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Ferreira J, Sheflin-Findling S. Update on Pediatric Hepatitis C Infection. Curr Gastroenterol Rep 2025; 27:18. [PMID: 40019674 PMCID: PMC11870864 DOI: 10.1007/s11894-024-00955-3] [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] [Accepted: 12/03/2024] [Indexed: 03/01/2025]
Abstract
PURPOSEOF REVIEW Hepatitis C virus (HCV) infections continue to steadily increase in the United States and remain a major public health challenge. This review aims to provide a comprehensive overview of HCV infection in children, focusing on recent advancements in screening, diagnosis, and treatment. RECENT FINDINGS Effective screening strategies, including universal screening of pregnant women and nucleic acid testing for all perinatally exposed infants at 2 to 6 months of age, have been implemented to identify infected individuals early. Direct-acting antiviral agents have revolutionized treatment, offering high cure rates for children of all ages. Despite significant progress, challenges remain in achieving HCV elimination. These include the need for improved access to testing and treatment, as well as ongoing efforts to develop a preventive vaccine. Continued research and implementation of effective strategies are essential to reduce the burden of HCV infection.
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Affiliation(s)
- Johanna Ferreira
- Division of Pediatric Gastroenterology, Liver Disease and Nutrition, Cohen Children's Medical Center/Northwell, The Zucker School of Medicine at Hofstra, 1991 Marcus Avenue, Suite M100 , Lake Success, NY, 11042, USA.
| | - Shari Sheflin-Findling
- Division of Pediatric Gastroenterology, Liver Disease and Nutrition, Cohen Children's Medical Center/Northwell, The Zucker School of Medicine at Hofstra, 1991 Marcus Avenue, Suite M100 , Lake Success, NY, 11042, USA
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Duarte-Rojo A, Taouli B, Leung DH, Levine D, Nayfeh T, Hasan B, Alsawaf Y, Saadi S, Majzoub AM, Manolopoulos A, Haffar S, Dundar A, Murad MH, Rockey DC, Alsawas M, Sterling RK. Imaging-based noninvasive liver disease assessment for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline. Hepatology 2025; 81:725-748. [PMID: 38489521 DOI: 10.1097/hep.0000000000000852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 01/19/2024] [Indexed: 03/17/2024]
Abstract
BACKGROUND AND AIMS Transient elastography (TE), shear wave elastography, and/or magnetic resonance elastography (MRE), each providing liver stiffness measurement (LSM), are the most studied imaging-based noninvasive liver disease assessment (NILDA) techniques. To support the American Association for the Study of Liver Diseases guidelines on NILDA, we summarized the evidence on the accuracy of these LSM methods to stage liver fibrosis (F). APPROACH AND RESULTS A comprehensive search for studies assessing LSM by TE, shear wave elastography, or MRE for the identification of significant fibrosis (F2-4), advanced fibrosis (F3-4), or cirrhosis (F4), using histopathology as the standard of reference by liver disease etiology in adults or children from inception to April 2022 was performed. We excluded studies with <50 patients with a single disease entity and mixed liver disease etiologies (with the exception of HCV/HIV coinfection). Out of 9447 studies, 240 with 61,193 patients were included in this systematic review. In adults, sensitivities for the identification of F2-4 ranged from 51% to 95%, for F3-4 from 70% to 100%, and for F4 from 60% to 100% across all techniques/diseases, whereas specificities ranged from 36% to 100%, 74% to 100%, and 67% to 99%, respectively. The largest body of evidence available was for TE; MRE appeared to be the most accurate method. Imaging-based NILDA outperformed blood-based NILDA in most comparisons, particularly for the identification of F3-4/F4. In the pediatric population, imaging-based NILDA is likely as accurate as in adults. CONCLUSIONS LSM from TE, shear wave elastography, and MRE shows acceptable to outstanding accuracy for the detection of liver fibrosis across various liver disease etiologies. Accuracy increased from F2-4 to F3-4 and was the highest for F4. Further research is needed to better standardize the use of imaging-based NILDA, particularly in pediatric liver diseases.
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Affiliation(s)
- Andres Duarte-Rojo
- Division of Gastroenterology and Hepatology, Northwestern Medicine and Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Bachir Taouli
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Daniel H Leung
- Department of Pediatrics, Baylor College of Medicine and Division of Gastroenterology, Hepatology and Nutrition, Texas Children's Hospital, Houston, Texas, USA
| | - Deborah Levine
- Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Tarek Nayfeh
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Bashar Hasan
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Yahya Alsawaf
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Samer Saadi
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | | | | | - Samir Haffar
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Ayca Dundar
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - M Hassan Murad
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Don C Rockey
- Digestive Disease Research Center, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Mouaz Alsawas
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Richard K Sterling
- Section of Hepatology, Department of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA
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Serai SD, Franchi-Abella S, Syed AB, Tkach JA, Toso S, Ferraioli G. MR and Ultrasound Elastography for Fibrosis Assessment in Children: Practical Implementation and Supporting Evidence- AJR Expert Panel Narrative Review. AJR Am J Roentgenol 2024; 223:e2330506. [PMID: 38170833 DOI: 10.2214/ajr.23.30506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2024]
Abstract
Quantitative MRI and ultrasound biomarkers of liver fibrosis have become important tools in the diagnosis and clinical management of children with chronic liver disease (CLD). In particular, MR elastography is now routinely performed in clinical practice to evaluate the liver for fibrosis. Ultrasound shear-wave elastography has also become widely performed for this purpose, especially in young children. These noninvasive methods are increasingly used to replace liver biopsy for the diagnosis, quantitative staging, and treatment monitoring of patients with CLD. Although ultrasound has the advantages of portability and lower equipment cost than MRI, available evidence indicates that MRI may have greater reliability and accuracy in liver fibrosis evaluation. In this AJR Expert Panel Narrative Review, we describe how, why, and when to use MRI- and ultrasound-based elastography methods for liver fibrosis assessment in children. Practical approaches are discussed for adapting and optimizing these methods in children, with consideration of clinical indications, patient preparation, equipment requirements, and acquisition technique, as well as pitfalls and confounding factors. Guidance is provided for interpretation and reporting, and representative case examples are presented.
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Affiliation(s)
- Suraj D Serai
- Department of Radiology, Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Stéphanie Franchi-Abella
- Faculté de Médecine, Université Paris-Saclay, Le Kremlin-Bicêtre, France
- Service de Radiologie Pédiatrique Diagnostique et Interventionnelle, Centre de Référence des Maladies Rares du Foie de L'enfant, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
- BIOMAPS, University Paris-Saclay, Orsay, France
| | - Ali B Syed
- Department of Radiology, Stanford University School of Medicine, Stanford, CA
| | - Jean A Tkach
- Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
- Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Seema Toso
- Department of Pediatric Radiology, University Children's Hospital Geneva, Geneva, Switzerland
| | - Giovanna Ferraioli
- Dipartimento di Scienze Clinico-Chirurgiche, Diagnostiche e Pediatriche, Medical School University of Pavia, Pavia, Italy
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Alvarenga LR, Sandy NS, Hessel G, Pereira TS, Bellomo-Brandão MÂ. GOOD CORRELATION BETWEEN LIVER STIFFNESS MEASUREMENT AND APRI, FIB-4, PLATELET COUNT, IN PEDIATRIC AUTOIMMUNE HEPATITIS. ARQUIVOS DE GASTROENTEROLOGIA 2024; 61:e24047. [PMID: 39442125 DOI: 10.1590/s0004-2803.24612024-047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Accepted: 07/04/2024] [Indexed: 10/25/2024]
Abstract
BACKGROUND There is limited evidence focusing on the use of non-invasive markers to assess liver fibrosis in pediatric chronic liver diseases. OBJECTIVE The aim of the study was to evaluate the correlation between liver stiffness measurement (LSM) using transient liver elastography (TLE) and serum non-invasive markers in pediatric autoimmune hepatitis (AIH). METHODS Cross-sectional study between May 2016 and February 2020. Twenty-eight children with AIH (age range between 3 and 20 years old) who had undergone TLE and had routine serum tests were enrolled. Patients were divided into 2 groups: (1) Liver fibrosis degree ≥F2 (TLE ≥6.45 kPa) and (2) RESULTS Twenty-eight AIH pediatric patients were enrolled, 21 were female and 22 had AIH type 1. Following the cut-off of 6.45 kPa in TLE, 20 patients (71%) were included in group 1, and 8 in group 2. A statistically significant difference was found between the two groups on APRI and FIB-4 results (P=0.0306 and P=0.0055, respectively). There was a significant correlation between TLE with APRI and FIB-4 (Rs=0.67 and 0.78, respectively; P<0.01) as well as with platelet count (Rs=-0.68; P<0.01). CONCLUSION APRI, FIB-4 and Platelet Count showed a good and positive correlation with transient liver elastography in pediatric patients with AIH.
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Affiliation(s)
- Lucas Rocha Alvarenga
- Faculdade de Ciências Médicas da Universidade Estadual de Campinas, Departamento de Pediatria, Campinas, SP, Brasil
| | - Natascha Silva Sandy
- Hospital Infantil Sabará, Programa Avançado de Tratamento da Insuficiência Intestinal (PATII), São Paulo, SP, Brasil
- Hospital Israelita Albert Einstein, Departamento de Pediatria, São Paulo, SP, Brasil
| | - Gabriel Hessel
- Faculdade de Ciências Médicas da Universidade Estadual de Campinas, Departamento de Pediatria, Campinas, SP, Brasil
| | - Tiago Sevá Pereira
- Faculdade de Ciências Médicas da Universidade Estadual de Campinas, Departamento de Gastroenterologia, Campinas, SP, Brasil
| | - Maria Ângela Bellomo-Brandão
- Faculdade de Ciências Médicas da Universidade Estadual de Campinas, Departamento de Pediatria, Campinas, SP, Brasil
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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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Koch RL, Kiely BT, Choi SJ, Jeck WR, Flores LS, Sood V, Alam S, Porta G, LaVecchio K, Soler-Alfonso C, Kishnani PS. Natural history study of hepatic glycogen storage disease type IV and comparison to Gbe1ys/ys model. JCI Insight 2024; 9:e177722. [PMID: 38912588 PMCID: PMC11383185 DOI: 10.1172/jci.insight.177722] [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: 11/29/2023] [Accepted: 05/08/2024] [Indexed: 06/25/2024] Open
Abstract
BackgroundGlycogen storage disease type IV (GSD IV) is an ultrarare autosomal recessive disorder that causes deficiency of functional glycogen branching enzyme and formation of abnormally structured glycogen termed polyglucosan. GSD IV has traditionally been categorized based on primary hepatic or neuromuscular involvement, with hepatic GSD IV subclassified as discrete subtypes: classic (progressive) and nonprogressive.MethodsTo better understand the progression of liver disease in GSD IV, we present clinical and histopathology data from 23 patients from around the world and characterized the liver involvement in the Gbe1ys/ys knockin mouse model.ResultsWe propose an alternative to the established subtype-based terminology for characterizing liver disease in GSD IV and recognize 3 tiers of disease severity: (i) "severe progressive" liver disease, (ii) "intermediate progressive" liver disease, and (iii) "attenuated" liver disease. Analysis of liver pathology revealed that risk for liver failure cannot be predicted from liver biopsy findings alone in individuals affected by GSD IV. Moreover, analysis of postmortem liver pathology from an individual who died over 40 years after being diagnosed with nonprogressive hepatic GSD IV in childhood verified that liver fibrosis did not regress. Last, characterization of the liver involvement in a mouse model known to recapitulate the adult-onset neurodegenerative form of GSD IV (Gbe1ys/ys mouse model) demonstrated hepatic disease.ConclusionOur findings challenge the established subtype-based view of GSD IV and suggest that liver disease severity among patients with GSD IV represents a disease continuum.Trial registrationClinicalTrials.gov NCT02683512FundingNone.
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Affiliation(s)
- Rebecca L Koch
- Division of Medical Genetics, Department of Pediatrics, and
| | | | - Su Jin Choi
- Division of Medical Genetics, Department of Pediatrics, and
| | - William R Jeck
- Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA
| | | | - Vikrant Sood
- Department of Pediatric Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Seema Alam
- Department of Pediatric Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Gilda Porta
- Hepatology and Liver Transplant Unit, Menino Jesus Hospital, São Paulo, Brazil
| | - Katy LaVecchio
- Department of Pathology, The Queen's Medical Center, Honolulu, Hawaii, USA
| | - Claudia Soler-Alfonso
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
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Nagi SAM, Yehia SA, Elhagali YA, Elkholy SS, Abd-Elaati BM. Have serum vitamin D and ferritin a role in predicting the prognosis of autoimmune hepatitis treatment in children? Clin Exp Hepatol 2024; 10:53-61. [PMID: 38765911 PMCID: PMC11100337 DOI: 10.5114/ceh.2024.136927] [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: 09/20/2023] [Accepted: 11/09/2023] [Indexed: 05/22/2024] Open
Abstract
Aim of the study To investigate whether serum ferritin and vitamin D levels before starting autoimmune hepatitis (AIH) treatment have a role in disease prognosis regarding a therapeutic response. Material and methods The prospective study included 100 children diagnosed with AIH according to simplified criteria for diagnosis of AIH. They attended the Pediatric Hepatology Department, National Liver Institute, Menoufia University. The patients underwent measurement of liver transaminases before starting AIH treatment after 6 months from starting therapy. They underwent liver biopsy before starting treatment for proper diagnosis, grading, and staging; only 25 cases were compliant and underwent liver biopsy before treatment withdrawal. Results Serum ferritin and 25 hydroxy vitamin D levels were significantly higher among those with a complete response (1000-3100 ng/ml, 29-48 ng/ml) than a partial response (550-600 ng/ml, 23-28 ng/ml) and non-response (29.28-92.14, 2.16-8.72) (p < 0.001). Conclusions Our study showed a relation between serum vitamin D before starting AIH treatment, the severity of AIH and response to therapy. This opens a new area of research on the potential use of vitamin D in patients with AIH. Also, hyperferritinemia at the diagnosis can predict the treatment response.
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Affiliation(s)
- Salma Abdel Megeed Nagi
- Pediatric Hepatology, Gastroenterology and Nutrition Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia, Egypt
| | - Sania Ali Yehia
- Epidemiology and Preventive Medicine Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia, Egypt
| | - Yasmen Abdelaziz Elhagali
- Laboratory Medicine Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia, Egypt
| | - Shimaa Saad Elkholy
- Pathology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia, Egypt
| | - Basma Mahmoud Abd-Elaati
- Pediatric Hepatology, Gastroenterology and Nutrition Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia, Egypt
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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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Niyasom C, Soponkanaporn S, Vilaiyuk S, Lertudomphonwanit C, Getsuwan S, Tanpawpong P, Kaewduang P, Sobhonslidsuk A. Use of transient elastography to assess hepatic steatosis and fibrosis in patients with juvenile idiopathic arthritis during methotrexate treatment. Clin Rheumatol 2024; 43:423-433. [PMID: 38062311 PMCID: PMC10774177 DOI: 10.1007/s10067-023-06835-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 11/08/2023] [Accepted: 11/26/2023] [Indexed: 01/09/2024]
Abstract
OBJECTIVES This study aimed to assess the prevalence and identify predictors of hepatic steatosis and fibrosis in patients with juvenile idiopathic arthritis (JIA) during methotrexate treatment. METHOD This cross-sectional study included JIA patients who had received methotrexate for > 1 year. Laboratory data including liver chemistry and lipid profiles were collected. Liver stiffness measurements (LSM) and controlled attenuation parameters (CAP) were determined by transient elastography. Significant hepatic fibrosis was defined as LSM > 7 kilopascal (kPa), and hepatic steatosis was defined as CAP > 225 decibel/meter (dB/m). Logistic regression analysis was performed to identify predictors associated with hepatic steatosis and fibrosis. RESULTS Of 60 patients, 66.7% were female, and the median age (IQR) was 12.8 (10.6-15.0) years. The median duration of methotrexate usage (IQR) was 45 (22-85) months, and the median cumulative dose of methotrexate (IQR) was 3768 (1806-6466) mg. The median LSM (IQR) and CAP (IQR) were 4.1 (3.4-4.6) kPa and 191.0 (170.3-223.8) dB/m, respectively. No patients had transient elastography-defined hepatic fibrosis, whereas 21.7% had hepatic steatosis. A body mass index Z-score > 1 (OR 5.71 [95%CI 1.31-24.98], p = 0.021) and higher cumulative dose of methotrexate (OR 1.02 [95%CI 1.00-1.04], p = 0.041) were associated with hepatic steatosis, whereas the cumulative dose of steroids was not (OR 1.00 [95%CI 1.00-1.01], p = 0.097). CONCLUSIONS Hepatic steatosis is common among JIA patients receiving methotrexate, but none had transient elastography-defined hepatic fibrosis. Overweight/obese JIA adolescents and patients with a high cumulative dose of methotrexate are at risk for hepatic steatosis. Key Points •Long-term low-dose methotrexate usage and the concomitant use of other DMARDs did not increase the risk of hepatic fibrosis in JIA patients. •The prevalence of hepatic steatosis in JIA patients receiving methotrexate was higher than in a healthy pediatric population. •Overweight/obesity and a higher cumulative dose of methotrexate were predictors of hepatic steatosis.
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Affiliation(s)
- Chayakamon Niyasom
- Division of Rheumatology, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Sirisucha Soponkanaporn
- Division of Rheumatology, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
| | - Soamarat Vilaiyuk
- Division of Rheumatology, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Chatmanee Lertudomphonwanit
- Division of Gastroenterology, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Songpon Getsuwan
- Division of Gastroenterology, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Pornthep Tanpawpong
- Division of Gastroenterology, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Piyaporn Kaewduang
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Abhasnee Sobhonslidsuk
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
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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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Nehring P, Szeligowska J, Przybyłkowski A. Elastography of the Liver in Wilson's Disease. Diagnostics (Basel) 2023; 13:diagnostics13111898. [PMID: 37296749 DOI: 10.3390/diagnostics13111898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 05/22/2023] [Accepted: 05/26/2023] [Indexed: 06/12/2023] Open
Abstract
Staging of liver fibrosis is of special significance in Wilson's disease as it determines the patient's prognosis and treatment. Histopathological examination is a standard method for fibrosis assessment; however, non-invasive methods like transient elastography and share wave elastography are believed to be reliable and repetitive and are expected to replace liver biopsy in Wilson's disease. This article presents a short description of available elastography techniques and the results of the most recent studies on elastography of the liver in patients with Wilson's disease.
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Affiliation(s)
- Piotr Nehring
- Department of Gastroenterology and Internal Medicine, Medical University of Warsaw, Banacha 1a, 02-097 Warsaw, Poland
| | - Jowita Szeligowska
- Department of Gastroenterology and Internal Medicine, Medical University of Warsaw, Banacha 1a, 02-097 Warsaw, Poland
| | - Adam Przybyłkowski
- Department of Gastroenterology and Internal Medicine, Medical University of Warsaw, Banacha 1a, 02-097 Warsaw, Poland
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12
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de Lange C, Möller T, Hebelka H. Fontan-associated liver disease: Diagnosis, surveillance, and management. Front Pediatr 2023; 11:1100514. [PMID: 36937979 PMCID: PMC10020358 DOI: 10.3389/fped.2023.1100514] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Accepted: 02/09/2023] [Indexed: 03/06/2023] Open
Abstract
The Fontan operation is a lifesaving procedure for patients with functional single-ventricle congenital heart disease, where hypoplastic left heart syndrome is the most frequent anomaly. Hemodynamic changes following Fontan circulation creation are now increasingly recognized to cause multiorgan affection, where the development of a chronic liver disease, Fontan-associated liver disease (FALD), is one of the most important morbidities. Virtually, all patients with a Fontan circulation develop liver congestion, resulting in fibrosis and cirrhosis, and most patients experience childhood onset. FALD is a distinctive type of congestive hepatopathy, and its pathogenesis is thought to be a multifactorial process driven by increased nonpulsatile central venous pressure and decreased cardiac output, both of which are inherent in the Fontan circulation. In the advanced stage of liver injury, complications of portal hypertension often occur, and there is a risk of developing secondary liver cancer, reported at young age. However, FALD develops with few clinical symptoms, a surprisingly variable degree of severity in liver disease, and with little relation to poor cardiac function. The disease mechanisms and modifying factors of its development are still not fully understood. As one of the more important noncardiac complications of the Fontan circulation, FALD needs to be diagnosed in a timely manner with a structured monitoring scheme of disease development, early detection of malignancy, and determination of the optimal time point for transplantation. There is also a clear need for consensus on the best surveillance strategy for FALD. In this regard, imaging plays an important role together with clinical scoring systems, biochemical workups, and histology. Patients operated on with a Fontan circulation are generally followed up in cardiology units. Ultimately, the resulting multiorgan affection requires a multidisciplinary team of healthcare personnel to address the different organ complications. This article discusses the current concepts, diagnosis, and management of FALD, with special emphasis on the role of different imaging techniques in the diagnosis and monitoring of disease progression, as well as current recommendations for liver disease surveillance.
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Affiliation(s)
- Charlotte de Lange
- Department of Pediatric Radiology, Queen Silvia Children’s Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden
- Institution of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Thomas Möller
- Department of Pediatric Cardiology, Oslo University Hospital, Oslo, Norway
| | - Hanna Hebelka
- Department of Pediatric Radiology, Queen Silvia Children’s Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden
- Institution of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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13
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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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14
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Wang J, Wang J, Wang H, Li B, Wang Y, Sun L, Wu X. Application of attenuation coefficient in the assessment of hepatic involvement in children and adolescents with Wilson's disease. BMC Med Imaging 2023; 23:24. [PMID: 36739392 PMCID: PMC9898910 DOI: 10.1186/s12880-023-00979-7] [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: 11/22/2022] [Accepted: 01/30/2023] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND To investigate whether the attenuation coefficient (ATT) can be used as a noninvasive index to assess liver involvement in children and adolescents with Wilson's disease (WD). METHODS Children and adolescents diagnosed with WD were retrospectively collected from the First Affiliated Hospital of the Anhui University of Traditional Chinese Medicine between May 2022 and August 2022. The findings on ATT, Shear Wave Measurement (SWM), AST to platelet ratio index (APRI), and fibrosis 4 (FIB-4) score were obtained. The liver involvement of WD was classified into 3 groups based on serum levels of collagen type IV (CIV), hyaluronic acid (HA), laminin (LN) and precollagen type III N-terminal peptide (PIIINP): (1) Group1 (n = 25), no abnormalities in CIV, HA, LN and PIIINP; (2) Group2 (n = 19), elevation of 1 or 2 indexes in CIV, HA, LN, and PIIINP; Group3 (n = 18), elevation of 3 or 4 indicators in CIV, HA, LN, and PIIINP. The levels of ATT, SWM, APRI and FIB-4 were compared between the 3 groups; and correlation of ATT with SWM and triglyceride (TG) was performed using Spearman's correlation analysis. The Receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of ATT alone and its combination with SWM, APRI, and FIB-4 in children and adolescents with WD. RESULTS A total of 62 children and adolescents with WD were retrospectively retrieved. ATT levels were significantly different in intergroup comparisons (P < 0.001). The ROC curve showed that the area under the curve (AUC) for the diagnosis of hepatic steatosis using ATT was 0.714, 0.712 and 0.867 in Group 1 versus Group 2, Group 2 versus Group 3, and Group 1 versus Group 3, respectively; the sensitivity for the diagnosis of hepatic steatosis in Group 1 versus Group 2 was 89.47% with the cutoff value of ATT of 0.73 dB/cm/MHz. No significant correlation found between ATT and TG (ρ = 0.154, P = 0.231). Compared to ATT alone, the combination of ATT with APRI and FIB-4 or the combination of ATT with SWM, APRI, and FIB-4 showed a better diagnostic efficacy in Group 1 versus Group 2 (both P = 0.038). CONCLUSION ATT could be used as a non-invasive index for the evaluation of liver steatosis in children and adolescents with WD, with a good clinical applicative value. Furthermore, ATT in combination with APRI, FIB-4, and SWM might have better diagnostic efficacy than ATT alone.
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Affiliation(s)
- Jiajia Wang
- grid.412679.f0000 0004 1771 3402Department of Ultrasound, The First Affiliated Hospital of Anhui University of Chinese Medicine, 117 Meishan Road, Shushan District, Hefei, 230031 Anhui China
| | - Jinping Wang
- Department of Ultrasound, The First Affiliated Hospital of Anhui University of Chinese Medicine, 117 Meishan Road, Shushan District, Hefei, 230031, Anhui, China.
| | - Han Wang
- grid.412679.f0000 0004 1771 3402Department of Encephalopathy, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China
| | - Boqi Li
- grid.412679.f0000 0004 1771 3402Department of Ultrasound, The First Affiliated Hospital of Anhui University of Chinese Medicine, 117 Meishan Road, Shushan District, Hefei, 230031 Anhui China
| | - Yixing Wang
- grid.412679.f0000 0004 1771 3402Department of Ultrasound, The First Affiliated Hospital of Anhui University of Chinese Medicine, 117 Meishan Road, Shushan District, Hefei, 230031 Anhui China
| | - Lanting Sun
- grid.412679.f0000 0004 1771 3402Department of Encephalopathy, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China
| | - Xiaoqian Wu
- grid.412679.f0000 0004 1771 3402Department of Ultrasound, The First Affiliated Hospital of Anhui University of Chinese Medicine, 117 Meishan Road, Shushan District, Hefei, 230031 Anhui China
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15
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Foster MA, Moorman AC, Teshale EH. Hepatitis C Virus. PRINCIPLES AND PRACTICE OF PEDIATRIC INFECTIOUS DISEASES 2023:1156-1160.e3. [DOI: 10.1016/b978-0-323-75608-2.00220-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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16
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ElShahawy A, El-Raziky MS, Sharaf SA, Elsharkawy A, Enayet A, Taher H. Accuracy of noninvasive methods for the diagnosis of liver fibrosis in children with chronic viral hepatitis. BMC Gastroenterol 2022; 22:508. [PMID: 36494622 PMCID: PMC9733352 DOI: 10.1186/s12876-022-02570-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 11/07/2022] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Liver biopsy is the reference standard for assessing liver fibrosis. Moreover, it is an invasive procedure. Transient elastography (TE) is an accurate, noninvasive method for evaluating liver stiffness as a surrogate of liver fibrosis. The aspartate aminotransferase to platelet ratio index (APRI) and Hyaluronic acid (HA) are noninvasive alternatives to liver biopsy for detecting hepatic fibrosis. This study aimed to identify the accuracy of APRI, HA, and TE concerning liver biopsy in children with chronic viral hepatitis. METHODS This cross-sectional study included 50 children, 5-18 years with chronic viral hepatitis B (HBV) or hepatitis C (HCV) who underwent liver biopsy within nine months of laboratory tests, determining APRI & performing TE. Twenty healthy children of age and sex-matching patients were included as a control group for the serum HA levels. RESULTS The histopathological findings of the studied cases showed seven cases with (F0) fibrosis, 36 cases with mild (F1,2), two children with moderate (F3,4), and five children with severe (F5,6). The median (IQR) of steatosis was 4 (three had HCV). When correlating TE, APRI, and HA values in all cases with their laboratory data, there was a positive correlation between ALT and APRI values (P-value = 0.000), a positive correlation between AST and HA values (P-value = 0.02), and a negative correlation between stiffness and APRI. The sensitivity of HA, APRI, and TE compared to fibrosis detected by histopathology was 60.5, 65.1, and 60.5%, and their specificity was 71.4, 57.1, and 85.7%, respectively. TE was significantly higher in a group with (moderate to severe) fibrosis. CONCLUSION APRI, HA, and TE are good indicators of the presence of fibrosis almost with the same accuracy. TE is the only method to differentiate mild cases from those with significant fibrosis.
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Affiliation(s)
- A ElShahawy
- Pediatrics in National Hepatology and Tropical Medicine Institiute, Cairo, Egypt
| | - MS El-Raziky
- grid.7776.10000 0004 0639 9286Pediatrics and Pediatric Hepatology, Faculty of Medicine, Cairo University, Giza City, Egypt
| | - SA Sharaf
- grid.7776.10000 0004 0639 9286Chemical Pathology, Faculty of Medicine, Cairo University, Giza City, Egypt
| | - A Elsharkawy
- grid.7776.10000 0004 0639 9286Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Giza City, Egypt
| | - A Enayet
- grid.7776.10000 0004 0639 9286Pediatrics and Pediatric Hepatology, Faculty of Medicine, Cairo University, Giza City, Egypt ,grid.7776.10000 0004 0639 9286Department of Pediatrics, Kasr Alainy Medical School, Faculty of Medicine, Cairo University, Giza City, Egypt
| | - H Taher
- grid.7776.10000 0004 0639 9286Pediatrics and Pediatric Hepatology, Faculty of Medicine, Cairo University, Giza City, Egypt
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17
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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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18
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Kim SW, Lee JM, Park S, Joo I, Yoon JH, Chang W, Kim H. Diagnostic Performance of Spin-Echo Echo-Planar Imaging Magnetic Resonance Elastography in 3T System for Noninvasive Assessment of Hepatic Fibrosis. Korean J Radiol 2022; 23:180-188. [PMID: 35029070 PMCID: PMC8814695 DOI: 10.3348/kjr.2021.0145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 08/08/2021] [Accepted: 08/09/2021] [Indexed: 11/15/2022] Open
Abstract
Objective To validate the performance of 3T spin-echo echo-planar imaging (SE-EPI) magnetic resonance elastography (MRE) for staging hepatic fibrosis in a large population, using surgical specimens as the reference standard. Materials and Methods This retrospective study initially included 310 adults (155 undergoing hepatic resection and 155 undergoing donor hepatectomy) with histopathologic results from surgical liver specimens. They underwent 3T SE-EPI MRE ≤ 3 months prior to surgery. Demographic findings, underlying liver disease, and hepatic fibrosis pathologic stage according to METAVIR were recorded. Liver stiffness (LS) was measured by two radiologists, and inter-reader reproducibility was evaluated using the intraclass correlation coefficient (ICC). The mean LS of each fibrosis stage (F0–F4) was calculated in total and for each etiologic subgroup. Comparisons among subgroups were performed using the Kruskal–Wallis test and Conover post-hoc test. The cutoff values for fibrosis staging were estimated using receiver operating characteristic (ROC) curve analysis. Results Inter-reader reproducibility was excellent (ICC, 0.98; 95% confidence interval, 0.97–0.99). The mean LS values were 1.91, 2.41, 3.24, and 5.41 kPa in F0–F1 (n = 171), F2 (n = 26), F3 (n = 38), and F4 (n = 72), respectively. The discriminating cutoff values for diagnosing ≥ F2, ≥ F3, and F4 were 2.18, 2.71, and 3.15 kPa, respectively, with the ROC curve areas of 0.97–0.98 (sensitivity 91.2%–95.9%, specificity 90.7%–99.0%). The mean LS was significantly higher in patients with cirrhosis (F4) of nonviral causes, such as primary biliary cirrhosis (9.56 kPa) and alcoholic liver disease (7.17 kPa) than in those with hepatitis B or C cirrhosis (4.28 and 4.92 kPa, respectively). There were no statistically significant differences in LS among the different etiologic subgroups in the F0–F3 stages. Conclusion The 3T SE-EPI MRE demonstrated high interobserver reproducibility, and our criteria for staging hepatic fibrosis showed high diagnostic performance. LS was significantly higher in patients with non-viral cirrhosis than in those with viral cirrhosis.
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Affiliation(s)
- Se Woo Kim
- Department of Radiology, Seoul National University Hospital, Seoul, Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Jeong Min Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Korea.,Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul National University Hospital, Seoul, Korea.
| | - Sungeun Park
- Department of Radiology, Konkuk University Medical Center, Seoul, Korea
| | - Ijin Joo
- Department of Radiology, Seoul National University Hospital, Seoul, Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Jeong Hee Yoon
- Department of Radiology, Seoul National University Hospital, Seoul, Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Won Chang
- Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Haeryoung Kim
- Department of Pathology, Seoul National University Hospital, Seoul, Korea.,Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
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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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20
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Lorton O, Toso S, El-Begri Talbi H, Anooshiravani M, Poletti PA, Hanquinet S, Salomir R. A tailored passive driver for liver MRE in pediatric patients. Front Pediatr 2022; 10:999830. [PMID: 36568430 PMCID: PMC9768363 DOI: 10.3389/fped.2022.999830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Accepted: 11/08/2022] [Indexed: 12/12/2022] Open
Abstract
Objectives Magnetic resonance elastography (MRE) is increasingly used in the pediatric population for diagnosis and staging of liver fibrosis. However, the MR-compatible driver and sequences are usually those used for adult patients. Our feasibility study aimed to adapt the standardized adult MRE passive driver and vibrational parameters to a pediatric population. Methods We designed an elliptic passive driver shaped on a torus equipped with an elastic membrane and adapted to children's morphologies. As a first step, eight children (aged 8-18 years) were enrolled in a prospective pilot study aiming to determine the threshold vibrational amplitude for MRE using a custom passive driver, based on phase aliasing assessment and the occurrence of signal void artifacts on magnitude MR images. In the second step, the practicality and the consistency of the custom driver were assessed in a further 11 pediatric patients (aged 7-18 years). In the third step, we compared our custom driver vs. the commercial driver on six adult volunteers, in terms of the reliable region of interest area within the acquired MRE slices, the shear wave maps' quality, and measured stiffness values obtained. Results Based on pediatric patient data, the threshold vibrational amplitude expressed as percentage of maximum output was found to be 0.4 and 1.1 times the body weight (kg) at 40 and 60 Hz frequencies, respectively. In comparison to the commercial passive driver, the custom driver improved threefold the contact with the body surface, also enabling a more comfortable examination as self-assessed by the volunteers. Conclusions Our custom driver was more comfortable for the volunteers and was able to generate more homogenous shear waves, yielding larger usable hepatic area, and more reliable stiffness values.
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Affiliation(s)
- Orane Lorton
- Image Guided Interventions Laboratory (GR 949), Faculty of Medicine, University of Geneva, Geneva, Switzerland
- Radiology Division, University Hospitals of Geneva, Geneva, Switzerland
- Correspondence: Orane Lorton
| | - Seema Toso
- Unit of Pediatric Radiology, Radiology Division, University Hospitals of Geneva, Geneva, Switzerland
| | - Hayat El-Begri Talbi
- Unit of Pediatric Radiology, Radiology Division, University Hospitals of Geneva, Geneva, Switzerland
| | - Mehrak Anooshiravani
- Unit of Pediatric Radiology, Radiology Division, University Hospitals of Geneva, Geneva, Switzerland
| | | | - Sylviane Hanquinet
- Unit of Pediatric Radiology, Radiology Division, University Hospitals of Geneva, Geneva, Switzerland
| | - Rares Salomir
- Image Guided Interventions Laboratory (GR 949), Faculty of Medicine, University of Geneva, Geneva, Switzerland
- Radiology Division, University Hospitals of Geneva, Geneva, Switzerland
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21
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Behairy OG, El-Shimi OS, Shalan NH. Comparative study between liver biopsy and non-invasive biomarkers in assessment of hepatic fibrosis in children with chronic liver diseases. EGYPTIAN PEDIATRIC ASSOCIATION GAZETTE 2021. [DOI: 10.1186/s43054-021-00072-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Liver biopsy is the gold standard for detecting the degree of liver fibrosis; however, invasiveness constitutes its main limiting factor in clinical application, so we aimed to evaluate the non-invasive biomarker formulas (APRI and FIB-4) and their modified forms by BMI z-score (M-APRI, M-FIB-4, and B-AST) compared to liver biopsy in the assessment of liver fibrosis in children with chronic liver diseases. Two hundred children aged 6.3 ± 3.8 years (98 males, 102 females) with chronic liver diseases underwent liver biopsy. The stage of fibrosis was assessed according to the METAVIR system for all children, and the following non-invasive biomarker formulas were calculated: APRI, modified APRI (M-APRI: BMI z-score × APRI), Fibrosis-4 index (FIB-4), modified FIB-4 (M-FIB-4: BMI z-score × FIB-4), and B-AST (BMI z-score × AST). The best cutoff value was calculated to detect early fibrosis (F1–F2) from advanced liver fibrosis (F3–F4).
Results
There were positive correlations between all studied non-invasive biomarker models (APRI, FIB-4, M-APRI, M-FIB-4, B-AST) and fibrosis score as an increase in fibrosis score was associated with an increase in mean ± SD of all studied biomarker formulas. The best cutoff values of non-invasive biomarker models in the diagnosis of early fibrosis (F1–F2) were APRI > 0.96, M-APRI > 0.16, FIB-4 > 0.019, M-FIB-4 > 0.005, and B-AST > −8 with an area under the curve above 0.7 each, while the best cutoff values of non-invasive biomarker models (APRI, M-APRI, FIB-4, M-FIB-4, and B-AST) in the diagnosis of advanced liver fibrosis (F3–F4) were >1.96, >2.2, >0.045, and >0.015, >92.1, respectively, with an area under the curve above 0.8 each.
Conclusion
APRI, M-APRI, FIB-4, M-FIB-4, and B-AST are good non-invasive alternatives to liver biopsy in the detection of liver fibrosis in children with chronic liver diseases of different etiologies especially those that include BMI z-scores in their formulas.
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22
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Behairy OG, El-Bakry MM, Mansour AI, Abdelrahman AMN, Emam GM. Matrix metalloproteinase-1 as a non-invasive biomarker to assess liver fibrosis in children with chronic liver disease. EGYPTIAN LIVER JOURNAL 2021. [DOI: 10.1186/s43066-021-00148-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Abnormal extracellular matrix (ECM) turnover is linked to liver fibrosis as it reflects an imbalance between repair and progressive substitution of the liver parenchyma by scar tissue. Matrix metalloproteinases (MMPs) are the primary enzymes involved in ECM breakdown. So, this study aims to measure the value of serum matrix metalloproteinase-1 (MMP-1) in children with chronic liver diseases (CLD) in comparison with liver biopsy and serum biomarkers. A hundred twenty children with chronic liver diseases and sixty healthy children as a control group were included in this study. Both groups were evaluated via medical history, clinical, radiological, laboratory investigations, and serum MMP-1 level was measured by ELISA. Liver biopsy was performed for studied patients only.
Results
The mean MMP-1 was 15.2 ± 5.1 ng/ml in children with CLD, and 64.7 ± 27.4 ng/ml in the control group. MMP-1 was statistically lower in the children with CLD than controls (p < 0.001). The mean ± SD of aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB-4) scores in all studied cases showed a significant trend of increase with progressive fibrosis stage evident with histological METAVIR scoring system, while serum MMP-1 concentration was decreased significantly with increasing the degree of fibrosis in CLD group (P 0.001). Serum MMP-1 was indirectly correlated with serum biomarkers and the degree of fibrosis in patients.
Conclusions
MMP-1 is a useful non-invasive marker for detection of the stage of liver fibrosis in children with chronic liver diseases.
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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: 17] [Impact Index Per Article: 4.3] [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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24
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Malbul K, Katwal S, Khetan S, Aryal N. A case report on serendipitous diagnosis of wilson's disease in a child with brucellosis and pseudomonal infection. Clin Case Rep 2021; 9:e04178. [PMID: 34194770 PMCID: PMC8222750 DOI: 10.1002/ccr3.4178] [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] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Revised: 03/28/2021] [Accepted: 03/31/2021] [Indexed: 12/18/2022] Open
Abstract
Wilson's disease can have varied clinical manifestations and initial presentation can be misleading as in our case. Our case depicts the necessity of suspicion of WD in variable presentation of liver disorders, especially in pediatrics population.
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Affiliation(s)
- Kiran Malbul
- Nepalese Army Institute of Health Sciences College of MedicineKathmanduNepal
| | - Srijana Katwal
- Nepalese Army Institute of Health Sciences College of MedicineKathmanduNepal
| | - Saurav Khetan
- Department of PediatricsShree Birendra HospitalKathmanduNepal
| | - Nirjala Aryal
- Department of PediatricsShree Birendra HospitalKathmanduNepal
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25
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Mogahed EA, El-Karaksy H, Abdullatif H, Yasin NA, Nagy A, Alem SA, Eldeen HG, El-Raziky MS. Improvement in Liver Stiffness in Pediatric Patients with Hepatitis C Virus after Treatment with Direct Acting Antivirals. J Pediatr 2021; 233:126-131. [PMID: 33577805 DOI: 10.1016/j.jpeds.2021.02.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Revised: 02/04/2021] [Accepted: 02/05/2021] [Indexed: 02/08/2023]
Abstract
OBJECTIVES To assess the degree of liver stiffness using transient elastography in Egyptian children infected with hepatitis C virus (HCV) at baseline and 1 year after achievement of sustained virologic response (SVR) with direct acting antivirals. STUDY DESIGN This prospective study included children infected with HCV who received treatment with sofosbuvir/ledipasvir and achieved SVR. At baseline and 1 year after achievement of SVR, the extent of hepatic fibrosis was assessed by transient elastography using FibroScan to measure liver stiffness, in addition to noninvasive markers including aspartate aminotransferase/platelet ratio index (APRI) and fibrosis-4 (FIB-4) index. RESULTS The study included 23 cases that had variable degrees of fibrosis at baseline; their ages ranged between 10 and 18 years. At baseline, 13 patients had F1; 3 patients had F1-F2; 1 patient had F2; 3 patients had F3; 2 had F3-F4; and 2 patients with F4. One year after achievement of SVR, there was a statistically significant improvement in liver stiffness, APRI, and FIB-4 index (P = .03, <.001, .02, respectively). In 13 patients (56.5%), the liver stiffness improved; in 7 patients, it was stationary; and the remaining 3 patients showed mild increase in liver stiffness that was, however, associated with improvement in APRI and FIB-4 index. Comorbid conditions and previous treatment with interferon were not associated with increased liver stiffness 1 year after SVR. CONCLUSIONS Egyptian children infected with HCV genotype 4 achieved significant regression in liver stiffness after treatment with direct acting antivirals.
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Affiliation(s)
- Engy A Mogahed
- Department of Pediatrics, Cairo University, Cairo, Egypt.
| | | | | | - Noha A Yasin
- Department of Pediatrics, Cairo University, Cairo, Egypt
| | - Ahmed Nagy
- Department of Tropical Medicine, Cairo University, Cairo, Egypt
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26
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Ferraioli G, Barr RG, Dillman JR. Elastography for Pediatric Chronic Liver Disease: A Review and Expert Opinion. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2021; 40:909-928. [PMID: 32881048 DOI: 10.1002/jum.15482] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 07/28/2020] [Accepted: 08/02/2020] [Indexed: 06/11/2023]
Abstract
In adults with chronic liver diseases, ultrasound and magnetic resonance shear wave elastography (SWE) can replace liver biopsy in several clinical scenarios. Several guidelines on the use of ultrasound SWE for the adult population have been published. However, the number of publications in the pediatric population is limited, and available guidelines on SWE do not specifically address pediatric chronic liver diseases. In this article, we review the literature on the use of SWE for pediatric chronic liver diseases and provide expert opinion on how to use SWE, both ultrasound and magnetic resonance techniques, in the pediatric population.
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Affiliation(s)
- Giovanna Ferraioli
- Ultrasound Unit, Department of Clinical Sciences and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | | | - Jonathan R Dillman
- Department of Radiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio
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Pons M, Núñez A, Esquinas C, Torres-Durán M, Rodríguez-Hermosa JL, Calle M, Tubio-Pérez R, Belmonte I, Rodríguez-Frías F, Rodríguez E, Genescà J, Miravitlles M, Barrecheguren M. Utility of Transient Elastography for the Screening of Liver Disease in Patients with Alpha1-Antitrypsin Deficiency. J Clin Med 2021; 10:jcm10081724. [PMID: 33923569 PMCID: PMC8073267 DOI: 10.3390/jcm10081724] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 04/12/2021] [Accepted: 04/13/2021] [Indexed: 02/07/2023] Open
Abstract
Screening of liver disease in alpha-1 antitrypsin deficiency (AATD) is usually carried out with liver enzymes, with low sensitivity. We conducted a multicenter cross-sectional study aiming to describe the utility of transient elastography for the identification of liver disease in patients with AATD. A total of 148 AATD patients were included. Among these, 54.7% were Pi*ZZ and 45.3% were heterozygous for the Z allele. Between 4.9% and 16.5% of patients had abnormal liver enzymes, without differences among genotypes. Liver stiffness measurement (LSM) was significantly higher in Pi*ZZ individuals than in heterozygous Z (5.6 vs. 4.6 kPa; p = 0.001). In total, in 8 (5%) individuals LSM was >7.5 kPa, considered significant liver fibrosis, and ≥10 kPa in 3 (1.9%) all being Pi*ZZ. Elevated liver enzymes were more frequently observed in patients with LSM > 7.5 kPa, but in 5 out of 8 of these patients all liver enzymes were within normal range. In patients with AATD, the presence of abnormal liver enzymes is frequent; however, most of these patients do not present significant liver fibrosis. Transient elastography can help to identify patients with liver fibrosis even with normal liver enzymes and should be performed in all Z-allele carriers to screen for liver disease.
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Affiliation(s)
- Mònica Pons
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain; (M.P.); (J.G.)
| | - Alexa Núñez
- Pneumology Department, Hospital Universitari Vall d’Hebron/Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain; (A.N.); (C.E.); (I.B.); (E.R.); (M.B.)
- Department of Medicine, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
| | - Cristina Esquinas
- Pneumology Department, Hospital Universitari Vall d’Hebron/Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain; (A.N.); (C.E.); (I.B.); (E.R.); (M.B.)
- Department of Medicine, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
| | - María Torres-Durán
- Pneumology Department, University Hospital Complex of Vigo, Instituto de Investigación Biomédica Galicia Sur, 36213 Vigo, Spain; (M.T.-D.); (R.T.-P.)
| | - Juan Luis Rodríguez-Hermosa
- Pneumology Department, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico de San Carlos, Departamento de Medicina, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain; (J.L.R.-H.); (M.C.)
| | - Myriam Calle
- Pneumology Department, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico de San Carlos, Departamento de Medicina, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain; (J.L.R.-H.); (M.C.)
| | - Ramón Tubio-Pérez
- Pneumology Department, University Hospital Complex of Vigo, Instituto de Investigación Biomédica Galicia Sur, 36213 Vigo, Spain; (M.T.-D.); (R.T.-P.)
| | - Irene Belmonte
- Pneumology Department, Hospital Universitari Vall d’Hebron/Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain; (A.N.); (C.E.); (I.B.); (E.R.); (M.B.)
| | - Francisco Rodríguez-Frías
- Department of Clinical Biochemistry, Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain;
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
| | - Esther Rodríguez
- Pneumology Department, Hospital Universitari Vall d’Hebron/Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain; (A.N.); (C.E.); (I.B.); (E.R.); (M.B.)
| | - Joan Genescà
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain; (M.P.); (J.G.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
| | - Marc Miravitlles
- Pneumology Department, Hospital Universitari Vall d’Hebron/Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain; (A.N.); (C.E.); (I.B.); (E.R.); (M.B.)
- Department of Medicine, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain
- Correspondence:
| | - Miriam Barrecheguren
- Pneumology Department, Hospital Universitari Vall d’Hebron/Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain; (A.N.); (C.E.); (I.B.); (E.R.); (M.B.)
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Lee S, Choi YH, Cho YJ, Lee SB, Cheon JE, Kim WS, Ko JS, Koh J, Kang GH. The usefulness of noninvasive liver stiffness assessment using shear-wave elastography for predicting liver fibrosis in children. BMC Med Imaging 2021; 21:68. [PMID: 33845776 PMCID: PMC8040233 DOI: 10.1186/s12880-021-00601-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Accepted: 04/01/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Pediatric patients with liver disease require noninvasive monitoring to evaluate the risk of fibrosis progression. This study aimed to identify the significant factors affecting liver stiffness values using two-dimensional shear-wave elastography (2D-SWE), and determine whether liver stiffness can predict the fibrosis stage of various childhood liver diseases. METHODS This study included 30 children (22 boys and 8 girls; mean age, 5.1 ± 6.1 years; range, 7 days-17.9 years) who had undergone biochemical evaluation, 2D-SWE examination, histopathologic analysis of fibrosis grade (F0 to F3), assessment of necroinflammatory activity, and steatosis grading between August 2016 and March 2020. The liver stiffness from 2D-SWE was compared between fibrosis stages using Kruskal-Wallis analysis. Factors that significantly affected liver stiffness were evaluated using univariate and multivariate linear regression analyses. The diagnostic performance was determined from the area under the receiver operating curve (AUC) values of 2D-SWE liver stiffness. RESULTS Liver stiffness at the F0-1, F2, and F3 stages were 7.9, 13.2, and 21.7 kPa, respectively (P < 0.001). Both fibrosis stage and necroinflammatory grade were significantly associated with liver stiffness (P < 0.001 and P = 0.021, respectively). However, in patients with alanine aminotransferase (ALT) levels below 200 IU/L, the only factor affecting liver stiffness was fibrosis stage (P = 0.030). The liver stiffness value could distinguish significant fibrosis (≥ F2) with an AUC of 0.950 (cutoff value, 11.3 kPa) and severe fibrosis (F3 stage) with an AUC of 0.924 (cutoff value, 18.1 kPa). The 2D-SWE values for differentiating significant fibrosis were 10.5 kPa (≥ F2) and 18.1 kPa (F3) in patients with ALT levels below 200 IU/L. CONCLUSION The liver stiffness values on 2D-SWE can be affected by both fibrosis and necroinflammatory grade and can provide excellent diagnostic performance in evaluating the fibrosis stage in various pediatric liver diseases. However, clinicians should be mindful of potential confounders, such as necroinflammatory activity or transaminase level, when performing 2D-SWE measurements for liver fibrosis staging.
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Affiliation(s)
- Seunghyun Lee
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Young Hun Choi
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. .,Department of Radiology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
| | - Yeon Jin Cho
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Seul Bi Lee
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Jung-Eun Cheon
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.,Department of Radiology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.,Institute of Radiation Medicine, Seoul National University Medical Research Center, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Woo Sun Kim
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.,Department of Radiology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.,Institute of Radiation Medicine, Seoul National University Medical Research Center, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Jae Sung Ko
- Department of Pediatrics, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Jaemoon Koh
- Department of Pathology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Gyeong Hoon Kang
- Department of Pathology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
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29
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Przybyłkowski A, Szeligowska J, Januszewicz M, Raszeja-Wyszomirska J, Szczepankiewicz B, Nehring P, Górnicka B, Litwin T, Członkowska A. Evaluation of liver fibrosis in patients with Wilson's disease. Eur J Gastroenterol Hepatol 2021; 33:535-540. [PMID: 32433421 PMCID: PMC8565503 DOI: 10.1097/meg.0000000000001754] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 04/06/2020] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Staging of fibrosis in chronic liver disease is important for prognosis and treatment planning. Liver biopsy is the gold standard in fibrosis assessment; however, new methods for fibrosis and stiffness measurement exist which have not been evaluated in patients with Wilson's disease. To evaluate the accuracy of collagen proportionate area (CPA), transient elastography and shear wave elastography (SWE) in the assessment of liver fibrosis in adult patients with Wilson's disease. METHODS In this retrospective study of 60 patients with Wilson's disease, results of percutaneous cutting liver biopsy assessed using the Ishak fibrosis score and CPA were compared with liver stiffness measured with transient elastography and SWE. RESULTS CPA correlated with the Ishak score (r = 0.45; P = 0.001) and transient elastography results correlated with SWE measurements (r = 0.80; P = 0.0001). In contrast, transient elastography or SWE did not significantly correlate with the Ishak score or CPA. CONCLUSION Collagen content assessment may be useful for estimation of liver fibrosis in patients with Wilson's disease. However, single time-point elastographic liver stiffness measurements have a limited diagnostic value in Wilson's disease.
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Affiliation(s)
| | | | | | | | | | - Piotr Nehring
- Department of Gastroenterology and Internal Medicine
| | - Barbara Górnicka
- Chair and Department of Pathomorphology, Medical University of Warsaw
| | - Tomasz Litwin
- Second Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland
| | - Anna Członkowska
- Second Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland
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30
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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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31
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Perucca G, de Lange C, Franchi-Abella S, Napolitano M, Riccabona M, Ključevšek D, Toso S, Herrmann J, Stafrace S, Darge K, Damasio MB, Bruno C, Woźniak MM, Lobo L, Ibe D, Smets AM, Petit P, Ording Müller LS. Surveillance of Fontan-associated liver disease: current standards and a proposal from the European Society of Paediatric Radiology Abdominal Task Force. Pediatr Radiol 2021; 51:2598-2606. [PMID: 34654967 PMCID: PMC8599216 DOI: 10.1007/s00247-021-05173-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 06/08/2021] [Accepted: 07/31/2021] [Indexed: 12/16/2022]
Abstract
Since Francis Fontan first introduced the eponymous technique, the Fontan procedure, this type of surgical palliation has allowed thousands of children affected by specific heart malformations to reach adulthood. Nevertheless, abdominal, thoracic, lymphatic and neurologic complications are the price that is paid by these patients. Our review focuses on Fontan-associated liver disease; the purpose is to summarize the current understanding of its physiopathology, the aim of follow-up and the specific radiologic follow-up performed in Europe. Finally, we as members of the Abdominal Task Force of the European Society of Paediatric Radiology propose a consensus-based imaging follow-up algorithm.
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Affiliation(s)
- Giulia Perucca
- Department of Pediatric Radiology, Regina Margherita Children’s Hospital, Turin, Italy
| | - Charlotte de Lange
- Department of Radiology and Clinical Physiology, Queen Silvia Children’s Hospital, Sahlgrenska University Hospital, Göteborg, Sweden
| | - Stéphanie Franchi-Abella
- Pediatric Radiology Department, Hôpital Bicêtre, Hôpitaux Universitaire Paris-Sud, Assistance Publique Hôpitaux de Paris, Le Kremlin-Bicêtre, France
| | - Marcello Napolitano
- Department of Paediatric Radiology and Neuroradiology, V. Buzzi Children’s Hospital, Milan, Italy
| | - Michael Riccabona
- Department of Radiology, Division of Pediatric Radiology, Medical University Graz and University Hospital LKH, Graz, Austria
| | - Damjana Ključevšek
- Department of Radiology, University Children’s Hospital Ljubljana, Ljubljana, Slovenia
| | - Seema Toso
- Department of Pediatric Radiology, University Hospital of Geneva, Geneva, Switzerland
| | - Jochen Herrmann
- Department of Pediatric Radiology, University Hospital Hamburg Eppendorf, Hamburg, Germany
| | - Samuel Stafrace
- Department of Diagnostic Imaging, Sidra Medicine, Doha, Qatar ,Weill Cornell Medicine, Doha, Qatar
| | - Kassa Darge
- Department of Radiology, The Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA USA
| | | | - Costanza Bruno
- Department of Radiology, Azienda Ospedaliera Universitaria Integrata Verona (AOUI), Verona, Italy
| | | | - Luisa Lobo
- Serviço de Imagiologia Geral, Hospital de Santa Maria–Centro Hospitalar Universitário Lisboa, Norte (CHULN), Lisbon, Portugal
| | - Donald Ibe
- Department of Radiology, Silhouette Diagnostic Consultants, Abuja, Nigeria
| | - Anne M. Smets
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Philippe Petit
- Aix Marseille Université, AP-HM, Equipe d’Accueil 3279 - IFR 125, Hôpital Timone Enfants, Service d’Imagerie Pédiatrique et Prénatale, Marseille, France
| | - Lil-Sofie Ording Müller
- Unit for Paediatric Radiology, Department of Radiology, Oslo University Hospital, Rikshospitalet, PB 4950 Nydalen, 0424 Oslo, Norway.
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Teufel-Schäfer U, Flechtenmacher C, Fichtner A, Hoffmann GF, Schenk JP, Engelmann G. Transient elastography correlated to four different histological fibrosis scores in children with liver disease. Eur J Pediatr 2021; 180:2237-2244. [PMID: 33704581 PMCID: PMC8195947 DOI: 10.1007/s00431-021-04001-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 01/15/2021] [Accepted: 02/18/2021] [Indexed: 12/17/2022]
Abstract
Currently, liver histology is the gold standard for the detection of liver fibrosis. In recent years, new methods such as transient elastography (TE) have been introduced into clinical practice, which allow a non-invasive assessment of liver fibrosis. The aim of the present study was to investigate the predictive value of TE for higher grade fibrosis and whether there is any relevance which histologic score is used for matching. For this purpose, we compared TE with 4 different histologic scores in pediatric patients with hepatopathies. Furthermore, we also determined the aspartate aminotransferase-to-platelet ratio (APRI) score, another non-invasive method, to investigate whether it is equally informative. Therefore, liver fibrosis in 75 children was evaluated by liver biopsy, TE and laboratory values. Liver biopsies were evaluated using four common histological scoring systems (Desmet, Metavir, Ishak and Chevalier's semi-quantitative scoring system). The median age of the patients was 12.3 years. TE showed a good correlation to the degree of fibrosis severity independent of the histological scoring system used. The accuracy of the TE to distinguish between no/minimal fibrosis and severe fibrosis/cirrhosis was good (p = 0.001, AUC-ROCs > 0.81). The optimal cut-off value for the prediction of severe fibrosis was 10.6 kPa. In contrast, the APRI score in our collective showed no correlation to fibrosis.Conclusion: TE shows a good correlation to the histological findings in children with hepatopathy, independent of the used histological scoring system. What is Known: • The current gold standard for detecting liver fibrosis is liver biopsy. Novel non-invasive ultrasound-based methods are introduced to clinical diagnostics. • Most histological scores have been developed and evaluated in adult populations and for only one specific liver disease. What is New: • Transient elastography (TE) in children showed a good correlation to fibrosis severity irrespective of the utilized histological scoring system. • The aspartate aminotransferase-to-platelet ratio (APRI) showed no correlation with different stages of liver fibrosis in children.
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Affiliation(s)
- Ulrike Teufel-Schäfer
- Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center, University of Freiburg, Mathildenstr. 1, 79106 Freiburg, Germany
- Division of Pediatric Gastroenterology and Hepatology, Center for Child and Adolescent Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany
| | - Christa Flechtenmacher
- Department of Pathology, University Medical Centre, University of Heidelberg, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany
| | - Alexander Fichtner
- Division of Pediatric Gastroenterology and Hepatology, Center for Child and Adolescent Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany
| | - Georg Friedrich Hoffmann
- Division of Pediatric Gastroenterology and Hepatology, Center for Child and Adolescent Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany
| | - Jens Peter Schenk
- Division of Pediatric Radiology, Department of Diagnostic and Interventional Radiology, University Medical Centre, University of Heidelberg, Heidelberg, Germany
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Progress and Barriers Towards Elimination of Chronic Hepatitis C in Children. KLINISCHE PADIATRIE 2020; 233:211-215. [PMID: 33339066 DOI: 10.1055/a-1304-3542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Chronic hepatitis C (CHC) is a global health burden. Mother-to-child transmission (MTCT) accounts for most HCV infections in pediatric patients. Spontaneous viral clearance may occur in early childhood but is uncommon thereafter. Infection is usually asymptomatic during childhood, although without an effective treatment, vertically infected children may develop serious liver complications including cirrhosis and hepatocellular carcinoma in adulthood. Despite the lack of vaccine against hepatitis C and effective post-exposure methods of prevention of MTCT, treatment with direct-acting antiviral agents (DAAs) raised the prospect of eliminating HCV on a population level. Highly effective, well-tolerated, oral, and interferon-free regimens of short duration have revolutionized treatment of CHC. However, access to these therapies might be limited because of its high cost. In this review, we provide the current state of knowledge on the epidemiology, testing, monitoring and treating of HCV in children. We outline the remaining gaps in therapy and barriers to disease eradication.
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Li DK, Khan MR, Wang Z, Chongsrisawat V, Swangsak P, Teufel-Schäfer U, Engelmann G, Goldschmidt I, Baumann U, Tokuhara D, Cho Y, Rowland M, Mjelle AB, Ramm GA, Lewindon PJ, Witters P, Cassiman D, Ciuca IM, Prokop LD, Haffar S, Corey KE, Murad MH, Furuya KN, Bazerbachi F. Normal liver stiffness and influencing factors in healthy children: An individual participant data meta-analysis. Liver Int 2020; 40:2602-2611. [PMID: 32901449 DOI: 10.1111/liv.14658] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 08/20/2020] [Accepted: 08/22/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Although transient elastography (TE) is used to determine liver stiffness as a surrogate to hepatic fibrosis, the normal range in children is not well defined. We performed a systematic review and individual participant data (IPD) meta-analysis to determine the range of liver stiffness in healthy children and evaluate the influence of important biological parameters. METHODS We pooled data from 10 studies that examined healthy children using TE. We divided 1702 children into two groups: ≥3 years (older group) and < 3 years of age (younger group). Univariate and multivariate linear regression models predicting liver stiffness were conducted. RESULTS After excluding children with obesity, diabetes, or abnormal liver tests, 652 children were analysed. Among older children, mean liver stiffness was 4.45 kPa (95% confidence interval 4.34-4.56), and increased liver stiffness was associated with age, sedation status, and S probe use. In the younger group, the mean liver stiffness was 4.79 kPa (95% confidence interval 4.46-5.12), and increased liver stiffness was associated with sedation status and Caucasian race. In a subgroup analysis, hepatic steatosis on ultrasound was significantly associated with increased liver stiffness. We define a reference range for normal liver stiffness in healthy children as 2.45-5.56 kPa. CONCLUSIONS We have established TE-derived liver stiffness ranges for healthy children and propose an upper limit of liver stiffness in healthy children to be 5.56 kPa. We have identified increasing age, use of sedation, probe size, and presence of steatosis on ultrasound as factors that can significantly increase liver stiffness.
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Affiliation(s)
- Darrick K Li
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Muhammad Rehan Khan
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Illinois College of Medicine at Peoria, Children's Hospital of Illinois, Peoria, IL, USA
| | - Zhen Wang
- Evidence-Based Practice Center, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
| | - Voranush Chongsrisawat
- Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Panida Swangsak
- Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Ulrike Teufel-Schäfer
- Department of Pediatrics and Adolescent Medicine, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | | | - Imeke Goldschmidt
- Division of Paediatric Gastroenterology and Hepatology, Hannover Medical School, Hannover, Germany
| | - Ulrich Baumann
- Division of Paediatric Gastroenterology and Hepatology, Hannover Medical School, Hannover, Germany.,Institute of Immunology and Immunotherapy, University of Birmingham, United Kingdom
| | - Daisuke Tokuhara
- Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Yuki Cho
- Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Marion Rowland
- School of Medicine and Medical Science, University College Dublin, Dublin, Ireland
| | - Anders B Mjelle
- Department of Pediatric and Adolescent Medicine, Haukeland University Hospital, Bergen, Norway.,Department of Clinical Medicine, University of Bergen, Bergen, Norway.,National Centre for Ultrasound in Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | - Grant A Ramm
- Hepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
| | - Peter J Lewindon
- Department of Gastroenterology, Hepatology and Liver Transplant, Queensland Children's Hospital, Brisbane, Australia
| | - Peter Witters
- Department of Paediatrics, University Hospitals Leuven, Leuven, Belgium
| | - David Cassiman
- Department of Gastroenterology-Hepatology and Metabolic Center, University of Leuven, Leuven, Belgium
| | - Ioana M Ciuca
- Pediatrics Department, University of Medicine and Pharmacy "Victor Babes", Timisoara, Romania
| | - Larry D Prokop
- Evidence-Based Practice Center, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
| | - Samir Haffar
- Digestive Center for Diagnosis and Treatment, Damascus, Syrian Arab Republic
| | - Kathleen E Corey
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - M H Murad
- Evidence-Based Practice Center, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
| | - Katryn N Furuya
- Department of Pediatrics, University of Wisconsin - Madison School of Medicine and Public Health, Madison, WI, USA
| | - Fateh Bazerbachi
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
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Tibuakuu M, Jjingo C, Kirk GD, Thomas DL, Gray R, Ssempijja V, Nalugoda F, Serwadda D, Ocama P, Opio CK, Kleiner DE, Quinn TC, Reynolds SJ. Elevated liver stiffness without histological evidence of liver fibrosis in rural Ugandans. J Viral Hepat 2020; 27:1022-1031. [PMID: 32388879 PMCID: PMC8919060 DOI: 10.1111/jvh.13320] [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: 11/07/2019] [Revised: 02/20/2020] [Accepted: 04/12/2020] [Indexed: 12/09/2022]
Abstract
Liver fibrosis may be assessed noninvasively with transient electrography (TE). Data on the performance of TE for detecting liver fibrosis in sub-Saharan Africa are limited. We evaluated the diagnostic accuracy of TE by performing liver biopsies on persons with liver fibrosis indicated by TE. We enrolled HIV-infected and HIV-uninfected participants with TE scores consistent with at least minimal disease (liver stiffness measurement [LSM]≥7.1 kPa). Biopsies were performed and staged using the Ishak scoring system. A concordant result was defined using accepted thresholds for significant fibrosis by TE (LSM ≥ 9.3 kPa) and liver biopsy (Ishak score ≥ 2). We used modified Poisson regression methods to quantify the univariate and adjusted prevalence risk ratios (PRR) of the association between covariates and the concordance status of TE and liver biopsy in defining the presence of liver fibrosis. Of 131 participants with valid liver biopsy and TE data, only 5 participants (3.8%) had Ishak score ≥ 2 of whom 4 had LSM ≥ 9.3 kPa (sensitivity = 80%); of the 126 (96.2%) with Ishak score < 2, 76 had LSM < 9.3 kPa (specificity = 61%). In multivariable analysis, discordance was associated with female gender (adjPRR = 1.80, 95%CI 1.1-2.9; P = .019), herbal medicine use (adjPRR 1.64, 95% CI = 1.0-2.5; P = .022), exposure to lake or river water (adjPRR 2.05, 95% CI = 1.1-3.7; P = .016), and current smoking (adjPRR 1.72, 95%CI 1.0-2.9; P = .045). These data suggest that TE among rural Ugandans has low specificity for detection of histologically confirmed liver fibrosis. Caution should be exercised when using this tool to confirm significant liver fibrosis.
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Affiliation(s)
- Martin Tibuakuu
- Department of Medicine, St. Luke’s Hospital, Chesterfield, Missouri
| | - Caroline Jjingo
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
| | - Gregory Dale Kirk
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland
| | - David Lee Thomas
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland
| | - Ronald Gray
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
- Rakai Health Sciences Program, Entebbe, Uganda
| | - Victor Ssempijja
- Clinical Research Directorate/Clinical Monitoring Research Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, Maryland
| | | | - David Serwadda
- Rakai Health Sciences Program, Entebbe, Uganda
- School of Public Health, Makerere University College of Health Sciences, Kampala, Uganda
| | - Ponsiano Ocama
- School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
| | | | | | - Thomas Charles Quinn
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland
| | - Steven James Reynolds
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland
- Rakai Health Sciences Program, Entebbe, Uganda
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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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Mercedes R, Brown J, Minard C, Tsai CM, Devaraj S, Munden M, Leung D. A Liver Biopsy Validation Pilot Study of Shear Wave Elastography, APRI, FIB-4, and Novel Serum Biomarkers for Liver Fibrosis Staging in Children With Chronic Viral Hepatitis. Glob Pediatr Health 2020; 7:2333794X20938931. [PMID: 32821773 PMCID: PMC7412911 DOI: 10.1177/2333794x20938931] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 03/12/2020] [Accepted: 05/26/2020] [Indexed: 01/04/2023] Open
Abstract
As liver biopsy in children poses inherent risks, noninvasive measures of liver fibrosis are needed. This was a cross-sectional, liver biopsy validation pilot study of 16 participants evaluating the ability of shear wave elastography, aspartate transaminase to platelet ratio index (APRI), fibrosis index based on the 4 factors, and novel serum biomarkers to stage liver fibrosis in children with chronic hepatitis B or C. There was very high intrasegmental shear wave speed variation in our participants and little correlation with fibrosis. APRI and monocyte chemoattractant protein (MCP-1) were higher in fibrosis stage F2-3 versus F0-1 (P = .02, P = .06, respectively). Soluble Fas (sFas) was lower in F2-3 versus F0-1 (P = .046). A logistic regression analysis calculated by (APRI × MCP-1)/sFas demonstrated an area under the receiver operating characteristic curve of 0.92 (P < .001), suggesting that this combination can differentiate fibrosis stage F0-1 from F2-3 in children with chronic viral hepatitis.
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Affiliation(s)
| | | | | | - Cynthia M Tsai
- Baylor College of Medicine, Houston, TX, USA.,Texas Children's Hospital, Houston, TX, USA
| | | | - Marthe Munden
- Wake Forest Baptist Medical Center, Winston-Salem, NC, USA
| | - Daniel Leung
- Baylor College of Medicine, Houston, TX, USA.,Texas Children's Hospital, Houston, TX, USA
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Dardanelli EP, Orozco ME, Lostra J, Laprida C, Lulkin S, Bosaleh AP, Cernadas C, Lipsich JE. Bidimensional shear-wave elastography for assessing liver fibrosis in children: a proposal of reference values that correlate with the histopathological Knodell-Ishak score. Pediatr Radiol 2020; 50:817-826. [PMID: 32072246 DOI: 10.1007/s00247-020-04632-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Revised: 12/10/2019] [Accepted: 01/24/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND A limited number of publications correlate bidimensional shear-wave elastography (2-D SWE) and stages of liver fibrosis in children. OBJECTIVE To correlate liver elastography values using 2-D SWE and liver biopsy classified by Knodell-Ishak score to evaluate fibrosis in pediatric patients with liver disease, and to propose values of 2-D SWE (kPa) correlating with Knodell-Ishak score, which have not been defined in the literature. MATERIALS AND METHODS We conducted a prospective cross-sectional observational study on the performance of diagnostic tests. Between June 2016 and June 2018, elastography was performed in 213 children and young adults who had undergone liver biopsy. B mode, Doppler and 2-D SWE were performed using an Aixplorer (SuperSonic Imagine, Aix-en-Provence, France). Histology samples were classified using the Knodell-Ishak score. We evaluated performance by assessing sensitivity, specificity, positive predictive value and negative predictive value. To determine cut-off points for the continuous variables, we used receiver operating characteristic (ROC) curves. All the cutoff values we established apply only to the SuperSonic Aixplorer system. RESULTS Measurement with 2-D SWE was successful, with a good correlation with fibrosis stage. The area under the curve (AUC) to differentiate between early (Stages 1-2) and moderate (Stages 3-4) fibrosis was 0.91 (95% confidence interval [CI]: 0.87-0.96), with a sensitivity of 92% and specificity of 86%, with a cutoff value 12 kPa (2 m/s). The AUC of severe fibrosis (early stages of cirrhosis; Stage 5) was 0.95 (95% CI: 0.92-0.97), with a sensitivity of 94% and specificity of 90%, with a cutoff value 18.5 kPa (2.48 m/s). In two patients with hematopoietic stem cell transplantation and suspicion of graft versus host disease we found high 2-D SWE values in correlation with the fibrosis stages (Stage 0 with a median of 13 kPa [2.08 m/s] with hemosiderosis Grade 2 in one child and Stage 2 with a median of 46 kPa [3.91 m/s] and hemosiderosis Grade 4 in the other). CONCLUSION Our study shows the usefulness and accuracy of 2-D SWE for detecting liver fibrosis in pediatric patients. We propose reference values for Knodell-Ishak Stages 1 and 5. We found hemosiderosis as a possible confounding factor that hasn't been described with 2-D SWE.
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Affiliation(s)
- Esteban P Dardanelli
- Department of Radiology, Hospital de Pediatría J. P. Garrahan Buenos Aires, Combate de los Pozos 1881 (C 1245 AAM), Buenos Aires, Argentina.
| | - Maria Eugenia Orozco
- Department of Radiology, Hospital de Pediatría J. P. Garrahan Buenos Aires, Combate de los Pozos 1881 (C 1245 AAM), Buenos Aires, Argentina
| | - Juliana Lostra
- Department of Radiology, Hospital de Pediatría J. P. Garrahan Buenos Aires, Combate de los Pozos 1881 (C 1245 AAM), Buenos Aires, Argentina
| | - Clarisa Laprida
- Department of Radiology, Hospital de Pediatría J. P. Garrahan Buenos Aires, Combate de los Pozos 1881 (C 1245 AAM), Buenos Aires, Argentina
| | - Solange Lulkin
- Department of Radiology, Hospital de Pediatría J. P. Garrahan Buenos Aires, Combate de los Pozos 1881 (C 1245 AAM), Buenos Aires, Argentina
| | - Andrea P Bosaleh
- Department of Pathology, Hospital de Pediatría J. P. Garrahan Buenos Aires, Buenos Aires, Argentina
| | - Carolina Cernadas
- Department of Research and Development, Hospital de Pediatría J. P. Garrahan Buenos Aires, Buenos Aires, Argentina
| | - José E Lipsich
- Department of Radiology, Hospital de Pediatría J. P. Garrahan Buenos Aires, Combate de los Pozos 1881 (C 1245 AAM), Buenos Aires, Argentina
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Mărginean CO, Meliţ LE, Ghiga DV, Săsăran MO. Reference values of normal liver stiffness in healthy children by two methods: 2D shear wave and transient elastography. Sci Rep 2020; 10:7213. [PMID: 32350349 PMCID: PMC7190848 DOI: 10.1038/s41598-020-64320-w] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2019] [Accepted: 04/09/2020] [Indexed: 12/03/2022] Open
Abstract
TE and 2D-SWE are well-documented in studies performed on adults, but those on pediatric patients are limited. The aim of this study was to establish pediatric reference values for liver stiffness using two elastography methods: 2D-SWE and TE. We performed an observational study on 206 healthy children. All children underwent anamnesis, clinical exam, laboratory tests, US exam, TE and 2D-SWE for liver stiffness assessment. The mean liver stiffness value by 2D-SWE for all children was 3.72 ± 0.48 kPa. The mean values ranged between 3.603 ± 0.2678 kPa (3–5 years of age) and 3.774 ± 0.4038 kPa (9–11 years). The reference values varied between 4.1386 kPa (3–5 years of age) and 4.88 kPa (12–15 years). The mean liver stiffness value by TE was 3.797 ± 0.4859 kPa. The values ranged between 3.638 ± 0.4088 kPa (6–8 years of age) and 3.961 ± 0.5695 kPa (15–18 years). The cutoff values varied from 4.4064 kPa (3–5 years of age) to 5.1 kPa (15–18 years). We found a significant positive correlation between E Median values by TE and age [95% CI: 0.1160 to 0.3798, r = 0.2526, p = 0.0002]. Our findings revealed that the mean values of liver stiffness for all children on 2D-SWE and TE were almost identical, 3.72 ± 0.48 kPa versus 3.797 ± 0.4859 kPa.
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Affiliation(s)
- Cristina Oana Mărginean
- Department of Pediatrics, "George Emil Palade" University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Gheorghe Marinescu Street no 38, Târgu Mureș, 540136, Romania
| | - Lorena Elena Meliţ
- Department of Pediatrics, "George Emil Palade" University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Gheorghe Marinescu Street no 38, Târgu Mureș, 540136, Romania.
| | - Dana Valentina Ghiga
- Department of Medical Informatics and Biostatistics, "George Emil Palade" University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Gheorghe Marinescu Street no 38, Târgu Mureș, 540136, Romania
| | - Maria Oana Săsăran
- Department of Pediatric Cardiology, "George Emil Palade" University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Gheorghe Marinescu Street no 38, Târgu Mureș, 540136, Romania
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40
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Morgan TR. Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases-Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Hepatology 2020; 71:686-721. [PMID: 31816111 PMCID: PMC9710295 DOI: 10.1002/hep.31060] [Citation(s) in RCA: 513] [Impact Index Per Article: 102.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Accepted: 11/21/2019] [Indexed: 02/06/2023]
Affiliation(s)
| | - Timothy R. Morgan
- Chief of Hepatology Veterans Affairs Long Beach Healthcare System Long Beach CA
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Mueller S. Introduction to Fibrosis Assessment by Liver Stiffness in Different Etiologies. LIVER ELASTOGRAPHY 2020:105-111. [DOI: 10.1007/978-3-030-40542-7_8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Ragusa R, Corsaro LS, Frazzetto E, Bertino E, Bellia MA, Bertino G. Hepatitis C Virus Infection in Children and Pregnant Women: An Updated Review of the Literature on Screening and Treatments. AJP Rep 2020; 10:e121-e127. [PMID: 32257593 PMCID: PMC7108952 DOI: 10.1055/s-0040-1709185] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2019] [Accepted: 02/20/2020] [Indexed: 12/14/2022] Open
Abstract
Objective The aim of the paper is to review the current information relating to the diagnosis and treatment of hepatitis C virus (HCV) infection in pregnant women and children, particularly those infected by mother-to-child transmission. Study Design A review of published literature was performed to identify relevant articles published between January 2015 and March 2019 on: HCV infection in pregnant woman, mother-to child-transmission of HCV and HCV infection in pediatrics. The results of the evaluation of the different studies were summarized in two sections describing separately the screening and effective treatments in pregnant women and children. Results The rate of mother-to-child transmission of HCV is approximately 5%. HCV infection is strongly associated with cholestasis and preterm birth. Prenatal diagnosis of hepatitis C virus has a dual benefit for mother and child. Perinatally infected children develop cirrhosis in earlier age than those who acquire HCV as adolescents. Pregnant women with cirrhosis have a higher risk of poor maternal and neonatal outcomes than those without cirrhosis. Conclusion To improve public health, universal screening of pregnant women for HCV infection should be performed. Early identification of women and children with HCV infection is important to enable them to be included in assessment and/or treatment programs.
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Affiliation(s)
- Rosalia Ragusa
- Health Technology Assessment Committee, Health Directorate, University Hospital “G. Rodolico,” Catania, Italy
| | - Liberato Simone Corsaro
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Evelise Frazzetto
- Hepatology Unit, A.O.U. Policlinico-Vittorio Emanuele, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Emanuele Bertino
- Department of Drug Sciences, University of Catania, Catania, Italy
| | | | - Gaetano Bertino
- Hepatology Unit, A.O.U. Policlinico-Vittorio Emanuele, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
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Performance of two--dimensional ultrasound shear wave elastography: reference values of normal liver stiffness in children. Pediatr Radiol 2019; 49:91-98. [PMID: 30267166 DOI: 10.1007/s00247-018-4244-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2018] [Revised: 07/14/2018] [Accepted: 08/15/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Two-dimensional (2-D) shear wave elastography is a new sonographic elastography method for noninvasive measurement of liver stiffness. OBJECTIVE The aim of this study was to establish reference values of normal liver stiffness on 2-D shear wave elastography in children. MATERIALS AND METHODS Two-dimensional shear wave elastography values were measured in 202 children with no liver disease from the neonatal period to puberty, who were divided into 4 age groups: newborns and infants, preschoolers, elementary school children and adolescents. We investigated the effects of age, depth of elastography measurement, transducer, number of measurements per child, liver size and Doppler parameters of hepatic blood flow on liver elasticity values. RESULTS The mean normal liver elasticity value in the study population was: 4.29±0.59 kilopascals (kPa). In neonates and infants, mean liver elasticity value was 4.63 (± 0.6) kPa, in preschoolers and elementary school children, 4.05 (± 0.57) kPa and 4.15 (± 0.52) kPa, respectively, and in adolescents, 4.39 (± 0.55) kPa. Values in neonates and infants as well as adolescents were significantly higher than in preschoolers and elementary school children (Kruskal-Wallis, P<0.001; Mann-Whitney U tests, P<0.05). There was no significant association between liver elasticity values and size of the right lobe or Doppler parameters of hepatic blood flow. Different depths and the number of elastography measurements had no effect on liver elasticity values. CONCLUSION Two-dimensional shear wave elastography is achievable in a wide range of age in children. We established the reference values of normal liver stiffness on 2-D shear wave elastography in children.
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Gălăţan AG, Grama A, Pop TL. Complications of cirrhosis in a biliary atresia patient. PEDIATRU.RO 2019; 2:32. [DOI: 10.26416/pedi.54.2.2019.2436] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
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Ruzman L, Mikolasevic I, Baraba Dekanic K, Milic S, Palcevski G. Advances in diagnosis of chronic liver diseases in pediatric patients. World J Pediatr 2018; 14:541-547. [PMID: 30306466 DOI: 10.1007/s12519-018-0197-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Accepted: 09/25/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Chronic liver diseases (CLD) present important clinical problem in children with various age-dependent causes. Nonalcoholic fatty liver disease (NAFLD) with its increasing prevalence is a major problem with regard to its timely recognition and the need for long-term disease monitoring. At present, a perfect non-invasive method for the evaluation of liver fibrosis is not available. METHODS A non-systematic literature search was performed to summarize the current knowledge about transient elastography (TE) with controlled attenuation parameter (CAP) in children with CLD. Ovid MEDLINE, Ovid EMBASE, Google scholar, and The Cochrane Library databases were searched for relevant articles evaluating TE in the pediatric population. RESULTS Normal values of liver stiffness measurements (LSM) according to the age are given, as well as the advantages and disadvantages of the method. The utility of TE in specific liver disease in pediatric population is summarized. CONCLUSIONS TE with CAP is a valuable non-invasive method for the liver-damage assessment. Clinical interpretation of TE results should be made in parallel with the assessment of the patient's demographics, disease etiology, and essential laboratory parameters.
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Affiliation(s)
- Lucija Ruzman
- Pediatric Clinic, UHC Rijeka, Istarska 43, 51 000, Rijeka, Croatia.
| | | | | | - Sandra Milic
- Department of Gastroenterology, UHC Rijeka, Rijeka, Croatia
| | - Goran Palcevski
- Pediatric Clinic, Department of Gastroenterology, UHC Rijeka, Rijeka, Croatia
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Ferraioli G, Wong VWS, Castera L, Berzigotti A, Sporea I, Dietrich CF, Choi BI, Wilson SR, Kudo M, Barr RG. Liver Ultrasound Elastography: An Update to the World Federation for Ultrasound in Medicine and Biology Guidelines and Recommendations. ULTRASOUND IN MEDICINE & BIOLOGY 2018; 44:2419-2440. [PMID: 30209008 DOI: 10.1016/j.ultrasmedbio.2018.07.008] [Citation(s) in RCA: 343] [Impact Index Per Article: 49.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Revised: 07/02/2018] [Accepted: 07/13/2018] [Indexed: 06/08/2023]
Abstract
The World Federation for Ultrasound in Medicine and Biology has produced these guidelines for the use of elastography techniques in liver diseases. For each available technique, the reproducibility, results and limitations are analyzed, and recommendations are given. This set of guidelines updates the first version, published in 2015. Since the prior guidelines, there have been several advances in technology. The recommendations are based on the international published literature, and the strength of each recommendation is judged according to the Oxford Centre for Evidence-Based Medicine. The document has a clinical perspective and is aimed at assessing the usefulness of elastography in the management of liver diseases.
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Affiliation(s)
- Giovanna Ferraioli
- Ultrasound Unit, Department of Clinical Sciences and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, School of Medicine, University of Pavia, Pavia, Italy
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong
| | - Laurent Castera
- Service d'Hepatologie, Hopital Beaujon, Clichy, Assistance Publique-Hopitaux de Paris, INSERM UMR 1149 CRI, Universite Denis Diderot Paris-VII, Paris, France
| | - Annalisa Berzigotti
- Swiss Liver Center, Hepatology, University Clinic for Visceral Surgery and Medicine, Inselspital, University of Bern, Switzerland
| | - Ioan Sporea
- Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy, Timisoara, Romania
| | | | - Byung Ihn Choi
- Department of Radiology, Seoul National University Hospital, Seoul, South Korea
| | - Stephanie R Wilson
- Department of Diagnostic Imaging, Foothills Medical Centre, University of Calgary, Calgary, Alberta, Canada
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University School of Medicine, Osaka Sayama, Japan
| | - Richard G Barr
- Department of Radiology, Northeastern Ohio Medical University and Southwoods Imaging, Youngstown, Ohio, USA.
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Hwang JY, Yoon HM, Kim JR, Lee JS, Jung AY, Kim KM, Cho YA. Diagnostic Performance of Transient Elastography for Liver Fibrosis in Children: A Systematic Review and Meta-Analysis. AJR Am J Roentgenol 2018; 211:W257-W266. [PMID: 30106615 DOI: 10.2214/ajr.18.19535] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
OBJECTIVE We aimed to assess the diagnostic performance of transient elastography for evaluating liver fibrosis in children and adolescents. MATERIALS AND METHODS A computerized search of Medline and Embase up to December 31, 2017, was performed to identify studies. Studies evaluating the diagnostic performance of transient elastography for the severity of liver fibrosis in children and adolescents were selected. Pooled sensitivity and specificity were calculated using hierarchic logistic regression modeling. Multiple subgroup analysis was performed. RESULTS In this meta-analysis that included 11 original articles involving 723 patients, transient elastography showed a summary sensitivity of 95% (95% CI, 74-99%) and a specificity of 90% (95% CI, 81-95%) for the diagnosis of significant liver fibrosis (stage ≥ F2) in children. The hierarchic summary ROC AUC was 0.96 (95% CI, 0.94-0.98). Multiple subgroup analysis for the diagnosis of significant hepatic fibrosis showed clinically acceptable ranges of sensitivity and specificity across all subgroups. In additional subgroup analysis, the diagnostic accuracies of transient elastography according to the Metavir system were also within a clinically acceptable range, measured up to a sensitivity of 86% and specificity of 86% for diagnosing Metavir stage F4 fibrosis. CONCLUSION Transient elastography showed highly accurate diagnostic performance for the diagnosis of liver fibrosis in children.
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Affiliation(s)
- Jae-Yeon Hwang
- 1 Department of Radiology, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University, Yangsan Hospital, Gyeongsangnam-do, Republic of Korea
| | - Hee Mang Yoon
- 2 Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea
| | - Jeong Rye Kim
- 2 Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea
| | - Jin Seong Lee
- 2 Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea
| | - Ah Young Jung
- 2 Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea
| | - Kyung Mo Kim
- 3 Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center, Songpa-gu, Seoul, Republic of Korea
| | - Young Ah Cho
- 2 Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea
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Zou H, Xue Y, Ou Y, Li S, Zhao Y, Shao L, Li Y. Factors Affecting the Quality of Breast Quasistatic Ultrasound Elastograms. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2018; 37:1701-1712. [PMID: 29288591 DOI: 10.1002/jum.14518] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Revised: 08/01/2017] [Accepted: 09/24/2017] [Indexed: 06/07/2023]
Abstract
OBJECTIVES To explore factors affecting the quality of quasistatic ultrasound elastograms of the breast and to evaluate their accuracy in distinguishing benign and malignant breast lesions. METHODS A total of 663 patients with 702 breast lesions were recruited. All patients received both conventional ultrasonography and quasistatic elastography. Patients' breast lesions were divided into A and B groups according to satisfactory and unsatisfactory elastographic examinations. Group A included 590 satisfactory elastograms, whereas Group B included 112 unsatisfactory elastograms. Various factors-maximum depth of the lesion, maximum transverse diameter of the lesion, thickness of the adipose layer, thickness of the glandular layer, thickness of the breast, distance between the nipple and lesion, age, body mass index, and menopausal status-were analyzed and compared between the groups to gauge their effects on the quality of the elastograms. RESULTS Significantly deeper lesions, higher maximum transverse lesion diameters, thicker adipose layers, thicker glandular layers, and thicker breasts were identified in group B patients compared to group A patients (P < .05). Multivariate logistic regression analyses showed that the maximum depth of the lesion, thickness of the adipose layer, and thickness of the breast were independent factors in the quality of elastograms. The area under the curve for the maximum depth of the lesion was 0.986 with the optimal cutoff threshold of 2.5 cm. CONCLUSIONS Quasistatic elastography can be a supplementary approach to conventional ultrasonography in helping improve the diagnostic accuracy of breast lesions. The depth and size of breast lesions are correlated with the quality of elastograms.
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Affiliation(s)
- Hongsheng Zou
- Department of Surgical Intensive Care Unit, People's Hospital of Rongcheng, Rongcheng, China
| | - Yan Xue
- Department of Statistics, Jinan Child Hospital, Jinan, China
| | - Yang Ou
- Department of Graduate School, School of Medical and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Zhangqiu, China
- Departments of Hepatobiliary Surgery, Shandong Cancer Hospital, affiliated with Shandong University, Shandong Academy of Medical Sciences, Jinan, China
| | - Sheng Li
- Departments of Hepatobiliary Surgery, Shandong Cancer Hospital, affiliated with Shandong University, Shandong Academy of Medical Sciences, Jinan, China
| | - Yuehuan Zhao
- Department of Special Diagnosis, Shandong Cancer Hospital, affiliated with Shandong University, Shandong Academy of Medical Sciences, Jinan, China
| | - Limei Shao
- Department of Special Diagnosis, Shandong Cancer Hospital, affiliated with Shandong University, Shandong Academy of Medical Sciences, Jinan, China
| | - Yunling Li
- Department of Special Diagnosis, Shandong Cancer Hospital, affiliated with Shandong University, Shandong Academy of Medical Sciences, Jinan, China
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Pawlowska M, Sobolewska-Pilarczyk M, Domagalski K. Hepatitis C virus infection in children in the era of direct-acting antiviral. World J Gastroenterol 2018; 24:2555-2566. [PMID: 29962813 PMCID: PMC6021773 DOI: 10.3748/wjg.v24.i24.2555] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Revised: 05/10/2018] [Accepted: 06/01/2018] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection remains an important global health problem with chronic infection affecting approximately 11 million children worldwide. The emergence of direct-acting antiviral (DAA) therapies and the development of non-invasive methods for the determination of liver fibrosis will significantly improve the management of paediatric patients with chronic HCV infection in subsequent years. For paediatric patients, a new era of highly effective DAA agents is beginning, and the first results of available clinical trials are very promising. In this era, the identification and monitoring of patients continues to be an important issue. The availability of non-invasive serological and imaging methods to measure hepatic fibrosis enables the identification of patients with significant or advanced liver fibrosis stages. This article summarizes the current data on the epidemiology and progress of research aimed to evaluate the new therapies and non-invasive methods for liver injury in paediatric patients with chronic hepatitis C.
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Affiliation(s)
- Malgorzata Pawlowska
- Department of Paediatric Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz 85-030, Poland
| | - Malgorzata Sobolewska-Pilarczyk
- Department of Paediatric Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz 85-030, Poland
| | - Krzysztof Domagalski
- Centre For Modern Interdisciplinary Technologies, Nicolaus Copernicus University, Toruń 87-100, Poland
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Dietrich CF, Sirli R, Ferraioli G, Popescu A, Sporea I, Pienar C, Kunze C, Taut H, Schrading S, Bota S, Schreiber-Dietrich D, Yi D. Current Knowledge in Ultrasound-Based Liver Elastography of Pediatric Patients. APPLIED SCIENCES 2018; 8:944. [DOI: 10.3390/app8060944] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Studies performed using transient elastography (TE), point shear wave elastography (pSWE) and two-dimensional shear wave elastography (2D-SWE) have shown that these techniques are all feasible and accurate in children for the evaluation of liver fibrosis due to several etiologies. However, for some specific pediatric pathologies, such as biliary atresia, the evidence is still limited. As shown in adults, inflammation is a confounding factor when assessing fibrosis severity and care should be taken when interpreting the results. Due to the scarce comparative data between serological tests and elastography techniques in children, a definite conclusion regarding which is the best cannot be drawn. Neither non-invasive elastographic techniques nor laboratory scores allow determination of the presence and the degree of inflammation, necrosis, iron or copper deposits.
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Affiliation(s)
- Christoph F. Dietrich
- Medizinische Klinik 2, Caritas-Krankenhaus Bad Mergentheim, Uhlandstraße 7, 97980 Bad Mergentheim, Germany
| | - Roxana Sirli
- Department of Gastroenterology and Hepatology, “Victor Babeș” University of Medicine and Pharmacy Timișoara, 300041 Timișoara, Romania
| | - Giovanna Ferraioli
- Ultrasound Unit, Clinical Sciences and Infectious Diseases Department, Fondazione IRCCS Policlinico San Matteo, Medical School University of Pavia, 27100 Pavia, Italy
| | - Alina Popescu
- Department of Gastroenterology and Hepatology, “Victor Babeș” University of Medicine and Pharmacy Timișoara, 300041 Timișoara, Romania
| | - Ioan Sporea
- Department of Gastroenterology and Hepatology, “Victor Babeș” University of Medicine and Pharmacy Timișoara, 300041 Timișoara, Romania
| | - Corina Pienar
- Pediatrics Department, “Victor Babeș” University of Medicine and Pharmacy Timișoara, 300041 Timișoara, Romania
| | - Christian Kunze
- Klinik für Radiologie, Abteilung Kinderradiologie, Universitätsklinikum Halle (Saale), Martin-Luther-Universität Halle-Wittenberg, 06120 Halle, Germany
| | - Heike Taut
- Klinik und Poliklinik für Kinder-und Jugendmedizin, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, 01307 Dresden, Germany
| | - Simone Schrading
- Klinik für Diagnostische und Interventionelle Radiologie, University of Aachen, 52062 Aachen, Germany
| | - Simona Bota
- Department of Gastroenterology, Hepatology, Nephrology and Endocrinology, Klinikum Klagenfurt am Wörthersee, 9020 Klagenfurt am Wörthersee, Austria
| | - Dagmar Schreiber-Dietrich
- Medizinische Klinik 2, Caritas-Krankenhaus Bad Mergentheim, Uhlandstraße 7, 97980 Bad Mergentheim, Germany
| | - Dong Yi
- Department of ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200433, China
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