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Dalekos G, Gatselis N, Drenth JP, Heneghan M, Jørgensen M, Lohse AW, Londoño M, Muratori L, Papp M, Samyn M, Tiniakos D, Lleo A. EASL Clinical Practice Guidelines on the management of autoimmune hepatitis. J Hepatol 2025:S0168-8278(25)00173-4. [PMID: 40348684 DOI: 10.1016/j.jhep.2025.03.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2025] [Accepted: 03/20/2025] [Indexed: 05/14/2025]
Abstract
Autoimmune hepatitis (AIH) is a chronic liver disease of unknown aetiology which may affect any patient irrespective of age, sex, and ethnicity. At baseline, the clinical spectrum of the disease varies largely from asymptomatic cases to acute liver failure with massive hepatocyte necrosis. The aim of these EASL guidelines is to provide updated guidance on the diagnosis and management of AIH both in adults and children. Updated guidance on the management of patients with variants and specific forms of AIH is also provided, as is detailed guidance on the management of AIH-associated cirrhosis, including surveillance for portal hypertension and hepatocellular carcinoma, as well as liver transplantation in decompensated cirrhosis.
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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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Varadarajan A, Rastogi A, Maiwall R, Bihari C, Thomas S, Shasthry SM. Serum IgG level in autoimmune liver diseases and its significance: Is there a need to revisit existing criteria? Experience from a tertiary care center. INDIAN J PATHOL MICR 2024; 67:846-851. [PMID: 38847214 DOI: 10.4103/ijpm.ijpm_865_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Accepted: 02/13/2024] [Indexed: 12/07/2024] Open
Abstract
BACKGROUND Serum immunoglobulin G (IgG) level is elevated in autoimmune liver diseases (AILDs), especially autoimmune hepatitis (AIH). However, its utility is limited in current practice as different criteria propose different cut-off values leading to considerable ambiguity. MATERIALS AND METHODS A cross-sectional study was conducted among patients with AILD who underwent a liver biopsy over a ten-year period. From 17644 liver biopsies, 630 patients were included and divided into three groups-AIH (455 patients), primary biliary cholangitis (PBC) (97 patients), and overlap (78 patients). Clinical and laboratory details were collected and histological findings were reviewed. Non-cirrhotic non-alcoholic steatohepatitis (NASH) cases were taken as the control group for IgG level comparison. RESULTS Among AIH patients, IgG values of >2 times the upper limit of normal (ULN) were associated with significant elevation of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), bilirubin, and necroinflammatory activity. IgG level of >1.1 times ULN lacks specificity in differentiating AIH from the control group. The receiver operating characteristic (ROC) curve demonstrates maximum sensitivity and specificity at a cut-off value of >1.3 times ULN. CONCLUSION Serum IgG cut-off value for diagnosing AIH, either in isolation or as a component of overlap syndrome, needs revision and uniformity. IgG value of >2 times ULN in AIH is associated with severe AIH. A new cut-off value of >1.3 times ULN is proposed.
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Affiliation(s)
| | - Archana Rastogi
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Chaggan Bihari
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Sherin Thomas
- Department of Biochemistry, Institute of Liver and Biliary Sciences, New Delhi, India
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Khonde P, Choudhury S, Spies NC, Naz N, Stoll J, Fleckenstein J, He M, Ballentine S, Kulkarni S. Worse fibro-inflammatory activity on diagnostic liver biopsy adversely impacts biochemical remission in autoimmune hepatitis. Clin Res Hepatol Gastroenterol 2024; 48:102442. [PMID: 39103121 DOI: 10.1016/j.clinre.2024.102442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 08/03/2024] [Indexed: 08/07/2024]
Abstract
BACKGROUND Autoimmune hepatitis (AIH) patients can present with advanced fibrosis at diagnosis or may progress to the same if biochemical remission on treatment is not achieved. METHODS We conducted a single-center retrospective analysis of 34 pediatrics and 39 adult AIH patients. Three pathologists, blinded to clinical information, reviewed the diagnostic liver biopsy (DLB) slides of AIH patients. We evaluated the impact of clinical, laboratory, and histopathologic parameters on outcomes including biochemical remission (BR). RESULTS Incidence of advanced (Ludwig stage 3 or 4) fibrosis on DLB was 45.2 %. AIH patients with advanced fibrosis had higher median Ishak score (p < 0.001) and higher IgG level (p = 0.01) at diagnosis. The incidence of BR at 6-month (31.2% vs. 88.6 %, p = 0.001) and 1-year (68.8% vs. 88.6 %, p = 0.04) post-diagnosis was significantly lower in AIH patients with advanced fibrosis. Although not statistically significant, a higher proportion of AIH patients with advanced fibrosis were on high dose of steroids (58% vs. 37.9 %, p = 0.1) at 1 year post diagnosis. Higher serum IgG level at diagnosis was associated with lower odds of achieving BR at 6-month (p = 0.004) and 1-year (p = 0.03) post-diagnosis in multivariate analysis. Pediatric age at diagnosis (p = 0.02) was associated with higher steroid dose at 1-year post-diagnosis in univariate analysis. CONCLUSIONS Findings of advanced fibrosis on DLB of AIH patients was accompanied by more pronounced necro-inflammatory activity and higher serum IgG level, which translated to lower rates of BR and higher exposure to steroids during the first year after diagnosis.
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Affiliation(s)
- Pooja Khonde
- Department of Pathology and Immunology, Washington University in St. Louis, MO, USA
| | - Shelley Choudhury
- Department of Pediatrics, Washington University in St. Louis, MO, USA
| | - Nicholas C Spies
- Department of Pathology and Immunology, Washington University in St. Louis, MO, USA
| | - Nadia Naz
- Department of Pediatrics, University of Iowa, Iowa City, IA, USA
| | - Janis Stoll
- Department of Pediatrics, Washington University in St. Louis, MO, USA
| | | | - Mai He
- Department of Pathology and Immunology, Washington University in St. Louis, MO, USA
| | - Samuel Ballentine
- Department of Pathology and Immunology, Washington University in St. Louis, MO, USA
| | - Sakil Kulkarni
- Department of Pediatrics, Washington University in St. Louis, MO, USA.
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Wang L, Du ZX, Liu HL, Zhang Y, Wang SS, Hu YF, Li LQ, Zhu P, Zhong YD, Xiong QF, Yang YF. IAIH-PG consensus for histological criteria of AIH: Multicentre validation with focus on chronic liver diseases in China. Liver Int 2024; 44:2282-2292. [PMID: 38775078 DOI: 10.1111/liv.15971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 04/28/2024] [Accepted: 04/30/2024] [Indexed: 08/30/2024]
Abstract
BACKGROUND AND AIMS The International AIH Pathology Group (IAIH-PG) put forward the new histological criteria of autoimmune hepatitis (AIH) in 2022, which have not undergone adequate verification. In this study, we verified the applicability of the new histological criteria in the population of Chinese patients with chronic liver disease, comparing it with the simplified criteria. METHODS The gold standard for diagnosis in all patients was based on histological findings, combined with clinical manifestations and laboratory tests and determined after a follow-up period of at least 3 years. A total of 640 patients with various chronic liver diseases from multiple centres underwent scoring using the new histological criteria and the simplified criteria, comparing their diagnostic performance. RESULTS In this study, the new histological criteria showed a sensitivity of 73.6% and 100% for likely and possible AIH, with specificities of 100% and 69.0% respectively. The coincidence rates of possible AIH for the new histological criteria, simplified histological criteria and simplified score were 81.7%, 72.8% and 69.7% respectively. For likely AIH, the rates were 89.2%, 75.9% and 65.6% respectively. Based on the new histological criteria, all patients with AIH were correctly diagnosed. Specifically, 73.6% were diagnosed with likely AIH and 26.4% were possible AIH. Additionally, the simplified histological criteria achieved a diagnosis rate of 98.6% for AIH, while the simplified score could only diagnose 53.8% of AIH. CONCLUSIONS Compared with the simplified score and simplified histological criteria, the sensitivity and specificity of the new histological criteria for AIH were significantly improved. The results indicate that the new histological criteria exhibit high sensitivity and specificity for diagnosing AIH in China.
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Affiliation(s)
- Li Wang
- Department of infectious disease and liver disease, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
- Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhi-Xiang Du
- Department of infectious disease and liver disease, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
| | | | - Yu Zhang
- Southeast University, Nanjing, China
| | | | - Yi-Fan Hu
- Department of infectious disease and liver disease, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
| | - Li-Qiu Li
- Department of infectious disease and liver disease, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
| | - Ping Zhu
- Nanjing University of Chinese Medicine, Nanjing, China
| | - Yan-Dan Zhong
- Department of infectious disease and liver disease, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
| | - Qing-Fang Xiong
- Department of infectious disease and liver disease, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
| | - Yong-Feng Yang
- Department of infectious disease and liver disease, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
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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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Jerregård Skarby A, Casswall T, Bergquist A, Lindström L. Good long-term outcomes of primary sclerosing cholangitis in childhood. JHEP Rep 2024; 6:101123. [PMID: 39139456 PMCID: PMC11321284 DOI: 10.1016/j.jhepr.2024.101123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 05/14/2024] [Accepted: 05/21/2024] [Indexed: 08/15/2024] Open
Abstract
Background & Aims Primary sclerosing cholangitis (PSC) is a rare progressive liver disease associated with inflammatory bowel disease (IBD). It is usually diagnosed in adults but can also present in children. Data on long-term outcomes of pediatric PSC are limited. Our aim was to study the natural history of pediatric PSC in Sweden. Methods This is a cohort study, including all children (<18 years), diagnosed with PSC between January 2000 and December 2015 at the Pediatric Liver Unit at Karolinska University Hospital, Stockholm. Patients were followed until liver transplantation, death or last date of follow-up (August 2021). Results We identified 124 children with a median age of 14 (1.9-17.8) years at PSC diagnosis. Sixty percent were boys, 93% had IBD. Median follow-up time was 13 years (5.7-21.6). Overall event-free survival in the cohort was 91% (95% CI 0.84-0.95) at 5 years and 77% (95% CI 0.68-0.84) at 10 years after diagnosis. Autoimmune hepatitis (AIH) was present in 31% (n = 39). Portal hypertension developed in 13% (n = 16), biliary complications in 24% (n = 30), cholangiocarcinoma (CCA) in 0.8% (n = 1), while 13% (n = 16) underwent liver transplantation and three patients died. Transplant-free survival was 91% after 10 years. Individuals with a high SCOPE index at diagnosis had a 2.3-fold increased risk of requiring liver transplantation (hazard ratio 2.35, 95% CI 1.18-4.66, c-statistics = 0.70). Patients with an additional diagnosis of autoimmune hepatitis had slightly higher risk of reaching transplantation during follow-up (hazard ratio 2.85, 95% CI 1.06-7.67, p = 0.038). Conclusions Children diagnosed with PSC have a good prognosis during the first decade after diagnosis. A high SCOPE index at diagnosis was associated with a less favorable outcome. Impact and implications Data on long-term outcome in pediatric primary sclerosing cholangitis bridging over to adulthood is limited. There is a great need among children with primary sclerosing cholangitis and their parents for more knowledge about the natural history of this disease and what they can expect from the future. We hope that the data presented in this study may help counsel health professionals, young individuals and families affected by this disease.
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Affiliation(s)
- Anna Jerregård Skarby
- Department of Medicine Huddinge, Karolinska Institutet, Department of Acute Geriatrics, Stroke and Palliative care, Nyköping Hospital Nyköping, Sweden
| | - Thomas Casswall
- Department of Clinical Science, Intervention and Technology (CLINTEC), Unit of Pediatrics, Karolinska Institutet, Pediatric Gastroenterology, Hepatology and Nutrition, Karolinska University Hospital, Stockholm, Sweden
| | - Annika Bergquist
- Department of Medicine Huddinge, Karolinska Institutet, Department of Upper GI Disease, Division of Hepatology, Karolinska University Hospital, Stockholm, Sweden
| | - Lina Lindström
- Department of Medicine Huddinge, Karolinska Institutet, Department of Gastroenterology, Dermatovenereology and Rheumatology, Centre for Digestive Health, Karolinska University Hospital, Stockholm, Sweden
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Ricciuto A, Liu K, El-Matary W, Amin M, Amir AZ, Aumar M, Auth M, Di Guglielmo MD, Druve Tavares Fagundes E, Rodrigues Ferreira A, Furuya KN, Gupta N, Guthery S, Horslen SP, Jensen K, Kamath BM, Kerkar N, Koot BGP, Laborda TJ, Lee CK, Loomes KM, Mack C, Martinez M, Montano-Loza A, Ovchinsky N, Papadopoulou A, Perito ER, Sathya P, Schwarz KB, Shah U, Shteyer E, Soufi N, Stevens JP, Taylor A, Tessier ME, Valentino P, Woynarowski M, Deneau M. Oral vancomycin is associated with improved inflammatory bowel disease clinical outcomes in primary sclerosing cholangitis-associated inflammatory bowel disease (PSC-IBD): A matched analysis from the Paediatric PSC Consortium. Aliment Pharmacol Ther 2024; 59:1236-1247. [PMID: 38462727 DOI: 10.1111/apt.17936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 09/18/2023] [Accepted: 02/22/2024] [Indexed: 03/12/2024]
Abstract
BACKGROUND Data on oral vancomycin for primary sclerosing cholangitis (PSC)-associated inflammatory bowel disease (IBD) are limited. AIMS Using data from the Paediatric PSC Consortium, to examine the effect of vancomycin on IBD activity. METHODS In this retrospective multi-centre cohort study, we matched vancomycin-treated and untreated patients (1:3) based on IBD duration at the time of primary outcome assessment. The primary outcome was Physician Global Assessment (PGA) of IBD clinical activity after 1 year (±6 months) of vancomycin. We used generalised estimating equations (GEE) to examine the association between vancomycin and PGA remission, adjusting for IBD type, severity and medication exposures. Secondary outcomes included serum labs and endoscopic remission (global rating of no activity) among those with available data and also analysed with GEE. RESULTS 113 PSC-IBD patients received vancomycin (median age 12.7 years, 63% male). The matched cohort included 70 vancomycin-treated and 210 untreated patients. Vancomycin was associated with greater odds of IBD clinical remission (odds ratio [OR] 3.52, 95% CI 1.97-6.31; adjusted OR [aOR] 5.24, 95% CI 2.68-10.22). Benefit was maintained in sensitivity analyses restricted to non-transplanted patients and those with baseline moderate-severe PGA. Vancomycin was associated with increased odds of endoscopic remission (aOR 2.76, 95% CI 1.002-7.62; N = 101 with data), and with lower CRP (p = 0.03) and higher haemoglobin and albumin (both p < 0.01). CONCLUSION Vancomycin was associated with greater odds of IBD clinical and endoscopic remission. Additional, preferably randomised, controlled studies are needed to characterise efficacy using objective markers of mucosal inflammation, and to examine safety and define optimal dosing.
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Affiliation(s)
- Amanda Ricciuto
- The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Kuan Liu
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Wael El-Matary
- Max Rady College of Medicine, Children's Hospital Research Institute of Manitoba, Winnipeg, Manitoba, Canada
| | - Mansi Amin
- Duke University Medical Center, Durham, North Carolina, USA
| | - Achiya Z Amir
- Dana-Dwek Children's Hospital, Tel-Aviv Medical Center, Tel-Aviv University, Tel Aviv, Israel
| | | | - Marcus Auth
- Alder Hey Children's NHS Foundation Trust, University of Liverpool, Liverpool, UK
| | | | | | | | - Katryn N Furuya
- University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Nitika Gupta
- Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, Georgia, USA
| | - Stephen Guthery
- Intermountain Primary Children's Hospital, University of Utah, Salt Lake City, Utah, USA
| | - Simon P Horslen
- UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Kyle Jensen
- Intermountain Primary Children's Hospital, University of Utah, Salt Lake City, Utah, USA
| | - Binita M Kamath
- The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Nanda Kerkar
- Golisano Children's Hospital, University of Rochester Medical Center, Rochester, New York, USA
| | - B G P Koot
- Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Trevor J Laborda
- Intermountain Primary Children's Hospital, University of Utah, Salt Lake City, Utah, USA
| | | | - Kathleen M Loomes
- The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Cara Mack
- Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Children's Wisconsin, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Mercedes Martinez
- Columbia University Irving Medical Center, New York-Presbyterian, New York, New York, USA
| | - Aldo Montano-Loza
- Zeidler Ledcor Centre, University of Alberta, Edmonton, Alberta, Canada
| | - Nadia Ovchinsky
- NYU Grossman School of Medicine, New York City, New York, USA
| | - Alexandra Papadopoulou
- First Department of Pediatrics, Athens Children's Hospital "AGIA SOFIA", University of Athens, Athens, Greece
| | - Emily R Perito
- University of California San Francisco, San Francisco, California, USA
| | - Pushpa Sathya
- Memorial University of Newfoundland, St. John's, Newfoundland, Canada
| | | | - Uzma Shah
- Henry Ford Health, Detroit, Michigan, USA
| | | | - Nisreen Soufi
- Children's Hospital Los Angeles, Los Angeles, California, USA
| | | | - Amy Taylor
- Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | | | - Pamela Valentino
- University of Washington School of Medicine, Seattle Children's, Seattle, Washington, USA
| | | | - Mark Deneau
- Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Children's Wisconsin, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
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Sakhuja P, Goyal S. Autoimmune Hepatitis: From Evolution to Current Status-A Pathologist's Perspective. Diagnostics (Basel) 2024; 14:210. [PMID: 38248086 PMCID: PMC10814110 DOI: 10.3390/diagnostics14020210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 01/03/2024] [Accepted: 01/15/2024] [Indexed: 01/23/2024] Open
Abstract
Autoimmune hepatitis (AIH) is a chronic, relapsing and remitting, immune-mediated liver disease that progresses to cirrhosis if left untreated. A significant number of patients may present with acute hepatitis or acute liver failure, which are often misdiagnosed as toxic liver injury. AIH shows a preponderance in young women but may be seen in children and the elderly. Diagnosis requires the integration of clinical, biochemical, and serologic parameters, along with supportive liver histology and exclusion of other causes of liver disease. Liver biopsy is a prerequisite for diagnosis of AIH, to assess severity and stage of disease, exclude other entities, and recognize any concurrent morbidities. No single biomarker or histologic feature is pathognomonic for AIH. The diagnostic and histologic criteria have undergone several modifications since the original scoring system was proposed by the International Autoimmune Hepatitis Group (IAIHG) in 1993. Recently, the IAIHG has proposed consensus recommendations for histologic criteria, relevant for both acute and chronic AIH. This review article will describe the evolving diagnostic criteria for AIH, with their limitations and utility, and with an emphasis on the role of liver histology in the diagnosis and management of AIH.
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Buechter M, Dorn D, Möhlendick B, Siffert W, Baba HA, Gerken G, Kahraman A. Characteristics and Long-Term Outcome of 535 Patients with Autoimmune Hepatitis-The 20-Year Experience of a High-Volume Tertiary Center. J Clin Med 2023; 12:4192. [PMID: 37445225 DOI: 10.3390/jcm12134192] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 06/12/2023] [Accepted: 06/16/2023] [Indexed: 07/15/2023] Open
Abstract
Background and aims: Autoimmune hepatitis (AIH) is a complex and progressive inflammatory liver disease characterized by immune-mediated destruction of the liver parenchyma, hypergammaglobulinemia, the presence of circulating autoantibodies, and good response to immunosuppressive therapy. Since the prevalence of AIH is relatively rare, data on the clinical course and the long-term outcome are scarce. Patients and methods: We retrospectively analyzed the data of 535 well-documented AIH patients treated at the University Hospital Essen between 2000 and 2020. Results: The majority of patients were middle-aged females (75% women, mean age 45 years) with AIH type 1 (97%). Approximately 32% of patients were diagnosed with cirrhosis due to AIH, 29% had concomitant autoimmune (predominantly autoimmune thyroiditis), and 10% had psychiatric diseases, respectively. Skin tumors were the most common malignant diseases (47% of all tumors), while hepatocellular carcinoma rarely occurred (only six cases). Overall long-term mortality and liver-associated mortality were 9.16% and 4.67%, respectively. However, long-term survival was strongly associated with disease remission. Conclusions: Although AIH is a silent disease and cirrhosis is present in many cases, a favorable long-term prognosis can be achieved by consequent immunosuppressive therapy. The incidence of (liver-associated) complications seems to be lower in comparison to other etiologies, such as viral hepatitis or NASH, and mainly depends on the long-term side effects of immunosuppressive therapy.
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Affiliation(s)
- Matthias Buechter
- Department of Gastroenterology and Hepatology, University Clinic of Essen, University of Duisburg-Essen, 45122 Essen, Germany
- Department of Gastroenterology and Hepatology, Elisabeth Hospital, 58638 Iserlohn, Germany
| | - Dominik Dorn
- Department of Gastroenterology and Hepatology, University Clinic of Essen, University of Duisburg-Essen, 45122 Essen, Germany
| | - Birte Möhlendick
- Institute of Pharmacogenetics, University Clinic of Essen, University of Duisburg-Essen, 45122 Essen, Germany
| | - Winfried Siffert
- Institute of Pharmacogenetics, University Clinic of Essen, University of Duisburg-Essen, 45122 Essen, Germany
| | - Hideo A Baba
- Institute of Pathology, University Clinic of Essen, University of Duisburg-Essen, 45122 Essen, Germany
| | - Guido Gerken
- Department of Gastroenterology and Hepatology, University Clinic of Essen, University of Duisburg-Essen, 45122 Essen, Germany
- Department of Gastroenterology and Hepatology, Helios Clinic, 42549 Velbert, Germany
| | - Alisan Kahraman
- Department of Gastroenterology and Hepatology, University Clinic of Essen, University of Duisburg-Essen, 45122 Essen, Germany
- Department of Gastroenterology and Hepatology, Max Grundig Clinic, 77815 Bühl, Germany
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Stevens JP, Gupta NA. Recent Insights into Pediatric Primary Sclerosing Cholangitis. Clin Liver Dis 2022; 26:489-519. [PMID: 35868687 DOI: 10.1016/j.cld.2022.03.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
This article reviews recent literature on the pathogenesis, presentation, diagnosis, comorbidities, natural history, and management of pediatric primary sclerosing cholangitis (PSC). The authors shed light on the role of genetic and environmental factors in PSC, although recognize the limitations in the understanding of PSC pathogenesis. They reflect on presenting disease phenotypes, including the association with inflammatory bowel disease and frequent histologic presence of autoimmune hepatitis features. The current lack of effective medications is discussed, and disease complications and prognosis are described. Finally, the authors highlight available evidence while acknowledging the paucity of prospective pediatric data.
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Affiliation(s)
- James P Stevens
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, 1760 Haygood Drive, Atlanta GA 30322, USA
| | - Nitika A Gupta
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, 1760 Haygood Drive, Atlanta GA 30322, USA.
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12
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Hercun J, Willems P, Bilodeau M, Vincent C, Alvarez F. Long-Term Follow-Up into Adulthood of Pediatric-Onset Primary Sclerosing Cholangitis and Autoimmune Sclerosing Cholangitis. JPGN REPORTS 2022; 3:e220. [PMID: 37168634 PMCID: PMC10158455 DOI: 10.1097/pg9.0000000000000220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 05/03/2022] [Indexed: 05/13/2023]
Abstract
UNLABELLED Studies on pediatric patients with primary sclerosing cholangitis (PSC) have been limited by short follow-up and inconsistent classification of pediatric patients with autoimmune hepatitis-sclerosing cholangitis overlap (AIC). We conducted a retrospective study of patients diagnosed with AIC or PSC during childhood with extension of follow-up into adulthood. METHODS We reviewed records of patients followed for PSC or AIC between 1998 and 2019 at a pediatric referral center. Features at diagnosis, biochemical and liver-related outcomes (cholangitis, liver transplant, and cirrhosis) were compared. RESULTS Forty patients (27 PSC, 13 AIC) were followed for 92 months on average (standard deviation 79 months) with extension into adulthood in 52.5%; 70% had associated inflammatory bowel disease (IBD). The proportion of patients with significant fibrosis and abnormal baseline liver tests (serum bilirubin and transaminase levels) were similar in both groups. One year postdiagnosis, 55% (15/27) of PSC patients had normal liver tests versus only 15% (2/13) in the AIC group (P = 0.02). During follow-up, more liver-related events occurred in the AIC group (69% versus 27%, hazard ratio [HR] = 3.7 [95% confidence interval (CI): 1.4-10] P = 0.01). Baseline elevated serum bilirubin levels (HR = 5.3 [95% CI: 1.7-16.9] P = 0.005) and elevated transaminase levels at 1 year (HR = 9.09 [95% CI: 1.18-66.7) P = 0.03) were predictive of liver-related events, while having IBD was not (HR = 0.48 (95% CI: 0.15-1.5) P = 0.22). CONCLUSIONS Pediatric patients with AIC and PSC presented at a similar fibrosis stage, however, with a more severe hepatitis in AIC. In this cohort, AIC was associated with more liver-related events, primarily driven by a higher rate of cirrhosis compared with PSC; transplant rates were similar.
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Affiliation(s)
- Julian Hercun
- From the Liver Unit, Centre hospitalier de l’Université de Montréal, Montréal, Canada
| | - Philippe Willems
- From the Liver Unit, Centre hospitalier de l’Université de Montréal, Montréal, Canada
| | - Marc Bilodeau
- From the Liver Unit, Centre hospitalier de l’Université de Montréal, Montréal, Canada
| | - Catherine Vincent
- From the Liver Unit, Centre hospitalier de l’Université de Montréal, Montréal, Canada
| | - Fernando Alvarez
- Department of Gastroenterology, Hepatology and Nutrition, Centre Hospitalier Universitaire Sainte-Justine, Montréal, Canada
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13
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Associations between MRI T1 mapping, liver stiffness, quantitative MRCP, and laboratory biomarkers in children and young adults with autoimmune liver disease. Abdom Radiol (NY) 2022; 47:672-683. [PMID: 34932163 PMCID: PMC8847161 DOI: 10.1007/s00261-021-03378-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 12/02/2021] [Accepted: 12/03/2021] [Indexed: 12/15/2022]
Abstract
Purpose Define relationships between quantitative magnetic resonance imaging (MRI) metrics and clinical/laboratory data in a pediatric and young adult cohort with autoimmune liver disease (AILD). Materials and methods This prospective, cross-sectional study was institutional review board-approved. Patients enrolled in an institutional AILD registry were divided into groups: (1) autoimmune hepatitis (AIH) or (2) primary sclerosing cholangitis (PSC)/autoimmune sclerosing cholangitis (ASC). Participants underwent serum liver biochemistry testing and research MRI examinations, including 3D magnetic resonance cholangiopancreatography (MRCP), magnetic resonance elastography (MRE), and iron-corrected T1 mapping (cT1). MRCP + and LiverMultiScan (Perspectum Ltd., Oxford, UK) were used to post-process 3D MRCP and cT1 data. Multiple linear regression models were used to assess relationships. Results 58 patients, 35 male, median age 16 years were included; 30 in the AIH group, 28 in the PSC/ASC group. After statistical adjustments for patient age, sex, presence of inflammatory bowel disease (IBD), specific diagnosis (PSC/ASC vs. AIH), and time from diagnosis to MRI examination, left hepatic bile duct maximum diameter was a statistically significant predictor of whole liver mean cT1, cT1 interquartile range (IQR), and MRE liver stiffness (p = 0.01–0.04). Seven laboratory values were significant predictors of whole liver cT1 IQR (p < 0.0001–0.04). Eight laboratory values and right hepatic bile duct median and maximum diameter were significant predictors of liver stiffness (p < 0.0001–0.03). Conclusions Bile duct diameters and multiple laboratory biomarkers of liver disease are independent predictors of liver stiffness and cT1 IQR in pediatric patients with AILD. Supplementary Information The online version contains supplementary material available at 10.1007/s00261-021-03378-0.
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14
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Quantitative multiparametric MRI as a non-invasive stratification tool in children and adolescents with autoimmune liver disease. Sci Rep 2021; 11:15261. [PMID: 34315985 PMCID: PMC8316432 DOI: 10.1038/s41598-021-94754-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 07/08/2021] [Indexed: 12/12/2022] Open
Abstract
Autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC) are two very closely related autoimmune liver diseases with overlapping clinical features and similar management strategies. The purpose of this study was to assess the utility of quantitative imaging markers to distinguish ASC from AIH in paediatrics. 66 participants (N = 52 AIH, N = 14 ASC) aged 14.4 ± 3.3 years scheduled to undergo routine biopsy and baseline serum liver biochemistry testing were invited to undergo MRI (non-contrast abdominal MRI and 3D fast spin-echo MRCP). Multiparametric MRI was used to measure fibro-inflammation with corrected T1 (cT1), while the biliary tree was modelled using quantitative MRCP (MRCP +). Mann–Whitney U tests were performed to compare liver function tests with imaging markers between patient groups (ASC vs AIH). Receiver operating characteristic curves and stepwise logistic regressions were used to identify the best combination of markers to discriminate between ASC and AIH. Correlations between liver function tests and imaging markers were performed using Spearman’s rank correlation. cT1 was significantly correlated with liver function tests (range 0.33 ≤ R ≤ 56, p < 0.05), as well as with fibrosis, lobular and portal inflammation (range 0.31 ≤ R ≤ 42, p < 0.05). 19 MRCP + metrics correlated significantly with liver function tests (range 0.29 ≤ R ≤ 0.43, p < 0.05). GGT and MRCP + metrics were significantly higher in ASC compared to those with AIH. The best multivariable model for distinguishing ASC from AIH included total number of ducts and the sum of relative severity of both strictures and dilatations AUC: 0.91 (95% CI 0.78–1). Quantitative MRCP metrics are a good discriminator of ASC from AIH.
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15
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Imanieh M, Farzaneh NA, Dehghani SM, Shahrebabak MG, Hosseinabadi SH. Evaluation of Validity and Efficiency of Diagnostic Criteria in Autoimmune Hepatitis in Children. THE TURKISH JOURNAL OF GASTROENTEROLOGY : THE OFFICIAL JOURNAL OF TURKISH SOCIETY OF GASTROENTEROLOGY 2021; 32:526-531. [PMID: 34405819 DOI: 10.5152/tjg.2021.19305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Autoimmune hepatitis (AIH) is a progressive inflammatory liver disease with various clinical symptoms, but treatment and prevention of hepatic failure and cirrhosis is possible with early diagnosis. However, no specific test has been approved for the diagnosis of AIH. In 2008, the International Autoimmune Hepatitis Group (IAIHG) developed a simplified diagnostic scoring system that has been widely used in practice. Nevertheless, it cannot distinguish AIH from Primary Sclerosing Cholangitis (PSC) and consensus is lacking with respect to its validity, sensitivity, and applicability for children patients. The newer 2018 version also requires validation. The present study intends to evaluate the validity and efficiency of the IAIHG simplified scoring system and new scoring system in children with AIH. METHODS The present study is a non-interventional case-control study covering 152 patients with hepatic diseases (83 patients with AIH and 69 patients with Wilson disease (WD)). Titers of autoantibodies, IgG levels, hepatic histology, and absence of viral hepatitis were scored and calculated according to IAIHG diagnostic criteria. Statistics software package (SPSS) and draft receiver operating characteristic (ROC) curves was used to analyze data and determine value of diagnostic criteria. RESULT In our study, both scoring systems' accuracy was good in AIH diagnosis, although new score displays higher sensitivity and specificity, suggestive of greater accuracy and predictive strength. CONCLUSION Our study is the first validation study of the new scoring system in diagnosing AIH, and further studies require verifying this scoring system.
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Affiliation(s)
- Mohammadhadi Imanieh
- Division of Gastroenterology, Department of Pediatrics, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Nazanin Amin Farzaneh
- Division of Gastroenterology, Department of Pediatrics, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyed Mohsen Dehghani
- Division of Gastroenterology, Department of Pediatrics, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Maryam Gholami Shahrebabak
- Division of Gastroenterology, Department of Pediatrics, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Samaneh Hamzelou Hosseinabadi
- Division of Gastroenterology, Department of Pediatrics, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
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Muratori P, Granito A, Lenzi M, Muratori L. Limitation of the simplified scoring system for the diagnosis of autoimmune Hepatitis with acute onset. Liver Int 2021; 41:529-534. [PMID: 33389800 DOI: 10.1111/liv.14778] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 12/14/2020] [Accepted: 12/28/2020] [Indexed: 12/18/2022]
Abstract
Autoimmune Hepatitis (AIH) is a chronic inflammatory liver disease of unknown aetiology characterized by the presence of autoantibodies, hypergammaglobulinaemia with specific IgG increase and interface hepatitis on liver histology. The clinical course of AIH is classically characterized by fluctuating periods of decreased or increased disease activity and therefore its clinical spectrum is variable ranging from no symptoms to severe acute hepatitis and even fulminant hepatic failure. Acute presentation may not differ from acute hepatitis of other causes and diagnosis can be difficult. We describe our experience on diagnostic performance of the two AIH scoring systems in acute onset of AIH and found that revised version of the original criteria (1999) achieves the diagnosis in about 30% of patients who presented with normal IgG serum levels and lower frequency of autoantibody positivity in whom the simplified score did not allow the diagnosis.
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Affiliation(s)
- Paolo Muratori
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Center for the Study and Treatment of Autoimmune Diseases of the Liver and Biliary System, Bologna, Italy
- Department of Science for the Quality of Life, University of Bologna, Bologna, Italy
| | - Alessandro Granito
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Center for the Study and Treatment of Autoimmune Diseases of the Liver and Biliary System, Bologna, Italy
- Department of Medicine and Surgery, University of Bologna, Bologna, Italy
| | - Marco Lenzi
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Center for the Study and Treatment of Autoimmune Diseases of the Liver and Biliary System, Bologna, Italy
- Department of Medicine and Surgery, University of Bologna, Bologna, Italy
| | - Luigi Muratori
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Center for the Study and Treatment of Autoimmune Diseases of the Liver and Biliary System, Bologna, Italy
- Department of Medicine and Surgery, University of Bologna, Bologna, Italy
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Deneau MR, Mack C, Perito ER, Ricciuto A, Valentino PL, Amin M, Amir AZ, Aumar M, Auth M, Broderick A, DiGuglielmo M, Draijer LG, Tavares Fagundes ED, El-Matary W, Ferrari F, Furuya KN, Gupta N, Hochberg JT, Homan M, Horslen S, Iorio R, Jensen MK, Jonas MM, Kamath BM, Kerkar N, Kim KM, Kolho KL, Koot BG, Laborda TJ, Lee CK, Loomes KM, Martinez M, Miethke A, Miloh T, Mogul D, Mohammad S, Mohan P, Moroz S, Ovchinsky N, Palle S, Papadopoulou A, Rao G, Ferreira AR, Sathya P, Schwarz KB, Shah U, Shteyer E, Singh R, Smolka V, Soufi N, Tanaka A, Varier R, Vitola B, Woynarowski M, Zerofsky M, Zizzo A, Guthery SL. The Sclerosing Cholangitis Outcomes in Pediatrics (SCOPE) Index: A Prognostic Tool for Children. Hepatology 2021; 73:1074-1087. [PMID: 32464706 PMCID: PMC8557635 DOI: 10.1002/hep.31393] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 04/21/2020] [Accepted: 05/03/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS Disease progression in children with primary sclerosing cholangitis (PSC) is variable. Prognostic and risk-stratification tools exist for adult-onset PSC, but not for children. We aimed to create a tool that accounts for the biochemical and phenotypic features and early disease stage of pediatric PSC. APPROACH AND RESULTS We used retrospective data from the Pediatric PSC Consortium. The training cohort contained 1,012 patients from 40 centers. We generated a multivariate risk index (Sclerosing Cholangitis Outcomes in Pediatrics [SCOPE] index) that contained total bilirubin, albumin, platelet count, gamma glutamyltransferase, and cholangiography to predict a primary outcome of liver transplantation or death (TD) and a broader secondary outcome that included portal hypertensive, biliary, and cancer complications termed hepatobiliary complications (HBCs). The model stratified patients as low, medium, or high risk based on progression to TD at rates of <1%, 3%, and 9% annually and to HBCs at rates of 2%, 6%, and 13% annually, respectively (P < 0.001). C-statistics to discriminate outcomes at 1 and 5 years were 0.95 and 0.82 for TD and 0.80 and 0.76 for HBCs, respectively. Baseline hepatic fibrosis stage was worse with increasing risk score, with extensive fibrosis in 8% of the lowest versus 100% with the highest risk index (P < 0.001). The model was validated in 240 children from 11 additional centers and performed well. CONCLUSIONS The SCOPE index is a pediatric-specific prognostic tool for PSC. It uses routinely obtained, objective data to predict a complicated clinical course. It correlates strongly with biopsy-proven liver fibrosis. SCOPE can be used with families for shared decision making on clinical care based on a patient's individual risk, and to account for variable disease progression when designing future clinical trials.
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Affiliation(s)
- Mark R. Deneau
- University of Utah and Intermountain Primary Children’s Hospital, Salt Lake City, UT
| | - Cara Mack
- University of Colorado School of Medicine, Aurora, CO
| | | | | | | | - Mansi Amin
- Phoenix Children’s Hospital, Phoenix, AZ
| | - Achiya Z. Amir
- The Dana-Dwek Children’s Hospital, The Tel-Aviv Medical Center, Tel-Aviv University, Tel Aviv, Israel
| | | | - Marcus Auth
- Alder Hey Children’s Hospital, Liverpool, United Kingdom
| | - Annemarie Broderick
- Children’s Health Ireland at Crumlin & University College Dublin, Dublin, Ireland
| | | | | | | | | | | | - Katryn N. Furuya
- University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI
| | - Nitika Gupta
- Emory University School of Medicine, Atlanta, GA
| | | | | | | | | | - M. Kyle Jensen
- University of Utah and Intermountain Primary Children’s Hospital, Salt Lake City, UT
| | - Maureen M. Jonas
- Boston Children’s Hospital and Harvard Medical School, Boston, MA
| | | | - Nanda Kerkar
- University of Rochester Medical Center, Rochester, NY
| | | | - Kaija-Leena Kolho
- University of Helsinki Hospital and Tampere University, Helsinki, Finland
| | - Bart G.P. Koot
- Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Trevor J. Laborda
- University of Utah and Intermountain Primary Children’s Hospital, Salt Lake City, UT
| | - Christine K. Lee
- Boston Children’s Hospital and Harvard Medical School, Boston, MA
| | | | | | | | | | | | | | | | - Stacy Moroz
- University of Southern California, Los Angeles, CA
| | - Nadia Ovchinsky
- Children’s Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY
| | | | - Alexandra Papadopoulou
- First Department of Pediatrics, University of Athens, Children’s Hospital Agia Sofia, Athens, Greece
| | | | | | - Pushpa Sathya
- Memorial University, St. John’s, Newfoundland, Canada
| | - Kathleen B. Schwarz
- Johns Hopkins University, Baltimore, MD
- University of California San Diego, San Diego, CA
| | - Uzma Shah
- Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | | | - Ruchi Singh
- Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
| | | | | | | | - Raghu Varier
- Northwest Pediatric Gastroenterology LLC, Portland, OR
| | | | | | | | - Andréanne Zizzo
- London Health Sciences Center, Western University, London, Ontario, Canada
| | - Stephen L. Guthery
- University of Utah and Intermountain Primary Children’s Hospital, Salt Lake City, UT
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18
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Deneau MR, Mack C, Mogul D, Perito ER, Valentino PL, Amir AZ, DiGuglielmo M, Draijer LG, El-Matary W, Furuya KN, Gupta N, Hochberg JT, Horslen S, Jensen MK, Jonas MM, Kerkar N, Koot BG, Laborda TJ, Lee CK, Loomes KM, Martinez M, Miethke A, Miloh T, Mohammad S, Ovchinsky N, Rao G, Ricciuto A, Sathya P, Schwarz KB, Shah U, Singh R, Vitola B, Zizzo A, Guthery SL. Oral Vancomycin, Ursodeoxycholic Acid, or No Therapy for Pediatric Primary Sclerosing Cholangitis: A Matched Analysis. Hepatology 2021; 73:1061-1073. [PMID: 32946600 PMCID: PMC8557636 DOI: 10.1002/hep.31560] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 08/21/2020] [Accepted: 08/27/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Many children with primary sclerosing cholangitis (PSC) receive oral vancomycin therapy (OVT) or ursodeoxycholic acid (UDCA). There is a paucity of data on whether these medications improve outcomes. APPROACH AND RESULTS We analyzed retrospective data from the Pediatric PSC Consortium. Children treated with OVT were matched 1:1:1 to those treated with UDCA or managed with observation (no treatment) based on the closest propensity score, ensuring similar baseline characteristics. Two hundred sixty-four patients (88 each with OVT, UDCA, or observation) had matching propensity scores and were similar in demographics, phenotype, immunosuppression, baseline biochemistry, and hepatic fibrosis. After 1 year in an intention-to-treat analysis, all outcome metrics were similar regardless of treatment group. In OVT, UDCA, and untreated groups, respectively: Gamma-glutamyltransferase normalized in 53%, 49%, and 52% (P = not significant [NS]), liver fibrosis stage was improved in 20%, 13%, and 18% and worsened in 11%, 29%, and 18% (P = NS), and the 5-year probability of liver transplant listing was 21%, 10%, and 12% (P = NS). Favorable outcome was associated with having a mild phenotype of PSC and minimal hepatic fibrosis. CONCLUSIONS We presented the largest-ever description of outcomes on OVT in PSC and compared them to carefully matched patients on UDCA or no therapy. Neither OVT nor UDCA showed improvement in outcomes compared to a strategy of observation. Patients progressed to end-stage liver disease at similar rates. Spontaneous normalization of biochemistry is common in children receiving no therapy, particularly in the majority of children with a mild phenotype and an early stage of disease. Placebo-controlled treatment trials are needed to identify effective treatments for pediatric PSC.
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Affiliation(s)
- Mark R. Deneau
- University of Utah and Intermountain Primary Children’s Hospital, Salt Lake City, UT
| | - Cara Mack
- University of Colorado School of Medicine, Aurora, CO
| | | | | | | | - Achiya Z. Amir
- The Dana-Dwek Children’s Hospital, The Tel-Aviv Medical Center, Tel-Aviv University, Tel Aviv, Israel
| | | | | | | | - Katryn N. Furuya
- Mayo Clinic, Rochester, MN
- University of Wisconsin–Madison School of Medicine and Public Health, Madison, WI
| | - Nitika Gupta
- Emory University School of Medicine, Atlanta, GA
| | | | | | - M. Kyle Jensen
- University of Utah and Intermountain Primary Children’s Hospital, Salt Lake City, UT
| | - Maureen M. Jonas
- Boston Children’s Hospital and Harvard Medical School, Boston, MA
| | - Nanda Kerkar
- University of Rochester Medical Center, Rochester, NY
| | - Bart G.P. Koot
- Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Trevor J. Laborda
- University of Utah and Intermountain Primary Children’s Hospital, Salt Lake City, UT
| | - Christine K. Lee
- Boston Children’s Hospital and Harvard Medical School, Boston, MA
| | | | | | | | | | | | - Nadia Ovchinsky
- Children’s Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY
| | | | | | - Pushpa Sathya
- Memorial University, St. John’s, Newfoundland and Labrador, Canada
| | - Kathleen B. Schwarz
- Johns Hopkins University, Baltimore, MD
- University of California San Diego, San Diego, CA
| | - Uzma Shah
- Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Ruchi Singh
- Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
| | | | - Andréanne Zizzo
- London Health Sciences Center, Western University, London, Ontario, Canada
| | - Stephen L. Guthery
- University of Utah and Intermountain Primary Children’s Hospital, Salt Lake City, UT
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19
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Lam S, Singh R, Dillman JR, Trout AT, Serai SD, Sharma D, Sheridan R, Su W, Fei L, Karns R, Haramija MM, Ridgway G, Goldfinger M, Squires JE, Denson LA, Hyams JS, Miethke AG. Serum Matrix Metalloproteinase 7 Is a Diagnostic Biomarker of Biliary Injury and Fibrosis in Pediatric Autoimmune Liver Disease. Hepatol Commun 2020; 4:1680-1693. [PMID: 33163837 PMCID: PMC7603534 DOI: 10.1002/hep4.1589] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 07/08/2020] [Accepted: 07/11/2020] [Indexed: 12/17/2022] Open
Abstract
In autoimmune liver disease (AILD), including autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), and overlap syndrome of AIH and PSC (ASC), the presence of biliary injury portends a worse prognosis. We studied serum matrix metalloproteinase 7 (sMMP7) as a biomarker for pediatric sclerosing cholangitis (SC). We prospectively enrolled 54 children (median age, 16 years) with AILD (AIH, n = 26; ASC, n = 16; and PSC, n = 12) at our center. The sMMP7 concentrations were higher in patients with SC compared to those without cholangiopathy (P < 0.001). An sMMP7 concentration >23.7 ng/mL had a sensitivity and specificity of 79% and 96%, respectively, and outperformed alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) in segregating patients with SC. Serum concentrations correlated with liver gene expression levels for MMP7 (r = 0.70; P < 0.001). Using immunofluorescence, MMP7 was localized primarily to the cholangiocytes of patients with SC. In 46 subjects with liver biopsy available for blinded review, elevation in sMMP7 concentrations segregated with the presence of lymphocytic and neutrophilic cholangitis and periductal fibrosis and correlated with Ishak, Ludwig, and Nakanuma scoring systems. Liver stiffness measured by magnetic resonance elastography also correlated with sMMP7 concentrations (r = 0.56; P < 0.01). Using magnetic resonance cholangiopancreatography plus (MRCP+), sMMP7 in 34 patients correlated with the number of biliary dilatations (r = 0.54; P < 0.01) and strictures (r = 0.56; P < 0.01). MMP7 as a marker of biliary injury was validated in an independent cohort of children with ulcerative colitis. Higher sMMP7 concentrations also correlated with a history of SC-related complication. Conclusion: MMP7 is a promising biomarker for pediatric SC that diagnostically outperforms ALP and GGT. sMMP7 may directly reflect biliary injury and fibrosis, the main drivers of disease progression in SC.
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Affiliation(s)
- Simon Lam
- Division of Gastroenterology, Hepatology and NutritionCincinnati Children's Hospital Medical CenterCincinnatiOHUSA
- Department of PediatricsUniversity of Cincinnati College of MedicineCincinnatiOHUSA
- Section of Pediatric GastroenterologyDepartment of PediatricsAlberta Children’s HospitalUniversity of CalgaryCalgaryCanada
| | - Ruchi Singh
- Division of Gastroenterology, Hepatology and NutritionCincinnati Children's Hospital Medical CenterCincinnatiOHUSA
| | - Jonathan R. Dillman
- Department of PediatricsUniversity of Cincinnati College of MedicineCincinnatiOHUSA
- Department of RadiologyCincinnati Children's Hospital Medical CenterUniversity of Cincinnati College of MedicineCincinnatiOHUSA
| | - Andrew T. Trout
- Department of PediatricsUniversity of Cincinnati College of MedicineCincinnatiOHUSA
- Department of RadiologyCincinnati Children's Hospital Medical CenterUniversity of Cincinnati College of MedicineCincinnatiOHUSA
| | - Suraj D. Serai
- Department of RadiologyChildren’s Hospital of PhiladelphiaPhiladelphiaPAUSA
| | - Divya Sharma
- Division of PathologyUniversity of CincinnatiCincinnatiOHUSA
| | - Rachel Sheridan
- Department of PathologyDayton Children’s HospitalDaytonOHUSA
| | - Weizhe Su
- Division of Biostatistics and EpidemiologyCincinnati Children's Hospital Medical CenterCincinnatiOHUSA
| | - Lin Fei
- Division of Biostatistics and EpidemiologyCincinnati Children's Hospital Medical CenterCincinnatiOHUSA
| | - Rebekah Karns
- Division of Gastroenterology, Hepatology and NutritionCincinnati Children's Hospital Medical CenterCincinnatiOHUSA
| | | | - Ged Ridgway
- Perspectum Diagnostics Ltd.South San FranciscoCAUSA
| | | | | | - Lee A. Denson
- Division of Gastroenterology, Hepatology and NutritionCincinnati Children's Hospital Medical CenterCincinnatiOHUSA
- Department of PediatricsUniversity of Cincinnati College of MedicineCincinnatiOHUSA
| | - Jeffery S. Hyams
- Division of Digestive DiseasesHepatology, and NutritionConnecticut Children’s Hospital Medical CenterHartfordCTUSA
| | - Alexander G. Miethke
- Division of Gastroenterology, Hepatology and NutritionCincinnati Children's Hospital Medical CenterCincinnatiOHUSA
- Department of PediatricsUniversity of Cincinnati College of MedicineCincinnatiOHUSA
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Freedman BL, Danford CJ, Patwardhan V, Bonder A. Treatment of Overlap Syndromes in Autoimmune Liver Disease: A Systematic Review and Meta-Analysis. J Clin Med 2020; 9:jcm9051449. [PMID: 32414025 PMCID: PMC7291241 DOI: 10.3390/jcm9051449] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 04/30/2020] [Accepted: 05/07/2020] [Indexed: 12/13/2022] Open
Abstract
The treatment of overlap syndromes is guided by small observational studies whose data have never been synthesized in a rigorous, quantitative manner. We conducted a systematic review and meta-analysis to evaluate the efficacy of available treatments for these rare and morbid conditions. We searched the literature for studies comparing ≥2 therapies for autoimmune hepatitis (AIH)-primary biliary cholangitis (PBC), AIH-primary sclerosing cholangitis (PSC), PBC-PSC, AIH-PBC-PSC, autoimmune cholangitis (AIC), or autoimmune sclerosing cholangitis (ASC) with respect to various clinical outcomes, including biochemical improvement and transplant-free survival. A total of 28 studies met the inclusion criteria for AIH-PBC, AIH-PSC, AIC, and ASC. AIH-PBC patients tended to experience more biochemical improvement with ursodeoxycholic acid (UDCA) + [corticosteroids and/or antimetabolites], i.e., "combination therapy", than with corticosteroids ± azathioprine (RR = 4.00, 95% CI 0.93-17.18). AIH-PBC patients had higher transplant-free survival with combination therapy than with UDCA, but only when studies with follow-up periods ≤90 months were excluded (RR = 6.50, 95% CI 1.47-28.83). Combination therapy may therefore be superior to both UDCA and corticosteroids ± azathioprine for the treatment of AIH-PBC, but additional studies are needed to show this definitively and to elucidate optimal treatments for other overlap syndromes.
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Affiliation(s)
- Benjamin L. Freedman
- Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215, USA;
| | - Christopher J. Danford
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Dana 603, Boston, MA 02215, USA;
| | - Vilas Patwardhan
- Liver Center, Autoimmune and Cholestatic Liver Disease Program, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis St. Suite 8E, Boston, MA 02215, USA;
| | - Alan Bonder
- Liver Center, Autoimmune and Cholestatic Liver Disease Program, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis St. Suite 8E, Boston, MA 02215, USA;
- Correspondence: ; Tel.: +1-617-632-1070
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21
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Utility and accuracy of transient elastography in determining liver fibrosis: a case-control study. Eur J Pediatr 2020; 179:671-677. [PMID: 31960149 DOI: 10.1007/s00431-019-03561-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Revised: 12/19/2019] [Accepted: 12/23/2019] [Indexed: 12/15/2022]
Abstract
The objectives of this prospective case-control study were to determine liver stiffness (LSM) by transient elastography (TE) in children with newly diagnosed chronic liver disease (CLD) and to find out normal values in healthy Indian children. Two groups (A: 50 CLD who underwent liver biopsy and B: 50 healthy) aged 5-18 years were recruited prospectively. Liver biopsies were scored as per Metavir scoring and compared with TE. The median age of 100 recruited children was 13.6 years. In group B, normal LSM was 4.9 (2.5-7.3) kPa with significantly higher LSM in adolescent males (5.6 (4.1-7.3) kPa) as compared with females (4.3 (3.7-4.9) kPa), p = 0.001. In group A, TE was excellent in discriminating significant fibrosis (≥ F2) (P = 0.001) at a cut-off value of 10.6 kPa with area under receiver operating characteristic curve of 0.96. Metavir fibrosis stage (β = 0.611; R2 = 0.586) and age (β = 0.230; R2 = 0.586) were independent variables associated with higher LSM in stepwise multiple logistic regression analysis.Conclusions: TE is an excellent non-invasive tool to assess significant liver fibrosis and can be used as an alternative to liver biopsy. Normative value of TE in adolescent males is higher than in females.What is Known:• Transient elastography is a good non-invasive test for liver fibrosis assessment.• Normal liver stiffness depends on race, gender, and age.What is New:• This is the first study from India to show the normative data of transient elastography in healthy Indian children.• We have documented that liver stiffness measurement by fibroscan in treatment naïve chronic liver disease has excellent correlation in significant fibrosis, severe fibrosis, and cirrhosis.
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22
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Smolka V, Tkachyk O, Ehrmann J, Karaskova E, Zapalka M, Volejnikova J. Acute onset of autoimmune hepatitis in children and adolescents. Hepatobiliary Pancreat Dis Int 2020; 19:17-21. [PMID: 31474443 DOI: 10.1016/j.hbpd.2019.08.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Accepted: 08/15/2019] [Indexed: 02/05/2023]
Abstract
BACKGROUND Autoimmune hepatitis (AIH) is a rare progressive liver disease, which manifests as acute hepatitis in 40%-50% of pediatric cases. This refers predominantly to spontaneous exacerbations of previously unrecognized subclinical AIH with laboratory and histological signs of chronic hepatitis, or to acute exacerbations of known chronic disease. Only a few of these patients fulfill criteria for acute liver failure (ALF). METHODS Forty children diagnosed with AIH in our center between 2000 and 2018 were included in this study. All of them fulfilled revised diagnostic criteria of the International Autoimmune Hepatitis Group (IAIHG) for probable or confirmed AIH, and other etiologies of liver diseases were excluded. Patients were divided into two groups: acute AIH (A-AIH) or chronic AIH (C-AIH). RESULTS Acute onset of AIH occurred in 19/40 children (48%). Six of them fulfilled the criteria of ALF with coagulopathy and encephalopathy. Five of 6 children with ALF suffered from exacerbation of previously undiagnosed chronic AIH, among which 4 children were histologically confirmed as micronodular cirrhosis. The remaining one patient had fulminant AIH with centrilobular necrosis, but no histological signs of previous chronic liver damage. We observed significantly lower levels of albumin, higher levels of aminotransferases, bilirubin, INR, IgG, higher IAIHG score and more severe histological findings in A-AIH than in C-AIH. No differences in patient age and presence of autoantibodies were observed between A-AIH and C-AIH. All children, including those with ALF and cirrhosis, were treated with corticosteroids, and are alive and achieved AIH remission. Liver transplant was not indicated in any patient. CONCLUSION Rapid and accurate diagnosis of A-AIH may be difficult. However, timely start of immunosuppressive therapy improves prognosis and decreases number of indicated liver transplantations in children with AIH.
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Affiliation(s)
- Vratislav Smolka
- Department of Pediatrics, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, I. P. Pavlova 185/6, Olomouc 779 00, Czech Republic.
| | - Oksana Tkachyk
- Department of Pediatrics, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, I. P. Pavlova 185/6, Olomouc 779 00, Czech Republic
| | - Jiri Ehrmann
- Department of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, I. P. Pavlova 185/6, Olomouc 779 00, Czech Republic
| | - Eva Karaskova
- Department of Pediatrics, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, I. P. Pavlova 185/6, Olomouc 779 00, Czech Republic
| | - Martin Zapalka
- Department of Pediatrics, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, I. P. Pavlova 185/6, Olomouc 779 00, Czech Republic
| | - Jana Volejnikova
- Department of Pediatrics, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, I. P. Pavlova 185/6, Olomouc 779 00, Czech Republic
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23
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Deneau MR, Valentino PL, Mack C, Alqoaer K, Amin M, Amir AZ, Aumar M, Auth M, Broderick A, DiGuglielmo M, Draijer LG, El-Matary W, Ferrari F, Furuya KN, Gottrand F, Gupta N, Homan M, Jensen MK, Kamath BM, Kim KM, Kolho KL, Koot B, Iorio R, Martinez M, Miloh T, Mohan P, Palle S, Papadopoulou A, Ricciuto A, Saubermann L, Sathya P, Shteyer E, Smolka V, Tanaka A, Varier R, Venkat V, Vitola B, Woynarowski M, Guthery S. Assessing the Validity of Adult-derived Prognostic Models for Primary Sclerosing Cholangitis Outcomes in Children. J Pediatr Gastroenterol Nutr 2020; 70:e12-e17. [PMID: 31651664 DOI: 10.1097/mpg.0000000000002522] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Natural history models for primary sclerosing cholangitis (PSC) are derived from adult patient data, but have never been validated in children. It is unclear how accurate such models are for children with PSC. METHODS We utilized the pediatric PSC consortium database to assess the Revised Mayo Clinic, Amsterdam-Oxford, and Boberg models. We calculated the risk stratum and predicted survival for each patient within each model using patient data at PSC diagnosis, and compared it with observed survival. We evaluated model fit using the c-statistic. RESULTS Model fit was good at 1 year (c-statistics 0.93, 0.87, 0.82) and fair at 10 years (0.78, 0.75, 0.69) in the Mayo, Boberg, and Amsterdam-Oxford models, respectively. The Mayo model correctly classified most children as low risk, whereas the Amsterdam-Oxford model incorrectly classified most as high risk. All of the models underestimated survival of patients classified as high risk. Albumin, bilirubin, AST, and platelets were most associated with outcomes. Autoimmune hepatitis was more prevalent in higher risk groups, and over-weighting of AST in these patients accounted for the observed versus predicted survival discrepancy. CONCLUSIONS All 3 models offered good short-term discrimination of outcomes but only fair long-term discrimination. None of the models account for the high prevalence of features of autoimmune hepatitis overlap in children and the associated elevated aminotransferases. A pediatric-specific model is needed. AST, bilirubin, albumin, and platelets will be important predictors, but must be weighted to account for the unique features of PSC in children.
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Affiliation(s)
| | | | - Cara Mack
- University of Colorado School of Medicine, Aurora, CO
| | | | - Mansi Amin
- Phoenix Children's Hospital, Phoenix, AZ
| | - Achiya Z Amir
- The Dana-Dwek Children's Hospital, The Tel-Aviv Medical Center, Tel-Aviv University, Tel Aviv, Israel
| | | | - Marcus Auth
- Alder Hey Children's Hospital, Liverpool, United Kingdom
| | | | | | | | | | | | | | | | - Nitika Gupta
- Emory University School of Medicine, Atlanta, GA
| | | | | | | | | | | | - Bart Koot
- Academic Medical Centre, Amsterdam, The Netherlands
| | | | - Mercedes Martinez
- Columbia University College of Physicians and Surgeons, New York, NY
| | | | | | - Sirish Palle
- Emory University School of Medicine, Atlanta, GA
| | | | | | | | - Pushpa Sathya
- Memorial University, St. John's, Newfoundland and Labrador, Canada
| | | | | | | | - Raghu Varier
- Northwest Pediatric Gastroenterology LLC, Portland, OR
| | - Veena Venkat
- University of Pittsburgh Medical Center, Pittsburgh, PA
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24
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Gilligan LA, Trout AT, Lam S, Singh R, Tkach JA, Serai SD, Miethke AG, Dillman JR. Differentiating pediatric autoimmune liver diseases by quantitative magnetic resonance cholangiopancreatography. Abdom Radiol (NY) 2020; 45:168-176. [PMID: 31422438 DOI: 10.1007/s00261-019-02184-z] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
PURPOSE Autoimmune liver diseases (AILD), including primary sclerosing cholangitis (PSC), autoimmune sclerosing cholangitis (ASC), and autoimmune hepatitis (AIH), have overlapping clinical features but distinct management strategies and outcomes. The purpose of this study was to assess the diagnostic performance of quantitative magnetic resonance cholangiopancreatography (MRCP) parameters for distinguishing PSC/ASC from AIH in children and young adults. MATERIALS AND METHODS This IRB-approved, cross-sectional study included participants from an institutional AILD registry that underwent baseline serum liver biochemistry testing and 3D fast spin-echo MRCP. The biliary tree was extracted and modeled from MRCP images using novel proprietary software (MRCP+ ™; Perspectum Diagnostics; Oxford, United Kingdom), and quantitative parameters were generated (e.g., biliary tree volume; number and length of bile ducts, strictures, and dilations; bile duct median/maximum diameters). Mann-Whitney U tests were performed to compare laboratory values and MRCP metrics between patient cohorts (clinical diagnosis of PSC/ASC versus AIH). Receiver operating characteristic (ROC) curves and multivariable logistic regression were used to assess diagnostic performance of serum biochemistry values and MRCP parameters for discriminating PSC/ASC from AIH. RESULTS Thirty percent (14/47) of MRCP exams failed post-processing due to motion artifact. The remaining 33 patients included 20 males and 13 females, with a mean age of 15.1 ± 3.9 years. Eighteen patients were assigned the clinical diagnosis of PSC or ASC and 15 of AIH. All but one quantitative MRCP parameter were significantly different between cohorts (p < 0.05) and predictive of diagnosis (ROC p < 0.05), including numbers of bile duct strictures (area under curve [AUC] = 0.86, p < 0.0001) and dilations (AUC = 0.87, p < 0.0001) and total length of dilated ducts (AUC = 0.89, p < 0.0001). Laboratory values were not significantly different between cohorts (p > 0.05). The best multivariable model for distinguishing PSC/ASC from AIH included total length of dilated ducts (odds ratio [OR], 1.08; 95% CI 1.02-1.14) and maximum left hepatic duct diameter (OR, 1.21; 95% CI 0.57-2.56) [AUC = 0.92]. CONCLUSION Quantitative MRCP parameters provide good discrimination of PSC/ASC from AIH.
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Affiliation(s)
- Leah A Gilligan
- Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
| | - Andrew T Trout
- Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Simon Lam
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Ruchi Singh
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Jean A Tkach
- Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Suraj D Serai
- Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Alexander G Miethke
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Jonathan R Dillman
- Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
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25
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Almaas R. Diagnosing autoimmune hepatitis in paediatric patients - we still haven't found what we are looking for. Acta Paediatr 2019; 108:1562-1563. [PMID: 31264728 DOI: 10.1111/apa.14890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Runar Almaas
- Department of Pediatric Research Division of Paediatric and Adolescent Medicine Rikshospitalet Oslo University Hospital Nydalen Norway
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26
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Joosse ME, Haisma SM, Sterk MFM, van Munster KN, Ponsioen CIJ, Houwen RHJ, Koot BGP, de Meij T, van Rheenen PF, de Koning BAE. Disease progression in paediatric- and adult-onset sclerosing cholangitis: Results from two independent Dutch registries. Liver Int 2019; 39:1768-1775. [PMID: 31152478 DOI: 10.1111/liv.14159] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Revised: 05/15/2019] [Accepted: 05/20/2019] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS Sclerosing cholangitis (SC) is a severe liver disease leading to destruction of bile ducts. It is believed to run a milder course in children than in adults. To test this assumption, we evaluated time-to-complication curves in two independent paediatric-onset cohorts from the same geographical area. METHODS Short-term disease outcomes were evaluated with an online clinical registry that was filled with data on children with SC diagnosed between 2000 and 2017 and who were followed bi-annually thereafter. Long-term disease outcomes were evaluated in a paediatric-onset subcohort derived from a previously published population-based study from the Netherlands. Time-to-complication in the first cohort was defined as the time from diagnosis until portal hypertension, biliary obstructions and infections, development of malignancy, or liver transplantation, whichever came first. In the second cohort time-to-complication was defined as the time until liver transplantation or PSC-related death. RESULTS Median age at diagnosis in the first cohort (n = 86) was 12.3 years. In the first 5 years post-diagnosis 23% of patients developed complications. The patients in the population-based study (n = 683) were stratified into those diagnosed before the age of 18 years ('paediatric-onset' subcohort, n = 43) and those diagnosed after the age of 18 years ('adult-onset' subcohort, n = 640). Median age at diagnosis was 14.6 and 40.2 years, respectively. Median time-to-complication in the paediatric-onset and adult-onset subcohorts was not statistically different. CONCLUSION Paediatric and adult-onset SC run a similar long-term disease course. Paediatricians who treat children with SC should monitor them closely to recognize early complications and control long-term sequelae.
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Affiliation(s)
- Maria E Joosse
- Department of Pediatric Gastroenterology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands
| | - Sjoukje M Haisma
- University of Groningen, University Medical Center Groningen, Pediatric Gastroenterology Hepatology and Nutrition, Groningen, the Netherlands
| | - Marlou F M Sterk
- Department of Pediatric Gastroenterology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands
| | - Kim N van Munster
- Department of Gastroenterology & Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Cyriel I J Ponsioen
- Department of Gastroenterology & Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Roderick H J Houwen
- Department of Pediatric Gastroenterology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Bart G P Koot
- Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Tim de Meij
- Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.,Department of Pediatric Gastroenterology, VU University Medical Center, Amsterdam, The Netherlands
| | - Patrick F van Rheenen
- University of Groningen, University Medical Center Groningen, Pediatric Gastroenterology Hepatology and Nutrition, Groningen, the Netherlands
| | - Barbara A E de Koning
- Department of Pediatric Gastroenterology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands
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27
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Arcos-Machancoses JV, Molera Busoms C, Julio Tatis E, Bovo MV, Quintero Bernabeu J, Juampérez Goñi J, Crujeiras Martínez V, Martín de Carpi J. Development and validation of a new simplified diagnostic scoring system for pediatric autoimmune hepatitis. Dig Liver Dis 2019; 51:1308-1313. [PMID: 30928421 DOI: 10.1016/j.dld.2019.02.018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Revised: 02/25/2019] [Accepted: 02/25/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Children with autoimmune hepatitis (AIH) often exhibit particular features. Accordingly, seven pediatric-specific criteria have been proposed. AIM To develop a prediction model based on them, transform it into a scoring system and study its accuracy. METHODS A cohort of children under study for liver disease was consecutively selected. AIH diagnosis was based on classical criteria. Already proposed pediatric criteria were recorded. The best possible regression model was selected, and the beta coefficient of each criterion was translated into a whole number (points). Total scores were obtained following the points system and the best cut-off was calculated. Subsequently, accuracy of the diagnostic score was studied in the validation set. RESULTS Among 212 included patients, 100 had AIH. The score included 5 criteria: autoantibodies (0-2 points), hypergammaglobulinemia, exclusion of viral hepatitis, exclusion of Wilson's disease (1 point each) and liver histology (3 points). In addition, a normal cholangiogram is mandatory. The validation set was formed of 70 patients (24 with AIH). In this subsample, a score of ≥6 renders a sensitivity/specificity of 95.8%/100%. The area under the receiver operating characteristic curve was 97.1%. CONCLUSION Pediatric-specific criteria for the diagnosis of AIH can be reliably used as a scoring system.
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Affiliation(s)
| | - Cristina Molera Busoms
- Sant Joan de Déu Hospital (HSJD), Department of Pediatric Gastroenterology, Hepatology and Nutrition, Barcelona, Spain; HSJD-HVH Comprehensive Unit of Complex Hepatology and Pediatric Liver Transplantation, Barcelona, Spain.
| | - Ecaterina Julio Tatis
- Sant Joan de Déu Hospital (HSJD), Department of Pediatric Gastroenterology, Hepatology and Nutrition, Barcelona, Spain.
| | - María Victoria Bovo
- Sant Joan de Déu Hospital (HSJD), Department of Pediatric Gastroenterology, Hepatology and Nutrition, Barcelona, Spain.
| | - Jesús Quintero Bernabeu
- Vall d'Hebron Hospital (HVH), Department of Pediatric Gastroenterology, Hepatology and Nutrition, Barcelona, Spain; HSJD-HVH Comprehensive Unit of Complex Hepatology and Pediatric Liver Transplantation, Barcelona, Spain.
| | - Javier Juampérez Goñi
- Vall d'Hebron Hospital (HVH), Department of Pediatric Gastroenterology, Hepatology and Nutrition, Barcelona, Spain; HSJD-HVH Comprehensive Unit of Complex Hepatology and Pediatric Liver Transplantation, Barcelona, Spain.
| | - Vanessa Crujeiras Martínez
- University Hospital Complex of Santiago de Compostela, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Spain.
| | - Javier Martín de Carpi
- Sant Joan de Déu Hospital (HSJD), Department of Pediatric Gastroenterology, Hepatology and Nutrition, Barcelona, Spain; HSJD-HVH Comprehensive Unit of Complex Hepatology and Pediatric Liver Transplantation, Barcelona, Spain.
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Lam S. 50 Years Ago in TheJournalof Pediatrics: Active Chronic Hepatitis in Infancy: Possible Presence of the Disease in Siblings. J Pediatr 2019; 211:32. [PMID: 31349918 DOI: 10.1016/j.jpeds.2019.01.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Affiliation(s)
- Simon Lam
- Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
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29
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Porta G, Carvalho ED, Santos JL, Gama J, Borges CV, Seixas RB, Ferreira AR, Miura IK, Silveira TR, Silva LR, Fagundes ED, Bellomo‐Brandao MA, Sawamura R, Vieira SM, Melere MU, Marques CD, Pugliese RP, Danesi VL, Porta A, Marsillac ME, Valladares MA, Menezes DG, Kieling C, Paula MND, Vasconcelos JR, Ferreira CT, Perin N, Resende LR, Maia J, De Tommaso AM, Hessel G. Autoimmune hepatitis in 828 Brazilian children and adolescents: clinical and laboratory findings, histological profile, treatments, and outcomes. JORNAL DE PEDIATRIA (VERSÃO EM PORTUGUÊS) 2019. [DOI: 10.1016/j.jpedp.2018.06.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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30
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Porta G, Carvalho ED, Santos JL, Gama J, Borges CV, Seixas RBPM, Ferreira AR, Miura IK, Silveira TR, Silva LR, Fagundes EDT, Bellomo-Brandao MA, Sawamura R, Vieira SM, Melere MU, Marques CDF, Pugliese RP, Danesi VL, Porta A, Marsillac ME, Valladares MA, Menezes DG, Kieling C, Paula MND, Vasconcelos JR, Ferreira CT, Perin N, Resende LR, Maia J, Tommaso AMAD, Hessel G. Autoimmune hepatitis in 828 Brazilian children and adolescents: clinical and laboratory findings, histological profile, treatments, and outcomes. J Pediatr (Rio J) 2019; 95:419-427. [PMID: 29856944 DOI: 10.1016/j.jped.2018.04.007] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2017] [Revised: 04/16/2018] [Accepted: 04/16/2018] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVE This large study with a long-term follow-up aimed to evaluate the clinical presentation, laboratory findings, histological profile, treatments, and outcomes of children and adolescents with autoimmune hepatitis. METHODS The medical records of 828 children and adolescents with autoimmune hepatitis were reviewed. A questionnaire was used to collect anonymous data on clinical presentation, biochemical and histological findings, and treatments. RESULTS Of all patients, 89.6% had autoimmune hepatitis-1 and 10.4% had autoimmune hepatitis-2. The female sex was predominant in both groups. The median age at symptom onset was 111.5 (6; 210) and 53.5 (8; 165) months in the patients with autoimmune hepatitis 1 and autoimmune hepatitis-2, respectively. Acute clinical onset was observed in 56.1% and 58.8% and insidious symptoms in 43.9% and 41.2% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively. The risk of hepatic failure was 1.6-fold higher for autoimmune hepatitis-2. Fulminant hepatic failure occurred in 3.6% and 10.6% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively; the risk was 3.1-fold higher for autoimmune hepatitis-2. The gamma globulin and immunoglobulin G levels were significantly higher in autoimmune hepatitis-1, while the immunoglobulin A and C3 levels were lower in autoimmune hepatitis-2. Cirrhosis was observed in 22.4% of the patients; biochemical remission was achieved in 76.2%. The actuarial survival rate was 93.0%. A total of 4.6% underwent liver transplantation, and 6.9% died (autoimmune hepatitis-1: 7.5%; autoimmune hepatitis-2: 2.4%). CONCLUSIONS In this large clinical series of Brazilian children and adolescents, autoimmune hepatitis-1 was more frequent, and patients with autoimmune hepatitis-2 exhibited higher disease remission rates with earlier response to treatment. Patients with autoimmune hepatitis-1 had a higher risk of death.
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Affiliation(s)
- Gilda Porta
- Hospital Sírio Libanês, Hospital Menino Jesus, Grupo de Hepatologia e Transplante Pediátrico, São Paulo, SP, Brazil.
| | - Elisa de Carvalho
- Hospital de Base do Distrito Federal, Hospital da Criança de Brasília, Departamento de Gastroenterologia e Hepatologia, Brasília, DF, Brazil
| | - Jorge L Santos
- Universidade da Beira Interior, Faculdade de Ciências da Saúde, Centro de Pesquisa em Ciências da Saúde (CICS-UBI), Covilhã, Portugal
| | - Jorge Gama
- Universidade da Beira Interior, Centro de Matemática e Aplicações, Departamento de Matemática, Covilhã, Portugal
| | - Cristian V Borges
- Hospital Sírio Libanês, Hospital Menino Jesus, Grupo de Hepatologia e Transplante Pediátrico, São Paulo, SP, Brazil
| | - Renata B P M Seixas
- Hospital de Base do Distrito Federal, Hospital da Criança de Brasília, Departamento de Gastroenterologia Pediátrica, Brasília, DF, Brazil
| | - Alexandre R Ferreira
- Universidade Federal de Minas Gerais (UFMG), Departamento de Gastroenterologia e Hepatologia Pediátrica, Belo Horizonte, MG, Brazil
| | - Irene K Miura
- Hospital Sírio Libanês, Hospital Menino Jesus, Grupo de Hepatologia e Transplante Pediátrico, São Paulo, SP, Brazil
| | - Themis R Silveira
- Hospital Santo Antônio, Departamento de Gastroenterologia e Hepatologia Pediátrica, Porto Alegre, RS, Brazil
| | - Luciana R Silva
- Universidade Federal da Bahia (UFBA), Departamento de Gastroenterologia e Hepatologia Pediátrica, Salvador, BA, Brazil
| | - Eleonora D T Fagundes
- Universidade Federal de Minas Gerais (UFMG), Departamento de Gastroenterologia e Hepatologia Pediátrica, Belo Horizonte, MG, Brazil
| | - Maria A Bellomo-Brandao
- Universidade Estadual de Campinas (Unicamp), Departamento de Gastroenterologia e Hepatologia Pediátrica, Campinas, SP, Brazil
| | - Regina Sawamura
- Universidade de São Paulo (USP), Faculdade de Medicina de Ribeirão Preto (FMRP), Departamento de Gastroenterologia e Hepatologia Pediátrica, Ribeirão Preto, SP, Brazil
| | - Sandra M Vieira
- Universidade Federal do Rio Grande do Sul (UFRGS), Unidade de Transplante de Fígado, Porto Alegre, RS, Brazil
| | - Melina U Melere
- Hospital Santo Antônio, Departamento de Gastroenterologia e Hepatologia Pediátrica, Porto Alegre, RS, Brazil
| | - Cibele D F Marques
- Universidade Federal da Bahia (UFBA), Departamento de Gastroenterologia e Hepatologia Pediátrica, Salvador, BA, Brazil
| | - Renata P Pugliese
- Hospital Sírio Libanês, Hospital Menino Jesus, Grupo de Hepatologia e Transplante Pediátrico, São Paulo, SP, Brazil
| | - Vera L Danesi
- Hospital Sírio Libanês, Hospital Menino Jesus, Grupo de Hepatologia e Transplante Pediátrico, São Paulo, SP, Brazil
| | - Adriana Porta
- Hospital Sírio Libanês, Hospital Menino Jesus, Grupo de Hepatologia e Transplante Pediátrico, São Paulo, SP, Brazil
| | - Marise E Marsillac
- Universidade do Estado do Rio de Janeiro (UERJ), Departamento de Gastroenterologia Pediátrica, Rio de Janeiro, RJ, Brazil; Hospital Federal dos Servidores do Estado, Rio de Janeiro, RJ, Brazil
| | - Marcia A Valladares
- Universidade Federal do Rio de Janeiro (UFRJ), Departamento de Gastroenterologia e Hepatologia Pediátrica, Rio de Janeiro, RJ, Brazil
| | - Daniela G Menezes
- Universidade Federal de Sergipe (UFS), Departamento de Gastroenterologia e Hepatologia Pediátrica, São Cristóvão, SE, Brazil
| | - Carlos Kieling
- Universidade Federal do Rio Grande do Sul (UFRGS), Unidade de Transplante de Fígado, Porto Alegre, RS, Brazil
| | - Mariana N de Paula
- Irmandade da Santa Casa Misericórdia de São Paulo, Departamento de Gastroenterologia e Hepatologia Pediátrica, São Paulo, SP, Brazil
| | - Juliana R Vasconcelos
- Universidade Federal da Paraíba (UFPB), Departamento de Gastroenterologia e Hepatologia Pediátrica, João Pessoa, PB, Brazil
| | - Cristina T Ferreira
- Hospital Santo Antônio, Departamento de Gastroenterologia e Hepatologia Pediátrica, Porto Alegre, RS, Brazil
| | - Nilza Perin
- Hospital Infantil Joana de Gusmão, Departamento de Gastroenterologia e Hepatologia Pediátrica, Florianópolis, SC, Brazil
| | - Leonardo R Resende
- Universidade Federal de Mato Grosso do Sul (UFMS), Departamento de Gastroenterologia Pediátrica, Campo Grande, MS, Brazil
| | - Jussara Maia
- Universidade Federal do Rio Grande do Norte (UFRN), Departamento de Gastroenterologia e Hepatologia Pediátrica, Natal, RN, Brazil
| | - Adriana M A De Tommaso
- Universidade Estadual de Campinas (Unicamp), Departamento de Gastroenterologia e Hepatologia Pediátrica, Campinas, SP, Brazil
| | - Gabriel Hessel
- Universidade Estadual de Campinas (Unicamp), Departamento de Gastroenterologia e Hepatologia Pediátrica, Campinas, SP, Brazil
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Deneau M, Perito E, Ricciuto A, Gupta N, Kamath BM, Palle S, Vitola B, Smolka V, Ferrari F, Amir AZ, Miloh T, Papadopoulou A, Mohan P, Mack C, Kolho KL, Iorio R, El-Matary W, Venkat V, Chan A, Saubermann L, Valentino PL, Shah U, Miethke A, Lin H, Jensen MK. Ursodeoxycholic Acid Therapy in Pediatric Primary Sclerosing Cholangitis: Predictors of Gamma Glutamyltransferase Normalization and Favorable Clinical Course. J Pediatr 2019; 209:92-96.e1. [PMID: 30878206 PMCID: PMC6535363 DOI: 10.1016/j.jpeds.2019.01.039] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2018] [Revised: 01/17/2019] [Accepted: 01/18/2019] [Indexed: 12/18/2022]
Abstract
OBJECTIVE To investigate patient factors predictive of gamma glutamyltransferase (GGT) normalization following ursodeoxycholic acid (UDCA) therapy in children with primary sclerosing cholangitis. STUDY DESIGN We retrospectively reviewed patient records at 46 centers. We included patients with a baseline serum GGT level ≥50 IU/L at diagnosis of primary sclerosing cholangitis who initiated UDCA therapy within 1 month and continued therapy for at least 1 year. We defined "normalization" as a GGT level <50 IU/L without experiencing portal hypertensive or dominant stricture events, liver transplantation, or death during the first year. RESULTS We identified 263 patients, median age 12.1 years at diagnosis, treated with UDCA at a median dose of 15 mg/kg/d. Normalization occurred in 46%. Patients with normalization had a lower prevalence of Crohn's disease, lower total bilirubin level, lower aspartate aminotransferase to platelet ratio index, greater platelet count, and greater serum albumin level at diagnosis. The 5-year survival with native liver was 99% in those patients who achieved normalization vs 77% in those who did not. CONCLUSIONS Less than one-half of the patients treated with UDCA have a complete GGT normalization in the first year after diagnosis, but this subset of patients has a favorable 5-year outcome. Normalization is less likely in patients with a Crohn's disease phenotype or a laboratory profile suggestive of more advanced hepatobiliary fibrosis. Patients who do not achieve normalization could reasonably stop UDCA, as they are likely not receiving clinical benefit. Alternative treatments with improved efficacy are needed, particularly for patients with already-advanced disease.
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Affiliation(s)
- Mark Deneau
- Department of Pediatrics, University of Utah, Salt Lake City, UT.
| | - Emily Perito
- Department of Pediatrics, University of California San Francisco, San Francisco, CA
| | - Amanda Ricciuto
- Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Nitika Gupta
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA
| | - Binita M Kamath
- Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Sirish Palle
- Department of Pediatrics, Oklahoma University, Oklahoma City, OK
| | - Bernadette Vitola
- Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI
| | - Vratislav Smolka
- Department of Pediatrics, Palacky University, Olomouc, Czech Republic
| | - Federica Ferrari
- Department of Pediatrics and Pediatric Neuropsychiatry, Sapienza University of Rome, Rome, Italy
| | - Achiya Z Amir
- Division of Gastroenterology, Liver and Nutrition, The Dana-Dwek Children's Hospital, Tel-Aviv University, Tel Aviv, Israel
| | - Tamir Miloh
- Department of Pediatrics, Texas Children's Hospital, Houston, TX
| | | | - Parvathi Mohan
- Department of Gastroenterology, Hepatology, and Nutrition, Children's National Medical Center, Washington, DC
| | - Cara Mack
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
| | | | - Raffaele Iorio
- Department of Pediatrics, University of Naples Federico II, Naples, Italy
| | - Wael El-Matary
- Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Veena Venkat
- Department of Pediatrics, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Albert Chan
- Department of Pediatrics, University of Rochester Medical Center, Rochester, NY
| | - Lawrence Saubermann
- Department of Pediatrics, University of Rochester Medical Center, Rochester, NY
| | - Pamela L Valentino
- Department of Pediatrics, Yale University School of Medicine, New Haven, CT
| | - Uzma Shah
- Department of Pediatrics, Harvard University, Boston, MA
| | - Alexander Miethke
- Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Henry Lin
- Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA
| | - M K Jensen
- Department of Pediatrics, University of Utah, Salt Lake City, UT
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32
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Arcos-Machancoses JV, Molera Busoms C, Julio Tatis E, Bovo MV, Martín de Carpi J. Accuracy of the Simplified Criteria for Autoimmune Hepatitis in Children: Systematic Review and Decision Analysis. J Clin Exp Hepatol 2019; 9:147-155. [PMID: 31024195 PMCID: PMC6477136 DOI: 10.1016/j.jceh.2018.10.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Accepted: 10/30/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND/OBJECTIVES Several studies have been conducted on the accuracy of simplified criteria for autoimmune hepatitis that were presented in 2008 as an alternative to original criteria. Our purpose is to summarize the evidence available regarding their accuracy in children and to carry out a basic clinical decision analysis based on it. METHODS Electronic and manual searches were performed with keywords related to diagnostic validity terms. Data from included studies were extracted, and summary estimates of accuracy measures were calculated. An effect model was chosen depending on heterogeneity, and the presence of publication bias was also studied. Therapeutic threshold was calculated based on the already published data. Through a Bayesian approach, simplified criteria's clinical utility was simulated, taking into account the meta-analyzed indicators and several assumptions on the prevalence of autoimmune hepatitis. RESULTS The search yielded 166 studies, four of which were finally included, providing a total population of 437 patients. Pooled sensitivity and specificity of the simplified criteria for the diagnosis of autoimmune hepatitis in children was 77% and 95%, respectively, with a diagnostic odds ratio of 67. No evidence of publication bias was found. For prevalences ranging from 8.5 to 85.7, the predictive value of either a positive or a negative result moved beyond the therapeutic threshold (estimated at 56%). CONCLUSIONS The simplified criteria show high specificity and moderate sensitivity for the diagnosis of autoimmune hepatitis in children. A positive result can justify starting a therapeutic assay, but a negative result does not seem sufficient to rule out this condition.
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Affiliation(s)
- José V. Arcos-Machancoses
- Address for correspondence: J. V. Arcos-Machancoses, Sant Joan de Déu Hospital, Barcelona. Department of Pediatric Gastroenterology, Hepatology and Nutrition. Passeig de Sant Joan de Déu, 2, 08950 Esplugues de Llobregat, Barcelona (Catalonia), Spain.
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33
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Deneau MR, Mack C, Abdou R, Amin M, Amir A, Auth M, Bazerbachi F, Marie Broderick A, Chan A, DiGuglielmo M, El‐Matary W, El‐Youssef M, Ferrari F, Furuya KN, Gottrand F, Gupta N, Homan M, Jensen M, Kamath BM, Mo Kim K, Kolho K, Konidari A, Koot B, Iorio R, Martinez M, Mohan P, Palle S, Papadopoulou A, Ricciuto A, Saubermann L, Sathya P, Shteyer E, Smolka V, Tanaka A, Valentino PL, Varier R, Venkat V, Vitola B, Vos MB, Woynarowski M, Yap J, Miloh T. Gamma Glutamyltransferase Reduction Is Associated With Favorable Outcomes in Pediatric Primary Sclerosing Cholangitis. Hepatol Commun 2018; 2:1369-1378. [PMID: 30411083 PMCID: PMC6211333 DOI: 10.1002/hep4.1251] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Accepted: 07/13/2018] [Indexed: 12/15/2022] Open
Abstract
Adverse clinical events in primary sclerosing cholangitis (PSC) happen too slowly to capture during clinical trials. Surrogate endpoints are needed, but no such validated endpoints exist for children with PSC. We evaluated the association between gamma glutamyltransferase (GGT) reduction and long-term outcomes in pediatric PSC patients. We evaluated GGT normalization (< 50 IU/L) at 1 year among a multicenter cohort of children with PSC who did or did not receive treatment with ursodeoxycholic acid (UDCA). We compared rates of event-free survival (no portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or liver-related death) at 5 years. Of the 287 children, mean age of 11.4 years old, UDCA was used in 81% at a mean dose of 17 mg/kg/day. Treated and untreated groups had similar GGT at diagnosis (314 versus 300, P= not significant [NS]). The mean GGT was reduced at 1 year in both groups, with lower values seen in treated (versus untreated) patients (99 versus 175, P= 0.002), but 5-year event-free survival was similar (74% versus 77%, P= NS). In patients with GGT normalization (versus no normalization) by 1 year, regardless of UDCA treatment status, 5-year event-free survival was better (91% versus 67%, P< 0.001). Similarly, larger reduction in GGT over 1 year (> 75% versus < 25% reduction) was also associated with improved outcome (5-year event-free survival 88% versus 61%, P= 0.005). Conclusion:A GGT < 50 and/or GGT reduction of > 75% by 1 year after PSC diagnosis predicts favorable 5-year outcomes in children. GGT has promise as a potential surrogate endpoint in future clinical trials for pediatric PSC.
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Affiliation(s)
| | - Cara Mack
- University of Colorado School of MedicineAuroraCO
| | - Reham Abdou
- Nassau University Medical CenterEast MeadowNY
| | | | - Achiya Amir
- Dana‐Dwek Children’s Hospital, Tel‐Aviv Medical Center, Tel‐Aviv UniversityTel AvivIsrael
| | - Marcus Auth
- Alder Hey Children’s HospitalLiverpoolUnited Kingdom
| | | | | | - Albert Chan
- University of Rochester Medical CenterRochesterNY
| | | | | | | | | | | | | | | | | | | | | | | | | | - Anastasia Konidari
- University of LiverpoolLiverpoolUnited Kingdom
- University of ManchesterManchesterUnited Kingdom
| | - Bart Koot
- Academic Medical CentreAmsterdamthe Netherlands
| | | | | | | | | | | | | | | | - Pushpa Sathya
- Memorial UniversitySt. John’s, Newfoundland and LabradorCanada
| | | | | | | | | | - Raghu Varier
- Northwest Pediatric Gastroenterology LLCPortlandOR
| | - Veena Venkat
- University of Pittsburgh Medical CenterPittsburghPA
| | | | | | | | | | - Tamir Miloh
- Phoenix Children’s HospitalPhoenixAZ
- Texas Children’s HospitalHoustonTX
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Spectrum of Pediatric Autoimmune Liver Disease and Validation of Its Diagnostic Scores in Indian Children. J Pediatr Gastroenterol Nutr 2018; 67:e65-e72. [PMID: 29901555 DOI: 10.1097/mpg.0000000000002050] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES There is limited literature on the spectrum of pediatric autoimmune liver disease (AILD, encompassing both autoimmune hepatitis/AIH and autoimmune sclerosing cholangitis [ASC]) in Asian populations and its diagnostic scores similarly require further validation. This work thus aimed to study the clinical characteristics, and to validate available diagnostic criteria in the local pediatric AILD cohort. METHODS A review of all pediatric AILD cases, presenting over a 6-year (2011-2017) period was done, along with comparison of the available diagnostic scores: original (1999), simplified (2008) score, and new proposed (2017) score. RESULTS A total of 85 subjects (AIH = 70 and ASC = 15) were diagnosed as having AILD. Majority of the cases in both groups presented with advanced hepatic disease (portal hypertension and/or hepatic decompensation). Overall 38 (44.7%) subjects had extrahepatic autoimmune disorders. Good outcome (survival with native liver with medically controllable disease), was seen in 80% AIH subjects, while poor outcome (death/need for liver transplantation or LT) was seen in 13% subjects, with similar results in the ASC cohort. All the 3 available scores had area under receiver operating characteristic (AUROC) curves exceeding 0.9 suggestive of excellent discrimination of AILD (to non-AILD patients), with no statistical difference between them (P >0.05). CONCLUSIONS In Indian subcontinent, pediatric AILD subjects usually present with advanced hepatic disease, but may have a good outcome if timely therapy can be instituted. Associated autoimmune disorders should be carefully screened. There is no difference in the predictive value of the available diagnostic scores for pediatric AILD.
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35
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Salivary immunoglobulin levels in juvenile autoimmune hepatitis. Arch Oral Biol 2018; 92:51-56. [DOI: 10.1016/j.archoralbio.2018.04.014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Revised: 04/04/2018] [Accepted: 04/26/2018] [Indexed: 12/26/2022]
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Concurrent extrahepatic autoimmune disorders: unexplored dimension of autoimmune liver disease in children. Eur J Gastroenterol Hepatol 2018; 30:910-917. [PMID: 29634666 DOI: 10.1097/meg.0000000000001122] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND AND AIM No comprehensive and prospective data are available for concurrent extrahepatic autoimmune disorders (CEAIDs) in children with autoimmune liver disease (AILD). The aim of this study was to evaluate CEAIDs in AILD and their effect on AILD outcome. PATIENTS AND METHODS Enrolled AILD and CEAIDs children were diagnosed on the basis of simplified and standard diagnostic criteria, respectively. The clinicopathological profile, treatment response, and outcome were compared between AILD with CEAIDs (group A) and AILD without CEAIDs (group B). RESULTS In 62 AILD children, CEAIDs were found in 42% (n=26) [vitiligo (42%), celiac disease (CD) (15%), potential CD (15%), autoimmune hemolytic anemia (AIHA) (15%)]. CEAIDs were asymptomatic in 75%. Single CEAID was found in 81% (21/26) and multiple CEAID was found in 19% (5/26). Significantly less biochemical remission (46.1 vs. 74.2%, P=0.03), more treatment failure (23 vs. 3.2%, P=0.04), and higher mortality (15.3 vs. 3.2%, P=0.04) were encountered in group A compared with group B. On multivariate analysis (n=57), less biochemical remission in vitiligo (P=0.04); more treatment failure in AIHA (P=0.004) and vitiligo (P=0.04); and high mortality in AIHA (P=0.02) subgroups were reported. CD treatment has good impact on AILD outcome. All cases of diabetes mellitus in AILD were steroid-induced rather than because of autoimmunity (absence of antibody against tyrosine phosphatase and glutamic acid decarboxylase and elevated C-peptide). CONCLUSION All AILD children should be screened for CEAIDs as the majority are asymptomatic. The AILD outcome was favorable in CD, but poor in vitiligo and AIHA. We suggest the incorporation of CEAIDs in a pediatric AILD scoring system.
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Arcos-Machancoses JV, Molera Busoms C, Julio Tatis E, Victoria Bovo M, Quintero Bernabeu J, Juampérez Goñi J, Crujeiras Martínez V, Martin de Carpi J. Accuracy of the 2008 Simplified Criteria for the Diagnosis of Autoimmune Hepatitis in Children. Pediatr Gastroenterol Hepatol Nutr 2018; 21:118-126. [PMID: 29713609 PMCID: PMC5915689 DOI: 10.5223/pghn.2018.21.2.118] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Revised: 11/28/2017] [Accepted: 12/18/2017] [Indexed: 02/07/2023] Open
Abstract
PURPOSE Classical criteria for diagnosis of autoimmune hepatitis (AIH) are intended as research tool and are difficult to apply at patient's bedside. We aimed to study the accuracy of simplified criteria and the concordance with the expert diagnosis based on the original criteria. METHODS A cohort of children under study for liver disorder was selected through consecutive sampling to obtain the prevalence of AIH within the group of differential diagnoses. AIH was defined, based on classical criteria, through committee review of medical reports. Validity indicators of the simplified criteria were obtained in an intention to diagnose approach. Optimal cut-off and the area under the receiver operating characteristic (ROC) curve were calculated. RESULTS Out of 212 cases reviewed, 47.2% were AIH. For the optimal cut-off (6 points), the simplified criteria showed a sensitivity of 72.0% and a specificity of 96.4%, with a 94.7% positive and a 79.4% negative predictive value. The area under the ROC curve was 94.3%. There was a good agreement in the pre-treatment concordance between the classical and the simplified criteria (kappa index, 0.775). CONCLUSION Simplified criteria provide a moderate sensitivity for the diagnosis of AIH, but may help in indicating treatment in cases under suspicion with 6 or more points.
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Affiliation(s)
| | - Cristina Molera Busoms
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Sant Joan de Déu Hospital (SJDH), Barcelona, Spain.,SJDH-VHH Comprehensive Unit of Complex Hepatology and Pediatric Liver Transplantation, Barcelona, Spain
| | - Ecaterina Julio Tatis
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Sant Joan de Déu Hospital (SJDH), Barcelona, Spain
| | - María Victoria Bovo
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Sant Joan de Déu Hospital (SJDH), Barcelona, Spain
| | - Jesús Quintero Bernabeu
- Department of Pediatric Gastroenterology and Hepatology, Vall d'Hebron Hospital (VHH), Barcelona, Spain.,SJDH-VHH Comprehensive Unit of Complex Hepatology and Pediatric Liver Transplantation, Barcelona, Spain
| | - Javier Juampérez Goñi
- Department of Pediatric Gastroenterology and Hepatology, Vall d'Hebron Hospital (VHH), Barcelona, Spain.,SJDH-VHH Comprehensive Unit of Complex Hepatology and Pediatric Liver Transplantation, Barcelona, Spain
| | - Vanessa Crujeiras Martínez
- Department of Pediatric Gastroenterology and Hepatology, University Hospital Complex of Santiago de Compostela, Santiago de Compostela, Spain
| | - Javier Martin de Carpi
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Sant Joan de Déu Hospital (SJDH), Barcelona, Spain.,SJDH-VHH Comprehensive Unit of Complex Hepatology and Pediatric Liver Transplantation, Barcelona, Spain
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Chen JH, Deshpande V. Inflammatory Nodules Identify Steroid-Responsive Primary Sclerosing Cholangitis. Int J Surg Pathol 2018; 26:402-409. [PMID: 29464971 DOI: 10.1177/1066896918758451] [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] [Indexed: 12/24/2022]
Abstract
Primary sclerosing cholangitis (PSC) is a cholangiopathy-usually associated with inflammatory bowel disease-that leads to cirrhosis and liver failure. Based on a multitude of clinical trials, there is general consensus that PSC progression is unchanged by current therapies, including steroids. However, there are scattered reports in the literature of PSC patients responsive to steroids. Recently, several steroid-responsive PSC mimics have been described, most notably immunoglobulin G4-related sclerosing cholangitis. Following these discoveries, many assume that cases in the literature previously reported as steroid-responsive PSC would now be classified as one of these mimics. We reviewed liver biopsies and the medical histories of patients diagnosed with PSC with documented response to steroids. We identified 3 cases of steroid-responsive PSC in patients with inflammatory bowel disease that do not fit criteria of known PSC mimics. All 3 were adults (age range = 18-44 years) with inflammatory bowel disease, and included 2 males and 1 female. All 3 patients had abnormal liver function tests that normalized on prednisone. Histologically, these 3 cases share a common feature, hepatic fibroinflammatory nodules in a collagen-rich background. They lacked clinical, serologic, and histologic features of immunoglobulin G4-related sclerosing cholangitis. These cases suggest that fibroinflammatory nodules may identify a unique subset of PSC patients who are responsive to steroids.
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Affiliation(s)
- Jonathan H Chen
- 1 Massachusetts General Hospital, Boston, MA, USA.,2 Harvard Medical School, Boston, MA, USA
| | - Vikram Deshpande
- 1 Massachusetts General Hospital, Boston, MA, USA.,2 Harvard Medical School, Boston, MA, USA
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[Autoimmune hepatitis in the pediatric age]. BOLETIN MEDICO DEL HOSPITAL INFANTIL DE MEXICO 2018; 74:324-333. [PMID: 29382475 DOI: 10.1016/j.bmhimx.2017.05.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Revised: 04/25/2017] [Accepted: 05/11/2017] [Indexed: 11/23/2022] Open
Abstract
In pediatrics, autoimmune hepatitis and sclerosing cholangitis are liver disorders with an immunological damage mechanism. Autoimmune hepatitis is a disease of unknown etiology characterized by interface hepatitis, hypergammaglobulinemia, circulating autoantibodies and a favorable response to immunosuppression. It is an eminently pediatric disease with a prevalent condition in young women. Therapy should be instituted promptly to prevent rapid deterioration, promote remission of disease and long-term survival. The persistent lack of response or lack of adherence to treatment results in terminal liver failure; these patients, and those with fulminant hepatic insufficiency at the time of diagnosis, will require liver transplantation.
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40
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Mieli-Vergani G, Vergani D, Baumann U, Czubkowski P, Debray D, Dezsofi A, Fischler B, Gupte G, Hierro L, Indolfi G, Jahnel J, Smets F, Verkade HJ, Hadžić N. Diagnosis and Management of Pediatric Autoimmune Liver Disease: ESPGHAN Hepatology Committee Position Statement. J Pediatr Gastroenterol Nutr 2018; 66:345-360. [PMID: 29356770 DOI: 10.1097/mpg.0000000000001801] [Citation(s) in RCA: 192] [Impact Index Per Article: 27.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Paediatric autoimmune liver disease is characterized by inflammatory liver histology, circulating autoantibodies, and increased levels of IgG, in the absence of a known etiology. Three conditions have a likely autoimmune pathogenesis: autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis, and de novo AIH after liver transplantation. Two types of pediatric AIH are recognized according to seropositivity for smooth muscle and/or antinuclear antibody (AIH-1) or liver kidney microsomal type 1 and/or anti-liver cytosol type 1 antibodies (AIH-2).Pertinent issues addressing the diagnosis, treatment, and long-term follow-up were formulated by a core group of ESPGHAN members. They have commissioned the first authors with execution of this project. Initially, they have performed a systematic literature search on MEDLINE, ResearchGate, and Mendeley databases during the last 30 years and produced a document focusing on prospective and retrospective studies in children. The ESPGHAN core group and ESPGHAN Hepatology Committee members voted on each recommendation, using a formal voting technique.
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Affiliation(s)
| | - Diego Vergani
- MowatLabs, Paediatric Liver, GI & Nutrition Centre, King's College Hospital, London, UK
| | - Ulrich Baumann
- Pädiatrische Gastroenterologie und Hepatologie, Medizinische Hochschule, Hannover, Germany
| | - Piotr Czubkowski
- Department of Gastroenterology, Hepatology, Nutrition Disturbances and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland
| | - Dominique Debray
- Pediatric Hepatology Unit, AP-HP-Hôpital Necker Enfants Malades, Paris, France
| | - Antal Dezsofi
- First Department of Paediatrics, Semmelweis University, Budapest, Hungary
| | - Björn Fischler
- Department of Pediatrics, Karolinska University Hospital, CLINTEC, Karolinska Institutet, Stockholm, Sweden
| | - Girish Gupte
- Liver Unit (Including Small Bowel Transplantation), Department of Gastroenterology and Nutrition, Birmingham Children's Hospital, Birmingham, UK
| | - Loreto Hierro
- Hospital Infantil Universitario La Paz, Madrid, Spain
| | - Giuseppe Indolfi
- Paediatric and Liver Unit, Meyer Children's University Hospital of Florence, Firenze, Italy
| | - Jörg Jahnel
- Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria
| | - Françoise Smets
- UCL, Cliniques Universitaires Saint-Luc, Pediatric Gastroenterology and Hepatology, Brussels, Belgium
| | - Henkjan J Verkade
- Dept of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, Groningen, the Netherlands
| | - Nedim Hadžić
- MowatLabs, Paediatric Liver, GI & Nutrition Centre, King's College Hospital, London, UK
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Abstract
Autoimmune hepatitis (AIH) is an immune-mediated, inflammatory liver disease. Clinical presentation of AIH in children is highly variable. It can present acutely, chronically, or silently. There are two main types of AIH-type 1 and type 2, which are differentiated and defined by the presence of specific autoantibodies. AIH eventually progresses to cirrhosis when left untreated, and occasionally even with treatment. AIH must be suspected and excluded in all children presenting with signs of acute, prolonged, or severe liver disease. The diagnosis of AIH is made by a combination of clinical manifestations, laboratory evaluation, histopathology, and the exclusion of other more common liver diseases. The best outcome for AIH is dependent on early diagnosis as well as early initiation of immunosuppressant therapy. [Pediatr Ann. 2018;47(2):e81-e86.].
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Autoimmune acute liver failure and seronegative autoimmune liver disease in children: Are they different from classical disease? Eur J Gastroenterol Hepatol 2017; 29:1408-1415. [PMID: 28914695 DOI: 10.1097/meg.0000000000000975] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVES Presentation as autoimmune acute liver failure (AI-ALF) and seronegative autoimmune liver disease (SN-AILD) represents two uncommon variants of AILD. We compared the clinical profile and outcome of AI-ALF with autoimmune-non-acute liver failure (AI-non-ALF) and also SN-AILD with seropositive autoimmune liver disease (SP-AILD). MATERIALS AND METHODS Children managed as AI-ALF and AI-non-ALF including SN-AILD and SP-AILD were enrolled and compared. AI-non-ALF was diagnosed by simplified diagnostic criteria and AI-ALF by Pediatric Acute Liver Failure Study Group criteria with positive autoantibody, exclusion of other etiologies, elevated immunoglobulin G and histology when available. RESULTS Seventy children [AI-ALF=15 and AI-non-ALF=55 (SN-AILD=11, SP-AILD=44)] were evaluated. Age at presentation [7 (1.2-16) vs. 9 (2-17) years] percentage of female patients (67 vs. 62%), and AILD type (type II, 53 vs. 31%) were similar in AI-ALF and AI-non-ALF patients], respectively. 8/15 AI-ALF cases were treated with steroids (improved-4, liver transplant-1, and death-3) and 7/15 died before initiation of therapy. Hepatic encephalopathy (100 vs. 16.3%; P<0.001), massive hepatic necrosis (60 vs. 0%; P<0.001), and higher pediatric end-stage liver disease [n=53, 29.9 (13.1-56.9) vs. 9.8 (-10-28.7) P<0.001], model for end-stage liver disease [n=17, 38.5 (24-46) vs. 18 (6-24); P=0.005], and Child-Turcotte-Pugh [n=70, 13 (8-13) vs. 9 (5-13); P<0.001] scores were features of AI-ALF. Poorer response to immunosuppression (4/8 vs. 48/55; P=0.02) and higher mortality (11/15 vs. 4/55; P=0.0001) were seen in AI-ALF than in AI-non-ALF patients. Clinicolaboratory profile, therapeutic response, and outcome were similar in SN-AILD and SP-AILD. CONCLUSION AI-ALF is characterized by poorer liver function, lower response to immunosuppression, and higher mortality compared with SP or SN AI-non-ALF, which are similar.
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Deneau MR, El-Matary W, Valentino PL, Abdou R, Alqoaer K, Amin M, Amir AZ, Auth M, Bazerbachi F, Broderick A, Chan A, Cotter J, Doan S, El-Youssef M, Ferrari F, Furuya KN, Gottrand M, Gottrand F, Gupta N, Homan M, Kamath BM, Kim KM, Kolho KL, Konidari A, Koot B, Iorio R, Ledder O, Mack C, Martinez M, Miloh T, Mohan P, O'Cathain N, Papadopoulou A, Ricciuto A, Saubermann L, Sathya P, Shteyer E, Smolka V, Tanaka A, Varier R, Venkat V, Vitola B, Vos MB, Woynarowski M, Yap J, Jensen MK. The natural history of primary sclerosing cholangitis in 781 children: A multicenter, international collaboration. Hepatology 2017; 66:518-527. [PMID: 28390159 DOI: 10.1002/hep.29204] [Citation(s) in RCA: 145] [Impact Index Per Article: 18.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2016] [Revised: 02/07/2017] [Accepted: 04/04/2017] [Indexed: 12/14/2022]
Abstract
UNLABELLED There are limited data on the natural history of primary sclerosing cholangitis (PSC) in children. We aimed to describe the disease characteristics and long-term outcomes of pediatric PSC. We retrospectively collected all pediatric PSC cases from 36 participating institutions and conducted a survival analysis from the date of PSC diagnosis to dates of diagnosis of portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or death. We analyzed patients grouped by disease phenotype and laboratory studies at diagnosis to identify objective predictors of long-term outcome. We identified 781 patients, median age 12 years, with 4,277 person-years of follow-up; 33% with autoimmune hepatitis, 76% with inflammatory bowel disease, and 13% with small duct PSC. Portal hypertensive and biliary complications developed in 38% and 25%, respectively, after 10 years of disease. Once these complications developed, median survival with native liver was 2.8 and 3.5 years, respectively. Cholangiocarcinoma occurred in 1%. Overall event-free survival was 70% at 5 years and 53% at 10 years. Patient groups with the most elevated total bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis had the worst outcomes. In multivariate analysis PSC-inflammatory bowel disease and small duct phenotypes were associated with favorable prognosis (hazard ratios 0.6, 95% confidence interval 0.5-0.9, and 0.7, 95% confidence interval 0.5-0.96, respectively). Age, gender, and autoimmune hepatitis overlap did not impact long-term outcome. CONCLUSION PSC has a chronic, progressive course in children, and nearly half of patients develop an adverse liver outcome after 10 years of disease; elevations in bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis can identify patients at highest risk; small duct PSC and PSC-inflammatory bowel disease are more favorable disease phenotypes. (Hepatology 2017;66:518-527).
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Affiliation(s)
| | | | | | - Reham Abdou
- State University of New York Buffalo, Buffalo, NY
| | - Khaled Alqoaer
- Prince Salman North West Armed Forces Hospital, Tabuk, Saudi Arabia
| | - Mansi Amin
- University of California San Francisco, San Francisco, CA, and Texas Children's Hospital, Houston, TX
| | - Achiya Z Amir
- The Dana-Dwek Children's Hospital, The Tel-Aviv Medical Center, Tel-Aviv University, Tel Aviv, Israel
| | - Marcus Auth
- Alder Hey Children's Hospital, Liverpool, UK
| | | | | | - Albert Chan
- University of Rochester Medical Center, Rochester, NY
| | | | | | | | | | - Katryn N Furuya
- Mayo Clinic, Rochester, MN
- Nemours Alfred I duPont Hospital For Children, Wilmington, DE
| | | | | | - Nitika Gupta
- Emory University School of Medicine, Atlanta, GA
| | | | | | | | | | - Anastasia Konidari
- University of Liverpool, Liverpool, and University of Manchester, Manchester, UK
| | - Bart Koot
- Academic Medical Centre, Amsterdam, The Netherlands
| | | | - Oren Ledder
- Shaare Zedek Medical Center, Jerusalem, Israel
| | - Cara Mack
- University of Colorado School of Medicine, Aurora, CO
| | - Mercedes Martinez
- Columbia University College of Physicians and Surgeons, New York, NY
| | - Tamir Miloh
- Texas Children's Hospital, Houston, TX, and Phoenix Children's Hospital, Phoenix, AZ
| | | | | | | | | | | | - Pushpa Sathya
- Memorial University, St. John's, Newfoundland and Labrador, Canada
| | | | | | | | - Raghu Varier
- Northwest Pediatric Gastroenterology LLC, Portland, OR
| | - Veena Venkat
- University of Pittsburgh Medical Center, Pittsburgh, PA
| | | | - Miriam B Vos
- Emory University School of Medicine, Atlanta, GA
| | | | - Jason Yap
- University of Alberta, Edmonton, Alberta, Canada
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Ylinen E, Salmela L, Peräsaari J, Jaatinen T, Tenca A, Vapalahti O, Färkkilä M, Jalanko H, Kolho K. Human leucocyte antigens B*08, DRB1*03 and DRB1*13 are significantly associated with autoimmune liver and biliary diseases in Finnish children. Acta Paediatr 2017; 106:322-326. [PMID: 27759901 DOI: 10.1111/apa.13641] [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: 06/15/2016] [Revised: 09/05/2016] [Accepted: 10/17/2016] [Indexed: 12/13/2022]
Abstract
AIM The human leucocyte antigen (HLA) allele and haplotype frequencies of the Finnish population are unique because of the restricted and homogenous gene population. There are no published data on HLA genotype associations in paediatric autoimmune liver diseases in Scandinavia. This study characterised the HLA genotypes of children with autoimmune liver or biliary disease in Finland. METHODS The study cohort comprised 19 paediatric patients (13 female) aged three years to 15 years treated for autoimmune liver or biliary disease at the Children's Hospital, Helsinki University Hospital, between 2000 and 2011, and followed up for four years and three months to 14.6 years. We genotyped HLA-B and HLA-DRB1 in the children, and the HLA antigen frequencies were compared with 19 807 records from the Finnish Bone Marrow Donor Registry. RESULTS All paediatric patients with autoimmune liver or biliary disease had either autoimmune HLA haplotype B*08;DRB1*03 or DRB1*13. These were significantly more common among patients with autoimmune hepatitis, primary sclerosing cholangitis and autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome than the Finnish control population. HLA RB1*04 was not found in the study cohort. CONCLUSION Our study found that B*08, DRB1*03 and DRB1*13 were significantly associated with autoimmune liver and biliary diseases in Finnish paediatric patients.
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Affiliation(s)
- E Ylinen
- Department of Paediatric Nephrology and Transplantation Children's Hospital University of Helsinki Helsinki University Hospital Helsinki Finland
- Department of Gastroenterology Children's Hospital University of Helsinki Helsinki University Hospital Helsinki Finland
| | - L Salmela
- Medical School University of Helsinki Helsinki Finland
| | - J Peräsaari
- Clinical Laboratory Finnish Red Cross Blood Service Helsinki Finland
| | - T Jaatinen
- Clinical Laboratory Finnish Red Cross Blood Service Helsinki Finland
| | - A Tenca
- Clinic of Gastroenterology University of Helsinki Helsinki University Hospital Helsinki Finland
| | - O Vapalahti
- Department of Virology and Immunology HUSLAB Hospital District of Helsinki and Uusimaa Helsinki Finland
| | - M Färkkilä
- Clinic of Gastroenterology University of Helsinki Helsinki University Hospital Helsinki Finland
| | - H Jalanko
- Department of Paediatric Nephrology and Transplantation Children's Hospital University of Helsinki Helsinki University Hospital Helsinki Finland
| | - K‐L Kolho
- Department of Gastroenterology Children's Hospital University of Helsinki Helsinki University Hospital Helsinki Finland
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45
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Smolka V, Karaskova E, Tkachyk O, Aiglova K, Ehrmann J, Michalkova K, Konecny M, Volejnikova J. Long-term follow-up of children and adolescents with primary sclerosing cholangitis and autoimmune sclerosing cholangitis. Hepatobiliary Pancreat Dis Int 2016; 15:412-8. [PMID: 27498582 DOI: 10.1016/s1499-3872(16)60088-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Sclerosing cholangitis (SC) is a chronic cholestatic hepatobiliary disease with uncertain long-term prognosis in pediatric patients. This study aimed to evaluate long-term results in children with SC according to the types of SC. METHODS We retrospectively followed up 25 children with SC over a period of 4-17 years (median 12). The diagnosis of SC was based on biochemical, histological and cholangiographic findings. Patients fulfilling diagnostic criteria for probable or definite autoimmune hepatitis at the time of diagnosis were defined as having autoimmune sclerosing cholangitis (ASC); other patients were included in a group of primary sclerosing cholangitis (PSC). The incidence of the following complications was studied: obstructive cholangitis, portal hypertension, advanced liver disease and death associated with the primary disease. RESULTS Fourteen (56%) patients had PSC and 11 (44%) had ASC. Patients with ASC were significantly younger at the time of diagnosis (12.3 vs 15.4 years, P=0.032) and had higher IgG levels (22.7 vs 17.2 g/L, P=0.003). The mentioned complications occurred in 4 (16%) patients with SC, exclusively in the PSC group: one patient died from colorectal cancer, one patient underwent liver transplantation and two patients, in whom severe bile duct stenosis was present at diagnosis, were endoscopically treated for acute cholangitis. Furthermore, two other children with ASC and 2 children with PSC had elevated aminotransferase levels. The 10-year overall survival was 95.8% in all patients, 100% in patients without complicated liver disease, and 75.0% in patients with complications. CONCLUSION In children, ASC is a frequent type of SC, whose prognosis may be better than that in patients with PSC.
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Affiliation(s)
- Vratislav Smolka
- Department of Pediatrics, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, I. P. Pavlova 6, Olomouc 779 00, Czech Republic.
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Rodrigues AT, Liu PM, Fagundes ED, Queiroz TC, de Souza Haueisen Barbosa P, Silva SL, Simões e Silva AC, Miranda DM, Ferreira AR, Alberti LR. Clinical Characteristics and Prognosis in Children and Adolescents With Autoimmune Hepatitis and Overlap Syndrome. J Pediatr Gastroenterol Nutr 2016; 63:76-81. [PMID: 26825768 DOI: 10.1097/mpg.0000000000001125] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
ABSTRACTObjectives:This is a cohort study of 134 children and adolescents with a known diagnosis of autoimmune hepatitis (AIH). During follow‐up, some of them developed autoimmune sclerosing cholangitis (ASC). This study describes the characteristics of the patients upon diagnosis, and their response to treatment and any complications, and compares the patients who developed ASC during follow‐up (ASC group) with those who did not (AIH group).Methods:A total of 73.1% of the patients were girls with a median age upon diagnosis of 10.41 (7.41–12.53) years.Results:Of 134 patients, 28 (20.9%) developed cholestatic manifestations, with features of ASC. A few differences were observed between the AIH and ASC groups when they were analyzed by χ2 test, such as the smaller predominance of girls in ASC group (P = 0.04), and more common asymptomatic presentation in the ASC group (P = 0.01). Cirrhosis was observed in 68% of biopsies, with no significant difference between groups (P = 0.43). Of 16 deaths, 15 were in the AIH group and 1 in the ASC group (P = 0.22). Of 11 transplants, 10 were in the AIH group and one in the ASC group (P = 0.53). The presence of cirrhosis at baseline was associated with a smaller survival probability (P = 0.015). The survival rate by Kaplan‐Meier method was 94% at 5 years and 80% at 10 years, and was similar in both the groups (P = 0.08).Conclusions:No statistically significant difference was observed between the groups in relation to prognosis and response to treatment.
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Affiliation(s)
| | - Priscila M.F. Liu
- Department of Pediatrics Faculty of Medicine Federal University of Minas Gerais (UFMG) Brazil
| | - Eleonora D.T. Fagundes
- Department of Pediatrics Faculty of Medicine Federal University of Minas Gerais (UFMG) Brazil
| | | | | | - Soraya L.C. Silva
- Faculty of Medicine Federal University of Minas Gerais (UFMG) Brazil
| | - Ana C. Simões e Silva
- Department of Pediatrics Interdisciplinary Laboratory of Medical Investigation Faculty of Medicine Federal University of Minas Gerais (UFMG) Brazil
| | - Débora M. Miranda
- Department of Pediatrics Faculty of Medicine Federal University of Minas Gerais (UFMG) Brazil
| | | | - Luiz R. Alberti
- Department of Surgery Faculty of Medicine Federal University of Minas Gerais (UFMG) Brazil
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Sarda G, Harvey R. Severe transaminitis in a paediatric patient with systemic lupus erythaematosus and a discussion of the literature. BMJ Case Rep 2016; 2016:10.1136/bcr-2015-214159. [PMID: 27090540 DOI: 10.1136/bcr-2015-214159] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
A 15-year-old African-American girl with known systemic lupus erythaematosus (SLE) presented to the emergency room with fever, abdominal distension, pain and vomiting. She was found to have severe transaminitis on laboratory examination, which prompted further work up including imaging and liver biopsy. Although complete diagnostic criteria were not met, histology was suggestive of autoimmune hepatitis (AIH). She was treated with steroids and azathioprine with good response and resolution of liver function tests. Availability of the literature discussing patients of any age with SLE and AIH is minimal, and consists mostly of small case series and some case reports. The juvenile literature on SLE and AIH occurring in the same patient is even scarcer and should be further studied at a multicentre level.
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Affiliation(s)
- Garima Sarda
- Baystate Medical Center Children's Hospital, Springfield, Massachusetts, USA
| | - Rohini Harvey
- Baystate Medical Center Children's Hospital, Springfield, Massachusetts, USA
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48
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Environmental Risk Factors of Pediatric-Onset Primary Sclerosing Cholangitis and Autoimmune Hepatitis. J Pediatr Gastroenterol Nutr 2016; 62:437-42. [PMID: 26465796 DOI: 10.1097/mpg.0000000000000995] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
OBJECTIVES The aim of this population-based observational case-control questionnaire study was to investigate the possible role of environmental risk factors associated with pediatric-onset autoimmune liver diseases. METHODS Seventy-one patients with autoimmune liver diseases (<16 years) received a questionnaire with 22 items, evaluating contact with environmental factors (eg, family manners, type of housing, pets) before the diagnosis. Two age- and sex-matched control groups were used: inflammatory bowel disease (IBD; n = 91) and healthy subjects (n = 716; matched also for place of residence at birth). Univariate analysis (odds ratio [OR] and 95% confidence interval) for all variables was calculated. Fisher exact test was performed to depict associations between variables and the multivariate logistic regression to test their interactions. RESULTS In the final analyses, the responses of 51 autoimmune liver diseases cases (n = 51/71, 72%), 59 IBD controls (n = 59/91, 65%), and 292 healthy controls (n = 292/716, 41%) were investigated. In univariate analysis only having a cat, a dog, and a cat or a dog were risk factors of autoimmune liver diseases (OR varying between 2.6-3.4); no other significant associations (eg, place of residence, number of siblings, family manners) were found. Multivariate logistic regression analyses showed that especially living with a cat in block of flats was a risk factor (OR 3.6, 1.2-10.8). CONCLUSIONS Living in a close contact with a pet (especially a cat) was a risk factor of autoimmune liver diseases. This finding may suggest an involvement of an unidentified agent (ie, toxin/microbe) among the triggers of these diseases.
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Jiménez-Rivera C, Ling SC, Ahmed N, Yap J, Aglipay M, Barrowman N, Graitson S, Critch J, Rashid M, Ng VL, Roberts EA, Brill H, Dowhaniuk JK, Bruce G, Bax K, Deneau M, Guttman OR, Schreiber RA, Martin S, Alvarez F. Incidence and Characteristics of Autoimmune Hepatitis. Pediatrics 2015; 136:e1237-48. [PMID: 26482664 DOI: 10.1542/peds.2015-0578] [Citation(s) in RCA: 76] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/20/2015] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Autoimmune hepatitis (AIH) is a progressive inflammatory liver disease of unknown etiology, with limited population-based estimates of pediatric incidence. We reported the incidence of pediatric AIH in Canada and described its clinical characteristics. METHODS We conducted a retrospective cohort study of patients aged <18 years diagnosed with AIH between 2000-2009 at all pediatric centers in Canada. RESULTS A total of 159 children with AIH (60.3% female, 13.2% type 2 AIH) were identified. Annual incidence was 0.23 per 100000 children. Median age at presentation for type 1 was 12 years (interquartile range: 11-14) versus 10 years for type 2 (interquartile range: 4.5-13) (P = .03). Fatigue (58%), jaundice (54%), and abdominal pain (49%) were the most common presenting symptoms. Serum albumin (33 vs 38 g/L; P = .03) and platelet count (187 000 vs 249 000; P <.001) were significantly lower and the international normalized ratio (1.4 vs 1.2; P <.001) was higher in cirrhotic versus noncirrhotic patients. Initial treatment included corticosteroids (80%), azathioprine (32%), and/or cyclosporine (13%). Response to treatment at 1 year was complete in 90%, and partial in 3%. 3% of patients had no response, and 3% responded and later relapsed. Nine patients underwent liver transplantation, and 4 patients died at a mean follow-up of 4 years. CONCLUSIONS AIH is uncommon in children and adolescents in Canada. Type 1 AIH was diagnosed 5.5 times more frequently than type 2 AIH. Most patients respond well to conventional therapy, diminishing the need for liver transplantation.
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Affiliation(s)
| | - Simon C Ling
- University of Toronto and The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Najma Ahmed
- McGill University and Montreal Children's Hospital, Montreal, Quebec, Canada
| | - Jason Yap
- University of Alberta and Stollery Children's Hospital, Edmonton, Alberta, Canada
| | - Mary Aglipay
- University of Ottawa and Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
| | - Nick Barrowman
- University of Ottawa and Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
| | - Samantha Graitson
- University of Ottawa and Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
| | - Jeff Critch
- Memorial University of Newfoundland and Janeway Children's Hospital, St. John's, Newfoundland, Canada
| | - Mohsin Rashid
- Dalhousie University and IWK Health Center, Halifax, Nova Scotia, Canada
| | - Vicky L Ng
- University of Toronto and The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Eve A Roberts
- University of Toronto and The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Herbert Brill
- McMaster University and McMaster Children's Hospital, Hamilton, Ontario, Canada
| | - Jenna K Dowhaniuk
- McMaster University and McMaster Children's Hospital, Hamilton, Ontario, Canada
| | - Garth Bruce
- University of Saskatchewan and Children's Hospital of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Kevin Bax
- University of Western Ontario and London Health Science Center, London, Ontario, Canada
| | - Mark Deneau
- University of Manitoba and The Children's Hospital of Winnipeg, Winnipeg, Manitoba, Canada
| | - Orlee R Guttman
- University of British Columbia and BC Children's Hospital, Vancouver, British Columbia, Canada
| | - Richard A Schreiber
- University of British Columbia and BC Children's Hospital, Vancouver, British Columbia, Canada
| | - Steven Martin
- University of Calgary and Alberta Children's Hospital Calgary, Alberta, Canada; and
| | - Fernando Alvarez
- University of Montreal and Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
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50
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Evaluation of the effectiveness of treatment with prednisone and azathioprine of autoimmune hepatitis in children. GASTROENTEROLOGY REVIEW 2015; 11:18-23. [PMID: 27110306 PMCID: PMC4814537 DOI: 10.5114/pg.2015.52566] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/01/2014] [Accepted: 02/26/2015] [Indexed: 12/03/2022]
Abstract
Introduction Autoimmune hepatitis is rarely diagnosed in children, but the course of the disease is often aggresive. Combination therapy with prednisone and azathioprine improves the prognosis of patients. Aim To evaluate the effectiveness of combination therapy with prednisone and azathioprine of autoimmune hepatitis (AIH) in children. Material and methods There was a retrospective analysis of the medical records of 15 patients with AIH, diagnosed before18 years of age, treated in the Provincial Infectious Diseases Hospital in Bydgoszcz in the years 2002 to 2013. We analysed the results of laboratory tests, ultrasound examination, endoscopy, and morphological liver pictures, as well as periods of exacerbation of inflammation and side effects of therapy. Results Biochemical remission of the disease was achieved on average after 36 days of treatment. Histopathological regression in the control liver biopsy was found in 7/15 patients and progression in 2/15 patients. In the study group 10/15 patients experienced exacerbation of the disease from 1 to 3 times during observation, with an increase of ALT activity to greater than 3 norm, and the remaining 5/15 patients had no increase of ALT activity. In total, 10 patients in the study group experienced 17 exacerbations. In 13/17 cases of exacerbations they were associated with a reduction in the dose of immunosuppressive drugs. There was no correlation between the biochemical exacerbation and changes in the histopathological image. Steroidside effects occurred in 14/15 patients. Conclusions The treatment allows for biochemical remission of the disease and significantly improves the prognosis of most patients. However, significant side effects of treatment indicate the need for further exploration of effective and safe therapy, especially in the paediatric population.
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