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Kelgeri C, Kanthimathinathan HK, Couper M, Alnagar A, Biradar V, Sharif K, Hartley J, Mirza D, Gupte GL. Etiology, Characteristics, and Outcomes of Neonatal Liver Failure: Lessons Learned Over the Last 3 Decades. J Pediatr 2024; 275:114245. [PMID: 39151605 DOI: 10.1016/j.jpeds.2024.114245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 08/07/2024] [Accepted: 08/12/2024] [Indexed: 08/19/2024]
Abstract
OBJECTIVE To evaluate trends in etiology and outcomes of neonatal liver failure (NLF) over 30 years retrospectively at a single institution. STUDY DESIGN Inclusion criteria for this retrospective cohort study were babies presenting at a chronological age of ≤28 days between 1991 and 2020 with prothrombin time ≥20 seconds and biochemical liver injury. Demographics, etiology, laboratory investigations, need for extrahepatic organ support, acute kidney injury, and intervention with liver transplant (LT) were recorded. Survival outcomes were measured as discharge from the hospital alive with native liver or LT. The study period was stratified into 3 10-year blocks. Trends were analyzed for hospital admissions, etiology, and survival outcomes. RESULTS One hundred twenty-six babies met the NLF criteria. Admissions to the hospital increased from 21 in 1991-2000 to 65 in 2011-2020. An increasing trend in infectious and metabolic causes, while a decreasing trend in indeterminate etiology, was noted. Survival with native liver improved from 23.8% in 1991-2000 to 55.4% in 2011-20 (P = .021), and mortality reduced from 52.4% to 35.4% during the same periods (P = .213). Twenty-three (18.2%) neonates received LT. Post-LT survival outcomes were 100% for gestational alloimmune liver disease, 66.6% in the indeterminate group, and 25% for herpes simplex virus. Specific etiologies (gestational alloimmune liver disease, OR = 0.07 [0-0.77, P = .048]), presence of acute kidney injury (OR = 6.22 [1.45, 29.38, P = .015]) and need for inotropes (OR = 6.22 [1.45, 29.38, P = .028]) influenced mortality in multivariable logistic regression analysis. CONCLUSIONS In the last 30 years, advances in diagnosis, treatment, and increasing experience with LT have improved survival in NLF.
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Affiliation(s)
- Chayarani Kelgeri
- Liver Unit Including Small Bowel Transplant, Birmingham Women's and Children's Hospital, Birmingham, United Kingdom.
| | | | - Michael Couper
- Liver Unit Including Small Bowel Transplant, Birmingham Women's and Children's Hospital, Birmingham, United Kingdom
| | - Amr Alnagar
- Liver Unit Including Small Bowel Transplant, Birmingham Women's and Children's Hospital, Birmingham, United Kingdom
| | - Vishnu Biradar
- Paediatric Gastroenetrology and Hepatology, Jupiter Hospital, Pune, Maharashtra, India
| | - Khalid Sharif
- Liver Unit Including Small Bowel Transplant, Birmingham Women's and Children's Hospital, Birmingham, United Kingdom
| | - Jane Hartley
- Liver Unit Including Small Bowel Transplant, Birmingham Women's and Children's Hospital, Birmingham, United Kingdom
| | - Darius Mirza
- Liver Unit Including Small Bowel Transplant, Birmingham Women's and Children's Hospital, Birmingham, United Kingdom
| | - Girish L Gupte
- Liver Unit Including Small Bowel Transplant, Birmingham Women's and Children's Hospital, Birmingham, United Kingdom
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Wang H, Vannilam A, Hafberg ET, Gillis LA, Kassardjian A, Naini BV, Prasad V, Kelly DR, Mroczek-Musulman EC, Knox K, Correa H, Liang J. Clinical and Histopathologic Characteristics of Acute Severe Hepatitis Associated With Human Herpesvirus 6 Infection. Am J Surg Pathol 2024; 48:1117-1130. [PMID: 38907627 DOI: 10.1097/pas.0000000000002266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/24/2024]
Abstract
Acute severe hepatitis associated with active human herpesvirus 6 (HHV-6) infection is a rare life-threatening condition with unclear clinical course and histopathology. In this study, we retrospectively analyzed 5 patients with indeterminate acute severe hepatitis found to have active hepatic HHV-6 infection during care. All patients were previously healthy children presenting with a nonspecific prodrome. Four developed acute liver failure (ALF) and 3 received liver transplantation. The explanted livers and biopsies demonstrated a centrilobular pattern of necroinflammation characterized by moderate to marked central perivenulitis and confluent centrilobular to panlobular necrosis in 4 cases, accompanied by marked hepatocellular swelling and milder portal inflammation in 3. Central perivenulitis was more prominent in comparison to a control of group of ALF without HHV-6 ( P =0.01). When compared with the children with acute severe hepatitis associated with adenovirus encountered in the recent outbreak, both central perivenulitis and centrilobular necrosis were significant predictors for association with HHV-6 ( P <0.01). Liver immunohistochemistry detected HHV-6 structural protein in biliary epithelium in all cases and a predominance of CD8 + T cells in the perivenular inflammatory infiltrate. Among the 4 patients with ALF, one received early anti-HHV-6 therapy and had transplant-free survival, while the other 3 received either general prophylactic antiviral treatment only (n=2) or late anti-HHV-6 therapy (n=1) and needed liver transplantation. Our findings were similar to those in previously reported cases. In summary, acute severe hepatitis associated with HHV-6 tends to affect children, progress to ALF, and exhibit characteristic centrilobular necroinflammation which likely represents an immune-mediated process.
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Affiliation(s)
- Huiying Wang
- Department of Pathology, Microbiology and Immunology
| | - Annette Vannilam
- Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, TN
| | - Einar T Hafberg
- Landspitali University Hospital, Reykjavík, Capital Region, Iceland
| | - Lynette A Gillis
- Division of Gastroenterology, Department of Pediatrics, University of Louisville, Louisville, KY
| | | | - Bita V Naini
- Department of Pathology, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Vinay Prasad
- Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH
| | - David R Kelly
- Department of Pathology and Laboratory Medicine, Children's of Alabama, Birmingham, AL
| | | | | | - Hernan Correa
- Department of Pathology, Microbiology and Immunology
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Uchida H, Hong SK, Okumura S, Cherukuru R, Sanada Y, Yamada Y, Reddy MS, Matsuura T, Hara T, Chen CL, Yi NJ, Ikegami T, Kasahara M. Current Status and Outcomes of Living Donor Liver Transplantation for Pediatric Acute Liver Failure: Results From a Multicenter Retrospective Study Over Two Decades. Pediatr Transplant 2024; 28:e14838. [PMID: 39158111 DOI: 10.1111/petr.14838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 07/03/2024] [Accepted: 07/26/2024] [Indexed: 08/20/2024]
Abstract
BACKGROUND Although the outcomes of living donor liver transplantation (LDLT) for pediatric acute liver failure (PALF) have improved, patient survival remains lower than in patients with chronic liver disease. We investigated whether the poor outcomes of LDLT for PALF persisted in the contemporary transplant era. METHODS We analyzed 193 patients who underwent LDLT between December 2000 and December 2020. The outcomes of patients managed in 2000-2010 (era 1) and 2011-2020 (era 2) were compared. RESULTS The median age at the time of LDLT was 1.2 years both eras. An unknown etiology was the major cause in both groups. Patients in era 1 were more likely to have surgical complications, including hepatic artery and biliary complications (p = 0.001 and p = 0.013, respectively). The era had no impact on the infection rate after LDLT (cytomegalovirus, Epstein-Barr virus, and sepsis). The mortality rates of patients and grafts in era one were significantly higher (p = 0.03 and p = 0.047, respectively). The 1- and 5-year survival rates were 76.4% and 70.9%, respectively, in era 1, while they were 88.3% and 81.9% in era 2 (p = 0.042). Rejection was the most common cause of graft loss in both groups. In the multivariate analysis, sepsis during the 30 days after LDLT was independently associated with graft loss (p = 0.002). CONCLUSIONS The survival of patients with PALF has improved in the contemporary transplant era. The early detection and proper management of rejection in patients, while being cautious of sepsis, should be recommended to improve outcomes further.
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Affiliation(s)
- Hajime Uchida
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Suk Kyun Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Shinya Okumura
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Ramkiran Cherukuru
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Chennai, India
| | - Yukihiro Sanada
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Yohei Yamada
- Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Mettu Srinivas Reddy
- Institute of Liver Disease and Transplantation, Gleneagles Global Health City, Chennai, India
| | - Toshiharu Matsuura
- Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takanobu Hara
- Department of Surgery, Nagasaki University Graduate School of Medical Sciences, Nagasaki, Japan
| | - Chao-Long Chen
- Department of Surgery, Liver Transplantation Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Toru Ikegami
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Mureo Kasahara
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
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Oue H, Hiejima E, Okajima H, Okamoto T, Ogawa E, Uebayashi EY, Hatano E, Suga T, Hanami Y, Ashina K, Kai S, Sogo T, Inui A, Matsubara T, Sakai K, Yanagita M, Haga H, Minamiguchi S, Yamada Y, Nihira H, Izawa K, Yasumi T, Takita J. Efficacy of steroid therapy for improving native liver survival after pediatric acute liver failure with immune activation. Hepatol Res 2024. [PMID: 39167365 DOI: 10.1111/hepr.14107] [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: 04/06/2024] [Revised: 07/27/2024] [Accepted: 08/06/2024] [Indexed: 08/23/2024]
Abstract
AIM Recent evidence suggests that acute liver failure (ALF) in some patients may reflect a dysregulated immune response, and that corticosteroids improve survival of the native liver in ALF patients with high serum alanine aminotransferase levels, which are an indication of liver inflammation. However, it is unclear whether steroids are effective for pediatric acute liver failure (PALF). The aim of this retrospective case-control study is to examine whether steroid therapy for PALF accompanied by immune activation improves the survival of native liver and to identify factors that predict responses to steroid treatment. METHODS Of 38 patients with PALF treated at Kyoto University Hospital from February 2006 to August 2022, 19 receiving steroids who met the specific criteria for identifying the pathophysiology of immune activity in the liver (the "Steroid group"), and seven steroid-free patients who also met the criteria ("Nonsteroid group") were enrolled. Patients in the "Steroid group" were categorized as "responders" or "nonresponders" according to treatment outcome. Clinical and histological data were analyzed. RESULTS Survival of the native liver in the Steroid group was significantly higher than that in the Nonsteroid group (68% vs. 0%, respectively; p = 0.0052). Nonresponders were significantly younger, with higher Model for End-stage Liver Disease and pediatric end-stage liver disease scores, higher prothrombin time - international normalized ratio, and higher serum ferritin levels than responders. Massive hepatic necrosis was more common in nonresponders. CONCLUSION Steroid therapy is effective for PALF patients with liver inflammation; however, liver transplantation should be prioritized for young children with ALF accompanied by severe coagulopathy or massive hepatic necrosis.
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Affiliation(s)
- Hiroshi Oue
- Department of Pediatrics, Kyoto University, Kyoto, Japan
| | - Eitaro Hiejima
- Department of Pediatrics, Kyoto University, Kyoto, Japan
| | - Hideaki Okajima
- Department of Surgery (HBP and Transplantation/Pediatric Surgery), Kyoto University, Kyoto, Japan
- Department of Pediatric Surgery, Kanazawa Medical University Hospital, Kanazawa, Japan
| | - Tatsuya Okamoto
- Department of Surgery (HBP and Transplantation/Pediatric Surgery), Kyoto University, Kyoto, Japan
| | - Eri Ogawa
- Department of Surgery (HBP and Transplantation/Pediatric Surgery), Kyoto University, Kyoto, Japan
| | - Elena Yukie Uebayashi
- Department of Surgery (HBP and Transplantation/Pediatric Surgery), Kyoto University, Kyoto, Japan
| | - Etsuro Hatano
- Department of Surgery (HBP and Transplantation/Pediatric Surgery), Kyoto University, Kyoto, Japan
| | - Takenori Suga
- Department of Pediatrics, Kyoto University, Kyoto, Japan
| | - Yotaro Hanami
- Department of Pediatrics, Kyoto University, Kyoto, Japan
| | | | - Shinichi Kai
- Department of Anesthesia, Kyoto University, Kyoto, Japan
| | - Tsuyoshi Sogo
- Department of Pediatric Hepatology and Gastroenterology, Saiseikai Yokohama City Tobu Hospital, Yokohama, Japan
| | - Ayano Inui
- Department of Pediatric Hepatology and Gastroenterology, Saiseikai Yokohama City Tobu Hospital, Yokohama, Japan
| | | | - Kaoru Sakai
- Department of Nephrology, Kyoto University, Kyoto, Japan
| | | | - Hironori Haga
- Department of Diagnostic Pathology, Kyoto University, Kyoto, Japan
| | | | - Yosuke Yamada
- Department of Diagnostic Pathology, Kyoto University, Kyoto, Japan
| | - Hiroshi Nihira
- Department of Pediatrics, Kyoto University, Kyoto, Japan
| | - Kazushi Izawa
- Department of Pediatrics, Kyoto University, Kyoto, Japan
| | | | - Junko Takita
- Department of Pediatrics, Kyoto University, Kyoto, Japan
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Hegarty R, Thompson RJ. Genetic aetiologies of acute liver failure. J Inherit Metab Dis 2024; 47:582-597. [PMID: 38499319 DOI: 10.1002/jimd.12733] [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: 12/01/2023] [Revised: 03/11/2024] [Accepted: 03/12/2024] [Indexed: 03/20/2024]
Abstract
Acute liver failure (ALF) is a rare, rapidly evolving, clinical syndrome with devastating consequences where definitive treatment is by emergency liver transplantation. Establishing a diagnosis can be challenging and, historically, the cause of ALF was unidentified in up to half of children. However, recent technological and clinical advances in genomic medicine have led to an increasing proportion being diagnosed with monogenic aetiologies of ALF. The conditions encountered include a diverse group of inherited metabolic disorders each with prognostic and treatment implications. Often these disorders are clinically indistinguishable and may even mimic disorders of immune regulation or red cell disorders. Rapid genomic sequencing for children with ALF is, therefore, a key component in the diagnostic work up today. This review focuses on the monogenic aetiologies of ALF.
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Affiliation(s)
- Robert Hegarty
- Paediatric Liver, GI and Nutrition Centre, King's College Hospital, London, UK
- Institute of Liver Studies, King's College London, London, UK
| | - Richard J Thompson
- Paediatric Liver, GI and Nutrition Centre, King's College Hospital, London, UK
- Institute of Liver Studies, King's College London, London, UK
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Abduljalil R, Ben Turkia H, Fakhroo A, Skrypnyk C. Fulminant Neonatal Liver Failure in MPV 17-Related Mitochondrial DNA Depletion Syndrome. Case Reports Hepatol 2023; 2023:4514552. [PMID: 37384111 PMCID: PMC10299873 DOI: 10.1155/2023/4514552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 05/03/2023] [Accepted: 05/10/2023] [Indexed: 06/30/2023] Open
Abstract
Mitochondrial depletion syndromes are well established causes of liver failure in infants. Hepatocerebral variant related to MPV17 gene defect is characterized by infantile onset of progressive liver failure, developmental delay, neurological manifestations, lactic acidosis, hypoglycemia, and mtDNA depletion in liver tissue. We report a hepatocerebral variant of mitochondrial DNA depletion syndrome in a neonate who presented with septic shock picture, hypoglycemia, jaundice, hypotonia, and rotatory nystagmus. Family history was significant for consanguinity and a brother who died at the age of 4 months. Investigations showed mild liver function derangement contrasting with severe coagulopathy, hyperlactatemia, and generalized aminoaciduria. The brain MRI was normal. Next generation sequencing (NGS) panel identified a MPV17 gene missense homozygous pathogenic variant. The infant expired at the age of 2 weeks with refractory ascites. This case illustrates a challenging diagnosis causing liver failure and death in neonatal period. Genetic testing of mitochondrial DNA depletion syndromes should be a part of liver failure workup in addition to other treatable disorders presenting with encephalo-hepatopathy in infancy.
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Affiliation(s)
- Razan Abduljalil
- Department of Pediatrics, King Hamad University Hospital, Manama, Bahrain
| | - Hadhami Ben Turkia
- Department of Pediatrics, King Hamad University Hospital, Manama, Bahrain
| | - Aysha Fakhroo
- Department of Pediatrics, King Hamad University Hospital, Manama, Bahrain
| | - Cristina Skrypnyk
- Department of Molecular Medicine, Al‐Jawhara Centre for Molecular Medicine, Arabian Gulf University, Manama, Bahrain
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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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Gong K, Xu X, Yao J, Ye S, Yu X, Tu H, Lan Y, Fan YC, Shi Y. Acute hepatitis of unknown origin in children: A combination of factors. Front Pharmacol 2022; 13:1056385. [PMID: 36438816 PMCID: PMC9698116 DOI: 10.3389/fphar.2022.1056385] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 10/31/2022] [Indexed: 08/16/2023] Open
Abstract
On 5 April 2022, the World Health Organization was notified of 10 cases of severe acute hepatitis of unknown etiology in children under 10 years of age in the United Kingdom. Although the exact cause of a proportion of pediatric acute hepatitis and acute liver failure cases was unclear, the above event has caused widespread concern worldwide. As of 14 September 2022, approximately 1,296 probable cases of acute hepatitis of unknown etiology have been reported from 37 countries/regions, of which approximately 55 required or received liver transplantation and 29 died. Although the etiology of acute hepatitis of unknown origin in children remains unclear, many hypotheses have been proposed about the disease. Instead of individual factors such as "adenovirus infection," "SARS-CoV-2 related," and "Adeno-associated virus 2 with helper virus coinfection," it is more likely due to a combination of factors. Accordingly, there is an urgent need for more data and research to clarify the disease etiology. This review aims to provide a historical perspective of acute hepatitis of unknown etiology in children in the past decades and summarize the current hypothesis and evidence on this emerging disease.
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Affiliation(s)
- Kai Gong
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Xianbin Xu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Junjie Yao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Shaoheng Ye
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Xia Yu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Huilan Tu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Yan Lan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Yu-chen Fan
- Department of Hepatology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Yu Shi
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
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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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10
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Tsuge M, Kodera A, Sumitomo H, Araki T, Yoshida R, Yasui K, Sato H, Washio Y, Washio K, Shigehara K, Yashiro M, Yagi T, Tsukahara H. Neonatal hemochromatosis with εγδβ-thalassemia: a case report and analysis of serum iron regulators. BMC Pediatr 2022; 22:622. [PMID: 36309641 PMCID: PMC9617355 DOI: 10.1186/s12887-022-03706-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 10/24/2022] [Indexed: 12/05/2022] Open
Abstract
Background Neonatal hemochromatosis causes acute liver failure during the neonatal period, mostly due to gestational alloimmune liver disease (GALD). Thalassemia causes hemolytic anemia and ineffective erythropoiesis due to mutations in the globin gene. Although neonatal hemochromatosis and thalassemia have completely different causes, the coexistence of these diseases can synergistically exacerbate iron overload. We report that a newborn with εγδβ-thalassemia developed neonatal hemochromatosis, which did not respond to iron chelators and rapidly worsened, requiring living-donor liver transplantation. Case presentation A 1-day-old Japanese boy with hemolytic anemia and targeted red blood cells was diagnosed with εγδβ-thalassemia by genetic testing, and required frequent red blood cell transfusions. At 2 months after birth, exacerbation of jaundice, grayish-white stool, and high serum ferritin levels were observed, and liver biopsy showed iron deposition in hepatocytes and Kupffer cells. Magnetic resonance imaging scans showed findings suggestive of iron deposits in the liver, spleen, pancreas, and bone marrow. The total amount of red blood cell transfusions administered did not meet the criteria for post-transfusion iron overload. Administration of an iron-chelating agent was initiated, but iron overload rapidly progressed to liver failure without improvement in jaundice and liver damage. He underwent living-donor liver transplantation from his mother, after which iron overload disappeared, and no recurrence of iron overload was observed. Immunohistochemical staining for C5b-9 in the liver was positive. Serum hepcidin levels were low and serum growth differentiation factor-15 levels were high prior to living-donor liver transplantation. Conclusions We reported that an infant with εγδβ-thalassemia developed NH due to GALD, and that coexistence of ineffective erythropoiesis in addition to erythrocyte transfusions may have exacerbated iron overload. Low serum hepcidin levels, in this case, might have been caused by decreased hepcidin production arising from fetal liver damage due to neonatal hemochromatosis and increased hepcidin-inhibiting hematopoietic mediators due to the ineffective hematopoiesis observed in thalassemia. Supplementary Information The online version contains supplementary material available at 10.1186/s12887-022-03706-3.
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11
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Wang LC, Tsai HP, Chen SH, Wang SM. Therapeutics for fulminant hepatitis caused by enteroviruses in neonates. Front Pharmacol 2022; 13:1014823. [PMID: 36339581 PMCID: PMC9630557 DOI: 10.3389/fphar.2022.1014823] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Accepted: 10/04/2022] [Indexed: 01/01/2025] Open
Abstract
Neonatal infection with nonpolio enteroviruses (EVs) causes nonspecific febrile illnesses and even life-threatening multiorgan failure. Hepatitis, which often results in hepatic necrosis followed by disseminated intravascular coagulopathy, is one of the most severe and frequent fatal neonatal EV infection complications. Coxsackievirus B (CVB) 1-5 and many echoviruses have been most commonly identified. Neonatal EV infection treatment has usually involved initial supportive care. Studies for CVB and echovirus infection treatments were developed for more than thirty years. Intravenous immunoglobulin and pleconaril therapy was performed in some clinical trials. Additionally, other studies demonstrated antiviral and/or anti-inflammatory pathogenesis mechanisms of neonatal EV hepatitis in in vitro or in vivo models. These treatments represented promising options for the clinical practice of neonatal EV hepatitis. However, further investigation is needed to elucidate the whole therapeutic potential and safety problems.
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Affiliation(s)
- Li-Chiu Wang
- School of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Huey-Pin Tsai
- Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Shun-Hua Chen
- Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan
| | - Shih-Min Wang
- Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan
- Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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12
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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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13
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Coilly A, Samuel D. Paediatric acute liver failure: Confirm the outbreak, find the cause and explore the mechanisms. United European Gastroenterol J 2022; 10:789-790. [PMID: 36094884 PMCID: PMC9557952 DOI: 10.1002/ueg2.12306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Affiliation(s)
- Audrey Coilly
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France.,University Paris-Saclay, UMR-S 1193, Villejuif, France.,Inserm, Unité 1193, Villejuif, France.,Hepatinov, Villejuif, France
| | - Didier Samuel
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France.,University Paris-Saclay, UMR-S 1193, Villejuif, France.,Inserm, Unité 1193, Villejuif, France.,Hepatinov, Villejuif, France
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14
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Valentine SL, Cholette JM, Goobie SM. Transfusion Strategies for Hemostatic Blood Products in Critically Ill Children: A Narrative Review and Update on Expert Consensus Guidelines. Anesth Analg 2022; 135:545-557. [PMID: 35977364 DOI: 10.1213/ane.0000000000006149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Critically ill children commonly receive coagulant products (plasma and/or platelet transfusions) to prevent or treat hemorrhage or correct coagulopathy. Unique aspects of pediatric developmental physiology, and the complex pathophysiology of critical illness must be considered and balanced against known transfusion risks. Transfusion practices vary greatly within and across institutions, and high-quality evidence is needed to support transfusion decision-making. We present recent recommendations and expert consensus statements to direct clinicians in the decision to transfuse or not to transfuse hemostatic blood products, including plasma, platelets, cryoprecipitate, and recombinant products to critically ill children.
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Affiliation(s)
- Stacey L Valentine
- From the Department of Pediatrics, Division of Pediatric Critical Care Medicine, University of Massachusetts Medical School, Worcester, Massachusetts
| | - Jill M Cholette
- Department of Pediatrics, Divisions of Critical Care Medicine and Cardiology, University of Rochester Golisano Children's Hospital, Rochester, New York
| | - Susan M Goobie
- Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts
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15
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Abstract
Mitochondrial hepatopathies are a subset of mitochondrial diseases defined by primary dysfunction of hepatocyte mitochondria leading to a phenotype of hepatocyte cell injury, steatosis, or liver failure. Increasingly, the diagnosis is established by new sequencing approaches that combine analysis of both nuclear DNA and mitochondrial DNA and allow for timely diagnosis in most patients. Despite advances in diagnostics, for most affected children their disorders are relentlessly progressive, and result in substantial morbidity and mortality. Treatment remains mainly supportive; however, novel therapeutics and a more definitive role for liver transplantation hold promise for affected children.
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Affiliation(s)
- Mary Ayers
- University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, 4401 Penn Avenue, Pittsburgh, PA 15224, USA
| | - Simon P Horslen
- University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, 4401 Penn Avenue, Pittsburgh, PA 15224, USA
| | - Anna María Gómez
- University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, 4401 Penn Avenue, Pittsburgh, PA 15224, USA
| | - James E Squires
- University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
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16
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Kulkarni SS, Goss CW, Khan AS, Nadler ML, Stoll JM, Doyle MB, Turmelle YP, Rudnick DA. Outcomes Analyses of Pediatric Acute Liver Failure Subjects Listed for Liver Transplantation. J Pediatr Gastroenterol Nutr 2022; 74:750-756. [PMID: 35442235 PMCID: PMC9296584 DOI: 10.1097/mpg.0000000000003448] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND We characterized recent outcomes in US pediatric acute liver failure (PALF) subjects listed for liver transplantation (LT) using the Scientific Registry of Transplant Recipients (SRTR) database. METHODS Pediatric subjects listed for LT from 2002 to 2015 were assigned to the "PALF" group based on status 1/1A listing, INR >2, no hepatic artery thrombosis, and no primary graft nonfunction (N = 397). Subjects were assigned to the "non-PALF" group if listed with any status other than 1/1A (N = 4509). RESULTS The PALF group had more infants <3 months of age and males at listing for LT compared to the non-PALF group. Two-thirds of PALF subjects had an indeterminate etiology. LT waitlist survival was significantly worse in the PALF group compared to the non-PALF group. Likelihood of removal from the LT waitlist for being "too sick" was higher, while that of removal for "spontaneous recovery" was lower in PALF subjects. Post-LT short-term (30 days) and long-term (60 months) outcomes were also significantly worse in PALF versus non-PALF subjects. PALF subjects who underwent living-donor-liver-transplant (LDLT) had similar LT waitlist times and post-LT survival compared to those undergoing deceased-donor-liver-transplant (DDLT). Over the study period, we observed a decreased number of liver transplants, and increase in LT waitlist- and short-term post-LT-survival in PALF subjects. CONCLUSION LT waitlist and post-LT outcomes are worse in PALF subjects compared to non-PALF subjects. PALF subjects who undergo LDLT have similar waitlist times and post-LT outcomes compared to those undergoing DDLT.
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Affiliation(s)
- Sakil S. Kulkarni
- Department of Pediatrics, Washington University in St. Louis, St. Louis Children’s Hospital, St. Louis, MO, U.S.A
| | - Charles W. Goss
- Department of Biostatistics, Washington University in St. Louis, St. Louis, MO, U.S.A
| | - Adeel S. Khan
- Department of Surgery, Washington University in St. Louis, Barnes Jewish Hospital, St. Louis, MO, U.S.A
| | - Michelle L. Nadler
- Department of Pediatrics, Washington University in St. Louis, St. Louis Children’s Hospital, St. Louis, MO, U.S.A
| | - Janis M. Stoll
- Department of Pediatrics, Washington University in St. Louis, St. Louis Children’s Hospital, St. Louis, MO, U.S.A
| | - Maria B. Doyle
- Department of Surgery, Washington University in St. Louis, Barnes Jewish Hospital, St. Louis, MO, U.S.A
| | - Yumirle P. Turmelle
- Department of Pediatrics, Washington University in St. Louis, St. Louis Children’s Hospital, St. Louis, MO, U.S.A
| | - David A. Rudnick
- Department of Pediatrics, Washington University in St. Louis, St. Louis Children’s Hospital, St. Louis, MO, U.S.A
- Department of Developmental Biology, Washington University in St. Louis, St. Louis Children’s Hospital, St. Louis, MO, U.S.A
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17
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18
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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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19
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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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20
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Gopan A, Sarma MS. Mitochondrial hepatopathy: Respiratory chain disorders- ‘breathing in and out of the liver’. World J Hepatol 2021; 13:1707-1726. [PMID: 34904040 PMCID: PMC8637684 DOI: 10.4254/wjh.v13.i11.1707] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 06/30/2021] [Accepted: 08/18/2021] [Indexed: 02/06/2023] Open
Abstract
Mitochondria, the powerhouse of a cell, are closely linked to the pathophysiology of various common as well as not so uncommon disorders of the liver and beyond. Evolution supports a prokaryotic descent, and, unsurprisingly, the organelle is worthy of being labeled an organism in itself. Since highly metabolically active organs require a continuous feed of energy, any dysfunction in the structure and function of mitochondria can have variable impact, with the worse end of the spectrum producing catastrophic consequences with a multisystem predisposition. Though categorized a hepatopathy, mitochondrial respiratory chain defects are not limited to the liver in time and space. The liver involvement is also variable in clinical presentation as well as in age of onset, from acute liver failure, cholestasis, or chronic liver disease. Other organs like eye, muscle, central and peripheral nervous system, gastrointestinal tract, hematological, endocrine, and renal systems are also variably involved. Diagnosis hinges on recognition of subtle clinical clues, screening metabolic investigations, evaluation of the extra-hepatic involvement, and role of genetics and tissue diagnosis. Treatment is aimed at both circumventing the acute metabolic crisis and long-term management including nutritional rehabilitation. This review lists and discusses the burden of mitochondrial respiratory chain defects, including various settings when to suspect, their evolution with time, including certain specific disorders, their tiered evaluation with diagnostic algorithms, management dilemmas, role of liver transplantation, and the future research tools.
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Affiliation(s)
- Amrit Gopan
- Department of Gastroenterology, Seth G.S Medical College and K.E.M Hospital, Mumbai 400012, India
| | - Moinak Sen Sarma
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
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21
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Lemoine CP, Wall A, Testa G, Superina R. Ethical considerations in pediatric solid organ transplantation. Semin Pediatr Surg 2021; 30:151104. [PMID: 34635280 DOI: 10.1016/j.sempedsurg.2021.151104] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Solid organ transplantation is now an accepted therapeutic modality for children and teenagers suffering from a wide variety of complex medical conditions. Unfortunately, patients continue to die while on the organ waiting list as there remains an imbalance between the number of recipients listed for transplantation and the number of donors available. The organ allocation process continues to generate ethical questions and debates. In this publication, we discuss some of the most frequently reported ethical matters in the field of pediatric solid organ transplantation.
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Affiliation(s)
- Caroline P Lemoine
- Division of Transplant and Advanced Hepatobiliary Surgery, Ann & Robert H Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, 225 E Chicago avenue Box 57, Chicago, IL 60611, United States
| | - Anji Wall
- Annette C. And Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX, United States
| | - Giuliano Testa
- Annette C. And Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX, United States
| | - Riccardo Superina
- Division of Transplant and Advanced Hepatobiliary Surgery, Ann & Robert H Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, 225 E Chicago avenue Box 57, Chicago, IL 60611, United States.
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22
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Applying an Age-specific Definition to Better Characterize Etiologies and Outcomes in Neonatal Acute Liver Failure. J Pediatr Gastroenterol Nutr 2021; 73:80-85. [PMID: 33633086 DOI: 10.1097/mpg.0000000000003103] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVE Neonatal acute liver failure (ALF) is a rare disease with high mortality for which no standard age-specific definition exists. To advance the understanding of neonatal ALF, we characterize the etiology, presenting features, treatment, and outcomes in infants within 1 month of life. METHODS We performed a single-center 11-year retrospective chart review of neonates ≤30 days of life with ALF as defined by an INR of ≥2.0. Comparisons were made by etiology and survival with native liver (SNL). Estimated survival was performed using the Kaplan-Meier method. RESULTS Forty-three patients met inclusion criteria for neonatal ALF. Etiologies included viral infection (23%), gestational alloimmune liver disease with neonatal hemochromatosis (GALD-NH) (21%), cardiac-associated ischemia (16%), other ischemia (14%), genetic etiologies (9%), Trisomy 21-associated myelodysplasia (TAM) (7%), hemophagocytic lymphohistiocytosis (HLH) (2%), and not identified (7%). Infants with viral etiologies had the highest alanine aminotransferase (ALT) at presentation (1179 IU/L, interquartile range [IQR] 683-1585 IU/L) in contrast to low levels in GALD-NH (23 IU/L, IQR 18-64 IU/L). Across all etiologies, only 33% were alive at 1 year. Overall median survival was 74 days; 17 days for viral infection and 74 days for GALD-NH. Among laboratory values at presentation, alpha-fetoprotein (AFP) was significantly higher in patients that survived with their native liver (P = 0.04). CONCLUSIONS Overall, outcome for neonatal ALF is poor. Although initial laboratory values can differentiate viral infection or GALD-NH, further studies are needed to identify laboratory parameters that predict SNL by etiology to ultimately improve patient outcomes.
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Kulkarni S, Chi L, Goss C, Lian Q, Nadler M, Stoll J, Doyle M, Turmelle Y, Khan A. Random forest analysis identifies change in serum creatinine and listing status as the most predictive variables of an outcome for young children on liver transplant waitlist. Pediatr Transplant 2021; 25:e13932. [PMID: 33232568 PMCID: PMC8058171 DOI: 10.1111/petr.13932] [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: 07/04/2020] [Revised: 10/09/2020] [Accepted: 11/09/2020] [Indexed: 11/27/2022]
Abstract
Young children listed for liver transplant have high waitlist mortality (WL), which is not fully predicted by the PELD score. SRTR database was queried for children < 2 years listed for initial LT during 2002-17 (n = 4973). Subjects were divided into three outcome groups: bad (death or removal for too sick to transplant), good (spontaneous improvement), and transplant. Demographic, clinical, listing history, and laboratory variables at the time of listing (baseline variables), and changes in variables between listing and prior to outcome (trajectory variables) were analyzed using random forest (RF) analysis. 81.5% candidates underwent LT, and 12.3% had bad outcome. RF model including both baseline and trajectory variables improved prediction compared to model using baseline variables alone. RF analyses identified change in serum creatinine and listing status as the most predictive variables. 80% of subjects listed with a PELD score at time of listing and outcome underwent LT, while ~70% of subjects in both bad and good outcome groups were listed with either Status 1 (A or B) prior to an outcome, regardless of initial listing status. Increase in creatinine on LT waitlist was predictive of bad outcome. Longer time spent on WL was predictive of good outcome. Subjects with biliary atresia, liver tumors, and metabolic disease had LT rate >85%, while >20% of subjects with acute liver failure had a bad outcome. Change in creatinine, listing status, need for RRT, time spent on LT waitlist, and diagnoses were the most predictive variables.
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Affiliation(s)
- Sakil Kulkarni
- Department of Pediatrics, Washington University in St. Louis, St. Louis Children’s Hospital, St. Louis, MO, U.S.A
| | - Lisa Chi
- Department of Pediatrics, Washington University in St. Louis, St. Louis Children’s Hospital, St. Louis, MO, U.S.A
| | - Charles Goss
- Division of Biostatistics, Washington University in St. Louis, St. Louis, MO, U.S.A
| | - Qinghua Lian
- Division of Biostatistics, Washington University in St. Louis, St. Louis, MO, U.S.A
| | - Michelle Nadler
- Department of Surgery, Washington University in St. Louis, Barnes Jewish Hospital, St. Louis, MO, U.S.A
| | - Janis Stoll
- Department of Pediatrics, Washington University in St. Louis, St. Louis Children’s Hospital, St. Louis, MO, U.S.A
| | - Maria Doyle
- Department of Surgery, Washington University in St. Louis, Barnes Jewish Hospital, St. Louis, MO, U.S.A
| | - Yumirle Turmelle
- Department of Pediatrics, Washington University in St. Louis, St. Louis Children’s Hospital, St. Louis, MO, U.S.A
| | - Adeel Khan
- Department of Surgery, Washington University in St. Louis, Barnes Jewish Hospital, St. Louis, MO, U.S.A
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24
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Karadağ N, Okbay Güneş A, Karatekin G. Acute liver failure in newborns. Turk Arch Pediatr 2021; 56:108-114. [PMID: 34286318 DOI: 10.5152/turkarchpediatr.2021.190205] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Accepted: 02/09/2020] [Indexed: 11/22/2022]
Abstract
Acute liver failure is a condition that is defined as a sudden, complete, or nearly complete loss of liver functions without any previous liver disease, usually accompanied by encephalopathy, which can be reversible, but with a mortality rate of 55-70%. Acute liver failure newborns is an acute liver failure in the first 28 days of life. The Pediatric Acute Liver Failure Working Group identified the presence of coagulopathy as the main finding for the identification of acute liver failure in childhood following vitamin K administration. Although the incidence of acute liver failure is reported to be 17/100 000 in all ages, its incidence is not known exactly in newborn and childhood. The most common cause of acute liver failure in the newborn period is the gestational alloimmune liver disease that was previously known as neonatal hemochromatosis. This is followed by viral infections, metabolic diseases, hemophagocytic lymphohistiocytosis, and other rare causes. In the neonatal period, acute liver failure is a rare condition with a high mortality rate. For this reason, the vital signs of the patients should be closely monitored and supportive treatments should be planned according to the follow-up and the etiology of the disease should be clarified urgently. In this process, acyclovir treatment until herpes simplex virus infection is excluded and lactose-free feeding until galactosemia is excluded are recommended as life-saving treatments. In the literature, since there is a limited number of studies related to neonatal acute liver failure, prospective studies investigating the factors affecting treatment and prognosis are needed.
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Affiliation(s)
- Nilgün Karadağ
- Department of Neonatal, University of Health Sciences, Zeynep Kamil Women's and Children's Hospital, İstanbul, Turkey
| | - Aslı Okbay Güneş
- Department of Neonatal, University of Health Sciences, Zeynep Kamil Women's and Children's Hospital, İstanbul, Turkey
| | - Güner Karatekin
- Department of Neonatal, University of Health Sciences, Zeynep Kamil Women's and Children's Hospital, İstanbul, Turkey
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25
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Acute liver failure due to DGUOK deficiency-is liver transplantation justified? Clin Res Hepatol Gastroenterol 2021; 45:101408. [PMID: 32278775 DOI: 10.1016/j.clinre.2020.02.018] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Revised: 02/27/2020] [Accepted: 02/27/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Deoxyguanosine kinase (DGUOK) deficiency is one of the causes of the hepatocerebral form of mitochondrial depletion syndrome (MDS). It is characterized by an early onset of liver failure with concomitant neurological deterioration. In the current literature, there are only few reports regarding long-term observation of children with DGUOK deficiency. Liver transplantation (LTx) is controversial due to extrahepatic involvement and unpredictable outcome. METHODS Five patients (2 boys) from 4 different families with hepatocerebral MDS associated with DGUOK mutations diagnosed with liver failure were treated in our hospital between 2010-2019. RESULTS In all children clinical symptoms developed within the first days of live and hypoglycemia (hypoketotic), conjugated hyperbilirubinemia (cholestasis), severe lactic acidosis, and coagulopathy were observed. Two neonates had low birth-weight for gestational age and failed to thrive. Mild neurological involvement as hypotonia was observed in all children. Three children died at the age of 2, 6 months and 6,5 months of age, respectively, due to end-stage liver failure. In one case, LTx was not considered, in two patients (sisters) parents did not agree to this procedure. LTx was subsequently performed in two patients at the age of 6 and 7 months, respectively, one from deceased, and one from living related donor, in both before the final confirmation of DGUOK mutations. One boy died 2 months after LTx due to post-LTx procedure-related complications; one is still alive with 3years of follow-up, with good liver function and mild neurological disturbances. The diagnosis of DGUOK deficiency was confirmed by biallelic DGUOK mutations detection. Equally, patients were compound heterozygotes (three cases) and homozygotes (two cases). Three known molecular variants, including regulatory substitutions (c.1A>G, c.3G>A) and in-frame insertion (c.813_814insTTT) were identified. CONCLUSIONS Prognosis in patients with DGUOK deficiency is generally poor. Based on a review of the literature and our experience liver transplantation in selected patients with DGUOK mutation does not appear to be contraindicated, especially in those without or with minimal neurologic abnormalities.
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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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27
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Anand AC, Nandi B, Acharya SK, Arora A, Babu S, Batra Y, Chawla YK, Chowdhury A, Chaoudhuri A, Eapen EC, Devarbhavi H, Dhiman RK, Datta Gupta S, Duseja A, Jothimani D, Kapoor D, Kar P, Khuroo MS, Kumar A, Madan K, Mallick B, Maiwall R, Mohan N, Nagral A, Nath P, Panigrahi SC, Pawar A, Philips CA, Prahraj D, Puri P, Rastogi A, Saraswat VA, Saigal S, Shalimar, Shukla A, Singh SP, Verghese T, Wadhawan M, The INASL Task-Force on Acute Liver Failure. Indian National Association for the Study of Liver Consensus Statement on Acute Liver Failure (Part-2): Management of Acute Liver Failure. J Clin Exp Hepatol 2020; 10:477-517. [PMID: 33029057 PMCID: PMC7527855 DOI: 10.1016/j.jceh.2020.04.011] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Accepted: 04/12/2020] [Indexed: 12/12/2022] Open
Abstract
Acute liver failure (ALF) is not an uncommon complication of a common disease such as acute hepatitis. Viral hepatitis followed by antituberculosis drug-induced hepatotoxicity are the commonest causes of ALF in India. Clinically, such patients present with appearance of jaundice, encephalopathy, and coagulopathy. Hepatic encephalopathy (HE) and cerebral edema are central and most important clinical event in the course of ALF, followed by superadded infections, and determine the outcome in these patients. The pathogenesis of encephalopathy and cerebral edema in ALF is unique and multifactorial. Ammonia plays a crucial role in the pathogenesis, and several therapies aim to correct this abnormality. The role of newer ammonia-lowering agents is still evolving. These patients are best managed at a tertiary care hospital with facility for liver transplantation (LT). Aggressive intensive medical management has been documented to salvage a substantial proportion of patients. In those with poor prognostic factors, LT is the only effective therapy that has been shown to improve survival. However, recognizing suitable patients with poor prognosis has remained a challenge. Close monitoring, early identification and treatment of complications, and couseling for transplant form the first-line approach to manage such patients. Recent research shows that use of dynamic prognostic models is better for selecting patients undergoing liver transplantation and timely transplant can save life of patients with ALF with poor prognostic factors.
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Key Words
- ACLF, Acute on Chronic liver Failure
- AKI, Acute kidney injury
- ALF, Acute Liver Failure
- ALFED score
- ALT, alanine transaminase
- AST, aspartate transaminase
- CNS, central nervous system
- CT, Computerized tomography
- HELLP, Hemolysis, elevated liver enzymes, and low platelets
- ICH, Intracrainial hypertension
- ICP, Intracrainial Pressure
- ICU, Intensive care unit
- INR, International normalised ratio
- LAD, Liver assist device
- LDLT, Living donor liver transplantation
- LT, Liver transplantation
- MAP, Mean arterial pressure
- MELD, model for end-stage liver disease
- MLD, Metabolic liver disease
- NAC, N-acetyl cysteine
- PALF, Pediatric ALF
- WD, Wilson's Disease
- acute liver failure
- artificial liver support
- liver transplantation
- plasmapheresis
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Affiliation(s)
- Anil C. Anand
- Department of Gastroenterology, Kaliga Institute of Medical Sciences, Bhubaneswar, 751024, India
| | - Bhaskar Nandi
- Department of Gastroenterology, Sarvodaya Hospital and Research Centre, Faridababd, Haryana, India
| | - Subrat K. Acharya
- Department of Gastroenterology and Hepatology, KIIT University, Patia, Bhubaneswar, Odisha, 751 024, India
| | - Anil Arora
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110 060, India
| | - Sethu Babu
- Department of Gastroenterology, Krishna Institute of Medical Sciences, Hyderabad, 500003, India
| | - Yogesh Batra
- Department of Gastroenterology, Indraprastha Apollo Hospital, SaritaVihar, New Delhi, 110 076, India
| | - Yogesh K. Chawla
- Department of Gastroenterology, Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, Odisha, 751 024, India
| | - Abhijit Chowdhury
- Department of Hepatology, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education & Research, Kolkata, 700020, India
| | - Ashok Chaoudhuri
- Hepatology and Liver Transplant, Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, New Delhi, India
| | - Eapen C. Eapen
- Department of Hepatology, Christian Medical College, Vellore, India
| | - Harshad Devarbhavi
- Department of Gastroenterology and Hepatology, St. John's Medical College Hospital, Bangalore, 560034, India
| | - Radha K. Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Siddhartha Datta Gupta
- Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Dinesh Jothimani
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Chrompet, Chennai, 600044, India
| | | | - Premashish Kar
- Department of Gastroenterology and Hepatology, Max Super Speciality Hospital, Vaishali, Ghaziabad, Uttar Pradesh, 201 012, India
| | - Mohamad S. Khuroo
- Department of Gastroenterology, Dr Khuroo’ s Medical Clinic, Srinagar, Kashmir, India
| | - Ashish Kumar
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110 060, India
| | - Kaushal Madan
- Gastroenterology and Hepatology, Max Smart Super Specialty Hospital, Saket, New Delhi, India
| | - Bipadabhanjan Mallick
- Department of Gastroenterology, Kalinga Institute of Medical Sciences, Bhubaneswar, 751024, India
| | - Rakhi Maiwall
- Hepatology Incharge Liver Intensive Care, Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, New Delhi, India
| | - Neelam Mohan
- Department of Pediatric Gastroenterology, Hepatology & Liver Transplantation, Medanta – the MedicityHospital, Sector – 38, Gurgaon, Haryana, India
| | - Aabha Nagral
- Department of Gastroenterology, Apollo and Jaslok Hospital & Research Centre, 15, Dr Deshmukh Marg, Pedder Road, Mumbai, Maharashtra, 400 026, India
| | - Preetam Nath
- Department of Gastroenterology, Kaliga Institute of Medical Sciences, Bhubaneswar, 751024, India
| | - Sarat C. Panigrahi
- Department of Gastroenterology, Kaliga Institute of Medical Sciences, Bhubaneswar, 751024, India
| | - Ankush Pawar
- Liver & Digestive Diseases Institute, Fortis Escorts Hospital, Okhla Road, New Delhi, 110 025, India
| | - Cyriac A. Philips
- The Liver Unit and Monarch Liver Lab, Cochin Gastroenterology Group, Ernakulam Medical Centre, Kochi 682028, Kerala, India
| | - Dibyalochan Prahraj
- Department of Gastroenterology, Kaliga Institute of Medical Sciences, Bhubaneswar, 751024, India
| | - Pankaj Puri
- Department of Hepatology and Gastroenterology, Fortis Escorts Liver & Digestive Diseases Institute (FELDI), Fortis Escorts Hospital, Delhi, India
| | - Amit Rastogi
- Department of Liver Transplantation, Medanta – the MedicityHospital, Sector – 38, Gurgaon, Haryana, India
| | - Vivek A. Saraswat
- Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raibareli Road, Lucknow, Uttar Pradesh, 226 014, India
| | - Sanjiv Saigal
- Department of Hepatology, Department of Liver Transplantation, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 29, India
| | - Akash Shukla
- Department of Gastroenterology, LTM Medical College & Sion Hospital, India
| | - Shivaram P. Singh
- Department of Gastroenterology, SCB Medical College, Dock Road, Manglabag, Cuttack, Odisha, 753 007, India
| | - Thomas Verghese
- Department of Gastroenterology, Government Medical College, Kozikhode, India
| | - Manav Wadhawan
- Institute of Liver & Digestive Diseases and Head of Hepatology & Liver Transplant (Medicine), BLK Super Speciality Hospital, Delhi, India
| | - The INASL Task-Force on Acute Liver Failure
- Department of Gastroenterology, Kaliga Institute of Medical Sciences, Bhubaneswar, 751024, India
- Department of Gastroenterology, Sarvodaya Hospital and Research Centre, Faridababd, Haryana, India
- Department of Gastroenterology and Hepatology, KIIT University, Patia, Bhubaneswar, Odisha, 751 024, India
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110 060, India
- Department of Gastroenterology, Krishna Institute of Medical Sciences, Hyderabad, 500003, India
- Department of Gastroenterology, Indraprastha Apollo Hospital, SaritaVihar, New Delhi, 110 076, India
- Department of Gastroenterology, Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, Odisha, 751 024, India
- Department of Hepatology, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education & Research, Kolkata, 700020, India
- Hepatology and Liver Transplant, Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, New Delhi, India
- Department of Hepatology, Christian Medical College, Vellore, India
- Department of Gastroenterology and Hepatology, St. John's Medical College Hospital, Bangalore, 560034, India
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
- Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Chrompet, Chennai, 600044, India
- Gleneagles Global Hospitals, Hyderabad, Telangana, India
- Department of Gastroenterology and Hepatology, Max Super Speciality Hospital, Vaishali, Ghaziabad, Uttar Pradesh, 201 012, India
- Department of Gastroenterology, Dr Khuroo’ s Medical Clinic, Srinagar, Kashmir, India
- Gastroenterology and Hepatology, Max Smart Super Specialty Hospital, Saket, New Delhi, India
- Department of Gastroenterology, Kalinga Institute of Medical Sciences, Bhubaneswar, 751024, India
- Hepatology Incharge Liver Intensive Care, Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, New Delhi, India
- Department of Pediatric Gastroenterology, Hepatology & Liver Transplantation, Medanta – the MedicityHospital, Sector – 38, Gurgaon, Haryana, India
- Department of Gastroenterology, Apollo and Jaslok Hospital & Research Centre, 15, Dr Deshmukh Marg, Pedder Road, Mumbai, Maharashtra, 400 026, India
- Liver & Digestive Diseases Institute, Fortis Escorts Hospital, Okhla Road, New Delhi, 110 025, India
- The Liver Unit and Monarch Liver Lab, Cochin Gastroenterology Group, Ernakulam Medical Centre, Kochi 682028, Kerala, India
- Department of Hepatology and Gastroenterology, Fortis Escorts Liver & Digestive Diseases Institute (FELDI), Fortis Escorts Hospital, Delhi, India
- Department of Liver Transplantation, Medanta – the MedicityHospital, Sector – 38, Gurgaon, Haryana, India
- Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raibareli Road, Lucknow, Uttar Pradesh, 226 014, India
- Department of Hepatology, Department of Liver Transplantation, India
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 29, India
- Department of Gastroenterology, LTM Medical College & Sion Hospital, India
- Department of Gastroenterology, SCB Medical College, Dock Road, Manglabag, Cuttack, Odisha, 753 007, India
- Department of Gastroenterology, Government Medical College, Kozikhode, India
- Institute of Liver & Digestive Diseases and Head of Hepatology & Liver Transplant (Medicine), BLK Super Speciality Hospital, Delhi, India
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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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29
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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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30
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Güven B, Sağ E, Karagüzel G, Çakır M. Acute liver failure associated with metabolic diseases: A 10-year single-center experience. Pediatr Int 2020; 62:609-614. [PMID: 32170978 DOI: 10.1111/ped.14230] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Revised: 02/01/2020] [Accepted: 03/11/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Acute liver failure (ALF) is a rare multisystemic disease occurring in individuals with no history of liver disease, characterized by coagulopathy and / or hepatic encephalopathy secondary to acute liver injury. It is mostly caused by viral infections, drug intoxication, and metabolic diseases (MD), and can also have an indeterminate etiology. In this study, we aimed to evaluate the demographic and clinical characteristics and clinical outcomes of the patients that presented to our clinic with MD-associated ALF. METHODS This retrospective study reviewed age, gender, parental consanguinity, family history, presence of encephalopathy, laboratory parameters, and clinical outcomes of the patients that presented to our clinic between January 2009 and January 2019. Patients with MD-associated ALF were compared with patients in whom ALF was associated with other etiologies. RESULTS The study included 39 patients (53.8% boys; mean age + SD 6.13 ± 1.43 years). The total and direct bilirubin, international normalized ratio, and ammoniac levels were significantly higher in patients with MD than in the others (P < 0.05). Moreover, the incidences of hypoglycemia, death of a sibling and / or a family history of liver disease were also higher in patients with MD than in the others (P < 0.05). On the other hand, alanine aminotransferase (ALT) levels were significantly higher in patients with other etiologies. CONCLUSIONS Metabolic diseases should be kept in mind in patients with a history of parental consanguinity and a positive family history of liver disease along with less increased alanine aminotransferase than expected, and increased bilirubin, international normalized ratio, and ammoniac levels and hypoglycemia. As the number of these parameters increases, the chance of diagnosis increases.
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Affiliation(s)
- Burcu Güven
- Department of Pediatric Gastroenterology, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey
| | - Elif Sağ
- Department of Pediatric Gastroenterology, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey
| | - Gülay Karagüzel
- Department of Pediatric Endocrinology, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey
| | - Murat Çakır
- Department of Pediatric Gastroenterology, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey
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31
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Abstract
Neonatal acute liver failure (NALF) is a rare disease with a few known primary causes: gestational alloimmune liver disease (GALD), viral infections, metabolic diseases, and ischemic injury. Many cases still do not have a known cause. Laboratory evaluation may suggest a diagnosis. Most of the known causes have disease-specific treatments that improve outcomes. Survival is improving with better knowledge about and treatment options for GALD; however, overall mortality for NALF is still 24%. Liver transplant remains an important option for neonates with an indeterminate cause of NALF and those who do not respond to established treatments.
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Affiliation(s)
- Catherine Larson-Nath
- Pediatric Gastroenterology, Hepatology & Nutrition, University of Minnesota, 2450 Riverside Avenue, Minneapolis, MN 55454, USA
| | - Bernadette E Vitola
- Pediatric Gastroenterology, Hepatology & Nutrition, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
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32
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Abstract
OBJECTIVES The published data on early infantile liver failure (EILF) are scarce and limited to Caucasians. We conducted this study to describe the etiology and outcome of EILF among Arabs and identify prognostic factors. METHODS We retrospectively reviewed our database of 524 infants presenting with liver impairment from 2008 to 2018, and identified cases of EILF defined as presence of biochemical pattern of liver disease and INR ≥2 (unresponsive to vitamin K) with onset before 3 months of life. Primary outcomes included death or liver transplantation (LT) (poor outcome group) and survival with native liver (good outcome group). RESULTS Forty-two cases of EILF (22 girls) were identified (8%). The etiology was indeterminate in 14 (33.3%) and established in 27 (64.3%): galactosemia (7 cases, 16.6%), tyrosinemia (5, 12%), neonatal hemochromatosis (NH), and hemophagocytic lymphohistiocytosis (HLH) (4 each, 9.5%]) mitochondrial hepatopathy (3, 7%), and miscellaneous (5, 12%). LF resolved in 15 cases (35.7%), either spontaneously or in response to specific therapy, 23 (54.7%) died, and 4 underwent LT (9.5%). ROC analysis for the best cut-off value of serum total bilirubin for prediction of study outcomes was 120 μmol/L (sensitivity 81.5%, specificity 80%). Among the diagnostic groups, galactosemia and tyrosinemia predicted good outcome, whereas the idiopathic diagnosis predicted poor outcome (OR = 13). CONCLUSIONS Similar to Western countries, galactosemia, tyrosinemia, NH, HLH, and mitochondrial hepatopathy are the main players in EILF in Saudi Arabia. Galactosemia and tyrosinemia predict good prognosis and idiopathic diagnosis predicts poor prognosis.
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Hunt A, Tasker RC, Deep A. Neurocritical care monitoring of encephalopathic children with acute liver failure: A systematic review. Pediatr Transplant 2019; 23:e13556. [PMID: 31407855 DOI: 10.1111/petr.13556] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Revised: 06/14/2019] [Accepted: 07/04/2019] [Indexed: 12/15/2022]
Abstract
Research on non-invasive neuromonitoring specific to PALF is limited. This systematic review identifies and synthesis the existing literature on non-invasive approaches to monitoring for neurological sequelae in patients with PALF. A series of literature searches were performed to identify all publications pertaining to five different non-invasive neuromonitoring modalities, in line with PRISMA guidelines. Each modality was selected on the basis of its potential for direct or indirect measurement of cerebral perfusion; studies on electroencephalographic monitoring were therefore not sought. Data were recorded on study design, patient population, comparator groups, and outcomes. A preponderance of observational studies was observed, most with a small sample size. Few incorporated direct comparisons of different modalities; in particular, comparison to invasive intracranial pressure monitoring was largely lacking. The integration of current evidence is considered in the context of the clinically significant distinctions between pediatric and adult ALF, as well as the implications for planning of future investigations to best support the evidence-based clinical care of these patients.
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Affiliation(s)
- Adam Hunt
- University College Hospital, London, UK
| | - Robert C Tasker
- Harvard Medical School, Chair in Neurocritical Care, Boston Children's Hospital, Boston, MA
| | - Akash Deep
- Paediatric Intensive Care, King's College Hospital, London, UK
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Yamamoto H, Khorsandi SE, Cortes‐Cerisuelo M, Kawano Y, Dhawan A, McCall J, Vilca‐Melendez H, Rela M, Heaton N. Outcomes of Liver Transplantation in Small Infants. Liver Transpl 2019; 25:1561-1570. [PMID: 31379050 PMCID: PMC6856963 DOI: 10.1002/lt.25619] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Accepted: 07/14/2019] [Indexed: 12/12/2022]
Abstract
Liver transplantation (LT) for small infants remains challenging because of the demands related to graft selection, surgical technique, and perioperative management. The aim of this study was to evaluate the short-term and longterm outcomes of LT regarding vascular/biliary complications, renal function, growth, and patient/graft survival in infants ≤3 months compared with those of an age between >3 and 6 months at a single transplant center. A total of 64 infants ≤6 months underwent LT and were divided into 2 groups according to age at LT: those of age ≤3 months (range, 6-118 days; XS group, n = 37) and those of age >3 to ≤6 months (range, 124-179 days; S group, n = 27) between 1989 and 2014. Acute liver failure was the main indication for LT in the XS group (n = 31, 84%) versus S (n = 7, 26%). The overall incidence of hepatic artery thrombosis and portal vein thrombosis/stricture were 5.4% and 10.8% in the XS group and 7.4% and 11.1% in the S group, respectively (not significant). The overall incidence of biliary stricture and leakage were 5.4% and 2.7% in the XS group and 3.7% and 3.7% in the S group, respectively (not significant). There was no significant difference between the 2 groups in terms of renal function. No significant difference was found between the 2 groups for each year after LT in terms of height and weight z score. The 1-, 5-, and 10-year patient survival rates were 70.3%, 70.3%, and 70.3% in the XS group compared with 92.6%, 88.9%, and 88.9% in the S group, respectively (not significant). In conclusion, LT for smaller infants has acceptable outcomes despite the challenges of surgical technique, including vascular reconstruction and graft preparation, and perioperative management.
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Affiliation(s)
- Hidekazu Yamamoto
- Liver Transplantation, Institute of Liver StudiesKing’s College HospitalLondonUnited Kingdom
| | - Shirin E. Khorsandi
- Liver Transplantation, Institute of Liver StudiesKing’s College HospitalLondonUnited Kingdom
| | - Miriam Cortes‐Cerisuelo
- Liver Transplantation, Institute of Liver StudiesKing’s College HospitalLondonUnited Kingdom
| | - Yoichi Kawano
- Liver Transplantation, Institute of Liver StudiesKing’s College HospitalLondonUnited Kingdom
| | - Anil Dhawan
- Liver Transplantation, Institute of Liver StudiesKing’s College HospitalLondonUnited Kingdom
| | - John McCall
- Liver Transplantation, Institute of Liver StudiesKing’s College HospitalLondonUnited Kingdom
| | - Hector Vilca‐Melendez
- Liver Transplantation, Institute of Liver StudiesKing’s College HospitalLondonUnited Kingdom
| | - Mohamed Rela
- Liver Transplantation, Institute of Liver StudiesKing’s College HospitalLondonUnited Kingdom
| | - Nigel Heaton
- Liver Transplantation, Institute of Liver StudiesKing’s College HospitalLondonUnited Kingdom
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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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Warrillow S, Bailey M, Pilcher D, Kazemi A, McArthur C, Young P, Bellomo R. Characteristics and outcomes of patients with acute liver failure admitted to Australian and New Zealand intensive care units. Intern Med J 2019; 49:874-885. [PMID: 30479057 DOI: 10.1111/imj.14167] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2018] [Revised: 11/20/2018] [Accepted: 11/20/2018] [Indexed: 12/22/2022]
Abstract
BACKGROUND Knowledge about patients with acute liver failure (ALF) in Australia and New Zealand (ANZ) is lacking. AIMS To evaluate whether the pattern of ALF would be similar to previous studies and whether, despite potentially low transplantation rates, mortality would be comparable. METHODS We obtained data from the ANZ Intensive Care Society Adult Patient Database and the ANZ Liver Transplant Registry for 10 years commencing 2005 and analysed for patient outcomes. RESULTS During the study period, 1 022 698 adults were admitted to intensive care units across ANZ, of which 723 had ALF. The estimated annual incidence of ALF over this period was 3.4/million people and increased over time (P = 0.001). ALF patients had high illness severity (Acute Physiology And Chronic Health Evaluation III 79.8 vs 50.1 in non-ALF patients; P < 0.0001) and were more likely to be younger, female, pregnant and immunosuppressed. ALF was an independent predictor of mortality (odds ratio 1.5 (1.26-1.79); P < 0.0001). At less than 23%, the use of liver transplantation was low, but the mortality of 39% was similar to previous studies. CONCLUSIONS ALF is a rare but increasing diagnosis in ANZ intensive care units. Low transplantation rates in ANZ for ALF do not appear to be associated with higher mortality rates than reported in the literature.
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Affiliation(s)
- Stephen Warrillow
- Department of Intensive Care, Austin Health, Melbourne, Australia
- School of Medicine, University of Melbourne, Melbourne, Australia
| | - Michael Bailey
- Australian and New Zealand Intensive Care Research Centre, Monash University School of Public Health and Preventive Medicine, Melbourne, Australia
| | - David Pilcher
- Australian and New Zealand Intensive Care Research Centre, Monash University School of Public Health and Preventive Medicine, Melbourne, Australia
- Department of Intensive Care, Alfred Health, Melbourne, Australia
| | - Alex Kazemi
- Intensive Care Unit, Middlemore Hospital, Auckland, New Zealand
| | - Colin McArthur
- Department of Critical Care Medicine, Auckland City Hospital, Auckland, New Zealand
- Medical Research Institute of New Zealand, Auckland, New Zealand
| | - Paul Young
- Medical Research Institute of New Zealand, Auckland, New Zealand
- Intensive Care Unit, Wellington Hospital, Wellington, New Zealand
| | - Rinaldo Bellomo
- Department of Intensive Care, Austin Health, Melbourne, Australia
- School of Medicine, University of Melbourne, Melbourne, Australia
- Department of Intensive Care, Alfred Health, Melbourne, Australia
- Department of Intensive Care Royal Melbourne Hospital, Melbourne, Australia
- Data Analytics Research and Evaluation (DARE) Centre, Austin Hospital and University of Melbourne, Melbourne, Australia
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Ferreira CR, Cassiman D, Blau N. Clinical and biochemical footprints of inherited metabolic diseases. II. Metabolic liver diseases. Mol Genet Metab 2019; 127:117-121. [PMID: 31005404 PMCID: PMC10515611 DOI: 10.1016/j.ymgme.2019.04.002] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Revised: 03/25/2019] [Accepted: 04/05/2019] [Indexed: 12/14/2022]
Abstract
Inherited metabolic diseases account for about one third of pediatric patients with hepatomegaly, acute liver failure, cirrhosis or cholestasis. Specifically for pediatric acute liver failure, they account for 10-15% of cases, with a mortality of 22-65%. The percentage of acute liver failure caused by an inherited metabolic disease in children <2-3 years of age is even higher, ranging from a third to half of all cases. Metabolic liver disease accounts for 8-13% of all pediatric liver transplantations. Despite this high burden of disease, underdiagnosis remains common. We reviewed and updated the list of known metabolic etiologies associated with various types of metabolic liver involvement, and found 142 relevant inborn errors of metabolism. This represents the second of a series of articles attempting to create and maintain a comprehensive list of clinical and metabolic differential diagnoses according to system involvement.
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Affiliation(s)
- Carlos R Ferreira
- National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
| | - David Cassiman
- Department of Gastroenterology-Hepatology and Metabolic Center, University of Leuven, Leuven, Belgium.
| | - Nenad Blau
- Dietmar-Hopp Metabolic Center, University Children's Hospital, Heidelberg, Germany; Division of Metabolism, Children's Hospital, Zürich, Switzerland.
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Li X, Cheng Q, Li N, Chang G, Ding Y, Li J, Shen Y, Wang J, Wang X. SOPH Syndrome with Growth Hormone Deficiency, Normal Bone Age, and Novel Compound Heterozygous Mutations in NBAS. Fetal Pediatr Pathol 2018; 37:404-410. [PMID: 30592236 DOI: 10.1080/15513815.2018.1509406] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
BACKGROUND Short stature with optic atrophy and Pelger-Huet anomaly (SOPH; MIM 614800) syndrome is a genetic disease caused by mutation in the neuroblastoma amplified sequence (NBAS) gene. CASE REPORT We present a 11-year-old Chinese boy with SOPH syndrome, growth hormone deficiency with a normal bone age. Gene sequencing in the patient revealed a novel compound heterozygous mutation of c.5752A > C (Thr1918Pro) and c.500_501delTT (Phe167Cysfs*7) in the NBAS gene. CONCLUSIONS To our best knowledge, these novel mutations in the NBAS gene have not been reported. Normal bone age with growth hormone deficiency in this patient is different from the patients with SOPH syndrome that have been previously reported. These findings enrich the mutant spectrum of the NBAS gene and add our understanding of SOPH syndrome.
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Affiliation(s)
- Xin Li
- a Department of Endocrinology, Shanghai Children's Medical Center , Shanghai Jiaotong University School of Medicine , Shanghai , China
| | - Qing Cheng
- a Department of Endocrinology, Shanghai Children's Medical Center , Shanghai Jiaotong University School of Medicine , Shanghai , China
| | - Niu Li
- b Department of Medical Genetics, Shanghai Children's Medical Center , Shanghai Jiaotong University School of Medicine , Shanghai , China
| | - Guoying Chang
- a Department of Endocrinology, Shanghai Children's Medical Center , Shanghai Jiaotong University School of Medicine , Shanghai , China
| | - Yu Ding
- a Department of Endocrinology, Shanghai Children's Medical Center , Shanghai Jiaotong University School of Medicine , Shanghai , China
| | - Juan Li
- a Department of Endocrinology, Shanghai Children's Medical Center , Shanghai Jiaotong University School of Medicine , Shanghai , China
| | - Yiping Shen
- c Department of Laboratory Medicine , Boston Children's Hospital , Boston , MA , USA
| | - Jian Wang
- b Department of Medical Genetics, Shanghai Children's Medical Center , Shanghai Jiaotong University School of Medicine , Shanghai , China
| | - Xiumin Wang
- a Department of Endocrinology, Shanghai Children's Medical Center , Shanghai Jiaotong University School of Medicine , Shanghai , China
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40
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Szewc AM, Taylor S, Cage GD, Jacobsen J, Bulut OP, de Mello DE. Acute Liver Failure in an Adolescent Male Induced by Human Herpesvirus 6 (HHV-6): A Case Report With Literature Review. Lab Med 2018; 49:165-174. [PMID: 29390152 DOI: 10.1093/labmed/lmx088] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
A previously healthy 11-year-old Caucasian boy presented with a 2-week history of nonspecific symptoms of nausea and nonbilious, nonbloody emesis. He developed significant jaundice and hepatic encephalopathy within 1 week of beginning symptoms and was discovered to have fulminant liver failure. Extensive work-ups for underlying etiologies included serologic evaluation for underlying chronic liver diseases, toxicology screening, inborn errors of metabolism, and infectious diseases. The results of the entire assessment were negative except for human herpesvirus 6B, which was detected in the liver by quantitative real-time polymerase chain reaction and immunohistochemical analysis. The patient underwent ABO-compatible liver transplantation and has had clinically stable health, with no evidence to date of complications associated with HHV-6 or other members of the herpesvirus family.
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Affiliation(s)
- Adam M Szewc
- Department of Microbiology and Molecular Diagnostics, Phoenix Children's Hospital, Phoenix, AZ.,Bacterial Special Pathogens Branch (BSPB), Division of High-Consequence Pathogens and Pathology (DHCPP), National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Centers for Disease Control and Prevention (CDC), Atlanta, GA
| | - Steve Taylor
- Department of Pathology and Laboratory Medicine, Phoenix Children's Hospital, Phoenix, AZ
| | - Gary D Cage
- Department of Microbiology and Molecular Diagnostics, Phoenix Children's Hospital, Phoenix, AZ
| | - Jeffery Jacobsen
- Department of Pathology and Laboratory Medicine, Phoenix Children's Hospital, Phoenix, AZ
| | - Ozlem Pinar Bulut
- Division of Pediatric Gastroenterology and Hepatology, Phoenix Children's Hospital, Phoenix, AZ
| | - Daphne E de Mello
- Department of Pathology and Laboratory Medicine, Phoenix Children's Hospital, Phoenix, AZ
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Abstract
BACKGROUND There are limited data on utility of magnetic resonance imaging (MRI) in the assessment of suspected neonatal hemochromatosis (NH). OBJECTIVES The aim of the study was to present our experience with utilization of multi-echo sequence MRI technique in the evaluation of NH and to compare MRI findings in infants with and without NH. METHODS MRI performed for suspected NH were retrospectively reviewed to note the presence and severity of iron deposition (ID) in liver, spleen, pancreas, and kidneys on multi-echo sequences. Findings were compared in infants with and without NH. RESULTS Of 20 infants (9 boys and 11 girls; median age of 12.5 days) included in the study, 7 of 20 had NH and 13 of 20 were assigned to the non-NH group. Higher degree of pancreatic ID was seen in the NH group (P = 0.001) with 4 of 7 evaluable pancreas showing moderate-to-severe degree and 1 of 7 showing mild degree of ID whereas none of the 13 infants in non-NH group showed moderate or severe degree of pancreatic ID. Even though the severity of hepatic ID was higher in NH group (P = 0.033), variable severity of hepatic ID was seen in both groups with most infants in both groups showing moderate-to-severe degree of ID. The severity of splenic ID was not particularly associated with any group (P = 0.774) but there was no moderate or severe degree of ID in NH. Renal ID was seen in two infants in non-NH group. CONCLUSIONS A moderate-to-severe degree of pancreatic ID seen on MRI tends to be associated with NH and should be sought to establish a timely diagnosis of NH. Presence and severity of hepatic ID cannot be used for differentiation of NH from other causes of neonatal liver failure.
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Dias Costa F, Moinho R, Ferreira S, Garcia P, Diogo L, Gonçalves I, Pinto C. Fallo hepático aguda asociado a enfermedades metabólicas hereditarias en niños pequeños. An Pediatr (Barc) 2018; 88:69-74. [DOI: 10.1016/j.anpedi.2017.02.012] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2016] [Revised: 02/10/2017] [Accepted: 02/15/2017] [Indexed: 01/24/2023] Open
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Dias Costa F, Moinho R, Ferreira S, Garcia P, Diogo L, Gonçalves I, Pinto C. Acute liver failure related to inherited metabolic diseases in young children. ANALES DE PEDIATRÍA (ENGLISH EDITION) 2018. [DOI: 10.1016/j.anpede.2017.03.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
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Ivanovski I, Ješić M, Ivanovski A, Garavelli L, Ivanovski P. Metabolically based liver damage pathophysiology in patients with urea cycle disorders - A new hypothesis. World J Gastroenterol 2017; 23:7930-7938. [PMID: 29209134 PMCID: PMC5703922 DOI: 10.3748/wjg.v23.i44.7930] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2017] [Revised: 05/15/2017] [Accepted: 06/19/2017] [Indexed: 02/06/2023] Open
Abstract
The underlying pathophysiology of liver dysfunction in urea cycle disorders (UCDs) is still largely elusive. There is some evidence that the accumulation of urea cycle (UC) intermediates are toxic for hepatocyte mitochondria. It is possible that liver injury is directly caused by the toxicity of ammonia. The rarity of UCDs, the lack of checking of iron level in these patients, superficial knowledge of UC and an underestimation of the metabolic role of fumaric acid, are the main reasons that are responsible for the incomprehension of the mechanism of liver injury in patients suffering from UCDs. Owing to our routine clinical practice to screen for iron overload in severely ill neonates, with the focus on the newborns suffering from acute liver failure, we report a case of citrullinemia with neonatal liver failure and high blood parameters of iron overload. We hypothesize that the key is in the decreased-deficient fumaric acid production in the course of UC in UCDs that causes several sequentially intertwined metabolic disturbances with final result of liver iron overload. The presented hypothesis could be easily tested by examining the patients suffering from UCDs, for liver iron overload. This could be easily performed in countries with a high population and comprehensive national register for inborn errors of metabolism. Conclusion: Providing the hypothesis is correct, neonatal liver damage in patients having UCD can be prevented by the supplementation of pregnant women with fumaric or succinic acid, prepared in the form of iron supplementation pills. After birth, liver damage in patients having UCDs can be prevented by supplementation of these patients with zinc fumarate or zinc succinylate, as well.
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Affiliation(s)
- Ivan Ivanovski
- Clinical Genetics Unit, Department of Obstetrics and Pediatrics, AUSL-IRCCS of Reggio Emilia, 42123 Reggio Emilia, Italy
- Department of Surgical, Medical, Dental and Morphological Sciences with interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, 41121 Modena, Italy
| | - Miloš Ješić
- School of Medicine University of Belgrade, Belgrade 11000, Serbia
- University Children’s Hospital, Belgrade 11000, Serbia
| | - Ana Ivanovski
- Faculty of Chemistry University of Belgrade, Belgrade 11000, Serbia
| | - Livia Garavelli
- Clinical Genetics Unit, Department of Obstetrics and Pediatrics, AUSL-IRCCS of Reggio Emilia, 42123 Reggio Emilia, Italy
| | - Petar Ivanovski
- School of Medicine University of Belgrade, Belgrade 11000, Serbia
- University Children’s Hospital, Belgrade 11000, Serbia
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Uchida H, Sakamoto S, Fukuda A, Sasaki K, Shigeta T, Nosaka S, Kubota M, Nakazawa A, Nakagawa S, Kasahara M. Sequential analysis of variable markers for predicting outcomes in pediatric patients with acute liver failure. Hepatol Res 2017; 47:1241-1251. [PMID: 28032939 DOI: 10.1111/hepr.12859] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Revised: 12/01/2016] [Accepted: 12/26/2016] [Indexed: 02/08/2023]
Abstract
AIM Our aim was to analyze serial changes in the predictive variables and a scoring system retrospectively adapted to evaluate outcomes in pediatric patients with acute liver failure (ALF). METHODS We retrospectively collected data on 65 patients with ALF. The 65 patients were divided into two groups according to the need for liver transplantation (LT) as follows: LT group (n = 54) and non-LT group (n = 11). The early determination scoring system of the indications for LT proposed by the Intractable Hepato-Biliary Diseases Study Group of Japan (JIHBDSG) was used in our study. The area under the receiver operating characteristic curve (AUROC) was calculated for the JIHBDSG score between the LT group and non-LT group at the time of diagnosis (day 0) and day 3, and day 5 after the diagnosis. RESULTS A JIHBDSG score of >3 at day 5 was found to identify the patients requiring LT with 83.7% sensitivity, 81.8% specificity, and 83.3% diagnostic accuracy. Based on a comparison of AUROC values, the JIHBDSG score on day 5 (AUROC 0.91) was higher than that on day 0 (AUROC 0.75) and day 3 (AUROC 0.84). CONCLUSION We showed that a serial analysis of the JIHBDSG score might be useful for predicting outcomes of ALF in pediatric patients who fulfilled the criteria of LT indication in our center. However, further studies are needed to validate our results.
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Affiliation(s)
- Hajime Uchida
- Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Seisuke Sakamoto
- Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Akinari Fukuda
- Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Kengo Sasaki
- Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Takanobu Shigeta
- Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Shunsuke Nosaka
- Division of Radiology, National Center for Child Health and Development, Tokyo, Japan
| | - Masaya Kubota
- Division of Neurology, National Center for Child Health and Development, Tokyo, Japan
| | - Atsuko Nakazawa
- Division of Pathology, National Center for Child Health and Development, Tokyo, Japan
| | - Satoshi Nakagawa
- Division of Critical Care and Anesthesia, National Center for Child Health and Development, Tokyo, Japan
| | - Mureo Kasahara
- Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
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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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Nishimura N, Kasahara M, Ishikura K, Nakagawa S. Current status of pediatric transplantation in Japan. J Intensive Care 2017; 5:48. [PMID: 28729907 PMCID: PMC5518126 DOI: 10.1186/s40560-017-0241-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2017] [Accepted: 07/06/2017] [Indexed: 01/01/2023] Open
Abstract
Brain-dead donor organ transplantation has been available to children in Japan since the 2010 revision of the Organ Transplant Law. Of the 50–60 brain-dead donor organ transplants performed annually in Japan, however, very few (0–4 per year) are performed in children. Again, while those receiving liver, heart, and kidney transplants are reported to fare better than their counterparts in the rest of the world, organ shortage is becoming a matter of great concern. Very few organs become available from brain-dead donors or are transplanted to adults if made available at all, with some children dying while on the brain-dead organ waiting list. Against this background, living-donor transplants, split-liver transplants, domino transplants, and hepatocyte transplants represent alternative modalities, each of which is shown to be associated with favorable outcomes. Challenges exist, include streamlining the existing framework for promoting organ donation for children and between children.
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Affiliation(s)
- Nao Nishimura
- Division of Critical Care Medicine, Department of Critical Care and Anesthesia, National Center for Child Health and Development, Ohkura 2-1-1, Setagaya, Tokyo, Japan
| | - Mureo Kasahara
- Organ Transplantation Center, National Center for Child Health and Development, Ohkura 2-1-1, Setagaya, Tokyo, Japan
| | - Kenji Ishikura
- Division of Nephrology and Rheumatology, National Center for Child Health and Development, Ohkura 2-1-1, Setagaya, Tokyo, Japan
| | - Satoshi Nakagawa
- Division of Critical Care Medicine, Department of Critical Care and Anesthesia, National Center for Child Health and Development, Ohkura 2-1-1, Setagaya, Tokyo, Japan
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Li JQ, Qiu YL, Gong JY, Dou LM, Lu Y, Knisely AS, Zhang MH, Luan WS, Wang JS. Novel NBAS mutations and fever-related recurrent acute liver failure in Chinese children: a retrospective study. BMC Gastroenterol 2017. [PMID: 28629372 PMCID: PMC5477288 DOI: 10.1186/s12876-017-0636-3] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Background Underlying causes in Chinese children with recurrent acute liver failure (RALF), including liver crises less than full acute liver failure, are incompletely understood. We sought to address this by searching for genes mutated in such children. Methods Five unrelated Chinese boys presenting between 2012 and 2015 with RALF of unexplained etiology were studied. Results of whole exome sequencing were screened for mutations in candidate genes. Mutations were verified in patients and their family members by Sanger sequencing. All 5 boys underwent liver biopsy. Results NBAS was the only candidate gene mutated in more than one patient (biallelic mutations, 3 of 5 patients; 5 separate mutations). All NBAS mutations were novel and predictedly pathogenic (frameshift insertion mutation c.6611_6612insCA, missense mutations c.2407G > A and c.3596G > A, nonsense mutation c.586C > T, and splicing-site mutation c.5389 + 1G > T). Of these mutations, 3 lay in distal (C-terminal) regions of NBAS, a novel distribution. Unlike the 2 patients without NBAS mutations, the 3 patients with confirmed NBAS mutations all suffered from a febrile illness before each episode of liver crisis (fever-related RALF), with markedly elevated alanine aminotransferase and aspartate aminotransferase activities 24-72 h after elevation of body temperature, succeeded by severe coagulopathy and mild to moderate jaundice. Conclusions As in other countries, so too in China; NBAS disease is a major cause of fever-related RALF in children. The mutation spectrum of NBAS in Chinese children seems different from that described in other populations. Electronic supplementary material The online version of this article (doi:10.1186/s12876-017-0636-3) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Jia-Qi Li
- Department of Pediatrics, Jinshan Hospital of Fudan University, Shanghai, 201508, China
| | - Yi-Ling Qiu
- The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai, 201102, China
| | - Jing-Yu Gong
- Department of Pediatrics, Jinshan Hospital of Fudan University, Shanghai, 201508, China
| | - Li-Min Dou
- The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai, 201102, China
| | - Yi Lu
- The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai, 201102, China
| | - A S Knisely
- Institut für Pathologie, Medizinische Universität Graz, Auenbruggerplatz 25, A-8036, Graz, Austria
| | - Mei-Hong Zhang
- Department of Pediatrics, Jinshan Hospital of Fudan University, Shanghai, 201508, China
| | - Wei-Sha Luan
- Department of Pediatrics, Jinshan Hospital of Fudan University, Shanghai, 201508, China
| | - Jian-She Wang
- The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai, 201102, China.
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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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Bitar R, Thwaites R, Davison S, Rajwal S, McClean P. Liver Failure in Early Infancy: Aetiology, Presentation, and Outcome. J Pediatr Gastroenterol Nutr 2017; 64:70-75. [PMID: 27007398 DOI: 10.1097/mpg.0000000000001202] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
OBJECTIVE Acute liver failure (ALF) in early infancy is rare and challenging to recognize and manage. We aim to describe the presentation and outcome of infants with ALF according to their final aetiology to elucidate features to facilitate early recognition leading to prompt diagnosis and management. METHODS All infants presenting within 120 days from birth with liver failure were included in a retrospective review over a 19-year period. The aetiology, clinical features, presenting investigations, and outcome were collected. RESULTS Seventy-eight young infants presented with ALF. The aetiology was established in 94% and included metabolic disease (36%), hypoxic-ischaemic (HI) insult (19%), infection (17%), neonatal haemochromatosis (9%), and infiltrative disease (9%). Infections, infiltrative disease, and acute HI insult usually resulted in higher transaminases and international normalized ratio, whereas neonatal haemochromatosis and tyrosinaemia were characterized by lower or near normal transaminases. Overall jaundice was not visible in 24% of infants at presentation. Forty-five (58%) infants were alive at discharge from hospital. Survival at 1 year was 53% and survival with native liver 50%. Later deaths occurred in infants with mitochondrial disease. Six infants received a liver transplant and 4 subsequently died from their underlying disease. CONCLUSION ALF should be considered in any young infant with a coagulopathy as transaminases and/or bilirubin levels can be near normal at presentation. Better intensive care and the judicious use of liver transplantation may have contributed to the improved outcomes for this group compared with previous decades.
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Affiliation(s)
- Rana Bitar
- *Paediatric Gastroenterology, Great North Children's Hospital, Newcastle †Paediatrics, James Cook University Hospital, Middlesbrough ‡Children's Liver Unit, Leeds Children's Hospital, Leeds, UK
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