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Cipriano C, Deutsch L, Kopczynska M, Rabinowich L, Sasdelli AS, Pironi L, Lal S. Prediction of chronic severe intestinal failure-associated liver disease by current criteria in adults: A descriptive cohort study. JPEN J Parenter Enteral Nutr 2025; 49:349-357. [PMID: 39731261 DOI: 10.1002/jpen.2719] [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: 08/06/2024] [Revised: 12/03/2024] [Accepted: 12/05/2024] [Indexed: 12/29/2024]
Abstract
INTRODUCTION Intestinal failure-associated liver disease covers a spectrum of conditions from mild to end-stage disease. Currently, there are 9 diagnostic criteria divided to four categories: cholestasis, steatosis, fibrosis, and unclassified. Our aim was to evaluate the application of these criteria to patients with chronic severe liver disease in patients with intestinal failure. METHODS This was a cross-sectional study of patients attending the home parenteral nutrition clinic of a national UK reference intestinal failure center from March 2015 to December 2019. Exclusion criteria included active malignancy, home parenteral nutrition for <6 months duration, and liver transplantation. Clinically significant intestinal failure-associated liver disease was defined as moderate-severe fibrosis or cirrhosis on liver biopsy and/or radiological imaging compatible with liver cirrhosis. RESULTS Two hundred and twenty-one patients were included (age at home parenteral nutrition initiation: 50 ± 16.0 years; 63.6% female). There was a wide range of intestinal failure-associated liver disease point prevalence depending on the established criteria used (2.9%-35.1%). Twenty-three patients (9.5%) were diagnosed with clinically significant intestinal failure-associated liver disease, but no patient with clinically significant intestinal failure-associated liver disease met all diagnostic criteria, and 6 of 23 (26.1%) did not fit any of the established criteria. CONCLUSIONS Intestinal failure-associated liver disease is a poorly defined medical condition, and current noninvasive diagnostic methods are unreliable in predicting disease severity. Further studies are needed to develop the definition to reflect that intestinal failure-associated liver disease is a spectrum of disease that includes chronic severe liver disease and improve methods of disease diagnosis.
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Affiliation(s)
- Claudia Cipriano
- Intestinal Failure Unit, Salford Royal, NHS Foundation Trust, Salford, UK
| | - Liat Deutsch
- Intestinal Failure Unit, Salford Royal, NHS Foundation Trust, Salford, UK
- The Department of Gastroenterology and Liver Diseases, Tel-Aviv Sourasky Medical Centre, Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Maja Kopczynska
- Intestinal Failure Unit, Salford Royal, NHS Foundation Trust, Salford, UK
- Academic Health Sciences Centre, University of Manchester, Manchester, UK
| | - Liane Rabinowich
- The Department of Gastroenterology and Liver Diseases, Tel-Aviv Sourasky Medical Centre, Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Anna Simona Sasdelli
- Department of Digestive System, Centre for Chronic Intestinal Failure, St. Orsola-Malpighi University Hospital, Bologna, Italy
| | - Loris Pironi
- Department of Digestive System, Centre for Chronic Intestinal Failure, St. Orsola-Malpighi University Hospital, Bologna, Italy
| | - Simon Lal
- Intestinal Failure Unit, Salford Royal, NHS Foundation Trust, Salford, UK
- Academic Health Sciences Centre, University of Manchester, Manchester, UK
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Jin HY, Noh ES, Jeong H, Hwang IIT. Prediction of hepatic fibrosis using the aspartate transaminase-to-platelet ratio index in children and adolescents with metabolic dysfunction-associated steatotic liver disease. BMC Pediatr 2024; 24:788. [PMID: 39614232 DOI: 10.1186/s12887-024-05263-3] [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: 09/03/2024] [Accepted: 11/19/2024] [Indexed: 12/01/2024] Open
Abstract
BACKGROUND Aspartate transaminase-to-platelet ratio index (APRI) is an easy and useful predictor of hepatic fibrosis in patients with chronic hepatic disease, and it significantly correlates with the degree of hepatic fibrosis in adult patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to evaluate the use of APRI in assessing the severity of MASLD in children and adolescents. METHODS Medical records of 115 patients (males: 78; females: 37) with MASLD were retrospectively reviewed. The correlations between the APRI and clinical parameters that indicate the severity of MASLD were analyzed. Their ages ranged between 7.3 and 18.8 years old. Patients with hepatitis B or C infections were excluded from the study. The APRI score was calculated, and transient elastography for liver stiffness measurement (LSM) was performed for all the patients. RESULTS The mean APRI score was 0.46 ± 0.26, ranging between 0.16 and 1.57. The LSM values ranged between 2.94 and 7.72 kPa. Body mass index-standard deviation score, transaminase levels, and HbA1c levels were higher in a group with abnormal LSM when divided into two groups according to LSM. The APRI score was greater in the group with abnormal LSM (0.40 ± 0.17 vs. 0.64 ± 0.40, P < 0.001). The APRI score was associated with LSM (r = 0.354, P < 0.001). Area under the curve of APRI for predicting abnormal LSM was 0.650 (95% confidence interval, 0.517-0.784) with a cutoff value of 0.74. CONCLUSIONS APRI score showed weak correlation with LSM. Further study encompassing various severity of hepatic fibrosis is needed for identifying better and sensitive non-invasive indicators in pediatric MASLD.
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Affiliation(s)
- Hye Young Jin
- Department of Pediatrics, Kangdong Sacred Heart hospital, Hallym University College of Medicine, 150, Seongan-ro, Gangdong-gu, Seoul, 05355, Republic of Korea
| | - Eu Seon Noh
- Department of Pediatrics, Kangdong Sacred Heart hospital, Hallym University College of Medicine, 150, Seongan-ro, Gangdong-gu, Seoul, 05355, Republic of Korea
| | - Hwalrim Jeong
- Department of Pediatrics, Soonchunhyang University, Cheonan hospital, Cheonan, Korea
| | - I I Tae Hwang
- Department of Pediatrics, Kangdong Sacred Heart hospital, Hallym University College of Medicine, 150, Seongan-ro, Gangdong-gu, Seoul, 05355, Republic of Korea.
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Di Dato F, Iorio R, Spagnuolo MI. IFALD in children: What's new? A narrative review. Front Nutr 2022; 9:928371. [PMID: 35958249 PMCID: PMC9358220 DOI: 10.3389/fnut.2022.928371] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 06/27/2022] [Indexed: 11/19/2022] Open
Abstract
Intestinal failure-associated liver disease (IFALD) is a progressive liver disease complicating intestinal failure (IF). It is a preventable and reversible condition, but at the same time, a potential cause of liver cirrhosis and an indication to combined or non-combined liver and small bowel transplantation. The diagnostic criteria are not yet standardized, so that its prevalence varies widely in the literature. Pathophysiology seems to be multifactorial, related to different aspects of intestinal failure and not only to the long-term parenteral nutrition treatment. The survival rates of children with IF have increased, so that the main problems today are preventing complications and ensuring a good quality of life. IFALD is one of the most important factors that limit long-term survival of patients with IF. For this reason, more and more interest is developing around it and the number of published articles is increasing rapidly. The purpose of this narrative review was to focus on the main aspects of the etiology, pathophysiology, management, prevention, and treatment of IFALD, based on what has been published mainly in the last 10 years. Controversies and current research gaps will be highlighted with the aim to pave the way for new project and high-quality clinical trials.
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Affiliation(s)
| | | | - Maria Immacolata Spagnuolo
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy
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4
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Long-term follow-up of biliary atresia using liver transient elastography. Pediatr Surg Int 2022; 38:1013-1018. [PMID: 35523886 DOI: 10.1007/s00383-022-05137-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/01/2022] [Indexed: 10/18/2022]
Abstract
OBJECTIVE Liver transient elastography (TE) using FibroScan® has gained popularity as a non-invasive technique to assess hepatic fibrosis by measuring liver stiffness. This study focused on biliary atresia patients post Kasai operation for more than 10 years to prospectively correlate the hepatic fibrosis score to the biochemical changes of liver fibrosis and clinical development of portal hypertensive complications. METHODS TE was performed in 37 patients who had biliary atresia post Kasai operation done at median age of 60 days. Biochemical indices of liver fibrosis including aspartate aminotransferase/platelet ratio index (APRI) and Fibrosis-4 (FIB-4) score based on age, platelet count, alanine aminotransferase and aspartate aminotransferase level were calculated at the time of TE. Platelet count, spleen size, varices, ascites and hepatic encephalopathy were evaluated as clinical markers of portal hypertension. RESULTS There were 22 female and 15 male with TE done at median age of 17.0 years. Median FibroScan® fibrosis score was 11.4. Fibrosis score of 6.8 kilopascal (kPa) was taken as the upper reference limit of normal. Nine patients (24%) had normal fibrosis score. Score above or equal to 6.8 kPa was significantly associated with lower platelet level (p = 0.001), higher INR (p = 0.043), higher APRI (p = 0.021), higher FIB-4 score (p = 0.013), and larger splenic diameter (p = 0.004). Higher FibroScan® fibrosis score was also significantly associated with portal hypertensive complications (p = 0.001). CONCLUSIONS The FibroScan® fibrosis score correlated well with the biochemical changes of liver fibrosis and development of portal hypertensive complications clinically. Screening of portal hypertensive complications such as varices is recommended for patients with raised fibrosis score upon long-term follow-up. LEVEL OF EVIDENCE Level III, retrospective comparative study.
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Turudic D, Milosevic D, Bilic K, Prohászka Z, Bilic E. A Limited Course of Eculizumab in a Child with the Atypical Hemolytic Uremic Syndrome and Pre-B Acute Lymphoblastic Leukemia on Maintenance Therapy: Case Report and Literature Review. J Clin Med 2022; 11:jcm11102779. [PMID: 35628906 PMCID: PMC9142928 DOI: 10.3390/jcm11102779] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Revised: 04/25/2022] [Accepted: 05/10/2022] [Indexed: 02/06/2023] Open
Abstract
Acute lymphoblastic leukemia (ALL) is considered a possible risk for the occurrence of thrombotic microangiopathies. We present a girl with pre-B ALL successfully treated according to the BFM ALL IC-2009 protocol on maintenance therapy followed by aHUS occurrence. This is the seventh case of HUS/aHUS on ALL maintenance therapy and the first with clearly documented eculizumab use in the early stage of aHUS/secondary TMA. Standard and additional parameters were used in aHUS monitoring alongside the reticulocyte production index adjusted for age (RPI/A) and the aspartate aminotransferase-to-platelet ratio index (APRI) as markers of hemolysis and rapid response following treatment. RPI/A and APRI are markers of bone marrow response to anemia serving as red blood cell vs. platelet recovery markers. Together they mark the exact recovery point of thrombotic microangiopathy and serve as a prognostic marker of eculizumab treatment success. During the 8-month treatment and 6-month follow-up, no recurrence of hemolysis, ALL relapse, or renal damage were observed. A systematic review of the literature revealed 14/312 articles; five children had aHUS before the onset of ALL, and two children had both diseases concurrently. At least 3/7 patients are attributed to aHUS, of whom 2/7 have renal damage. Potential undiagnosed/unpublished cases may be assumed.
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Affiliation(s)
- Daniel Turudic
- Department of Pediatric Hematology and Oncology, University Hospital Centre Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia; (D.T.); (E.B.)
| | - Danko Milosevic
- School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia;
- Department of Pediatrics, General Hospital Zabok and Hospital of Croatian Veterans, Bracak 8, 49210 Bracak, Croatia
- Correspondence:
| | - Katarina Bilic
- School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia;
| | - Zoltán Prohászka
- Department of Internal Medicine and Haematology, Semmelweis University, 1085 Budapest, Hungary;
- Research Group for Immunology and Haematology, Semmelweis University, 1085 Budapest, Hungary
| | - Ernest Bilic
- Department of Pediatric Hematology and Oncology, University Hospital Centre Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia; (D.T.); (E.B.)
- School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia;
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Micic D, Huard G, Lee SM, Fiel MI, Moon J, Schiano TD, Iyer K. Evaluation of the fibrosis-4 index for detection of advanced fibrosis among individuals at risk for intestinal failure-associated liver disease. JPEN J Parenter Enteral Nutr 2021; 46:678-684. [PMID: 33928656 DOI: 10.1002/jpen.2135] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND Intestinal failure-associated liver disease (IFALD) refers to the spectrum of liver injury secondary to IF and parenteral nutrition use. Our aim was to evaluate the use of noninvasive indices of liver fibrosis to detect advanced fibrosis among individuals at risk for IFALD. METHODS We performed a secondary analysis of a retrospective study, including all liver biopsies performed on individuals undergoing intestinal transplantation (ITx) between January 2000 and May 2014. To determine the clinical utility of detecting advanced fibrosis, receiver operating characteristic curves were developed. Comparison between the area under the curves was performed by DeLong test. RESULTS Fifty-three patients had a liver biopsy performed at the time of ITx; 13 of 53 (24.5%) patients had advanced fibrosis. The fibrosis-4 (FIB-4) index positively correlated to the stage of fibrosis on liver biopsy (r = 0.426, P = .002). When compared against the FIB-4 index, the aspartate aminotransferase to platelet ratio index had a significantly decreased ability to correctly identify the presence of advanced fibrosis (P = .019). When determining the cutoff value with 90% specificity for the detection of advanced fibrosis, a FIB-4 index of ≥4.4 had a sensitivity of 0.462 and a positive predictive value of 0.6. CONCLUSION In this retrospective cohort study, we found a positive correlation between the FIB-4 index and the liver fibrosis stage as characterized by the Brunt classification. This evaluation of the FIB-4 index against liver biopsies supports the use of the FIB-4 index in the detection of liver fibrosis in IF.
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Affiliation(s)
- Dejan Micic
- Department of Internal Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, Chicago, Illinois, USA
| | - Genevieve Huard
- Department of Medicine, Division of Liver Diseases, Centre Hospitalier de l'Universite de Montreal, Montreal, Quebec, Canada
| | - Sang Mee Lee
- Biostatistics Laboratory and Research Computing Group, Department of Public Health Sciences, University of Chicago, Chicago, Illinois, USA
| | - M Isabel Fiel
- Department of Pathology, Division of Liver Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Jang Moon
- Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Department of Surgery, Intestinal Transplantation and Rehabilitation Program, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Thomas D Schiano
- Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Department of Medicine, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Kishore Iyer
- Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Department of Surgery, Intestinal Transplantation and Rehabilitation Program, Icahn School of Medicine at Mount Sinai, New York, New York, USA
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Torres C, Badalyan V, Mohan P. Twelve-year outcomes of intestinal failure-associated liver disease in children with short-bowel syndrome: 97% transplant-free survival and 81% enteral autonomy. JPEN J Parenter Enteral Nutr 2021; 46:197-206. [PMID: 33794031 DOI: 10.1002/jpen.2112] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 03/19/2021] [Accepted: 03/25/2021] [Indexed: 01/28/2023]
Abstract
Our aim was to analyze the outcomes in children with short-bowel syndrome (SBS), parenteral nutrition dependence (PND), and intestinal failure-associated liver disease (IFALD) treated in our Intestinal Rehabilitation Program (IRP) during 2007-2018. We retrospectively reviewed charts of 135 patients with SBS-PND at the time of enrollment in IRP; of these, 89 (66%) had IFALD, defined as conjugated bilirubin (CB) of ≥2 mg/dl at enrollment and/or abnormal liver biopsy showing stage 2-4 fibrosis. Outcomes included resolution of CB, enteral autonomy, laboratory parameters (platelets, aspartate aminotransferase to platelet ratio index), growth trends, transplant rates, and mortality. Of the 89 patients, 74 had elevated CB at enrollment; the other 15 had normalized CB but had fibrosis on liver biopsy. Thirty-eight patients had liver biopsies: 36 (95%) had fibrosis, including 21/36 with bridging fibrosis/cirrhosis. The median proportion of residual small bowel was 23% (interquartile range, 13%-38%) of the expected length for age and median, daily energy requirement by PN was 100%. Two received a transplant, three died (one posttransplant), and the remaining 85 survived; 69 (81%) achieved enteral autonomy. Seventy-three (99%) of the 74 patients with hyperbilirubinemia normalized their CB with medical treatment. In a subset of eight of 89 patients with initial platelet count of <100,000/μl(median 50,500/μl) and median CB of 21 mg/dl, seven achieved CB normalization and had improved platelet count. Overall survival was 97% (censored 96.3%). We demonstrate high transplant-free survival and enteral autonomy rates among children with SBS-IFALD relying on low-dose soybean lipid emulsion.
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Affiliation(s)
- Clarivet Torres
- Intestinal Rehabilitation Program, Division of Gastroenterology, Hepatology, and Nutrition, Children's National Hospital, Washington, DC, USA.,George Washington University School of Medicine, Washington, DC, USA
| | - Vahe Badalyan
- Intestinal Rehabilitation Program, Division of Gastroenterology, Hepatology, and Nutrition, Children's National Hospital, Washington, DC, USA.,George Washington University School of Medicine, Washington, DC, USA
| | - Parvathi Mohan
- Intestinal Rehabilitation Program, Division of Gastroenterology, Hepatology, and Nutrition, Children's National Hospital, Washington, DC, USA.,George Washington University School of Medicine, Washington, DC, USA
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Gura KM, Premkumar MH, Calkins KL, Puder M. Fish Oil Emulsion Reduces Liver Injury and Liver Transplantation in Children with Intestinal Failure-Associated Liver Disease: A Multicenter Integrated Study. J Pediatr 2021; 230:46-54.e2. [PMID: 33038344 PMCID: PMC7914137 DOI: 10.1016/j.jpeds.2020.09.068] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Revised: 09/30/2020] [Accepted: 09/30/2020] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To compare the aspartate aminotransferase to platelet ratio index, liver transplantation, and mortality rates between children with intestinal failure-associated liver disease who received fish oil lipid emulsion (FOLE) or soybean oil intravenous lipid emulsion (SOLE). STUDY DESIGN In this multicenter integrated analysis, FOLE recipients (1 g/kg/d) (n = 189) were compared with historical controls administered SOLE (≤3 g/kg/d) (n = 73). RESULTS Compared with SOLE, FOLE recipients had a higher direct bilirubin level at baseline (5.8 mg/dL vs 3.0 mg/dL; P < .0001). Among FOLE recipients, 65% experienced cholestasis resolution vs 16% of SOLE recipients (P < .0001). The aspartate aminotransferase to platelet ratio index scores improved in FOLE recipients (1.235 vs 0.810 and 0.758, P < .02) but worsened in SOLE recipients (0.540 vs 2.564 and 2.098; P ≤ .0003) when baseline scores were compared with cholestasis resolution and end of study, respectively. Liver transplantation was reduced in FOLE vs SOLE (4% vs 12%; P = .0245). The probability of liver transplantation in relation to baseline direct or conjugated bilirubin (DB) was lower in FOLE vs SOLE recipients (1% vs 9% at DB of 2 mg/dL; 8% vs 35% at DB of 12.87 mg/dL; P = .0022 for both). Death rates were similar (FOLE vs SOLE: 10% vs 14% at DB of 2 mg/dL; 17% vs 23% at a DB of 12.87 mg/dL; P = .36 for both). CONCLUSIONS FOLE recipients experienced a higher rate of cholestasis resolution, lower aspartate aminotransferase to platelet ratio index, and fewer liver transplants compared with SOLE. This study demonstrates that FOLE may be the preferred parenteral lipid emulsion in children with intestinal failure-associated liver disease when DB reaches 2 mg/dL. TRIAL REGISTRATION Clinicaltrials.gov: NCT00910104 and NCT00738101.
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Affiliation(s)
- Kathleen M. Gura
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pharmacy (KG); Department of Surgery and the Vascular Biology Program (MPU); Boston Children’s Hospital, 300 Longwood Ave, Boston, MA 02115, USA
| | - Muralidhar H. Premkumar
- Baylor College of Medicine, Section of Neonatology, Department of Pediatrics, Texas Children’s Hospital, Houston TX, 77030, USA
| | - Kara L. Calkins
- Department of Pediatrics, Division of Neonatology & Developmental Biology, Neonatal Research Center of the UCLA Children’s Discovery and Innovation Institute, David Geffen School of Medicine at UCLA, Mattel Children’s Hospital, University of California Los Angeles, 757 Westwood Plaza, Los Angeles, CA 90095, USA
| | - Mark Puder
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pharmacy (KG); Department of Surgery and the Vascular Biology Program (MPU); Boston Children’s Hospital, 300 Longwood Ave, Boston, MA 02115, USA
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9
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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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10
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Shiau H, Guffey D, Loomes KM, Seidman C, Ragozzino E, Molleston JP, Schady D, Leung DH. Biopsy Validated Study of Biomarkers for Liver Fibrosis and Transplant Prediction in Inherited Cholestasis. Hepatol Commun 2020; 4:1516-1526. [PMID: 33024920 PMCID: PMC7527690 DOI: 10.1002/hep4.1569] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 05/29/2020] [Accepted: 06/18/2020] [Indexed: 12/12/2022] Open
Abstract
Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC) are inherited cholestatic disorders with risk of developing end‐stage liver disease requiring liver transplantation (LT). We investigated aspartate aminotransferase‐to‐platelet ratio index (APRI), Fibrosis‐4 score (FIB‐4), and conjugated bilirubin as biomarkers to assess fibrosis severity and risk for LT among children with ALGS and PFIC. This multicenter, cross‐sectional study included 64 children with ALGS or PFIC (per genetics or strict clinical criteria) with APRI, FIB‐4, and conjugated bilirubin levels collected within ±90 days of their most recent liver biopsy. A single, blinded pathologist staged all biopsies (metavir; F0‐F2: nonsevere, F3‐F4: severe). Logistic regression and area under the receiver operating characteristic curve analysis (AUC) were used to assess biomarker associations with fibrosis severity and risk for LT. In ALGS, only APRI distinguished F3‐F4 (AUC 0.72, P = 0.012), with a cutoff greater than 2.97 demonstrating a sensitivity of 61.5% (95% confidence interval 0.32, 0.86) and specificity of 81.5% (0.62, 0.94). In ALGS, a 50% increase of APRI increased the odds of F3‐F4 by 1.31‐fold (1.04, 1.65; P = 0.023). In ALGS, APRI (AUC 0.87; P < 0.001) and FIB‐4 (AUC 0.84; P < 0.001) were able to predict risk for LT. In PFIC, only APRI distinguished F3‐4 (AUC 0.74, P = 0.039), with a cutoff greater than 0.99 demonstrating a sensitivity of 80% (0.44, 0.98) and specificity of 64.3% (0.35, 0.87). In PFIC, only FIB‐4 was able predict risk for LT (AUC 0.80; P = 0.002). In ALGS or PFIC, conjugated bilirubin could not distinguish F3‐F4 or predict risk for LT. Conclusion: This liver biopsy–validated study suggests that APRI is able to distinguish F3‐F4 from F0‐F2 in ALGS and PFIC. APRI and FIB‐4 may also serve as predictors of risk for LT in ALGS (APRI and FIB‐4) and PFIC (FIB‐4).
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Affiliation(s)
- Henry Shiau
- Pediatric Gastroenterology, Hepatology, and Nutrition Baylor College of Medicine Houston TX.,Texas Children's Hospital Houston TX
| | - Danielle Guffey
- Institute for Clinical and Translational Research Baylor College of Medicine Houston TX
| | - Kathleen M Loomes
- Pediatric Gastroenterology, Hepatology, and Nutrition University of Pennsylvania Perelman School of Medicine Philadelphia PA.,Children's Hospital of Philadelphia Philadelphia PA
| | | | | | - Jean P Molleston
- Pediatric Gastroenterology, Hepatology, and Nutrition Indiana University-Riley Hospital for Children Indianapolis IN
| | - Deborah Schady
- Pathology and Immunology Baylor College of Medicine Houston TX
| | - Daniel H Leung
- Pediatric Gastroenterology, Hepatology, and Nutrition Baylor College of Medicine Houston TX.,Texas Children's Hospital Houston TX
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11
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Fragkos KC, Picasso Bouroncle MC, Kumar S, Caselton L, Menys A, Bainbridge A, Taylor SA, Torrealdea F, Kumagai T, Di Caro S, Rahman F, Macnaughtan J, Chouhan MD, Mehta S. Serum Scoring and Quantitative Magnetic Resonance Imaging in Intestinal Failure-Associated Liver Disease: A Feasibility Study. Nutrients 2020; 12:E2151. [PMID: 32707726 PMCID: PMC7400956 DOI: 10.3390/nu12072151] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2020] [Revised: 07/08/2020] [Accepted: 07/13/2020] [Indexed: 01/20/2023] Open
Abstract
(1) Background: Intestinal failure-associated liver disease (IFALD) in adults is characterized by steatosis with variable progression to fibrosis/cirrhosis. Reference standard liver biopsy is not feasible for all patients, but non-invasive serological and quantitative MRI markers for diagnosis/monitoring have not been previously validated. Here, we examine the potential of serum scores and feasibility of quantitative MRI used in non-IFALD liver diseases for the diagnosis of IFALD steatosis; (2) Methods: Clinical and biochemical parameters were used to calculate serum scores in patients on home parenteral nutrition (HPN) with/without IFALD steatosis. A sub-group underwent multiparameter quantitative MRI measurements of liver fat fraction, iron content, tissue T1, liver blood flow and small bowel motility; (3) Results: Compared to non-IFALD (n = 12), patients with IFALD steatosis (n = 8) demonstrated serum score elevations in Enhanced Liver Fibrosis (p = 0.032), Aspartate transaminase-to-Platelet Ratio Index (p < 0.001), Fibrosis-4 Index (p = 0.010), Forns Index (p = 0.001), Gamma-glutamyl transferase-to-Platelet Ratio Index (p = 0.002) and Fibrosis Index (p = 0.001). Quantitative MRI scanning was feasible in all 10 sub-group patients. Median liver fat fraction was higher in IFALD steatosis patients (10.9% vs 2.1%, p = 0.032); other parameter differences were non-significant; (4) Conclusion: Serum scores used for non-IFALD liver diseases may be useful in IFALD steatosis. Multiparameter MRI is feasible in patients on HPN.
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Affiliation(s)
- Konstantinos C. Fragkos
- Intestinal Failure Service, Gastrointestinal Services, University College London Hospitals NHS Foundation Trust, London NW1 2BU, UK; (K.C.F.); (M.C.P.B.); (S.D.C.); (F.R.)
- UCL Division of Medicine, University College London, London WC1E 6BT, UK;
| | - María Claudia Picasso Bouroncle
- Intestinal Failure Service, Gastrointestinal Services, University College London Hospitals NHS Foundation Trust, London NW1 2BU, UK; (K.C.F.); (M.C.P.B.); (S.D.C.); (F.R.)
- UCL Division of Medicine, University College London, London WC1E 6BT, UK;
| | - Shankar Kumar
- UCL Centre for Medical Imaging, University College London, London WC1E 6BT, UK; (S.K.); (L.C.); (A.M.); (S.A.T.)
| | - Lucy Caselton
- UCL Centre for Medical Imaging, University College London, London WC1E 6BT, UK; (S.K.); (L.C.); (A.M.); (S.A.T.)
| | - Alex Menys
- UCL Centre for Medical Imaging, University College London, London WC1E 6BT, UK; (S.K.); (L.C.); (A.M.); (S.A.T.)
| | - Alan Bainbridge
- Department of Medical Physics, University College London Hospitals NHS Foundation Trust, London WC1N 3BG, UK; (A.B.); (F.T.)
| | - Stuart A. Taylor
- UCL Centre for Medical Imaging, University College London, London WC1E 6BT, UK; (S.K.); (L.C.); (A.M.); (S.A.T.)
| | - Francisco Torrealdea
- Department of Medical Physics, University College London Hospitals NHS Foundation Trust, London WC1N 3BG, UK; (A.B.); (F.T.)
| | - Tomoko Kumagai
- UCL Division of Medicine, University College London, London WC1E 6BT, UK;
| | - Simona Di Caro
- Intestinal Failure Service, Gastrointestinal Services, University College London Hospitals NHS Foundation Trust, London NW1 2BU, UK; (K.C.F.); (M.C.P.B.); (S.D.C.); (F.R.)
- UCL Division of Medicine, University College London, London WC1E 6BT, UK;
| | - Farooq Rahman
- Intestinal Failure Service, Gastrointestinal Services, University College London Hospitals NHS Foundation Trust, London NW1 2BU, UK; (K.C.F.); (M.C.P.B.); (S.D.C.); (F.R.)
- UCL Division of Medicine, University College London, London WC1E 6BT, UK;
| | - Jane Macnaughtan
- UCL Institute for Liver and Digestive Health, University College London, London WC1E 6BT, UK;
| | - Manil D. Chouhan
- UCL Centre for Medical Imaging, University College London, London WC1E 6BT, UK; (S.K.); (L.C.); (A.M.); (S.A.T.)
| | - Shameer Mehta
- Intestinal Failure Service, Gastrointestinal Services, University College London Hospitals NHS Foundation Trust, London NW1 2BU, UK; (K.C.F.); (M.C.P.B.); (S.D.C.); (F.R.)
- UCL Division of Medicine, University College London, London WC1E 6BT, UK;
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12
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Nagelkerke SCJ, Draijer LG, Benninga MA, Koot BGP, Tabbers MM. The prevalence of liver fibrosis according to non-invasive tools in a pediatric home parenteral nutrition cohort. Clin Nutr 2020; 40:460-466. [PMID: 32636112 DOI: 10.1016/j.clnu.2020.05.039] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 05/12/2020] [Accepted: 05/25/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Liver biopsy is no viable tool to routinely screen for liver fibrosis in children suffering from chronic intestinal failure (IF). We aim to assess the prevalence of liver fibrosis in a cohort of children with chronic IF by non-invasive tests: transient elastography (TE), aspartate-aminotransferase-to-platelet-ratio-index (APRI) and enhanced liver fibrosis (ELF) score. METHODS Cross sectional study where patients with chronic IF, receiving parenteral nutrition (PN) for at least 3 months, were enrolled. TE, APRI and ELF score were measured. Using Spearman's rank correlation coefficient and Kruskal-Wallis H test, the correlation between TE, APRI, ELF score and known risk factors for development of intestinal failure-associated liver disease (IFALD) were calculated. RESULTS 32 patients were included (50% female), median age was 8 years and 4 months, median PN duration was 45 months. Six patients (21%) had TE ≥6.5 kPa, indicating significant fibrosis. Twelve patients (38%) had APRI ≥.5, indicating fibrosis. ELF score indicated moderate fibrosis in 17 patients (63%) and significant fibrosis in 10 patients (37%). TE and APRI correlated significantly with known risk factors for IFALD, but ELF showed poor correlation with known risk factors for IFALD. CONCLUSION In a cohort of pediatric patients suffering from chronic IF, TE measurement, APRI and ELF test show a varying, but substantial proportion of subjects with fibrosis. The diagnostic value of these tests and their role in the management of pediatric IF must be determined in larger cohorts with liver biopsy as reference standard. TRIAL REGISTRATION Academic Medical Center medical ethics committee number: METC 2017_185.
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Affiliation(s)
- Sjoerd C J Nagelkerke
- Amsterdam UMC, University of Amsterdam, Amsterdam Reproduction and Development Research Institute, Amsterdam, the Netherlands; Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam, the Netherlands; Amsterdam UMC, University of Amsterdam, Emma Children's Hospital, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Amsterdam, the Netherlands.
| | - Laura G Draijer
- Amsterdam UMC, University of Amsterdam, Amsterdam Reproduction and Development Research Institute, Amsterdam, the Netherlands; Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam, the Netherlands; Amsterdam UMC, University of Amsterdam, Emma Children's Hospital, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Amsterdam, the Netherlands
| | - Marc A Benninga
- Amsterdam UMC, University of Amsterdam, Emma Children's Hospital, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Amsterdam, the Netherlands
| | - Bart G P Koot
- Amsterdam UMC, University of Amsterdam, Emma Children's Hospital, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Amsterdam, the Netherlands
| | - Merit M Tabbers
- Amsterdam UMC, University of Amsterdam, Emma Children's Hospital, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Amsterdam, the Netherlands
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13
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Assessment of Selected Parameters of Liver Fibrosis and Inflammation in Patients with Diagnosed Cystic Fibrosis. Mediators Inflamm 2020; 2020:5696185. [PMID: 32308556 PMCID: PMC7132586 DOI: 10.1155/2020/5696185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2019] [Revised: 02/23/2020] [Accepted: 03/14/2020] [Indexed: 11/17/2022] Open
Abstract
Changes in the liver and bile ducts observed in patients diagnosed with cystic fibrosis result from inflammatory processes as well as fibrosis, remodeling, apoptosis, and cholestasis. As a consequence, portal hypertension, cirrhosis, and hepatic failure may develop. So far, the complexity of these processes has not been elucidated. Study Objectives. The aim of the study was to evaluate the selected parameters of hepatitis and fibrosis (Fibrotest, Actitest, and APRI) in patients diagnosed with cystic fibrosis. Material and Methods. The study included 79 patients with cystic fibrosis, aged 1 to 20 years (mean age 9.8 years), 49 girls (62%) and 30 boys (38%). The analysis involved the following: age, sex, clinical manifestations, laboratory tests evaluating pancreas function, parameters of liver damage, and cholestasis. Fibrotest, Actitest, and APRI were performed in all subjects. Results. Elevated parameters of hepatic cell damage (hypertransaminasemia) were found in 31/79 (39.2%) patients, while abnormal cholestasis parameters in 21/79 (26.6%). The abnormal results of Fibrotest were reported in 15% of patients (12/79), while of Actitest in 10% (8/79). In contrast, elevated APRI values were found in only 7.6% (6/79) of subjects. There was a statistically significant correlation between APRI and age (higher values were observed in younger children) and between Fibrotest and Actitest and pancreatic insufficiency (higher values were found in subjects without this abnormality). Moreover, Fibrotest values were significantly higher in girls. There was no correlation between Fibrotest, Actitest, and APRI values and the type of mutation. Conclusion. It appears that Fibrotest may be used as an early marker of liver fibrosis in patients with cystic fibrosis. Increased APRI values were only found in subjects with advanced hepatic lesions, most often in the form of portal hypertension.
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14
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Wang J, Wamuo O, Micic D. Evaluation of Fibrosis in Intestinal Failure–Associated Liver Disease in the Sustain Registry. JPEN J Parenter Enteral Nutr 2020; 44:1285-1290. [DOI: 10.1002/jpen.1758] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Accepted: 11/20/2019] [Indexed: 12/11/2022]
Affiliation(s)
- Jennifer Wang
- Section of Gastroenterology Hepatology and Nutrition Department of Internal Medicine University of Chicago Medicine Chicago Illinois USA
| | - Obinnaya Wamuo
- Maclean Center for Clinical Medical Ethics University of Chicago Medicine Chicago Illinois USA
| | - Dejan Micic
- Section of Gastroenterology Hepatology and Nutrition Department of Internal Medicine University of Chicago Medicine Chicago Illinois USA
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15
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Knop V, Neuberger SC, Marienfeld S, Bojunga J, Herrmann E, Poynard T, Zeuzem S, Blumenstein I, Friedrich-Rust M. Intestinal failure-associated liver disease in patients with short bowel syndrome: Evaluation by transient elastography. Nutrition 2019; 63-64:134-140. [DOI: 10.1016/j.nut.2019.02.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2018] [Revised: 12/27/2018] [Accepted: 02/11/2019] [Indexed: 12/13/2022]
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Hong CR, Han SM, Staffa SJ, Carey AN, Lee CK, Modi BP. Noninvasive assessment of liver fibrosis in pediatric intestinal failure patients using liver stiffness measurement by Vibration-Controlled Transient Elastography. J Pediatr Surg 2019; 54:1174-1178. [PMID: 30879747 DOI: 10.1016/j.jpedsurg.2019.02.038] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2019] [Accepted: 02/21/2019] [Indexed: 12/13/2022]
Abstract
PURPOSE The purpose of this study was to evaluate the diagnostic utility of noninvasive Vibration-Controlled Transient Elastography (VCTE) for assessing liver fibrosis in pediatric intestinal failure (PIF) patients. METHODS Data from children with severe intestinal failure (≥90 days parenteral nutrition dependence) who underwent liver stiffness measurement (LSM), as measured by VCTE, at our institution between December 2015 and March 2018 were reviewed. LSM was compared to METAVIR fibrosis score (F0-F4) on liver biopsy performed within 1 year of VCTE. RESULTS Seventy children underwent 75 LSM. Sixty-three patients (38% female) had at least one valid LSM, and 63% had a history of cholestasis (direct bilirubin ≥2 mg/dL). Median (IQR) age at first valid LSM was 4.5 years (2.6, 8.7). Sixteen patients had a liver biopsy. LSM differentiated between METAVIR F0-F1 (n = 6) and F2-F4 (n = 10) with an area under the receiver operating characteristic (AUROC) curve of 0.883 (95% CI: 0.686-0.999). The optimal cut-point derived to predict F2-F4 was an LSM ≥6 kPa (sensitivity 80%, specificity 100%). CONCLUSION LSM as determined by VCTE can distinguish mild (F0-F1) from moderate/severe (F2-F4) liver fibrosis in PIF. VCTE could allow for serial noninvasive monitoring of liver injury, potentially facilitating timely modifications to hepatoprotective management. TYPE OF STUDY Study of Diagnostic Test. LEVEL OF EVIDENCE II.
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Affiliation(s)
- Charles R Hong
- Center for Advanced Intestinal Rehabilitation; Boston Children's Hospital, Boston, MA; Department of Surgery; Boston Children's Hospital and Harvard Medical School, Boston, MA
| | - Sam M Han
- Center for Advanced Intestinal Rehabilitation; Boston Children's Hospital, Boston, MA; Department of Surgery; Boston Children's Hospital and Harvard Medical School, Boston, MA
| | - Steven J Staffa
- Department of Surgery; Boston Children's Hospital and Harvard Medical School, Boston, MA
| | - Alexandra N Carey
- Center for Advanced Intestinal Rehabilitation; Boston Children's Hospital, Boston, MA; Division of Gastroenterology, Hepatology, and Nutrition; Boston Children's Hospital and Harvard Medical School, Boston, MA
| | - Christine K Lee
- Division of Gastroenterology, Hepatology, and Nutrition; Boston Children's Hospital and Harvard Medical School, Boston, MA
| | - Biren P Modi
- Center for Advanced Intestinal Rehabilitation; Boston Children's Hospital, Boston, MA; Department of Surgery; Boston Children's Hospital and Harvard Medical School, Boston, MA.
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17
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Blüthner E, Bednarsch J, Pape UF, Karber M, Maasberg S, Gerlach UA, Pascher A, Wiedenmann B, Pratschke J, Stockmann M. Advanced liver function assessment in patients with intestinal failure on long-term parenteral nutrition. Clin Nutr 2019; 39:540-547. [PMID: 30885502 DOI: 10.1016/j.clnu.2019.02.039] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Revised: 02/19/2019] [Accepted: 02/24/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS Intestinal failure associated liver disease (IFALD) is one of the leading complications and causes of deaths in adult patients receiving home parenteral nutrition for chronic intestinal failure (CIF). Early diagnosis of IFALD is key to alleviate the progression of hepatic dysfunction. The aim of this study was to evaluate the capability of noninvasive liver function tests. METHODS 90 adult patients with CIF receiving long-term home parenteral nutrition were included in a prospective cross-sectional study at our department between 2014 and 2017. All participants underwent dynamic liver function assessment (maximum liver function capacity [LiMAx] test, indocyanine green [ICG] test), transient elastography (FibroScan), blood tests and comprehensive nutritional status assessment. Univariate and multivariable analysis were performed to identify predictors of liver function. RESULTS LiMAx, ICG test, and FibroScan highly correlated with standard liver function tests. Multivariable analysis identified intact ileum (B = 520.895; p = 0.010), digestive anatomy type 3 (B = 75.612; p = 0.025), citrulline level (B = 3.428; p = 0.040), parenteral olive oil intake (B = -0.570; p = 0.043), and oral intake (B = 182.227; p = 0.040) as independent risk factors affecting liver function determined by LiMAx test. ICG test and FibroScan showed no correlation with gastrointestinal and nutrition-related parameters. CONCLUSION The LiMAx test is significantly associated with widely accepted risk factors for IFALD by multivariable analysis, whereas ICG test and FibroScan failed to show significant correlations. Liver function assessment by LiMAx test may therefore have the potential to detect alterations in liver function and identify patients at risk for the development of IFALD. Longitudinal studies are needed to investigate the impact of liver function determined by LiMAx test on long-term outcome in patients with CIF.
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Affiliation(s)
- Elisabeth Blüthner
- Department of Gastroenterology and Hepatology, Campus Virchow-Klinikum and Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; Department of Surgery, Campus Virchow-Klinikum and Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
| | - Jan Bednarsch
- Department of General, Visceral and Transplantation Surgery, University Hospital Aachen, Rhine-Westphalia Institute of Technology, Pauwelsstraße 30, 52074 Aachen, Germany.
| | - Ulrich-Frank Pape
- Department of Gastroenterology and Hepatology, Campus Virchow-Klinikum and Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; Department of Internal Medicine and Gastroenterology, Asklepios Klinik St. Georg, Asklepios Medical School, Lohmühlenstr. 5, 20099 Hamburg, Germany.
| | - Mirjam Karber
- Department of Gastroenterology and Hepatology, Campus Virchow-Klinikum and Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; Berlin Institute of Health (BIH), Anna-Louisa-Karsch-Str. 2, 10178 Berlin, Germany.
| | - Sebastian Maasberg
- Department of Gastroenterology and Hepatology, Campus Virchow-Klinikum and Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; Department of Internal Medicine and Gastroenterology, Asklepios Klinik St. Georg, Asklepios Medical School, Lohmühlenstr. 5, 20099 Hamburg, Germany.
| | - Undine A Gerlach
- Department of Surgery, Campus Virchow-Klinikum and Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
| | - Andreas Pascher
- Department of Surgery, Campus Virchow-Klinikum and Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Department of General, Visceral and Transplantation Surgery, Münster University Hospital, Albert-Schweitzer-Campus 1, 48149 Münster, Germany.
| | - Bertram Wiedenmann
- Department of Gastroenterology and Hepatology, Campus Virchow-Klinikum and Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
| | - Johann Pratschke
- Department of Surgery, Campus Virchow-Klinikum and Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
| | - Martin Stockmann
- Department of Surgery, Campus Virchow-Klinikum and Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Department of General, Visceral and Vascular Surgery, Evangelisches Krankenhaus Paul Gerhardt Stift, Paul-Gerhardt-Str. 42-45, 06886 Lutherstadt Wittenberg, Germany.
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Dou J, Zhou Y, Cui Y, Chen M, Wang C, Zhang Y. AST-to-Platelet Ratio Index as Potential Early-Warning Biomarker for Sepsis-Associated Liver Injury in Children: A Database Study. Front Pediatr 2019; 7:331. [PMID: 31497584 PMCID: PMC6713043 DOI: 10.3389/fped.2019.00331] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Accepted: 07/23/2019] [Indexed: 12/29/2022] Open
Abstract
Background: Sepsis-associated liver injury (SALI) is a risk factor of poor outcome in patients with sepsis. The early warning biomarkers for identifying SALI remain poorly defined. Aims: To identify the potential predictors of occurrence of SALI in pediatric patients with sepsis. Methods: We retrospectively analyzed the sepsis database based on the medical records of patients admitted to the pediatric intensive care unit (PICU) in Shanghai Children's Hospital from July 2014 to June 2018. Patients' demographics, co-morbidities and laboratory variables were collected. Univariate and multivariate logistic analysis were used to explore risk factors of SALI, and receiver operating characteristic (ROC) curve analysis was used to evaluate their predictive significances for SALI occurrence. Results: Of 1,645 eligible patients, 1,147 patients were included, and 105 cases had SALI. The indexes including AST-to-platelet ratio index (APRI), γ-GT and lactate dehydrogenase (LDH) were independent risk factors for SALI. Moreover, APRI was powerful to predict SALI in children (AUC: 0.889, 95% CI: 0.851-0.927) with a sensitivity of 84.6 % and a specificity of 84.3 % at the cutoff point of 0.340. APRI was superior to LDH and not inferior to γ-GT for predicting SALI. Conclusion: APRI is an independent risk factor of SALI occurrence, and elevated APRI within 24 h after PICU admission (>0.340) is a potential predictor for SALI in children.
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Affiliation(s)
- Jiaying Dou
- Department of Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Yiping Zhou
- Department of Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Yun Cui
- Department of Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Min Chen
- Department of Information Technology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Chunxia Wang
- Department of Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.,Institute of Pediatric Critical Care, Shanghai Jiao Tong University, Shanghai, China
| | - Yucai Zhang
- Department of Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.,Institute of Pediatric Critical Care, Shanghai Jiao Tong University, Shanghai, China
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Authors' Response. J Pediatr Gastroenterol Nutr 2018; 67:e41. [PMID: 29746343 DOI: 10.1097/mpg.0000000000002026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
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Vongbhavit K, Underwood MA. Predictive Value of the Aspartate Aminotransferase to Platelet Ratio Index for Parenteral Nutrition-Associated Cholestasis in Premature Infants With Intestinal Perforation. JPEN J Parenter Enteral Nutr 2017; 42:797-804. [PMID: 28792861 DOI: 10.1177/0148607117722755] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Accepted: 06/30/2017] [Indexed: 12/18/2022]
Abstract
BACKGROUND Parenteral nutrition-associated cholestasis (PNAC) is a major cause of morbidity and mortality in premature infants. Early predictors of PNAC would have clinical value. We sought to evaluate risk factors and liver function testing as predictors of PNAC in premature infants with intestinal perforation. METHODS Medical records of infants with a gestational age <34 weeks, birth weight <2000 g, and intestinal perforation due to either necrotizing enterocolitis or spontaneous intestinal perforation were reviewed. We analyzed clinical data and the maximum values of the aspartate aminotransferase (AST) to platelet ratio index (APRI), alanine aminotransferase (ALT), AST to ALT ratio, and total bilirubin (TB). RESULTS Sixty infants were identified, 17 infants with PNAC and 43 infants without PNAC. Sepsis, time to initiation of enteral feeds after perforation, and duration of PN were associated with PNAC. Within 2 weeks following intestinal perforation, APRI, ALT, and TB each differed significantly between infants who later developed PNAC and those that did not. The best APRI cut-point was 0.4775 within 2 weeks after perforation (area under the receiver operating characteristic curve, 0.90; positive predictive value, 85%; and negative predictive value, 87%); the cut-point for ALT was 13.5 (0.90, 85%, 84%), and the cut-point for TB was 3.55 (0.82, 69%, 83%), respectively, at 2 weeks after perforation. AST to ALT ratio did not differ between groups. CONCLUSIONS APRI and ALT had reasonable predictive value for PNAC in premature infants with intestinal perforation, with the APRI the best predictor within 2 weeks after perforation.
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Affiliation(s)
- Kannikar Vongbhavit
- Department of Pediatrics, Faculty of Medicine, Srinakharinwirot University, Nakhon-Nayok, Thailand.,Department of Pediatrics, University of California Davis School of Medicine, Sacramento, California, USA
| | - Mark A Underwood
- Department of Pediatrics, University of California Davis School of Medicine, Sacramento, California, USA
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Engelmann G, Quader J, Teufel U, Schenk JP. Limitations and opportunities of non-invasive liver stiffness measurement in children. World J Hepatol 2017; 9:409-417. [PMID: 28357028 PMCID: PMC5355763 DOI: 10.4254/wjh.v9.i8.409] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2016] [Revised: 11/29/2016] [Accepted: 01/14/2017] [Indexed: 02/06/2023] Open
Abstract
Changes in liver structure are an important issue in chronic hepatopathies. Until the end of the 20th century, these changes could only be determined by histological analyses of a liver specimen obtained via biopsy. The well-known limitations of this technique (i.e., pain, bleeding and the need for sedation) have precluded its routine use in follow-up of patients with liver diseases. However, the introduction of non-invasive technologies, such as ultrasound and magnetic resonance imaging, for measurement of liver stiffness as an indirect marker of fibroses has changed this situation. Today, several non-invasive tools are available to physicians to estimate the degree of liver fibrosis by analysing liver stiffness. This review describes the currently available tools for liver stiffness determination that are applicable to follow-up of liver fibrosis/cirrhosis with established clinical use in children, and discusses their features in comparison to the “historical” tools.
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D’Souza A, Algotar A, Pan L, Schwarz SM, Treem WR, Valencia G, Rabinowitz SS. Packed red blood cell transfusions as a risk factor for parenteral nutrition associated liver disease in premature infants. World J Clin Pediatr 2016; 5:365-369. [PMID: 27872824 PMCID: PMC5099588 DOI: 10.5409/wjcp.v5.i4.365] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2016] [Revised: 08/13/2016] [Accepted: 10/24/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To determine if packed red blood cell transfusions contribute to the development of parenteral nutrition associated liver disease.
METHODS A retrospective chart review of 49 premature infants on parenteral nutrition for > 30 d who received packed red blood cell (PRBC) transfusions was performed. Parenteral nutrition associated liver disease was primarily defined by direct bilirubin (db) > 2.0 mg/dL. A high transfusion cohort was defined as receiving > 75 mL packed red blood cells (the median value). Kaplan-Meier plots estimated the median volume of packed red blood cells received in order to develop parenteral nutrition associated liver disease.
RESULTS Parenteral nutritional associated liver disease (PNALD) was noted in 21 (43%) infants based on db. Among the 27 high transfusion infants, PNALD was present in 17 (64%) based on elevated direct bilirubin which was significantly greater than the low transfusion recipients. About 50% of the infants, who were transfused 101-125 mL packed red blood cells, developed PNALD based on elevation of direct bilirubin. All infants who were transfused more than 200 mL of packed red blood cells developed PNALD. Similar results were seen when using elevation of aspartate transaminase or alanine transaminase to define PNALD.
CONCLUSION In this retrospective, pilot study there was a statistically significant correlation between the volume of PRBC transfusions received by premature infants and the development of PNALD.
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A Prospective Comparison of Noninvasive Methods in the Assessment of Liver Fibrosis and Esophageal Varices in Pediatric Chronic Liver Diseases. J Clin Gastroenterol 2016; 50:658-63. [PMID: 27105175 DOI: 10.1097/mcg.0000000000000532] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
GOALS AND BACKGROUND We compared liver stiffness (LS), the aspartate aminotransferase-to-platelet ratio index (APRi), and the platelet-to-spleen size z score ratio (P/SZC) in the prediction of liver fibrosis and esophageal varices in children. STUDY LS, APRi, SZC, and P/SZC were prospectively determined in 99 unselected consecutive children, who underwent liver biopsy for the follow-up of chronic liver disorders. LS was assessed by transient elastography. The spleen size was evaluated as the SD from age-specific and gender-specific normative values. Varices were assessed endoscopically (n=64). Biopsies were staged according to Metavir. RESULTS The median patient age was 6.0 (interquartile range, 1.8 to 12.9) years. Underlying diagnoses included intestinal failure (n=31), biliary atresia (n=24), and others (n=44). LS showed the strongest correlation with the fibrosis stage (r=0.639, P<0.001) compared with P/SZC (r=-0.427, P=0.003), APRi (r=0.419, P=0.001), or SZC (r=0.396, P=0.004). LS clearly performed the best in predicting fibrosis with area under the receiver operator curve (AUROC) values of 0.789 [95% confidence interval (CI), 0.698-0.879; P<0.001] for any (Metavir≥1), and 0.831 (95% CI, 0.745-0.918; P<0.001) for significant (Metavir≥2) fibrosis. For the prediction of the presence of esophageal varices, APRi had a higher AUROC of 0.832 (95% CI, 0.730-0.934; P<0.001), when compared with LS, SZC, or P/SZC with AUROCs of 0.818 (95% CI, 0.706-0.930; P<0.001), 0.795 (95% CI, 0.683-0.904; P=0.001), and 0.760 (95% CI, 0.610-0.909; P=0.004), respectively. CONCLUSIONS LS performed the best in predicting liver fibrosis, whereas APRi had the highest predictive accuracy for esophageal varices. An LS value over 7.7 kPa identified significant liver fibrosis with high accuracy, whereas low APRi ascertained the absence of esophageal varices.
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Hanquinet S, Courvoisier DS, Rougemont AL, Wildhaber BE, Merlini L, McLin VA, Anooshiravani M. Acoustic radiation force impulse sonography in assessing children with biliary atresia for liver transplantation. Pediatr Radiol 2016; 46:1011-6. [PMID: 26939975 DOI: 10.1007/s00247-016-3565-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2015] [Revised: 01/05/2016] [Accepted: 01/26/2016] [Indexed: 12/17/2022]
Abstract
BACKGROUND Children with biliary atresia are prone to developing progressive hepatic fibrosis and biliary cirrhosis following the Kasai operation. The only treatment is liver transplantation. OBJECTIVE To assess liver fibrosis by acoustic radiation force impulse elastography (ARFI) in children who had Kasai operation, with the goal of identifying an ARFI value cut-off for children requiring liver transplantation. MATERIALS AND METHODS Of the 32 post-Kasai children included, 19 were transplanted or listed for transplantation (group A), while 13 were not on the list during their follow-up (group B). We recorded biopsies, blood samples and ARFI values over time, including at Kasai operation and at transplantation. We estimated an association between groups and continuous variables using generalized estimating equations, and we compared categorical variables using the Fisher exact test. RESULTS Portal hypertension signs were similar in both groups, whereas ARFI values were higher in group A (mean±standard deviation=3.3±1.2 m/s) than in group B (2.0±0.7 m/s; P=.0003). Eighteen of 19 (94.7%) children in group A and 6/13 (46.2%) children in group B presented with two consecutive ARFI values ≥2 m/s (sensitivity=7%, specificity=53.8%; P=0.003). CONCLUSION We found that children who were transplanted had two consecutive ARFI values ≥2 m/s during follow-up. ARFI for evaluation of post-Kasai liver fibrosis may assist the long-term assessment of biliary atresia and may even guide treatment decisions.
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Affiliation(s)
- Sylviane Hanquinet
- Department of Pediatric Radiology, Children's University Hospital of Geneva, 6 rue Willy Donzé, Ch 1211, Genève 14, Switzerland.
| | | | - Anne-Laure Rougemont
- Division of Clinical Pathology, University Hospital of Geneva, Geneva, Switzerland
| | - Barbara E Wildhaber
- Department of Pediatric Surgery, Children's University Hospital of Geneva, Geneva, Switzerland
| | - Laura Merlini
- Department of Pediatric Radiology, Children's University Hospital of Geneva, 6 rue Willy Donzé, Ch 1211, Genève 14, Switzerland
| | - Valérie A McLin
- Department of Pediatric Gastroenterology, Children's University Hospital of Geneva, Geneva, Switzerland
| | - Mehrak Anooshiravani
- Department of Pediatric Radiology, Children's University Hospital of Geneva, 6 rue Willy Donzé, Ch 1211, Genève 14, Switzerland
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Hukkinen M, Kivisaari R, Lohi J, Heikkilä P, Mutanen A, Merras-Salmio L, Pakarinen MP. Transient elastography and aspartate aminotransferase to platelet ratio predict liver injury in paediatric intestinal failure. Liver Int 2016; 36:361-9. [PMID: 26058319 DOI: 10.1111/liv.12887] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2015] [Accepted: 06/01/2015] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS We aimed to evaluate the value of AST to platelet ratio (APRI) and transient elastography (TE) as predictors of liver histopathology in children with intestinal failure (IF). METHODS Altogether 93 liver biopsies from 57 children with parenteral nutrition (PN) duration ≥3 months were analysed. APRI measurement and TE (n = 46) were performed at the time of biopsy. RESULTS IF was caused by short bowel syndrome in 75% of patients. At the time of liver biopsy, PN dependent patients (n = 42) were younger with longer PN duration compared to those weaned off PN (n = 51) (2.2 vs. 7.6 years, P < 0.001; 26 vs. 10.5 months, P = 0.043). Elevated transaminase or bilirubin levels were found in 51%, splenomegaly in 26%, and oesophageal varices in 3.5%. Histological fibrosis was present in 61% (Metavir stage F1; 27%, F2; 26%, F3-4; 9%), cholestasis in 25% and steatosis in 22% of biopsy specimens. TE was superior to APRI in prediction of any liver histopathology (fibrosis, cholestasis or steatosis) with areas under the receiving operating curve (AUROC) of 0.86 (95% CI 0.74-0.97) and 0.67 (95% CI 0.58-0.78) respectively. For prediction of ≥F1 and ≥F2 fibrosis, AUROC values for TE were 0.78 (95% CI 0.64-0.93) and 0.73 (95% CI 0.59-0.88), whereas APRI did not correlate with fibrosis stages. For detection of histological cholestasis, the AUROC for APRI was 0.77 (95% CI 0.64-0.89). CONCLUSIONS Both TE and APRI are promising noninvasive methods for monitoring the development of IF-related liver histopathology. TE values reflected the degree of fibrosis better while APRI detected histological cholestasis more accurately.
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Affiliation(s)
- Maria Hukkinen
- Pediatric Liver and Gut Research Group, Children's Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| | - Reetta Kivisaari
- HUS Medical Imaging Center, Children's Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| | - Jouko Lohi
- Department of Pathology, HUSLAB, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| | - Päivi Heikkilä
- Department of Pathology, HUSLAB, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| | - Annika Mutanen
- Pediatric Liver and Gut Research Group, Children's Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.,Section of Pediatric Surgery, Children's Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| | - Laura Merras-Salmio
- Pediatric Liver and Gut Research Group, Children's Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.,Section of Pediatric Gastroenterology, Children's Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| | - Mikko P Pakarinen
- Pediatric Liver and Gut Research Group, Children's Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.,Section of Pediatric Surgery, Children's Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
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26
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Rumbo C, Martinez MI, Cabanne A, Trentadue J, Fernández A, Gondolesi G. Utility of Aminotransferase/Platelet Ratio Index to Predict Liver Fibrosis in Intestinal Failure–Associated Liver Disease in Pediatric Patients. JPEN J Parenter Enteral Nutr 2016; 41:884-889. [DOI: 10.1177/0148607115625779] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Affiliation(s)
- Carolina Rumbo
- Multi-Organ Transplant Institute, Hospital Universitario Fundación Favaloro, CABA, Argentina
| | - María Inés Martinez
- Multi-Organ Transplant Institute, Hospital Universitario Fundación Favaloro, CABA, Argentina
| | - Ana Cabanne
- Department of Pathology, Hospital Universitario Fundación Favaloro, CABA, Argentina
| | - Julio Trentadue
- Department of Pediatrics, Hospital Universitario Fundación Favaloro, CABA, Argentina
| | - Adriana Fernández
- Multi-Organ Transplant Institute, Hospital Universitario Fundación Favaloro, CABA, Argentina
| | - Gabriel Gondolesi
- Multi-Organ Transplant Institute, Hospital Universitario Fundación Favaloro, CABA, Argentina
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Fullerton BS, Sparks EA, Hall AM, Duggan C, Jaksic T, Modi BP. Enteral autonomy, cirrhosis, and long term transplant-free survival in pediatric intestinal failure patients. J Pediatr Surg 2016; 51:96-100. [PMID: 26561248 PMCID: PMC4713317 DOI: 10.1016/j.jpedsurg.2015.10.027] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2015] [Accepted: 10/07/2015] [Indexed: 12/12/2022]
Abstract
PURPOSE Patient selection for transplant evaluation in pediatric intestinal failure is predicated on the ability to assess long-term transplant-free survival. In light of trends toward improved survival of intestinal failure patients in recent decades, we sought to determine if the presence of biopsy-proven hepatic cirrhosis or the eventual achievement of enteral autonomy were associated with transplant-free survival. METHODS After IRB approval, records of all pediatric intestinal failure patients (parenteral nutrition (PN) >90 days) treated at a single intestinal failure center from February 2002 to September 2014 were reviewed. Chi-squared, Mann-Whitney, and log-rank testing were performed as appropriate. RESULTS Of 313 patients, 174 eventually weaned off PN. Liver biopsies were available in 126 patients (most common indication was intestinal failure associated liver disease, IFALD), and 23 met histologic criteria for cirrhosis. Transplant-free survival for the whole cohort of 313 patients was 94.7% at 1 year and 89.2% at 5 years. Among patients with liver biopsies, transplant-free survival in cirrhotics vs. noncirrhotics was 95.5% vs. 94.1% at one year and 95.5% vs. 86.7% at 5 years (P=0.29). Transplant-free survival in patients who achieved enteral autonomy compared with patients who remained PN dependent was 98.2% vs. 90.3% at one year and 98.2% vs. 76.9% at 5 years (P<0.001). There was no association between cirrhosis and eventual enteral autonomy (P=0.88). CONCLUSIONS Achieving enteral autonomy was associated with improved transplant-free survival in pediatric intestinal failure patients. There was no association between histopathological diagnosis of cirrhosis and transplant-free survival in the cohort. These data suggest that automatic transplant referral may not be required for histopathological diagnosis of cirrhosis alone, and that ongoing efforts aimed at achievement of enteral autonomy remain paramount in pediatric intestinal failure.
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Affiliation(s)
- Brenna S. Fullerton
- Center for Advanced Intestinal Rehabilitation, Boston Children’s Hospital, Boston, MA
,Department of Surgery, Boston Children’s Hospital, Boston, MA
| | - Eric A. Sparks
- Center for Advanced Intestinal Rehabilitation, Boston Children’s Hospital, Boston, MA
,Department of Surgery, Boston Children’s Hospital, Boston, MA
| | - Amber M. Hall
- Department of Surgery, Boston Children’s Hospital, Boston, MA
| | - Christopher Duggan
- Center for Advanced Intestinal Rehabilitation, Boston Children’s Hospital, Boston, MA
,Division of Gastroenterology, Hepatology and Nutrition, Boston Children’s Hospital, Boston, MA
| | - Tom Jaksic
- Center for Advanced Intestinal Rehabilitation, Boston Children’s Hospital, Boston, MA
,Department of Surgery, Boston Children’s Hospital, Boston, MA
| | - Biren P. Modi
- Center for Advanced Intestinal Rehabilitation, Boston Children’s Hospital, Boston, MA
,Department of Surgery, Boston Children’s Hospital, Boston, MA
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28
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Hanquinet S, Courvoisier DS, Rougemont AL, Dhouib A, Rubbia-Brandt L, Wildhaber BE, Merlini L, McLin VA, Anooshiravani M. Contribution of acoustic radiation force impulse (ARFI) elastography to the ultrasound diagnosis of biliary atresia. Pediatr Radiol 2015; 45:1489-95. [PMID: 25943691 DOI: 10.1007/s00247-015-3352-6] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2014] [Accepted: 04/01/2015] [Indexed: 02/08/2023]
Abstract
BACKGROUND Children with biliary atresia rapidly develop liver fibrosis secondary to inflammatory destruction of the biliary tract. Noninvasive detection of liver fibrosis in neonatal/infantile cholestasis is an additional criterion for the diagnosis of biliary atresia, leading to prompt surgical exploration. OBJECTIVE To assess the value of US with acoustic radiation force impulse (ARFI) elastography to detect biliary atresia in the workup of neonatal/infantile cholestasis. MATERIALS AND METHODS In this retrospective study, 20 children with cholestasis suspected of having biliary atresia were investigated by US and ARFI. We evaluated the association between US findings and the diagnosis of biliary atresia and with two scores of liver fibrosis obtained from liver biopsy. RESULTS In univariate analyses, gallbladder size, triangular cord sign, spleen size and ARFI values were found to be associated with biliary atresia, though only the triangular cord sign remained significant when elevated gamma glutamyltransferase (GGT) was included as a predictor. In contrast, spleen size and ARFI correlated with the degree of liver fibrosis on biopsy (r > 0.70, P < 0.001), which remained significant when gamma glutamyltransferase elevation was included as a predictor. CONCLUSION The addition of ARFI to a standard abdominal US in the initial workup of the neonate with possible infantile cholestasis can provide reliable information on liver fibrosis and help in the diagnosis of biliary atresia.
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Affiliation(s)
- Sylviane Hanquinet
- Department of Pediatric Radiology, University Children's Hospital, 6 rue Willy Donzé, Ch 1211, Geneva 14, Switzerland,
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Role of the Aspartate Transaminase and Platelet Ratio Index in Assessing Hepatic Fibrosis and Liver Inflammation in Adolescent Patients with HBeAg-Positive Chronic Hepatitis B. Gastroenterol Res Pract 2015; 2015:906026. [PMID: 26236336 PMCID: PMC4506824 DOI: 10.1155/2015/906026] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2015] [Revised: 06/11/2015] [Accepted: 06/14/2015] [Indexed: 01/01/2023] Open
Abstract
This study described an index of aspartate aminotransferase-to-platelet ratio index (APRI) to assess hepatic fibrosis with limited expense and widespread availability compared to the liver biopsy in adolescent patients with CHB.
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30
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Khan FA, Squires RH, Litman HJ, Balint J, Carter BA, Fisher JG, Horslen SP, Jaksic T, Kocoshis S, Martinez JA, Mercer D, Rhee S, Rudolph JA, Soden J, Sudan D, Superina RA, Teitelbaum DH, Venick R, Wales PW, Duggan C. Predictors of Enteral Autonomy in Children with Intestinal Failure: A Multicenter Cohort Study. J Pediatr 2015; 167:29-34.e1. [PMID: 25917765 PMCID: PMC4485931 DOI: 10.1016/j.jpeds.2015.03.040] [Citation(s) in RCA: 119] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2014] [Revised: 02/27/2015] [Accepted: 03/18/2015] [Indexed: 11/12/2022]
Abstract
OBJECTIVES In a large cohort of children with intestinal failure (IF), we sought to determine the cumulative incidence of achieving enteral autonomy and identify patient and institutional characteristics associated with enteral autonomy. STUDY DESIGN A multicenter, retrospective cohort analysis from the Pediatric Intestinal Failure Consortium was performed. IF was defined as severe congenital or acquired gastrointestinal diseases during infancy with dependence on parenteral nutrition (PN) >60 days. Enteral autonomy was defined as PN discontinuation >3 months. RESULTS A total of 272 infants were followed for a median (IQR) of 33.5 (16.2-51.5) months. Enteral autonomy was achieved in 118 (43%); 36 (13%) remained PN dependent and 118 (43%) patients died or underwent transplantation. Multivariable analysis identified necrotizing enterocolitis (NEC; OR 2.42, 95% CI 1.33-4.47), care at an IF site without an associated intestinal transplantation program (OR 2.73, 95% CI 1.56-4.78), and an intact ileocecal valve (OR 2.80, 95% CI 1.63-4.83) as independent risk factors for enteral autonomy. A second model (n = 144) that included only patients with intraoperatively measured residual small bowel length found NEC (OR 3.44, 95% CI 1.36-8.71), care at a nonintestinal transplantation center (OR 6.56, 95% CI 2.53-16.98), and residual small bowel length (OR 1.04 cm, 95% CI 1.02-1.06 cm) to be independently associated with enteral autonomy. CONCLUSIONS A substantial proportion of infants with IF can achieve enteral autonomy. Underlying NEC, preserved ileocecal valve, and longer bowel length are associated with achieving enteral autonomy. It is likely that variations in institutional practices and referral patterns also affect outcomes in children with IF.
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Affiliation(s)
| | - Robert H Squires
- Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA
| | | | - Jane Balint
- Nationwide Children's Hospital, Columbus, OH
| | | | | | | | | | - Samuel Kocoshis
- Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | | | - David Mercer
- Children's Hospital and Medical Center, Omaha, NE
| | - Susan Rhee
- University of California, San Francisco, Benioff Children's Hospital, San Francisco, CA
| | - Jeffrey A Rudolph
- Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Jason Soden
- Children's Hospital Colorado Medical Center, Denver, CO
| | - Debra Sudan
- Duke Children's Hospital and Health Center, Durham, NC
| | | | | | - Robert Venick
- Mattel Children's Hospital University of California, Los Angeles, Los Angeles, CA
| | - Paul W Wales
- Hospital for Sick Children, Toronto, Ontario, Canada
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31
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Yang LY, Fu J, Peng XF, Pang SY, Gao KK, Chen ZR, He LJ, Wen Z, Wang H, Li L, Wang FH, Yu JK, Xu Y, Gong ST, Xia HM, Liu HY. Validation of aspartate aminotransferase to platelet ratio for diagnosis of liver fibrosis and prediction of postoperative prognosis in infants with biliary atresia. World J Gastroenterol 2015; 21:5893-5900. [PMID: 26019453 PMCID: PMC4438023 DOI: 10.3748/wjg.v21.i19.5893] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2014] [Revised: 01/12/2015] [Accepted: 02/13/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To validate the value of aspartate aminotransferase to platelet ratio index (APRI) in assessment of liver fibrosis and prediction of postoperative prognosis of biliary atresia (BA) infants from Mainland China.
METHODS: Medical records of 153 BA infants who were hospitalized from January 2010 to June 2013 were reviewed. The efficacy of APRI for diagnosis of liver fibrosis was assessed using the receiver operator characteristic (ROC) curve compared to the pathological Metavir fibrosis score of the liver wedge specimens of 91 BA infants. The prognostic value of preoperative APRI for jaundice persistence, liver injury, and occurrence of cholangitis within 6 mo after KP was studied based on the follow-up data of 48 BA infants.
RESULTS: APRI was significantly correlated with Metavir scores (rs = 0.433; P < 0.05). The mean APRI value was 0.76 in no/mild fibrosis group (Metavir score F0-F1), 1.29 in significant fibrosis group (F2-F3), and 2.51 in cirrhosis group (F4) (P < 0.001). The area under the ROC curve (AUC) of APRI for diagnosing significant fibrosis and cirrhosis was 0.75 (P < 0.001) and 0.81 (P = 0.001), respectively. The APRI cut-off of 0.95 was 60.6% sensitive and 76.0% specific for significant fibrosis diagnosis, and a threshold of 1.66 was 70.6% sensitive and 82.7% specific for cirrhosis. The preoperative APRI in infants who maintained jaundice around 6 mo after KP was higher than that in those who did not (1.86 ± 2.13 vs 0.87 ± 0.48, P < 0.05). The AUC of APRI for prediction of postoperative jaundice occurrence was 0.67. A cut-off value of 0.60 showed a sensitivity of 66.7% and a specificity of 83.3% for the prediction of jaundice persistence. Preoperative APRI had no significant association with later liver injury or occurrence of cholangitis.
CONCLUSION: Our study demonstrated that APRI could diagnose significant liver fibrosis, especially cirrhosis in BA infants, and the elevated preoperative APRI predicts jaundice persistence after KP.
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Preservation of biochemical liver function with low-dose soy-based lipids in children with intestinal failure-associated liver disease. J Pediatr Gastroenterol Nutr 2015; 60:375-7. [PMID: 25714580 PMCID: PMC4341952 DOI: 10.1097/mpg.0000000000000609] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Intestinal failure-associated liver disease (IFALD) contributes to significant morbidity in pediatric patients with intestinal failure (IF); however, the use of parenteral nutrition (PN) with a fish oil-based intravenous (IV) emulsion (FO) has been associated with biochemical reversal of cholestasis and improved outcomes. Unfortunately, FO increases the complexity of care: because it can be administered only under Food and Drug Administration compassionate use protocols requiring special monitoring, it is not available as a 3-in-1 solution and is more expensive than comparable soy-based IV lipid emulsion (SO). Because of these pragmatic constraints, a series of patient families were switched to low-dose (1 g kg(-1) day(-1)) SO following biochemical resolution of cholestasis. The present study examines whether reversal of cholestasis and somatic growth are maintained following this transition. METHODS The present study is a chart review of all children with IFALD who switched from FO to SO following resolution of cholestasis. Variables are presented as medians (interquartile ranges). Comparisons were performed using the Wilcoxon signed-rank test. RESULTS Seven patients ages 25.9 (16.2-43.2) months were transitioned to SO following reversal of cholestasis using FO. At a median follow-up of 13.9 (4.3-50.1) months, there were no significant differences between pretransition and post-transition serum alanine and aspartate aminotransferases, direct bilirubin, and weight-for-age z scores. Because of recurrence of cholestasis, 1 patient was restarted on FO after 4 months on SO. CONCLUSIONS Biochemical reversal of IFALD and growth were preserved after transition from FO to SO in 6 of 7 (86%) patients. Given the challenges associated with the use of FO, SO may be a viable alternative in select patients with home PN.
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Intestinal failure-associated liver disease: a position paper of the ESPGHAN Working Group of Intestinal Failure and Intestinal Transplantation. J Pediatr Gastroenterol Nutr 2015; 60:272-83. [PMID: 25272324 DOI: 10.1097/mpg.0000000000000586] [Citation(s) in RCA: 148] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Intestinal failure-associated liver disease is the most prevalent complication affecting children with intestinal failure receiving long-term parenteral nutrition. This paper reviews the definition, diagnostic criteria, pathogenesis, and risk factors. The authors discuss the role of enteral nutrition, parenteral nutrition, and its components, especially lipid emulsions. The authors also discuss the surgical treatment, including intestinal transplantation, its indications, technique, and results, and emphasise the importance of specialised intestinal failure centres.
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Sira MM, Behairy BE, Abd-Elaziz AM, Abd Elnaby SA, Eltahan EE. Serum Inter-Alpha-Trypsin Inhibitor Heavy Chain 4 (ITIH4) in Children with Chronic Hepatitis C: Relation to Liver Fibrosis and Viremia. HEPATITIS RESEARCH AND TREATMENT 2014; 2014:307942. [PMID: 25295185 PMCID: PMC4177773 DOI: 10.1155/2014/307942] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/05/2014] [Revised: 09/02/2014] [Accepted: 09/03/2014] [Indexed: 02/07/2023]
Abstract
Liver fibrosis and viremia are determinant factors for the treatment policy and its outcome in chronic hepatitis C virus (HCV) infection. We aimed to investigate serum level of inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) and its relation to liver fibrosis and viremia in children with chronic HCV. ITIH4 was measured by ELISA in 33 treatment-naive children with proved chronic HCV and compared according to different clinical, laboratory and histopathological parameters. Liver histopathological changes were assessed using Ishak score and compared with aspartate transaminase-to-platelet ratio (APRI) and FIB-4 indices as simple noninvasive markers of fibrosis. ITIH4 was measured in a group of 30 age- and sex-matched healthy controls. ITIH4 was significantly higher in patients than in controls (54.2 ± 30.78 pg/mL versus 37.21 ± 5.39 pg/mL; P = 0.021). ITIH4, but not APRI or FIB-4, had a significant direct correlation with fibrosis stage (P = 0.015, 0.961, and 0.389, resp.), whereas, the negative correlation of ITIH4 with HCV viremia was of marginal significance (P = 0.071). In conclusion, ITIH4 significantly correlated with higher stages of fibrosis indicating a possible relation to liver fibrogenesis. The trend of higher ITIH4 with lower viremia points out a potential antiviral properties and further studies in this regard are worthwhile.
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Affiliation(s)
- Mostafa M. Sira
- 1Department of Pediatric Hepatology, National Liver Institute, Menofiya University, Shebin El-koom, Menofiya 32511, Egypt
- *Mostafa M. Sira:
| | - Behairy E. Behairy
- 1Department of Pediatric Hepatology, National Liver Institute, Menofiya University, Shebin El-koom, Menofiya 32511, Egypt
| | - Azza M. Abd-Elaziz
- 2Department of Microbiology and Immunology, National Liver Institute, Menofiya University, Shebin El-koom, Menofiya 32511, Egypt
| | - Sameh A. Abd Elnaby
- 3Department of Pediatrics, Faculty of Medicine, Menofiya University, Shebin El-koom, Menofiya 32511, Egypt
| | - Ehab E. Eltahan
- 3Department of Pediatrics, Faculty of Medicine, Menofiya University, Shebin El-koom, Menofiya 32511, Egypt
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