthesia might have various effects on porcine EGG. The aim of this study was to evaluate the impact of different anaesthetic agents on EGG in experimental pigs. Methods Four 15-minute EGG intervals were recorded and analysed. A baseline EGG recording was started 20 minutes after intramuscular injection of ketamine and azaperone (periods A and B). Four different regimens of general anaesthesia followed immediately after the baseline EGG (5 pigs in each experimental group): thiopental, isoflurane, nitrous oxide and isoflurane plus nitrous oxide. EGG recordings followed for the next 30 minutes under general anaesthesia (periods C and D). The dominant frequencies of slow waves were compared between the baseline intervals A and B and periods C and D under general anaesthesia. Results The mean dominant frequency was within the normal range (2.3 – 3.5 cycles per minute) in all animals in all regimens. Thiopental general anaesthesia did not influence any change of the dominant frequency of slow waves. Nitrous oxide general anaesthesia increased the dominant frequency of slow waves in a statistically significant manner (baseline: 2.93 ± 0.53 and 3.01 ± 0.53; under general anaesthesia: 3.25 ± 0.34 and 3.29 ± 0.38 cycles per minute; p < 0.001, p = 0.003, p < 0.001, p < 0.001). Nitrous oxide together with isoflurane induced a statistically significant decrease of dominant frequency in the last 15-minute interval (2.66 ± 0.55 cycles per minute) compared to the baseline recording (2.81 ± 0.49; p = 0.030). Conclusions All changes of porcine gastric myoelectric activity assessed by the dominant frequency of slow waves during EGG remained within the normal range although some of them achieved statistical significance. Thus all tested agents used for general anaesthesia can be recommended in preclinical studies with porcine models focused on gastric myoelectric activity without any risk of compromising the results. Thiopental seems to be the most suitable as it did not cause any changes at all.
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Affiliation(s)
- Ilja Tachecí
- 2nd Department of Internal Medicine - Gastroenterology, Charles University in Prague, Faculty of Medicine and University Hospital, Hradec Králové, Czech Republic.
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Abstract
Autoimmune hepatitis has two major variant phenotypes in which the features of classical disease are co-mingled with those of primary biliary cirrhosis or primary sclerosing cholangitis. These overlap syndromes lack codified diagnostic criteria, established pathogenic mechanisms, and confident management strategies. Their clinical importance relates mainly to the identification of patients who respond poorly to conventional corticosteroid treatment. Scoring systems that lack discriminative power have been used in their definition, and a clinical phenotype based on pre-defined laboratory and histological findings has not been promulgated. The frequency of overlap with primary biliary cirrhosis is 7-13 %, and the frequency of overlap with primary sclerosing cholangitis is 8-17 %. Patients with autoimmune hepatitis and features of cholestatic disease must be distinguished from patients with cholestatic disease and features of autoimmune hepatitis. Variants of the overlap syndromes include patients with small duct primary sclerosing cholangitis, antimitochondrial antibody-negative primary biliary cirrhosis, autoimmune sclerosing cholangitis, and immunoglobulin G4-associated disease. Conventional corticosteroid therapy alone or in conjunction with ursodeoxycholic acid (13-15 mg/kg daily) has been variably effective, and cyclosporine, mycophenolate mofetil, and budesonide have been beneficial in selected patients. The key cholestatic features that influence the prognosis of autoimmune hepatitis must be defined and incorporated into the definition of the syndrome rather than rely on designations that imply the co-mingling of different diseases with manifestations of variable clinical relevance. The overlap syndromes in autoimmune hepatitis are imprecise, heterogeneous, and unfounded, but they constitute a clinical reality that must be accepted, diagnosed, refined, treated, and studied.
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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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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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Trivedi PJ, Hirschfield GM. Review article: overlap syndromes and autoimmune liver disease. Aliment Pharmacol Ther 2012; 36:517-33. [PMID: 22817525 DOI: 10.1111/j.1365-2036.2012.05223.x] [Citation(s) in RCA: 89] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2012] [Revised: 03/30/2012] [Accepted: 07/01/2012] [Indexed: 12/12/2022]
Abstract
BACKGROUND Autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) all nestle within the family of autoimmune liver diseases, whereby the result of immune-mediated liver injury gives rise to varied clinical presentations. Some patients demonstrate a phenotype whereby there is evidence of either PBC or PSC together with overlapping features of AIH. Due to an absence of well-validated diagnostic criteria and a lack of large therapeutic trials, treatment of overlap conditions is empiric and extrapolated from data derived from the primary autoimmune liver diseases. AIMS To review overlaps in the context of autoimmune liver diseases. METHODS General and specific review of published articles using PubMed, Medline and Ovid search engines, alongside pre-existing clinical management protocols, guidelines, and the authors' own knowledge of the published literature. RESULTS The challenges in diagnosis, clinical presentation, determining natural history and outcome of overlaps are presented, as well as present-day management suggestions, some based on evidence, others on consensus and opinion. CONCLUSIONS Overlapping autoimmune features, be they clinical, serological, histological or radiological are not infrequent, but appropriate diagnosis remains hindered by a lack of standardised diagnostic criteria. Optimum care for those with suspected overlap should thus focus on attention to detail over the fundamental aspects of timely secure diagnosis of the dominant disease entity. Clinicians should counsel patients carefully with regard to the risks and benefits of treatment, bearing in mind the paucity of randomised and controlled outcome data for medical interventions.
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Affiliation(s)
- P J Trivedi
- Centre for Liver Research and NIHR Biomedical Research Unit, University of Birmingham, Birmingham, UK
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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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Auto-antibodies in autoimmune hepatitis: anti-smooth muscle antibodies (ASMA). Clin Res Hepatol Gastroenterol 2012; 36:189-91. [PMID: 22206849 DOI: 10.1016/j.clinre.2011.10.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2011] [Accepted: 10/14/2011] [Indexed: 02/04/2023]
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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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Muñoz-Espinosa L, Alarcon G, Mercado-Moreira A, Cordero P, Caballero E, Avalos V, Villarreal G, Senties K, Puente D, Soto J, Esqueda B, Campos G, Martínez M, Jaquez J, Ramirez A, Reyes I, Kershenobich D, Montano-Loza AJ. Performance of the international classifications criteria for autoimmune hepatitis diagnosis in Mexican patients. Autoimmunity 2011; 44:543-8. [PMID: 21875376 DOI: 10.3109/08916934.2011.592884] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
The revised score of the International Autoimmune Hepatitis Group (R-IAIHG) and the simplified criteria (SC) are used for diagnosis of autoimmune hepatitis (AIH). Our aim is to evaluate the performance of these classifications to differentiate AIH from other autoimmune liver diseases. The frequency of diagnosis of definite AIH was similar both by the R-IAIHG and the SC systems (41% versus 40%), whereas diagnosis of probable AIH was made more commonly by the R-IAIHG than the SC (59% versus 29%), and 23 patients that have been graded as definite (n = 7) or probable (n = 16) AIH by the R-IAIHG had non-diagnostic scores by the SC system. The scoring systems rendered concordant diagnosis of definite (n = 15) and probable (n = 13) AIH in 28/73 patients (38%). Discordant diagnoses of AIH were rendered in 45/73 patients (62%). The R-IAIHG exhibited a sensitivity of 95%, specificity of 90%, and positive predictive value (PPV) and negative predictive value (NPV) of 93% for both. On the other hand, the SC had a lower sensitivity (65%) but a higher specificity (100%), PPV of 100%, and NPV of 68%. In conclusion, both international scoring systems diagnosed the same number of cases as definite AIH. The R-IAIHG showed a higher sensitivity in diagnosing AIH, whereas the SC showed a higher specificity. SC are easier to apply at the bedside and exclude more patients that could have a different etiology.
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Affiliation(s)
- Linda Muñoz-Espinosa
- Liver Unit, "Dr. Jose E. Gonzalez" University Hospital, UANL, Monterrey, Nuevo Leon, Mexico.
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Björnsson E, Talwalkar J, Treeprasertsuk S, Neuhauser M, Lindor K. Patients with typical laboratory features of autoimmune hepatitis rarely need a liver biopsy for diagnosis. Clin Gastroenterol Hepatol 2011; 9:57-63. [PMID: 20723617 DOI: 10.1016/j.cgh.2010.07.016] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2010] [Revised: 07/20/2010] [Accepted: 07/23/2010] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The importance of histologic analysis of biopsy samples in the diagnosis and management of patients with autoimmune hepatitis (AIH) is unclear. METHODS Patients with AIH were identified from a 10-year database. Individuals with overlap syndromes and decompensated liver disease were excluded. The proportion of patients who fulfilled the new simplified criteria for AIH was calculated. RESULTS A total of 257 patients (203 female) with a median age of 52 years (interquartile range, 39-63 y) were diagnosed with AIH. Overall, 183 of 257 (71%) were positive for antinuclear antibodies, 116 (45%) had positive smooth muscle antibodies, and 29 of 257 (11%) were seronegative. A total of 250 (97%) patients had increased levels of autoantibodies and/or γ-globulins. In 95% (243 of 257 cases), the histology was compatible with AIH whereas 5% (14 cases) had atypical histology. Overall, 77% had a score of at least 6, indicating probable or definite AIH according to most recent criteria; 22% were diagnosed with AIH with less than 6 points and 1 patient had nonalcoholic steatohepatitis based on biopsy analysis. Immunosuppression occurred in 93% of patients. Patients with atypical versus compatible histology were similar in terms of seronegativity or γ-globulins; 86% (12 of 14) received immunosuppressive therapy despite atypical histology. CONCLUSIONS Most patients with features of AIH, based on laboratory analyses, are likely to have a compatible liver histology. Few patients have atypical histology and these findings have little impact on patient management. These findings indicate biopsy samples might not need to be collected from patients who meet other clinical criteria for AIH.
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Affiliation(s)
- Einar Björnsson
- Department of Internal Medicine, Landspitali University Hospital, Reykjavik, Iceland.
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Abstract
Autoimmune hepatitis does not have a pathognomonic feature, and its laboratory, serologic, and histologic manifestations are shared with a variety of acute and chronic liver diseases. The disease has active and quiescent phases and thus variable histologic appearances. This article outlines the many histologic faces of autoimmune hepatitis. It discusses the fulminant and acute forms, as well as the chronic hepatitic forms. Overlap syndromes with primary biliary cirrhosis and primary sclerosing cholangitis are described. The role of the pathologist in reporting the biopsies is discussed.
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Affiliation(s)
- Maha Guindi
- Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
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Knight C, Murray KF. Hepatobiliary associations with inflammatory bowel disease. Expert Rev Gastroenterol Hepatol 2009; 3:681-91. [PMID: 19929587 DOI: 10.1586/egh.09.53] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Hepatobiliary disease is not uncommon in patients with inflammatory bowel disease (IBD). The most common autoimmune hepatic associations are primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH). The immunosuppressant medications used in the treatment of IBD also have potential hepatotoxicity. PSC is most commonly associated with IBD, specifically ulcerative colitis. AIH, a more classic autoimmune disease diagnosed commonly in isolation of other conditions in the same individual, is less commonly associated with IBD. Additionally, a subgroup of patients have features of both PSC and AIH, termed overlap syndrome, that is also sometimes seen in IBD patients. This review will discuss the most common liver disease associations seen in patients with IBD: PSC, AIH and overlap syndrome. Additionally, the most common drug-related hepatotoxicities encountered when treating IBD will be reviewed.
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Affiliation(s)
- Crystal Knight
- Seattle Children's and University of Washington School of Medicine, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, 4800 Sand Point Way, NE, PO Box 5371/W-7830, Seattle, WA 98105, USA.
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