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Olivas I, Cobreros M, Londoño MC, Díaz-González Á. Budesonide in the first line treatment of patients with autoimmune hepatitis. GASTROENTEROLOGIA Y HEPATOLOGIA 2021; 45:561-570. [PMID: 34923033 DOI: 10.1016/j.gastrohep.2021.11.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 11/12/2021] [Accepted: 11/29/2021] [Indexed: 10/19/2022]
Abstract
Budesonide is a glucocorticoid characterized by its local action, with a low systemic bioavailability. Since the original trial comparing budesonide with prednisone in 2010, it is recommended as an effective alternative for the treatment of non-severe acute or chronic autoimmune hepatitis. In this document, we review the general pharmacologic properties of glucocorticoids, the available evidence for the use of budesonide as first line option for autoimmune hepatitis as well as the safety profile of the drug.
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Affiliation(s)
- Ignasi Olivas
- Liver Unit. Hospital Clínic of Barcelona. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). CIBERehd. Universitat de Barcelona, Barcelona, Spain
| | - Marina Cobreros
- Digestive Diseases Department. Marqués de Valdecilla University Hospital. Instituto de investigación sanitaria Valdecilla (IDIVAL), Santander, Spain
| | - María-Carlota Londoño
- Liver Unit. Hospital Clínic of Barcelona. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). CIBERehd. Universitat de Barcelona, Barcelona, Spain
| | - Álvaro Díaz-González
- Digestive Diseases Department. Marqués de Valdecilla University Hospital. Instituto de investigación sanitaria Valdecilla (IDIVAL), Santander, Spain
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Wang G, Tanaka A, Zhao H, Jia J, Ma X, Harada K, Wang FS, Wei L, Wang Q, Sun Y, Hong Y, Rao H, Efe C, Lau G, Payawal D, Gani R, Lindor K, Jafri W, Omata M, Sarin SK. The Asian Pacific Association for the Study of the Liver clinical practice guidance: the diagnosis and management of patients with autoimmune hepatitis. Hepatol Int 2021; 15:223-257. [PMID: 33942203 PMCID: PMC8144150 DOI: 10.1007/s12072-021-10170-1] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 02/27/2021] [Indexed: 02/06/2023]
Affiliation(s)
- Guiqiang Wang
- Peking University First Hospital, Beijing, China.
- Peking University International Hospital, Beijing, China.
| | | | - Hong Zhao
- Peking University First Hospital, Beijing, China
- Peking University International Hospital, Beijing, China
| | - Jidong Jia
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xiong Ma
- Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Kenichi Harada
- Department of Human Pathology, Kanazawa University Graduate School of Medicine Kanazawa, Kanazawa, Japan
| | - Fu-Sheng Wang
- Fifth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Lai Wei
- Beijing Tsinghua Changgung Hospital, Beijing, China
| | - Qixia Wang
- Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Ying Sun
- Fifth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Yuan Hong
- Peking University First Hospital, Beijing, China
| | - Huiying Rao
- Peking University People's Hospital, Beijing, China
| | - Cumali Efe
- Department of Gastroenterology, Harran University, Şanlıurfa, Turkey
| | - George Lau
- Humanity and Health Medical Group, Hong Kong Special Administrative Region, China
| | - Diana Payawal
- Department of Hepatology, Cardinal Santos Medical Center, Manila, Philippines
| | - Rino Gani
- Department of Internal Medicine, Cipto Mangunkusumo Hospital, University of Indonesia, Jakarta, Indonesia
| | - Keith Lindor
- College of Health Solutions, Arizona State University, Phoenix, AZ, USA
| | | | - Masao Omata
- Department of Gastroenterology, Yamanashi Prefectural Central Hospital, Kofu-City, Yamanashi, Japan
- The University of Tokyo, Tokyo, Japan
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Fawaz R, Jonas MM. Acute and Chronic Hepatitis. PEDIATRIC GASTROINTESTINAL AND LIVER DISEASE 2021:819-837.e6. [DOI: 10.1016/b978-0-323-67293-1.00075-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Bari K, Shah SA, Kaiser TE, Cohen RM, Anwar N, Kleesattel D, Sherman KE. Safety and Efficacy of Budesonide for Liver Transplant Immune Suppression: Results of a Pilot Phase 2a Trial. Liver Transpl 2020; 26:1430-1440. [PMID: 32602616 PMCID: PMC7606621 DOI: 10.1002/lt.25837] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 06/04/2020] [Accepted: 06/19/2020] [Indexed: 02/06/2023]
Abstract
Despite adverse effects like hyperglycemia, new-onset diabetes after transplant (NODAT), and infectious complications, corticosteroid use remains an important part of liver transplantation (LT) immune suppression. Budesonide, a synthetic corticosteroid, undergoes extensive first-pass hepatic metabolism with only 10% systemic bioavailability, providing an opportunity for an improved toxicity-therapeutic ratio. Although effective in the treatment of autoimmune hepatitis, the effects of budesonide for LT immune suppression are unknown. We conducted a single-center phase 2a trial to study the safety and efficacy of budesonide immunosuppressive therapy. From July 2017 to November 2018, 20 patients undergoing a first LT received budesonide tapering doses (from 9 to 3 mg) for 12 weeks. Patients were compared with matched control patients who received prednisone from the same time period. Additionally, both groups received calcineurin inhibitors and mycophenolate mofetil. Outcome measures at week 24 included rates of biopsy-proven acute cellular rejection (ACR), NODAT (hemoglobin A1c >6.4%), and infectious complications. In the budesonide arm, 1 patient developed ACR at week 5 and was removed from the study. Another patient stopped the study drug at week 8 due to persistent nausea. Rates of ACR were similar between the budesonide and control groups (5% versus 5%, P = 1.00). Three patients in the control group developed NODAT versus none in the budesonide group (15% versus 0%; P = 0.23). There were 6 infections in the control group compared with none in the budesonide group (30% versus 0; P = 0.02). These pilot data suggest that budesonide has the potential to be a safe and effective alternative to prednisone for LT immune suppression while reducing steroid-induced infections and NODAT. Randomized controlled trials are required to validate these findings.
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Affiliation(s)
- Khurram Bari
- University of Cincinnati, Division of Digestive Diseases, Department of Medicine, Cincinnati, Ohio
| | - Shimul A. Shah
- University of Cincinnati, Division of Transplant Surgery, Department of Surgery, Cincinnati, Ohio
| | - Tiffany E. Kaiser
- University of Cincinnati, Division of Digestive Diseases, Department of Medicine, Cincinnati, Ohio
| | - Robert M Cohen
- University of Cincinnati, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cincinnati, Ohio
| | - Nadeem Anwar
- University of Cincinnati, Division of Digestive Diseases, Department of Medicine, Cincinnati, Ohio
| | - David Kleesattel
- University of Cincinnati, Department of Internal Medicine, Cincinnati, Ohio
| | - Kenneth E. Sherman
- University of Cincinnati, Division of Digestive Diseases, Department of Medicine, Cincinnati, Ohio
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Binicier OB, Günay S. The efficacy and adverse effects of budesonide in remission induction treatment of autoimmune hepatitis: a retrospective study. Croat Med J 2019; 60:345-351. [PMID: 31483120 PMCID: PMC6734566 DOI: 10.3325/cmj.2019.60.345] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
AIM To compare the early biochemical response and rate of adverse effects in patients who received prednisolone (PRED)/azathioprine (AZA) and those who received budesonide (BUD)/AZA as the first-line treatment for autoimmune hepatitis. METHODS The study involved 25 patients receiving PRED 30 mg/day + AZA 50 mg/day and 25 patients receiving BUD 9 mg/day + AZA 50 mg/day from February 2015 to February 2018. Biochemical and hemogram data at baseline and after 6 months of treatment, and adverse effects observed in the follow-up, were compared. RESULTS There was no difference between the groups in biochemical response (17 patients receiving PRED/AZA and 18 receiving BUD/AZA) and the rate of adverse effects (9 patients receiving PRED/AZA and 5 receiving BUD/AZA). The total number of adverse effects in the BUD/AZA group was lower (15 vs 7) and the treatment was discontinued in 2 (8%) patients in PRED/AZA group, while no treatment discontinuation was observed in BUD/AZA group. CONCLUSIONS This study showed no differences in biochemical response between the groups. Lower, although not significantly, rate of adverse effects and lower total number of adverse effects indicate that BUD/AZA may potentially be used as the first-line treatment of choice, especially in patients with obesity, diabetes, resistant hypertension, glaucoma, or osteoporosis.
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Affiliation(s)
- Omer Burcak Binicier
- Omer Burcak Binicier, Department of Gastroenterology, Tepecik Training and Research Hospital, Güney mahallesi, 1140/1 Sokak, No: 1, Yenişehir-Konak-İzmir, Turkey,
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Rizvi S, Gawrieh S. Autoimmune Hepatitis in the Elderly: Diagnosis and Pharmacologic Management. Drugs Aging 2018; 35:589-602. [PMID: 29971609 DOI: 10.1007/s40266-018-0556-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Autoimmune hepatitis (AIH) may present as acute or chronic hepatitis in the elderly. Advanced hepatic fibrosis and cirrhosis are common on first presentation in this population. In this review, we discuss the presentation, approach to diagnosis and management of AIH in the elderly. As polypharmacy is common in the elderly, careful medication use history is essential for detecting drug-induced AIH-like hepatitis. Steroid-sparing or minimizing therapeutic regimens are preferred to treat AIH in the elderly. For the purpose of induction, budesonide or lower dose prednisone in combination with azathioprine (AZA) regimens are preferred over high-dose prednisone monotherapy due to the higher risk of side effects of the later in the elderly. The goal of maintenance therapy should be to achieve full biochemical and histologic remission. Bone density monitoring and interventions to prevent steroid-related bone disease should be implemented throughout the course of the disease. Liver transplantation should be considered in the elderly patient with liver failure or early hepatocellular carcinoma if there are no significant comorbidities or compromise in functional status.
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Affiliation(s)
- Syed Rizvi
- Gastroenterology and Hepatology Division, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI, 53226, USA.
| | - Samer Gawrieh
- Gastroenterology and Hepatology Division, Indiana University School of Medicine, 702 Rotary Cir, Indianapolis, IN, 46202-5175, USA.
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[Autoimmune hepatitis in the pediatric age]. BOLETIN MEDICO DEL HOSPITAL INFANTIL DE MEXICO 2018; 74:324-333. [PMID: 29382475 DOI: 10.1016/j.bmhimx.2017.05.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Revised: 04/25/2017] [Accepted: 05/11/2017] [Indexed: 11/23/2022] Open
Abstract
In pediatrics, autoimmune hepatitis and sclerosing cholangitis are liver disorders with an immunological damage mechanism. Autoimmune hepatitis is a disease of unknown etiology characterized by interface hepatitis, hypergammaglobulinemia, circulating autoantibodies and a favorable response to immunosuppression. It is an eminently pediatric disease with a prevalent condition in young women. Therapy should be instituted promptly to prevent rapid deterioration, promote remission of disease and long-term survival. The persistent lack of response or lack of adherence to treatment results in terminal liver failure; these patients, and those with fulminant hepatic insufficiency at the time of diagnosis, will require liver transplantation.
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Efficacy and Limitations of Budesonide as a Second-Line Treatment for Patients With Autoimmune Hepatitis. Clin Gastroenterol Hepatol 2018; 16:260-267.e1. [PMID: 28126427 DOI: 10.1016/j.cgh.2016.12.040] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2016] [Revised: 12/12/2016] [Accepted: 12/15/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Many patients with autoimmune hepatitis (AIH) develop steroid-specific side effects or require doses of steroids that are unacceptable for long-term treatment. We investigated the efficacy of budesonide as an alternative steroid for patients previously treated with prednisolone who developed side effects or were unable to reduce their dose of prednisolone below acceptable levels. We also report the effects of more than 12 months of budesonide treatment in a large cohort of patients with AIH. METHODS We performed a retrospective analysis of data from 60 patients (51 female) with AIH who were treated initially with prednisolone (mean time, 47 mo) but then switched to budesonide, managed at a single center in Germany from 2001 through June 2016. Patients were evaluated after 6 months, 12 months, 24 months, 36 months, and at the last follow-up evaluation; response to treatment with budesonide was assessed based on normal serum levels of aminotransferases and IgG (biochemical response). RESULTS Thirty patients were switched to budesonide therapy because of prednisolone-induced side effects and 30 patients switched because of prednisolone dependency. Overall, a biochemical response was detected in 55% of patients after 6 months of budesonide treatment, in 70% after 12 months, and in 67% after 24 months. At the last follow-up evaluation (mean time, 63 mo) 23 patients (38%) still were receiving budesonide treatment. Fifteen patients (25%) had switched back to prednisolone therapy because of insufficient response to budesonide or its side effects. Fifteen patients with osteopenia at the beginning of budesonide treatment were followed up and evaluated by dual-energy X-ray absorptiometry. After a median of 24 months of budesonide treatment, bone mineral density had improved in 6 patients, remained stable in 8 patients, and worsened in 1 patient. CONCLUSIONS We performed a retrospective analysis of patients with AIH that confirmed the therapeutic value of budesonide beyond 12 months of treatment in patients who are intolerant to or dependent on prednisolone. Although budesonide-induced side effects appear to be mild in real life, effectiveness was limited in a considerable proportion of patients; close monitoring is advised.
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Manns MP, Jaeckel E, Taubert R. Budesonide in Autoimmune Hepatitis: The Right Drug at the Right Time for the Right Patient. Clin Gastroenterol Hepatol 2018; 16:186-189. [PMID: 29128475 DOI: 10.1016/j.cgh.2017.11.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2017] [Revised: 10/05/2017] [Accepted: 11/05/2017] [Indexed: 02/07/2023]
Affiliation(s)
- Michael P Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; German Center for Infection Research, Partner Site Hannover, Braunschweig, Germany; Helmholtz Center for Infection Research, Braunschweig, Germany
| | - Elmar Jaeckel
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Richard Taubert
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
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Abstract
Autoimmune hepatitis (AIH) is an immune-mediated, inflammatory liver disease. Clinical presentation of AIH in children is highly variable. It can present acutely, chronically, or silently. There are two main types of AIH-type 1 and type 2, which are differentiated and defined by the presence of specific autoantibodies. AIH eventually progresses to cirrhosis when left untreated, and occasionally even with treatment. AIH must be suspected and excluded in all children presenting with signs of acute, prolonged, or severe liver disease. The diagnosis of AIH is made by a combination of clinical manifestations, laboratory evaluation, histopathology, and the exclusion of other more common liver diseases. The best outcome for AIH is dependent on early diagnosis as well as early initiation of immunosuppressant therapy. [Pediatr Ann. 2018;47(2):e81-e86.].
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Terziroli Beretta-Piccoli B, Mieli-Vergani G, Vergani D. Autoimmune hepatitis: Standard treatment and systematic review of alternative treatments. World J Gastroenterol 2017; 23:6030-6048. [PMID: 28970719 PMCID: PMC5597495 DOI: 10.3748/wjg.v23.i33.6030] [Citation(s) in RCA: 92] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Revised: 07/18/2017] [Accepted: 08/02/2017] [Indexed: 02/06/2023] Open
Abstract
Autoimmune hepatitis is a rare chronic inflammatory liver disease, affecting all ages, characterised by elevated transaminase and immunoglobulin G levels, positive autoantibodies, interface hepatitis at liver histology and good response to immunosuppressive treatment. If untreated, it has a poor prognosis. The aim of this review is to summarize the evidence for standard treatment and to provide a systematic review on alternative treatments for adults and children. Standard treatment is based on steroids and azathioprine, and leads to disease remission in 80%-90% of patients. Alternative first line treatment has been attempted with budesonide or cyclosporine, but their superiority compared to standard treatment remains to be demonstrated. Second-line treatments are needed for patients not responding or intolerant to standard treatment. No randomized controlled trials have been performed for second-line options. Mycophenolate mofetil is the most widely used second-line drug, and has good efficacy particularly for patients intolerant to azathioprine, but has the major disadvantage of being teratogenic. Only few and heterogeneous data on cyclosporine, tacrolimus, everolimus and sirolimus are available. More recently, experience with the anti-tumour necrosis factor-alpha infliximab and the anti-CD20 rituximab has been published, with ambivalent results; these agents may have severe side-effects and their use should be restricted to specialized centres. Clinical trials with new therapeutic options are ongoing.
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Affiliation(s)
| | - Giorgina Mieli-Vergani
- Paediatric Liver, GI and Nutrition Centre, MowatLabs, King’s College Hospital, Denmark Hill, London SE5 9RS, United Kingdom
| | - Diego Vergani
- Institute of Liver Studies, MowatLabs, King’s College Hospital, Denmark Hill, London SE5 9RS, United Kingdom
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Della Corte C, Mosca A, Vania A, Alterio A, Alisi A, Nobili V. Pediatric liver diseases: current challenges and future perspectives. Expert Rev Gastroenterol Hepatol 2016; 10:255-65. [PMID: 26641319 DOI: 10.1586/17474124.2016.1129274] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Chronic liver diseases in children represent a rising problem with significant effects on public health. In fact, several pediatric liver diseases are precursors of adult chronic hepatopathies, cirrhosis and hepatocellular carcinoma. The prevalence of liver diseases in children is unknown. In the USA, every year, 15,000 children are hospitalized for liver diseases, but these disorders continue to be under-recognized or diagnosed late. The main reason is due to the frequent absence of symptoms in the vast majority of liver diseases, especially in the early stages. In the last few decades several advances have been made in understanding the pathogenesis of liver diseases, permitting the discovery of new therapeutic targets to treat liver diseases, thus improving the natural history of these disorders. In this article we discuss the most recent advances in the understanding of the pathogenesis, diagnosis and treatment of the most frequent pediatric liver diseases.
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Affiliation(s)
- Claudia Della Corte
- a Hepato-Metabolic Department , Bambino Gesù Children's Hospital, IRCCS , Rome , Italy
| | - Antonella Mosca
- b Center of Dietetics and Nutrition , Pediatric Clinic, 'La Sapienza' University , Rome , Italy
| | - Andrea Vania
- b Center of Dietetics and Nutrition , Pediatric Clinic, 'La Sapienza' University , Rome , Italy
| | - Arianna Alterio
- a Hepato-Metabolic Department , Bambino Gesù Children's Hospital, IRCCS , Rome , Italy
| | - Anna Alisi
- c Liver Research Unit , Bambino Gesù Children's Hospital, IRCCS , Rome , Italy
| | - Valerio Nobili
- a Hepato-Metabolic Department , Bambino Gesù Children's Hospital, IRCCS , Rome , Italy
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Affiliation(s)
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- EASL office, 7 Rue Daubin, CH 1203 Geneva, Switzerland,
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Bose T. Bitter correlationship between autoimmune hepatitis and smoking. Med Hypotheses 2015; 84:118-21. [DOI: 10.1016/j.mehy.2014.12.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2014] [Accepted: 12/06/2014] [Indexed: 01/12/2023]
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Zhang H, Yang J, Zhu R, Zheng Y, Zhou Y, Dai W, Wang F, Chen K, Li J, Wang C, Li S, Liu T, Abudumijiti H, Zhou Z, Wang J, Lu W, Wang J, Xia Y, Zhou Y, Lu J, Guo C. Combination therapy of ursodeoxycholic acid and budesonide for PBC-AIH overlap syndrome: a meta-analysis. Drug Des Devel Ther 2015; 9:567-574. [PMID: 25632224 PMCID: PMC4304592 DOI: 10.2147/dddt.s74515] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
In this study, a meta-analysis of randomized controlled trials comparing ursodeoxycholic acid (UDCA) monotherapy with combination therapies utilizing UDCA and budesonide was performed. We found that combination therapy with UDCA and budesonide was more effective than UDCA monotherapy for primary biliary cirrhosis-autoimmune hepatitis overlap syndrome. Moreover, compared to prednisone, budesonide has fewer side effects.
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Affiliation(s)
- Huawei Zhang
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China
- The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China
| | - Jing Yang
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China
| | - Rong Zhu
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China
- The First Clinical Medical College of Nanjing Medical University, Nanjing, People’s Republic of China
| | - Yuanyuan Zheng
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China
| | - Yuqing Zhou
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China
- The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China
| | - Weiqi Dai
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China
| | - Fan Wang
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China
| | - Kan Chen
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China
| | - Jingjing Li
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China
| | - Chengfen Wang
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China
| | - Sainan Li
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China
| | - Tong Liu
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China
| | - Huerxidan Abudumijiti
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China
| | - Zheng Zhou
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China
- The First Clinical Medical College of Nanjing Medical University, Nanjing, People’s Republic of China
| | - Jianrong Wang
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China
- The First Clinical Medical College of Nanjing Medical University, Nanjing, People’s Republic of China
| | - Wenxia Lu
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China
- The First Clinical Medical College of Nanjing Medical University, Nanjing, People’s Republic of China
| | - Junshan Wang
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China
| | - Yujing Xia
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China
| | - Yingqun Zhou
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China
| | - Jie Lu
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China
| | - Chuanyong Guo
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China
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Silveira MG, Lindor KD. Obeticholic acid and budesonide for the treatment of primary biliary cirrhosis. Expert Opin Pharmacother 2014; 15:365-72. [PMID: 24382005 DOI: 10.1517/14656566.2014.873404] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of adults. Treatments are needed when patients have incomplete response to ursodeoxycholic acid (UDCA). AREAS COVERED Discoveries of the key role played by bile acids (BAs) and nuclear receptors (NRs) in regulating liver and metabolic homeostasis have led to promising therapeutic approaches in liver diseases. A PubMed search for the recent literature on NRs in liver disease was conducted. In particular, obeticholic acid (OCA) is a farnesoid X receptor (FXR) agonist that has an important role in the enterohepatic circulation of BAs. Preliminary studies of OCA in patients with PBC have demonstrated marked biochemical improvement when administered in combination with UDCA and alone. Pruritus is the most common side effect, limiting treatment at higher doses. Budesonide is a glucocorticoid receptor/pregnane X receptor (PXR) agonist also involved in BA synthesis, metabolism and transport. Studies with budesonide have shown positive effects of short-term combination therapy in selected patients with early stage disease and overlapping features of autoimmune hepatitis. EXPERT OPINION Though larger studies are needed, preliminary results of agents targeting FXR and PXR have been encouraging, particularly in subsets of patients with PBC and may mark a new therapeutic era.
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Affiliation(s)
- Marina G Silveira
- Case Western Reserve University, Louis Stokes Cleveland VA Medical Center and Case Medical Center, Division of Gastroenterology and Hepatology , 10701 East Blvd 111E (W), Cleveland, OH 44106 , USA
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Zhang Y, Lu J, Dai W, Wang F, Shen M, Yang J, Zhu R, Zhang H, Chen K, Cheng P, He L, Wang C, Xu L, Zhou Y, Guo C. Combination therapy of ursodeoxycholic Acid and corticosteroids for primary biliary cirrhosis with features of autoimmune hepatitis: a meta-analysis. Gastroenterol Res Pract 2013; 2013:490731. [PMID: 24369456 PMCID: PMC3867832 DOI: 10.1155/2013/490731] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2013] [Accepted: 10/09/2013] [Indexed: 12/12/2022] Open
Abstract
A meta-analysis was performed of RCTs comparing therapies that combine UDCA and corticosteroids with UDCA monotherapy. In this paper, we found that the combination therapy of UDCA and corticosteroids was more effective for PBC-AIH.
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Affiliation(s)
- Yan Zhang
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Jie Lu
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Weiqi Dai
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Fan Wang
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Miao Shen
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Jing Yang
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Rong Zhu
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Huawei Zhang
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Kan Chen
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Ping Cheng
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Lei He
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Chengfen Wang
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Ling Xu
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Yingqun Zhou
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Chuanyong Guo
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
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Kapila N, Higa JT, Longhi MS, Robson SC. Autoimmune Hepatitis: Clinical Review with Insights into the Purinergic Mechanism of Disease. J Clin Transl Hepatol 2013; 1:79-86. [PMID: 26356124 PMCID: PMC4521285 DOI: 10.14218/jcth.2013.00015] [Citation(s) in RCA: 3] [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] [Received: 08/30/2013] [Revised: 10/04/2013] [Accepted: 10/15/2013] [Indexed: 12/11/2022] Open
Abstract
Autoimmune hepatitis (AIH) is an important disorder that predominantly results in inflammatory liver disease in genetically predisposed women. The clinicopathological picture is characterized by symptoms associated with both systemic inflammation and hepatic dysfunction, and with increased serum aminotransferases, elevated IgG, autoantibodies, and interface hepatitis on liver biopsy. AIH usually results in liver injury as a consequence of chronic hepatitis and cirrhosis. However, rarely, patients may present with fulminant liver failure. Early diagnosis is important in all instances because the disease can be highly responsive to immunosuppressive therapeutic options. Left untreated, the disease is associated with high morbidity and mortality. Here we provide an overview of the current state of knowledge on AIH and summarize the treatment options for this serious condition in adults. We also discuss the pathogenesis of the disease as a possible consequence of autoimmunity and the breakdown of hepatic tolerance. We focus on regulatory T cell impairments as a consequence of changes in CD39 ectonucleotidase expression and altered purinergic signaling. Further understanding of hepatic tolerance may aid in the development of specific and well-tolerated therapies for AIH.
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Affiliation(s)
- Nikhil Kapila
- Department of Medicine, University of Connecticut, Farmington, CT, USA
- These authors contributed equally to this work
| | - Jennifer T. Higa
- Gastroenterology Division and Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
- These authors contributed equally to this work
| | - Maria Serena Longhi
- Gastroenterology Division and Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
- Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, Denmark Hill, London, UK
| | - Simon C. Robson
- Gastroenterology Division and Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
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Abstract
Autoimmune hepatitis is a disease of the hepatic parenchyma that can present in acute or chronic forms. In common with many autoimmune diseases, autoimmune hepatitis is associated with non-organ-specific antibodies in the context of hepatic autoimmunity. This dichotomy has made definition of a unifying hypothesis in the pathophysiology of the disease difficult, although data from the past 8 years have drawn attention to the role of regulatory T cells. Several triggers have been identified, and the disease arises in genetically susceptible individuals. Clinical and biochemical remission is achievable in up to 85% of cases. For the remaining patients, alternative immunosuppression strategies are an option. Liver transplantation provides an excellent outcome for patients with acute liver failure or complications of end-stage liver disease, including hepatocellular carcinoma. Variant or overlapping syndromes are worthy of consideration when unexpected disease features arise.
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Affiliation(s)
- Michael A Heneghan
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK.
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20
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Czaja AJ. Review article: the management of autoimmune hepatitis beyond consensus guidelines. Aliment Pharmacol Ther 2013; 38:343-64. [PMID: 23808490 DOI: 10.1111/apt.12381] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2013] [Revised: 05/30/2013] [Accepted: 06/03/2013] [Indexed: 12/17/2022]
Abstract
BACKGROUND Consensus guidelines aid in the diagnosis and management of autoimmune hepatitis, but they are frequently based on low-quality clinical evidence, conflicting experiences and divergent opinions. Recommendations may be weak, discrepant or non-existent at critical decision points. AIMS To identify the decision points where guidelines are weak or non-existent and review the evidence essential in the decision process. METHODS Full-text articles published in English using the keyword 'autoimmune hepatitis' were identified by PubMed from 1972 to 2013. Personal experience and investigations in autoimmune hepatitis also identified important contributions. RESULTS Seventy per cent of the guidelines developed by the American Association for the Study of Liver Diseases and 48% of those proposed by the British Society of Gastroenterology are based on low-quality evidence, conflicting experiences or divergent opinions. The key uncertainties in diagnosis relate to the timing of liver biopsy, recognising acute severe (fulminant) disease, interpreting coincidental nonclassical histological changes, accommodating atypical or deficient features in non-White patients, differentiating drug-induced from classical disease and identifying overlap syndromes. The key uncertainties in management relate to pre-treatment testing for thiopurine methyltransferase activity, treating asymptomatic mild disease, determining treatment end points, managing suboptimal responses, incorporating nonstandard medications as front-line and salvage agents, using azathioprine in pregnancy and instituting surveillance for hepatocellular carcinoma. CONCLUSIONS Consensus guidelines are fraught with uncertainties in the diagnosis and management of autoimmune hepatitis. Each decision point must counterbalance the current available evidence and tailor the application of this evidence to the individual patient.
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Affiliation(s)
- A J Czaja
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
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21
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Autoimmune hepatitis: focusing on treatments other than steroids. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2013; 26:615-20. [PMID: 22993733 DOI: 10.1155/2012/512132] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Corticosteroid therapy has been the time-honoured treatment for autoimmune hepatitis; however, the emergence of new immunosuppressive agents has afforded opportunities to improve or replace the standard regimens. OBJECTIVE To describe technological advances and feasible treatment interventions that promise to supplant the current generation of corticosteroids. METHODS A review of the MEDLINE database for published experiences from 1984 to 2011 was conducted. RESULTS Cyclosporine and tacrolimus have been uniformly successful as salvage therapies for steroid-refractory autoimmune hepatitis. Ten reports of cyclosporine therapy involving 133 patients had positive outcomes in 93%, whereas therapy with tacrolimus in three reports involving 41 patients had positive outcomes in 98%. Salvage therapy with mycophenolate mofetil had a favourable outcome in 47%, especially in patients with azathioprine intolerance. Front-line therapy with mycophenolate mofetil normalized liver parameters in 88% and allowed corticosteroid tapering in 58%. Front-line therapy with budesonide combined with azathioprine for six months normalized liver parameters more frequently (47% versus 18%) and with fewer side effects (28% versus 53%) than prednisone combined with azathioprine. Monoclonal antibodies to CD3 and recombinant cytotoxic T lymphocyte antigen 4 fused with immunoglobulin represent feasible molecular interventions for study in autoimmune hepatitis. DISCUSSION Nonstandard drug therapies must be used in highly selected clinical situations including steroid failure (calcineurin inhibitors), azathioprine intolerance (mycophenolate mofetil), and mild disease or fragile patients (budesonide combined with azathioprine). Molecular interventions for autoimmune hepatitis are feasible for study because of their use in other immune-mediated diseases. CONCLUSION Opportunities to improve or replace standard corticosteroid regimens have emerged.
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22
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Talukdar A, Khanra D, Mukherjee K, Saha M. Autoimmune hepatitis in a teenage boy: 'overlap' or 'outlier' syndrome--dilemma for internists. BMJ Case Rep 2013; 2013:bcr2012008335. [PMID: 23396934 PMCID: PMC3604308 DOI: 10.1136/bcr-2012-008335] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
An 18-year-old boy presented with upper gastrointestinal bleeding and jaundice. Investigations revealed coarse hepatomegaly, splenomegaly and advanced oesophageal varices. Blood reports showed marked rise of alkaline phosphatase and more than twofold rise of transaminases and IgG. Liver histology was suggestive of piecemeal necrosis, interphase hepatitis and bile duct proliferation. Antinuclear antibody was positive in high titre along with positive antismooth muscle antibody and antimitochondrial antibody. The patient was positive for human leukocyte antigen DR3 type. Although an 'overlap' syndrome exists between autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), a cholestatic variant of AIH, a rare 'outlier' syndrome could not be excluded in our case. Moreover, 'the chicken or the egg', AIH or PBC, the dilemma for the internists continued. The patient was put on steroid and ursodeoxycholic acid with unsatisfactory response. The existing international criteria for diagnosis of AIH are not generous enough to accommodate its variant forms.
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Affiliation(s)
- Arunansu Talukdar
- Department of Medicine, Medical College Kolkata, Kolkata, West Bengal, India.
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Selvarajah V, Montano-Loza AJ, Czaja AJ. Systematic review: managing suboptimal treatment responses in autoimmune hepatitis with conventional and nonstandard drugs. Aliment Pharmacol Ther 2012; 36:691-707. [PMID: 22973822 DOI: 10.1111/apt.12042] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2012] [Revised: 07/17/2012] [Accepted: 08/21/2012] [Indexed: 12/13/2022]
Abstract
BACKGROUND Corticosteroid treatment for autoimmune hepatitis has been shown by randomised controlled clinical trials to ameliorate symptoms, normalise liver tests, improve histological findings and extend survival. Nevertheless, suboptimal responses to corticosteroid treatment still occur. AIM To describe the current definitions, frequencies, clinical relevance and treatment options for suboptimal responses, and to discuss alternative medications that have been used off-label for these occurrences. METHODS Literature search was made for full-text papers published in English using the keyword 'autoimmune hepatitis'. Authors' personal experience and investigational studies also helped to identify important contributions to the literature. RESULTS Suboptimal responses to standard therapy include treatment failure (7%), incomplete response (14%), drug toxicity (13%) and relapse after drug withdrawal (50-86%). The probability of a suboptimal response prior to treatment is higher in young patients and in patients with a severe presentation, jaundice, high MELD score at diagnosis, multilobular necrosis or cirrhosis, antibodies to soluble liver antigen, or inability to improve by clinical indices within two weeks or by MELD score within 7 days of conventional corticosteroid treatment. Management strategies have been developed for the adverse responses and nonstandard drugs, including mycophenolate mofetil, budesonide, ciclosporin, tacrolimus, sirolimus and rituximab, are emerging as rescue therapies or alternative frontline agents. CONCLUSIONS Once diagnosed, the suboptimal response should be treated by a highly individualised and well-monitored regimen, preferentially using first-line therapy. Nonstandard drugs warrant consideration as salvage or second-line therapies.
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Affiliation(s)
- V Selvarajah
- Division of Gastroenterology & Liver Unit, University of Alberta Hospital, Edmonton, AB, Canada
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Abstract
Prednisone and prednisolone are the mainstays of treatment for autoimmune hepatitis. Prednisone is converted in the liver to the active metabolite, prednisolone. The principal therapeutic action of prednisolone is to suppress cytokine gene expression and to inhibit the differentiation and proliferation of activated lymphocytes. It also has anti-inflammatory effects that include decreased production of adhesion molecules, increased apoptosis of lymphocytes and decreased hepatic collagen deposition. Advanced liver disease does not sufficiently suppress hepatic conversion of prednisone to warrant the preferential use of prednisolone. Budesonide combined with azathioprine has been more effective and safer than the conventional prednisone-based regimen when given for 6 months to treatment-naive patients. It is emerging as a frontline treatment, especially for noncirrhotic patients with uncomplicated disease.
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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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25
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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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26
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Advances in the current treatment of autoimmune hepatitis. Dig Dis Sci 2012; 57:1996-2010. [PMID: 22476586 DOI: 10.1007/s10620-012-2151-2] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2011] [Accepted: 03/16/2012] [Indexed: 12/17/2022]
Abstract
Current treatment strategies for autoimmune hepatitis are complicated by frequent relapse after drug withdrawal, medication intolerance, and refractory disease. The objective of this review is to describe advances that have improved treatment outcomes by defining the optimum objectives of initial therapy, managing relapse more effectively, identifying problematic patients early, and incorporating the new pharmacological interventions that have emerged as frontline and salvage therapies. Initial corticosteroid treatment should be continued until serum aminotransferase, γ-globulin, and immunoglobulin G levels are normal, and maintenance of this improvement for 3-8 months before liver tissue assessment. Improvement to normal liver tissue is the ideal histological result that justifies drug withdrawal, but it is achievable in only 22 % of patients. Minimum portal hepatitis, inactive cirrhosis, or minimally active cirrhosis is the most common treatment end point. Relapse after drug withdrawal warrants institution of a long-term maintenance regimen, preferably with azathioprine. Mathematical models can identify problematic adult patients early, as also can clinical phenotype (age ≤ 30 years and HLA DRB1 03), rapidity of treatment response (≤ 24 months), presence of antibodies to soluble liver antigen, and non-white ethnicity. The calcineurin inhibitors (cyclosporine and tacrolimus) can be effective in steroid-refractory disease; mycophenolate mofetil can be corticosteroid-sparing and effective for azathioprine intolerance; budesonide combined with azathioprine can be effective for treatment-naïve, non-cirrhotic patients. Standard treatment regimens for autoimmune hepatitis can be upgraded without adjustments that require major new expertise.
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27
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Abstract
Autoimmune hepatitis (AIH) is an immune-mediated necroinflammatory disease of the liver characterized by elevation of IgG, presence of characteristic autoantibodies, and histological features of interface hepatitis. Two types of juvenile AIH have been recognized according to seropositivity for smooth muscle and/or antinuclear antibody (AIH type 1) or liver kidney microsomal antibody (AIH type 2). The exact pathogenesis of AIH is still unclear, but it is known that unidentified environmental factors, and occasionally drugs, might trigger disease in genetically susceptible individuals. The clinical spectrum of this disease is very wide, ranging from asymptomatic individuals with abnormal liver function to those with fulminant liver failure. The diagnosis is based on a combination of biochemical and histological parameters and on exclusion of other liver diseases. It is a relatively rare but devastating disease, which progresses rapidly unless immunosuppressive treatment is started promptly. Standard therapy consists of a combination of corticosteroids and azathioprine, which is efficacious in 80% of patients. Alternative therapies are increasingly being explored in patients who do not respond to standard treatment and/or have intolerable side-effects. The purpose of this paper is to review our current knowledge about AIH in children, evaluating mainly the therapeutic options for its treatment, considering also the newer immunosuppressant agents used in difficult-to-treat cases.
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Efe C, Ozaslan E, Kav T, Purnak T, Shorbagi A, Ozkayar O, Berlot AH, Sökmensuer C, Muratori P. Liver fibrosis may reduce the efficacy of budesonide in the treatment of autoimmune hepatitis and overlap syndrome. Autoimmun Rev 2012; 11:330-334. [PMID: 22001521 DOI: 10.1016/j.autrev.2011.09.006] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2011] [Accepted: 09/26/2011] [Indexed: 12/25/2022]
Abstract
BACKGROUND AND AIM The aim of the present study was to assess the efficacy and tolerability of budesonide as an alternative first line treatment option for autoimmune hepatitis (AIH) and the overlap syndrome. METHODS A total of 18 AIH or overlap syndrome patients were evaluated. Outcomes of treatment by the end of the study were defined as treatment failure, partial response, complete response and remission. RESULTS Complete response and remission were achieved in 61.1% (11/18) of patients, while 38.9% (7/18) of patients were considered treatment failures. Liver fibrosis was observed in 55.5% of patients' biopsies. More patients with liver fibrosis failed to respond to treatment compared to patients without fibrosis, a difference bordering on statistical significance (60% vs. 12.5%; p=0.066). Although statistically insignificant, the presence of at least one side effect was observed more frequently in patients with fibrosis compared to those without fibrosis (80% vs. 37.5%; p=0.145). Overall, side effects occurred significantly more commonly in non-responders than responders (100% vs. 36%; p=0.013). CONCLUSIONS Budesonide is an effective treatment option for the management of AIH, with a low incidence of side effects in patients without findings of advanced liver disease. The presence of liver fibrosis may increase the likelihood of treatment failure as well as the risk of developing side effects. Our study findings suggest that budesonide may be effective in a select group of AIH patients. Further studies are needed to determine its exact place for the treatment of AIH and overlap syndrome.
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Affiliation(s)
- Cumali Efe
- Department of Gastroenterology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
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Snider KR, Potter TG. Budesonide for the treatment of autoimmune hepatitis. Ann Pharmacother 2011; 45:1144-50. [PMID: 21878659 DOI: 10.1345/aph.1q244] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
OBJECTIVE To evaluate the use of budesonide for the treatment of autoimmune hepatitis (AIH). DATA SOURCES Literature was accessed through PubMed/MEDLINE (1966-June 2011) and Web of Science (1965-June 2011) using the terms autoimmune hepatitis and budesonide. Literature was limited to English-language publications. In addition, references from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION All articles in English identified from the data sources were evaluated. DATA SYNTHESIS The initial treatment of choice for AIH is prednisone alone or with azathioprine. However, a significant number of patients do not respond adequately or have adverse reactions to this regimen; therefore, alternative treatments are required. Budesonide is an orally administered synthetic corticosteroid with high affinity for the glucocorticoid receptor that undergoes extensive first-pass metabolism. It has Food and Drug Administration-approved labeling for the treatment and maintenance of remission of mild-to-moderate Crohn disease involving the ileum and/or ascending colon. One prospective, active-controlled study of budesonide in the treatment of AIH was identified, as well as 5 small open-label studies and 1 retrospective chart review. Budesonide appears to have efficacy in the treatment of AIH, including in patients intolerant to standard therapy with prednisone alone or with azathioprine, with a reduced incidence of corticosteroid-related adverse reactions. However, in patients with AIH and cirrhosis, the efficacy of budesonide may be reduced and the incidence of corticosteroid-related adverse reactions may be increased. CONCLUSIONS Budesonide may be an additional treatment option for patients with AIH but without cirrhosis who are intolerant to standard therapy with prednisone or prednisone with azathioprine.
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Affiliation(s)
- Kenneth R Snider
- Internal Medicine, Virginia Commonwealth University Health System/Medical College of Virginia Hospitals, Richmond, VA, USA.
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Abstract
PURPOSE OF REVIEW Autoimmune hepatitis (AIH) is a chronic, progressive hepatitis of uncertain cause which has fluctuating activity characterized by periods of flares and remissions. Initial placebo-controlled trials carried out in the 1970s demonstrated that immunosuppression with steroids was extremely effective in reducing flares and progression of disease. The late 1980s-1990s could be described as the 'Dark Ages' of AIH treatment research. Very few clinical studies were performed during this time, although it became increasingly apparent that not all patients tolerated or responded to traditional immunosuppression, and that not all patients were easy to diagnose because of overlapping features with other autoimmune conditions. Fortunately, clinical research in the treatment of AIH has experienced a renaissance in the 21st century. RECENT FINDINGS This review highlights some of the more important recent discoveries, including the creation of the clinically useful short form of the autoimmune hepatitis diagnostic scoring system; accumulation of data supporting the use of mycophenolate and tacrolimus as second-line treatment; and the recent completion of the largest, double-blind, placebo-controlled trial of AIH treatment to date, comparing budesonide to prednisone. SUMMARY These new findings are pertinent to the everyday clinical management of patients with AIH.
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31
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Jothimani D, Cramp ME, Mitchell JD, Cross TJS. Treatment of autoimmune hepatitis: a review of current and evolving therapies. J Gastroenterol Hepatol 2011; 26:619-27. [PMID: 21073674 DOI: 10.1111/j.1440-1746.2010.06579.x] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Autoimmune hepatitis (AIH) is an immune-mediated necroinflammatory condition of the liver. Presentation can vary from the asymptomatic individual with abnormal liver function test to fulminant liver failure. The diagnosis is based on the combination of biochemical, autoimmune, and histological parameters, and exclusion of other liver diseases. Standard therapy consists of a combination of corticosteroids and azathioprine, which is efficacious in 80% of patients. Alternative therapies are increasingly being explored in patients who do not respond to the standard treatment and/or have unacceptable adverse effects. This review examines the role of alternative drugs (second-line agents) available for AIH treatment non-responders. These agents include budesonide, mycophenolate mofetil, cyclosporin, tacrolimus, 6-mercaptopurine, 6-thioguanine, rituximab, ursodeoxycholic acid, rapamycin, and methotrexate. In addition, the risk of opportunistic infections and malignancies are discussed. A treatment algorithm is proposed for the management of patients with AIH treatment non-responders.
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Affiliation(s)
- Dinesh Jothimani
- The Southwest Liver Unit, Derriford Hospital, Plymouth, Devon, UK
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32
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Fawaz R, Jonas MM. Acute and Chronic Hepatitis. PEDIATRIC GASTROINTESTINAL AND LIVER DISEASE 2011:811-828.e5. [DOI: 10.1016/b978-1-4377-0774-8.10075-2] [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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Muratori L, Muratori P, Granito A, Pappas G, Cassani F, Lenzi M. Current topics in autoimmune hepatitis. Dig Liver Dis 2010; 42:757-764. [PMID: 20615766 DOI: 10.1016/j.dld.2010.05.019] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2010] [Revised: 05/23/2010] [Accepted: 05/31/2010] [Indexed: 12/11/2022]
Abstract
Autoimmune hepatitis is a chronic liver disease of unknown aetiology characterized by interface hepatitis, hypergammaglobulinaemia and circulating autoantibodies. In the last decade a number of advancements have been made in the field of clinical and basic research: the simplified diagnostic criteria, the complete response defined as normalization of transaminase levels, the molecular identification of the antigenic targets of anti-liver cytosol antibody type 1 and anti-soluble liver antigen, the detection of anti-actin antibodies, the description of de novo autoimmune hepatitis after liver transplantation for non-autoimmune liver diseases, the characterization of autoimmune hepatitis with overlapping features of primary biliary cirrhosis or primary sclerosing cholangitis, the preliminary experience with novel treatment strategies based on cyclosporine, mycophenolate mofetil and budesonide, the role played by "impaired" regulatory T cells and the development of novel animal models of autoimmune hepatitis.
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MESH Headings
- Animals
- Autoantibodies/immunology
- Autoantigens/immunology
- Biomarkers/blood
- Budesonide/therapeutic use
- Cholangitis, Sclerosing/complications
- Cholangitis, Sclerosing/diagnosis
- Cholangitis, Sclerosing/immunology
- Cholangitis, Sclerosing/therapy
- Cyclosporine/therapeutic use
- Glucocorticoids/therapeutic use
- Hepatitis, Autoimmune/complications
- Hepatitis, Autoimmune/diagnosis
- Hepatitis, Autoimmune/immunology
- Hepatitis, Autoimmune/therapy
- Humans
- Hypergammaglobulinemia
- Immunity, Cellular
- Immunoglobulin G/blood
- Immunosuppressive Agents/therapeutic use
- Liver Cirrhosis, Biliary/complications
- Liver Cirrhosis, Biliary/diagnosis
- Liver Cirrhosis, Biliary/immunology
- Liver Cirrhosis, Biliary/therapy
- Liver Transplantation/adverse effects
- Mice
- Mycophenolic Acid/analogs & derivatives
- Mycophenolic Acid/therapeutic use
- Rats
- Transaminases/blood
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Affiliation(s)
- Luigi Muratori
- Department of Clinical Medicine, Alma Mater Studiorum - University of Bologna, Policlinico Sant'Orsola-Malpighi, Padiglione 11, Bologna, Italy.
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Czaja AJ, Manns MP. Advances in the diagnosis, pathogenesis, and management of autoimmune hepatitis. Gastroenterology 2010; 139:58-72.e4. [PMID: 20451521 DOI: 10.1053/j.gastro.2010.04.053] [Citation(s) in RCA: 194] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2010] [Revised: 04/27/2010] [Accepted: 04/30/2010] [Indexed: 12/13/2022]
Abstract
Autoimmune hepatitis (AIH) is characterized by chronic inflammation of the liver, interface hepatitis (based on histologic examination), hypergammaglobulinemia, and production of autoantibodies. Many clinical and basic science studies have provided important insights into the pathogenesis and treatment of AIH. Transgenic mice that express human antigens and develop autoantibodies, liver-infiltrating CD4(+) T cells, liver inflammation, and fibrosis have been developed as models of AIH. AIH has been associated with autoantibodies against members of the cytochrome P450 superfamily of enzymes, transfer RNA selenocysteine synthase, formiminotransferase cyclodeaminase, and the uridine diphosphate glucuronosyltransferases, whereas alleles such as DRB1*0301 and DRB1*0401 are genetic risk factors in white North American and northern European populations. Deficiencies in the number and function of CD4(+)CD25(+) (regulatory) T cells disrupt immune homeostasis and might be corrected as a therapeutic strategy. Treatment can be improved by continuing corticosteroid therapy until normal liver test results and normal liver tissue are within normal limits, instituting ancillary therapies to prevent drug-related side effects, identifying problematic patients early, and providing long-term maintenance therapy after patients experience a first relapse. Calcineurin inhibitors and mycophenolate mofetil are potential salvage therapies, and reagents such as recombinant interleukin-10, abatacept, and CD3-specific antibodies are feasible as therapeutics. Liver transplantation is an effective salvage therapy, even in the elderly, and AIH must be considered in all patients with graft dysfunction after liver transplantation. Identification of the key defects in immune homeostasis and antigen targets will direct new therapies.
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Affiliation(s)
- Albert J Czaja
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
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Abstract
Treatment decisions in autoimmune hepatitis are complicated by the diversity of its clinical presentations, uncertainties about its natural history, evolving opinions regarding treatment end points, varied nature of refractory disease, and plethora of alternative immunosuppressive agents. The goals of this article are to review the difficult treatment decisions and to provide the bases for making sound therapeutic judgments. The English literature on the treatment problems in autoimmune hepatitis were identified by Medline search up to October 2009 and 32 years of personal experience. Autoimmune hepatitis may have an acute severe presentation, mild inflammatory activity, lack autoantibodies, exhibit atypical histological changes (centrilobular zone 3 necrosis or bile duct injury), or have variant features reminiscent of another disease (overlap syndrome). Corticosteroid therapy must be instituted early, applied despite the absence of symptoms, or modified in an individualized fashion. Pursuit of normal liver tests and tissue is the ideal treatment end point, but this objective must be tempered against the risk of side effects. Relapse after treatment withdrawal requires long-term maintenance therapy, preferably with azathioprine. Treatment failure or an incomplete response warrants salvage therapy that can include conventional medications in modified dose or empirical therapies with calcineurin inhibitors or mycophenolate mofetil. Liver transplantation supersedes empirical drug therapy in decompensated patients. Elderly and pregnant patients warrant treatment modifications. Difficult treatment decisions in autoimmune hepatitis can be simplified by recognizing its diverse manifestations and individualizing treatment, pursuing realistic goals, applying appropriate salvage regimens, and identifying problematic patients early.
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Wolf DC, Bojito L, Facciuto M, Lebovics E. Mycophenolate mofetil for autoimmune hepatitis: a single practice experience. Dig Dis Sci 2009; 54:2519-22. [PMID: 19082888 DOI: 10.1007/s10620-008-0632-0] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2008] [Accepted: 11/12/2008] [Indexed: 12/12/2022]
Abstract
Autoimmune hepatitis (AIH) is refractory to standard therapy with prednisone and azathioprine in 20% of patients. Investigators are exploring alternative immunosuppressant treatments, including mycophenolate mofetil (MMF). We assessed the outcome of MMF therapy in patients with AIH and related disorders. A retrospective analysis was performed in 16 patients with AIH, immune cholangitis, and overlap syndromes between AIH, primary biliary cirrhosis, and primary sclerosing cholangitis. MMF was used in lieu of azathioprine on account of patients' intolerance to azathioprine, disease that was refractory to prednisone plus azathioprine, or the perceived potency of MMF. With initiation of MMF, median ALT decreased from 81.5 U/l to 42.5 U/l (P = 0.03). Median prednisone dose decreased from 10 mg to 2.5 mg (P = 0.01). Prednisone was completely withdrawn in three patients. Five of 16 patients (31%) achieved biochemical remission, defined as a reduction in ALT from greater than to less than twice normal. Seven additional patients (44%) were maintained in biochemical remission. Two patients had an incomplete response to MMF and two patients experienced treatment failure. MMF was tolerated well in all but one patient, who discontinued the drug on account of paresthesias. MMF may be a safe and effective alternative to azathioprine in patients with AIH and related disorders.
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Affiliation(s)
- David C Wolf
- Division of Gastroenterology and Hepatobiliary Diseases, New York Medical College, Valhalla, NY 10595, USA.
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MESH Headings
- Adult
- Child
- Cholangitis/diagnosis
- Cholangitis/immunology
- Cholangitis/therapy
- Cholangitis, Sclerosing/diagnosis
- Cholangitis, Sclerosing/therapy
- Cholestasis, Intrahepatic/diagnosis
- Cholestasis, Intrahepatic/etiology
- Cholestasis, Intrahepatic/prevention & control
- Cholestasis, Intrahepatic/therapy
- Cystic Fibrosis/complications
- Female
- Hepatitis, Autoimmune/diagnosis
- Hepatitis, Autoimmune/therapy
- Humans
- Immunoglobulin G/metabolism
- Infant
- Liver Cirrhosis, Biliary/diagnosis
- Liver Cirrhosis, Biliary/therapy
- Male
- Osteoporosis/etiology
- Osteoporosis/therapy
- Pregnancy
- Pregnancy Complications/diagnosis
- Pregnancy Complications/therapy
- Syndrome
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Collaborators
Ulrich Beuers, Kirsten M Boberg, Roger W Chapman, Olivier Chazouillères, Pietro Invernizzi, David E J Jones, Frank Lammert, Albert Parès, Michael Trauner,
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Gluud LL, Dahl EE, Al-Rifai A, Prince M. Medical treatments for autoimmune hepatitis. Hippokratia 2009. [DOI: 10.1002/14651858.cd004543.pub2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Lise Lotte Gluud
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 3344, Rigshospitalet, Copenhagen University Hospital; Cochrane Hepato-Biliary Group; Blegdamsvej 9 Copenhagen Denmark DK-2100
| | | | | | - Martin Prince
- Manchester Royal Infirmary; Oxford Road Manchester UK M13 9WL
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The use of budesonide in the treatment of autoimmune hepatitis in Canada. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2008; 22:388-92. [PMID: 18414714 DOI: 10.1155/2008/509459] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND Autoimmune hepatitis (AIH) is a chronic inflammatory disease that is successfully treated with prednisone and/or azathioprine immunosuppressive therapy in 70% to 80% of patients. The remaining patients are intolerant or refractory to these standard medications. Budesonide, a synthetic glucocorticoid, undergoes a high degree of first-pass metabolism, reducing its systemic bioavailability, and has a 15-fold greater affinity for the glucocorticoid receptor than prednisolone. Budesonide may be a potentially useful systemic steroid-sparing immunosuppressive agent in the treatment of AIH. OBJECTIVE To review the Canadian experience using budesonide to treat AIH. METHODS Patients with AIH currently or previously treated with budesonide were identified through the Canadian Association for the Study of the Liver membership. Data were collected regarding their clinical and treatment history. RESULTS A total of nine patients were identified. All patients were female, with an average age of 39 years (range 12 to 66 years). The indications for budesonide were adverse side effects of prednisone in two patients, noncompliance with prednisone and azathioprine in one patient and intolerance to azathioprine resulting in prednisone dependence in the remaining six patients. Patients were treated in doses ranging from 9 mg daily to 3 mg every other day for 24 weeks to eight years. Seven of nine patients had a complete response, defined as sustained normalization of the aminotransferase levels. The remaining two patients were classified as nonresponders (less than a 50% reduction in pretreatment aminotransferase levels). CONCLUSIONS In Canada, budesonide has been successfully used in seven of nine patients with autoimmune hepatitis who were either intolerant to prednisone and azathioprine or prednisone-dependent. No adverse effects were reported with budesonide. Budesonide is potentially a valuable treatment option for AIH patients refractory or intolerant to standard therapy, and is deserving of further study.
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Abstract
The three major immune disorders of the liver are autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Variant forms of these diseases are generally called overlap syndromes, although there has been no standardized definition. Patients with overlap syndromes present with both hepatitic and cholestatic serum liver tests and have histological features of AIH and PBC or PSC. The AIH-PBC overlap syndrome is the most common form, affecting almost 10% of adults with AIH or PBC. Single cases of AIH and autoimmune cholangitis (AMA-negative PBC) overlap syndrome have also been reported. The AIH-PSC overlap syndrome is predominantly found in children, adolescents and young adults with AIH or PSC. Interestingly, transitions from one autoimmune to another have also been reported in a minority of patients, especially transitions from PBC to AIH-PBC overlap syndrome. Overlap syndromes show a progressive course towards liver cirrhosis and liver failure without treatment. Therapy for overlap syndromes is empiric, since controlled trials are not available in these rare disorders. Anticholestatic therapy with ursodeoxycholic acid is usually combined with immunosuppressive therapy with corticosteroids and/or azathioprine in both AIH-PBC and AIH-PSC overlap syndromes. In end-stage disease, liver transplantation is the treatment of choice.
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Abstract
Autoimmune hepatitis (AIH) is a chronic hepatitis of unknown etiology which can progress to cirrhosis. Its clinical manifestations are highly variable and sometimes follow a fluctuating course. Diagnosis is based on characteristic histologic, clinical, biochemical and serological findings. Anti-inflammatory/immunosuppressive treatment frequently induces remission but long-term maintenance therapy is often required. Liver transplantation is generally successful in patients with decompensated cirrhosis unresponsive to or intolerant of medical therapy.
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Czaja AJ. Clinical Features, Differential Diagnosis and Treatment of Autoimmune Hepatitis in the Elderly. Drugs Aging 2008; 25:219-39. [DOI: 10.2165/00002512-200825030-00005] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Abstract
BACKGROUND AND AIMS Drug-related side effects are considered the major consequences of relapse and re-treatment in patients with autoimmune hepatitis. Our goals were to determine whether relapse is associated with disease progression and whether treatment end points can be refined. METHODS The outcomes of 132 patients with definite type 1 autoimmune hepatitis who had been treated comparably until remission were assessed retrospectively after drug withdrawal. RESULTS Patients who had relapsed repeatedly after initial treatment withdrawal developed cirrhosis more commonly than patients who sustained remission (18/48 vs 1/22, P=0.004), and those who relapsed once (18/48 vs 2/21, P=0.02). Hepatic death or the need for liver transplantation was also more frequent in the patients who had multiple relapses than those who sustained remission (13/64 vs 0/30, P=0.008) and those who relapsed once (13/64 vs 1/38, P=0.02). Patients who sustained their remission had a higher frequency of normal laboratory indices at drug withdrawal than patients who relapsed (88% vs 46%, P=0.003). Adverse outcomes after relapse did not distinguish patients until after 5 years of observation. CONCLUSIONS Multiple relapses are associated with a poorer prognosis than sustained remission or single relapse episodes. Initial treatment to resolution of laboratory abnormalities may afford the greatest opportunity to prevent relapse.
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Affiliation(s)
- Aldo J Montano-Loza
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
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Montano Loza AJ, Czaja AJ. Current therapy for autoimmune hepatitis. ACTA ACUST UNITED AC 2007; 4:202-14. [PMID: 17404588 DOI: 10.1038/ncpgasthep0768] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2006] [Accepted: 01/12/2007] [Indexed: 12/14/2022]
Abstract
The treatment of autoimmune hepatitis is evolving as the pathogenic pathways that underlie the disease are defined, new immunosuppressive agents are tested, and site-specific molecular interventions become feasible. Prednisone alone or at a reduced dose combined with azathioprine is the conventional treatment. Patients with HLA genotype DRB1*0301 have a poorer treatment response and a more frequent need for liver transplantation than those with HLA genotype DRB1*0401. Therapy to the point when liver test results and histological findings are normal reduces, but does not eliminate, the occurrence of relapse. Treatment failure warrants reassessment with regard to the accuracy of the original diagnosis and the exclusion of variant forms of hepatitis or concomitant alternative diseases. Ciclosporin might be effective as short-term, front-line therapy in infants and adults, and calcineurin inhibitors might salvage patients who are refractory to corticosteroid regimens. Mycophenolate mofetil can induce an improvement in laboratory test results and reduce the requirement for corticosteroids. Sirolimus is effective for treatment of de novo autoimmune hepatitis that develops after liver transplantation. Synthetic peptides that block autoantigen presentation, cytokine manipulations, oral tolerance regimens, T-cell vaccination, and gene therapy are all interventions that will be able to emerge after a reliable animal model of the human disease has been developed.
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Affiliation(s)
- Aldo J Montano Loza
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
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Sipe WE, Rosenthal P. Autoimmune hepatitis in children: diagnosis, pathology and treatment. Expert Rev Clin Immunol 2007; 3:159-69. [PMID: 20477105 DOI: 10.1586/1744666x.3.2.159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Autoimmune hepatitis (AIH) is characterized by progressive inflammation of the liver and destruction of liver parenchyma. Rare in absolute terms, it is nevertheless an important cause of noninfectious chronic liver disease in children. In many ways, the diagnosis and treatment of children with AIH has changed little over the last 10 years. However, in recent years, steady progress in defining the genetic, immunologic and potential environmental triggers that underlie this disease, in addition to increasing experience with a wider array of therapeutic agents, promises to expand our understanding and ability to treat AIH effectively. This review will summarize the current clinical and pathophysiological understanding of AIH in children, along with therapeutic options.
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Affiliation(s)
- Walter Eb Sipe
- University of California, Division of Pediatric Gastroenterology, Hepatology and Nutrition, 500 Parnassus Avenue, Box 0136, San Francisco, CA 94143-0136, USA.
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Csepregi A, Malfertheiner P. Do we need alternative treatment options for autoimmune hepatitis? Curr Gastroenterol Rep 2006; 8:177-8. [PMID: 16764782 DOI: 10.1007/s11894-006-0069-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Antal Csepregi
- Department of Gastroenterology, Hepatology, and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Leipziger Strasse 44, D-39120, Magdeburg, Germany
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