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Costaguta A, Costaguta G, Álvarez F. Autoimmune hepatitis: Towards a personalized treatment. World J Hepatol 2024; 16:1225-1242. [PMID: 39606175 PMCID: PMC11586748 DOI: 10.4254/wjh.v16.i11.1225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 09/02/2024] [Accepted: 10/11/2024] [Indexed: 11/06/2024] Open
Abstract
Autoimmune hepatitis is an uncommon condition that affects both adults and children and is characterized by chronic and recurrent inflammatory activity in the liver. This inflammation is accompanied by elevated IgG and autoantibody levels. Historically, treatment consists of steroids with the addition of azathioprine, which results in remission in approximately 80% of patients. Despite significant advancements in our understanding of the immune system over the past two decades, few modifications have been made to treatment algorithms, which have remained largely unchanged since they were first proposed more than 40 years ago. This review summarized the various treatment options currently available as well as our experiences using them. Although steroids are the standard treatment for induction therapy, other medications may be considered. Cyclosporin A, a calcineurin inhibitor that decreases T cell activation, has proven effective for induction of remission, but its long-term side effects limit its appeal for maintenance. Tacrolimus, a drug belonging to the same family, has been used in patients with refractory diseases with fewer side effects. Sirolimus and everolimus have interesting effects on regulatory T cell populations and may become viable options in the future. Mycophenolate mofetil is not effective for induction but is a valid alternative for patients who are intolerant to azathioprine. B cell-depleting drugs, such as rituximab and belimumab, have been successfully used in refractory cases and are useful in both the short and long term. Other promising treatments include anti-tumor necrosis factors, Janus kinases inhibitors, and chimeric antigen receptor T cell therapy. This growing armamentarium allows us to imagine a more tailored approach to the treatment of autoimmune hepatitis in the near future.
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Affiliation(s)
- Alejandro Costaguta
- Department of Hepatology and Liver Transplant Unit, Sanatorio de Niños de Rosario, Rosario 2000, Santa Fe, Argentina.
| | - Guillermo Costaguta
- Department of Gastroenterology, Hepatology, and Nutrition, CHU Sainte-Justine, Montreal H3T 1C5, Quebec, Canada
| | - Fernando Álvarez
- Department of Pediatrics, CHU Sainte-Justine, Montreal H3T 1C5, Quebec, Canada
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Costaguta GA, Álvarez F. B cell depletion for autoimmune liver diseases: A retrospective review of indications and outcomes. JPGN REPORTS 2024; 5:326-333. [PMID: 39149184 PMCID: PMC11322033 DOI: 10.1002/jpr3.12098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Revised: 04/08/2024] [Accepted: 05/19/2024] [Indexed: 08/17/2024]
Abstract
Objectives Pediatric autoimmune hepatitis has an incidence of 0.23/100.000 children in North America, with a bleak prognosis if left untreated. Steroids are the therapy of choice but are not always effective. B cell depletion is a safe and effective therapy that allows for a steroid-sparing protocol, especially in patients who do not tolerate side effects. Methods We retrospectively reviewed rituximab-treated patients between 2017 and 2022. Demographics, previous treatments, reasons for B cell depletion, response, and adverse effects were noted. Results Six patients with a mean age of 10.2 years were included. All patients had comorbidities that rendered treatment with steroids unsuccessful or undesirable. Rituximab was started at a mean follow-up of 8 months. After 6 months, the mean alanine transaminase and aspartate transaminase levels decreased from 575 IU/L and 342 IU/L, respectively, to 28 IU/L (p = 0.02) and 36 IU/L (p = 0.008), respectively. Mean γ-glutamyl transpeptidase decreased from 105 to 25 IU/L (p = 0.01). Immunoglobulin G levels were normalized in all patients (p = 0.01). No severe adverse events were observed. One patient had persistent hypogammaglobulinemia, and another had lymphopenia. Conclusion B-cell depletion is an effective and safe treatment for autoimmune liver diseases and should be included as an option, particularly for relapsing patients in whom steroids are undesirable or have shown nonadherence.
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Affiliation(s)
| | - Fernando Álvarez
- Gastroenterology, Hepatology and NutritionCHU Sainte‐JustineMontrealQuebecCanada
- Department of PediatricsUniversity of MontrealMontrealQuebecCanada
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Khan SA, Ali N, Farooq MA, Hasan S, Malik MI. Spectrum of Pediatric Autoimmune Hepatitis in a Cohort of Pakistani Children. Glob Pediatr Health 2024; 11:2333794X241251644. [PMID: 38694564 PMCID: PMC11062213 DOI: 10.1177/2333794x241251644] [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: 10/24/2023] [Revised: 03/26/2024] [Accepted: 04/12/2024] [Indexed: 05/04/2024] Open
Abstract
Background. Autoimmune hepatitis (AIH) is increasingly seen in children worldwide and it is more severe in children compared to adults. This study highlights the biochemical and clinical aspect, treatment given and outcome of the disease including pediatric liver transplantation. Study. Retrospective review (2012-2022) was done in Shifa International Hospital, Islamabad. Patients under 18 years diagnosed with AIH were included. Data related to age, gender, clinical features, laboratory investigations including liver function test, liver biopsy findings and imaging modalities were included. Results. Fifteen patients were included 7 (47%) were males and 8 (53%) females. AIH type 1 was the most common type seen in 7 (46%), AIH type 2 in 5 (33%) and seronegative in 3 (20%). Jaundice was the most common symptom. Liver biopsy showed findings characteristic of AIH. Liver transplant performed in 3 patients. Conclusion. The study highlights the varied clinical presentation of AIH in Pakistani children.
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Affiliation(s)
- Sabeen Abid Khan
- Shifa college of medicine, Shifa Tameer-e-Millat University, Islamabad, Pakistan
| | - Naurin Ali
- Shifa college of medicine, Shifa Tameer-e-Millat University, Islamabad, Pakistan
| | | | | | - Munir Iqbal Malik
- Shifa college of medicine, Shifa Tameer-e-Millat University, Islamabad, Pakistan
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The Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines for management of autoimmune hepatitis 2022. Clin Mol Hepatol 2023; 29:542-592. [PMID: 37137334 PMCID: PMC10366804 DOI: 10.3350/cmh.2023.0087] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 03/27/2023] [Accepted: 04/03/2023] [Indexed: 05/05/2023] Open
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Maggiore G, Bernard O, Mosca A, Ballot E, Johanet C, Jacquemin E. Long-term outcomes of patients with type 1 or 2 autoimmune hepatitis presenting in childhood. J Hepatol 2023; 78:979-988. [PMID: 36708813 DOI: 10.1016/j.jhep.2023.01.013] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 12/14/2022] [Accepted: 01/12/2023] [Indexed: 01/26/2023]
Abstract
BACKGROUND & AIMS In children with autoimmune hepatitis, uncertainties include outcomes associated with type 2 hepatitis, the possibility of and criteria for attempting withdrawal of treatment, and long-term outcomes. We report our experience on these issues. METHODS From 1973 to 2002, 117 children with type 1 (n = 65) or type 2 (n = 52) hepatitis, excluding fulminant hepatitis, were treated, primarily with prednisone and azathioprine. Median follow-up was 20 years in survivors. RESULTS Normalisation of aminotransferases and prothrombin ratio were observed in 93% and 84% of children, respectively; sustained remission after treatment withdrawal was recorded in 24% of the entire population, with a median follow-up of 7 years. Sustained treatment-free remission was obtained in 11 of 24 children with follow-ups of 4-22 years based on durable normalisation of aminotransferases (without histological assessment). Gastrointestinal bleeding from varices and the emergence of extrahepatic autoimmune disorders occurred in 10 and 22 patients, respectively. Liver transplantation was performed in 23 patients at a median age of 21 years. The 30-year probabilities of overall and native liver survival were 81% and 61%, respectively. No differences were observed between type 1 and 2 hepatitis for any of the component parts of outcome. In the multivariate analysis, a persistent abnormal prothrombin ratio was associated with worse probabilities of overall and native liver survival. CONCLUSIONS In terms of liver outcome, type 2 hepatitis is not different from type 1. Withdrawal of treatment is possible without prior liver histology. A persistent abnormal prothrombin ratio identifies patients who will require liver transplantation in adolescence or early adulthood. IMPACT AND IMPLICATIONS In children with autoimmune hepatitis, there are conflicting reports on the differences in outcome between type 1 and type 2 hepatitis, and on the possibility of treatment withdrawal, before which liver histology is required; data concerning >10-year overall and native liver survival rates are limited. In this study, we found no differences in outcomes between type 1 and 2 hepatitis; a durable treatment-free state was achieved in 19% of all patients throughout childhood and early adulthood, and in 45% of children for whom treatment withdrawal was attempted without prior liver histology; prothrombin was found to be predictive of 30-year overall and native liver survival. The results allow for a less-strict approach to treatment withdrawal in children, avoiding the risks of a liver biopsy, and they provide a tool to help anticipate the need for liver transplantation before complications occur.
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Affiliation(s)
- Giuseppe Maggiore
- Hepatogastroenterology, Rehabilitative Nutrition, Digestive Endoscopy and Liver Transplant Unit, ERN RARE LIVER, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
| | - Olivier Bernard
- Paediatric Hepatology and Liver Transplantation Unit, National Reference Centre for Inflammatory Biliary Diseases and Autoimmune Hepatitis, FILFOIE, ERN RARE LIVER, Bicetre Hospital, APHP, University Paris-Saclay, Le Kremlin-Bicetre, France
| | - Antonella Mosca
- Hepatogastroenterology, Rehabilitative Nutrition, Digestive Endoscopy and Liver Transplant Unit, ERN RARE LIVER, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Eric Ballot
- Laboratory of Autoimmunity, Department of Immunology, St Antoine Hospital, APHP, Sorbonne University, Paris, France
| | - Catherine Johanet
- Laboratory of Autoimmunity, Department of Immunology, St Antoine Hospital, APHP, Sorbonne University, Paris, France
| | - Emmanuel Jacquemin
- Paediatric Hepatology and Liver Transplantation Unit, National Reference Centre for Inflammatory Biliary Diseases and Autoimmune Hepatitis, FILFOIE, ERN RARE LIVER, Bicetre Hospital, APHP, University Paris-Saclay, Le Kremlin-Bicetre, France; Inserm U1193, Hepatinov, University Paris-Saclay, Orsay, France
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Sutton H, Tayler R, Chalmers I, Cowieson J, Fraser K, Henderson P, Hansen R. The Epidemiology of Pediatric Autoimmune Hepatitis in Scotland: A National Cohort Study. JPGN REPORTS 2022; 3:e223. [PMID: 37168624 PMCID: PMC10158286 DOI: 10.1097/pg9.0000000000000223] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 05/02/2022] [Indexed: 05/13/2023]
Abstract
Autoimmune hepatitis (AIH) is a rare, but potentially severe, cause of liver disease in children. We aimed to summarize how children with AIH in Scotland presented, were investigated and managed in addition to producing novel epidemiological data and outcomes. Methods All prevalent pediatric patients with AIH cared for in pediatric services between January 2013 and September 2018 were included. Individual patient data were obtained from electronic patient records in the 3-main academic pediatric centers in Scotland covering the entire population. Results Thirty-eight patients were included (25 female) with median follow-up of 33 months (range, 2-145 mo) and 136 total patient years. The incidence between 2014 and 2017 was 0.49/100 000/y (95% confidence interval, 0.29-0.78) and point prevalence between 2013 and 2018 was 1.75/100 000 (95% confidence interval, 1.42-2.13). Thirty-five (92%) patients were autoantibody positive, most commonly anti-nuclear antibody (63%) and anti-smooth muscle antibody (42%). Thirty-seven (97%) patients had induction therapy with oral corticosteroids, 30 (79%) required maintenance treatment with azathioprine, and 23 (61%) received ursodeoxycholic acid. There were 1.4 disease flares per 10 patient years and 3 patients required liver transplantation with an overall 5-year survival rate without the need for transplantation of 95%. Conclusions We calculated a novel incidence and prevalence rate for pediatric AIH in Scotland. Nearly all were invariably treated initially with corticosteroids with most placed-on azathioprine as maintenance therapy. Outcomes were generally favorable with low rates of disease flares and the need for transplantation being rare.
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Affiliation(s)
- Harry Sutton
- From the Department of Paediatric Gastroenterology, Royal Hospital for Children, Glasgow, United Kingdom
| | - Rachel Tayler
- From the Department of Paediatric Gastroenterology, Royal Hospital for Children, Glasgow, United Kingdom
| | - Iain Chalmers
- Department of Paediatric Gastroenterology, Royal Aberdeen Children’s Hospital, Aberdeen, United Kingdom
| | - Jennifer Cowieson
- From the Department of Paediatric Gastroenterology, Royal Hospital for Children, Glasgow, United Kingdom
| | - Karen Fraser
- From the Department of Paediatric Gastroenterology, Royal Hospital for Children, Glasgow, United Kingdom
| | - Paul Henderson
- Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for Children and Young People, Edinburgh, United Kingdom
- Child Life and Health, University of Edinburgh, Edinburgh, United Kingdom
| | - Richard Hansen
- From the Department of Paediatric Gastroenterology, Royal Hospital for Children, Glasgow, United Kingdom
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Adil N, Siddiqui AJ, Musharraf SG. Metabolomics‐based Researches in Autoimmune Liver Disease: A
Mini‐Review. Scand J Immunol 2022. [DOI: 10.1111/sji.13208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Affiliation(s)
- Nurmeen Adil
- H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences University of Karachi Karachi Pakistan
| | - Amna Jabbar Siddiqui
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences University of Karachi Karachi Pakistan
| | - Syed Ghulam Musharraf
- H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences University of Karachi Karachi Pakistan
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences University of Karachi Karachi Pakistan
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Kim DK, Yoon H, Han K, Kim J, Lee MJ, Kim S, Koh H, Han SJ, Shin HJ. Effect of different driver power amplitudes on liver stiffness measurement in pediatric liver MR elastography. Abdom Radiol (NY) 2021; 46:4729-4735. [PMID: 34216244 DOI: 10.1007/s00261-021-03197-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 06/22/2021] [Accepted: 06/23/2021] [Indexed: 12/22/2022]
Abstract
PURPOSE To assess how different driver power amplitudes affect the measurement of liver stiffness in pediatric liver magnetic resonance elastography (MRE). METHODS From January 2018 to May 2018, pediatric patients (≤ 18 years) who underwent liver MRE with 20% and 56% driver power amplitudes were included in this retrospective study. Region-of-interests (ROIs) were drawn on four stiffness maps to include the largest area of the liver parenchyma. Intraclass correlation coefficients (ICCs) were used to assess agreements for the area, mean, maximum, minimum and standard deviation of liver stiffness between the driver power amplitudes. RESULTS 128 MRE stiffness maps from 16 patients (M:F = 10:6, median 12.5 years old) were included. On MRE, median ROI areas of liver were 83.1 cm2 (range, 46.9-144.1 cm2) and 63.0 cm2 (range, 5.4-123.4 cm2) for the driver power amplitudes of 20% and 56%, respectively. Median liver stiffness values were 2.3 kPa (range, 1.7-8.0 kPa) and 2.8 kPa (range, 1.7-8.5 kPa). Maximum and minimum liver stiffness values were 5.3 kPa and 1.0 kPa for 20% and 7.8 kPa and 1.1 kPa for 56%. Standard deviation was 0.6 kPa for 20% and 1.0 kPa for 56%. ICC values between the two power amplitudes were 0.33-0.51 for the ROI area and the maximum, minimum and standard deviation values of liver stiffness. The ICC value for liver stiffness was 0.857 (95% confidence interval, 0.760-0.915). CONCLUSION Liver stiffness with two driver power amplitudes on MRE showed good reliability in pediatric patients. Driver power amplitudes need to be optimized according to the pediatric liver size.
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Affiliation(s)
- Dong-Kyu Kim
- Department of Radiology, the Armed Forces Capital Hospital, Seongnam, Republic of Korea
- Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Haesung Yoon
- Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Republic of Korea
- Severance Pediatric Liver Disease Research Group, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Kyunghwa Han
- Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jisoo Kim
- Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Republic of Korea
- Severance Pediatric Liver Disease Research Group, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Mi-Jung Lee
- Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Republic of Korea
- Severance Pediatric Liver Disease Research Group, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Seung Kim
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
- Severance Pediatric Liver Disease Research Group, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hong Koh
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
- Severance Pediatric Liver Disease Research Group, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Seok Joo Han
- Department of Pediatric Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
- Severance Pediatric Liver Disease Research Group, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hyun Joo Shin
- Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
- Severance Pediatric Liver Disease Research Group, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
- Department of Radiology, Yongin Severance Hospital, Yonsei University College of Medicine, 363, Dongbaekjukjeon-daero, Giheung-gu, Yongin-si, Gyeonggi-do, 16995, Republic of Korea.
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Grama A, Pop TL. Etiology of acute liver failure in children. PEDIATRU.RO 2021; 3:22. [DOI: 10.26416/pedi.63.3.2021.5483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
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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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Alsayed MAL, Elbeah SM, El-Desoky MM, Elziny SM, Megahed A. Polymorphism in Macrophage Migration Inhibitory Factor -173GC in Pediatric Patients with Autoimmune Hepatitis. Pediatr Gastroenterol Hepatol Nutr 2020; 23:63-71. [PMID: 31988876 PMCID: PMC6966214 DOI: 10.5223/pghn.2020.23.1.63] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Accepted: 09/13/2019] [Indexed: 12/12/2022] Open
Abstract
PURPOSE Autoimmune hepatitis (AIH) is a chronic disease that may lead to cirrhosis. The immunopathogenesis of AIH is not fully understood and it mainly involves T-cell mediated mechanism. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that promotes T cell response and its polymorphism may serve as a severity marker of AIH. No previous study has considered investigating MIF polymorphism in children with AIH. METHODS Forty-two children with definite diagnosis of AIH were enrolled along with 100 age and sex matched controls. All participants were tested for polymorphism at -173GC (rs755622) of MIF gene. All patients received the standard protocol of steroid plus azathioprine to achieve remission. Liver biopsy was performed at time of diagnosis for all patients and only 18 of them underwent a second biopsy after treatment. RESULTS No statistically significant differences in the frequency of the genotypes GG and GC or in allele distribution were found in both patient and control groups (p=0.590, 0.640 respectively). Initial alanine aminotransferase (ALT) levels at the time of presentation was significantly higher in the GC group than GG group (p=0.020). GC genotype significantly correlated with disease relapse (r=0.41, p=0.007). Regression of necroinflammation and the fibrosis score in the second liver biopsy was statistically significant in the GG group (p<0.0001, p=0.010 respectively). CONCLUSION MIF -173GC polymorphism is associated with clinically significant markers of pediatric AIH, including increased initial serum ALT levels, may help predict necroinflammatory/fibrosis regression effectively, following immunosuppressive treatment.
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Affiliation(s)
- Mona Abdel Latif Alsayed
- Pediatric Gastroenterology and Hepatology Unit, Mansoura University Children's Hospital, Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Shymaa Mohsen Elbeah
- Biochemistry Department, Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Manal M El-Desoky
- Biochemistry Department, Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Shereen Magdy Elziny
- Pediatric Gastroenterology and Hepatology Unit, Mansoura University Children's Hospital, Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Ahmed Megahed
- Pediatric Gastroenterology and Hepatology Unit, Mansoura University Children's Hospital, Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egypt
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Fuchs S, Bayer M, Taubert R, Manns MP, Pfeilschifter JM, Christen U, Hintermann E. Effects of adenovirus-induced hepatocyte damage on chronic bile duct inflammation in a sclerosing cholangitis mouse model. Liver Int 2019; 39:2330-2340. [PMID: 31225929 DOI: 10.1111/liv.14183] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Revised: 05/10/2019] [Accepted: 06/15/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS Four major autoimmune diseases target the liver. They develop because of bile duct destruction, leading to chronic cholestasis or result from hepatocyte damage like autoimmune hepatitis (AIH). Interestingly, some patients simultaneously show features of both cholangitis and AIH. Our goal was to mimic such concurrent characteristics in a mouse model that would help deciphering mechanisms possibly involved in an inflammatory crosstalk between cholestatic disease and hepatitis. METHODS Mdr2-/- mice, which spontaneously develop sclerosing cholangitis because of accumulation of toxic bile salts, were infected with adenovirus (Ad) encoding human Cytochrome P4502D6 (hCYP2D6), the major target autoantigen in type-2 AIH, to trigger hepatocyte injury. Wild type FVB mice were controls. RESULTS Resulting Ad-Mdr2-/- mice presented with cholangitis, fibrosis and cellular infiltrations that were higher than in Mdr2-/- or Ad-FVB mice. Increased levels of anti-neutrophil cytoplasmic antibodies but similar anti-hCYP2D6 antibody titres were detected in Ad-Mdr2-/- compared to Mdr2-/- and Ad-FVB mice respectively. IFNγ-expressing hCYP2D6-specific CD4 T cells declined, whereas hCYP2D6-specific CD8 T cells increased in Ad-Mdr2-/- compared to Ad-FVB mice. The overall T cell balance in Ad-Mdr2-/- mice was a combination of a type 17 T cell response typically found in Mdr2-/- mice with a type 1 dominated T cell response characteristic for Ad-FVB mice. Simultaneously, the type 2 T cell compartment was markedly reduced. CONCLUSIONS Experimental hepatitis induction in a mouse with sclerosing cholangitis results in a disorder which represents not simply the sum of the individual characteristics but depicts a more complex entity which urges on further analysis.
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Affiliation(s)
- Sina Fuchs
- Pharmazentrum Frankfurt / ZAFES, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Monika Bayer
- Pharmazentrum Frankfurt / ZAFES, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Richard Taubert
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Michael P Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Josef M Pfeilschifter
- Pharmazentrum Frankfurt / ZAFES, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Urs Christen
- Pharmazentrum Frankfurt / ZAFES, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Edith Hintermann
- Pharmazentrum Frankfurt / ZAFES, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany
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Aljumah AA, Al-Ashgar H, Fallatah H, Albenmousa A. Acute onset autoimmune hepatitis: Clinical presentation and treatment outcomes. Ann Hepatol 2019; 18:439-444. [PMID: 31040094 DOI: 10.1016/j.aohep.2018.09.001] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2018] [Revised: 09/10/2018] [Accepted: 09/13/2018] [Indexed: 02/07/2023]
Abstract
INTRODUCTION AND AIM Autoimmune hepatitis (AIH) may present acutely, which can rapidly progress to fulminant type. This pattern has been described worldwide but is generally under-reported. We aim to describe the clinical presentation and treatment outcomes of patients with acute onset AIH. MATERIALS AND METHODS A multicenter retrospective cohort study of patients with acute onset AIH. Clinical, biochemical, and histological data were analyzed and the outcomes were reported. RESULTS Seventy patients were included. The mean age was 33.8±1.5 years and 58.6% were female. Upon initial presentation, 94% had jaundice, 44% had fatigue, 31% had pruritus, and 29% had abdominal pain. Biochemical analysis revealed elevated alanine transaminase (733±463.6), aspartate transaminase (699±423), and total bilirubin (210±181.8). Antinuclear antibody (ANA) was positive in 61% of patients, anti-smooth muscle antibody (ASMA) in 69%, and both in 31%; immunoglobulin G (IgG) was elevated in 86% of patients. Advanced fibrosis was found in 39%. Complete remission was achieved in 74.3%, two patients required liver transplants and six died. No specific biomarkers were identified as predictive of remission; however, advanced age was associated with poor prognosis. CONCLUSION Acute onset AIH is a disease that requires early diagnosis and management. We confirmed that elevated transaminases are the hallmark of biochemical presentation of acute AIH. High IgG, ANA and ASMA are typically present in such patients upon presentation, however, their absence does not totally exclude the diagnosis. Initial response to treatment was excellent; however, the long-term mortality was higher than the general patient population.
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Affiliation(s)
- Abdulrahman A Aljumah
- Hepatology Division, Department of Hepatobiliary Sciences and Organ Transplant Center, King Abdulaziz Medical City, King Saud bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
| | - Hamad Al-Ashgar
- Section of Gastroenterology, Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Hind Fallatah
- Division of Gastroenterology and Hepatology, Department of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Ali Albenmousa
- Department of Gastroenterology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
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Lee CZ, Peng SSF, Lee CS, Chen HL, Ni YH, Chang MH, Wu JF. Transient elastography correlated with diffusion-weighted magnetic resonance imaging and cholestatic complications. J Formos Med Assoc 2019; 118:1522-1527. [PMID: 30621960 DOI: 10.1016/j.jfma.2018.12.018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Revised: 11/20/2018] [Accepted: 12/21/2018] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND/PURPOSE The study aim to investigate the correlation between diffusion-weighted magnetic resonance imaging (DW-MRI) and transient elastography (TE) liver fibrosis findings in children with cholestatic liver diseases, and the utility of TE findings to predict cholestatic complications in children. METHODS This cross-sectional study enrolled 36 cholestatic children (21 boys and 15 girls). All study subjects underwent TE and DW-MRI studies to assess liver stiffness. All study subjects were followed prospectively, and their cholestatic complications were analyzed. The optimum cut-off TE value for the prediction of cholestatic complications was determined by receiver operating characteristic (ROC) analysis. RESULTS A significant negative correlation between liver stiffness measurements (LSMs) and right-liver-to-psoas apparent diffusion coefficient ratios (LTPARs) was found in the study cohort (correlation coefficient = -0.52, p = 0.001). An LSM cut-off > 8.6 kPa was optimal for predicting complications of cholestasis in 6 months of this cohort (p < 0.001). Survival analysis revealed that an LSM of >8.6 kPa was significantly predictive of cholestatic complications in 6 months (hazard ratio = 4.89; 95% CI = 1.41-16.97; p = 0.01). CONCLUSION TE and DW-MRI findings showed a similar ability to predict liver fibrosis in cholestatic children. The LSMs measured by TE are predictive of the occurrence of cholestatic complications in 6 months in children with cholestatic liver diseases.
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Affiliation(s)
- Chai-Zhaou Lee
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Department of Pediatrics, Changhua Christian Hospital, Yun Lin Branch, Xiluo Township, Yunlin County, Taiwan
| | | | - Chee-Seng Lee
- Department of Pediatrics, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan
| | - Huey-Ling Chen
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Department of Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Yen-Hsuan Ni
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Department of Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Mei-Hwei Chang
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Department of Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Jia-Feng Wu
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
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Sciveres M, Nastasio S, Maggiore G. Novel Diagnostic and Therapeutic Strategies in Juvenile Autoimmune Hepatitis. Front Pediatr 2019; 7:382. [PMID: 31616649 PMCID: PMC6763601 DOI: 10.3389/fped.2019.00382] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Accepted: 09/04/2019] [Indexed: 12/12/2022] Open
Abstract
Juvenile autoimmune hepatitis (JAIH) is a rare, chronic, inflammatory disease of the liver characterized by a complex interaction between genetic, immunological, and environmental factors leading to loss of immunotolerance to hepatic antigens. It affects both children and adolescents, most commonly females, and its clinical manifestations are quite variable. JAIH is progressive in nature and if left untreated may lead to cirrhosis and terminal liver failure. Although JAIH was first described almost 50 years ago, there have been few significant advances in the clinical management of these patients, both in terms of available diagnostic tools and therapeutic options. Aminotransferase activity, class G immunoglobulins and autoantibodies are the biomarkers used to diagnose AIH and monitor treatment response alongside clinical and histological findings. Despite their utility and cost-effectiveness, these biomarkers are neither an accurate expression of AIH pathogenic mechanism nor a precise measure of treatment response. Current standard of care is mainly based on the administration of steroids and azathioprine. This combination of drugs has been proven effective in inducing remission of disease in the majority of patients dramatically improving their survival; however, it not only fails to restore tolerance to hepatic autoantigens, but it also does not halt disease progression in some patients, it is often needed life-long and finally, it has deleterious side-effects. The ideal therapy should be enough selective to contrast immune-mediated live damage while preserving or potentiating the ability to develop permanent tolerance vs. pathogenic autoantigens. By reviewing the state of the art literature, this article highlights novel diagnostic and therapeutic strategies for managing pediatric AIH with a special focus on new strategies of immunotherapy. These promising tools could improve the diagnostic algorithm, more accurately predict disease prognosis, and provide targeted, individualized treatment.
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Affiliation(s)
- Marco Sciveres
- Pediatric Hepatology and Liver Transplantation, ISMETT-University of Pittsburgh Medical Center Italy, Palermo, Italy
| | - Silvia Nastasio
- Division of Gastroenterology, Hepatology, and Nutrition, Harvard Medical School, Boston Children's Hospital, Boston, MA, United States
| | - Giuseppe Maggiore
- Pediatric Hepatology and Liver Transplantation, ISMETT-University of Pittsburgh Medical Center Italy, Palermo, Italy.,Section of Pediatrics, Department of Medical Sciences, University of Ferrara, Ferrara, Italy
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Acute Liver Failure in Children. PEDIATRIC HEPATOLOGY AND LIVER TRANSPLANTATION 2019. [PMCID: PMC7122201 DOI: 10.1007/978-3-319-96400-3_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
“Acute liver failure” (ALF) and “fulminant liver failure” are terms used interchangeably to describe severe and sudden onset of liver cell dysfunction leading on to synthetic and detoxification failure across all age groups. Considerable variations exist between ALF in children and adults, in terms of aetiology and prognosis. Encephalopathy is not essential to make a diagnosis of ALF in children but when present has a bad prognosis. Early recognition of ALF and initiation of supportive management improve the outcome. Liver transplantation remains the only definitive treatment when supportive medical management fails.
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Ferrari F, Ranucci G, Aloi M, Della Volpe L, Viola F, Miele E, Cucchiara S, Iorio R. A promising medium-term follow-up of pediatric sclerosing cholangitis: Mild phenotype or early diagnosis? Hepatol Res 2018; 48:556-565. [PMID: 29316057 DOI: 10.1111/hepr.13059] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2017] [Revised: 01/02/2018] [Accepted: 01/05/2018] [Indexed: 12/24/2022]
Abstract
AIM Sclerosing cholangitis (SC) is a chronic cholestatic liver disease that is being increasingly diagnosed in childhood. The long-term course and prognosis of pediatric SC are poorly described. METHODS We reviewed data of pediatric SC patients, followed in two referral centers, during a period of up to 20 years. We aimed to evaluate long-term outcomes according to SC phenotype. RESULTS Among 45 patients (median age, 10.4 years; male patients, 73.4%) 29 (64.4%) were asymptomatic at presentation. Twenty patients (44%) had a concomitant inflammatory bowel disease (SC/IBD). Autoimmune features were found in 20 patients (44%). Liver biopsy showed severe fibrosis or cirrhosis in 32% of cases. Patients with SC alone had a higher rate of interface hepatitis at liver biopsy than SC/IBD patients. All children received ursodeoxycholic acid at diagnosis, and 17 received steroids and/or azathioprine. After a mean follow-up of 8.7 ± 5.6 years, all patients were alive and seven developed at least one liver-related complication. At the end of follow-up, 10 patients stopped immunosuppressants and two had no therapy. Only two patients underwent liver transplantation. Complication-free survival did not differ between SC/IBD and SC patients, but survival was longer in patients without autoimmune features. CONCLUSIONS In our early diagnosed cohort, the 9-year survival with native liver was better than that reported in other studies. Approximately 15% of patients developed liver-related disease complications, less than previously reported. The long-term course of SC was negatively influenced by the presence of autoimmune features, but not by concomitant IBD.
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Affiliation(s)
- Federica Ferrari
- Pediatric Gastroenterology and Liver Unit, Department of Pediatrics, Sapienza University of Rome, Italy
| | - Giusy Ranucci
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy
| | - Marina Aloi
- Pediatric Gastroenterology and Liver Unit, Department of Pediatrics, Sapienza University of Rome, Italy
| | - Luca Della Volpe
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy
| | - Franca Viola
- Pediatric Gastroenterology and Liver Unit, Department of Pediatrics, Sapienza University of Rome, Italy
| | - Erasmo Miele
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy
| | - Salvatore Cucchiara
- Pediatric Gastroenterology and Liver Unit, Department of Pediatrics, Sapienza University of Rome, Italy
| | - Raffaele Iorio
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy
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18
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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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19
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Roberts SK, Lim R, Strasser S, Nicoll A, Gazzola A, Mitchell J, Siow W, Khoo T, Hamarneh Z, Weltman M, Gow P, Janko N, Tse E, Mishra G, Cheng EH, Levy M, Cheng W, Sood S, Skoien R, Mitchell J, Zekry A, George J, MacQuillan G, Wigg A, Stuart K, Sievert W, McCaughan G. Efficacy and Safety of Mycophenolate Mofetil in Patients With Autoimmune Hepatitis and Suboptimal Outcomes After Standard Therapy. Clin Gastroenterol Hepatol 2018; 16:268-277. [PMID: 29050991 DOI: 10.1016/j.cgh.2017.09.063] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2017] [Revised: 08/18/2017] [Accepted: 09/25/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Little is known about outcomes of patients with autoimmune hepatitis (AIH) who have a suboptimal outcome to standard therapy and are then given mycophenolate mofetil as rescue therapy. We evaluated the efficacy and safety of mycophenolate mofetil in patients failed by or intolerant to corticosteroids, with or without azathioprine. METHODS We performed a retrospective study of 105 patients with AIH who received mycophenolate mofetil therapy after an inadequate response or intolerance to standard therapy (98% received combination therapy with corticosteroids plus thiopurines). Patients were recruited from 17 liver clinics via the Australian Liver Association Clinical Research Network. We reviewed records for baseline demographic features and characteristics of liver disease, initial therapy, mycophenolate mofetil indications, treatment outcome, and side effects. The primary outcome was biochemical remission, defined as levels of alanine and aspartate transferase and IgG level within the normal reference range, with or without normal liver histology within the first 2 years of treatment. RESULTS The indication for mycophenolate mofetil therapy was non-response to treatment for 40% of cases and intolerance to therapy for 60%. Overall, 63 patients (60%) achieved biochemical remission following a median 12 weeks treatment with mycophenolate mofetil. The proportion of patients who achieved biochemical remission was similar between patients receiving mycophenolate mofetil for non-response to standard therapy (57%) and patients with intolerance to standard therapy (62%). However, a lower proportion of patients with cirrhosis achieved biochemical remission (47%) than patients without cirrhosis (6%) (P = .07). Serious adverse events occurred in 3 patients (2.7%) including 1 death, and 10 patients (9.2%) discontinued mycophenolate mofetil because of adverse events. CONCLUSION In this retrospective study of patients with AIH who received mycophenolate mofetil as a rescue therapy, we found the drug to be well tolerated and moderately effective, inducing biochemical remission in 60% of subjects. Rates of response are lower and rates of infection are higher in patients with AIH and cirrhosis. Prospective studies of mycophenolate mofetil are warranted for this population.
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Affiliation(s)
| | - Ricky Lim
- Royal Prince Alfred Hospital, Sydney
| | - Simone Strasser
- Royal Prince Alfred Hospital, Sydney; Centenary Research Institute, Sydney
| | - Amanda Nicoll
- Eastern Health, Box Hill Hospital, and Monash University, Box Hill
| | | | | | - Way Siow
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney
| | | | | | | | | | - Natasha Janko
- The Alfred, Melbourne; Eastern Health, Box Hill Hospital, and Monash University, Box Hill
| | | | - Gauri Mishra
- Monash Medical Centre and Monash University, Melbourne
| | | | | | | | | | | | | | | | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney
| | | | | | | | | | - Geoffrey McCaughan
- Royal Prince Alfred Hospital, Sydney; Centenary Research Institute, Sydney
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Jemilohun A, Adewoye O. LIVER CIRRHOSIS FROM AUTOIMMUNE HEPATITIS IN A NIGERIAN WOMAN: A CASE REPORT. Ann Ib Postgrad Med 2017; 15:133-136. [PMID: 29556169 PMCID: PMC5846176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
Autoimmune hepatitis (AIH) is a rare cause of chronic liver disease (CLD). It presents with varied clinical features from acute hepatitis to CLDs like chronic viral hepatitis and alcoholic liver disease, making it difficult to diagnose in the absence of a high index of suspicion and adequate laboratory support. Autoantibody-mediated hepatocyte injury is the major feature of AIH. We present a 44 year old woman with recurrent jaundice, ascites, splenomegaly, coagulopathy, negative chronic viral hepatitis screening, elevated IgG and positive anti-smooth muscle antibody. The patient responded well to immunosuppressive therapy. This report brings to the fore the need for physicians to maintain a high index of suspicion and thoroughly evaluate all CLD cases of seemingly 'unknown' etiology for AIH in order to prevent progression to end-stageliver- disease, since the disease is highly amenable to immunosuppressive therapy.
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Affiliation(s)
- A.C. Jemilohun
- Department of Medicine, Ladoke Akintola University of Technology/Ladoke Akintola University of Technology Teaching Hospital, Ogbomoso, Oyo State, Nigeria
| | - O.G. Adewoye
- Department of Medicine, Ladoke Akintola University of Technology Teaching Hospital, Ogbomoso, Oyo State, Nigeria
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21
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Díaz-Ramírez GS, Marín-Zuluaga JI, Donado-Gómez JH, Muñoz-Maya O, Santos-Sánchez Ó, Restrepo-Gutiérrez JC. Characterization of patients with autoimmune hepatitis at an university hospital in Medellín-Colombia: cohort study. GASTROENTEROLOGIA Y HEPATOLOGIA 2017; 41:87-96. [PMID: 29126693 DOI: 10.1016/j.gastrohep.2017.09.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Revised: 08/17/2017] [Accepted: 09/15/2017] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Autoimmune hepatitis is a chronic liver disease that impacts on morbidity and mortality of patients. Few epidemiological data exist of this in Latin America and Colombia. OBJECTIVES The aim of this study is to describe the demographic, clinical and laboratory characteristics of the patients; the treatment and the response to it, the evolution and course of the disease, requirement of liver transplantation and mortality. METHODS Historical cohort study that include patients attended at an University Hospital in Medellin, Colombia between January 2010 and December 2016 with ≥16 years age at the time of diagnosis of autoimmune hepatitis. Data collection was done from the review of medical records. Statistical analysis was performed using SPSS version 20. RESULTS The study included 278 patients, 90% of the patients were women, the median age at diagnosis was 50 years. 37.8% were cirrhotic at the time of diagnosis. The biochemical remission was 85%. In patients who developed cirrhosis it was found a higher proportion of men (21.2 vs. 7.8%, p=.027), a greater frequency of overlap autoimmune-primary sclerosant cholangitis (6.0 vs. 0% p=.006) and a greater frequency of non-response to treatment (12.1 vs. 1.6%, p=.004). CONCLUSION Autoimmune hepatitis is not a rare disease in Colombian population; it predominates in women but has a less favourable course in men. An important number of patients are cirrhotic at the time of diagnosis, the response to treatment and complications in our population are similar to those described worldwide.
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Affiliation(s)
| | - Juan Ignacio Marín-Zuluaga
- Grupo de Gastrohepatología, Universidad de Antioquia, Medellín, Colombia; Unidad de Hepatología y Trasplante Hepático, Hospital Pablo Tobón Uribe, Medellín, Colombia
| | | | - Octavio Muñoz-Maya
- Grupo de Gastrohepatología, Universidad de Antioquia, Medellín, Colombia; Unidad de Hepatología y Trasplante Hepático, Hospital Pablo Tobón Uribe, Medellín, Colombia
| | - Óscar Santos-Sánchez
- Grupo de Gastrohepatología, Universidad de Antioquia, Medellín, Colombia; Unidad de Hepatología y Trasplante Hepático, Hospital Pablo Tobón Uribe, Medellín, Colombia
| | - Juan Carlos Restrepo-Gutiérrez
- Grupo de Gastrohepatología, Universidad de Antioquia, Medellín, Colombia; Unidad de Hepatología y Trasplante Hepático, Hospital Pablo Tobón Uribe, Medellín, Colombia
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Jarasvaraparn C, Imran H, Siddiqui A, Wilson F, Gremse DA. Association of autoimmune hepatitis type 1 in a child with Evans syndrome. World J Hepatol 2017; 9:1008-1012. [PMID: 28878866 PMCID: PMC5569276 DOI: 10.4254/wjh.v9.i23.1008] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Revised: 04/26/2017] [Accepted: 07/10/2017] [Indexed: 02/06/2023] Open
Abstract
Autoimmune hepatitis (AIH) is a progressive liver disease that is often associated with extrahepatic autoimmune disorders. Evans syndrome (ES) is a rare autoimmune disorder, which is characterized by immune thrombocytopenia and autoimmune hemolytic anemia. Association of AIH with ES is rare, especially in children. We report a 3-year-old female with a past medical history of ES who presented with jaundice and significant transaminitis due to AIH type 1. She required multiple treatments with steroids as well as azathioprine, intravenous immunoglobulin and a course of rituximab.
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Gutierrez MJ, Gilson J, Zacharias J, Ishmael F, Bingham CA. Childhood Polyarthritis As Early Manifestation of Autoimmune Polyendocrinopathy with Candidiasis and Ectodermal Dystrophy Syndrome. Front Immunol 2017; 8:377. [PMID: 28458664 PMCID: PMC5394715 DOI: 10.3389/fimmu.2017.00377] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Accepted: 03/16/2017] [Indexed: 12/13/2022] Open
Abstract
Autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy (APECED) is a rare disorder of immune dysregulation caused by mutations in the autoimmune regulator (AIRE) gene. Individuals affected with APECED develop a clinical syndrome characterized by ectodermal abnormalities, autoantibody production, and organ-specific autoimmune manifestations. Inflammatory arthritis is usually not described as a part of the syndrome, and only sporadic cases are reported. We describe the case of a preschool-age girl who presented with hypoparathyroidism, hepatitis, interstitial pneumonitis, and chronic polyarthritis at 4 years of age and was found to have two compound heterozygous disease-associated mutations in the AIRE gene. We also conducted a literature review of the main characteristics of inflammatory arthritis in APECED patients. Our case and review demonstrate that (1) inflammatory arthritis, although rare, can be an early manifestation of APECED; (2) the diagnosis of APECED should be considered if mucocutaneous candidiasis, multiple organ-specific autoimmune manifestations, polyendocrinopathy, especially hypoparathyroidism or adrenal failure, or ectodermal dystrophy accompany joint symptoms; and (3) genotyping interpretation should take into account that mutations are found in the 14 exons of the gene, compound heterozygosity is common, and in some cases, only one or no mutated alleles are found.
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Affiliation(s)
- Maria J Gutierrez
- Division of Pediatric Allergy Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | - Jamie Zacharias
- Section of Allergy, Asthma and Immunology, Pennsylvania State University College of Medicine, Hershey, PA, USA
| | - Faoud Ishmael
- Section of Allergy, Asthma and Immunology, Pennsylvania State University College of Medicine, Hershey, PA, USA
| | - C April Bingham
- Division of Pediatric Rheumatology, Penn State Children's Hospital, Hershey, PA, USA
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Haerskjold A, Linder M, Henriksen L, Thomsen SF, Kieler H, Ravn H, Stensballe LG. Palivizumab Exposure and the Risk of Autoimmune Disease: A Cross-National Cohort Study. Paediatr Drugs 2016; 18:435-441. [PMID: 27665287 DOI: 10.1007/s40272-016-0191-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND Treatment with biologic pharmaceuticals may be associated with an increased risk of immune-mediated disease. Palivizumab is a humanized monoclonal antibody designed to provide passive immunity against respiratory syncytial virus infection. Palivizumab is primarily used in preterm children known to be immunologically immature. The long-term effect of palivizumab in terms of autoimmune diseases has not yet been investigated. AIM Our objective was to investigate whether exposure to palivizumab was associated with the development of autoimmune diseases in children. METHODS This was a population-based cohort study including data from 769,523 Danish children born between 1 January 1999 and 31 December 2010 and data from 581,742 Swedish children born between 1 July 2005 and 31 December 2010. RESULTS Of the 1,351,265 children included, 1192 (0.09 %) were exposed to palivizumab. Nine cases of autoimmune disease were diagnosed among palivizumab-exposed children during the period of observation. Among the children exposed to palivizumab, one child in Denmark developed inflammatory bowel disease; in Sweden, children developed juvenile arthritis (one child), diabetes mellitus (two children), celiac disease (four children), and inflammatory bowel disease (one child). The risk of autoimmune disease was not significantly increased after palivizumab exposure (hazard ratio adjusted for age and country: 1.54; 95 % confidence interval 0.80-2.95). CONCLUSION The risk of autoimmune disease was not increased after palivizumab exposure. Given the small number of incident cases of autoimmune disease observed, this finding should be interpreted with caution.
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Affiliation(s)
- Ann Haerskjold
- The Child and Adolescent Clinic 4072, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. .,Department of Dermato-Allergology, Herlev and Gentofte Hospital, University of Copenhagen, Kildegaardsvej 28, Entrance 15, Hellerup, Denmark.
| | - Marie Linder
- Centre for Pharmacoepidemiology, Karolinska Institutet, Stockholm, Sweden
| | - Lonny Henriksen
- The Child and Adolescent Clinic 4072, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
| | | | - Helle Kieler
- Centre for Pharmacoepidemiology, Karolinska Institutet, Stockholm, Sweden
| | | | - Lone Graff Stensballe
- The Child and Adolescent Clinic 4072, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
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Karakoyun M, Ecevit CO, Kilicoglu E, Aydogdu S, Yagci RV, Ozgenc F. Autoimmune hepatitis and long-term disease course in children in Turkey, a single-center experience. Eur J Gastroenterol Hepatol 2016; 28:927-30. [PMID: 27254777 DOI: 10.1097/meg.0000000000000648] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION The aim of this study is to determine clinic and laboratory features, treatment protocols, treatment responses, and long term follow-up of children with autoimmune hepatitis (AIH) in a region of Turkey followed at Ege University. MATERIALS AND METHODS The records of 47 children with AIH between 1998 and 2012 were retrospectively analyzed for clinical profiles, treatment response, relapse rate, and long-term side effects. RESULTS The median age of the children was 10±4.1 years (55.3% females). A total of 29 patients presented with chronic hepatitis (61.7%). According to the autoantibody profiles, 40 (85.1%) and seven (14.9%) cases were classified as type 1 and type 2, respectively. Presentation with acute hepatitis and chronic hepatitis was significantly higher in type 1 disease. Laboratory findings at presentation was found similar among races as well as AIH types (P>0.05). The prednisolone was used for remission induction in 37 patients; 86.4% (n: 32) achieved a complete response, 2.7% (n: 1) achieved a partial response, and four patients (10.8%) showed no response. Maintenance was attained by low-dose steroid plus thiopurine and relapse in steroid responders (n: 32) was 9.4% (n: 3) at 8, 12, and 48 months. A total of 36% (n: 24) had neither acute nor chronic treatment side effects. Bone marrow suppression was observed in five patients and hyperglycemia was observed in one patient (10.6 and 2.1%), respectively. CONCLUSION AIH type 1 prevails in children in a region of Turkey during the second decade of life. Low-dose corticosteroids combined with azathioprine are found.
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Affiliation(s)
- Miray Karakoyun
- aDepartment of Pediatric Gastroenterology, Hepatalogy and Nutrition, Gaziantep Children's Hospital, Gaziantep bDepartment of Pediatric Gastroenterology, Hepatology and Nutrition cDepartment of Pediatrics, Dr. Behcet Uz Children's Hospital dDepartment of Pediatric Gastroenterology, Hepatology and Nutrition, Ege University, Izmir, Turkey
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Mitra S, Minz RW. Autoantibodies in Autoimmune Liver Diseases-Methods of Detection and Interpretation: An Update for the Reporting Pathologist. Int J Surg Pathol 2016; 24:576-85. [PMID: 27388199 DOI: 10.1177/1066896916657643] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Autoimmune liver disease (AILD) is a type of chronic liver disease with autoimmune etiology. The diagnosis of the disease is multipronged and detection of autoantibodies in AILDs is an important diagnostic tool and it also helps in the classification of the disease. There are multiple autoantibodies that are detected in AILDs but none is diagnostic. Moreover, these autoantibodies are detected in many other pathological and nonpathological conditions. So the significance of seropositivity for these autoantibodies should be known by both the pathologists as well as the clinicians. In addition, there is prognostic significance associated with some of the antibodies and they also sometimes help in the disease monitoring. The whole array of antibodies detected in AILDs is discussed in detail in this review along with their clinical significance and interpretation.
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Affiliation(s)
- Suvradeep Mitra
- PGIMER (Post-Graduate Institute of Medical Education and Research), Chandigarh, India
| | - Ranjana Walker Minz
- PGIMER (Post-Graduate Institute of Medical Education and Research), Chandigarh, India
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27
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Mullin S, Rabah R, Malas S, Bitar A. Autoimmune Hepatitis Type 2 Associated With Positive Antimitochondrial Antibodies: An Overlap Syndrome? Clin Pediatr (Phila) 2016; 55:479-82. [PMID: 26025341 DOI: 10.1177/0009922815588980] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Affiliation(s)
| | - Raja Rabah
- University of Michigan Health System, Ann Arbor, MI, USA
| | | | - Anas Bitar
- Michigan State University, Lansing, MI, USA
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Lian JS, Liu W, Hao SR, Chen DY, Wang YY, Yang JL, Jia HY, Huang JR. A serum metabolomic analysis for diagnosis and biomarker discovery of primary biliary cirrhosis and autoimmune hepatitis. Hepatobiliary Pancreat Dis Int 2015; 14:413-21. [PMID: 26256087 DOI: 10.1016/s1499-3872(15)60393-9] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Because of the diversity of the clinical and laboratory manifestations, the diagnosis of autoimmune liver disease (AILD) remains a challenge in clinical practice. The value of metabolomics has been studied in the diagnosis of many diseases. The present study aimed to determine whether the metabolic profiles, based on ultraperformance liquid chromatography-mass spectrometry (UPLC-MS), differed between autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), to identify specific metabolomic markers, and to establish a model for the diagnosis of AIH and PBC. METHODS Serum samples were collected from 20 patients with PBC, 19 patients with AIH, and 25 healthy individuals. UPLC-MS data of the samples were analyzed using principal component analysis, partial least squares discrimination analysis and orthogonal partial least squares discrimination analysis. RESULTS The partial least squares discrimination analysis model (R2Y=0.991, Q2=0.943) was established between the AIH and PBC groups and exhibited both sensitivity and specificity of 100%. Five groups of biomarkers were identified, including bile acids, free fatty acids, phosphatidylcholines, lysolecithins and sphingomyelin. Bile acids significantly increased in the AIH and PBC groups compared with the healthy control group. The other biomarkers decreased in the AIH and PBC groups compared with those in the healthy control group. In addition, the biomarkers were downregulated in the AIH group compared with the PBC group. CONCLUSIONS The biomarkers identified revealed the pathophysiological changes in AILD and helped to discriminate between AIH and PBC. The predictability of this method suggests its potential application in the diagnosis of AILD.
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Affiliation(s)
- Jiang-Shan Lian
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
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Serai SD, Yin M, Wang H, Ehman RL, Podberesky DJ. Cross-vendor validation of liver magnetic resonance elastography. ABDOMINAL IMAGING 2015; 40:789-94. [PMID: 25476489 PMCID: PMC4523216 DOI: 10.1007/s00261-014-0282-y] [Citation(s) in RCA: 54] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE To evaluate and validate the reproducibility of MR Elastography (MRE)-derived liver stiffness values on two different MR vendor platforms performed on the same subject on the same day. METHODS This investigation was approved by the hospital IRB. MRE exams were performed twice in identical fashion in eight volunteers and in five clinical patients on two different 1.5 T MR scanners-once on a Philips MR scanner and immediately afterward in back-to-back fashion on a General Electric MR scanner, or vice versa. All scan parameters were kept identical on the two platforms to the best extent possible. After the MRE magnitude and phase images were obtained, the data were converted into quantitative images displaying the stiffness of the liver parenchyma. Mean liver stiffness values between the two platforms were compared using interclass correlation with a p value <0.05 considered statistically significant. RESULTS Interclass correlation coefficient (ICC) value of 0.994 was obtained for 13 subjects with p value <0.001 indicating a significantly positive correlation. CONCLUSION As MRE gains in acceptance and as its availability becomes more widespread, it is important to ascertain and confirm that liver stiffness values obtained on different MRE vendor platforms are consistent and reproducible. In this small pilot investigation, we demonstrate that liver stiffness measurement with MRE is reproducible and has very good consistency across two vendor platforms.
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Affiliation(s)
- Suraj D Serai
- Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA,
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Anticuerpos antimúsculo liso sin hepatitis autoinmune. An Pediatr (Barc) 2014; 81:e48-9. [DOI: 10.1016/j.anpedi.2014.02.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2013] [Revised: 02/08/2014] [Accepted: 02/12/2014] [Indexed: 11/19/2022] Open
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Abstract
AIH is characterized by chronic inflammation of the liver, interface hepatitis, hypergammaglobulinemia, and production of autoantibodies. Based on the nature of the serum autoantibodies, two types of AIH are recognized: type 1 (AIH-1), positive for ANA and/or anti-smooth muscle antibody, and type 2 (AIH-2), defined by the positivity for anti-liver kidney microsomal type 1 antibody or for anti-liver cytosol type 1 antibody. AIH demonstrates a female preponderance with the female-to-male ratio of 4:1 in AIH-1 and 10:1 in AIH-2. Several genes confer susceptibility to AIH and influence clinical manifestation, response to treatment, and overall prognosis. Most are located within the human leukocyte antigen (HLA) region, which is involved in the presentation of antigenic peptides to T cells and thus in the initiation of adaptive immune responses. The strongest associations are found within the HLA-DRB1 locus. In patients with increased genetic susceptibility to AIH, immune responses to liver autoantigens could be triggered by molecular mimicry. Because of molecular mimicry, different environmental agents, drugs, and viruses might produce AIH. In AIH, T cells are numerically and functionally impaired, permitting the perpetuation of effector immune responses with ensuing persistent liver destruction. AIH is rare but highly treatable inflammatory condition of the liver. Subclinical and asymptomatic disease is common. AIH therefore needs to be considered in the differential diagnosis of all patients with elevated liver enzymes. Clinical response to immunosuppressive therapy is characteristic and supports the diagnosis.
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Affiliation(s)
- Libia Moy
- Division of Pediatric Gastroenterology, New York University School of Medicine, New York, NY
| | - Jeremiah Levine
- Division of Pediatric Gastroenterology, New York University School of Medicine, New York, NY.
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Domingos JP, Garrido C, Moreira Silva H, Monteiro C, Silva ES, Figueiroa S, Carrilho IC. Chronic inflammatory demyelinating polyneuropathy associated with autoimmune hepatitis. Pediatr Neurol 2014; 51:e13-4. [PMID: 25160557 DOI: 10.1016/j.pediatrneurol.2014.04.017] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2014] [Revised: 04/13/2014] [Accepted: 04/15/2014] [Indexed: 12/15/2022]
Affiliation(s)
- Joana P Domingos
- Department of Neurology, Centro Hospitalar do Porto - Hospital de Santo António, Porto, Portugal.
| | - Cristina Garrido
- Division of Pediatric Neurology, Department of Child and Adolescent, Centro Hospitalar do Porto - Hospital de Santo António, Porto, Portugal
| | - Helena Moreira Silva
- Division of Pediatrics, Department of Child and Adolescent, Centro Hospitalar do Porto - Hospital de Santo António, Porto, Portugal
| | - Claúdia Monteiro
- Department of Pediatrics, Centro Hospitalar do Tâmega e Sousa, Penafiel, Portugal
| | - Ermelinda S Silva
- Division of Pediatric Gastroenterology, Department of Child and Adolescent, Centro Hospitalar do Porto - Hospital de Santo António, Porto, Portugal
| | - Sónia Figueiroa
- Division of Pediatric Neurology, Department of Child and Adolescent, Centro Hospitalar do Porto e Hospital de Santo António, Porto, Portugal
| | - Inês C Carrilho
- Division of Pediatric Neurology, Department of Child and Adolescent, Centro Hospitalar do Porto e Hospital de Santo António, Porto, Portugal
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Squires RH, Ng V, Romero R, Ekong U, Hardikar W, Emre S, Mazariegos GV. Evaluation of the pediatric patient for liver transplantation: 2014 practice guideline by the American Association for the Study of Liver Diseases, American Society of Transplantation and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Hepatology 2014; 60:362-98. [PMID: 24782219 DOI: 10.1002/hep.27191] [Citation(s) in RCA: 142] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2014] [Accepted: 04/22/2014] [Indexed: 12/16/2022]
Affiliation(s)
- Robert H Squires
- Department of Pediatrics, University of Pittsburgh School of Medicine; Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA
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Deneau M, Book LS, Guthery SL, Jensen MK. Outcome after discontinuation of immunosuppression in children with autoimmune hepatitis: a population-based study. J Pediatr 2014; 164:714-719.e2. [PMID: 24423432 DOI: 10.1016/j.jpeds.2013.12.008] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2013] [Revised: 10/29/2013] [Accepted: 12/05/2013] [Indexed: 01/01/2023]
Abstract
OBJECTIVE To assess sustained immunosuppression-free remission (SIFR) in children with autoimmune hepatitis (AIH). STUDY DESIGN We retrospectively reviewed all children with AIH in the region between 1986 and 2011 using a population-based methodology. RESULTS We identified 56 children with AIH (62.5% females; median age, 11.1 years [IQR, 5.7-14.4 years], followed for a median of 5.6 years [IQR, 2.8-8.6 years]). Liver disease was characterized by type II AIH in 8.9%, cirrhosis in 14.0%, and primary sclerosing cholangitis in 21.4%. Coexisting nonhepatic immune-mediated diseases occurred in 37.5%. Biochemical remission on immunosuppressive therapy was achieved in 76.4% of all patients with AIH at a median of 1.2 years (IQR, 0.4-3.6 years); 23.1% of these patients experienced a subsequent relapse. Discontinuation of all immunosuppressive medications was attempted in 16 patients and was successful in 14 patients (87.5%) with type 1 AIH (median age at discontinuation, 8.9 years [IQR, 3.5-17.9 years], treated for a median of 2.0 years [IQR, 1.3-3.5 years] after diagnosis), with SIFR occurring at a median of 3.4 years (IQR, 2.6-5.8 years) of follow-up. Excluding patients with inflammatory bowel disease who received immunosuppressive therapy independent of their liver disease, the probability of achieving SIFR within 5 years of diagnosis of AIH was 41.6% (95% CI, 25.3%-62.9%). Baseline patient characteristics associated with an inability to achieve biochemical remission on immunosuppression or SIFR were elevated international normalized ratio, positive antineutrophil cytoplasmic antibody titer, cirrhosis, and a nonhepatic autoimmune disorder. CONCLUSION We found a high rate of successful discontinuation of all immunosuppressive medications in carefully selected patients with AIH in a population-based cohort. SIFR is an achievable goal for children with AIH, particularly those with type I disease in stable biochemical remission on immunosuppressive therapy.
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Affiliation(s)
- Mark Deneau
- Section of Pediatric Gastroenterology, Department of Pediatrics, University of Manitoba, Winnipeg, Manitoba, Canada.
| | - Linda S Book
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Utah, Salt Lake City, UT
| | - Stephen L Guthery
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Utah, Salt Lake City, UT
| | - M Kyle Jensen
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Utah, Salt Lake City, UT
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Noble-Jamieson G, Heuschkel RB, Torrente F, Hadzic N, Zilbauer M. Colitis-associated sclerosing cholangitis in children: a single centre experience. J Crohns Colitis 2013; 7:e414-8. [PMID: 23485432 DOI: 10.1016/j.crohns.2013.01.016] [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: 11/12/2012] [Revised: 01/26/2013] [Accepted: 01/26/2013] [Indexed: 02/08/2023]
Abstract
OBJECTIVE Sclerosing cholangitis (SC) is an important immune-mediated extra-intestinal manifestation of inflammatory bowel disease (IBD), primarily affecting patients with ulcerative colitis (UC). The reported prevalence of SC in adults and children with UC is low at between 2 and 7%. We present findings from a hepatological work-up in children with inflammatory colitis and elevated liver function tests (LFT) from a tertiary paediatric gastroenterology unit. DESIGN This study is designed as a retrospective review of the medical records of 17 children and adolescents with inflammatory colitis and abnormal LFTs who presented to our IBD service between April 2004 and April 2012. RESULTS Over the eight year period a total of 52 patients were diagnosed with inflammatory colitis (ulcerative colitis and unclassified colitis). Seventeen of the 52 patients had abnormal liver function tests and underwent liver biopsy and cholangiography. All 17 patients (32.6%) were diagnosed with hepato-biliary disease. CONCLUSION This is one of the largest reported series of children with inflammatory colitis and associated hepato-biliary disease. The data from this patient group indicate that the prevalence of IBD-associated hepato-biliary disease in children with abnormal LFTs is much higher than previously reported. As the diagnosis of IBD-associated hepato-biliary disease affects patient management, we recommend liver biopsy and cholangiography in all children with inflammatory colitis and abnormal liver function tests.
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Affiliation(s)
- G Noble-Jamieson
- Department of Paediatric Gastroenterology, Addenbrooke's Hospital, Cambridge University, UK.
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Type 2 autoimmune hepatitis overlapping with primary sclerosing cholangitis in a 10-year-old boy. Arch Pediatr 2013; 20:1325-8. [PMID: 24182664 DOI: 10.1016/j.arcped.2013.09.020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2013] [Revised: 05/08/2013] [Accepted: 09/19/2013] [Indexed: 01/04/2023]
Abstract
BACKGROUND Overlap syndrome of autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) is considered when the patient presents with the diagnostic criteria of both diseases at some stage of the medical history, either simultaneously or consecutively. AIM To report on a new case of overlap syndrome and describe the clinical presentation, progression, radiological studies, histological characteristics, and therapeutic options of this rare association. CASE REPORT A 10-year-old boy presented with jaundice and hepatosplenomegaly. Levels of plasma aminotransferases, gamma-glutamyl transferase, serum alkaline phosphatase and gammaglobulins were elevated. Anti-liver cytosol and perinuclear antineutrophilic cytoplasmic antibodies were positive. Liver biopsy showed features of interface hepatitis with ductopenia. Magnetic resonance cholangiography revealed bile duct stenosis and dilations. Serological findings associated with radiological and histological features confirmed the diagnosis of overlap syndrome of AIH with PSC. Treatment with prednisone, azathioprine, and ursodeoxycholic acid led to a good response. CONCLUSION The possibility of AIH-PSC overlap syndrome should be considered in all children with AIH and, with clinical, biochemical, or histological signs of PSC, complementary investigations should be done to confirm the diagnosis so as to urgently initiate appropriate treatment with immunosuppressive medication and ursodeoxycholic acid.
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Significance of histopathological features in differentiating autoimmune liver disease from nonautoimmune chronic liver disease in children. Eur J Gastroenterol Hepatol 2013; 25:333-7. [PMID: 23085577 DOI: 10.1097/meg.0b013e32835a68a1] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
OBJECTIVES Autoimmune liver disease (AILD) requires a constellation of clinical, serological, biochemical, and histological findings for diagnosis. Liver biopsy forms the cornerstone for the definite diagnosis of AILD, despite histological features not being pathognomonic. Liver biopsies of AILD and nonautoimmune chronic liver disease (NACLD) were reviewed blindly to assess the role of typical histological findings in differentiating AILD from NACLD in a pediatric population. PARTICIPANTS AND METHODS Twenty-five liver biopsies of AILD and 34 liver biopsies of NACLD were reviewed retrospectively without knowledge of the final diagnosis. RESULTS The typical histology comprising all four features, interface hepatitis, portal lymphoplasmacytic infiltrate, rosette formation, and emperipolesis, was observed in 56% of AILD. Rosette formation and emperipolesis were associated significantly with the diagnosis of AILD. Rosette formation alone or in combination with emperipolesis or lymphoplasmacytic infiltrate had high specificity (96.2% each) but low sensitivity (68, 60, and 60%, respectively) for AILD. The diagnostic accuracy of typical histology comprising of a combination of at least three of four features, rosette formation, emperipolesis, and lymphoplasmacytic infiltrate, was 76.9%, with a positive predictive value of 93.3% and a negative predictive value of 70.2%. CONCLUSION Characteristic patterns of liver injury comprising typical histological features on liver biopsy may strongly suggest the diagnosis of AILD irrespective of other laboratory parameters in children. Rosette formation was the only independent significant histological factor to predict AILD. High specificity and predictability of typical histological features may be helpful in diagnosing seronegative AILD among cases of cryptogenic liver disease in the absence of other supportive findings.
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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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Girard M, Franchi-Abella S, Lacaille F, Debray D. Specificities of sclerosing cholangitis in childhood. Clin Res Hepatol Gastroenterol 2012; 36:530-5. [PMID: 22633198 DOI: 10.1016/j.clinre.2012.04.003] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2012] [Revised: 04/15/2012] [Accepted: 04/17/2012] [Indexed: 02/04/2023]
Abstract
Sclerosing cholangitis (SC) is a chronic cholestatic disease characterized by inflammation and obliterative fibrosis of the bile ducts, leading to biliary cirrhosis and ultimately to liver failure. Four main clinical forms can be distinguished in children: i) neonatal SC, most probably a genetic disease transmitted by autosomal recessive inheritance; ii) SC associated with strong features of autoimmunity (referred as autoimmune sclerosing cholangitis) with quite good response to immuno-suppression iii) primary SC of unknown etiology (i.e. without features of autoimmunity) and iv) SC secondary to various diseases, including Langerhans cell histiocytosis and immunodeficiencies. Ursodesoxycholic acid is considered the treatment of choice for all forms of SC but without proof of its effectiveness in preventing progression to secondary biliary cirrhosis. In patients with immunodeficiencies, early bone marrow transplantation is the only way to prevent secondary SC. Liver transplantation remains the only validated treatment in children with biliary cirrhosis. Recurrence of SC after liver transplantation has not been clearly demonstrated in children; however, recurrence of Langerhans cell histiocytosis with bile duct injury has been reported. For patients with severe immunodeficiency, a two-step liver then bone marrow transplantation protocol may be proposed.
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Affiliation(s)
- Muriel Girard
- Pôle médicochirurgical, Hépatologie Pédiatrique, Hôpital Universitaire Necker-Enfants-Malades, AP-HP, 149, rue de Sèvres, 75015 Paris, France
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Trivedi PJ, Chapman RW. PSC, AIH and overlap syndrome in inflammatory bowel disease. Clin Res Hepatol Gastroenterol 2012; 36:420-36. [PMID: 22306055 DOI: 10.1016/j.clinre.2011.10.007] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2011] [Revised: 10/08/2011] [Accepted: 10/14/2011] [Indexed: 02/07/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a progressive, cholestatic disorder characterised by chronic inflammation and stricture formation of the biliary tree. Symptoms include pruritus, fatigue and in advanced cases ascending cholangitis, cirrhosis and end-stage hepatic failure. Patients are at an increased risk of malignancy arising from the bile ducts, gallbladder, liver and colon. The majority (>80%) of Northern European patients with PSC also have inflammatory bowel disease (IBD), usually ulcerative colitis (UC). IBD commonly presents before the onset of PSC, although the opposite can occur and the onset of both conditions can be separated by many years. The colitis associated with PSC is characteristically mild although frequently involves the whole colon. Despite the majority of patients having relatively inactive colonic disease, paradoxically the risk of colorectal malignancy is substantially increased. Patients may also develop dominant, stenotic lesions of the biliary tree which may be difficult to differentiate from cholangiocarcinoma and the coexistence of IBD may influence the development of this complication. Ursodeoxycholic acid may offer a chemoprotective effect against colorectal malignancy and improve liver biochemical indices. Evidence of any beneficial effect on histological progression of hepatobiliary disease is less clear. High doses (∼25-30 mg/kg/d) may be harmful and should be avoided. Autoimmune hepatitis (AIH) is less common in patients with IBD than PSC, however, an association has been observed. A small subgroup may have an overlap syndrome between AIH and PSC and management should be individualised dependant on liver histology, serum immunoglobulin levels, autoantibodies, degree of biochemical cholestasis and cholangiography.
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Affiliation(s)
- P J Trivedi
- Centre for Liver Research and NIHR Biomedical Research Unit, University of Birmingham, Wolfson Drive, Edgbaston, Birmingham, B15 2TT United Kingdom.
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Serai SD, Towbin AJ, Podberesky DJ. Pediatric liver MR elastography. Dig Dis Sci 2012; 57:2713-9. [PMID: 22569825 DOI: 10.1007/s10620-012-2196-2] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2011] [Accepted: 04/14/2012] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Many chronic pediatric liver disorders are complicated by the development of fibrosis and ultimately cirrhosis. Although hepatic fibrogenesis progresses along a common pathway irrespective of the specific etiology, fibrosis in pediatric liver diseases has different histopathological patterns than in adults. In pediatric liver disease, as in adults, management choices may depend upon the stage of fibrosis at diagnosis. With early intervention, the progression of hepatic fibrosis can be slowed or halted, and in some situations, reversed. While liver biopsy is the gold standard for diagnosing and assessing the presence and degree of fibrosis, it has several disadvantages including the potential for sampling error, the risk of complications, the relatively high cost, and general poor acceptance by pediatric patients and their parents. MR elastography (MRE) is a relatively new imaging technique with the potential for allowing a safe, rapid, cost-effective, and non-invasive evaluation of a wide variety of hepatic diseases by quantitatively evaluating the stiffness of the liver parenchyma. The purpose of this article is to present our initial clinical experience and illustrate our modified technique for the application of liver MRE in pediatric patients at our medical center. METHODS AND MATERIALS Pediatric MRE techniques were developed and applied to over 45 patients scanned with our new protocol. CONCLUSION Liver MRE is a safe, non-invasive method for assessing hepatic fibrosis in pediatric patients.
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Affiliation(s)
- Suraj D Serai
- Department of Radiology, MLC 5031, Cincinnati Children's Hospital and Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229, USA.
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Invernizzi P, Alessio MG, Smyk DS, Lleo A, Sonzogni A, Fabris L, Candusso M, Bogdanos DP, Iorio R, Torre G. Autoimmune hepatitis type 2 associated with an unexpected and transient presence of primary biliary cirrhosis-specific antimitochondrial antibodies: a case study and review of the literature. BMC Gastroenterol 2012; 12:92. [PMID: 22816667 PMCID: PMC3464927 DOI: 10.1186/1471-230x-12-92] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2012] [Accepted: 07/20/2012] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Unlike other autoimmune liver diseases, primary biliary cirrhosis (PBC) has never been reported in early childhood, while type 2 autoimmune hepatitis (AIH) is eminently a paediatric disease. CASE PRESENTATION We describe a case of type 2 AIH with serological positivity for PBC-specific anti-mitochondrial antibodies (AMA) in a 3-year old girl. We found this observation intriguing as AMA and indeed an overlap with PBC are virtually absent in Type 2 AIH, a pediatric form of AIH which is distinct precisely because it is characterized by pathognomonic anti-liver kidney microsomal type 1 (LKM-1) showing a remarkable antigen-specificity directed against cytochrome P4502D6. We also review the literature in relation to AMA positivity in paediatric age and adolescence. In our case, the presence of AIH-2-specific anti-LKM-1 and PBC-specific AMA was confirmed by indirect immunofluorescence (IIF), and immunoblotting and ELISA based on recombinant mitochondrial antigens. The clinical, laboratory and histological features of the child are given in detail. Interestingly the mother was AMA positive without other features of PBC. The child was successfully treated with immunosuppression and five years after the original diagnosis is on a low dose of prednisolone and azathioprine, with no signs of relapse. Anti-LKM-1 antibodies are still present in low titres. AMA were detectable for the first 4 years after the diagnosis and disappeared later. CONCLUSION This is the first case report in the literature of AIH type 2 with an unexpected PBC-specific AMA positivity in a young child. Response to immunosuppressive treatment was satisfactory and similar to that described in AIH. A review of published reports on AMA positivity in paediatric age shows that the antibody may arise in the context of immunodeficiency and is variably associated with liver damage.
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Affiliation(s)
- Pietro Invernizzi
- Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Via Manzoni 56, 20089, Rozzano(MI), Italy
- Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA, USA
| | | | - Daniel S Smyk
- Institute of Liver Studies, King’s College London School of Medicine at King’s College Hospital, Denmark Hill Campus, London, UK
| | - Ana Lleo
- Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Via Manzoni 56, 20089, Rozzano(MI), Italy
| | - Aurelio Sonzogni
- Department of Medicine and Transplantation, Ospedali Riuniti, Bergamo, Italy
| | - Luca Fabris
- Department of Surgical and Gastroenterological Sciences, University of Padova, Padova, Italy
- Center for Liver Research (CeLiveR), Ospedali Riuniti, Bergamo, Italy
| | | | - Dimitrios P Bogdanos
- Institute of Liver Studies, King’s College London School of Medicine at King’s College Hospital, Denmark Hill Campus, London, UK
| | - Raffaele Iorio
- Department of Pediatrics, Federico II University, Naples, Italy
| | - Giuliano Torre
- Division of Pediatrics, Ospedali Riuniti, Bergamo, Italy
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Epstein-barr virus as a trigger of autoimmune liver diseases. Adv Virol 2012; 2012:987471. [PMID: 22693505 PMCID: PMC3368154 DOI: 10.1155/2012/987471] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2012] [Accepted: 03/09/2012] [Indexed: 02/08/2023] Open
Abstract
The pathogenesis of autoimmune diseases includes a combination of genetic factors and environmental exposures including infectious agents. Infectious triggers are commonly indicated as being involved in the induction of autoimmune disease, with Epstein-Barr virus (EBV) being implicated in several autoimmune disorders. EBV is appealing in the pathogenesis of autoimmune disease, due to its high prevalence worldwide, its persistency throughout life in the host's B lymphocytes, and its ability to alter the host's immune response and to inhibit apoptosis. However, the evidence in support of EBV in the pathogenesis varies among diseases. Autoimmune liver diseases (AiLDs), including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC), have a potential causative link with EBV. The data surrounding EBV and AiLD are scarce. The lack of evidence surrounding EBV in AiLD may also be reflective of the rarity of these conditions. EBV infection has also been linked to other autoimmune conditions, which are often found to be concomitant with AiLD. This paper will critically examine the literature surrounding the link between EBV infection and AiLD development. The current evidence is far from being conclusive of the theory of a link between EBV and AiLD.
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Smyk DS, Bogdanos DP, Kriese S, Billinis C, Burroughs AK, Rigopoulou EI. Urinary tract infection as a risk factor for autoimmune liver disease: from bench to bedside. Clin Res Hepatol Gastroenterol 2012; 36:110-21. [PMID: 21907008 DOI: 10.1016/j.clinre.2011.07.013] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2011] [Revised: 07/18/2011] [Accepted: 07/21/2011] [Indexed: 02/08/2023]
Abstract
Autoimmune liver diseases include autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis. A variety of environmental and genetic risk factors have been associated with these conditions. Recurrent urinary tract infections (rUTI) have been strongly associated with PBC, and to a lesser extent with AIH. These observations were initially based on the observation of significant bacteriuria in female patients with PBC. Larger epidemiological studies demonstrated that there was indeed a strong correlation between recurrent UTI and PBC. AIH has not been linked to recurrent UTI in epidemiological studies; however treatment of UTI with nitrofurantoin can induce AIH. As Escherichia coli is the most prevalent organism isolated in women with UTI, it has been suggested that molecular mimicry between microbial and human PDC-E2 (the main autoantigenic target in PBC) epitopes may explain the link between UTI and PBC. Multiple studies have demonstrated molecular mimicry and immunological cross-reactivity involving microbial and self-antigen mimics. This review will examine the literature surrounding UTI and autoimmune liver disease. This will include case reports and epidemiological studies, as well as experimental data.
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Affiliation(s)
- Daniel S Smyk
- Liver Immunopathology, Institute of Liver Studies and Liver Unit, King's College London School of Medicine at King's College Hospital, Denmark Hill Campus, London SE5 9RS, UK
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Krones E, Graziadei I, Trauner M, Fickert P. Evolving concepts in primary sclerosing cholangitis. Liver Int 2012; 32:352-69. [PMID: 22097926 DOI: 10.1111/j.1478-3231.2011.02607.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2011] [Accepted: 06/27/2011] [Indexed: 02/13/2023]
Abstract
Patients suffering from primary sclerosing cholangitis (PSC) show considerable differences regarding clinical manifestations (i.e. large duct versus small-duct PSC, presence or absence of concomitant inflammatory bowel disease), disease progression, risk for malignancy and response to therapy, raising the question whether PSC may represent a mixed bag of diseases of different aetiologies. The growing list of secondary causes and diseases 'mimicking' or even overlapping with PSC (e.g. IgG4-associated sclerosing cholangitis), which frequently causes problems in clear-cut discrimination from classic PSC and the emerging knowledge about potential disease modifier genes (e.g. variants of CFTR, TGR5 and MDR3) support such a conceptual view. In addition, PSC in children differs significantly from PSC in adults in several aspects resulting in distinct therapeutic concepts. From a clinical perspective, appropriate categorization and careful differential diagnosis are essential for the management of concerned patients. Therefore, the aim of the current review is to summarize current and evolving pathophysiological concepts and to provide up-to-date perspectives including future treatment strategies for PSC.
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Affiliation(s)
- Elisabeth Krones
- Department of Internal Medicine, Medical University of Graz, Graz, Austria
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Cho JM, Kim KM, Oh SH, Lee YJ, Rhee KW, Yu E. De novo autoimmune hepatitis in Korean children after liver transplantation: a single institution's experience. Transplant Proc 2012; 43:2394-6. [PMID: 21839275 DOI: 10.1016/j.transproceed.2011.05.030] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
INTRODUCTION De novo autoimmune hepatitis (AIH) after orthotopic liver transplantation (OLT) has been described as a new type of late graft dysfunction in children who have not undergone transplantation for previous autoimmune liver disease. The purpose of this study was to evaluate the clinical aspects of de novo AIH among children following OLT. PATIENTS AND METHODS Between January 1994 and May 2007, 149 children underwent OLT, including 1 with recurrent AIH who was excluded from this study, whereas 4 others developed de novo AIH (2.7%; n = 4/148). We analyzed the demographics, laboratory characteristics, and response to treatment of the 4 children with de novo AIH following OLT. RESULTS The 4 patients were all girls with a median interval after OLT to presentation of 6.5 years (range, 0.7-8.8 years). The median age when de novo AIH developed was 12.4 years (range, 8.7-17.3 years). All cases were detected by abnormal liver function tests, namely, increased aspartate aminotransferase (AST; median, 322 IU/L; range, 181-919 IU/L). One patient showed elevated immunoglobulin G. Three patients displayed positive antinuclear antibodies. All were seronegative for smooth muscle antibody and liver-kidney microsomal type 1 antibody. One patient showed anti-mitochondrial antibody. All patients were treated with steroids with or without azathioprine. The liver function tests in these 4 patients, improved by at least 50% during the first month of treatment, responding to steroid treatment with or without azathioprine. CONCLUSION In preadolescent or adolescent female patients with unexplained graft dysfunction after OLT, it is important to recognize de novo AIH rapidly and to develop an adequate diagnostic strategy, including evaluation of serum autoantibodies, immunoglobulin G, and liver biopsy.
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Affiliation(s)
- J M Cho
- Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Clinico-laboratory study on children with auto-immune hepatitis in Upper Egypt. Arab J Gastroenterol 2011; 12:178-83. [DOI: 10.1016/j.ajg.2011.11.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2011] [Revised: 06/24/2011] [Accepted: 11/14/2011] [Indexed: 12/31/2022]
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Nobili V, Monti L, Alisi A, Lo Zupone C, Pietrobattista A, Tomà P. Transient elastography for assessment of fibrosis in paediatric liver disease. Pediatr Radiol 2011; 41:1232-8. [PMID: 21678114 DOI: 10.1007/s00247-011-2143-y] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2011] [Revised: 02/23/2011] [Accepted: 03/01/2011] [Indexed: 02/06/2023]
Abstract
The prognosis and management of chronic liver diseases in children largely depend on the extent and progression of liver fibrosis, which is often the most important predictor of disease outcome, and thus influences the indication for potential therapy. Unfortunately, liver biopsy continues to be the gold standard for the staging and grading of fibrosis. Liver biopsy is an invasive and painful technique with several limitations. These limitations have led to the development of alternative noninvasive methods for the accurate assessment of fibrosis and for the maintenance of an acceptable risk/benefit ratio. In the last decades, transient elastography (TE) has received increasing consideration as a means of evaluating disease progression in paediatric chronic liver disease. TE is an accurate and reproducible methodology for identifying subjects without fibrosis or significant fibrosis, or with advanced fibrosis. In this review, we provide an outline of liver fibrosis in paediatric liver diseases, including fibrogenesis, and noninvasive techniques for the diagnosis and follow-up of fibrosis, and then focus on the characteristics of TE and on its strength in the assessment of liver fibrosis, paying particular attention to studies conducted in children.
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Affiliation(s)
- Valerio Nobili
- Liver Unit, Research Institute, Bambino Gesù Children's Hospital, Piazza S Onofrio 4, 00165 Rome, Italy.
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Fallatah HI, Akbar HO. Mycophenolate mofetil as a rescue therapy for autoimmune hepatitis patients who are not responsive to standard therapy. Expert Rev Gastroenterol Hepatol 2011; 5:517-522. [PMID: 21780898 DOI: 10.1586/egh.11.45] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Autoimmune hepatitis (AIH) is a chronic liver disease of unknown etiology that is responsive to steroid and azathioprine treatment in more than 80% of patients after 3 years of treatment. There are few alternative treatment options for individuals with AIH who are unresponsive to steroids and azathioprine, and research on this is limited to open-label studies of a variety of immunosuppressive agents that involve only small numbers of patients. Mycophenolate mofetil is one of the most frequently used alternative agents for the treatment of AIH patients not responsive to standard therapy. In this article, we review and summarize currently available data regarding the use of mycophenolate mofetil as an alternative treatment option for patients with AIH.
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