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1
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Bresch J, König J, Konrad M, Kollmann S, Dahmer-Heath M, Heinzow HS, Praktiknjo M, Trebicka J, Bergmann C, Schmidt HHJ, Schlevogt B. Non-invasive screening for liver fibrosis by acoustic radiation force impulse in patients with ciliopathies. Sci Rep 2025; 15:13345. [PMID: 40247009 PMCID: PMC12006320 DOI: 10.1038/s41598-025-96246-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Accepted: 03/26/2025] [Indexed: 04/19/2025] Open
Abstract
Primary cilia are antenna-like structures on the surface of epithelial cells involved in multiple signaling pathways. Their malfunction can cause a heterogenous group of diseases called ciliopathies with a broad spectrum of organ involvements, including liver fibrosis. The aim of this exploratory study was to evaluate elastography measurement via ultrasound based acoustic radiation force impulse imaging (ARFI) as a screening tool for liver fibrosis in ciliopathies. In a prospective cohort of 51 patients with ciliopathies (aged between 2 months and 66 years) from the NEOCYST registry stiffness of the right liver lobe and spleen was measured via ARFI and results were then compared with laboratory parameters, endoscopic, ultrasonographic and histological findings. ARFI screening of the liver identified 27 patients without increased liver stiffness suggesting no or insignificant fibrosis, 11 with intermediate fibrosis, and 12 with liver fibrosis F4. Four patients showed increased spleen stiffness in ARFI. In all 10 patients with histologically confirmed fibrosis, ARFI results perfectly matched fibrosis stages. In the ARFI-based overall fibrosis subgroup, ALT, AST, GGT and spleen size were significantly increased, whereas platelets were significantly decreased compared to the no fibrosis subgroup. Normal GGT excluded ARFI-defined F4 fibrosis (negative predictive value 100%). Gene variants in PKHD1, TMEM67, and TULP3 were primarily detected in our patients with liver fibrosis whereas NPHP1 and HNF1B were not associated with increased liver stiffness. ARFI is a valuable screening tool for the detection of liver involvement in ciliopathies and may be useful in addition to laboratory and clinical parameters alone.Trial registration: NEOCYST registry DRKS00011003, registered 06.09.2016, https://drks.de/search/en/trial/DRKS00011003 .
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Affiliation(s)
- Johanna Bresch
- Department of Medicine B, Muenster University Hospital, Albert-Schweitzer-Campus 1, Building A14, 48149, Muenster, Germany.
| | - Jens König
- Department of General Pediatrics, Muenster University Hospital, Muenster, Germany
| | - Martin Konrad
- Department of General Pediatrics, Muenster University Hospital, Muenster, Germany
| | - Sabine Kollmann
- Department of General Pediatrics, Muenster University Hospital, Muenster, Germany
| | - Mareike Dahmer-Heath
- Department of General Pediatrics, Muenster University Hospital, Muenster, Germany
| | - Hauke Sebastian Heinzow
- Department of Medicine B, Muenster University Hospital, Albert-Schweitzer-Campus 1, Building A14, 48149, Muenster, Germany
- Brüderkrankenhaus Trier, Trier, Germany
| | - Michael Praktiknjo
- Department of Medicine B, Muenster University Hospital, Albert-Schweitzer-Campus 1, Building A14, 48149, Muenster, Germany
| | - Jonel Trebicka
- Department of Medicine B, Muenster University Hospital, Albert-Schweitzer-Campus 1, Building A14, 48149, Muenster, Germany
| | - Carsten Bergmann
- Medizinische Genetik Mainz, Limbach Genetics, Mainz, Germany
- Department of Medicine IV, Faculty of Medicine, Medical Center-University of Freiburg, Freiburg, Germany
| | - Hartmut H-J Schmidt
- Department of Medicine B, Muenster University Hospital, Albert-Schweitzer-Campus 1, Building A14, 48149, Muenster, Germany
- Department of Gastroenterology, Hepatology and Transplant Medicine, University Hospital Essen, Essen, Germany
| | - Bernhard Schlevogt
- Department of Medicine B, Muenster University Hospital, Albert-Schweitzer-Campus 1, Building A14, 48149, Muenster, Germany
- Department of Gastroenterology and Endoscopy, Medical Center Osnabrueck, Osnabrueck, Germany
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Fajrudheen M, Mahapatro S, Panigrahi MK, Naik S, Satapathy AK. Noninvasive Assessment of Nonalcoholic Fatty Liver Disease in Children with Overweight and Obesity by Transient Elastography. Indian J Endocrinol Metab 2025; 29:230-236. [PMID: 40416463 PMCID: PMC12101759 DOI: 10.4103/ijem.ijem_150_24] [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: 05/01/2024] [Revised: 08/03/2024] [Accepted: 12/09/2024] [Indexed: 05/27/2025] Open
Abstract
Introduction Childhood obesity and nonalcoholic fatty liver disease (NAFLD) are emerging as significant health concerns. While liver biopsy remains the gold standard for diagnosis, there is a pressing need for a noninvasive alternative to identify early fibrosis. Methods A cross-sectional investigation was carried out from January 2020 to December 2021 involving overweight and obese children attending the pediatric outpatient department (OPD). The aim is to determine the occurrence of fibrotic and steatotic changes in the liver of overweight and obese children using transient elastography (TE) and to establish correlations between TE results, Pediatric NAFLD Fibrosis Index (PNFI), and other biochemical parameters. TE was utilized to assess both fibrotic and steatosis changes, while ultrasound (USG) was employed to detect steatosis in the liver. Results Two hundred and fifty-nine eligible children participated in the study. Mean age of the study cohort was 10.8 years, with males constituting 63%. Mean Z score for BMI was 1.71 ± 0.57. Fibrosis was detected in 29.3% of children by TE, while steatosis was observed in 27.7% of children. Steatosis was identified in 23.8% of cases through USG. BMI Z score, ALT (Alanine aminotransferase), AST and PNFI score exhibited significant associations with grades of liver fibrosis and steatosis as determined by TE, as well as with grades of steatosis according to USG findings. Conclusion A notable prevalence of increased liver stiffness was observed in overweight and obese children. TE proves to be a valuable tool in identifying fibrotic and steatotic changes in these children, complementing existing noninvasive modalities.
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Affiliation(s)
- Mohamed Fajrudheen
- Department of Pediatrics, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
| | - Samarendra Mahapatro
- Department of Pediatrics, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
| | - Manas K. Panigrahi
- Department of Gastroenterology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
| | - Suprava Naik
- Department of Radiodiagnosis, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
| | - Amit K. Satapathy
- Department of Pediatrics, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
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Arteaga I, Chacón C, Martínez-Escudé A, Rojano IR, Diez-Fadrique G, Carmona-Cervelló M, Torán-Monserrat P. Evaluating Pediatric NAFLD with Controlled Attenuation Parameter: A Comprehensive Narrative Review. Diagnostics (Basel) 2025; 15:299. [PMID: 39941229 PMCID: PMC11816681 DOI: 10.3390/diagnostics15030299] [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: 11/27/2024] [Revised: 01/09/2025] [Accepted: 01/24/2025] [Indexed: 02/16/2025] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) in the pediatric population has emerged as a significant health concern due to its alarming rise in prevalence. In children, the characteristics of the disease differ from those seen in adults. NAFLD may progress to more severe liver disease in children compared to adults with similar profiles. Liver biopsy remains the gold standard for diagnosis; its invasive nature and high cost limit its use as a first-line tool. Alternatively, magnetic resonance imaging (MRI) techniques, such as magnetic resonance imaging-estimated liver proton density fat fraction (MRI-PDFF), have shown a good correlation with the degree of histological steatosis, although their use is limited by high costs and limited accessibility. Controlled attenuation parameter (CAP), integrated with vibration-controlled transient elastography (VCTE) (FibroScan®), is a novel non-invasive, accessible, and effective method for diagnosing hepatic steatosis. In this article, we reviewed the existing literature on the diagnostic accuracy of CAP in pediatric NAFLD. The PubMed and EMBASE databases were searched. Seven relevant studies were identified, conducted in pediatric hospital populations with specific demographic characteristics. Two of these studies compared CAP with liver biopsy, one compared CAP with liver biopsy and MRI-PDFF, and the remaining four compared CAP with MRI. Overall, CAP proved to be accurate in detecting the presence or absence of fatty infiltration, positioning it as a promising tool to simplify the diagnosis of NAFLD in children. However, further studies in larger populations are needed to confirm these findings and facilitate its implementation in routine clinical practice.
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Affiliation(s)
- Ingrid Arteaga
- Unitat de Suport a la Recerca (USR) Metropolitana Nord, Fundació Institut Universitari d’Investigació en Atenció Primària Jordi Gol i Gurina (IDIAP Jordi Gol), 08303 Mataró, Spain; (I.A.); (C.C.); (A.M.-E.); (I.R.R.); (G.D.-F.); (M.C.-C.)
- Grup de Recerca en Malalties Hepàtiques a l’Atenció Primària (GRemHAp), IDIAP Jordi Gol, USR Metro-Nord, 08303 Mataró, Spain
- Primary Healthcare Center Vall del Tenes, Gerència d’Àmbit d’Atenció Primària Metropolitana Nord, Institut Català de la Salut, 08186 Llicà d’Amunt, Spain
| | - Carla Chacón
- Unitat de Suport a la Recerca (USR) Metropolitana Nord, Fundació Institut Universitari d’Investigació en Atenció Primària Jordi Gol i Gurina (IDIAP Jordi Gol), 08303 Mataró, Spain; (I.A.); (C.C.); (A.M.-E.); (I.R.R.); (G.D.-F.); (M.C.-C.)
- Grup de Recerca en Malalties Hepàtiques a l’Atenció Primària (GRemHAp), IDIAP Jordi Gol, USR Metro-Nord, 08303 Mataró, Spain
- Ph.D. Programme in Medicine and Translational Research, Faculty of Medicine, University of Barcelona, 08193 Barcelona, Spain
| | - Alba Martínez-Escudé
- Unitat de Suport a la Recerca (USR) Metropolitana Nord, Fundació Institut Universitari d’Investigació en Atenció Primària Jordi Gol i Gurina (IDIAP Jordi Gol), 08303 Mataró, Spain; (I.A.); (C.C.); (A.M.-E.); (I.R.R.); (G.D.-F.); (M.C.-C.)
- Grup de Recerca en Malalties Hepàtiques a l’Atenció Primària (GRemHAp), IDIAP Jordi Gol, USR Metro-Nord, 08303 Mataró, Spain
- Primary Healthcare Center La Llagosta, Gerència d’Àmbit d’Atenció Primària Metropolitana Nord, Institut Català de la Salut, 08120 La Llagosta, Spain
- Department of Medicine, Faculty of Medicine, Autonomous University of Barcelona, 08193 Bellaterra, Spain
| | - Irene Ruiz Rojano
- Unitat de Suport a la Recerca (USR) Metropolitana Nord, Fundació Institut Universitari d’Investigació en Atenció Primària Jordi Gol i Gurina (IDIAP Jordi Gol), 08303 Mataró, Spain; (I.A.); (C.C.); (A.M.-E.); (I.R.R.); (G.D.-F.); (M.C.-C.)
- Grup de Recerca en Malalties Hepàtiques a l’Atenció Primària (GRemHAp), IDIAP Jordi Gol, USR Metro-Nord, 08303 Mataró, Spain
- Primary Healthcare Center Dr. Barraquer, Gerència d’Àmbit d’Atenció Primària Metropolitana Nord, Institut Català de la Salut, 08930 Sant Adrià del Besos, Spain
| | - Galadriel Diez-Fadrique
- Unitat de Suport a la Recerca (USR) Metropolitana Nord, Fundació Institut Universitari d’Investigació en Atenció Primària Jordi Gol i Gurina (IDIAP Jordi Gol), 08303 Mataró, Spain; (I.A.); (C.C.); (A.M.-E.); (I.R.R.); (G.D.-F.); (M.C.-C.)
| | - Meritxell Carmona-Cervelló
- Unitat de Suport a la Recerca (USR) Metropolitana Nord, Fundació Institut Universitari d’Investigació en Atenció Primària Jordi Gol i Gurina (IDIAP Jordi Gol), 08303 Mataró, Spain; (I.A.); (C.C.); (A.M.-E.); (I.R.R.); (G.D.-F.); (M.C.-C.)
| | - Pere Torán-Monserrat
- Unitat de Suport a la Recerca (USR) Metropolitana Nord, Fundació Institut Universitari d’Investigació en Atenció Primària Jordi Gol i Gurina (IDIAP Jordi Gol), 08303 Mataró, Spain; (I.A.); (C.C.); (A.M.-E.); (I.R.R.); (G.D.-F.); (M.C.-C.)
- Grup de Recerca en Malalties Hepàtiques a l’Atenció Primària (GRemHAp), IDIAP Jordi Gol, USR Metro-Nord, 08303 Mataró, Spain
- Germans Trias i Pujol Research Institute (IGTP), 08916 Badalona, Spain
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Stroes ASR, Vos M, Benninga MA, Koot BGP. Pediatric MASLD: current understanding and practical approach. Eur J Pediatr 2024; 184:29. [PMID: 39560782 DOI: 10.1007/s00431-024-05848-1] [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: 09/25/2024] [Revised: 10/17/2024] [Accepted: 10/24/2024] [Indexed: 11/20/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the most prevalent chronic liver disease in children in industrialized countries mainly due to the rise in obesity and overweight. Besides risk of progressive liver damage, MASLD also carries an increased risk of extra-hepatic morbidity, most importantly type 2 diabetes mellitus and cardiovascular disease. Important challenges remain in the prevention, detection, and treatment of this prevalent disorder. This review outlines the epidemiology and risk factors of MASLD and provides an approach to screening, diagnosis, and treatment based on current best available evidence and expert opinion. What is known: • NAFLD/MASLD is a common disorder in children strongly related to obesity/overweight and insulin resistance. • This silent disorder is underdiagnosed due to lack of awareness and lack of simple diagnostic criteria. What is new: • New diagnostic criteria have transformed NAFLD/MASLD from a diagnosis of exclusion to a positive diagnosis with simple criteria. • Effective treatments are emerging for adults and will likely become available for children. • Identifying children with NAFLD/MASLD has become even more important due to this new treatment perspective.
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Affiliation(s)
- Anne-Sophie R Stroes
- Department of Pediatric Gastroenterology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Miriam Vos
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory University School of Medicine & Children's Healthcare of Atlanta, Atlanta, GA, USA
| | - Marc A Benninga
- Department of Pediatric Gastroenterology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Bart G P Koot
- Department of Pediatric Gastroenterology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
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Dogan B, Kunay B, Umman V, Kıran Taşçı E, Kumcuoğlu Z, Gulbahar F, Nart D, Karakoyun M, Cetin F, Aydogdu S. Transient Elastography for Noninvasive Evaluation of Posttransplant Liver Graft Fibrosis in Turkish Children, Ege University Children Hospital Experience. Clin Transplant 2024; 38:e15474. [PMID: 39367765 DOI: 10.1111/ctr.15474] [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] [Received: 05/07/2024] [Revised: 08/18/2024] [Accepted: 09/14/2024] [Indexed: 10/07/2024]
Abstract
OBJECTIVES The influence of advancing fibrosis on graft survival in the context of pediatric liver transplantation accentuates the critical role of protocol-driven liver biopsies, a practice adopted by numerous medical centers. Consequently, the exigency for noninvasive methodologies to assess graft fibrosis assumes heightened importance when conventional clinical and laboratory parameters fail to reveal signs of liver damage. METHODS This study aimed to assess the reliability of transient elastography (TE) in pediatric liver transplant recipients to detect graft fibrosis and compare the results of TE in patients who underwent biopsy. RESULTS This prospective cohort study included liver transplanted children who underwent biopsy at Ege University Children's Hospital between October 1, 2021, and October 31, 2022, and a healthy control group. According to TE, fibrosis was detected in 40 patients, and no fibrosis was detected in 50. The median time to develop fibrosis was 100 months (95% CI [83.1-116.8]). A statistically significant positive correlation existed between LSM and METAVIR fibrosis score (r = 0.562, p = 0.001). There was a statistically significant difference in LSM between patients with F2 fibrosis (7.8-8.8 kPa ± 3.2) compared to patients with F0 fibrosis (5.2 kPa ± 0.7) (p = 0.005) and F1 fibrosis (6.1 kPa ± 1.5) (p = 0.041), on ANOVA. CONCLUSION Liver allograft fibrosis is common in long-term follow-up in children who have undergone liver transplantation. Abnormal TE may guide physicians to consider liver biopsy to detect late allograft fibrosis in these children.
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Affiliation(s)
- Barut Dogan
- Division of Gastroenterology, Hepatology and Nutrition Disease, Department of Pediatrics, Medical School of Ege University, Izmir, Turkey
| | - Bora Kunay
- Division of Gastroenterology, Hepatology and Nutrition Disease, Department of Pediatrics, Medical School of Ege University, Izmir, Turkey
| | - Veysel Umman
- Department of General Surgery, Medical School of Ege University, İzmir, Turkey
| | - Ezgi Kıran Taşçı
- Department of Pediatrics, Gastroenterology, Hepatology, and Nutrition Disease, Medical School of Ege University, Sivas, Turkey
| | - Ziya Kumcuoğlu
- Department of Radiology, Ege-Rad Radiology and Nuclear Medicine Laboratory, İzmir, Bornova, Turkey
| | - Fatih Gulbahar
- Department of Radiology, Ege-Rad Radiology and Nuclear Medicine Laboratory, İzmir, Bornova, Turkey
| | - Deniz Nart
- Department of Pathology, Medical School of Ege University, İzmir, Bornova, Turkey
| | - Miray Karakoyun
- Division of Gastroenterology, Hepatology and Nutrition Disease, Department of Pediatrics, Medical School of Ege University, Izmir, Turkey
| | - Funda Cetin
- Division of Gastroenterology, Hepatology and Nutrition Disease, Department of Pediatrics, Medical School of Ege University, Izmir, Turkey
| | - Sema Aydogdu
- Division of Gastroenterology, Hepatology and Nutrition Disease, Department of Pediatrics, Medical School of Ege University, Izmir, Turkey
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Kim MN, Han JW, An J, Kim BK, Jin YJ, Kim SS, Lee M, Lee HA, Cho Y, Kim HY, Shin YR, Yu JH, Kim MY, Choi Y, Chon YE, Cho EJ, Lee EJ, Kim SG, Kim W, Jun DW, Kim SU, on behalf of The Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines for noninvasive tests to assess liver fibrosis in chronic liver disease. Clin Mol Hepatol 2024; 30:S5-S105. [PMID: 39159947 PMCID: PMC11493350 DOI: 10.3350/cmh.2024.0506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 08/12/2024] [Accepted: 08/16/2024] [Indexed: 08/21/2024] Open
Affiliation(s)
- Mi Na Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Ji Won Han
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jihyun An
- Department of Gastroenterology and Hepatology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Young-Joo Jin
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Seung-seob Kim
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Minjong Lee
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Han Ah Lee
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Hee Yeon Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yu Rim Shin
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Jung Hwan Yu
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Moon Young Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
| | - Young Eun Chon
- Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Eun Joo Lee
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Won Kim
- Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - on behalf of The Korean Association for the Study of the Liver (KASL)
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Gastroenterology and Hepatology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
- Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
- Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Korea
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Rose PC, Davies C, Cotton MF, Otwombe K, Browne SH, Vaida F, Innes S, Nel EDLR. Longitudinal controlled attenuation parameter and liver stiffness in children with and without perinatal HIV infection in South Africa. AIDS 2024; 38:1638-1647. [PMID: 38905492 PMCID: PMC11317452 DOI: 10.1097/qad.0000000000003964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/23/2024]
Abstract
OBJECTIVES Metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging cause of liver disease in HIV. Transient elastography (TE) with controlled attenuation parameter (CAP) measures liver stiffness as a marker of liver fibrosis and CAP as a measure of hepatic steatosis. Our aim was to evaluate longitudinal CAP and liver stiffness in children with perinatally acquired HIV (PHIV) on antiretroviral therapy (ART) from early life compared to children without HIV (HU). DESIGN Prospective cohort study. METHODS PHIV and HU were followed annually for two years. During the study, 60% of PHIV switched from older ART regimens to tenofovir disoproxil, lamivudine and dolutegravir (TLD). Longitudinal evolution of CAP and liver stiffness were investigated in two PHIV groups - on older ART and on TLD - compared to HU children using linear mixed effects models. RESULTS 263 children and adolescents (112 PHIV, 151 HU) aged 7-20 years were followed. PHIV on older ART had CAP 8.61% (95% CI 4.42-12.97, P < 0.001) greater than HU and no significant difference in CAP between PHIV on TLD and HU. No significant difference in liver stiffness was found between PHIV on older ART regimens and PHIV on TLD compared to HU. CONCLUSION PHIV on older ART had higher CAP than HU, whereas in PHIV switched to TLD there was no difference in CAP compared to HU. There was no difference in liver stiffness between either PHIV group and HU. This suggests starting ART early in life might protect PHIV from developing hepatic fibrosis.
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Affiliation(s)
- Penelope C Rose
- Department of Paediatrics of Child Health, Tygerberg Hospital, Stellenbosch University
| | - Claire Davies
- Division of Epidemiology and Biostatistics, Faculty of Medicine and Health Sciences
| | - Mark F Cotton
- Department of Paediatrics of Child Health, Tygerberg Hospital, Stellenbosch University
- Family Center for Research with Ubuntu, Department of Paediatrics and Child Health, Stellenbosch University
| | - Kennedy Otwombe
- Perinatal HIV Research Unit, Chris Hani Baragwanath Academic Hospital, Faculty of Health Sciences
- School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | | | - Florin Vaida
- Division of Biostatistics and Bioinformatics, School of Public Health, University of California, San Diego, CA, USA
| | - Steve Innes
- Family Center for Research with Ubuntu, Department of Paediatrics and Child Health, Stellenbosch University
- Desmond Tutu HIV Centre, University of Cape Town, South Africa
| | - Etienne De la Rey Nel
- Department of Paediatrics of Child Health, Tygerberg Hospital, Stellenbosch University
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Musto F, Stracuzzi M, Crivellaro E, Rubinacci V, Cibarelli A, Porro C, Ghidoni E, Zuccotti GV, Giacomet V. Natural History and Management of Hepatitis C in Children: 25 Years Experience of a Reference Center in Northern Italy. Pediatr Infect Dis J 2024; 43:813-818. [PMID: 38753999 PMCID: PMC11319081 DOI: 10.1097/inf.0000000000004374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/23/2024] [Indexed: 05/18/2024]
Abstract
Hepatitis C virus (HCV) infection natural history and management in the pediatric population are still debated. We retrospectively evaluated the outcome of a HCV pediatric population managed at the Pediatric Infectious Disease Unit of Luigi Sacco Hospital (Milan, Italy) from January 1997 to January 2022 (median follow-up 10 years) and we focused on the role of new drugs and transient elastography. Fifty-seven patients were enrolled: 8 (14%) had a spontaneous clearance, 33 were treated (58%), 7 (12%) were not treated because they were under 12 years old and 9 were lost at follow-up. HCV RNA was undetectable in all treated patients at the end of therapy, after 12 weeks (SVR12) and for the rest of their follow-up. All patients treated underwent elastography before and 1 year after therapy. Median stiffness pretherapy was 5.6 kPa, and 9 patients (16%) had abnormal transient elastography (>7 kPa, median 8.7 kPa). Median stiffness after treatment in the abnormal group was 6.8 kPa. Direct-acting antiviral agents are a safe and effective therapy for HCV chronic infection in the pediatric population. Liver elastography is normal in many vertically infected children before 12 years, but, when abnormal, it shows a significant improvement after direct-acting antiviral agent treatment. Further studies are needed to evaluate the role of elastography at diagnosis and follow-up in children.
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Affiliation(s)
- Francesca Musto
- From the Paediatric Infectious Disease Unit, Department of Paediatrics, Luigi Sacco Hospital Milan, University of Milan
| | - Marta Stracuzzi
- From the Paediatric Infectious Disease Unit, Department of Paediatrics, Luigi Sacco Hospital Milan, University of Milan
| | - Elisa Crivellaro
- From the Paediatric Infectious Disease Unit, Department of Paediatrics, Luigi Sacco Hospital Milan, University of Milan
| | - Valeria Rubinacci
- From the Paediatric Infectious Disease Unit, Department of Paediatrics, Luigi Sacco Hospital Milan, University of Milan
| | - Alessandro Cibarelli
- From the Paediatric Infectious Disease Unit, Department of Paediatrics, Luigi Sacco Hospital Milan, University of Milan
| | - Cecilia Porro
- From the Paediatric Infectious Disease Unit, Department of Paediatrics, Luigi Sacco Hospital Milan, University of Milan
| | - Elena Ghidoni
- From the Paediatric Infectious Disease Unit, Department of Paediatrics, Luigi Sacco Hospital Milan, University of Milan
| | - Gian Vincenzo Zuccotti
- Pediatric Department, Buzzi Children’s Hospital
- Department of Biosciences, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, University of Milan, Milan, Italy
| | - Vania Giacomet
- From the Paediatric Infectious Disease Unit, Department of Paediatrics, Luigi Sacco Hospital Milan, University of Milan
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9
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Bicha S, Boumaraf H, Lakehal A. Shear wave elastography as a non-invasive tool for staging liver fibrosis in children: A study in Algerian pediatric patients. Indian J Gastroenterol 2024; 43:601-608. [PMID: 37962819 DOI: 10.1007/s12664-023-01464-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 09/18/2023] [Indexed: 11/15/2023]
Abstract
BACKGROUND Traditionally, liver biopsy has been the gold standard for fibrosis staging. However, it is an invasive, expensive and uncomfortable procedure that is associated with the risk of complications. Thus, non-invasive methods such as shear wave elastography (SWE) have been developed as potential alternatives to liver biopsy. The aim of this study is to evaluate the diagnostic performance of SWE in pediatric patients with liver fibrosis, specifically in a group of Algerian children and to determine whether this method can be a reliable alternative to liver biopsy. METHODS This prospective, descriptive, monocentric study evaluated the non-invasive diagnostic performance of 2D-SWE in assessing liver fibrosis in pediatric patients. The assessment was carried out using various statistical methods, including Spearman's correlation coefficient, Kappa concordance coefficients, regression analysis, as well as the calculation of area under the receiver operating characteristic (AUROC) values and corresponding cut-off points based on the receiver operating characteristic (ROC) curve. RESULTS Our study found that 2D-SWE is strongly correlated with liver biopsy in estimating liver fibrosis in children, with a correlation coefficient greater than 0.8. Furthermore, the Kappa correlation coefficients exceeded 0.8, indicating a strong agreement between 2D-SWE and liver biopsy results. The AUROC value was not less than 0.9 for significant fibrosis and above (≥ F2), indicating that it has satisfactory diagnostic performance in detecting liver fibrosis in children. CONCLUSION 2D-SWE shows promise as a non-invasive method for evaluating liver fibrosis in children, offering a potential alternative to liver biopsy. Larger studies are needed to substantiate the findings of this study and to confirm the accuracy and reliability of 2D-SWE for assessing liver fibrosis in children.
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Affiliation(s)
- Samia Bicha
- Department of Medicine, University of Constantine, 3- Salah Boubnider, Constantine, Algeria.
- Research Laboratory, LR2M, Constantine, Algeria.
| | - Habiba Boumaraf
- Department of Medicine, University of Constantine, 3- Salah Boubnider, Constantine, Algeria
| | - Abdelhak Lakehal
- Department of Medicine, University of Constantine, 3- Salah Boubnider, Constantine, Algeria
- Research Laboratory, LR2M, Constantine, Algeria
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10
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Medyńska-Przęczek A, Stochel-Gaudyn A, Wędrychowicz A. Liver fibrosis assessment in pediatric population - can ultrasound elastography be an alternative method to liver biopsy? A systematic review. Adv Med Sci 2024; 69:8-20. [PMID: 38198895 DOI: 10.1016/j.advms.2023.12.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Revised: 09/17/2023] [Accepted: 12/19/2023] [Indexed: 01/12/2024]
Abstract
Liver diseases of various etiologies are becoming increasingly common in the pediatric population. So far, the gold diagnostic standard in these disorders is liver biopsy. This procedure is invasive, painful and requires general anesthesia in this group of patients. Due to the continuous development of new research techniques, such as liver elastography, it is necessary to evaluate them in the context of their diagnostic usefulness. Ultrasound elastography, as a quick and effective method, is being used more and more often in the assessment and monitoring of liver dysfunction in both adults and children. There are several techniques of liver elastography, such as transient elastography, shear wave elastography consisting of various subtypes such as two-dimensional shear wave elastography, acoustic radiation force impulse and point shear wave elastography, which differ in terms of the measurement technique and the achieved results. The purpose of our review was to determine whether techniques of liver elastography could replace liver biopsy. Although now, based on the analyzed papers, elastography cannot replace liver biopsy, in our opinion, the role of this tool in monitoring pediatric patients with liver diseases will grow in the coming years.
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Affiliation(s)
- Aleksandra Medyńska-Przęczek
- School of Medical and Health Sciences, Faculty of Medicine, Jagiellonian University Medical College, Krakow, 31-530, Poland.
| | - Anna Stochel-Gaudyn
- Department of Paediatrics, Gastroenterology and Nutrition, Pediatric Institute, Faculty of Medicine, Jagiellonian University Medical College, Krakow, 30-663, Poland
| | - Andrzej Wędrychowicz
- Department of Paediatrics, Gastroenterology and Nutrition, Pediatric Institute, Faculty of Medicine, Jagiellonian University Medical College, Krakow, 30-663, Poland
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11
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Zeng J, Jin Q, Yang J, Yang RX, Zhang RN, Zhao J, Fan JG. Prevalence and incidence of MAFLD and associated anthropometric parameters among prepubertal children of the Shanghai Birth Cohort. Hepatol Int 2023; 17:1416-1428. [PMID: 37728728 DOI: 10.1007/s12072-023-10574-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 07/21/2023] [Indexed: 09/21/2023]
Abstract
BACKGROUND AND AIM Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease in adolescent and adult population. However, the epidemiologic data of MAFLD in prepubertal children remain limited. This study aimed to investigate the prevalence and incidence of MAFLD and assess the role of anthropometric parameters in identifying and predicting MAFLD in this population. METHODS Children from the Shanghai Birth Cohort Study who underwent an 8-year follow-up with anthropometric measurements and transient elastography FibroScan-502 examination (M probe, Echosens, Paris, France) were enrolled. Some of them also completed a 5-year follow-up. Diagnosis of fatty liver disease (FLD) was based on the controlled attenuation parameter (CAP) value exceeding 248 dB/m, and MAFLD was defined as FLD combined with obesity or central obesity. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic accuracy of anthropometric parameters for MAFLD. RESULTS A total of 848 children (431 boys) from the Shanghai Birth Cohort Study were followed up for 8 years, and among them, 385 children (189 boys) also participated in the 5-year follow-up. The prevalence of FLD and MAFLD at 5 years old was 3.90% and 0.52%, respectively, while at 8 years old, the prevalence rates increased to 5.07% for FLD and 3.42% for MAFLD. The 8-year-old children with MAFLD exhibited significantly higher weight, body mass index (BMI), chest circumference, waist circumference, hip circumference, waist-to-height ratio, waist-to-hip ratio, and liver stiffness measurement compared to those without MAFLD (all p < 0.05). The incidence rates of FLD and MAFLD at 8 years old, considering the 5-year follow-up data, were 3.78% (14/370) and 3.13% (12/383), respectively. Obese or centrally obese children at 5 years old had a higher incidence of FLD and MAFLD at the 8-year follow-up. Waist circumference and BMI showed significant associations with the presence and incidence of MAFLD, respectively, with the largest AUC values in ROC curve analysis. In addition, chest circumference was significantly associated with MAFLD in obese children. CONCLUSION This study provides insights into the incidence and prevalence of MAFLD in prepubertal children. It underscores the importance of anthropometric parameters in identifying and predicting MAFLD in this population. Further research encompassing a broader age range and incorporating these indicators and additional metabolic markers is necessary to enhance the understanding and management of MAFLD in children.
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Affiliation(s)
- Jing Zeng
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No.1665, Kongjiang Road, Yangpu District, Shanghai, 200092, China
| | - Qian Jin
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No.1665, Kongjiang Road, Yangpu District, Shanghai, 200092, China
| | - Jing Yang
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No.1665, Kongjiang Road, Yangpu District, Shanghai, 200092, China
| | - Rui-Xu Yang
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No.1665, Kongjiang Road, Yangpu District, Shanghai, 200092, China
| | - Rui-Nan Zhang
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No.1665, Kongjiang Road, Yangpu District, Shanghai, 200092, China
| | - Jian Zhao
- The Ministry of Education and Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No.1665, Kongjiang Road, Yangpu District, Shanghai, 200092, China.
- Department of Maternal and Child Health, School of Public Health, Shanghai Jiao Tong University, Shanghai, China.
| | - Jian-Gao Fan
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No.1665, Kongjiang Road, Yangpu District, Shanghai, 200092, China.
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12
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Naume MM, Jørgensen MH, Høi-Hansen CE, Nielsen MR, Born AP, Vissing J, Borgwardt L, Stærk DMR, Ørngreen MC. Low skeletal muscle mass and liver fibrosis in children with cerebral palsy. Eur J Pediatr 2023; 182:5047-5055. [PMID: 37656239 PMCID: PMC10640414 DOI: 10.1007/s00431-023-05177-9] [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: 05/05/2023] [Revised: 08/21/2023] [Accepted: 08/23/2023] [Indexed: 09/02/2023]
Abstract
The purpose of the study was to conduct a nutritional and metabolic assessment of children with cerebral palsy, including an investigation of liver status, body composition, and bone mineral density. In this cross-sectional study we included 22 children with cerebral palsy. By using ultrasound, transient elastography, dual x-ray absorptiometry (DXA) scan, blood samples, anthropometric measurements, and a three-day diet registration, the nutritional and metabolic status was evaluated. Liver fibrosis and steatosis were found in four patients (18.2%), all with severe motor impairments, low skeletal muscle mass, and epilepsy. All patients with liver involvement had normal liver-related blood samples. Decreased bone mineral density was found in 26.3%, and 91.0% had low skeletal muscle mass. Fat mass and muscle mass were significantly lower in the patients with severe motor impairments compared to the patients with less severe motor impairments. Within the children classified as 'underweight' or 'normal' according to body mass index, body fat determined by DXA scan was normal or high in 50% of these patients. CONCLUSIONS This study is the first to report liver fibrosis and steatosis in children with cerebral palsy. Possible causes of liver fibrosis and/or steatosis are altered body composition with low skeletal muscle mass, decreased mobility and medical drug intake. Further investigations of liver involvement and risk factors are needed. WHAT IS KNOWN • Children and adolescents with cerebral palsy are at risk of malnutrition and altered body composition, both of which can lead to fatty liver disease. • It is unknown whether children with cerebral palsy are at increased risk of metabolic disturbances such as fatty liver disease. WHAT IS NEW • Altered body composition and low skeletal muscle mass, regardless of ambulation is present in 91% of the children with cerebral palsy. • Liver fibrosis and/or steatosis were found in 18.2% of the patients. Possible causes are altered body composition, decreased mobility and medical drug intake.
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Affiliation(s)
- Marie Mostue Naume
- Copenhagen Neuromuscular Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
| | - Marianne Hørby Jørgensen
- Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Christina Engel Høi-Hansen
- Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark
| | - Maja Risager Nielsen
- Copenhagen Neuromuscular Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Alfred Peter Born
- Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - John Vissing
- Copenhagen Neuromuscular Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Lise Borgwardt
- Department of Clinical Physiology, Nuclear Medicine & PET, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | | | - Mette Cathrine Ørngreen
- Copenhagen Neuromuscular Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
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13
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Groth M, Fischer L, Herden U, Brinkert F, Beime J, Deindl P, Adam G, Herrmann J. Impact of probe-induced abdominal compression on two-dimensional shear wave elastography measurement of split liver transplants in children. ROFO-FORTSCHR RONTG 2023; 195:905-912. [PMID: 37137318 DOI: 10.1055/a-2049-9369] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/05/2023]
Abstract
PURPOSE To evaluate the effect of probe-induced abdominal compression of split liver transplants (SLT) in children on 2D-shear wave elastography (SWE) values. MATERIALS AND METHODS Data from 11 children (4.7 ± 4.8 years) who had undergone SLT and SWE were evaluated retrospectively. Elastograms were obtained with probes placed in an epigastric, midline position on the abdominal wall, with no and slight compression, using convex and linear transducers. For each identically positioned probe and condition, 12 serial elastograms were obtained and the SLT diameter was measured. Liver stiffness and degree of SLT compression were compared. RESULTS Slight probe pressure resulted in SLT compression, with a shorter distance between the cutis and the posterior margin of the liver transplant than in the measurement with no pressure (curved array, 5.0 ± 1.1 vs. 5.9 ± 1.3 cm, mean compression 15 %± 8 %; linear array, 4.7 ± 0.9 vs. 5.3 ± 1.0 cm, mean compression 12 %± 8 %; both p < 0.0001). The median liver stiffness was significantly greater with slight pressure than with no pressure (curved transducer, 13.38 ± 3.0 vs. 7.02 ± 1.7 kPa, p < 0.0001; linear transducer, 18.53 ± 7.1 vs. 9.03 ± 1.5 kPa, p = 0.0003). CONCLUSION Slight abdominal compression can significantly increase SWE values in children with left-lateral SLT. To obtain meaningful results and reduce operator dependency in free-hand examinations, probe pressure must be controlled carefully. KEY POINTS · Probe-induced compression can increase elastography values in split liver transplants in children. · In free-hand examination, probe pressure must be controlled carefully. · Pressure loading can be determined indirectly by the anteroposterior transplant diameter. CITATION FORMAT · Groth M, Fischer L, Herden U et al. Impact of probe-induced abdominal compression on two-dimensional shear wave elastography measurement of split liver transplants in children. Fortschr Röntgenstr 2023; 195: 905 - 912.
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Affiliation(s)
- Michael Groth
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, Section of Pediatric Radiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Lutz Fischer
- Hepatobiliary Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Uta Herden
- Hepatobiliary Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Florian Brinkert
- Pediatric Gastroenterology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Jan Beime
- Pediatric Gastroenterology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Philipp Deindl
- Department of Neonatology and Pediatric Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Gerhard Adam
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Jochen Herrmann
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, Section of Pediatric Radiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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14
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Rose PC, Cotton MF, Otwombe K, Innes S, Nel ED. Liver transient elastography values in healthy South African children. BMC Pediatr 2023; 23:355. [PMID: 37443011 PMCID: PMC10339605 DOI: 10.1186/s12887-023-04170-3] [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: 05/01/2023] [Accepted: 06/30/2023] [Indexed: 07/15/2023] Open
Abstract
BACKGROUND Transient elastography (TE) is a rapid noninvasive ultrasound-based technology that measures liver stiffness as a surrogate for liver fibrosis and controlled attenuation parameter (CAP) as a measure of liver steatosis. However, normal ranges in children are not well defined in all populations. The aim of this study was to determine transient elastography values in healthy South African children. METHODS From April 2019 to December 2021, children were recruited from the HIV negative control group of a cohort study. Only children neither overweight nor obese, without evidence of liver disease, no medical condition or medication associated with hepatic steatosis or fibrosis and normal metabolic profile were included in this cross-sectional analysis. Clinical data, anthropometry and blood samples were collected on the same day as transient elastography with controlled attenuation parameter was performed. RESULTS 104 children (median age 12.8 years [IQR 11.4-14.8, range 7.9-17.7 years]; 59 [57%] boys) were included. Liver stiffness was positively correlated with age (Pearson's r = 0.39, p < 0.001). Median liver stiffness in boys (5.2 kPa [5th to 95th percentiles 3.6 to 6.8 kPa]) was greater than in girls (4.6 kPa [5th to 95th percentiles 3.6 to 6.1 kPa; p = 0.004]), but there was no difference by ethnicity. Median CAP was 179dB/m (5th to 95th percentiles 158 to 233dB/m). There was a positive correlation between CAP and body mass index (BMI) z-score, but no difference by age, sex, ethnicity or pubertal status. CONCLUSION Liver stiffness values increase with age and are higher in healthy South African boys than girls, whereas CAP values vary with BMI, but not with age or sex.
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Affiliation(s)
- Penelope C Rose
- Department of Paediatrics and Child Health, Tygerberg Hospital and Stellenbosch University, PO Box 241, Cape Town, 8000, South Africa.
| | - Mark F Cotton
- Department of Paediatrics and Child Health, Tygerberg Hospital and Stellenbosch University, PO Box 241, Cape Town, 8000, South Africa
- Family Center for Research with Ubuntu (FAMCRU), Cape Town, South Africa
| | - Kennedy Otwombe
- Perinatal HIV Research Unit, School of Public Health, Chris Hani Baragwanath Academic Hospital, University of the Witwatersrand, Johannesburg, South Africa
| | - Steve Innes
- Department of Paediatrics and Child Health, Tygerberg Hospital and Stellenbosch University, PO Box 241, Cape Town, 8000, South Africa
- Family Center for Research with Ubuntu (FAMCRU), Cape Town, South Africa
- Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa
| | - Etienne D Nel
- Department of Paediatrics and Child Health, Tygerberg Hospital and Stellenbosch University, PO Box 241, Cape Town, 8000, South Africa
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15
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Rose PC, De la Rey Nel E, Cotton MF, Otwombe K, Browne SH, Frigati LJ, Rabie H, Innes S. Decreased Hepatic Steatosis in South African Adolescents With Perinatal HIV Switching to Dolutegravir-containing Regimens. Pediatr Infect Dis J 2023; 42:564-572. [PMID: 36917035 PMCID: PMC10257761 DOI: 10.1097/inf.0000000000003904] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/16/2023]
Abstract
BACKGROUND Although dolutegravir (DTG) has a favorable metabolic profile, it has been linked to excess weight gain. We evaluated changes in hepatic steatosis in adolescents with perinatally acquired HIV switching to DTG-containing antiretroviral therapy (ART). METHODS Virologically suppressed adolescents switched to dolutegravir for a minimum of 4 months or on unchanged ART (84% protease inhibitor) were assessed prospectively with anthropometry, transient elastography with controlled attenuation parameter (CAP) and fasting metabolic profiles. ART regimens were determined independently of the study. RESULTS In total 68 adolescents [baseline median age 13.5 years [interquartile range (IQR): 12.5-14.4 years]; 42 (62%) female] were recruited. However, 38 remained on the same regimen and were followed for a median of 98 weeks (IQR: 48-108 weeks), and 30 switched to DTG and were followed for a median of 52 weeks (IQR: 49-101). There was no baseline difference in CAP between groups. There was no significant change in body mass index z-score in either group, but the median CAP in the DTG group decreased by -40dB/m (IQR: -51 to -31 dB/m) after a median of 44 weeks (IQR: 28-50 weeks) on DTG, compared to +1dB/m (IQR: -29 to +14 dB/m) in adolescents not switched ( P < 0 .01). Cholesterol and triglycerides were lower in those switched. Whereas hepatic steatosis prevalence decreased from 17% to 3% in adolescents who switched to dolutegravir, its prevalence doubled from 8% to 16% in those not switched ( P = 0.1). CONCLUSIONS In this exploratory study, adolescents switched to DTG-containing regimens had reduced hepatic steatosis, cholesterol and triglycerides with no excess weight gain compared to those on unchanged ART.
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Affiliation(s)
- Penelope C. Rose
- Department of Paediatrics and Child Health, Tygerberg Hospital and Stellenbosch University, Cape Town, South Africa
| | - Etienne De la Rey Nel
- Department of Paediatrics and Child Health, Tygerberg Hospital and Stellenbosch University, Cape Town, South Africa
| | - Mark F. Cotton
- Department of Paediatrics and Child Health, Tygerberg Hospital and Stellenbosch University, Cape Town, South Africa
- Family Center for Research with Ubuntu (FAMCRU), Cape Town, South Africa
| | - Kennedy Otwombe
- Perinatal HIV Research Unit, Chris Hani Baragwanath Academic Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Sara H. Browne
- Department of Medicine, University of California San Diego
| | - Lisa J. Frigati
- Department of Paediatrics and Child Health, Tygerberg Hospital and Stellenbosch University, Cape Town, South Africa
| | - Helena Rabie
- Department of Paediatrics and Child Health, Tygerberg Hospital and Stellenbosch University, Cape Town, South Africa
| | - Steve Innes
- Department of Paediatrics and Child Health, Tygerberg Hospital and Stellenbosch University, Cape Town, South Africa
- Family Center for Research with Ubuntu (FAMCRU), Cape Town, South Africa
- Desmond Tutu HIV Centre, University of Cape Town, South Africa
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16
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Naume MM, Jørgensen MH, Høi-Hansen CE, Born AP, Vissing J, Borgwardt L, Staerk DMR, Ørngreen MC. Metabolic assessment in children with neuromuscular disorders shows risk of liver enlargement, steatosis and fibrosis. Acta Paediatr 2023; 112:846-853. [PMID: 36579362 DOI: 10.1111/apa.16649] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 12/20/2022] [Accepted: 12/27/2022] [Indexed: 12/30/2022]
Abstract
AIM The aim of this study was to conduct a metabolic and nutritional assessment of children with neuromuscular disorders, including the investigation of the liver and bone mineral density. METHODS In this observational study, we included 44 children with neuromuscular disorders. The nutritional status, bone health and liver were assessed by ultrasound, transient elastography, dual X-ray absorptiometry scan, blood samples, anthropometric measurements and 3-day diet registration. RESULTS Liver involvement was found in 31.0%: liver enlargement in 7.1%, steatosis in 4.8%, fibrosis in 14.3% and liver enlargement together with steatosis or fibrosis was found in 4.8%. These changes were found in 9/23 patients with Duchenne muscular dystrophy, 4/9 patients with spinal muscular atrophy type II and 0/12 patients with other neuromuscular diagnoses. Low bone mineral density was found in 44.0% of the patients, though the majority used daily vitamin D and calcium supplements. Vitamin D insufficiency or deficiency was found in 22.6%. CONCLUSION The metabolic assessment in children with neuromuscular disorders shows an increased risk of liver enlargement, steatosis and fibrosis. Possible causes are obesity, decreased mobility, low skeletal muscle mass and for a subgroup the use of glucocorticoids. The findings suggest that monitoring liver function should be part of the nutritional assessment in patients with neuromuscular disorders.
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Affiliation(s)
- Marie Mostue Naume
- Copenhagen Neuromuscular Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Marianne Hørby Jørgensen
- Department of Paediatrics and adolescent medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Christina Engel Høi-Hansen
- Department of Paediatrics and adolescent medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.,Department of Clinical Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Alfred Peter Born
- Department of Paediatrics and adolescent medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - John Vissing
- Copenhagen Neuromuscular Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Lise Borgwardt
- Department of Clinical physiology, Nuclear Medicine & PET, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | | | - Mette Cathrine Ørngreen
- Copenhagen Neuromuscular Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.,Department of Paediatrics and adolescent medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
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Ozdogan E, Arikan C. Liver fibrosis in children: a comprehensive review of mechanisms, diagnosis, and therapy. Clin Exp Pediatr 2023; 66:110-124. [PMID: 36550776 PMCID: PMC9989719 DOI: 10.3345/cep.2022.00367] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Accepted: 09/14/2022] [Indexed: 12/23/2022] Open
Abstract
Chronic liver disease incidence is increasing among children worldwide due to a multitude of epidemiological changes. Most of these chronic insults to the pediatric liver progress to fibrosis and cirrhosis to different degrees. Liver and immune physiology differs significantly in children from adults. Because most of pediatric liver diseases have no definitive therapy, a better understanding of population and disease-specific fibrogenesis is mandatory. Furthermore, fibrosis development has prognostic significance and often guide treatment. Evaluation of liver fibrosis continues to rely on the gold-standard liver biopsy. However, many high-quality studies put forward the high diagnostic accuracy of numerous diagnostic modalities in this setting. Herein, we summarize and discuss the recent literature on fibrogenesis with an emphasis on pediatric physiology along with a detailed outline of disease-specific signatures, noninvasive diagnostic modalities, and the potential for antifibrotic therapies.
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Affiliation(s)
- Elif Ozdogan
- Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA
| | - Cigdem Arikan
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Koc University School of Medicine, Istanbul, Turkey
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18
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Clinical study of the value of shear wave elastography in evaluating the degree of liver fibrosis in children. Abdom Radiol (NY) 2023; 48:1298-1305. [PMID: 36811726 DOI: 10.1007/s00261-023-03837-w] [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: 11/19/2022] [Revised: 01/27/2023] [Accepted: 01/27/2023] [Indexed: 02/24/2023]
Abstract
OBJECTIVES To explore the clinical application of shear wave elastography (SWE) in evaluating the degree of liver fibrosis in children. METHODS To explore the value of SWE in assessing liver fibrosis in children, the correlation between elastography values and the METAVIR grade of liver fibrosis in children with biliary system or liver diseases was studied. Children with significant liver enlargement were enrolled, and the fibrosis grade was analyzed to explore the value of SWE in assessing the degree of liver fibrosis in the presence of significant liver enlargement. RESULTS A total of 160 children with bile system or liver diseases were recruited. The areas under the receiver operating characteristic curve (AUROCs) for liver biopsy from stage F1 to F4 were 0.990, 0.923, 0.819, and 0.884. According to the degree of liver fibrosis at liver biopsy, there was a high correlation between the SWE value and the degree of liver fibrosis (correlation coefficient 0.74). There was no significant correlation between the Young's modulus value of the liver and the degree of liver fibrosis (correlation coefficient 0.16). CONCLUSIONS Supersonic SWE can generally accurately evaluate the degree of liver fibrosis in children with liver disease. However, When the liver is significantly enlarged, SWE can only evaluate liver stiffness based on Young's modulus values, and the degree of liver fibrosis must still be determined by pathologic biopsy.
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Jańczyk W, Bierła JB, Trojanowska I, Wierzbicka-Rucińska A, Cukrowska B, Socha P. Prevalence and Significance of Autoantibody Seropositivity in Children with Wilson's Disease. Diagnostics (Basel) 2023; 13:diagnostics13040768. [PMID: 36832258 PMCID: PMC9955693 DOI: 10.3390/diagnostics13040768] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 02/03/2023] [Accepted: 02/15/2023] [Indexed: 02/22/2023] Open
Abstract
Autoantibodies occur in healthy subjects as well as in children with Wilson's disease (WD), but their prevalence and significance are unknown. Thus, we aimed to assess the prevalence of autoantibodies and autoimmune markers, and their relationship to liver injury in WD children. The study included 74 WD and 75 healthy children as a control group. Patients with WD underwent transient elastography (TE) examinations, as well as determination of liver function tests, copper metabolism markers, and serum immunoglobulins (Ig). In the sera of the WD patients and controls, anti-nuclear (ANA), anti-smooth muscle, anti-mitochondrial, anti-parietal cell, anti-liver/kidney microsomal, anti-neutrophil cytoplasmic autoantibodies, and specific celiac antibodies were determined. Among the autoantibodies, only the prevalence of ANA in children with WD was higher than in the controls. There was no significant relationship between the presence of autoantibodies and liver steatosis or stiffness after TE. However, advanced liver stiffness (E > 8.2 kPa) was related to IgA, IgG, and gamma globulin production. The type of treatment did not influence the prevalence of autoantibodies. Our results suggest that autoimmune disturbances in WD might not be directly related to liver damage as expressed by steatosis and/or liver stiffness after TE.
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Affiliation(s)
- Wojciech Jańczyk
- Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, Children’s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland
- Correspondence: ; Tel.: +48-22-8151874
| | - Joanna B. Bierła
- Department of Pathomorphology, Children’s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland
| | - Ilona Trojanowska
- Department of Pathomorphology, Children’s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland
| | - Aldona Wierzbicka-Rucińska
- Department of Biochemistry, Radioimmunology and Experimental Medicine, Children’s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland
| | - Bożena Cukrowska
- Department of Pathomorphology, Children’s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland
| | - Piotr Socha
- Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, Children’s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland
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20
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Nielsen J, Kjær MS, Rasmussen A, Chiranth D, Willemoe GL, Henriksen BM, Borgwardt L, Grand MK, Borgwardt L, Christensen VB. Noninvasive Prediction of Advanced Fibrosis in Pediatric Liver Disease-Discriminatory Performance of 2D Shear Wave Elastography, Transient Elastography and Magnetic Resonance Elastography in Comparison to Histopathology. Diagnostics (Basel) 2022; 12:diagnostics12112785. [PMID: 36428845 PMCID: PMC9689483 DOI: 10.3390/diagnostics12112785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 11/07/2022] [Accepted: 11/10/2022] [Indexed: 11/16/2022] Open
Abstract
Background: Elastography can be measured with different imaging techniques and is increasingly used for noninvasive assessment of hepatic fibrosis. Little is known about the performance, and interrelation of different elastographic techniques, in prediction of hepatic fibrosis in pediatric liver disease. Objectives: We aimed to determine the discriminatory value for advanced fibrosis (Metavir F3-4) and evaluate the applicability of 2D shear wave ultrasound elastography (USe), Transient Elastography (TE) and Magnetic Resonance elastography (MRe) in pediatric liver disease. Methods: In patients with pediatric liver disease aged 0−19 years, USe, TE and MRe were compared with histopathological fibrosis stage. Multivariate logistic regression models for advanced fibrosis were considered. Discriminative performance was assessed by the area under the receiver operating characteristic curve and the Brier Score. Primary analyses included complete cases. Multiple imputation was used as sensitivity analysis. Results: In 93 histologically evaluated patients USe, TE and MRe were performed 89, 93 and 61 times respectively. With increased liver stiffness values, significantly increased odds for presenting F3-4 were seen in individual models for ALT < 470 U/L, whereas the effect for ALT > 470 U/L was non-significant. Area under the curve and Brier Score for discrimination of advanced fibrosis were 0.798 (0.661−0.935) and 0.115 (0.064−0.166); 0.862 (0.758−0.966) and 0.118 (0.065−0.171); 0.896 (0.798−0.994) and 0.098 (0.049−0.148) for USe, TE and MRe respectively. No significant increase in discriminatory ability was found when combining elastographic modalities. Conclusions: In pediatric liver disease, USe, TE and MRe had a good discriminatory ability for assessment of advanced liver fibrosis, although TE and MRe performed best. In most children with pediatric liver disease, TE is a reliable and easily applicable measure.
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Affiliation(s)
- Jon Nielsen
- Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark
- Correspondence: ; Tel.: +45-23839149
| | - Mette Skalshøi Kjær
- Department of Medical Gastroenterology and Hepatology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark
| | - Allan Rasmussen
- Department of Surgical Gastroenterology and Transplantation, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark
| | - Deepthi Chiranth
- Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark
| | - Gro Linno Willemoe
- Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark
| | - Birthe Merete Henriksen
- Department of Diagnostic Radiology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark
| | - Lotte Borgwardt
- Department of Diagnostic Radiology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark
| | - Mia Klinten Grand
- Department of Biostatistics, Faculty of Health Sciences, Institute of Public Health, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
| | - Lise Borgwardt
- Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark
| | - Vibeke Brix Christensen
- Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark
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21
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Lefere S, Dupont E, De Guchtenaere A, Van Biervliet S, Vande Velde S, Verhelst X, Devisscher L, Van Vlierberghe H, Geerts A, De Bruyne R. Intensive Lifestyle Management Improves Steatosis and Fibrosis in Pediatric Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol 2022; 20:2317-2326.e4. [PMID: 34871812 DOI: 10.1016/j.cgh.2021.11.039] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 11/18/2021] [Accepted: 11/29/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Childhood obesity, with associated comorbidities such as nonalcoholic fatty liver disease (NAFLD), is an increasing global health problem. Although lifestyle management is the mainstay of treatment, its efficacy on liver fibrosis has not yet been established. METHODS Children and adolescents admitted for severe obesity at a tertiary center (Zeepreventorium, De Haan, Belgium) were enrolled in this prospective study. Intensive lifestyle therapy encompassed caloric restriction, physical activity, education on a healthy lifestyle, and psychosocial support. At baseline, 6 months, and 12 months, liver ultrasound and transient elastography with controlled attenuation parameter were performed to assess liver steatosis and fibrosis. RESULTS A total of 204 patients (median age, 14.0 y; body mass index Z-score, +2.8) were evaluated at admission. NAFLD on ultrasound was present in 71.1%, whereas 68.6% had controlled attenuation parameter values of 248 dB/m or greater. A total of 32.8% of patients had at least F2 fibrosis, including 10.3% with transient elastography of 9 kPa or greater. After 6 months, the median body weight loss was 16.0% in the 167 patients evaluated. Fibrosis improved in 75.0% (P < .001). Baseline severity of liver fibrosis and steatosis were predictors of fibrosis resolution. Seventy-nine patients had reached the 1-year time point. The improvements were sustained because fibrosis regressed at least 1 stage in all patients with baseline fibrosis. Fasting serum alanine aminotransferase and homeostasis model assessment of insulin resistance decreased significantly over the 1-year period (P < .001). CONCLUSIONS NAFLD and associated fibrosis are highly prevalent in children and adolescents with severe obesity. An intensive multidisciplinary lifestyle management program that causes significant weight loss not only improves liver steatosis, but also fibrosis.
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Affiliation(s)
- Sander Lefere
- Hepatology Research Unit, Department of Internal Medicine and Pediatrics, Liver Research Center Ghent, Ghent, Belgium; Gut-Liver Immunopharmacology Unit, Department of Basic and Applied Medical Sciences, Liver Research Center Ghent, Ghent, Belgium.
| | | | - Ann De Guchtenaere
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
| | - Stephanie Van Biervliet
- Pediatric Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine and Pediatrics, Ghent, Belgium
| | - Saskia Vande Velde
- Pediatric Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine and Pediatrics, Ghent, Belgium
| | - Xavier Verhelst
- Hepatology Research Unit, Department of Internal Medicine and Pediatrics, Liver Research Center Ghent, Ghent, Belgium
| | - Lindsey Devisscher
- Gut-Liver Immunopharmacology Unit, Department of Basic and Applied Medical Sciences, Liver Research Center Ghent, Ghent, Belgium
| | - Hans Van Vlierberghe
- Hepatology Research Unit, Department of Internal Medicine and Pediatrics, Liver Research Center Ghent, Ghent, Belgium
| | - Anja Geerts
- Hepatology Research Unit, Department of Internal Medicine and Pediatrics, Liver Research Center Ghent, Ghent, Belgium
| | - Ruth De Bruyne
- Pediatric Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine and Pediatrics, Ghent, Belgium
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22
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Flores-Calderón J, Cisneros-Garza LE, Chávez-Barrera JA, Vázquez-Frias R, Reynoso-Zarzosa FA, Martínez-Bejarano DL, Consuelo-Sánchez A, Reyes-Apodaca M, Zárate-Mondragón FE, Sánchez-Soto MP, Alcántara-García RI, González-Ortiz B, Ledesma-Ramírez S, Espinosa-Saavedra D, Cura-Esquivel IA, Macías-Flores J, Hinojosa-Lezama JM, Hernández-Chávez E, Zárate-Guerrero JR, Gómez-Navarro G, Bilbao-Chávez LP, Sosa-Arce M, Flores-Fong LE, Lona-Reyes JC, Estrada-Arce EV, Aguila-Cano R. Consensus on the management of complications of cirrhosis of the liver in pediatrics. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2022; 87:462-485. [PMID: 35810090 DOI: 10.1016/j.rgmxen.2022.06.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 03/08/2022] [Indexed: 12/07/2022]
Abstract
The Asociación Mexicana de Hepatología A.C. carried out the Consensus on the Management of Complications of Cirrhosis of the Liver in Pediatrics to provide physicians with useful information for treating said complications. A group of pediatric gastroenterologists and experts in nutrition, nephrology, and infectious diseases participated and reviewed the medical literature. The Delphi method was applied to obtain the level of agreement on the statements that were formulated. The statements were sent to the participants to be analyzed and voted upon, after which they were discussed in virtual sessions, and the final versions were produced. The aim of the consensus results was to issue indications for the management of pediatric patients with liver cirrhosis, to prevent or control complications.
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Affiliation(s)
- J Flores-Calderón
- UMAE Hospital de Pediatría, CMN XXI Dr. Silvestre Frenk Freund IMSS, Cd, México, Mexico.
| | | | - J A Chávez-Barrera
- UMAE Hospital General CMN La Raza, Dr. Gaudencio González Garza IMSS, Cd, México, Mexico
| | | | | | | | | | | | | | - M P Sánchez-Soto
- Hospital de Especialidades del Niño y la mujer de Querétaro Dr. Felipe Núñez Lara, Querétaro, Mexico
| | | | - B González-Ortiz
- UMAE Hospital de Pediatría, CMN XXI Dr. Silvestre Frenk Freund IMSS, Cd, México, Mexico
| | - S Ledesma-Ramírez
- UMAE Hospital de Pediatría, CMN XXI Dr. Silvestre Frenk Freund IMSS, Cd, México, Mexico
| | - D Espinosa-Saavedra
- UMAE Hospital de Pediatría, CMN XXI Dr. Silvestre Frenk Freund IMSS, Cd, México, Mexico
| | | | - J Macías-Flores
- Hospital Infantil de Especialidades de Chihuahua, Chihuahua, Mexico
| | | | - E Hernández-Chávez
- UMAE Hospital de Pediatría Centro Médico de Occidente, IMSS, Guadalajara, Mexico
| | - J R Zárate-Guerrero
- UMAE Hospital de Pediatría Centro Médico de Occidente, IMSS, Guadalajara, Mexico
| | - G Gómez-Navarro
- UMAE Hospital de Pediatría Centro Médico de Occidente, IMSS, Guadalajara, Mexico
| | - L P Bilbao-Chávez
- UMAE Hospital General CMN La Raza, Dr. Gaudencio González Garza IMSS, Cd, México, Mexico
| | - M Sosa-Arce
- UMAE Hospital General CMN La Raza, Dr. Gaudencio González Garza IMSS, Cd, México, Mexico
| | - L E Flores-Fong
- Nuevo Hospital Civil de Guadalajara "Dr. Juan I. Menchaca", Guadalajara, Mexico
| | - J C Lona-Reyes
- Nuevo Hospital Civil de Guadalajara "Dr. Juan I. Menchaca", Guadalajara, Mexico
| | - E V Estrada-Arce
- Nuevo Hospital Civil de Guadalajara "Dr. Juan I. Menchaca", Guadalajara, Mexico
| | - R Aguila-Cano
- Nuevo Hospital Civil de Guadalajara "Dr. Juan I. Menchaca", Guadalajara, Mexico
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23
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Theel W, Boxma-de Klerk BM, Dirksmeier-Harinck F, van Rossum EFC, Kanhai DA, Apers J, van Dalen BM, de Knegt RJ, Holleboom AG, Tushuizen ME, Grobbee DE, Wiebolt J, Castro Cabezas M. Evaluation of nonalcoholic fatty liver disease (NAFLD) in severe obesity using noninvasive tests and imaging techniques. Obes Rev 2022; 23:e13481. [PMID: 35692179 DOI: 10.1111/obr.13481] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Revised: 05/25/2022] [Accepted: 05/26/2022] [Indexed: 12/15/2022]
Abstract
The prevalence of nonalcoholic fatty liver disease (NAFLD) and the more severe and inflammatory type, nonalcoholic steatohepatitis (NASH), is increasing rapidly. Especially in high-risk patients, that is those with obesity, metabolic syndrome, and type 2 diabetes mellitus, the prevalence of NAFLD can be as high as 80% while NASH may be present in 20% of these subjects. With the worldwide increase of obesity, it is most likely that these numbers will rise. Since advanced stages of NAFLD and NASH are strongly associated with morbidity and mortality-in particular, cardiovascular disease, liver cirrhosis, and hepatocellular carcinoma-it is of great importance to identify subjects at risk. A great variety of noninvasive tests has been published to diagnose NAFLD and NASH, especially using blood- and imaging-based tests. Liver biopsy remains the gold standard for NAFLD/NASH. This review aims to summarize the different mechanisms leading to NASH and liver fibrosis, the different noninvasive liver tests to diagnose and evaluate patients with severe obesity.
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Affiliation(s)
- Willy Theel
- Department of Internal Medicine, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands.,Obesity Center CGG, Rotterdam, The Netherlands
| | - Bianca M Boxma-de Klerk
- Department of Statistics and Education, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands
| | - Femme Dirksmeier-Harinck
- Department of Gastroenterology and Hepatology, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands
| | - Elisabeth F C van Rossum
- Obesity Center CGG, Rotterdam, The Netherlands.,Department of Internal Medicine, Division of Endocrinology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Danny A Kanhai
- Department of Pediatrics, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands
| | - Jan Apers
- Department of Bariatric Surgery, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands
| | - Bas M van Dalen
- Department of Cardiology, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands
| | - Robert J de Knegt
- Department of Gastroenterology and Hepatology, Erasmus Medical Centre, Rotterdam, The Netherlands
| | | | - Maarten E Tushuizen
- Department of Gastroenterology and Hepatology, Leiden UMC, Leiden, The Netherlands
| | - Diederick E Grobbee
- Julius Centre for Health Science and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.,Julius Clinical, Zeist, The Netherlands
| | - Janneke Wiebolt
- Department of Internal Medicine, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands.,Obesity Center CGG, Rotterdam, The Netherlands
| | - Manuel Castro Cabezas
- Department of Internal Medicine, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands.,Department of Internal Medicine, Division of Endocrinology, Erasmus University Medical Center, Rotterdam, The Netherlands.,Julius Clinical, Zeist, The Netherlands
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24
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Wang C, Pai AK, Putra J. Paediatric non-alcoholic fatty liver disease: an approach to pathological evaluation. J Clin Pathol 2022; 75:443-451. [PMID: 35414523 DOI: 10.1136/jclinpath-2022-208246] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 03/30/2022] [Indexed: 11/03/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is becoming an increasingly important healthcare issue along with the rising rates of obesity worldwide. It is the most common chronic liver disease in the paediatric population and the fastest growing indication for liver transplant in young adults. The pathogenesis is complex with contributions from multiple factors and genetic predisposition. While non-invasive laboratory tests and imaging modalities are being increasingly used, the liver biopsy continues to play a crucial role in the diagnosis and prognosis of NAFLD. Histologically, the assessment of paediatric fatty liver disease requires special considerations with respect to a periportal predominant pattern seen in prepubertal patients, as well as a different set of disease processes in the differential diagnosis. In this review, we provide a summary of current knowledge on the epidemiology, pathogenesis and clinical course of paediatric NAFLD as well as the clinical guidelines on diagnosis and management. We discuss the indications and limitations of liver biopsy, histological patterns seen in paediatric NAFLD, other entities to be considered in the differential diagnosis, and conclude with appropriate triaging of liver biopsies and essential elements of pathology reporting.
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Affiliation(s)
- Chiyun Wang
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York City, New York, USA
| | - Anita K Pai
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Juan Putra
- Department of Pathology, Boston Children's Hospital, Boston, Massachusetts, USA
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25
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Rose PC, Nel ED, Cotton MF, Pitcher RD, Otwombe K, Browne SH, Innes S. Prevalence and Risk Factors for Hepatic Steatosis in Children With Perinatal HIV on Early Antiretroviral Therapy Compared to HIV-Exposed Uninfected and HIV-Unexposed Children. Front Pediatr 2022; 10:893579. [PMID: 35757117 PMCID: PMC9218275 DOI: 10.3389/fped.2022.893579] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 05/13/2022] [Indexed: 11/13/2022] Open
Abstract
Objectives We evaluated the prevalence and risk factors for hepatic steatosis in South African children with perinatally acquired HIV (PHIV) who started treatment early and remain on long-term antiretroviral therapy (ART) compared to HIV-uninfected children. Design A cross-sectional study from April 2019 to October 2021. PHIV, HIV-exposed uninfected (HEU) and HIV-unexposed (HU) children were enrolled from an ongoing cohort study. Methods All children had transient elastography (TE) with controlled attenuation parameter (CAP). Liver enzymes, lipogram, insulin and glucose were sent after an overnight fast. Multivariable linear regression analyses identified predictors of CAP. Hepatic steatosis was defined as CAP>248kPa. Results 215 children (111 [52%] male; median age 14.1 years; IQR 12.7-14.9) participated in the study, 110 PHIV, 105 HIV-uninfected (36 HEU, 69 HU). PHIV initiated ART at a median age of 2.7 months (IQR 1.8-8.5). Hepatic steatosis prevalence was 9% in PHIV, 3% in HEU and 1% in HU children (p = 0.08). However, 8% of lean (body mass index z-score ≤ +1) PHIV had hepatic steatosis compared to zero lean HEU or HU children (p = 0.03). In multivariable linear regression analysis of all PHIV, body mass index (BMI) z-score was positively associated with CAP (p = 0.001) while CD4 count (p = 0.02) and duration of suppression of HIV viraemia (p = 0.009) were negatively associated with CAP, adjusting for age, sex and ethnicity. Conclusions Hepatic steatosis prevalence was higher in lean PHIV than lean HIV-uninfected South African children. Longer suppression of HIV viraemia and higher CD4 count were associated with lower CAP and might be protective factors for hepatic steatosis in PHIV children.
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Affiliation(s)
- Penelope C. Rose
- Department of Paediatrics and Child Health, Tygerberg Hospital and Stellenbosch University, Cape Town, South Africa
| | - Etienne D. Nel
- Department of Paediatrics and Child Health, Tygerberg Hospital and Stellenbosch University, Cape Town, South Africa
| | - Mark F. Cotton
- Department of Paediatrics and Child Health, Tygerberg Hospital and Stellenbosch University, Cape Town, South Africa
- Family Center for Research With Ubuntu (FAMCRU), Cape Town, South Africa
| | - Richard D. Pitcher
- Division of Radiodiagnosis, Department of Medical Imaging and Clinical Oncology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Kennedy Otwombe
- Perinatal HIV Research Unit, Chris Hani Baragwanath Academic Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Sara H. Browne
- Department of Medicine, University of California, San Diego, San Diego, CA, United States
| | - Steve Innes
- Department of Paediatrics and Child Health, Tygerberg Hospital and Stellenbosch University, Cape Town, South Africa
- Family Center for Research With Ubuntu (FAMCRU), Cape Town, South Africa
- Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa
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26
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Sivunen J, Karlberg S, Kivisaari R, Lohi J, Karlberg N, Jokinen E, Sarkola T, Jahnukainen T, Lipsanen‐Nyman M, Jalanko H. Liver pathology and biochemistry in patients with mutations in TRIM37 gene (Mulibrey nanism). Liver Int 2022; 42:1369-1378. [PMID: 35220664 PMCID: PMC9545472 DOI: 10.1111/liv.15213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 02/01/2022] [Accepted: 02/16/2022] [Indexed: 02/13/2023]
Abstract
BACKGROUND AND AIMS Mulibrey nanism (MUL) is a multiorgan disease caused by recessive mutations in the TRIM37 gene. Chronic heart failure and hepatopathy are major determinants of prognosis in MUL patients, which prompted us to study liver biochemistry and pathology in a national cohort of MUL patients. METHODS Clinical, laboratory and imaging data were collected in a cross-sectional survey and retrospectively from hospital records. Liver histology and immunohistochemistry for 10 biomarkers were assessed. RESULTS Twenty-one MUL patients (age 1-51 years) with tumour suspicion showed moderate congestion, steatosis and fibrosis in liver biopsies and marginally elevated levels of serum GGT, AST, ALT and AST to platelet ratio index (APRI) in 20%-66%. Similarly, GGT, AST, ALT and APRI levels were moderately elevated in 12%-69% of 17 MUL patients prior to pericardiectomy. In a cross-sectional evaluation of 36 MUL outpatients, GGT, total bilirubin and galactose half-life (Gal½) correlated with age (r = 0.45, p = .017; r = 0.512, p = .007; r = 0.44, p = .03 respectively). The frequency of clearly abnormal serum values of 15 parameters analysed, however, was low even in patients with signs of restrictive cardiomyopathy. Transient elastography (TE) of the liver revealed elevated levels in 50% of patients with signs of heart failure and TE levels correlated with several biochemistry parameters. Biomarkers of fibrosis, sinusoidal capillarization and hepatocyte metaplasia showed increased expression in autopsy liver samples from 15 MUL patients. CONCLUSION Liver disease in MUL patients was characterized by sinusoidal dilatation, steatosis and fibrosis with individual progression to cirrhosis and moderate association of histology with cardiac function, liver biochemistry and elastography.
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Affiliation(s)
- Johanna Sivunen
- Children´s Hospital, University of Helsinki and Helsinki University HospitalHelsinkiFinland
| | - Susann Karlberg
- Children´s Hospital, University of Helsinki and Helsinki University HospitalHelsinkiFinland,Folkhälsan Research CenterHelsinkiFinland
| | - Reetta Kivisaari
- Children´s Hospital, University of Helsinki and Helsinki University HospitalHelsinkiFinland,Department of Pediatric Radiology, HUS Medical Imaging CentreUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland
| | - Jouko Lohi
- Department of PathologyUniversity of HelsinkiHelsinkiFinland
| | - Niklas Karlberg
- Children´s Hospital, University of Helsinki and Helsinki University HospitalHelsinkiFinland
| | - Eero Jokinen
- Children´s Hospital, University of Helsinki and Helsinki University HospitalHelsinkiFinland
| | - Taisto Sarkola
- Children´s Hospital, University of Helsinki and Helsinki University HospitalHelsinkiFinland,Minerva Foundation Institute for Medical ResearchHelsinkiFinland
| | - Timo Jahnukainen
- Children´s Hospital, University of Helsinki and Helsinki University HospitalHelsinkiFinland
| | - Marita Lipsanen‐Nyman
- Children´s Hospital, University of Helsinki and Helsinki University HospitalHelsinkiFinland
| | - Hannu Jalanko
- Children´s Hospital, University of Helsinki and Helsinki University HospitalHelsinkiFinland
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27
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Rocque B, Zaldana A, Weaver C, Huang J, Barbetta A, Shakhin V, Goldbeck C, Yanni G, Zielsdorf S, Kwon Y, Etesami K, Genyk Y, Zhou S, Kohli R, Emamaullee J. Clinical Value of Surveillance Biopsies in Pediatric Liver Transplantation. Liver Transpl 2022; 28:843-854. [PMID: 34954868 PMCID: PMC9078451 DOI: 10.1002/lt.26399] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 12/10/2021] [Accepted: 12/15/2021] [Indexed: 02/07/2023]
Abstract
Although pediatric liver transplantation (LT) results in excellent long-term outcomes, a high incidence of early acute cellular rejection and late graft fibrosis persists. Routine measurement of allograft enzymes may not reliably detect rejection episodes, identify candidates for immunosuppression minimization, or indicate allograft fibrosis. Surveillance biopsies (SBs) can provide valuable information in this regard, but their role in pediatric LT is not fully established. A retrospective cohort of 236 pediatric LT recipients from a high-volume center was studied to characterize the risks and benefits of SB versus for-cause biopsies (FCBs). The study population was 47.1% male and 54.7% Hispanic, and 31% received living donor grafts. Our data suggest that patients in the SB group had better transplant outcomes (rejection-free, graft, and patient survival) compared with patients who had FCBs or who never underwent biopsy. Among 817 biopsies obtained from 236 patients, 150 (18.4%) were SBs. Only 6 patients had a biopsy-related complication, and none were observed in the SB subset. Graft biochemical blood tests did not accurately predict rejection severity on biopsy, with aspartate aminotransferase area under the receiver operating characteristic curve (AUROC) 0.66, alanine aminotransferase AUROC 0.65 (very poor predictions), and gamma-glutamyltransferase AUROC 0.58 (no prediction). SBs identified subclinical rejection in 18.6% of biopsies, whereas 63.3% of SBs had evidence of fibrosis. SBs prompted changes in immunosuppression including dose reduction. Our experience suggests that SB in pediatric LT is safe, offers valuable information about subclinical rejection episodes, and can guide management of immunosuppression, including minimization. Improved outcomes with SB were likely multifactorial, potentially relating to a more favorable early posttransplant course and possible effect of management optimization through SB. Further multicenter studies are needed to examine the role of SBs on long-term outcomes in pediatric LT.
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Affiliation(s)
- Brittany Rocque
- Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Southern California, Los Angeles, CA
| | - Aaron Zaldana
- Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Southern California, Los Angeles, CA
| | - Carly Weaver
- Division of Hepatobiliary and Abdominal Organ Transplantation Surgery, Children’s Hospital Los Angeles, Los Angeles, CA
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Children’s Hospital Los Angeles, Los Angeles, CA
| | - Julia Huang
- Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Southern California, Los Angeles, CA
| | - Arianna Barbetta
- Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Southern California, Los Angeles, CA
| | - Victoria Shakhin
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Children’s Hospital Los Angeles, Los Angeles, CA
| | - Cameron Goldbeck
- Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Southern California, Los Angeles, CA
| | - George Yanni
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Children’s Hospital Los Angeles, Los Angeles, CA
| | - Shannon Zielsdorf
- Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Southern California, Los Angeles, CA
- Division of Hepatobiliary and Abdominal Organ Transplantation Surgery, Children’s Hospital Los Angeles, Los Angeles, CA
| | - Yong Kwon
- Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Southern California, Los Angeles, CA
- Division of Hepatobiliary and Abdominal Organ Transplantation Surgery, Children’s Hospital Los Angeles, Los Angeles, CA
| | - Kambiz Etesami
- Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Southern California, Los Angeles, CA
- Division of Hepatobiliary and Abdominal Organ Transplantation Surgery, Children’s Hospital Los Angeles, Los Angeles, CA
| | - Yuri Genyk
- Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Southern California, Los Angeles, CA
- Division of Hepatobiliary and Abdominal Organ Transplantation Surgery, Children’s Hospital Los Angeles, Los Angeles, CA
| | - Shengmei Zhou
- Department of Pathology and Laboratory Medicine, Children’s Hospital Los Angeles, Los Angeles, CA
| | - Rohit Kohli
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Children’s Hospital Los Angeles, Los Angeles, CA
| | - Juliet Emamaullee
- Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Southern California, Los Angeles, CA
- Division of Hepatobiliary and Abdominal Organ Transplantation Surgery, Children’s Hospital Los Angeles, Los Angeles, CA
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28
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Cusi K, Isaacs S, Barb D, Basu R, Caprio S, Garvey WT, Kashyap S, Mechanick JI, Mouzaki M, Nadolsky K, Rinella ME, Vos MB, Younossi Z. American Association of Clinical Endocrinology Clinical Practice Guideline for the Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Primary Care and Endocrinology Clinical Settings: Co-Sponsored by the American Association for the Study of Liver Diseases (AASLD). Endocr Pract 2022; 28:528-562. [PMID: 35569886 DOI: 10.1016/j.eprac.2022.03.010] [Citation(s) in RCA: 550] [Impact Index Per Article: 183.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 03/11/2022] [Accepted: 03/11/2022] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To provide evidence-based recommendations regarding the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) to endocrinologists, primary care clinicians, health care professionals, and other stakeholders. METHODS The American Association of Clinical Endocrinology conducted literature searches for relevant articles published from January 1, 2010, to November 15, 2021. A task force of medical experts developed evidence-based guideline recommendations based on a review of clinical evidence, expertise, and informal consensus, according to established American Association of Clinical Endocrinology protocol for guideline development. RECOMMENDATION SUMMARY This guideline includes 34 evidence-based clinical practice recommendations for the diagnosis and management of persons with NAFLD and/or NASH and contains 385 citations that inform the evidence base. CONCLUSION NAFLD is a major public health problem that will only worsen in the future, as it is closely linked to the epidemics of obesity and type 2 diabetes mellitus. Given this link, endocrinologists and primary care physicians are in an ideal position to identify persons at risk on to prevent the development of cirrhosis and comorbidities. While no U.S. Food and Drug Administration-approved medications to treat NAFLD are currently available, management can include lifestyle changes that promote an energy deficit leading to weight loss; consideration of weight loss medications, particularly glucagon-like peptide-1 receptor agonists; and bariatric surgery, for persons who have obesity, as well as some diabetes medications, such as pioglitazone and glucagon-like peptide-1 receptor agonists, for those with type 2 diabetes mellitus and NASH. Management should also promote cardiometabolic health and reduce the increased cardiovascular risk associated with this complex disease.
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Affiliation(s)
- Kenneth Cusi
- Guideine and Algorithm Task Forces Co-Chair, Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida
| | - Scott Isaacs
- Guideline and Algorithm Task Forces Co-Chair, Division of Endocrinology, Emory University School of Medicine, Atlanta, Georgia
| | - Diana Barb
- University of Florida, Gainesville, Florida
| | - Rita Basu
- Division of Endocrinology, University of Virginia School of Medicine, Charlottesville, Virginia
| | - Sonia Caprio
- Yale University School of Medicine, New Haven, Connecticut
| | - W Timothy Garvey
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama
| | | | - Jeffrey I Mechanick
- The Marie-Josee and Henry R. Kravis Center for Cardiovascular Health at Mount Sinai Heart, Icahn School of Medicine at Mount Sinai
| | | | - Karl Nadolsky
- Michigan State University College of Human Medicine, Grand Rapids, Michigan
| | - Mary E Rinella
- AASLD Representative, University of Pritzker School of Medicine, Chicago, Illinois
| | - Miriam B Vos
- Center for Clinical and Translational Research, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, Georgia
| | - Zobair Younossi
- AASLD Representative, Inova Medicine, Inova Health System, Falls Church, Virginia
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29
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Tran LC, Ley D, Bourdon G, Coopman S, Lerisson H, Tillaux C, Béhal H, Gottrand F, Aumar M. Noninvasive Pediatric Liver Fibrosis Measurement: Two-Dimensional Shear Wave Elastography Compared With Transient Elastography. Front Pediatr 2022; 10:849815. [PMID: 35573968 PMCID: PMC9095976 DOI: 10.3389/fped.2022.849815] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Accepted: 03/10/2022] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVES Although transient elastography (TE) is the primary noninvasive method for assessing liver fibrosis, its use remains to be validated in children. This study aims to evaluate the agreement between two-dimensional ultrasound shear wave elastography (2D-SWE) and TE to assess pediatric liver stiffness method. METHODS During the 18-month study, we prospectively included 101 consecutive children (median age: 8.5 years, range: 1 month to 17 years) who required TE for medical reasons, and in whom 2D-SWE measurement was performed within a 3-month follow-up during a routine ultrasound. Liver elasticity values were classified according to the Metavir score using published pediatric norms for TE and according to the manufacturer's reference values for 2D-SWE. The Spearman's correlation coefficient was used to assess the relationship between the elasticity measured by the two techniques. Concordance was described by the Bland-Altman method. RESULTS A strong correlation (rho = 0.70, p < 0.001) was found between 2D-SWE and TE for the elasticity measures. The strength of correlation was higher among patients older than 6 years (rho = 0.79, p < 0.001). Concordance between liver fibrosis stages assessed by these techniques was moderate [weighted kappa = 0.46, (95% CI: 0.35-0.57)]. When considering stages over F2, 2D-SWE diagnostic performances showed a sensitivity of 85% (95% CI: 74-92) and a specificity of 57% (95% CI: 42-70) compared with TE. CONCLUSION Measurements of the liver stiffness using 2D-SWE and TE are strongly correlated. The moderate concordance between these techniques for assessing the liver fibrosis stage provides evidence against alternating between these methods during follow-up of patients with the chronic liver diseases.
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Affiliation(s)
- Léa Chantal Tran
- University of Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille, France
| | - Delphine Ley
- University of Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille, France.,Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, Jeanne de Flandre Children's Hospital, CHU Lille and University of Lille, Lille, France
| | - Gurvan Bourdon
- Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, Jeanne de Flandre Children's Hospital, CHU Lille and University of Lille, Lille, France
| | - Stéphanie Coopman
- Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, Jeanne de Flandre Children's Hospital, CHU Lille and University of Lille, Lille, France
| | - Héloïse Lerisson
- Department of Paediatric Imaging, Jeanne de Flandre Children's Hospital, CHU Lille, Lille, France
| | - Céline Tillaux
- Department of Paediatric Imaging, Jeanne de Flandre Children's Hospital, CHU Lille, Lille, France
| | - Hélène Béhal
- University of Lille, CHU Lille, ULR 2694 - METRICS: Évaluation des Technologies de Santé et des Pratiques Médicales, Lille, France
| | - Frédéric Gottrand
- University of Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille, France.,Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, Jeanne de Flandre Children's Hospital, CHU Lille and University of Lille, Lille, France
| | - Madeleine Aumar
- University of Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille, France.,Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, Jeanne de Flandre Children's Hospital, CHU Lille and University of Lille, Lille, France
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30
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Brunnert L, Puasa ID, Garten A, Penke M, Gaul S, Grafe N, Karlas T, Kiess W, Flemming G, Vogel M. Pediatric percentiles for transient elastography measurements - effects of age, sex, weight status and pubertal stage. Front Endocrinol (Lausanne) 2022; 13:1030809. [PMID: 36237190 PMCID: PMC9551398 DOI: 10.3389/fendo.2022.1030809] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 09/08/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND AND AIMS Transient Elastography is a non-invasive, cost-efficient, non-ionizing, observer-independent and reliable method to detect liver fibrosis using Liver Stiffness Measurement (LSM) and the degree of fat accumulation in the liver using Controlled Attenuation Parameter (CAP). This study aims to derive reference values for both measures from healthy children and adolescents. Further, we aim to assess the potential influence of age, sex, puberty, and BMI-SDS on CAP and LSM. METHODS Within the LIFE Child study, amongst others, anthropometric data and pubertal status were assessed. Transient Elastography (TE) was performed using the FibroScan® device in a population-based cohort at 982 study visits of 482 healthy children aged between 10 and 18 years. Percentiles for LSM and CAP were estimated, and the effects of age, sex, puberty and weight status were assessed through hierarchical regression models. RESULTS There was a strong age dependency for LSM with higher values for older children, most pronounced in the upper percentiles in boys. Contrarily, CAP was relatively stable across the age span without considerable difference between boys and girls. We found a significant positive correlation between BMI-SDS and both CAP and LSM for BMI-SDS >1.28. For BMI-SDS < 1.28, the association was also positive but reached statistical significance only for CAP. Further, the association between BMI-SDS and CAP was significantly stronger in younger than in older children. There was no association between pubertal status and CAP. For LSM, we found that children with a high BMI-SDS but not children with normal weight had significantly higher LSM values in Tanner stage 4. CONCLUSIONS Age, sex, pubertal status and weight status should be considered when interpreting LSM and CAP in pediatric patients to facilitate and improve early detection of abnormal liver function, which is associated with common pathologies, such as NAFLD.
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Affiliation(s)
- Lina Brunnert
- Center for Pediatric Research, University Hospital for Children and Adolescents, Leipzig, Germany
| | - Ika Damayanti Puasa
- Center for Pediatric Research, University Hospital for Children and Adolescents, Leipzig, Germany
| | - Antje Garten
- Center for Pediatric Research, University Hospital for Children and Adolescents, Leipzig, Germany
| | - Melanie Penke
- Center for Pediatric Research, University Hospital for Children and Adolescents, Leipzig, Germany
| | - Susanne Gaul
- Center for Pediatric Research, University Hospital for Children and Adolescents, Leipzig, Germany
- Clinic and Polyclinic for Cardiology, Leipzig University Medical Center, Leipzig, Germany
| | - Nico Grafe
- Leipzig Research Center for Civilization Diseases, LIFE Child, Leipzig, Germany
| | - Thomas Karlas
- Department of Medicine II, Division of Gastroenterology, Leipzig University Medical Center, Leipzig, Germany
| | - Wieland Kiess
- Center for Pediatric Research, University Hospital for Children and Adolescents, Leipzig, Germany
- Leipzig Research Center for Civilization Diseases, LIFE Child, Leipzig, Germany
| | - Gunter Flemming
- Center for Pediatric Research, University Hospital for Children and Adolescents, Leipzig, Germany
| | - Mandy Vogel
- Center for Pediatric Research, University Hospital for Children and Adolescents, Leipzig, Germany
- Leipzig Research Center for Civilization Diseases, LIFE Child, Leipzig, Germany
- *Correspondence: Mandy Vogel,
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31
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Chen BR, Pan CQ. Non-invasive assessment of fibrosis and steatosis in pediatric non-alcoholic fatty liver disease. Clin Res Hepatol Gastroenterol 2022; 46:101755. [PMID: 34311134 DOI: 10.1016/j.clinre.2021.101755] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Revised: 06/19/2021] [Accepted: 06/21/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Non-Alcoholic Fatty Liver Disease (NAFLD) has become one of the most common causes of chronic liver disease in the pediatric population. Recent advances have been made in developing non-invasive measures for NAFLD assessment. This review presents an analysis of these latest developments and also proposes an algorithm for screening pediatric patients at risk for NAFLD. METHODS A systematic literature search on PUBMED and EMBASE was conducted. Guidelines for clinical care of pediatric NAFLD were also reviewed. RESULTS In imaging tests, transient elastography (TE) combined with controlled attenuation parameter (CAP) is a promising, relatively low-cost method offering an intermediate level of accuracy on accessing patient's fibrosis and steatosis in a singular package. Liver biopsy remains the gold standard for diagnosis and/or evaluation of NAFLD, but with our proposed algorithm on utilizing non-invasive testing, the number of liver biopsies required could decrease. The current evidence supports the implementation of TE and CAP in an evaluation algorithm for pediatric NAFLD. CONCLUSIONS Current data support the use of TE and CAP as a first-line tool in the diagnosis and evaluation of adolescent NAFLD, to better stratify high-risk patients and cut down on the number of liver biopsies needed.
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Affiliation(s)
- Bryan R Chen
- University of California, Los Angeles, Los Angeles, CA 90025 USA.
| | - Calvin Q Pan
- Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; Division of Gastroenterology and Hepatology, Department of Medicine, NYU Langone Health, New York University Grossman School of Medicine, New York, NY, USA.
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32
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Enaud R, Frison E, Missonnier S, Fischer A, de Ledinghen V, Perez P, Bui S, Fayon M, Chateil JF, Lamireau T. Cystic fibrosis and noninvasive liver fibrosis assessment methods in children. Pediatr Res 2022; 91:223-229. [PMID: 33731812 DOI: 10.1038/s41390-021-01427-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 01/27/2021] [Accepted: 02/08/2021] [Indexed: 01/31/2023]
Abstract
BACKGROUND Noninvasive assessments of liver fibrosis are currently used to evaluate cystic fibrosis (CF)-related liver disease. However, there is scarce data regarding their repeatability and reproducibility, especially in children with CF. The present study aimed to evaluate the repeatability and reproducibility of transient elastography (TE) (FibroScan®) and point shear-wave elastography using virtual touch quantification (pSWE VTQ) in children with CF. METHODS TE and pSWE VTQ were performed in 56 children with CF by two different operators. Analysis of repeatability and reproducibility was available in 33 patients for TE and 46 patients for pSWE VTQ. Intra- and interobserver agreement were assessed using the intraclass correlation coefficient (ICC) and their 95% confidence interval (CI), and Bland and Altman graphs. RESULTS For TE, ICC was 0.91 (0.83-0.95) for intraobserver agreement and 0.92 (95% CI: 0.86-0.96) for interobserver agreement. For pSWE VTQ, ICC was 0.83 (0.72-0.90) for intraobserver agreement and 0.67 (0.48-0.80) for interobserver agreement. CONCLUSIONS Both technics can be proposed in the follow-up of patients, according to their availability in CF centers. IMPACT This study shows that TE and pSWE VTQ are reliable methods to evaluate liver fibrosis in children with CF. This study shows for the first time that TE and pSWE VTQ are both repeatable and reproducible in children with CF. These data indicate that both TE and pSWE VTQ can be proposed for the follow-up of patients with CF, according to their availability in each CF center.
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Affiliation(s)
- Raphael Enaud
- Pediatric Hepatology and Gastroenterology Unit, Bordeaux University Hospital, Pellegrin-Enfants Hospital, Bordeaux, France.,Bordeaux University Hospital, Pellegrin-Enfants Hospital, Pediatric Cystic Fibrosis-Center (CRCM), Bordeaux, France.,INSERM, Centre de Recherche Cardio-thoracique de Bordeaux (U1045), University of Bordeaux, Bordeaux, France
| | - Eric Frison
- Unité de soutien méthodologique à la recherche clinique et épidémiologique, Service d'information médicale, Pôle Santé Publique, Bordeaux University Hospital, Bordeaux, France.,Clinical Investigation Centre (CIC 1401), Bordeaux University Hospital, Bordeaux, France
| | - Sophie Missonnier
- Pediatric Imaging Unit, Bordeaux University Hospital, Pellegrin-Enfants Hospital, Bordeaux, France
| | - Aude Fischer
- Pediatric Hepatology and Gastroenterology Unit, Bordeaux University Hospital, Pellegrin-Enfants Hospital, Bordeaux, France
| | - Victor de Ledinghen
- Hepatology Unit, Bordeaux University Hospital, Haut-Lévêque Hospital, Pessac, France
| | - Paul Perez
- Unité de soutien méthodologique à la recherche clinique et épidémiologique, Service d'information médicale, Pôle Santé Publique, Bordeaux University Hospital, Bordeaux, France.,Clinical Investigation Centre (CIC 1401), Bordeaux University Hospital, Bordeaux, France
| | - Stéphanie Bui
- Bordeaux University Hospital, Pellegrin-Enfants Hospital, Pediatric Cystic Fibrosis-Center (CRCM), Bordeaux, France
| | - Michael Fayon
- Bordeaux University Hospital, Pellegrin-Enfants Hospital, Pediatric Cystic Fibrosis-Center (CRCM), Bordeaux, France.,INSERM, Centre de Recherche Cardio-thoracique de Bordeaux (U1045), University of Bordeaux, Bordeaux, France.,Clinical Investigation Centre (CIC 1401), Bordeaux University Hospital, Bordeaux, France
| | - Jean-François Chateil
- Pediatric Imaging Unit, Bordeaux University Hospital, Pellegrin-Enfants Hospital, Bordeaux, France.,CRMSB (UMR 5536), University of Bordeaux/CNRS, Bordeaux, France
| | - Thierry Lamireau
- Pediatric Hepatology and Gastroenterology Unit, Bordeaux University Hospital, Pellegrin-Enfants Hospital, Bordeaux, France. .,Clinical Investigation Centre (CIC 1401), Bordeaux University Hospital, Bordeaux, France.
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Metabolic Associated Fatty Liver Disease in Children-From Atomistic to Holistic. Biomedicines 2021; 9:biomedicines9121866. [PMID: 34944682 PMCID: PMC8698557 DOI: 10.3390/biomedicines9121866] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 12/06/2021] [Accepted: 12/07/2021] [Indexed: 12/12/2022] Open
Abstract
Non-alcoholic fatty liver disease has become the most common chronic liver disease in children due to the alarmingly increasing incidence of pediatric obesity. It is well-documented that MAFLD prevalence is directly related to an incremental increase in BMI. The multiple hits theory was designed for providing insights regarding the pathogenesis of steatohepatitis and fibrosis in MAFLD. Recent evidence suggested that the microbiome is a crucial contributor in the pathogenesis of MAFLD. Aside from obesity, the most common risk factors for pediatric MAFLD include male gender, low-birth weight, family history of obesity, MAFLD, insulin resistance, type 2 diabetes mellitus, obstructive sleep apnea, and polycystic ovarium syndrome. Usually, pediatric patients with MAFLD have nonspecific symptoms consisting of fatigue, malaise, or diffuse abdominal pain. A wide spectrum of biomarkers was proposed for the diagnosis of MAFLD and NASH, as well as for quantifying the degree of fibrosis, but liver biopsy remains the key diagnostic and staging tool. Nevertheless, elastography-based methods present promising results in this age group as potential non-invasive replacers for liver biopsy. Despite the lack of current guidelines regarding MAFLD treatment in children, lifestyle intervention was proven to be crucial in the management of these patients.
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Güngörer V, Öztürk M, Özlü MY, Arslan Ş. What is the impact of methotrexate on liver in patients with juvenile idiopathic arthritis? Results of liver SWE performed in a single centre. Mod Rheumatol 2021; 32:776-782. [PMID: 34918139 DOI: 10.1093/mr/roab064] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 06/02/2021] [Accepted: 08/12/2021] [Indexed: 12/22/2022]
Abstract
OBJECTIVES Long-term therapy with low-dose methotrexate (MTX) is widely used in treatment of rheumatic diseases, in children. The purpose of this study was to evaluate liver elasticity in patients with juvenile idiopathic arthritis (JIA) who received MTX and compare the results with control group. METHODS Liver elasticity was evaluated with shear wave elastography (SWE) technique in 25 patients aged 3-17 years who were followed up with JIA and received MTX and compared with 25 healthy controls of the same age and weight. Factors that had an effect on liver elasticity were examined. RESULTS The mean SWE value of patients was 2.64 ± 2.13 m/s and 24.10 ± 18.50 kPa, whereas 1.83 ± 0.16 m/s and 10.09 ± 1.83 kPa in control group. There was a significant difference in liver elasticity in the patient and control groups. When the patients were evaluated as Group 1 (< 1000 mg) and Group 2 (≥ 1000 mg) according to the cumulative MTX dose, no significant difference was obtained. There was positive correlation between liver elasticity and weekly MTX dose and age. CONCLUSIONS Our study revealed that liver elasticity significantly decreased in patients who received MTX when compared with the control group. The elastography technique will be understood better over time and used safely in many areas.
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Affiliation(s)
- Vildan Güngörer
- Department of Pediatric Rheumatology, Selcuk University Faculty of Medicine, Konya, Turkey
| | - Mehmet Öztürk
- Department of Radiology, Selcuk University Faculty of Medicine, Konya, Turkey
| | - Mustafa Yasir Özlü
- Department of Radiology, Selcuk University Faculty of Medicine, Konya, Turkey
| | - Şükrü Arslan
- Department of Pediatric Rheumatology, Selcuk University Faculty of Medicine, Konya, Turkey
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Xu Z, Zhao J, Liu J, Dong Y, Wang F, Yan J, Cao L, Wang P, Li A, Li J, Zhu S, Zhong Y, Zhang M, Wang FS. Assessment of liver fibrosis by transient elastography in young children with chronic hepatitis B virus infection. Hepatol Int 2021; 15:602-610. [PMID: 34240319 PMCID: PMC8286936 DOI: 10.1007/s12072-021-10194-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 04/17/2021] [Indexed: 12/13/2022]
Abstract
Background This study aimed to compare the diagnostic accuracy of transient elastography (TE) and biopsy for the detection of liver fibrosis in children with chronic hepatitis B (CHB). Methods This single-center prospective study included 157 CHB children aged 0–6 years. All patients underwent liver stiffness measurement (LSM) by TE and liver biopsy, separated by an interval of less than 1 week. Results The LSM, aspartate aminotransferase-platelet ratio index (APRI), and fibrosis-4 index (FIB-4) were positively correlated with activity grade and fibrosis stage in CHB children. The areas under the receiver operating characteristic curves (AUCs) of LSM for identifying significant (F ≥ 2) and advanced (F ≥ 3) fibrosis were 0.732 and 0.941, respectively. The cut-off values, specificity, and sensitivity for significant fibrosis were 5.6 kPa, 75.7%, and 67.4%, respectively; the corresponding values for advanced fibrosis were 6.9 kPa, 91.5%, and 81.3%, respectively. Compared to LSM, the overall diagnostic performances of APRI and FIB-4 for significant and advanced fibrosis were suboptimal, with low AUCs and sensitivity. Since LSM, platelet, and Log10 (hepatitis B surface antigen) were independent factors associated with the fibrosis stage (F < 2 and F ≥ 2), they were used to formulate the “LPS” index for the prediction of F ≥ 2. The AUC of LPS (for F ≥ 2) was higher than that of LSM (0.792 vs. 0.732, p < 0.05), and had an improved sensitivity (76.6% vs. 67.4%). Conclusions TE is a promising technology for the diagnosis of advanced fibrosis in CHB children aged 0–6 years. Supplementary Information The online version contains supplementary material available at 10.1007/s12072-021-10194-7.
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Affiliation(s)
- Zhiqiang Xu
- Medical School of Chinese PLA, Beijing, China.,Department of Liver Disease of Chinese, Fifth Medical Center of Chinese, PLA General Hospital, PLA General Hospital, Beijing, China
| | - Jinfang Zhao
- Treatment and Research Center for Infectious Diseases, Fifth Medical Center of Chinese, PLA General Hospital, 100 Western 4th Ring Road, Beijing, 100039, China
| | - Jiaye Liu
- Treatment and Research Center for Infectious Diseases, Fifth Medical Center of Chinese, PLA General Hospital, 100 Western 4th Ring Road, Beijing, 100039, China
| | - Yi Dong
- Department of Liver Disease of Chinese, Fifth Medical Center of Chinese, PLA General Hospital, PLA General Hospital, Beijing, China
| | - Fuchuan Wang
- Department of Liver Disease of Chinese, Fifth Medical Center of Chinese, PLA General Hospital, PLA General Hospital, Beijing, China
| | - Jianguo Yan
- Department of Liver Disease of Chinese, Fifth Medical Center of Chinese, PLA General Hospital, PLA General Hospital, Beijing, China
| | - Lili Cao
- Department of Liver Disease of Chinese, Fifth Medical Center of Chinese, PLA General Hospital, PLA General Hospital, Beijing, China
| | - Pu Wang
- Department of Liver Disease of Chinese, Fifth Medical Center of Chinese, PLA General Hospital, PLA General Hospital, Beijing, China
| | - Aiqin Li
- Department of Liver Disease of Chinese, Fifth Medical Center of Chinese, PLA General Hospital, PLA General Hospital, Beijing, China
| | - Jing Li
- Treatment and Research Center for Infectious Diseases, Fifth Medical Center of Chinese, PLA General Hospital, 100 Western 4th Ring Road, Beijing, 100039, China
| | - Shishu Zhu
- Department of Liver Disease of Chinese, Fifth Medical Center of Chinese, PLA General Hospital, PLA General Hospital, Beijing, China
| | - Yanwei Zhong
- Department of Liver Disease of Chinese, Fifth Medical Center of Chinese, PLA General Hospital, PLA General Hospital, Beijing, China
| | - Min Zhang
- Department of Liver Disease of Chinese, Fifth Medical Center of Chinese, PLA General Hospital, PLA General Hospital, Beijing, China.
| | - Fu-Sheng Wang
- Medical School of Chinese PLA, Beijing, China. .,Treatment and Research Center for Infectious Diseases, Fifth Medical Center of Chinese, PLA General Hospital, 100 Western 4th Ring Road, Beijing, 100039, China.
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Galina P, Alexopoulou E, Mentessidou A, Mirilas P, Zellos A, Lykopoulou L, Patereli A, Salpasaranis K, Kelekis NL, Zarifi M. Diagnostic accuracy of two-dimensional shear wave elastography in detecting hepatic fibrosis in children with autoimmune hepatitis, biliary atresia and other chronic liver diseases. Pediatr Radiol 2021; 51:1358-1368. [PMID: 33755748 DOI: 10.1007/s00247-020-04959-9] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 09/13/2020] [Accepted: 12/22/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Although fibrosis is the main determinant of liver stiffness, other disease-related factors usually disregarded in studies on liver elastography, such as inflammation and cholestasis, may influence liver stiffness. OBJECTIVE To evaluate the accuracy of two-dimensional (2-D) shear wave elastography in assessing liver fibrosis in children with chronic liver disease by controlling for the confounding role of several disease- and patient-related factors. MATERIALS AND METHODS Three disease groups were studied: 1) various chronic liver diseases, 2) autoimmune hepatitis and 3) biliary atresia. The METAVIR (meta-analysis of histological data in viral hepatitis) score was used for fibrosis staging and grading of necroinflammatory activity. Multiple linear regression was used to evaluate the relationship between liver stiffness measurements and disease-related factors. The diagnostic accuracy of elastography for predicting fibrosis stages was assessed by calculating the area under the receiver operating characteristic curves. RESULTS The various chronic liver diseases group (n=32; 7.1±4.9 [mean±standard deviation] years) showed liver stiffness of 8.9±5.0 (mean±standard deviation) kPa, the autoimmune hepatitis group (n=33; 8.1±4.4 years) of 7.1±2.7 kPa, and the biliary atresia group (n=19; 0.2±0.1 years) of 19.7±15.2 kPa. Liver stiffness measurements differed across METAVIR fibrosis categories in all disease groups. The highest values were found in biliary atresia, at fibrosis stages ≥F2 (F2: 12.4±1.6 kPa, F3: 17.8±2 kPa, F4: 41.5±12.4 kPa). Liver stiffness was strongly associated only with fibrosis (P<0.0001) in various chronic liver diseases, but with necroinflammatory activity (P<0.0001) and fibrosis (P=0.002) in autoimmune hepatitis, and with age (P<0.0001), fibrosis (P<0.0001) and cholestasis (P=0.009) in biliary atresia. Optimal cutoffs for detecting advanced fibrosis (≥F3) were 16 kPa (area under curve: 0.98; sensitivity: 87.5%; specificity: 96.7%) in biliary atresia and 8.7 kPa (area under curve: 0.98; sensitivity: 93.8%; specificity: 96.1%) in other chronic liver diseases. CONCLUSION Two-dimensional shear wave elastography is reliable in assessing liver fibrosis in children with chronic liver diseases.
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Affiliation(s)
- Paraskevi Galina
- Department of Radiology, Aghia Sofia General Children's Hospital, Thivon St. & Papadiamantopoulou St., Goudi, 115 27, Athens, Greece. .,2nd Department of Radiology, General University Hospital Attikon, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
| | - Efthymia Alexopoulou
- 2nd Department of Radiology, General University Hospital Attikon, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Anastasia Mentessidou
- Department of Pediatric Surgery, Aghia Sofia General Children's Hospital, Athens, Greece
| | - Petros Mirilas
- Department of Pediatric Surgery, Aghia Sofia General Children's Hospital, Athens, Greece
| | - Aglaia Zellos
- 1st Department of Pediatrics, Aghia Sofia General Children's Hospital, Athens, Greece
| | - Lilia Lykopoulou
- 1st Department of Pediatrics, Aghia Sofia General Children's Hospital, Athens, Greece
| | - Amalia Patereli
- Department of Pathology, Aghia Sofia General Children's Hospital, Athens, Greece
| | | | - Nikolaos L Kelekis
- 2nd Department of Radiology, General University Hospital Attikon, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria Zarifi
- Department of Radiology, Aghia Sofia General Children's Hospital, Thivon St. & Papadiamantopoulou St., Goudi, 115 27, Athens, Greece
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Fahmy DM, Shokeir M, El Zeiny SM, Jonas MM, Abdallah A. Changes in Liver Stiffness and Noninvasive Fibrosis Scores in Egyptian Adolescents Successfully Treated with Ledipasvir-Sofosbuvir for Chronic Hepatitis C Virus Infection. J Pediatr 2021; 231:110-116. [PMID: 33347957 DOI: 10.1016/j.jpeds.2020.12.031] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 11/22/2020] [Accepted: 12/14/2020] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To assess changes in noninvasive liver fibrosis measurements after chronic hepatitis C eradication by direct-acting antivirals in Egyptian adolescents. STUDY DESIGN Liver stiffness measurement (LSM), by vibration-controlled transient elastography and noninvasive fibrosis scores (Firbosis-4, aspartate aminotransferase-platelet ratio index), was obtained before and 12 months after eradication with ledipasvir-sofosbuvir. The primary outcome was a more than 30% decrease in LSM with resulting fibrosis stage regression for initial fibrosis of F2 or higher and nonprogression of F0-F1, using the Ishak score (F0-F6). The secondary outcome was change in noninvasive fibrosis scores after treatment. RESULTS Analyzing 85 patients, the median baseline LSM was 5.8 (IQR, 4.2-6.5) and at follow-up 5.1 kPa (IQR, 4-6 kPa) (P = .045); 62 (73%) met the primary outcome, 16 patients (19%) experienced regression, and 46 (54%) nonprogression of LSM. Of 18 with initial fibrosis of F2 0r higher, 13 regressed to F0-F1 and 2 from F6 to F5, 1 unchanged at F3, and 1 increased to F3 and 1 to F4. Among 67 patients with a baseline fibrosis of F0-F1, 62 were unchanged and 5 increased-4 to F2 and 1 to F3. Although 23 (27%) had a more than 30% LSM increase, only 7 (8%), with associated comorbidities (4 β-thalassemia, 3 hepatic steatosis), had increased fibrosis stage. The median baseline FIB-4 and aspartate aminotransferase-platelet ratio index scores were 0.34 (IQR, 0.22-0.47) and 0.35 (0.24-0.57), and at follow-up 0.3 (IQR, 0.22-0.34) and 0.2 (0.18-2.8) (P < .001, <.001), respectively. CONCLUSIONS Chronic hepatitis C eradication by direct-acting antiviral agents in Egyptian adolescents was associated with nonprogression or regression of liver fibrosis, by noninvasive fibrosis measurements, at 12 months after treatment in the majority of cases.
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Affiliation(s)
- Doaa M Fahmy
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, Egypt; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, MA.
| | - Mohamed Shokeir
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Sherine M El Zeiny
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Maureen M Jonas
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, MA
| | - Ahmed Abdallah
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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Performance Characteristics, Intra- and Inter-operator Agreement of Transient Elastography in Pediatric Nonalcoholic Fatty Liver Disease. J Pediatr Gastroenterol Nutr 2021; 72:430-435. [PMID: 33230078 DOI: 10.1097/mpg.0000000000002991] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Transient elastography (TE) is a valuable tool in assessment of hepatic steatosis and fibrosis using liver stiffness measurement (LSM) and controlled attenuation parameter (CAP), respectively. Although widely used in adults, little is known about performance characteristics and reproducibility of TE (using Fibroscan device) in evaluation of pediatric nonalcoholic fatty liver disease (NAFLD). METHODS We prospectively recruited children with NAFLD. Three consecutive Fibroscan examinations were performed during the same visit-twice by a single expert operator and once by a different novice operator. Intra and inter-operator agreement was calculated using concordance correlation coefficient (CCC). Failure was defined as inability to obtain 10 valid measurements and examination was considered unreliable if LSM interquartile range/median was greater 30%. RESULTS Fifty-one children (34 boys; median age 15 years) were recruited. Failure rates for expert and novice operator were 10% (5/51) and 12% (6/51) while unreliable readings were obtained in 2% (1/46) and 4% (2/45) of patients, respectively. Patients with failed/unreliable measurements were significantly more obese (median BMI 46.2 vs 33.1 kg/m2, P = 0.002) compared with those with reliable measurements. The intra-operator agreement was almost perfect for LSM and substantial for CAP values (CCC = 0.85 and 0.73, respectively). Inter-operator agreement was substantial for LSM and moderate for CAP values (CCC = 0.76 and 0.58, respectively). The inter-operator agreement in LSM did not vary significantly over time but showed an inverse correlation with BMI and CAP. CONCLUSION Our study demonstrated that use of TE in assessment of hepatic fibrosis and steatosis in children with NAFLD is highly reliable with low failure rate and highly reproducible with high intra- and inter-operator reproducibility.
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Motamed F, Heidari G, Heirati B, Rahmani P. Diagnostic Performance of Noninvasive Methods for Liver Biopsy by Fibroscan in Pediatric. JOURNAL OF CHILD SCIENCE 2021. [DOI: 10.1055/s-0041-1725079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
AbstractLiver biopsy is the gold standard for the diagnosis and management of various liver diseases; however, noninvasive diagnostic modalities may help prevent adverse effects of anesthesia, prolonged hospitalization, sampling error, and other serious complications, particularly in pediatric patients. The aim of this study is to compare the results of liver biopsy and fibroscan in children with chronic liver diseases. All patients presenting chronic liver disease admitted in the ward or clinic of Tehran's Children Medical Center were enrolled in the study. Required laboratory tests were performed to diagnose the disease, followed by elastography using fibroscan 402 (M-probe) Echosens machine and liver biopsy using Menghini technique. Samples were scored by using METAVIR scoring system. Thirty-two patients were reported (68.8%, female) with autoimmune hepatitis (18.8%), Wilson disease (12.5%), and glycogen storage disease (12.5%). The most common pathologic stage and fibroscan result was stage III and F0 (46.9%), respectively. Association between pathology and fibroscan results was not significant. Nonetheless, age and diagnosis, age and Fibroscan score, and pathology and liver function test were significantly associated with each other. Fibroscan cannot be used as an alternative to liver biopsy; however, it can be a useful accessory tool.
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Affiliation(s)
- Farzaneh Motamed
- Pediatric Gastroenterology and Hepatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Ghobad Heidari
- Department of Pediatric, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Bita Heirati
- Department of Pediatric, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Parisa Rahmani
- Pediatric Gastroenterology and Hepatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
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Woolfson JP, Schreiber RA, Raveendran S, Chilvers M, Barker C, Guttman OR. Role of transient elastography and APRI in the assessment of pediatric cystic fibrosis liver disease. CANADIAN LIVER JOURNAL 2021; 4:23-32. [PMID: 35991474 PMCID: PMC9203161 DOI: 10.3138/canlivj-2020-0008] [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: 04/16/2020] [Accepted: 07/05/2020] [Indexed: 08/31/2024]
Abstract
Background Diagnosis and monitoring of cystic fibrosis liver disease (CFLD) is challenging. Transient elastography (TE) is a rapid, non-invasive method for assessing liver fibrosis. Its role in detecting fibrosis in CFLD has only begun to be explored. The aspartate aminotransferase to platelet ratio index (APRI) has been validated as a predictor of hepatic fibrosis in other chronic liver diseases. The purpose of this study was to assess the utility of APRI and TE in identifying liver fibrosis in pediatric CF patients. Methods Patients aged 2-18 years were recruited from the British Columbia Children's Hospital CF clinic. Patients were determined to have CFLD using standard criteria. Charts were reviewed, and each patient underwent TE. Results Of the 55 patients included in the study (50.9% male, mean age 11.6 y), 22 (40%) had CFLD. All mean liver enzymes were higher in the CFLD group, notably alanine transaminase (p = 0.031). Mean liver stiffness (LS) and APRI were also higher in the CFLD group (LS: 5.9 versus 4.5 kPa, p = 0.015; APRI: 0.40 versus 0.32, p = 0.119). Linear regression showed a mild positive association between the two (r 2 = 0.386). Conclusions TE values were higher among CFLD patients and correlated with APRI values, suggesting that these tools may have clinical applications for identifying and following this population. Further research is needed on a larger scale to determine the relative value and clinical utility of TE and APRI among patients with CFLD.
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Affiliation(s)
- Jessica P Woolfson
- Division of Gastroenterology, Hepatology and Nutrition, British Columbia Children’s Hospital, Vancouver, British Columbia, Canada
- University of British Columbia, Vancouver, British Columbia, Canada
| | - Richard A Schreiber
- Division of Gastroenterology, Hepatology and Nutrition, British Columbia Children’s Hospital, Vancouver, British Columbia, Canada
- University of British Columbia, Vancouver, British Columbia, Canada
| | | | - Mark Chilvers
- University of British Columbia, Vancouver, British Columbia, Canada
- Division of Respiratory Medicine, British Columbia Children’s Hospital, Vancouver, British Columbia, Canada
| | - Collin Barker
- Division of Gastroenterology, Hepatology and Nutrition, British Columbia Children’s Hospital, Vancouver, British Columbia, Canada
- University of British Columbia, Vancouver, British Columbia, Canada
| | - Orlee R Guttman
- Division of Gastroenterology, Hepatology and Nutrition, British Columbia Children’s Hospital, Vancouver, British Columbia, Canada
- University of British Columbia, Vancouver, British Columbia, Canada
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Suri A, Song E, van Nispen J, Voigt M, Armstrong A, Murali V, Jain A. Advances in the Epidemiology, Diagnosis, and Management of Pediatric Fatty Liver Disease. Clin Ther 2021; 43:438-454. [PMID: 33597074 DOI: 10.1016/j.clinthera.2021.01.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 12/28/2020] [Accepted: 01/04/2021] [Indexed: 02/07/2023]
Abstract
PURPOSE Nonalcoholic fatty liver (NAFL) is a major contributor to pediatric liver disease. This review evaluated the current literature on prevalence, screening, diagnosis, and management of NAFL in children and explored recent advances in the field of pediatric NAFL. METHODS A PubMed search was performed for manuscripts describing disease burden, diagnosis, and management strategies in pediatric NAFL published within the past 15 years. Systematic reviews, clinical practice guidelines, randomized controlled trials, and cohort and case-control studies were reviewed for the purpose of this article. FINDINGS The prevalence of NAFL in children is increasing. It is a leading cause of liver-related morbidity and mortality in children. Screening and diagnosis of NAFL in children are a challenge. Lifestyle changes and exercise are the cornerstones of the management of NAFL. IMPLICATIONS Further research is needed to develop better screening and diagnostic tools for pediatric NAFL, including noninvasive diagnostics. NAFL therapeutics is another area of much-needed, ongoing research.
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Affiliation(s)
- Anandini Suri
- Department of Pediatrics, School of Medicine, St. Louis University, St. Louis, Missouri, USA.
| | - Eric Song
- Department of Pediatrics, School of Medicine, St. Louis University, St. Louis, Missouri, USA
| | - Johan van Nispen
- Department of Pediatrics, School of Medicine, St. Louis University, St. Louis, Missouri, USA
| | - Marcus Voigt
- Department of Pediatrics, School of Medicine, St. Louis University, St. Louis, Missouri, USA
| | - Austin Armstrong
- Department of Pediatrics, School of Medicine, St. Louis University, St. Louis, Missouri, USA
| | - Vidul Murali
- Department of Pediatrics, School of Medicine, St. Louis University, St. Louis, Missouri, USA
| | - Ajay Jain
- Department of Pediatrics, School of Medicine, St. Louis University, St. Louis, Missouri, USA
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Pokorska-Śpiewak M, Dobrzeniecka A, Lipińska M, Tomasik A, Aniszewska M, Marczyńska M. Liver Fibrosis Evaluated With Transient Elastography in 35 Children With Chronic Hepatitis C Virus Infection. Pediatr Infect Dis J 2021; 40:103-108. [PMID: 33021594 DOI: 10.1097/inf.0000000000002913] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The aim of this prospective study was to analyze liver fibrosis in teenagers with chronic hepatitis C (CHC) using noninvasive methods. METHODS Thirty-five patients with CHC, 12-17 years of age (mean 14.2 ± 1.8 years; 22/35, 63% male) were included. Most of them (29/35, 83%) were infected vertically, 21/35 (60%) were treatment-naive, 30/35 (86%) were infected with genotype 1 and 5/35 (14%) were infected with genotype 4 HCV. In all patients, evaluation of liver fibrosis was performed using transient elastography (TE) and measurement of the following serum biomarkers: aspartate transaminase-to-platelet ratio index (APRI) and Fibrosis-4 index (FIB-4). Using liver stiffness measurement (LSM) results as a reference, the diagnostic performance of APRI and FIB-4 was assessed by calculating area under the receiver operating characteristics curve. RESULTS Transient elastography results revealed no or mild fibrosis (F0/1 in METAVIR scale) in 31/35 (89%) patients. In 4/35 (11%) patients, significant fibrosis was observed (F ≥ 2), including 3/35 (9%) with cirrhosis (F4). The median APRI was 0.32, and the median FIB-4 was 0.32. LSM was associated with both APRI and FIB-4 [r = 0.61, 95% confidence interval (CI) 0.35-0.79, P = 0.0001; and r = 0.60, 95% CI 0.32-0.78, P = 0.0002, respectively]. For the diagnosis of significant fibrosis, the area under the receiver operating characteristics (95% CI) for both APRI and FIB-4 was 0.855 (0.695-0.951). APRI, with a cutoff >0.374, predicted significant fibrosis, with 100% sensitivity and 67.7% specificity, whereas FIB-4, with a cutoff >0.402, predicted significant fibrosis, with 75.0% sensitivity and 90.3% specificity. CONCLUSIONS Significant fibrosis, including cirrhosis, may occur in teenagers with CHC. Serum biomarkers (APRI, FIB-4) correlate positively with LSM.
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Affiliation(s)
- Maria Pokorska-Śpiewak
- From the Department of Children's Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
- Pediatric Infectious Diseases Unit, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
| | - Anna Dobrzeniecka
- Pediatric Infectious Diseases Unit, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
| | - Marta Lipińska
- From the Department of Children's Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
- Pediatric Infectious Diseases Unit, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
| | - Anna Tomasik
- From the Department of Children's Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
- Pediatric Infectious Diseases Unit, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
| | - Małgorzata Aniszewska
- From the Department of Children's Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
- Pediatric Infectious Diseases Unit, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
| | - Magdalena Marczyńska
- From the Department of Children's Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
- Pediatric Infectious Diseases Unit, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
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Ciardullo S, Monti T, Perseghin G. Prevalence of Liver Steatosis and Fibrosis Detected by Transient Elastography in Adolescents in the 2017-2018 National Health and Nutrition Examination Survey. Clin Gastroenterol Hepatol 2021; 19:384-390.e1. [PMID: 32623006 DOI: 10.1016/j.cgh.2020.06.048] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 06/19/2020] [Accepted: 06/23/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Metabolic-associated fatty liver disease (MAFLD) is common among adolescents, but the prevalence of significant fibrosis in this age group is not known. We aimed to estimate the prevalence of MAFLD and significant (≥F2) fibrosis by transient elastography (TE) in adolescents in the United States. METHODS We analyzed TE data from participants 12-18 years old included in the National Health and Nutrition Examination Survey 2017-2018 (data available from 867 adolescents). Steatosis was evaluated by the median controlled attenuation parameter (CAP) and fibrosis by median liver stiffness measurement. RESULTS Two-hundred forty participants (24.16%; 95% CI, 21.07-27.24) had any degree of steatosis (CAP≥248 dBm), 123 participants (11.6%; 95% CI, 9.19-14.06) had S3 steatosis (CAP≥280 dBm), and 51 participants (4.4%; 95% CI, 2.51-6.33) had significant fibrosis (liver stiffness ≥7.4 kPa). Multivariate analyses revealed that body mass index (odds ratio [OR] per unit increase, 1.2; 95% CI, 1.2-1.4), sex (OR female vs male participants , 0.5; 95% CI, 0.4-0.7), ethnicity (OR, Hispanic vs non-Hispanic white, 4.5; 95% CI, 1.7-11.8), and hypertension (OR, 3.5; 95% CI, 1.3-9.9) were associated with S3 steatosis, whereas body mass index (OR, 1.1 per unit increase; 95% CI, 1.0-1.2) and ethnicity (OR, non-Hispanic black vs non-Hispanic white, 3.9; 95% CI, 1.2-13.2) were associated with significant fibrosis. High proportions of participants with fibrosis were in the normal weight category (35%) and had normal levels of alanine aminotransferase (78%). CONCLUSIONS Prevalence of MAFLD and significant fibrosis are alarmingly high in adolescents in the National Health and Nutrition Examination Survey 2017-2018. Levels of alanine aminotransferase and blood biomarkers do not correctly identify adolescents with more advanced disease. Effective noninvasive strategies to differentiate simple steatosis from progressive forms are urgently needed.
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Affiliation(s)
- Stefano Ciardullo
- Department of Medicine and Rehabilitation, Policlinico di Monza, Monza, Italy; Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Tommaso Monti
- Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy
| | - Gianluca Perseghin
- Department of Medicine and Rehabilitation, Policlinico di Monza, Monza, Italy; Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.
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Chen H, Zhou L, Liao B, Cao Q, Jiang H, Zhou W, Wang G, Xie X. Two-Dimensional Shear Wave Elastography Predicts Liver Fibrosis in Jaundiced Infants with Suspected Biliary Atresia: A Prospective Study. Korean J Radiol 2021; 22:959-969. [PMID: 33569934 PMCID: PMC8154778 DOI: 10.3348/kjr.2020.0885] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Revised: 10/14/2020] [Accepted: 10/17/2020] [Indexed: 12/13/2022] Open
Abstract
Objective This study aimed to evaluate the role of preoperative two-dimensional (2D) shear wave elastography (SWE) in assessing the stages of liver fibrosis in patients with suspected biliary atresia (BA) and compared its diagnostic performance with those of serum fibrosis biomarkers. Materials and Methods This study was approved by the ethical committee, and written informed parental consent was obtained. Two hundred and sixteen patients were prospectively enrolled between January 2012 and October 2018. The 2D SWE measurements of 69 patients have been previously reported. 2D SWE measurements, serum fibrosis biomarkers, including fibrotic markers and biochemical test results, and liver histology parameters were obtained. 2D SWE values, serum biomarkers including, aspartate aminotransferase to platelet ratio index (APRi), and other serum fibrotic markers were correlated with the stages of liver fibrosis by METAVIR. Receiver operating characteristic (ROC) curves and area under the ROC (AUROC) curve analyses were used. Results The correlation coefficient of 2D SWE value in correlation with the stages of liver fibrosis was 0.789 (p < 0.001). The cut-off values of 2D SWE were calculated as 9.1 kPa for F1, 11.6 kPa for F2, 13.0 kPa for F3, and 15.7 kPa for F4. The AUROCs of 2D SWE in the determination of the stages of liver fibrosis ranged from 0.869 to 0.941. The sensitivity and negative predictive value of 2D SWE in the diagnosis of ≥ F3 was 93.4% and 96.0%, respectively. The diagnostic performance of 2D SWE was superior to that of APRi and other serum fibrotic markers in predicting severe fibrosis and cirrhosis (all p < 0.005) and other serum biomarkers. Multivariate analysis showed that the 2D SWE value was the only statistically significant parameter for predicting liver fibrosis. Conclusion 2D SWE is a more effective non-invasive tool for predicting the stage of liver fibrosis in patients with suspected BA, compared with serum fibrosis biomarkers.
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Affiliation(s)
- Huadong Chen
- Department of Pediatric Surgery, The First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, China
| | - Luyao Zhou
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, China.
| | - Bing Liao
- Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, China
| | - Qinghua Cao
- Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, China
| | - Hong Jiang
- Department of Pediatric Surgery, The First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, China
| | - Wenying Zhou
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, China
| | - Guotao Wang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, China
| | - Xiaoyan Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, China
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Associated Factors of Liver Disease After Fontan Operation in Relation to Ultrasound Liver Elastography. Pediatr Cardiol 2020; 41:1639-1644. [PMID: 32740670 DOI: 10.1007/s00246-020-02422-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Accepted: 07/21/2020] [Indexed: 10/23/2022]
Abstract
Although the Fontan operation can improve outcomes, surviving patients still face Fontan-associated liver disease (FALD). The aim of this study was to determine the associated factors of FALD in relation to ultrasound liver elastography. A cross-sectional study was conducted for all patients on whom an ultrasound upper-abdomen and ultrasound liver elastography was performed at more than 1 year after the Fontan operation. The data consisted of the age at operation, type of Fontan operation, and laboratory data such as gamma-glutamyl transferase (GGT), aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) score. Cardiovascular evaluations included echocardiography and cardiac catheterization. Eighty patients with a median age of 12 years (range 5-36 years) were eligible for the study. The prevalence of FALD was 41%. For the purpose of univariate logistic regression analysis, the age at the Fontan operation, time elapsed since the Fontan operation, previous Glenn shunt, presence of fenestration, mean pulmonary artery pressure and IVC pressure post-Fontan operation, platelet count, GGT, and FIB-4 score were considered to be factors significantly associated with FALD. Following an adjustment by multivariate logistic regression analysis, age greater than 7 years at the time of Fontan procedure, time elapsed of more than 9 years since the procedure, and GGT level > 130 U/L were found to be significantly associated with FALD. Patients with these factors should be investigated for FALD.
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Vo HD, Harp KA, Mauch TJ. Diagnostic performance of non-invasive tests for evaluation of hepatic graft fibrosis in pediatric liver transplantation: A scoping review. Transplant Rev (Orlando) 2020; 34:100568. [PMID: 32713759 DOI: 10.1016/j.trre.2020.100568] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 07/02/2020] [Accepted: 07/13/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND Hepatic graft fibrosis is a common histologic finding of pediatric liver transplant (LT) that might affect long-term graft outcome. However, its diagnosis and staging require an invasive liver biopsy. AIM To review the published literature on the diagnostic accuracy of elastography and serum-based fibrosis markers for assessing hepatic graft fibrosis in pediatric LT recipients. METHODS A scoping review was conducted using a systematic search of published literature in PubMed (MEDLINE), EMBASE, SCOPUS, and Cochrane Library between 2002 and 2019. We included all English conference abstracts or full-text articles that examined the diagnostic accuracy of the non-invasive test(s) to assess hepatic fibrosis in LT children, using liver biopsy as the reference test. RESULTS Eight studies were included, of which 6 examined transient elastography (TE), one investigated acoustic radiation force impulse elastography, and 5 examined serum-based fibrosis markers (AST/ALT ratio, AST-to-platelet ratio index, FibroTest, enhanced liver fibrosis test). TE reportedly had a good AUROC (range: 0.82-0.92) to distinguish children with hepatic graft fibrosis (≥F1) from those with no fibrosis. However, there was considerable overlap of liver stiffness cutoffs in the mild to significant fibrosis groups (≥F1 and ≥F2). Current serum-based fibrosis markers reportedly had an unsatisfactory diagnostic accuracy. CONCLUSIONS TE in LT children has similar diagnostic value and limitations as in the non-transplant setting. Prospective studies are warranted to validate an optimal liver stiffness cutoff for predicting significant hepatic graft fibrosis (≥F2) and to determine if a meaningful change in liver stiffness from baseline could identify patients at risk for fibrosis progression.
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Affiliation(s)
- Hanh D Vo
- Pediatric Gastroenterology, Hepatology, and Nutrition, University of Nebraska Medical Center, Omaha, NE, United States.
| | - Kimberly A Harp
- Education and Research Services, McGoogan Library of Medicine, University of Nebraska Medical Center, Omaha, NE, United States
| | - Teri J Mauch
- Pediatric Nephrology, University of Nebraska Medical Center, Omaha, NE, United States
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Castillo‐Leon E, Cioffi CE, Vos MB. Perspectives on youth-onset nonalcoholic fatty liver disease. Endocrinol Diabetes Metab 2020; 3:e00184. [PMID: 33102800 PMCID: PMC7576279 DOI: 10.1002/edm2.184] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 07/07/2020] [Accepted: 07/11/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The prevalence and incidence of youth-onset nonalcoholic fatty liver disease (NAFLD) far exceeds other paediatric chronic liver diseases and represents a considerable public health issue globally. METHODS Here, we performed a narrative review of current knowledge regarding the epidemiology of paediatric NAFLD, selected concepts in pathogenesis, comorbidities, diagnosis, and management, and issues related to the transition to adulthood. RESULTS Paediatric NAFLD has become increasingly more prevalent, especially in certain subgroups, such as children with obesity and certain races/ethnicities. The pathophysiology of paediatric NAFLD is complex and multifactorial, driven by an interaction of environmental and genetic factors. Once developed, NAFLD in childhood is associated with type 2 diabetes, hypertension, increased cardiovascular disease risk, and end-stage liver disease. This predicts an increased burden of morbidity and mortality in adolescents and young adults. Early screening and diagnosis are therefore crucial, and the development of noninvasive biomarkers remains an active area of investigation. Currently, treatment strategies are focused on lifestyle changes, but there is also research interest in pharmacological and surgical options. In the transition from paediatric to adult care, there are several potential challenges/barriers to treatment and research is needed to understand how best to support patients during this time. CONCLUSIONS Our understanding of the epidemiology and pathophysiology of paediatric NAFLD has increased considerably over recent decades, but several critical knowledge gaps remain and must be addressed in order to better mitigate the short-term and long-term risks of youth-onset NAFLD.
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Affiliation(s)
| | - Catherine E. Cioffi
- Department of PediatricsEmory University School of MedicineAtlantaGAUSA
- Nutrition & Health Sciences Doctoral ProgramLaney Graduate SchoolEmory UniversityAtlantaGAUSA
| | - Miriam B. Vos
- Department of PediatricsEmory University School of MedicineAtlantaGAUSA
- Children's Healthcare of AtlantaAtlantaGAUSA
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Repeatability of transient elastography in children. Pediatr Res 2020; 88:587-592. [PMID: 32357363 DOI: 10.1038/s41390-020-0916-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Revised: 03/30/2020] [Accepted: 04/01/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Poorly performing diagnostic tests can impact patient safety. Clinical investigations must have good precision and diagnostic accuracy before widespread use in clinical practice. Transient elastography (TE) measures liver stiffness, a surrogate marker of liver fibrosis in adults and children. Studies to evaluate its repeatability and reproducibility (precision) in children are limited. Our aim was to determine (i) the normal range of TE measurements and (ii) the repeatability and reproducibility of TE in healthy children. METHODS TE was performed in 257 healthy children, of whom 235 (91%, mean age 11.7 years, standard deviation (SD) 2.51, 107 were males (45.5%)) had two valid TE measurements performed, at least 24 h apart, by two operators under similar circumstances. High-quality TE images were obtained for each examination. RESULTS The normal range of TE was 2.88-6.52 kPa. The mean difference between paired measurements was 0.044 (SD 0.4). The 95% limits of agreement ranged from -0.8 to +0.76 kPa for repeat measurements. There was a difference of >1 kPa between measurements in 61/235 (25.9%) children. The lack of precision was similar across all age groups. CONCLUSIONS This study demonstrates that TE does not have acceptable precision in healthy children, because random measurement variation results in the lack of agreement between paired measurements. IMPACT The precision and diagnostic accuracy of a new technology must be determined before it is deployed in children in order to ensure that appropriate clinical decisions are made, and healthcare resources are not wasted. TE is widely used to diagnose liver disease in children without adequate evaluation of the precision (repeatability) of TE either in healthy children or children with liver disease. This study demonstrates that TE does not have adequate precision in children. This study was performed in accordance with methods previously published for children. Refinements to the test protocol, such as duration of fasting or probe size, will have to be evaluated for their impact on precision and accuracy before the test is deployed in research studies or clinical practice.
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Lee CK, Nastasio S, Mitchell PD, Fawaz R, Elisofon SA, Vakili K, Kim HB, Nguyen D, Jonas MM. Transient elastography assessment of liver allograft fibrosis in pediatric transplant recipients. Pediatr Transplant 2020; 24:e13736. [PMID: 32432836 DOI: 10.1111/petr.13736] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Revised: 02/12/2020] [Accepted: 04/17/2020] [Indexed: 01/06/2023]
Abstract
TE measures liver stiffness to assess fibrosis. Its use in post-transplant patients was reported in few small pediatric studies. We evaluated TE ability to predict liver graft fibrosis in a large cohort while comparing it to the performance of APRI and FIB-4. We also investigated the effect of graft type on LSMs. Patients at Boston Children's Hospital who underwent LT and LSM ≤ 1 year from biopsy (2007-2018) were eligible. Ninety-four patients (45%M) aged 1-21 years (89% < 18 years; 13% < 2 years) were eligible. Median time between transplant/biopsy and LSM was 5.1 years and 52 days, respectively. Thirty-nine percent received whole-liver grafts, 54% TV grafts, and 6% as part of MV. At LSM, median ALT was 25 [IQR 16-33] IU/L. Twenty-one percent had METAVIR ≥ F2. LSM was statistically higher among those with significant fibrosis (METAVIR ≥ F2) compared to those with METAVIR F0/F1 (median [IQR] 7.5 [4.6, 13.6] vs 5.1 [4.0, 6.4] kPa, respectively) (P = .005 by Wilcoxon rank-sum test). APRI and FIB-4 distributions were not different across METAVIR stages. The AUROC for LSM was 0.71 (95% CI 0.56-0.85) with an optimal cut-point of 6.5 kPa. Graft type had no influence on the AUROC for LSM. TE is useful for assessing significant graft fibrosis in children and young adult LT recipients and performs better than APRI and FIB-4. TV grafts demonstrate similar correlation with histology as whole-liver grafts.
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Affiliation(s)
- Christine K Lee
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, USA
| | - Silvia Nastasio
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, USA
| | - Paul D Mitchell
- Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Boston, MA, USA
| | - Rima Fawaz
- Section of Gastroenterology and Hepatology, Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA
| | - Scott A Elisofon
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, USA
| | - Khashayar Vakili
- Department of Surgery, Boston Children's Hospital, Boston, MA, USA
| | - Heung Bae Kim
- Department of Surgery, Boston Children's Hospital, Boston, MA, USA
| | - Denis Nguyen
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, USA
| | - Maureen M Jonas
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, USA
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Costa P, Kogan-Liberman D, Rudolph B, Silver E, Ewart M, Raizner A, Cunningham R, Ovchinsky N. Detection of graft fibrosis by vibration-controlled transient elastography in pediatric liver transplant recipients. Pediatr Transplant 2020; 24:e13731. [PMID: 32427407 DOI: 10.1111/petr.13731] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Revised: 12/05/2019] [Accepted: 04/17/2020] [Indexed: 11/27/2022]
Abstract
Pediatric liver transplant recipients are at risk of developing graft fibrosis which can affect patient survival. VCTE is a non-invasive tool that measures LSM and has been shown to correlate with hepatic fibrosis. The aim of this study was to therefore evaluate the ability of LSM to predict fibrosis in pediatric liver transplant recipients with different graft types. We performed a cross-sectional study evaluating LSM of 28 pediatric liver transplant recipients who underwent a total of 20 liver biopsies within 1 month of LSM. LSM was compared to liver histology as well as graft type: WL or PL. The median LSM of all post-transplant patients was 5.6 kPa (range = 2.7-18.3). There was a statistically significant correlation between LSM and METAVIR fibrosis score (P = .001) and LAF score (P < .001). There was no difference in LSM between graft type (P = .088). The AUROC curve for LSM predicting any significant fibrosis (F ≥ 2) was 0.863. A cutoff value of 7.25 had a sensitivity of 71%, specificity of 100%, NPV of 87%, and PPV of 100% for significant fibrosis. LSM by VCTE is feasible in pediatric liver transplant recipients regardless of graft type. We found a significant correlation between LSM and hepatic fibrosis and established a cutoff value that may help determine which patients warrant further evaluation for graft fibrosis.
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Affiliation(s)
- Peter Costa
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Debora Kogan-Liberman
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Bryan Rudolph
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Ellen Silver
- Division of Academic General Pediatrics, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Michelle Ewart
- Division of Pathology, Montefiore Medical Center, Bronx, NY, USA
| | - Aileen Raizner
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Ryan Cunningham
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Nadia Ovchinsky
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA
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