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Guo G, Yang W, Li J, Yang Z, Liang J, Sun C. The Development and Appraisal of MELD 3.0 in Liver Diseases: Good Things Never Come Easy. J Clin Transl Hepatol 2025; 13:62-68. [PMID: 39801783 PMCID: PMC11712091 DOI: 10.14218/jcth.2024.00303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 10/24/2024] [Accepted: 10/29/2024] [Indexed: 01/16/2025] Open
Abstract
Since its proposal, the Model for End-Stage Liver Disease (MELD) score has been employed to predict short-term mortality among patients with chronic liver disease and those awaiting liver transplantation, serving as the primary criterion for organ allocation. However, as the demographic and epidemiological characteristics of chronic liver disease and liver transplantation have evolved, a range of MELD-related scores has emerged, including MELD-Na, iMELD, delta MELD, MELD XI, MELD-LA, and pediatric end-stage liver disease, culminating in the recently proposed MELD 3.0, which builds upon MELD-Na. This study aimed to comprehensively review and summarize relevant studies on MELD 3.0 in various scenarios, assessing its effectiveness in organ allocation, post-transplantation outcomes, and mortality prediction for patients with end-stage liver disease. Our preliminary findings indicate superior predictive performance of MELD 3.0, warranting further in-depth investigations to broaden its clinical implications.
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Affiliation(s)
- Gaoyue Guo
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
- Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, Tianjin, China
| | - Wanting Yang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
- Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, Tianjin, China
| | - Jia Li
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
- Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, Tianjin, China
| | - Ziyi Yang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
- Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, Tianjin, China
| | - Jing Liang
- Gastroenterology and Hepatology Department, The Third Central Hospital of Tianjin, Tianjin, China
| | - Chao Sun
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
- Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, Tianjin, China
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Lal BB, Khanna R, Sood V, Alam S, Nagral A, Ravindranath A, Kumar A, Deep A, Gopan A, Srivastava A, Maria A, Pawaria A, Bavdekar A, Sindwani G, Panda K, Kumar K, Sathiyasekaran M, Dhaliwal M, Samyn M, Peethambaran M, Sarma MS, Desai MS, Mohan N, Dheivamani N, Upadhyay P, Kale P, Maiwall R, Malik R, Koul RL, Pandey S, Ramakrishna SH, Yachha SK, Lal S, Shankar S, Agarwal S, Deswal S, Malhotra S, Borkar V, Gautam V, Sivaramakrishnan VM, Dhawan A, Rela M, Sarin SK. Diagnosis and management of pediatric acute liver failure: consensus recommendations of the Indian Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ISPGHAN). Hepatol Int 2024; 18:1343-1381. [DOI: https:/doi.org/10.1007/s12072-024-10720-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 08/08/2024] [Indexed: 04/16/2025]
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Lal BB, Khanna R, Sood V, Alam S, Nagral A, Ravindranath A, Kumar A, Deep A, Gopan A, Srivastava A, Maria A, Pawaria A, Bavdekar A, Sindwani G, Panda K, Kumar K, Sathiyasekaran M, Dhaliwal M, Samyn M, Peethambaran M, Sarma MS, Desai MS, Mohan N, Dheivamani N, Upadhyay P, Kale P, Maiwall R, Malik R, Koul RL, Pandey S, Ramakrishna SH, Yachha SK, Lal S, Shankar S, Agarwal S, Deswal S, Malhotra S, Borkar V, Gautam V, Sivaramakrishnan VM, Dhawan A, Rela M, Sarin SK. Diagnosis and management of pediatric acute liver failure: consensus recommendations of the Indian Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ISPGHAN). Hepatol Int 2024; 18:1343-1381. [PMID: 39212863 DOI: 10.1007/s12072-024-10720-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 08/08/2024] [Indexed: 09/04/2024]
Abstract
Timely diagnosis and management of pediatric acute liver failure (PALF) is of paramount importance to improve survival. The Indian Society of Pediatric Gastroenterology, Hepatology, and Nutrition invited national and international experts to identify and review important management and research questions. These covered the definition, age appropriate stepwise workup for the etiology, non-invasive diagnosis and management of cerebral edema, prognostic scores, criteria for listing for liver transplantation (LT) and bridging therapies in PALF. Statements and recommendations based on evidences assessed using the modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were developed, deliberated and critically reappraised by circulation. The final consensus recommendations along with relevant published background information are presented here. We expect that these recommendations would be followed by the pediatric and adult medical fraternity to improve the outcomes of PALF patients.
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Affiliation(s)
- Bikrant Bihari Lal
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Rajeev Khanna
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Vikrant Sood
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Seema Alam
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India.
| | - Aabha Nagral
- Department of Gastroenterology, Jaslok Hospital and Research Center, Mumbai, India
- Apollo Hospital, Navi Mumbai, India
| | - Aathira Ravindranath
- Department of Pediatric Gastroenterology, Apollo BGS Hospital, Mysuru, Karnataka, India
| | - Aditi Kumar
- Department of Pediatrics, All India Institute of Medical Sciences, Bhubaneswar, India
| | - Akash Deep
- Department of Pediatric Intensive Care, King's College Hospital, London, UK
| | - Amrit Gopan
- Department of Pediatric Gastroenterology and Hepatology, Sir H.N Reliance Foundation Hospital, Mumbai, India
| | - Anshu Srivastava
- Department of Pediatric Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Arjun Maria
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Institute of Child Health, Sir Ganga Ram Hospital, New Delhi, India
| | - Arti Pawaria
- Department of Pediatric Hepatology and Gastroenterology, Amrita Institute of Medical Sciences, Faridabad, India
| | - Ashish Bavdekar
- Department of Pediatrics, KEM Hospital and Research Centre, Pune, India
| | - Gaurav Sindwani
- Department of Organ Transplant Anesthesia and Critical Care, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Kalpana Panda
- Department of Pediatrics, Institute of Medical Sciences & SUM Hospital, Bhubaneshwar, India
| | - Karunesh Kumar
- Department of Pediatric Gastroenterology and Liver Transplantation, Indraprastha Apollo Hospitals, New Delhi, India
| | | | - Maninder Dhaliwal
- Department of Pediatric Intensive Care, Amrita Institute of Medical Sciences, Faridabad, India
| | - Marianne Samyn
- Department of Pediatric Hepatology, King's College Hospital, London, UK
| | - Maya Peethambaran
- Department of Pediatric Gastroenterology and Hepatology, VPS Lakeshore Hospital, Kochi, Kerala, India
| | - Moinak Sen Sarma
- Department of Pediatric Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Moreshwar S Desai
- Department of Paediatric Critical Care and Liver ICU, Baylor College of Medicine &Texas Children's Hospital, Houston, TX, USA
| | - Neelam Mohan
- Department of Pediatric Gastroenterology and Hepatology, Medanta the Medicity Hospital, Gurugram, India
| | - Nirmala Dheivamani
- Department of Paediatric Gastroenterology, Institute of Child Health and Hospital for Children, Egmore, Chennai, India
| | - Piyush Upadhyay
- Department of Pediatrics, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, India
| | - Pratibha Kale
- Department of Microbiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Rohan Malik
- Department of Pediatric Gastroenterology and Hepatology, All India Institute of Medical Sciences, New Delhi, India
| | - Roshan Lal Koul
- Department of Neurology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Snehavardhan Pandey
- Department of Pediatric Hepatology and Liver Transplantation, Sahyadri Superspeciality Hospital Pvt Ltd Pune, Pune, India
| | | | - Surender Kumar Yachha
- Department of Pediatric Gastroenterology, Hepatology and Liver Transplantation, Sakra World Hospital, Bangalore, India
| | - Sadhna Lal
- Division of Pediatric Gastroenterology and Hepatology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Sahana Shankar
- Division of Pediatric Gastroenterology and Hepatology, Department of Pediatrics, Mazumdar Shaw Medical Centre, Narayana Health City, Bangalore, India
| | - Sajan Agarwal
- Department of Pediatric Gastroenterology and Hepatology, Gujarat Gastro Hospital, Surat, Gujarat, India
| | - Shivani Deswal
- Department of Pediatric Gastroenterology, Hepatology and Liver Transplant, Narayana Health, DLF Phase 3, Gurugram, India
| | - Smita Malhotra
- Department of Pediatric Gastroenterology and Hepatology, Indraprastha Apollo Hospitals, New Delhi, India
| | - Vibhor Borkar
- Department of Paediatric Hepatology and Gastroenterology, Nanavati Max Super Speciality Hospital, Mumbai, Maharashtra, India
| | - Vipul Gautam
- Department of Pediatric Gastroenterology, Hepatology and Liver Transplantation, Max Superspeciality Hospital, New Delhi, India
| | | | - Anil Dhawan
- Department of Pediatric Hepatology, King's College Hospital, London, UK
| | - Mohamed Rela
- Department of Liver Transplantation and HPB (Hepato-Pancreatico-Biliary) Surgery, Dr. Rela Institute & Medical Center, Chennai, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Hilberath J, Camelli V, Hofer C, Hartleif S, Nadalin S, Peters M, Kumpf M, Bevot A, Zirngibl M, Weitz M, Sturm E. Role of high-volume plasmapheresis in the management of paediatric acute liver failure. J Pediatr Gastroenterol Nutr 2024; 78:1364-1373. [PMID: 38623928 DOI: 10.1002/jpn3.12211] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Revised: 02/19/2024] [Accepted: 03/21/2024] [Indexed: 04/17/2024]
Abstract
OBJECTIVES Paediatric acute liver failure (PALF) is a life-threatening disease. Management aims to support hepatic regeneration or to bridge to liver transplantation. High-volume plasmapheresis (HVP) removes protein-bound substances, alleviates inflammation, and improves survival in adult acute liver failure. However, experience with HVP in PALF is limited. Aim of this study is to report on feasibility, safety, efficacy and outcomes of HVP in PALF. METHODS Retrospective observational study in children with PALF. HVP was performed upon identification of negative prognostic indicators, in toxic aetiology or multiorgan failure (MOF). Exchanged volume with fresh-frozen plasma corresponded to 1.5-2.0 times the patient's estimated plasma volume. One daily cycle was performed until the patient met criteria for discontinuation, that is, liver regeneration, liver transplantation, or death. RESULTS Twenty-two children with PALF (body weight 2.5-106 kg) received 1-7 HVP cycles. No bleeding or procedure-related mortality occurred. Alkalosis, hypothermia and reduction in platelets were observed. Haemolysis led to HVP termination in one infant. Seven children (32%) survived with their native livers, 13 patients (59%) underwent liver transplantation. Two infants died due to MOF. Overall survival was 86%. International normalization ratio (INR), alanine aminotransaminases (ALT), bilirubin and inotropic support were reduced significantly (p < 0.05) after the first HVP-cycle (median): INR 2.85 versus 1.5; ALT 1280 versus 434 U/L; bilirubin 12.7 versus 6.7 mg/dL; norepinephrine dosage 0.083 versus 0.009 µg/kg/min. Median soluble-interleukin-2-receptor dropped significantly following HVP (n = 7): 2407 versus 950 U/mL (p < 0.02). CONCLUSIONS HVP in PALF is feasible, safe, improves markers of liver failure and inflammation and is associated with lowering inotropic support. Prospective and controlled studies are required to confirm efficacy of HVP in PALF.
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Affiliation(s)
- Johannes Hilberath
- Paediatric Gastroenterology and Hepatology, University Children's Hospital Tübingen, Tübingen, Germany
| | - Vittoria Camelli
- Paediatric Gastroenterology and Hepatology, University Children's Hospital Tübingen, Tübingen, Germany
- SSD Paediatric Gastroenterology, Ospedale Infantile Regina Margherita, Torino, Italy
| | - Christiane Hofer
- Paediatric Cardiology and Intensive Care, University Children's Hospital Tübingen, Tübingen, Germany
| | - Steffen Hartleif
- Paediatric Gastroenterology and Hepatology, University Children's Hospital Tübingen, Tübingen, Germany
| | - Silvio Nadalin
- General, Visceral and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | - Maren Peters
- General, Visceral and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | - Matthias Kumpf
- Paediatric Cardiology and Intensive Care, University Children's Hospital Tübingen, Tübingen, Germany
| | - Andrea Bevot
- Paediatric Neurology, University Children's Hospital Tübingen, Tübingen, Germany
| | - Matthias Zirngibl
- Paediatric Nephrology, University Children's Hospital Tübingen, Tübingen, Germany
| | - Marcus Weitz
- Paediatric Nephrology, University Children's Hospital Tübingen, Tübingen, Germany
| | - Ekkehard Sturm
- Paediatric Gastroenterology and Hepatology, University Children's Hospital Tübingen, Tübingen, Germany
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Biswas T, Lal BB, Sood V, Ashritha A, Maheshwari A, Bajpai M, Kumar G, Khanna R, Alam S. Therapeutic plasma exchange provides native liver survival benefit in children with acute liver failure: A propensity score-matched analysis. J Clin Apher 2024; 39:e22130. [PMID: 38873972 DOI: 10.1002/jca.22130] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Revised: 04/06/2024] [Accepted: 05/14/2024] [Indexed: 06/15/2024]
Abstract
OBJECTIVES This study aimed to evaluate the safety and efficacy of therapeutic plasma exchange (TPE) in pediatric acute liver failure (PALF). METHODS All children aged 2-18 years with PALF were included. The intervention cohort included a subset of PALF patients undergoing complete three sessions of TPE, whereas the matching controls were derived by propensity score matching from the patient cohort who did not receive any TPE. Propensity matching was performed based on the international normalized ratio (INR), grade of hepatic encephalopathy (HE), age, bilirubin, and ammonia levels. The primary outcome measure was native liver survival (NLS) in the two arms on day 28. RESULTS Of the total cohort of 403 patients with PALF, 65 patients who received TPE and 65 propensity-matched controls were included in analysis. The 2 groups were well balanced with comparable baseline parameters. On day 4, patients in the TPE group had significantly lower INR (P = 0.001), lower bilirubin (P = 0.008), and higher mean arterial pressure (MAP) (P = 0.033) than controls. The NLS was 46.15% in the TPE arm and 26.15% in the control arm. The overall survival (OS) was 50.8% in the TPE arm and 35.4% in the control arm. Kaplan-Meier survival analysis showed a significantly higher NLS in patients receiving TPE than controls (P = 0.001). On subgroup analysis, NLS benefit was predominantly seen in hepatitis A-related and indeterminate PALF. CONCLUSION TPE improved NLS and OS in a propensity-matched cohort of patients with PALF. Patients receiving TPE had lower INR and bilirubin levels and higher MAP on day 4.
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Affiliation(s)
- Tamoghna Biswas
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Bikrant Bihari Lal
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Vikrant Sood
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Avalareddy Ashritha
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ashish Maheshwari
- Department of Transfusion Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Meenu Bajpai
- Department of Transfusion Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Guresh Kumar
- Department of Biostatistics, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Rajeev Khanna
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Seema Alam
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Samanta A, Poddar U. Pediatric acute liver failure: Current perspective in etiology and management. Indian J Gastroenterol 2024; 43:349-360. [PMID: 38466551 DOI: 10.1007/s12664-024-01520-6] [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: 10/17/2023] [Accepted: 12/28/2023] [Indexed: 03/13/2024]
Abstract
Pediatric acute liver failure (PALF) is a catastrophic clinical condition with very high morbidity and mortality without early detection and intervention. It is characterized by the acute onset of massive hepatocellular injury that releases circulating inflammatory mediators, resulting in metabolic disturbances, coagulopathy, hepatic encephalopathy and multi-organ failure. The etiological spectrum is dominated by hepatotropic viruses, drug-induced liver injury, metabolic and genetic disorders and immune-mediated diseases. Unlike adults, indeterminate causes for acute liver failure constitute a considerable proportion of cases of acute liver failure in children in the west. The heterogeneity of age and etiology in PALF has led to difficulties in developing prognostic scoring. The recent guidelines emphasize prompt identification of PALF, age-appropriate evaluation for hepatic encephalopathy and laboratory evaluation with careful monitoring. Current therapy focuses on supporting the failing liver and other organs, pending either spontaneous recovery or liver transplantation. Targeted therapy is available for a select group of etiologies. Liver transplantation can be lifesaving and a plan for the same should be organized, whenever indicated. The aim of this review is to define PALF, understand its etiopathogenesis, address the challenges encountered during the management and update the latest advances in liver transplantation and non-transplant treatment options in PALF.
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Affiliation(s)
- Arghya Samanta
- Department of Pediatric Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226 014, India
| | - Ujjal Poddar
- Department of Pediatric Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226 014, India.
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Verma SK, Upadhyay P, Shukla S, Jain A, Shukla S, Patwa AK. Prognostic markers in hepatitis A-related pediatric acute liver failure and validation of the Peds-hepatitis A virus prognostic model. Indian J Gastroenterol 2024; 43:459-467. [PMID: 38568354 DOI: 10.1007/s12664-024-01551-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 02/01/2024] [Indexed: 05/28/2024]
Abstract
OBJECTIVES Hepatitis A virus (HAV) is the commonest cause for pediatric acute liver failure (PALF) in India. The objective of the study was to identify the predictors of mortality and to evaluate the utility of Peds-HAV model in a cohort of non-LT HAV-PALF. METHODS The study included HAV-related PALF from two non-transplant centers. The predictors of outcome were identified by univariate analysis followed by Cox regression analysis. The prognostic accuracy of Peds-HAV model, King's College Hospital (KCH) criteria and pediatric end-stage liver disease score (PELD) were evaluated. RESULTS As many as 140 children with PALF were included, of whom 96 (68.6%) children had HAV-PALF. On Cox regression analysis, international normalized ratio (INR) (p < 0.001), jaundice to encephalopathy (JE) interval (p < 0.001) and hepatic encephalopathy (HE) grade 3/4 (p = 0.01) were independent predictors of mortality. The mortality rates were 0% (0/42), 14.3% (3/21), 60% (9/15) and 94.4% (17/18) when none, 1, 2 or 3 criteria of the Peds-HAV were met, respectively. Peds-HAV model at a listing cut-off of ≥ 2 criteria predicted death with 89.7% sensitivity and 89.6% specificity. In contrast, KCH criteria had a lower sensitivity of 62.1%. PELD score had a sensitivity of 89.7% and specificity of 85.1% at a cut-off of 30. The overall prognostic accuracy of Peds-HAV model (89.6%) was higher than those of KCH (83.3%) and PELD (86.5%). CONCLUSION INR, HE grade and JE interval were independent predictors of mortality. The study provides an external validation of Peds-HAV model as a prognostic score in HAV-PALF. CLINICAL TRIAL REGISTRY NUMBER Not applicable as this is a retrospective study.
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Affiliation(s)
- Sanjeev Kumar Verma
- Department of Pediatrics, King George Medical University, Lucknow, 226 003, India.
| | - Piyush Upadhyay
- Department of Pediatrics, Ram Manohar Lohiya Institute of Medical Sciences, Lucknow, 226 010, India
| | - Stuti Shukla
- Department of Pediatrics, King George Medical University, Lucknow, 226 003, India
| | - Amita Jain
- Department of Microbiology, King George Medical University, Lucknow, 226 003, India
| | - Suruchi Shukla
- Department of Microbiology, King George Medical University, Lucknow, 226 003, India
| | - Ajay Kumar Patwa
- Department of Medicine, King George Medical University, Lucknow, 226 003, India
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Pamecha V, Patil NS, Falari S, Mohapatra N, Kumar AH, Sindwani G, Garg N, Alam S, Khanna R, Sood V, Lal BB. Live donor liver transplantation for pediatric acute liver failure: challenges and outcomes. Hepatol Int 2023; 17:1570-1586. [PMID: 37587287 DOI: 10.1007/s12072-023-10571-4] [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: 04/27/2023] [Accepted: 07/07/2023] [Indexed: 08/18/2023]
Abstract
OBJECTIVE This study aimed at studying the challenges and outcomes of live-donor liver transplantation (LDLT) for pediatric acute liver failure (PALF). STUDY DESIGN A total of 315 patients with PALF were treated over a period of 11 years. 42 underwent LT (41 LDLT and one DDLT), constituting 38% (41/110) of all pediatric transplants during this duration. The outcomes of LDLT for PALF were analyzed. RESULTS All the 41 children who underwent LT met the Kings College criteria (KCC). The etiology was indeterminate in 46.3% (n = 19) children. 75.6% (n = 31) were on mechanical ventilation for grade 3/4 hepatic encephalopathy. There was presence of cerebral edema on a computed tomography scan of the brain in 50% of the children. One-third of our children required hemodynamic support with vasopressors. Systemic inflammatory response syndrome and sepsis were observed in 46.3% and 41.4% of patients, respectively. Post-LDLT 1- and 5-yr patient and graft survival were 75.6% and 70.9%, respectively. The survival in children satisfying KCC but did not undergo LT was 24% (38/161). Vascular and biliary complication rates were 2.4% and 4.8%, respectively. No graft loss occurred because of acute rejection. In multivariate analysis, pre-LT culture positivity and cerebral edema, persistence of brain edema after transplantation, and resultant pulmonary complications were significantly associated with post-LT death. Thirteen (32%) children who underwent plasmapheresis prior to LT had better post-LT neurological recovery, as evidenced by early extubation. CONCLUSION LDLT for PALF is lifesaving and provides a unique opportunity to time transplantation. Good long-term survival can be achieved, despite the majority of patients presenting late for transplantation. Early referral and better selection can save more lives through timely transplantation.
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Affiliation(s)
- Viniyendra Pamecha
- Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver and Biliary Sciences, D-1, Acharya Shree Tulsi Marg, Vasant Kunj, New Delhi, 110070, India.
| | - Nilesh Sadashiv Patil
- Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver and Biliary Sciences, D-1, Acharya Shree Tulsi Marg, Vasant Kunj, New Delhi, 110070, India
| | - Sanyam Falari
- Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver and Biliary Sciences, D-1, Acharya Shree Tulsi Marg, Vasant Kunj, New Delhi, 110070, India
| | - Nihar Mohapatra
- Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver and Biliary Sciences, D-1, Acharya Shree Tulsi Marg, Vasant Kunj, New Delhi, 110070, India
| | - Anubhav Harshit Kumar
- Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver and Biliary Sciences, D-1, Acharya Shree Tulsi Marg, Vasant Kunj, New Delhi, 110070, India
| | - Gaurav Sindwani
- Department of Anesthesiology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Neha Garg
- Department of Anesthesiology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Seema Alam
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Rajeev Khanna
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Vikrant Sood
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Bikrant Bihari Lal
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
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Hu J, Wang C, Bai K, Liu C. Clinical application of regional citrate anticoagulation for membrane-based therapeutic plasma exchange in children with liver failure. Front Pediatr 2023; 11:1206999. [PMID: 37928357 PMCID: PMC10621744 DOI: 10.3389/fped.2023.1206999] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Accepted: 10/10/2023] [Indexed: 11/07/2023] Open
Abstract
Background Regional citrate anticoagulation (RCA) is being used more commonly in children for continuous renal replacement therapy. Few reports describe the application of membrane-based therapeutic plasma exchange (mTPE) with RCA in children with liver failure (LF). Aims To explore the application of RCA-mTPE in children with LF. Methods We retrospectively analyzed data from children with LF who underwent RCA-mTPE in the Children's Hospital of Chongqing Medical University's pediatric intensive care unit. We used the total to ionized calcium ratio (T/iCa) > 2.5 as the diagnostic criteria for citrate accumulation (CA). The patients were divided into two groups according to the occureence of CA at the end of RCA-mTPE (CA group: T/iCa > 2.5; NCA group: T/iCa ≤ 2.5). To evaluate the clinical safety and efficacy of RCA-mTPE, the following data from medical records were assessed and compared between groups: clinical characteristics, reasons for LF, RCA-mTPE parameters and duration, laboratory findings, and complications. Results In total, 92 RCA-mTPE treatments were administered to 21 children with LF over 3.8 ± 0.9 h. The following mean values were determined: blood flow rate (QB) = 2.8 ml/kg/min, 4% sodium citrate dose/blood flow rate ratio (QCi/QB) = 1.1(QCi,ml/kg/h); plasma dose/body weight ratio(QP/BW) = 18.5 (QP, ml/kg/h); 10% calcium gluconate dose/blood flow rate ratio (QCa/QB) = 0.2(QCa, ml/kg/h). The mean concentration of iCa in vitro was 0.38 ± 0.07 mmol/L. Citrate accumulation was recorded after 34 (37%) treatments. Hypocalcemia occurred in 11 (12%) and 7 (7.6%) treatments, during and after mTPE, respectively. Three hypotensive and one convulsive events, related to hypocalcemia, and two clotting events occurred during RCA-mTPE. After RCA-mTPE, the patients' pH, HCO3- and Na+ levels, and T/iCa were significantly increased and the total bilirubin (TB), conjugated bilirubin (DB), prothrombin time (PT), activated partial thromboplastin time (APTT), alanine aminotransferase (ALT), aspartate aminotransferase (AST),and ammonia levels were significantly decreased. The TB, DB, and lactic acid levels, before RCA-mTPE, were significantly higher in the CA group than in the NCA group, but there were no significance between the two groups in QB/BW, QCi/QB, and QP/BW, mTPE duration, and estimated amount of citrate metabolized. Conclusions Children with LF undergoing RCA-mTPE are at risk of hypocalcemia. With proper protocol adjustment, however, RCA-mTPE can be used safely and effectively in these patients.
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Affiliation(s)
- Jun Hu
- IntensiveCare Unit, Ministry of Education Key Laboratory of Children Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, China
- International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China
| | - Chunxiao Wang
- IntensiveCare Unit, Ministry of Education Key Laboratory of Children Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, China
- International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China
| | - Ke Bai
- IntensiveCare Unit, Ministry of Education Key Laboratory of Children Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, China
- International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China
| | - Chengjun Liu
- IntensiveCare Unit, Ministry of Education Key Laboratory of Children Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, China
- International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China
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Pediatric acute liver failure in Saudi Arabia: prognostic indicators, outcomes and the role of genetic testing. Eur J Gastroenterol Hepatol 2023; 35:420-430. [PMID: 36574286 DOI: 10.1097/meg.0000000000002499] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/26/2023]
Abstract
OBJECTIVE The objective of this study was to determine the etiologies, outcomes, prognostic indicators and the role of genetic testing in children with acute liver failure (ALF). METHODS This retrospective study included 46 patients with pediatric acute liver failure (PALF) according to the PALF study group definition, admitted to King Fahad Specialist Hospital-Dammam, Saudi Arabia, between January 2014 and December 2021. Patients who survived with supportive therapy were designated as the recovery group, whereas those who died or underwent liver transplantation were designated as the death/transplant group. RESULTS There were 26 (56.5%) patients in the recovery group and 20 (43.5%) patients in the death/transplant group. Four patients (8.7%) underwent liver transplantation. After indeterminate causes (45.6%), genetic-metabolic diseases and drug-induced liver injury (DILI) were the most common cause with 15.2 and 13%, respectively. Genetic testing had a high yield of (6/31) in identifying monogenic disease associated with ALF. Younger age, lower Glasgow Coma Scale and higher international normalized ratio (INR) on admission were predictors for poor prognosis. The death/transplant group had longer intensive care unit stay ( P < 0.001), and on admission they had more advanced hepatic encephalopathy ( P < 0.005), more prolonged prothrombin time ( P < 0.001), higher lactate ( P < 0.006), higher total and direct bilirubin ( P < 0.008) and ( P < 0.001), respectively. CONCLUSION Genetic, metabolic and DILI causes constituted the most common cause of PALF after indeterminate causes. The use of genetic testing can improve diagnostic rates in special cases, but we could not assess the effect of genetic testing on prognosis. The overall survival rate in our study was 65.2%. Younger age, higher admission INR and lower Glasgow coma scale were indicators of poor prognosis.
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Hadžić N, Molnar E, Height S, Kovács G, Dhawan A, Andrikovics H, Worth A, Gilmour KC. High Prevalence of Hemophagocytic Lymphohistiocytosis in Acute Liver Failure of Infancy. J Pediatr 2022; 250:67-74.e1. [PMID: 35835228 DOI: 10.1016/j.jpeds.2022.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 07/01/2022] [Accepted: 07/07/2022] [Indexed: 10/17/2022]
Abstract
OBJECTIVES To investigate the prevalence of hemophagocytic lymphohistiocytosis (HLH) syndrome in pediatric acute liver failure (PALF) of infancy and assess the diagnostic role of rapid immunologic tests, genotype/phenotype correlations, and clinical outcomes. STUDY DESIGN We retrospectively analyzed 78 children with PALF aged <24 months referred over almost 2 decades. The studied patients with a phenotype of HLH syndrome had a comprehensive immunologic workup, including additional genetic analysis for primary immunologic causes. RESULTS Thirty of the 78 children had the HLH phenotype and underwent genetic assessment, which demonstrated positive findings in 19 (63.3%), including 9 (30%) with biallelic primary HLH mutations and 10 (33.3%) with heterozygous mutations and/or polymorphisms. The most common form of primary HLH was familial hemophagocytic lymphohistiocytosis (FHL)-2, diagnosed in 6 children, 4 of whom had a c.50delT (p.Leu17ArgfsTer34) mutation in the PRF1 gene. Three patients with primary HLH received genetic diagnoses of FHL-3, Griscelli syndrome, and LRBA (lipopolysaccharide-responsive vesicle trafficking, beach- and anchor-containing) protein deficiency. Overall mortality in the series was 52.6% (10 of 19), and mortality in children with a documented biallelic pathogenic HLH mutation (ie, primary HLH) was 66.6% (6 of 9). Two children underwent liver transplantation, and 4 children underwent emergency hematopoietic stem cell transplantation; all but 1 child survived medium term. CONCLUSIONS Primary HLH can be diagnosed retrospectively in approximately one-third of infants with indeterminate PALF (iPALF) who meet the clinical criteria for HLH, often leading to their death. The most common HLH type in iPALF is FHL-2, caused by biallelic mutations in PRF-1. The clinical relevance of observed heterozygous mutations and variants of uncertain significance requires further investigation. Prompt hematopoietic stem cell transplantation could be life-saving in infants who survive the liver injury.
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Affiliation(s)
- Nedim Hadžić
- Paediatric Liver Service, King's College Hospital, London, United Kingdom.
| | - Emese Molnar
- Department of Immunology, Camelia Bothnar Laboratories, Great Ormond Street Hospital, London, United Kingdom; Department of Rheumatology and Clinical Immunology, Semmelweis University, Budapest, Hungary
| | - Sue Height
- Department of Haematology, King's College Hospital, London, United Kingdom
| | - Gabor Kovács
- Department of Physiology, Semmelweis University, Budapest, Hungary
| | - Anil Dhawan
- Paediatric Liver Service, King's College Hospital, London, United Kingdom
| | - Hajnalka Andrikovics
- Laboratory of Molecular Genetics, Central Hospital of Southern Pest, Budapest, Hungary
| | - Austen Worth
- Department of Immunology, Camelia Bothnar Laboratories, Great Ormond Street Hospital, London, United Kingdom
| | - Kimberly C Gilmour
- Department of Immunology, Camelia Bothnar Laboratories, Great Ormond Street Hospital, London, United Kingdom
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Etiology, outcome and prognostic indicators of acute liver failure in Asian children. Hepatol Int 2022; 16:1390-1397. [PMID: 36131224 DOI: 10.1007/s12072-022-10417-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 08/24/2022] [Indexed: 11/04/2022]
Abstract
OBJECTIVE Outcome of pediatric acute liver failure (PALF) in countries with limited availability of LT is not well described. We evaluated the outcome and prognostic indicators of PALF in Malaysia where emergency LT for ALF is limited. METHODS In this retrospective review on children < 18 years with PALF, we compared clinical and laboratory parameters between survival after supportive treatment and after LT or succumbed without LT. The predictive values of Liver Injury Unit (LIU; peak laboratory values for international normalized ratio [INR], ammonia, total bilirubin) and upon admission (aLIU) on outcome of PALF was evaluated using receiver operator characteristic (ROC) curves. RESULTS Of 77 children (39 males [51%]; median age 2.8 years) with PALF, the overall survival was 55% (n = 42); 52% (n = 40) survived with supportive management, 2.6% (n = 2) after LT. As compared to children who survived without LT, children who had LT/died had lower hemoglobin, aspartate transferase, γ-glutamyl transpeptidase (GGT), and higher serum bilirubin, alkaline phosphatase, ammonia, and serum sodium (p < 0.05). On multivariate analysis, significant independent predictor for death or LT were peak bilirubin > 452 μmol/L and peak GGT < 96 IU/L. The C-index of LIU and aLIU score were 0.79 and 0.68, respectively, indicating that LIU score was a good model in predicting outcome of PALF. CONCLUSIONS Overall survival of PALF remained poor. High peak bilirubin and low GGT predict poor outcome of PALF. LIU score is a good model in predicting outcome of PALF and maybe useful in selecting children for emergency LT.
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Walabh P, Meyer A, de Maayer T, Moshesh PN, Hassan IE, Walabh P, Hajinicolaou C. Prognostic factors and scoring systems associated with outcome in pediatric acute liver failure. BMC Pediatr 2022; 22:516. [PMID: 36045327 PMCID: PMC9429365 DOI: 10.1186/s12887-022-03574-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 08/22/2022] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND Pediatric acute liver failure (PALF) is an uncommon, devastating illness with significant mortality. Liver transplantation remains the mainstay of treatment for irreversible PALF. The purpose of this study was to determine the etiology and prognostic factors associated with outcome of PALF in South Africa and to evaluate prognostic scoring systems used. METHODS Records of 45 pediatric patients younger than 16 years of age who presented with PALF from 1 January 2015 till 31 October 2020 were analysed. Patients were divided into two groups with one group consisting of patients with spontaneous recovery of the liver with supportive treatment (6/45:13.3%) and the second group consisting of patients with poor outcomes who demised (19/45: 42%) or underwent liver transplantation (20/45: 44%). RESULTS The median age of presentation was 3.3 years (IQR 1.8-6.9) with the 1-5 years age group constituting majority of patients (55.6%). Median time to follow up was 6.1 months (IQR 0.2-28.8). Higher liver injury unit scores were observed in patients who had poorer outcomes (P = 0.008) with a threshold of greater than 246 having a sensitivity of 84% and specificity of 83% (P < 0.001). Higher peak PELD/MELD (P = 0.006) and admission UKELD (P = 0.002) scores, were found in patients with poorer outcomes. Kings College Hospital criteria (KCHC) was useful in predicting which patients would die without liver transplantation (P = 0.002). Liver transplantation was performed in 20/45 (44%) patients with a post transplantation 1 year patient and graft survival of 80%. CONCLUSION Although, survival of PALF patients was lower than high and other low-middle income countries, outcomes post transplantation were good. Our study demonstrates the utility of dynamic scoring systems in PALF patients, it underscores the need for early referral and clinical monitoring in a tertiary center once the criteria for PALF have been met.
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Affiliation(s)
- Priya Walabh
- Department of Paediatrics and Child Health, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Princess of Wales Terrace, Parktown, Johannesburg, 2193, South Africa.
- Paediatric Gastroenterology, Hepatology and Nutrition Unit, Charlotte Maxeke Johannesburg Academic Hospital, University of Witwatersrand, Johannesburg, South Africa.
- Gauteng Provincial Solid Organ Transplant Division, Johannesburg, South Africa.
| | - Anja Meyer
- Gauteng Provincial Solid Organ Transplant Division, Johannesburg, South Africa
- Department of Surgery, Charlotte Maxeke Johannesburg Academic Hospital, University of Witwatersrand, Johannesburg, South Africa
| | - Tim de Maayer
- Department of Paediatrics and Child Health, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Princess of Wales Terrace, Parktown, Johannesburg, 2193, South Africa
- Paediatric Gastroenterology, Hepatology and Nutrition Unit, Rahima Moosa Mother and Child Hospital, University of Witwatersrand, Johannesburg, South Africa
| | - Porai N Moshesh
- Department of Paediatrics and Child Health, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Princess of Wales Terrace, Parktown, Johannesburg, 2193, South Africa
- Paediatric Intensive Care Unit, Nelson Mandela Children's Hospital, Johannesburg, South Africa
| | - Ibrahim E Hassan
- Department of Paediatrics and Child Health, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Princess of Wales Terrace, Parktown, Johannesburg, 2193, South Africa
- Paediatric Gastroenterology, Hepatology and Nutrition Unit, Charlotte Maxeke Johannesburg Academic Hospital, University of Witwatersrand, Johannesburg, South Africa
| | - Pravina Walabh
- Bachelor of Science, University of Cape Town, Cape Town, South Africa
| | - Christina Hajinicolaou
- Department of Paediatrics and Child Health, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Princess of Wales Terrace, Parktown, Johannesburg, 2193, South Africa
- Paediatric Gastroenterology, Hepatology and Nutrition Unit Head, Department of Paediatrics and Child health, Chris Hani Baragwanath Academic Hospital, University of Witwatersrand, Johannesburg, South Africa
- Head of Division of Paediatric Gastroenterology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
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Pop TL, Aldea CO, Delean D, Bulata B, Boghiţoiu D, Păcurar D, Ulmeanu CE, Grama A. The Role of Predictive Models in the Assessment of the Poor Outcomes in Pediatric Acute Liver Failure. J Clin Med 2022; 11:432. [PMID: 35054127 PMCID: PMC8778932 DOI: 10.3390/jcm11020432] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 01/05/2022] [Accepted: 01/13/2022] [Indexed: 02/05/2023] Open
Abstract
OBJECTIVES In children, acute liver failure (ALF) is a severe condition with high mortality. As some patients need liver transplantation (LT), it is essential to predict the fatal evolution and to refer them early for LT if needed. Our study aimed to evaluate the prognostic criteria and scores for assessing the outcome in children with ALF. METHODS Data of 161 children with ALF (54.66% female, mean age 7.66 ± 6.18 years) were analyzed based on final evolution (32.91% with fatal evolution or LT) and etiology. We calculated on the first day of hospitalization the PELD score (109 children), MELD, and MELD-Na score (52 children), and King's College Criteria (KCC) for all patients. The Nazer prognostic index and Wilson index for predicting mortality were calculated for nine patients with ALF in Wilson's disease (WD). RESULTS PELD, MELD, and MELD-Na scores were significantly higher in patients with fatal evolution (21.04 ± 13.28 vs. 13.99 ± 10.07, p = 0.0023; 36.20 ± 19.51 vs. 20.08 ± 8.57, p < 0.0001; and 33.07 ± 8.29 vs. 20.08 ± 8.47, p < 0.0001, respectively). Moreover, age, bilirubin, albumin, INR, and hemoglobin significantly differed in children with fatal evolution. Function to etiology, PELD, MELD, MELD-Na, and KCC accurately predicted fatal evolution in toxic ALF (25.33 vs. 9.90, p = 0.0032; 37.29 vs. 18.79, p < 0.0001; 34.29 vs. 19.24, p = 0.0002, respectively; with positive predicting value 100%, negative predicting value 88.52%, and accuracy 89.23% for King's College criteria). The Wilson index for predicting mortality had an excellent predictive strength (100% sensibility and specificity), better than the Nazer prognostic index. CONCLUSIONS Prognostic scores may be used to predict the fatal evolution of ALF in children in correlation with other parameters or criteria. Early estimation of the outcome of ALF is essential, mainly in countries where emergency LT is problematic, as the transfer to a specialized center could be delayed, affecting survival chances.
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Affiliation(s)
- Tudor Lucian Pop
- 2nd Pediatric Discipline, Department of Mother and Child, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
- Center of Expertise in Pediatric Liver Rare Disorders, 2nd Pediatric Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania
| | - Cornel Olimpiu Aldea
- Pediatric Nephrology, Dialysis and Toxicology Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania; (C.O.A.); (D.D.); (B.B.)
| | - Dan Delean
- Pediatric Nephrology, Dialysis and Toxicology Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania; (C.O.A.); (D.D.); (B.B.)
| | - Bogdan Bulata
- Pediatric Nephrology, Dialysis and Toxicology Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania; (C.O.A.); (D.D.); (B.B.)
| | - Dora Boghiţoiu
- Department of Pediatrics, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania; (D.B.); (D.P.); (C.E.U.)
- Department of Pediatrics, Grigore Alexandrescu Emergency Clinical Hospital for Children, 011743 Bucharest, Romania
| | - Daniela Păcurar
- Department of Pediatrics, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania; (D.B.); (D.P.); (C.E.U.)
- Department of Pediatrics, Grigore Alexandrescu Emergency Clinical Hospital for Children, 011743 Bucharest, Romania
| | - Coriolan Emil Ulmeanu
- Department of Pediatrics, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania; (D.B.); (D.P.); (C.E.U.)
- Department of Pediatrics, Grigore Alexandrescu Emergency Clinical Hospital for Children, 011743 Bucharest, Romania
| | - Alina Grama
- 2nd Pediatric Discipline, Department of Mother and Child, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
- Center of Expertise in Pediatric Liver Rare Disorders, 2nd Pediatric Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania
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Squires JE, Alonso EM, Ibrahim SH, Kasper V, Kehar M, Martinez M, Squires RH. North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position Paper on the Diagnosis and Management of Pediatric Acute Liver Failure. J Pediatr Gastroenterol Nutr 2022; 74:138-158. [PMID: 34347674 DOI: 10.1097/mpg.0000000000003268] [Citation(s) in RCA: 77] [Impact Index Per Article: 25.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
ABSTRACT Pediatric acute liver failure (PALF) is a rare, rapidly progressive clinical syndrome with significant morbidity and mortality. The phenotype of PALF manifests as abrupt onset liver dysfunction, which can be brought via disparate etiology. Management is reliant upon intensive clinical care and support, often provided by the collaborative efforts of hepatologists, critical care specialists, and liver transplant surgeons. The construction of an age-based diagnostic approach, the identification of a potential underlying cause, and the prompt implementation of appropriate therapy can be lifesaving; however, the dynamic and rapidly progressive nature of PALF also demands that diagnostic inquiries be paired with monitoring strategies for the recognition and treatment of common complications of PALF. Although liver transplantation can provide a potential life-saving therapeutic option, the ability to confidently determine the certainness that liver transplant is needed for an individual child has been hampered by a lack of adequately tested clinical decision support tools and accurate predictive models. Given the accelerated progress in understanding PALF, we will provide clinical guidance to pediatric gastroenterologists and other pediatric providers caring for children with PALF by presenting the most recent advances in diagnosis, management, pathophysiology, and associated outcomes.
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Affiliation(s)
- James E Squires
- Division of Gastroenterology, Hepatology and Nutrition, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA
| | - Estella M Alonso
- Department Pediatric Hepatology, Ann and Robert H Lurie Children's Hospital, Chicago, Illinois, USA
| | - Samar H Ibrahim
- Department of Pediatrics, Division of Pediatric Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Vania Kasper
- Division of Pediatric Gastroenterology, Nutrition and Liver Diseases, Hasbro Children's Hospital, Providence, RI
| | - Mohit Kehar
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children Hospital of Eastern Ontario, Ottawa, Ontario, Canada
| | - Mercedes Martinez
- Department of Pediatrics, Vagelos College of Physician and Surgeons, Columbia University, New York, NY
| | - Robert H Squires
- Division of Gastroenterology, Hepatology and Nutrition, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA
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Vijay P, Lal BB, Sood V, Khanna R, Patidar Y, Alam S. Dynamic Optic Nerve Sheath Diameter (ONSD) guided management of raised intracranial pressure in pediatric acute liver failure. Hepatol Int 2021; 15:502-509. [PMID: 33625660 DOI: 10.1007/s12072-021-10139-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 01/16/2021] [Indexed: 12/25/2022]
Abstract
BACKGROUND AND AIMS The objectives were to evaluate the role of optic nerve sheath diameter (ONSD) to detect raised intracranial pressure (ICP) in pediatric acute liver failure (PALF), study the variations in ONSD with ICP-lowering measures and to evaluate its prognostic role. METHODS PALF with clinical evidence of raised ICP were enrolled as cases, while those without raised ICP were control group A. ONSD was measured at admission and repeated regularly. It was also measured at time of each new episode of raised ICP and 2 h after the management of such episode. RESULTS 31 PALF with raised ICP were included as cases and 15 without as control group A. ONSD was significantly higher in cases: 5 mm (IQR: 4.7-5.4) as compared to control group A: 3.8 mm (IQR: 3.3-4). ONSD greater than 4.55 mm at baseline diagnosed clinically raised ICP with 87.5% sensitivity and 100% specificity. The mean ONSD was 5.44 ± 0.49 mm during a total of 90 events of acute raised ICP. Clinical responders had a decrease in ONSD by 0.59 ± 0.24 mm by 2 h, whereas non-responders showed a decrease of 0.18 ± 0.23 mm, p < 0.0005. ONSD persisting more than 4.6 mm by 24 h of management predicted poor outcome with sensitivity and specificity of 83.3% and 72.7%. CONCLUSION ONSD is a simple, bedside, inexpensive, reproducible and repeatable modality to assess ongoing change in ICP in PALF. ONSD more than 4.55 mm suggests raised ICP. The goal should be to bring ONSD down to less than 4.6 mm within 24 h by aggressive anti-ICP therapy to achieve favourable outcome.
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Affiliation(s)
- Priti Vijay
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Bikrant Bihari Lal
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Vikrant Sood
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Rajeev Khanna
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Yashwant Patidar
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Seema Alam
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India.
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Pediatric chronic liver failure-sequential organ failure assessment score and outcome of acute liver failure in children. Clin Exp Hepatol 2020; 6:228-234. [PMID: 33145429 PMCID: PMC7592098 DOI: 10.5114/ceh.2020.99129] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2019] [Accepted: 05/16/2020] [Indexed: 12/28/2022] Open
Abstract
Aim of the study Liver transplantation remains the only definitive treatment for children with acute liver failure proven to have irreversible liver injury. Many prognostic models have been used for outcome prediction in pediatric acute liver failure to select patients in a real need of liver transplantation, but unfortunately all have shown inconsistent reproducibility and prognostic accuracy. The aim of this study was to evaluate the pediatric chronic liver failure sequential organ failure assessment (pCLIF-SOFA) score as a predictor of pediatric acute liver failure outcome. Material and methods Clinical and laboratory data of 41 children with acute liver failure admitted to the National Liver Institute – Menoufia University were collected retrospectively and used for calculation of both pCLIF-SOFA and Pediatric End-Stage Liver Disease (PELD)/Model for End-Stage Liver Disease (MELD) scores on the day of admission, then statistical analysis was performed to identify the ability of these scores to predict the outcome. Results According to the outcome, children enrolled in this study were allocated to survived (n = 16) and died (n = 25) groups, which were age and sex matched. The non-survival group had significantly higher values of both pCLIF-SOFA score (11 [7-13]) and PELD/MELD score (36 [18-42]) than those of the survival group (8 [7-11], 27.5 [15-45]; p < 0.001, p = 0.004) respectively. Both pCLIF-SOFA and PELD/MELD scores at cut-off values > 8 and > 30 respectively on admission could predict death in children with acute liver failure (ALF) with high sensitivity, but with higher specificity, positive and negative predictive values for pCLIF-SOFA. Conclusions pCLIF-SOFA is a good predictor of death in pediatric acute liver failure.
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Berardi G, Tuckfield L, DelVecchio MT, Aronoff S. Differential Diagnosis of Acute Liver Failure in Children: A Systematic Review. Pediatr Gastroenterol Hepatol Nutr 2020; 23:501-510. [PMID: 33215021 PMCID: PMC7667230 DOI: 10.5223/pghn.2020.23.6.501] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 06/06/2020] [Accepted: 07/01/2020] [Indexed: 12/22/2022] Open
Abstract
PURPOSE To develop a probability-based differential diagnosis for pediatric acute liver failure (PALF) based on age and socioeconomic status of the country of origin. METHODS Comprehensive literature search using PubMed, EMBASE, and SCOPUS databases was performed. Children 0-22 years of age who met PALF registry criteria were included. Articles included >10 children, and could not be a case report, review article, or editorial. No language filter was utilized, but an English abstract was required. Etiology of PALF, age of child, and country of origin was extracted from included articles. RESULTS 32 full text articles were reviewed in detail; 2,982 children were included. The top diagnosis of PALF in developed countries was acetaminophen toxicity (9.24%; 95% CredI 7.99-10.6), whereas in developing countries it was Hepatitis A (28.9%; 95% CredI 26.3-31.7). In developed countries, the leading diagnosis of PALF in children aged <1 year was metabolic disorder (17.2%; 95% CredI 10.3-25.5), whereas in developing countries it was unspecified infection (39.3%; CredI 27.6-51.8). In developed countries, the leading diagnosis in children aged >1 year was Non-A-B-C Hepatitis (8.18%; CredI 5.28-11.7), whereas in developing countries it was Hepatitis A (32.4%; CredI 28.6-36.3). CONCLUSION The leading causes of PALF in children aged 0-22 years differ depending on the age and developmental status of their country of origin, suggesting that these factors must be considered in the evaluation of children with PALF.
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Affiliation(s)
- Giuliana Berardi
- Department of Pediatrics, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
| | - Lynnia Tuckfield
- Department of Pediatrics, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
| | - Michael T. DelVecchio
- Department of Pediatrics, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
- Section of Pediatric Infectious Diseases and Hospital Medicine, St. Christopher's Hospital for Children, Philadelphia, PA, USA
| | - Stephen Aronoff
- Department of Pediatrics, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
- Section of Pediatric Infectious Diseases and Hospital Medicine, St. Christopher's Hospital for Children, Philadelphia, PA, USA
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Getsuwan S, Lertudomphonwanit C, Tanpowpong P, Thirapattaraphan C, Tim-Aroon T, Wattanasirichaigoon D, Treepongkaruna S. Etiologies, Prognostic Factors, and Outcomes of Pediatric Acute Liver Failure in Thailand. Pediatr Gastroenterol Hepatol Nutr 2020; 23:539-547. [PMID: 33215025 PMCID: PMC7667225 DOI: 10.5223/pghn.2020.23.6.539] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 05/31/2020] [Accepted: 06/23/2020] [Indexed: 01/01/2023] Open
Abstract
PURPOSE Pediatric acute liver failure (PALF) is a serious condition; however, data on PALF in developing countries are sparse, particularly concerning molecular diagnosis and liver transplantation (LT). This study aimed to determine the causes, outcomes, and prognostic factors of PALF. METHODS We retrospectively reviewed the medical records of children (age <15 years) with PALF diagnosed using the American Association for the Study of Liver Diseases criteria at our center from 2011 to 2016. The collected data included laboratory results, complications, outcomes, and potential factors associated with death and LT. RESULTS We included a total of 27 patients, with a median age of 2 years (interquartile range, 3 months to 4 years). Viral infection was the most common etiology (n=8, 30%), predominantly dengue infection (n=4). A total of 16 patients (59%) died and 11 patients survived (3 patients with LT). The prognostic factors associated with death or LT requirement were grade IV hepatic encephalopathy (p<0.01), hypotension (p=0.02), gastrointestinal bleeding (p=0.03), increased intracranial pressure (p=0.04), and higher peak serum lactate level (p=0.01). Peak serum lactate ≥6 mmoL/L had a sensitivity of 79% and a specificity of 88% for predicting mortality or the necessity of LT. CONCLUSION Viral infection was the most common cause of PALF. The mortality rate remained high, and a considerable number of patients required LT. In addition to several clinical factors, peak serum lactate could be a potential marker for predicting poor outcomes in PALF.
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Affiliation(s)
- Songpon Getsuwan
- Division of Gastroenterology, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.,Ramathibodi Excellence Center for Organ Transplantation, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Chatmanee Lertudomphonwanit
- Division of Gastroenterology, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.,Ramathibodi Excellence Center for Organ Transplantation, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Pornthep Tanpowpong
- Division of Gastroenterology, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.,Ramathibodi Excellence Center for Organ Transplantation, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Chollasak Thirapattaraphan
- Ramathibodi Excellence Center for Organ Transplantation, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.,Division of Pediatric Surgery, Department of Surgery, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Thipwimol Tim-Aroon
- Division of Genetics, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Duangrurdee Wattanasirichaigoon
- Division of Genetics, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Suporn Treepongkaruna
- Division of Gastroenterology, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.,Ramathibodi Excellence Center for Organ Transplantation, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
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20
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Wands D, Tayler R, Kelly D, Pinto F, Simpson JH, Hansen R. Infantile acute liver failure in the West of Scotland. Arch Dis Child 2020; 105:794-796. [PMID: 31719120 DOI: 10.1136/archdischild-2019-317360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2019] [Revised: 07/25/2019] [Accepted: 07/27/2019] [Indexed: 11/04/2022]
Abstract
BACKGROUND Our current understanding regarding the aetiology of infantile acute liver failure largely derives from studies conducted by regional liver units. This may introduce selection bias and therefore not provide a true reflection of the wider population. METHODS Every coagulation screen with a prothrombin time ≥18 s in our centre was examined over one calendar year. All patients less than 1 year of age were included and their electronic records retrospectively reviewed. RESULTS 24 patients were identified, from 9989 coagulation screens, that fit the current definition of acute liver failure. Hypoxic birth injury and ischaemic events were the most common aetiologies. Survival was 75%. CONCLUSION The 'catch-all' methodology employed demonstrated that acute liver failure is more common than previously reported and suggests that current data may exclude large numbers who either have more minor self-resolving disease or conversely have severe disease leading to death prior to transfer.
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Affiliation(s)
- David Wands
- Department of Paediatric Gastroenterology, Hepatology and Nutrition, Royal Hospital for Children Glasgow, Glasgow, UK
| | - Rachel Tayler
- Department of Paediatric Gastroenterology, Hepatology and Nutrition, Royal Hospital for Children Glasgow, Glasgow, UK
| | - Deirdre Kelly
- Liver Unit, Birmingham Children's Hospital NHS Foundation Trust, Birmingham, UK
| | - Fernando Pinto
- Department of Haematology, Royal Hospital for Children Glasgow, Glasgow, UK
| | | | - Richard Hansen
- Department of Paediatric Gastroenterology, Hepatology and Nutrition, Royal Hospital for Children Glasgow, Glasgow, UK
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21
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Timing of liver transplantation for pediatric acute liver failure due to mushroom poisoning: a case report and literature review. BMC Pediatr 2020; 20:351. [PMID: 32698786 PMCID: PMC7376857 DOI: 10.1186/s12887-020-02249-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Accepted: 07/15/2020] [Indexed: 11/26/2022] Open
Abstract
Background Pediatric acute liver failure is a rare, life-threatening illness. Mushroom poisoning is a rare etiology. For patients with irreversible pediatric acute liver failure, liver transplantation is the ultimate lifesaving therapy. However, it is difficult to determine the optimal timing of transplantation. Here, we present a case of pediatric acute liver failure due to mushroom poisoning in northeastern China. He was treated with liver transplantation and recovered. To our knowledge, there are few reports about liver transplantation for pediatric acute liver failure caused by mushroom poisoning in mainland China. Case presentation The patient was a previously healthy 9-year-old boy who gradually developed nausea, vomiting, jaundice and coma within 5 days after ingesting mushrooms. He was diagnosed with mushroom poisoning and acute liver failure. He was treated with conservative care but still deteriorated. On the 7th day after poisoning, he underwent LT due to grade IV hepatic encephalopathy. Twenty days later, he recovered and was discharged. A review of the literature revealed that the specific criteria and optimal timing of transplantation remain to be determined. Conclusions Patients with pediatric acute liver failure should be transferred to a center with a transplant unit early. Once conservative treatment fails, liver transplantation should be performed.
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Development of a Prognostic Score to Predict Mortality in Patients With Pediatric Acute Liver Failure. J Pediatr Gastroenterol Nutr 2020; 70:777-782. [PMID: 32443030 DOI: 10.1097/mpg.0000000000002625] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES This study aims to develop a new prognostic score based on changes in serial laboratory data from patients with pediatric acute liver failure (PALF). METHODS We retrospectively reviewed data on 146 patients with PALF at the Seoul National University Children Hospital (SNUCH) and the Asan Medical Center (AMC). Daily morning laboratory records were obtained for up to 7 days after diagnosis of PALF: total bilirubin (TB) (mg/dL), international normalized ratio for prothrombin time (INR) at enrolment; peak TB, peak INR, peak ammonia (μmol/L); the difference between the peak TB and TB at enrollment (ie, Δpeak TB), the difference between the peak INR and INR at enrollment (ie, Δpeak INR), the maximum change in serial TB (ie, Δdaily TB), the maximum change in serial INR level (ie, Δdaily INR). We assigned nontransplanted patients in SNUCH and AMC to derivation and validation cohorts, respectively. RESULTS Δpeak TB, Δdaily TB, Δpeak INR, and Δdaily INR were significantly higher in the nonsurvival group. We developed a new score that can predict mortality in nontransplanted patients (derivation cohort n = 42, validation cohort n = 33). PALF-Delta score (PALF-Ds) = [0.232 × Δpeak TB (mg/dL)] + [2.263 × Δdaily INR] + [0.013 × peak ammonia (μmol/L)] - 4.498. The score yielded AUC 0.918 in the derivation cohort (sensitivity 81%, specificity 91%) and AUC 0.947 in the validation cohort (sensitivity 100%, specificity 89%). CONCLUSION A prognostic scoring system using the change of TB/INR may be useful for predicting mortality in patients with PALF.
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23
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Lal BB, Sood V, Snehavardhan P, Khanna R, Pasupuleti SSR, Siloliya M, Kumar G, Alam S. A novel, bedside, etiology specific prognostic model (Peds-HAV) in hepatitis A induced pediatric acute liver failure. Hepatol Int 2020; 14:483-490. [PMID: 32372333 DOI: 10.1007/s12072-020-10050-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Accepted: 04/18/2020] [Indexed: 01/05/2023]
Abstract
BACKGROUND Hepatitis A virus (HAV) is the commonest cause of pediatric acute liver failure (PALF) in developing countries. Our objective was to develop and validate a HAV-etiology specific prognostic model in PALF. METHODS All children with HAV induced PALF (IgM HAV reactive) were included. Outcome was defined at day 28. Only those with death or native liver survival were included. The model (Peds-HAV) was derived using the independent predictors of outcome and validated in a prospective independent cohort. RESULTS Hepatitis A accounted for 131 (45.9%) of total 285 PALF. After excluding 11 children who underwent liver transplant, 120 children (74 survivors and 46 death) were included. The first 75 patients formed the derivation cohort and the next 45 patients formed the prospective validation cohort. In the derivation cohort, INR: OR 2.208, (95% CI 1.321-3.690), p = 0.003, grade of hepatic encephalopathy (HE): OR 3.078, (95% CI 1.017-9.312), p = 0.047 and jaundice-to-HE interval: OR 1.171, (95% CI 1.044-1.314), p = 0.007 were independent predictors of death. The final model comprised three criteria: (1) presence of grade 3-4 HE, (2) INR greater than 3.1, and (3) jaundice to HE interval more than 10 days. Presence of 2 or more of these criteria predicted death with 90% sensitivity, 81.4% specificity and 84.9% accuracy. Peds-HAV model was superior to existing prognostic models. In the validation cohort, Peds-HAV model predicted death with 83.3% sensitivity and 92.6% specificity. CONCLUSION Peds-HAV model is a simple, bedside, dynamic, etiology (HAV) specific prognostic model based on 3 objective parameters with optimum sensitivity and specificity, hence should be used as liver transplant listing criteria in HAV induced PALF.
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Affiliation(s)
- Bikrant Bihari Lal
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Vikrant Sood
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Pandey Snehavardhan
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Rajeev Khanna
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Manish Siloliya
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Guresh Kumar
- Department of Biostatistics, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Seema Alam
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India.
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24
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Zhao S, Lu ZH, Cui JJ, Li D, Zhu YL, Gan JH. Nitroglycerin ameliorates liver injury and regulates adaptive immunity in mice. Drug Dev Res 2020; 81:557-563. [PMID: 32173888 DOI: 10.1002/ddr.21653] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 02/16/2020] [Accepted: 02/19/2020] [Indexed: 12/31/2022]
Abstract
This study aimed to assess the protective effect of nitroglycerin, a commonly used drug in cardiovascular diseases, on mice with acute liver injury induced by carbon tetrachloride (CCl4 ). The mice were randomly divided into three groups: control, CCl4 , and CCl4 + nitroglycerin. They were killed at 0, 6, 12, 24, and 48 h after treatment. Blood and liver tissue samples were collected for analysis. Analysis of the amounts of serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST), hepatic glutathione (GSH), and malondialdehyde (MDA) showed that nitroglycerin protected against CCl4 -induced acute liver injury. Liver histological analysis provided further evidence of the protective effect of nitroglycerin. Furthermore, we found that nitroglycerin suppressed the increase of T helper 17 (Th17) cells in CCl4 -induced acute liver injury mice. The results indicate that nitroglycerin is a potential candidate for hepatic disease.
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Affiliation(s)
- Shuang Zhao
- Department of Infectious Disease, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Zhong-Hua Lu
- Department of Liver Disease, Wuxi No. 5 People's Hospital Affiliated to Jiangnan University, Wuxi, Jiangsu Province, China
| | - Juan-Juan Cui
- Department of Infectious Disease, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Dong Li
- Department of Infectious Disease, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Yi-Ling Zhu
- Department of Infectious Disease, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Jian-He Gan
- Department of Infectious Disease, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
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25
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Di Giorgio A, Nicastro E, Dalla Rosa D, Nebbia G, Sonzogni A, D'Antiga L. Transplant-free Survival in Chronic Liver Disease Presenting as Acute Liver Failure in Childhood. Transplantation 2019; 103:544-551. [PMID: 30028785 DOI: 10.1097/tp.0000000000002367] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND In adults, the absence of a preexisting chronic liver disease (CLD) is required to diagnose acute liver failure (ALF). The pediatric classification does not consider this aspect, thus previous studies pooled together children with ALF and children with unknown CLD presenting with acute hepatic decompensation (ALF-CLD). We aimed to compare prevalence, features, and outcome of children with ALF-CLD to those with a proper ALF. METHODS Patients admitted between 1996 and 2017 because of ALF defined by Pediatric Acute Liver Failure criteria (raised transaminases, International Normal Ratio ≥2.0, no history of liver disease) were classified as ALF-CLD if diagnosed with autoimmune hepatitis, Wilson disease, Budd-Chiari syndrome, hepatitis B virus reactivation, inborn errors of metabolism. The others were classified as ALF. RESULTS Seventy-four children (median age, 4 years; 1.0-8.8; male/female, 36/38] with ALF were found; 18 of <1 year of age were excluded. Fifty-six (median age, 6.6 years; 2.7-11.7; male/female, 23/33], 22 with ALF-CLD (autoimmune hepatitis, n = 14; Wilson disease, n = 6; inborn errors of metabolism, n = 2) and 34 with ALF (paracetamol overdose, n = 6; viral infections, n = 3; mushroom poisoning, n = 5; indeterminate, n = 20) were compared. In ALF-CLD, the median age at onset was higher, alanine aminotransferase, albumin, and International Normal Ratio levels were lower, splenomegaly, ascites, and cirrhosis were more common (all P < 0.01). On multivariate analysis, the diagnosis of ALF-CLD was an independent predictor of transplant-free survival (P = 0.006). CONCLUSIONS In children, ALF-CLD is common, has peculiar features, and is associated with a favorable outcome. This study suggests the need to distinguish this entity from other forms of ALF in children.
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Affiliation(s)
- Angelo Di Giorgio
- Paediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII Bergamo, Italy
| | - Emanuele Nicastro
- Paediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII Bergamo, Italy
| | - Davide Dalla Rosa
- Paediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII Bergamo, Italy
| | - Gabriella Nebbia
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Aurelio Sonzogni
- Liver and Transplant Pathology, Hospital Papa Giovanni XXIII Bergamo, Italy
| | - Lorenzo D'Antiga
- Paediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII Bergamo, Italy
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Chien MM, Chang MH, Chang KC, Lu FT, Chiu YC, Chen HL, Ni YH, Hsu HY, Wu JF. Prognostic parameters of pediatric acute liver failure and the role of plasma exchange. Pediatr Neonatol 2019; 60:389-395. [PMID: 30361144 DOI: 10.1016/j.pedneo.2018.09.006] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Revised: 05/23/2018] [Accepted: 09/19/2018] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND This study investigated the prognostic parameters and beneficial effects of repeat plasma exchange in children with acute liver failure (ALF). METHODS Twenty-three patients under 18 years of age admitted to National Taiwan University Hospital due to ALF from 2003 to 2016 were included in this retrospective analysis. RESULTS Among the patients, 11 (48%) had native liver recovery (NLR), 9 (39.1%) died without liver transplant, and 3 (12.9%) received liver transplantation. The NLR group showed a lower proportion of idiopathic cases, lower peak ammonia level, higher peak alpha fetoprotein (AFP) level, and they had plasma exchange fewer times than the other groups. Receiver operating characteristic curve analyses yielded optimal cutoff values of plasma exchange (≤6 times), peak ammonia level (<190 μmol/L), and peak AFP level for predicting NLR in children with ALF. CONCLUSION Pediatric ALF with idiopathic etiology, high peak ammonia level, and low peak AFP level are associated with fewer cases of NLR. Plasma exchange for more than six times probably offers little benefit with regard to patient survival if liver transplantation is not performed promptly.
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Affiliation(s)
- Mu-Ming Chien
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Mei-Hwei Chang
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Kai-Chi Chang
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Fang-Ting Lu
- Department of Pediatrics, Changhua Christian Hospital, Changhua, Taiwan
| | - Yu-Chun Chiu
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Education, National Taiwan University Hospital, Taipei, Taiwan
| | - Huey-Ling Chen
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Education and Bioethics, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yen-Hsuan Ni
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Hong-Yuan Hsu
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Education and Bioethics, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jia-Feng Wu
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
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Pediatric living donor liver transplantation: A single center experiences. JOURNAL OF SURGERY AND MEDICINE 2019. [DOI: 10.28982/josam.542279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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Squires JE, Rudnick DA, Hardison RM, Horslen S, Ng VL, Alonso EM, Belle SH, Squires RH. Liver Transplant Listing in Pediatric Acute Liver Failure: Practices and Participant Characteristics. Hepatology 2018; 68:2338-2347. [PMID: 30070372 PMCID: PMC6275095 DOI: 10.1002/hep.30116] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2017] [Accepted: 05/24/2018] [Indexed: 12/19/2022]
Abstract
Liver transplant (LT) decisions in pediatric acute liver failure (PALF) are complex. Three phases of the PALF registry, containing data on 1,144 participants over 15 years, were interrogated to characterize clinical features associated with listing status. A decrease in the cumulative incidence of listing (P < 0.005) and receiving (P < 0.05) LT occurred without an increase in the cumulative incidence of death (P = 0.67). Time to listing was constant and early (1 day; quartiles 1-3 = 0-2; P = 0.88). The most frequent reasons for not listing were "not sick enough" and "medically unsuitable." Participants listed for LT were more likely male, with coma grade scores >0; had higher international normalized ratio, bilirubin, lactate, and venous ammonia; and had lower peripheral lymphocytes and transaminase levels compared to those deemed "not sick enough." Participants listed versus those deemed "medically unsuitable" were older; had higher serum aminotransferase levels, bilirubin, platelets, and albumin; and had lower lactate, venous ammonia, and lymphocyte count. An indeterminate diagnosis was more prevalent in listed participants. Ventilator (23.8%) and vasopressor (9.2%) support occurred in a significant portion of listed participants but less frequently than in those who were not "medically suitable." Removal from the LT list was a rare event. Conclusion: The cumulative incidence of listing for and receiving LT decreased throughout the PALF study without an increase in the cumulative incidence of death. While all participants fulfilled entry criteria for PALF, significant differences were noted between participants listed for LT and those deemed "not sick enough" as well as those who were "medically unsuitable." Having an indeterminate diagnosis and a requirement for cardiopulmonary support appeared to influence decisions toward listing; optimizing listing decisions in PALF may reduce the frequency of LT without increasing the frequency of death.
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Affiliation(s)
- James E Squires
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Pittsburgh School of Medicine and Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - David A Rudnick
- Pediatric Hepatology Departments of Pediatrics and Developmental Biology, Washington University School of Medicine, St. Louis, MO, United States
| | - Regina M Hardison
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States
| | - Simon Horslen
- Pediatric Hepatology, Seattle Children’s Hospital, Seattle, WA, United States
| | - Vicky L Ng
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, University of Toronto, ON, Canada
| | - Estella M Alonso
- Pediatric Hepatology, Ann and Robert H Lurie Children’s Hospital, Chicago, IL, United States
| | - Steven H Belle
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States,Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States
| | - Robert H Squires
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Pittsburgh School of Medicine and Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA, United States
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Kido J, Matsumoto S, Sakamoto R, Mitsubuchi H, Inomata Y, Nakamura K. Recovery of severe acute liver failure without transplantation in patients with Wilson disease. Pediatr Transplant 2018; 22:e13292. [PMID: 30368998 DOI: 10.1111/petr.13292] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2018] [Revised: 08/08/2018] [Accepted: 08/22/2018] [Indexed: 12/26/2022]
Abstract
Wilson disease (WD) is a disorder of copper metabolism that leads to liver cirrhosis. WD patients with a NWIS > 11 should receive LT; however, we encountered 2 WD patients with an NWIS > 11 who recovered from ALF without LT. The present report aimed to analyze cases of WD patients with a high NWIS who recovered from severe ALF and to discuss the clinical manifestations of the patients and the effects of treatments, including zinc (Zn) therapy, chelator therapy, PE, CHDF, and LT. We retrospectively evaluated the medical records of five patients (male, 2; female, 3) diagnosed with WD along with severe ALF. In cases 1, 2, and 3, complete recovery from ALF was noted without LT. In case 4, initial recovery from ALF was noted without LT; however, ALF worsened owing to bleeding from the esophageal varix. Thus, the patient eventually needed LT. In case 5, recovery from ALF was noted with LT. All cases, except case 2, showed ALF with maximum PELD/MELD scores ≥26 and NWISs ≥ 11, and had indications for LT. In cases of severe ALF with grade I or II encephalopathy, we recommend evaluations of the effects of Zn and chelator treatments while preparing for LT, as the condition may not improve without LT, and pediatricians or physicians can ask transplant surgeons to perform LT urgently if required.
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Affiliation(s)
- Jun Kido
- Department of Pediatrics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Kumamoto, Japan
| | - Shirou Matsumoto
- Department of Pediatrics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Kumamoto, Japan
| | - Rieko Sakamoto
- Department of Pediatrics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Kumamoto, Japan.,Department of Transplantation and Pediatric Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Kumamoto, Japan
| | - Hiroshi Mitsubuchi
- Department of Pediatrics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Kumamoto, Japan
| | - Yukihiro Inomata
- Department of Transplantation and Pediatric Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Kumamoto, Japan.,Labor Welfare Corporation, Kumamoto Rosai Hospital, Yatsushiro City, Kumamoto, Japan
| | - Kimitoshi Nakamura
- Department of Pediatrics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Kumamoto, Japan
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Acute Liver Failure: Outcome and Value of Pediatric End-Stage Liver Disease Score in Pediatric Cases. Pediatr Emerg Care 2018; 34:409-412. [PMID: 29851917 DOI: 10.1097/pec.0000000000000884] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
PURPOSE The aims of this study were to analyze the characteristics of patients with acute liver failure (ALF) in our center and evaluate the prognostic value of the Pediatric End-Stage Liver Disease (PELD) score calculated at admission. METHODS A retrospective analysis of patients with ALF younger than 15 years between 2005 and 2013 was performed. Information collected included age, sex, etiology of ALF, laboratory tests, PELD score, stage of encephalopathy, and need for liver support devices such as MARS and/or liver transplant (LT) and survival. A poor prognosis was defined as the need for LT or death. RESULTS Twenty patients (10 male patients, 50%) with a median age of 2.6 years (3 days-14.5 y old) were included. Acute liver failure was of indeterminate cause in 5 cases (25%). Within the recognized causes, the most frequent were viral hepatitis (herpes simplex virus, adenovirus, influenza B, Epstein-Barr virus), autoimmune hepatitis, and metabolopathies. Sixty percent presented with encephalopathy at diagnosis. Four patients were aided by a MARS liver support device. Six patients received a total of 7 transplants, all from deceased donors. The rate of spontaneous recovery was 45%. Currently 13 patients (65%) are living, 4 of them with an LT. Six patients died because of ALF. The mean PELD score of patients with spontaneous recovery was 15.31 (5.3-27.6) compared with a mean of 29.5 (17.2-39.4) in LT patients and 31.55 (15.8-52.4) for nonsurvivors (P = 0.013). CONCLUSIONS High PELD scores at diagnosis were accurate predictors of a poor prognosis in our patients with ALF. This model may help in the clinical management of this entity, although prospective validation is needed.
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Gilbert Pérez JJ, Jordano Moreno B, Rodríguez Salas M. Aetiology, outcomes and prognostic indicators of paediatric acute liver failure. ANALES DE PEDIATRÍA (ENGLISH EDITION) 2018. [DOI: 10.1016/j.anpede.2017.02.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
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Di Giorgio A, Sonzogni A, Piccichè A, Alessio G, Bonanomi E, Colledan M, D'Antiga L. Successful management of acute liver failure in Italian children: A 16-year experience at a referral centre for paediatric liver transplantation. Dig Liver Dis 2017; 49:1139-1145. [PMID: 28663066 DOI: 10.1016/j.dld.2017.05.026] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2017] [Revised: 04/18/2017] [Accepted: 05/30/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND Identifying the causes of acute liver failure (ALF) and predictors of death or liver transplantation (LTX) is crucial to decide its management. We aimed to describe features and outcome of ALF in Italian children. METHODS Retrospective review of cases presenting between 1996-2012. ALF was defined by high transaminases, INR ≥2.0 regardless of hepatic encephalopathy (HE), no evidence of underlying chronic liver disease. RESULTS 55 children (median age 2.6 years, range 0.1-15.1; M/F=31/24) had ALF due to autoimmune hepatitis (AIH) in 10 (18%), metabolic disorders in 9 (17%), paracetamol overdose in 6 (11%), mushroom poisoning in 3 (5%), viral infection in 1 (2%), indeterminate in 26 (47%); 25/55 recovered with supportive management (45%); 28/55 underwent LTX and 2 died on the waiting list (55%). On multivariate analysis severity of HE grade 3-4 and bilirubin ≥12mg/dl were independent predictors of death or LTX (p<0.05). After a median follow up of 4 years (range 2-15.0 years) the overall survival rate was 93%. CONCLUSION Children with ALF can be managed successfully with combined medical treatment and transplantation, warranting a survival rate similar to children transplanted because of chronic conditions. In our cohort of patients severe HE and high bilirubin on admission were independent predictors of the need of LTX.
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Affiliation(s)
- A Di Giorgio
- Paediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII Bergamo, Italy
| | - A Sonzogni
- Liver and Transplant Pathology, Hospital Papa Giovanni XXIII Bergamo, Italy
| | - A Piccichè
- Hospital Management, Hospital Papa Giovanni XXIII Bergamo, Italy
| | - G Alessio
- Laboratory Medicine, Hospital Papa Giovanni XXIII Bergamo, Italy
| | - E Bonanomi
- Paediatric Intensive Care Unit, Hospital Papa Giovanni XXIII Bergamo, Italy
| | - M Colledan
- General Surgery and Transplantation, Hospital Papa Giovanni XXIII Bergamo, Italy
| | - L D'Antiga
- Paediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII Bergamo, Italy.
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Alam S, Khanna R, Sood V, Lal BB, Rawat D. Profile and outcome of first 109 cases of paediatric acute liver failure at a specialized paediatric liver unit in India. Liver Int 2017; 37:1508-1514. [PMID: 28111909 DOI: 10.1111/liv.13370] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2016] [Accepted: 01/15/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The outcome of paediatric acute liver failure largely depends on age and aetiology. The aim of this work was to study the aetiological spectrum and outcome of the paediatric acute liver failure cases. METHODS This prospective observational study included all children (<18 years age) fulfilling paediatric acute liver failure study group definition. Aetiological evaluation was done and predictive factors for poor outcome (death or liver transplantation) were analysed. RESULTS There were 109 children in total. The commonest aetiology was viral infections (50, 45.8%) followed by metabolic liver diseases (14, 13.2%) and drug-induced liver injury (12, 11%). Viral, indeterminate and drug-induced liver injury group were older in age, had higher international normalized ratio and alanine transaminases in comparison with those with metabolic liver diseases and other aetiologies (P<.05). At 90 days from presentation, 52 (47.7%) children survived with native liver. On multivariate analysis, jaundice to encephalopathy interval >7 days (adjusted OR: 9.16, 95% CI: 1.55-53) and higher paediatric/model for end-stage liver disease scores at 72 hours (adjusted OR: 1.2, 95% CI: 1.08-1.32) were associated with poor outcome. CONCLUSION Viral infections, indeterminate and drug-induced liver injury-related paediatric acute liver failure usually present in older children with higher international normalized ratio and alanine transaminases. Jaundice to encephalopathy interval >7 days and paediatric/model for end stage liver disease score >24 at 72 hours are associated with poor outcome.
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Affiliation(s)
- Seema Alam
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Rajeev Khanna
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Vikrant Sood
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Bikrant B Lal
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Dinesh Rawat
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Abstract
Considerable strides have been made over the last several decades toward improving outcomes in pediatric liver transplantation. Refinements in surgical technique has allowed for the use of living donor and deceased donor split-liver grafts, thus expanding the pool of available organs and reducing waitlist mortality. The use of a multidisciplinary team continues to be paramount in the care of the transplant recipient. With improvements in overall graft and survival, indications for liver transplantation have also broadened. Currently, pediatric transplant patients have a 5-year survival of over 85%. Long-term morbidity is mainly associated with complications from immunosuppression and chronic rejection. Here we review indications for liver transplantation in children, surgical considerations, post-operative complications, and long-term outcomes.
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Affiliation(s)
- Alex G Cuenca
- Department of Surgery, Boston Children's Hospital, 300 Longwood Ave, Fegan 3, Boston 02115, MA
| | - Heung Bae Kim
- Department of Surgery, Pediatric Transplant Center, Boston Children's Hospital, Boston Children's Hospital, Harvard Medical School, Boston, MA
| | - Khashayar Vakili
- Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA.
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Abstract
OBJECTIVES To describe the epidemiological features, clinical characteristics and outcomes of neonates diagnosed with liver failure, as well as determine prognostic factors. METHODS Cohort study conducted at a single tertiary referral and university-affiliated pediatric center. Hospital records of all neonates diagnosed with liver failure between January 2003 and December 2015 were retrospectively reviewed, and data on clinical and laboratory findings, treatment, and outcomes were collected. Survival analysis (Kaplan-Meier) and Cox regression were performed to identify prognostic factors at diagnosis. Liver failure diagnosis was established using the pediatric acute liver failure study group's diagnostic criteria for every patient with coagulopathy and biochemical pattern of liver disease. RESULTS Forty-five patients were included. In our series, most cases were secondary to ischemia (28.9%). Other causes were neonatal hemochromatosis (17.8%), viral infections (13.3%), and inborn errors of metabolism (13.3%). A total 55.6% (25/45) of the patients died (median age: 16 days; range 1-235 days). Alanine aminotransferase (ALT) at diagnosis was associated with higher mortality or the need for liver transplantation on day 21 after diagnosis (P = .006). For every 500 IU/L increase in ALT serum levels, the mortality/liver transplantation rate increased 1.3 times (hazard ratio 95% confidence interval: 1.1-1.6). Although ischemic neonatal acute liver failure presents with higher ALT levels, these cases appear to have better outcomes. Higher international normalized ratio tended to increase mortality/transplantation (hazard ratio 1.02; 95% confidence interval 0.91-1.2). CONCLUSIONS Neonatal liver failure should perhaps be considered in the differential diagnoses of any coagulopathy. ALT and international normalized ratio levels at diagnosis could predict prognosis in the short term. Ischemic liver failure appears to have a better prognosis.
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Gilbert Pérez JJ, Jordano Moreno B, Rodríguez Salas M. [Aetiology, outcomes and prognostic indicators of paediatric acute liver failure]. An Pediatr (Barc) 2017; 88:63-68. [PMID: 28395968 DOI: 10.1016/j.anpedi.2017.02.017] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Revised: 02/23/2017] [Accepted: 02/28/2017] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION Acute liver failure (ALF) is a multisystem disease with severe impairment of liver function of acute onset. The Paediatric End-stage Liver Disease (PELD) score is used as a predictor of mortality in chronic liver disease, however experience is limited in ALF. OBJECTIVES To evaluate the aetiology and outcomes of children with ALF in a Children's Liver Transplant Centre, and to investigate the validity of PELD as a prognostic indicator. PATIENTS AND METHODS A retrospective study was conducted on patients diagnosed with ALF in our hospital from 2000 to 2013 using the criteria of the Paediatric ALF Study Group. RESULTS The study included 49 patients with an age range 0-14years. The most frequent aetiologies were: indeterminate (36.7%) and metabolic (26.5%). Liver transplant (LT) was required by 42.8%, and there were 16.3% deaths. Patients with higher levels of bilirubin, INR, or encephalopathy were more likely to require a liver transplant, yielding an OR for INR 1.93. A cut-off of 27 in the PELD score according to the ROC curve showed a sensitivity of 86% and a specificity of 85%, predicting a worse outcome (AUC: 0.90; P<.001). The survival of patients with ALF without transplantation seems more likely in those who have low values of PELD and absence of encephalopathy, with a RR of 0.326. CONCLUSIONS ALF patients with a high PELD score and the presence of encephalopathy had worse outcomes. The PELD score could be a useful tool to establish the optimum time for inclusion in the transplant list, however further studies are still needed.
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Affiliation(s)
- Juan José Gilbert Pérez
- Unidad de Gastroenterología, Hepatología, Nutrición y Trasplante Hepático Pediátrico, Unidad de Gestión Clínica, Críticos y Urgencias Pediátricas, Hospital Universitario Reina Sofía, Córdoba, España
| | - Belén Jordano Moreno
- Unidad de Gastroenterología, Hepatología, Nutrición y Trasplante Hepático Pediátrico, Unidad de Gestión Clínica, Críticos y Urgencias Pediátricas, Hospital Universitario Reina Sofía, Córdoba, España.
| | - Mónica Rodríguez Salas
- Unidad de Gastroenterología, Hepatología, Nutrición y Trasplante Hepático Pediátrico, Unidad de Gestión Clínica, Críticos y Urgencias Pediátricas, Hospital Universitario Reina Sofía, Córdoba, España
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Alam S, Sood V. Metabolic Liver Disease: When to Suspect and How to Diagnose? Indian J Pediatr 2016; 83:1321-1333. [PMID: 27130505 DOI: 10.1007/s12098-016-2097-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2015] [Accepted: 03/17/2016] [Indexed: 02/07/2023]
Abstract
Metabolic liver diseases are still considered by many as a 'rare' diagnosis, though scenario has definitely changed in recent times. With recent advances and wider availablility of newer techniques, many of these are now amenable to diagnosis and optimum management. Though the logistics involved are still out of reach of a significant proportion of our population, a stepwise and methodological approach with simple diagnostic tests can help point towards a probable diagnosis (with resultant directed investigations), helping to avoid unnecessary and costly workup. This review focuses on diagnostic protocol-based approach to common metabolic liver diseases encountered frequently in pediatric hepatology.
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Affiliation(s)
- Seema Alam
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India.
| | - Vikrant Sood
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
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Jain V, Dhawan A. Prognostic modeling in pediatric acute liver failure. Liver Transpl 2016; 22:1418-30. [PMID: 27343006 DOI: 10.1002/lt.24501] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2016] [Revised: 06/12/2016] [Accepted: 06/16/2016] [Indexed: 02/07/2023]
Abstract
Liver transplantation (LT) is the only proven treatment for pediatric acute liver failure (PALF). However, over a period of time, spontaneous native liver survival is increasingly reported, making us wonder if we are overtransplanting children with acute liver failure (ALF). An effective prognostic model for PALF would help direct appropriate organ allocation. Only patients who would die would undergo LT, and those who would spontaneously recover would avoid unnecessary LT. Deriving and validating such a model for PALF, however, encompasses numerous challenges. In particular, the heterogeneity of age and etiology in PALF, as well as a lack of understanding of the natural history of the disease, contributed by the availability of LT has led to difficulties in prognostic model development. Several prognostic laboratory variables have been identified, and the incorporation of these variables into scoring systems has been attempted. A reliable targeted prognostic model for ALF in Wilson's disease has been established and externally validated. The roles of physiological, immunological, and metabolomic parameters in prognosis are being investigated. This review discusses the challenges with prognostic modeling in PALF and describes predictive methods that are currently available and in development for the future. Liver Transplantation 22 1418-1430 2016 AASLD.
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Affiliation(s)
- Vandana Jain
- Paediatric Liver, GI and Nutrition Centre, King's College Hospital, London, UK
| | - Anil Dhawan
- Paediatric Liver, GI and Nutrition Centre, King's College Hospital, London, UK.
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Outcomes of Children With and Without Hepatic Encephalopathy From the Pediatric Acute Liver Failure Study Group. J Pediatr Gastroenterol Nutr 2016; 63:357-64. [PMID: 27367788 PMCID: PMC4992416 DOI: 10.1097/mpg.0000000000001178] [Citation(s) in RCA: 67] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Hepatic encephalopathy (HE) is challenging to identify in children with acute liver failure and was not a requirement for enrollment into the Pediatric Acute Liver Failure Study Group (PALFSG). The outcomes of PALFSG participants presenting with and without HE are presented. METHODS PALFSG participants were classified based on daily assessment of HE during the first 7 days following study enrollment: group 1-never developed HE; group 2-no HE at enrollment with subsequent HE development; and group 3-HE at study enrollment. Clinical and biochemical parameters and outcomes of death, spontaneous recovery, or liver transplantation were compared between groups. RESULTS Data from 769 PALFSG (54% boys; median age 4.2 years; range 0-17.9 years) participants were analyzed, with 277 in group 1 (36%), 83 in group 2 (11%), and 409 in group 3 (53%). Mortality occurred in 11% of all participants and was highest among group 3 participants who demonstrated persistent grade III-IV HE (55%) or showed progression of HE (26%). Eleven (4%) group 1 participants died within 21 days of enrollment. Spontaneous recovery was highest in group 1 (79%) and lowest in group 2 (25%; P < 0.001). CONCLUSIONS Mortality 21 days after enrollment was highest in participants enrolled with severe HE (grades III or IV) or demonstrating HE progression. Four percent of participants without recorded clinical HE in the 7 days after enrollment, however, died within 21 days. Improved assessment of neurological injury and pediatric acute liver failure prognostication schema are needed.
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Abstract
Liver transplantation (LT) is an important component in the therapeutic armamentarium of managing end-stage liver disease. In North American children, biliary atresia remains the most common indication for LT compared to hepatitis C in adults, while hepatoblastoma is the most common liver tumor requiring LT, versus Hepatocellular carcinoma in adults. Rejection, lymphoproliferative disease, renal insufficiency, metabolic syndrome, recurrent disease, 'de novo' autoimmune hepatitis and malignancy require careful surveillance and prompt action in adults and children after LT. In children, specific attention to EBV viremia, growth, development, adherence and transition to the adult services is also required. Antibody mediated rejection and screening for donor specific antibodies is becoming important in managing liver graft dysfunction. Biomarkers to identify and predict tolerance are being developed. Machine perfusion and stem cells (iPS) to synthesize organs are generating interest and are a focus for research.
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Affiliation(s)
- Nanda Kerkar
- a Keck School of Medicine, Medical Director Liver/Intestinal and Hepatology Transplant Program, Children's Hospital of Los Angeles , University of Southern California , Los Angeles , CA , USA
| | - Arathi Lakhole
- b Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Los Angeles , University of Southern California , Los Angeles , CA , USA
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Abstract
CONTEXT Suspecting metabolic liver disease in an infant or young child with acute liver failure, and a protocol-based workup for diagnosis is the need of the hour. EVIDENCE ACQUISITION Data over the last 15 years was searched through Pubmed using the keywords Metabolic liver disease and Acute liver failure with emphasis on Indian perspective. Those published in English language where full text was retrievable were included for this review. RESULTS Metabolic liver diseases account for 13-43% cases of acute liver failure in infants and young children. Etiology remains indeterminate in very few cases of liver failure in studies where metabolic liver diseases were recognized in large proportion. Galactosemia, tyrosinemia and mitochondrial disorders in young children and Wilsons disease in older children are commonly implicated. A high index of suspicion for metabolic liver diseases should be kept when there is strong family history of consanguinity, recurrent abortions or sibling deaths; and history of recurrent diarrhea, vomiting, failure to thrive or developmental delay. Simple dietary modifications and/or specific management can be life-saving if instituted promptly. CONCLUSION A high index of suspicion in presence of red flag symptoms and signs, and a protocol-based approach helps in timely diagnosis and prompt administration of lifesaving therapy.
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Affiliation(s)
- Seema Alam
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India. Correspondence to: Prof Seema Alam, Professor and Head, Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi 110 070, India.
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Li R, Belle SH, Horslen S, Chen LW, Zhang S, Squires RH. Clinical Course among Cases of Acute Liver Failure of Indeterminate Diagnosis. J Pediatr 2016; 171:163-70.e1-3. [PMID: 26831743 PMCID: PMC4808594 DOI: 10.1016/j.jpeds.2015.12.065] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2015] [Revised: 11/05/2015] [Accepted: 12/23/2015] [Indexed: 01/04/2023]
Abstract
OBJECTIVE To investigate the heterogeneity in clinical course among those with pediatric acute liver failure (PALF) of indeterminate disease etiology. STUDY DESIGN We studied participants enrolled in the PALF registry study with indeterminate final diagnosis. Growth mixture modeling was used to analyze participants' international normalized ratio, total bilirubin, and hepatic encephalopathy trajectories in the first 7 days following enrollment. Participants with at least 3 values for 1 or more of the measurements were included. We examined the association between the resulting latent subgroup classification with participants' characteristics and disease outcomes. Data from participants with PALF of specified etiologies were used to investigate the potential diagnostic value of the latent subgroups. RESULTS In this sample of 380 participants with indeterminate final diagnosis, 115 (30%) experienced mild and quickly improving disease trajectories and another 48 (13%) started with severe disease but improved by day 7. The majority of participants (216, 57%) had disease trajectories that worsened over time. The identified patterns of disease trajectories are predictive of outcome (P < .001). The trajectory patterns are associated with the underlying disease etiology (P < .001) for the 488 participants with PALF of specified etiologies. CONCLUSIONS The clinical courses of participants with PALF of indeterminate disease etiology exhibit distinct trajectory patterns, which have important prognostic and potentially diagnostic value.
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Affiliation(s)
- Ruosha Li
- Department of Biostatistics, University of Texas School of Public Health, Houston, TX
| | - Steven H Belle
- Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA
| | - Simon Horslen
- Division of Gastroenterology, Seattle Children's Hospital, Seattle, WA
| | - Ling-wan Chen
- Department of Statistics, University of Pittsburgh, Pittsburgh, PA
| | - Song Zhang
- Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA
| | - Robert H Squires
- Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, PA.
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Abstract
Pediatric acute liver failure (PALF) is a progressive, potentially fatal clinical syndrome occurring in previously healthy children. Our study aimed to determine the current leading causes of PALF in a single center in Germany, identifying possible prognostic markers. Thirty-seven pediatric patients with PALF were included. Medical records were reviewed for demographic, laboratory and clinical data. Laboratory results on admission and at peak value, PELD and MELD score on admission, and intensive care support were assessed. Fifteen patients recovered spontaneously, 14 died without transplantation, and 8 received a liver transplant. Patients who survived were significantly older than patients who died. Specific causes of PALF could be identified as infectious diseases (16%), metabolic diseases (14%), toxic liver injury (11%), immunologic diseases (8%), or vascular diseases (8%). Causes of PALF remained indeterminate in 43%. High ammonia, low albumin, and low ALT levels on admission were associated with worse outcome. Absence of need of ventilation, hemodialysis, and circulatory support predicted spontaneous recovery. In conclusion, infections are the most common known cause of PALF. However, in a large proportion of patients the cause for PALF remains cryptic. Ammonia and albumin levels may be of prognostic value to predict outcomes.
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Abstract
AIM OF THE STUDY To report the outcomes of children who underwent Sengstaken-Blakemore tube (SBT) insertion for life-threatening haemetemesis. METHODS Single institution retrospective review (1997-2012) of children managed with SBT insertion. Patient demographics, diagnosis and outcomes were noted. Data are expressed as median (range). MAIN RESULTS 19 children [10 male, age 1 (0.4-16) yr] were identified; 18 had gastro-oesophageal varices and 1 aorto-oesophageal fistula. Varices were secondary to: biliary atresia (n=8), portal vein thrombosis (n=5), alpha-1-anti-trypsin deficiency (n=1), cystic fibrosis (n=1), intrahepatic cholestasis (n=1), sclerosing cholangitis (n=1) and nodular hyperplasia with arterio-portal shunt (n=1). Three children deteriorated rapidly and did not survive to have post-SBT endoscopy. The child with an aortooesophageal fistula underwent aortic stent insertion and subsequently oesophageal replacement. Complications included gastric mucosal ulceration (n=3, 16%), pressure necrosis at lips and cheeks (n=6, 31%) and SBT dislodgment (n=1, 6%). Six (31%) children died. The remaining 13 have been followed up for 62 (2-165) months; five required liver transplantation, two underwent a mesocaval shunt procedure and 6 have completed endoscopic variceal obliteration and are under surveillance. CONCLUSIONS SBT can be an effective, albeit temporary, life-saving manoeuvre in children with catastrophic haematemesis.
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Lu ZH, Huang XP, Sun W, Zhu YL, Cui JJ, Chen W, Huang LH, Kuai SG, Du HJ, Ju ZX, Gan JH. T helper cell dysregulation with hepatitis B and rebalance with glucocorticoids. World J Gastroenterol 2014; 20:18354-18359. [PMID: 25561802 PMCID: PMC4277972 DOI: 10.3748/wjg.v20.i48.18354] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2014] [Revised: 06/08/2014] [Accepted: 07/11/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate T helper 17/regulatory T cell alterations in early severe hepatitis B and the effect of glucocorticoids.
METHODS: The study included 20 patients in the early stage of severe hepatitis B (SHB) and 11 healthy controls. All patients had elevated T helper 17 (Th17) levels, decreased regulatory T (Treg) cell levels, and significant Th17/Treg ratios.
RESULTS: After glucocorticoid treatment, 16 patients showed improvement with significant decreases in Th17 levels, increases in Treg, and rebalanced Th17/Treg ratios. The four patients who showed no improvement had increases in both Th17 and Treg levels and an even higher Th17/Treg ratio than before.
CONCLUSION: Glucocorticoid treatment can rectify Th17/Treg dysregulation in patients with SHB.
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McKenzie RB, Berquist WE, Nadeau KC, Louie CY, Chen SF, Sibley RK, Glader BE, Wong WB, Hofmann LV, Esquivel CO, Cox KL. Novel protocol including liver biopsy to identify and treat CD8+ T-cell predominant acute hepatitis and liver failure. Pediatr Transplant 2014; 18:503-9. [PMID: 24930635 DOI: 10.1111/petr.12296] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/24/2014] [Indexed: 12/21/2022]
Abstract
In the majority of children with ALF, the etiology is unknown and liver transplantation is often needed for survival. A patient case prompted us to consider that immune dysregulation may be the cause of indeterminate acute hepatitis and liver failure in children. Our study includes nine pediatric patients treated under a multidisciplinary clinical protocol to identify and treat immune-mediated acute liver injury. Patients with evidence of inflammation and no active infection on biopsy received treatment with intravenous immune globulin and methylprednisolone. Seven patients had at least one positive immune marker before or after treatment. All patients had a CD8+ T-cell predominant liver injury that completely or partially responded to immune therapy. Five of the nine patients recovered liver function and did not require liver transplantation. Three of these patients subsequently developed bone marrow failure and were treated with either immunosuppression or stem cell transplant. This series highlights the importance of this tissue-based approach to diagnosis and treatment that may improve transplant-free survival. Further research is necessary to better characterize the immune injury and to predict the subset of patients at risk for bone marrow failure who may benefit from earlier and stronger immunosuppressive therapy.
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Affiliation(s)
- Rebecca B McKenzie
- Division of Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, Stanford School of Medicine, Stanford, CA, USA
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Rajanayagam J, Frank E, Shepherd RW, Lewindon PJ. Artificial neural network is highly predictive of outcome in paediatric acute liver failure. Pediatr Transplant 2013; 17:535-42. [PMID: 23802584 DOI: 10.1111/petr.12100] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/29/2013] [Indexed: 12/28/2022]
Abstract
Current prognostic models in PALF are unreliable, failing to account for complex, non-linear relationships existing between multiple prognostic factors. A computational approach using ANN should provide superior modelling to PELD-MELD scores. We assessed the prognostic accuracy of PELD-MELD scores and ANN in PALF in children presenting to the QLTS, Australia. A comprehensive registry-based data set was evaluated in 54 children (32M, 22F, median age 17 month) with PALF. PELD-MELD scores calculated at (i) meeting PALF criteria and (ii) peak. ANN was evaluated using stratified 10-fold cross-validation. Outcomes were classified as good (transplant-free survival) or poor (death or LT) and predictive accuracy compared using AUROC curves. Mean PELD-MELD scores were significantly higher in non-transplanted non-survivors (i) 37 and (ii) 46 and transplant recipients (i) 32 and (ii) 43 compared to transplant-free survivors (i) 26 and (ii) 30. Threshold PELD-MELD scores ≥27 and ≥42, at meeting PALF criteria and peak, gave AUROC 0.71 and 0.86, respectively, for poor outcome. ANN showed superior prediction for poor outcome with AUROC 0.96, sensitivity 82.6%, specificity 96%, PPV 96.2% and NPV 85.7% (cut-off 0.5). ANN is superior to PELD-MELD for predicting poor outcome in PALF.
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Affiliation(s)
- J Rajanayagam
- Department of Pediatric Gastroenterology Hepatology and Nutrition, Starship Children's Hospital, Auckland, New Zealand
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