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Al Beloushi M, Saleh H, Ahmed B, Konje JC. Congenital and Perinatal Viral Infections: Consequences for the Mother and Fetus. Viruses 2024; 16:1698. [PMID: 39599813 PMCID: PMC11599085 DOI: 10.3390/v16111698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 10/13/2024] [Accepted: 10/26/2024] [Indexed: 11/29/2024] Open
Abstract
Viruses are the most common congenital infections in humans and an important cause of foetal malformations, neonatal morbidity, and mortality. The effects of these infections, which are transmitted in utero (transplacentally), during childbirth or in the puerperium depend on the timing of the infections. These vary from miscarriages (usually with infections in very early pregnancy), congenital malformations (when the infections occur during organogenesis) and morbidity (with infections occurring late in pregnancy, during childbirth or after delivery). The most common of these viruses are cytomegalovirus, hepatitis, herpes simplex type-2, parvovirus B19, rubella, varicella zoster and zika viruses. There are currently very few efficacious antiviral agents licensed for use in pregnancy. For most of these infections, therefore, prevention is mainly by vaccination (where there is a vaccine). The administration of immunoglobulins to those exposed to the virus to offer passive immunity or appropriate measures to avoid being infected would be options to minimise the infections and their consequences. In this review, we discuss some of the congenital and perinatal infections and their consequences on both the mother and fetus and their management focusing mainly on prevention.
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Affiliation(s)
- Mariam Al Beloushi
- Women’s Wellness and Research Centre Hamad Medical Corporation, Doha P.O. Box 3050, Qatar; (M.A.B.); (H.S.)
- Department of Obstetrics and Gynaecology, Qatar University, Doha P.O. Box 2713, Qatar;
| | - Huda Saleh
- Women’s Wellness and Research Centre Hamad Medical Corporation, Doha P.O. Box 3050, Qatar; (M.A.B.); (H.S.)
- Department of Obstetrics and Gynaecology, Qatar University, Doha P.O. Box 2713, Qatar;
| | - Badreldeen Ahmed
- Department of Obstetrics and Gynaecology, Qatar University, Doha P.O. Box 2713, Qatar;
- Feto Maternal Centre, Al Markhiya Doha, Doha P.O. Box 34181, Qatar
- Department of Obstetrics and Gynaecology Weill Cornell Medicine, Doha P.O. Box 24144, Qatar
| | - Justin C. Konje
- Feto Maternal Centre, Al Markhiya Doha, Doha P.O. Box 34181, Qatar
- Department of Obstetrics and Gynaecology Weill Cornell Medicine, Doha P.O. Box 24144, Qatar
- Department of Health Sciences, University of Leicester, P.O. Box 7717, Leicester LE2 7LX, UK
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Biswas T, Lal BB, Sood V, Ashritha A, Maheshwari A, Bajpai M, Kumar G, Khanna R, Alam S. Therapeutic plasma exchange provides native liver survival benefit in children with acute liver failure: A propensity score-matched analysis. J Clin Apher 2024; 39:e22130. [PMID: 38873972 DOI: 10.1002/jca.22130] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Revised: 04/06/2024] [Accepted: 05/14/2024] [Indexed: 06/15/2024]
Abstract
OBJECTIVES This study aimed to evaluate the safety and efficacy of therapeutic plasma exchange (TPE) in pediatric acute liver failure (PALF). METHODS All children aged 2-18 years with PALF were included. The intervention cohort included a subset of PALF patients undergoing complete three sessions of TPE, whereas the matching controls were derived by propensity score matching from the patient cohort who did not receive any TPE. Propensity matching was performed based on the international normalized ratio (INR), grade of hepatic encephalopathy (HE), age, bilirubin, and ammonia levels. The primary outcome measure was native liver survival (NLS) in the two arms on day 28. RESULTS Of the total cohort of 403 patients with PALF, 65 patients who received TPE and 65 propensity-matched controls were included in analysis. The 2 groups were well balanced with comparable baseline parameters. On day 4, patients in the TPE group had significantly lower INR (P = 0.001), lower bilirubin (P = 0.008), and higher mean arterial pressure (MAP) (P = 0.033) than controls. The NLS was 46.15% in the TPE arm and 26.15% in the control arm. The overall survival (OS) was 50.8% in the TPE arm and 35.4% in the control arm. Kaplan-Meier survival analysis showed a significantly higher NLS in patients receiving TPE than controls (P = 0.001). On subgroup analysis, NLS benefit was predominantly seen in hepatitis A-related and indeterminate PALF. CONCLUSION TPE improved NLS and OS in a propensity-matched cohort of patients with PALF. Patients receiving TPE had lower INR and bilirubin levels and higher MAP on day 4.
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Affiliation(s)
- Tamoghna Biswas
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Bikrant Bihari Lal
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Vikrant Sood
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Avalareddy Ashritha
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ashish Maheshwari
- Department of Transfusion Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Meenu Bajpai
- Department of Transfusion Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Guresh Kumar
- Department of Biostatistics, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Rajeev Khanna
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Seema Alam
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Samanta A, Poddar U. Pediatric acute liver failure: Current perspective in etiology and management. Indian J Gastroenterol 2024; 43:349-360. [PMID: 38466551 DOI: 10.1007/s12664-024-01520-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Accepted: 12/28/2023] [Indexed: 03/13/2024]
Abstract
Pediatric acute liver failure (PALF) is a catastrophic clinical condition with very high morbidity and mortality without early detection and intervention. It is characterized by the acute onset of massive hepatocellular injury that releases circulating inflammatory mediators, resulting in metabolic disturbances, coagulopathy, hepatic encephalopathy and multi-organ failure. The etiological spectrum is dominated by hepatotropic viruses, drug-induced liver injury, metabolic and genetic disorders and immune-mediated diseases. Unlike adults, indeterminate causes for acute liver failure constitute a considerable proportion of cases of acute liver failure in children in the west. The heterogeneity of age and etiology in PALF has led to difficulties in developing prognostic scoring. The recent guidelines emphasize prompt identification of PALF, age-appropriate evaluation for hepatic encephalopathy and laboratory evaluation with careful monitoring. Current therapy focuses on supporting the failing liver and other organs, pending either spontaneous recovery or liver transplantation. Targeted therapy is available for a select group of etiologies. Liver transplantation can be lifesaving and a plan for the same should be organized, whenever indicated. The aim of this review is to define PALF, understand its etiopathogenesis, address the challenges encountered during the management and update the latest advances in liver transplantation and non-transplant treatment options in PALF.
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Affiliation(s)
- Arghya Samanta
- Department of Pediatric Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226 014, India
| | - Ujjal Poddar
- Department of Pediatric Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226 014, India.
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Verma SK, Upadhyay P, Shukla S, Jain A, Shukla S, Patwa AK. Prognostic markers in hepatitis A-related pediatric acute liver failure and validation of the Peds-hepatitis A virus prognostic model. Indian J Gastroenterol 2024; 43:459-467. [PMID: 38568354 DOI: 10.1007/s12664-024-01551-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 02/01/2024] [Indexed: 05/28/2024]
Abstract
OBJECTIVES Hepatitis A virus (HAV) is the commonest cause for pediatric acute liver failure (PALF) in India. The objective of the study was to identify the predictors of mortality and to evaluate the utility of Peds-HAV model in a cohort of non-LT HAV-PALF. METHODS The study included HAV-related PALF from two non-transplant centers. The predictors of outcome were identified by univariate analysis followed by Cox regression analysis. The prognostic accuracy of Peds-HAV model, King's College Hospital (KCH) criteria and pediatric end-stage liver disease score (PELD) were evaluated. RESULTS As many as 140 children with PALF were included, of whom 96 (68.6%) children had HAV-PALF. On Cox regression analysis, international normalized ratio (INR) (p < 0.001), jaundice to encephalopathy (JE) interval (p < 0.001) and hepatic encephalopathy (HE) grade 3/4 (p = 0.01) were independent predictors of mortality. The mortality rates were 0% (0/42), 14.3% (3/21), 60% (9/15) and 94.4% (17/18) when none, 1, 2 or 3 criteria of the Peds-HAV were met, respectively. Peds-HAV model at a listing cut-off of ≥ 2 criteria predicted death with 89.7% sensitivity and 89.6% specificity. In contrast, KCH criteria had a lower sensitivity of 62.1%. PELD score had a sensitivity of 89.7% and specificity of 85.1% at a cut-off of 30. The overall prognostic accuracy of Peds-HAV model (89.6%) was higher than those of KCH (83.3%) and PELD (86.5%). CONCLUSION INR, HE grade and JE interval were independent predictors of mortality. The study provides an external validation of Peds-HAV model as a prognostic score in HAV-PALF. CLINICAL TRIAL REGISTRY NUMBER Not applicable as this is a retrospective study.
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Affiliation(s)
- Sanjeev Kumar Verma
- Department of Pediatrics, King George Medical University, Lucknow, 226 003, India.
| | - Piyush Upadhyay
- Department of Pediatrics, Ram Manohar Lohiya Institute of Medical Sciences, Lucknow, 226 010, India
| | - Stuti Shukla
- Department of Pediatrics, King George Medical University, Lucknow, 226 003, India
| | - Amita Jain
- Department of Microbiology, King George Medical University, Lucknow, 226 003, India
| | - Suruchi Shukla
- Department of Microbiology, King George Medical University, Lucknow, 226 003, India
| | - Ajay Kumar Patwa
- Department of Medicine, King George Medical University, Lucknow, 226 003, India
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Bolia R, Srivastava A. Ascites and Chronic Liver Disease in Children. Indian J Pediatr 2024; 91:270-279. [PMID: 37310583 DOI: 10.1007/s12098-023-04596-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 03/17/2023] [Indexed: 06/14/2023]
Abstract
Development of ascites in children with chronic liver disease is the most common form of decompensation. It is associated with a poor prognosis and increased risk of mortality. A diagnostic paracentesis should be performed in liver disease patients with- new-onset ascites, at the beginning of each hospital admission and when ascitic fluid infection (AFI) is suspected. The routine analysis includes cell count with differential, bacterial culture, ascitic fluid total protein and albumin. A serum albumin-ascitic fluid albumin gradient of ≥1.1 g/dL confirms the diagnosis of portal hypertension. Ascites has been reported in children with non-cirrhotic liver disease like acute viral hepatitis, acute liver failure and extrahepatic portal venous obstruction. The main steps in management of cirrhotic ascites include dietary sodium restriction, diuretics and large-volume paracentesis. Sodium should be restricted to maximum of 2 mEq/kg/d (max 90 mEq/d) of sodium/day. Oral diuretic therapy comprises of aldosterone antagonists (e.g., spironolactone) with or without loop-diuretics (e.g., furosemide). Once the ascites is mobilized, the diuretics should be gradually tapered to the minimum effective dosage. Tense ascites should be managed with a large-volume paracentesis (LVP) preferably with albumin infusion. Therapeutic options for refractory ascites include recurrent LVP, transjugular intrahepatic porto-systemic shunt and liver transplantation. AFI (fluid neutrophil count ≥250/mm3) is an important complication, and requires prompt antibiotic therapy. Hyponatremia, acute kidney injury, hepatic hydrothorax and hernias are the other complications.
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Affiliation(s)
- Rishi Bolia
- Department of Gastroenterology, Hepatology and Liver Transplant, Queensland Children's Hospital, 501, Stanley Street, South Brisbane, Queensland, 4101, Australia
| | - Anshu Srivastava
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226014, India.
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Singh R, Kapoor A. Severe Acute Hepatitis: An Emerging Grave Illness in Children. Indian Pediatr 2023; 60. [PMCID: PMC10052219 DOI: 10.1007/s13312-023-2831-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/31/2023]
Abstract
Acute hepatitis of unknown origin in children has been recently described in the literature, and a case definition has also been proposed for this condition. The exact etiology is unknown and exclusion of infectious, metabolic, autoimmune and toxin mediated injuries is essential. Management for this condition is supportive, but some may require liver transplantation. Infection prevention and control practices are important as the etiology remains unidentified.
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Affiliation(s)
- Raghvendra Singh
- Department of Pediatrics, Maulana Azad Medical College (University of Delhi) and Lok Nayak Hospital, New Delhi, India
- Department of Pediatrics, Maulana Azad Medical College, Bahadur Shah Zafar Marg, New Delhi, 110 002 India
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Chiou FK, Logarajah V, Ho CWW, Goh LSH, Karthik SV, Aw MM, Phua KB. Demographics, aetiology and outcome of paediatric acute liver failure in Singapore. Singapore Med J 2022; 63:659-666. [PMID: 34602977 PMCID: PMC9815169 DOI: 10.11622/smedj.2021138] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Introduction The aetiology of paediatric acute liver failure (PALF) varies widely according to age, and geographic and socioeconomic factors. This study aimed to examine the epidemiology, aetiology and outcome of PALF in Singapore at a single centre. Methods A retrospective review was performed of patients aged 0-18 years who were diagnosed with PALF from 2007 to 2019. PALF was defined by: absence of chronic liver disease; biochemical evidence of acute liver injury; and coagulopathy, non-correctible by vitamin K, defined as prothrombin time (PT) ≥20 seconds or international normalised ratio (INR) ≥2.0 regardless of hepatic encephalopathy (HE) or PT ≥15 seconds or INR ≥1.5 in the presence of HE. Results 34 patients were included. Median age at diagnosis was 10 months (range 7 days to 156 months). The top three causes of PALF were indeterminate (41.2%), metabolic (26.5%) and infectious (26.5%) aetiologies. A metabolic disorder was the most frequent aetiology in infants <12 months (38.9%), whereas an indeterminate cause was the most common in children >12 months (50%). No cases of viral hepatitis A or B presenting with PALF were detected. Overall spontaneous recovery rate (survival without liver transplantation [LT]) was 38.2%, and overall mortality rate was 47.1%. Six patients underwent living-donor LT, and the post-transplant survival at one year was 83.3%. Conclusion The aetiologic spectrum of PALF in Singapore is similar to that in developed Western countries, with indeterminate aetiology accounting for the majority. PALF is associated with poor overall survival; hence, timely LT for suitable candidates is critical to improve survival outcomes.
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Affiliation(s)
- Fang Kuan Chiou
- Gastroenterology, Hepatology and Nutrition Service, Paediatric Medicine, KK Women's and Children's Hospital, Singapore
| | - Veena Logarajah
- Gastroenterology, Hepatology and Nutrition Service, Paediatric Medicine, KK Women's and Children's Hospital, Singapore
| | - Christopher Wen Wei Ho
- Gastroenterology, Hepatology and Nutrition Service, Paediatric Medicine, KK Women's and Children's Hospital, Singapore
| | - Lynette Suk-Hui Goh
- Gastroenterology, Hepatology and Nutrition Service, Paediatric Medicine, KK Women's and Children's Hospital, Singapore
| | - Sivaramakrishnan Venkatesh Karthik
- Division of Paediatric Gastroenterology, Nutrition, Hepatology and Liver Transplantation, Department of Paediatrics, Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore
| | - Marion Margaret Aw
- Division of Paediatric Gastroenterology, Nutrition, Hepatology and Liver Transplantation, Department of Paediatrics, Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore
| | - Kong Boo Phua
- Gastroenterology, Hepatology and Nutrition Service, Paediatric Medicine, KK Women's and Children's Hospital, Singapore
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Shata MTM, Hetta HF, Sharma Y, Sherman KE. Viral hepatitis in pregnancy. J Viral Hepat 2022; 29:844-861. [PMID: 35748741 PMCID: PMC9541692 DOI: 10.1111/jvh.13725] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 12/17/2021] [Accepted: 06/13/2022] [Indexed: 12/09/2022]
Abstract
Viral hepatitis is caused by a heterogenous group of viral agents representing a wide range of phylogenetic groups. Many viruses can involve the liver and cause liver injury but only a subset are delineated as 'hepatitis viruses' based upon their primary site of replication and tropism for hepatocytes which make up the bulk of the liver cell population. Since their discovery, beginning with the agent that caused serum hepatitis in the 1960s, the alphabetic designations have been utilized. To date, we have five hepatitis viruses, A through E, though it is postulated that others may exist. This chapter will focus on those viruses. Note that hepatitis D is included as a subset of hepatitis B, as it cannot exist without concurrent hepatitis B infection. Pregnancy has the potential to affect all aspects of these viral agents due to the unique immunologic and physiologic changes that occur during and after the gestational period. In this review, we will discuss the most common viral hepatitis and their effects during pregnancy.
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Affiliation(s)
- Mohamed Tarek M. Shata
- Division of Digestive Disease, Department of Internal MedicineUniversity of CincinnatiCincinnatiOhioUSA
| | - Helal F. Hetta
- Division of Digestive Disease, Department of Internal MedicineUniversity of CincinnatiCincinnatiOhioUSA,Department of Medical Microbiology and Immunology, Faculty of MedicineAssiut UniversityAssiutEgypt
| | - Yeshika Sharma
- Division of Digestive Disease, Department of Internal MedicineUniversity of CincinnatiCincinnatiOhioUSA
| | - Kenneth E. Sherman
- Division of Digestive Disease, Department of Internal MedicineUniversity of CincinnatiCincinnatiOhioUSA
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Jagadisan B, Dhawan A. Emergencies in paediatric hepatology. J Hepatol 2022; 76:1199-1214. [PMID: 34990749 DOI: 10.1016/j.jhep.2021.12.027] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 12/17/2021] [Accepted: 12/21/2021] [Indexed: 12/12/2022]
Abstract
The aetiology of several liver diseases in children is age specific and many of these conditions have significant and potentially long-term clinical repercussions if not diagnosed early and managed in a timely fashion. We address 5 clinical scenarios that cover most of the diagnostic and therapeutic emergencies in children: infants with liver disease; acute liver failure; management of bleeding varices; liver-based metabolic disorders; and liver tumours and trauma. A wide spectrum of conditions that cause liver disease in infants may present as conjugated jaundice, which could be the only symptom of time-sensitive disorders - such as biliary atresia, metabolic disorders, infections, and haematological/alloimmune disorders - wherein algorithmic multistage testing is required for accurate diagnosis. In infantile cholestasis, algorithmic multistage tests are necessary for an accurate early diagnosis, while vitamin K, specific milk formulae and disease-specific medications are essential to avoid mortality and long-term morbidity. Management of paediatric acute liver failure requires co-ordination with a liver transplant centre, safe transport and detailed age-specific aetiological work-up - clinical stabilisation with appropriate supportive care is central to survival if transplantation is indicated. Gastrointestinal bleeding may present as the initial manifestation or during follow-up in patients with portal vein thrombosis or chronic liver disease and can be managed pharmacologically, or with endoscopic/radiological interventions. Liver-based inborn errors of metabolism may present as encephalopathy that needs to be recognised and treated early to avoid further neurological sequelae and death. Liver tumours and liver trauma are both rare occurrences in children and are best managed by a multidisciplinary team in a specialist centre.
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Affiliation(s)
- Barath Jagadisan
- Pediatric Liver GI and Nutrition Centre and MowatLabs, King's College Hospital, London, UK
| | - Anil Dhawan
- Pediatric Liver GI and Nutrition Centre and MowatLabs, King's College Hospital, London, UK.
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Amatya P, Kapalavai SK, Deep A, Sankaranarayanan S, Krupanandan R, Sadasivam K, Ramachandran B. Pediatric acute liver failure: An experience of a pediatric intensive care unit from resource limited settings. Front Pediatr 2022; 10:956699. [PMID: 36120651 PMCID: PMC9478462 DOI: 10.3389/fped.2022.956699] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 08/12/2022] [Indexed: 12/02/2022] Open
Abstract
INTRODUCTION Pediatric acute liver failure is a rare and serious disease. Though liver transplantation is considered as the established treatment option for patients who are unlikely to recover with medical management, however, with the advancement of medical care there has been an increase in spontaneous regeneration of liver, obviating the need for liver transplantation. We identified the etiologies, outcome and prognostic factors of acute liver failure and the validity of the existing liver transplantation criteria to predict the outcome of pediatric acute liver failure. MATERIALS AND METHODS This was a retrospective study done from January 2014 to December 2019 in a tertiary pediatric critical care unit in South India. All children aged between 1 month to 18 years admitted with acute liver failure were enrolled. RESULTS Of 125 children with acute liver failure, the main etiologies were infections (32%), indeterminate (23%), paracetamol toxicity (21%), metabolic (13%) and others (11%). Dengue was the most common infection (55%). The median pediatric logistic organ dysfunction score at admission was 12 (4-27). Of 125 patients, 63.2% (n = 79) had spontaneous regeneration which was higher in paracetamol induced (92.3%) compared to non-paracetamol induced acute liver failure (55.5%). Only two patients underwent liver transplantation and 35% died. Peak alanine transaminase and use of inotropes significantly predicted the outcome of disease. Of 38 children meeting King's College Hospital criteria for liver transplantation, 57.9% had spontaneous regeneration and 36.8% died. Of 74 children meeting INR > 4 criteria, 54% (n = 40) had spontaneous regeneration and 43.2% died. INR >4 criteria was more sensitive than King's College Hospital criteria for predicting the need for liver transplantation. CONCLUSION Pediatric acute liver failure is caused by varied etiologies and infections were the commonest cause. Despite having a seriously ill cohort of patients, medical management resulted in spontaneous regeneration in the majority of children with acute liver failure. The use of inotropes, advanced hepatic encephalopathy, and peak alanine transaminase were predictors of poor outcome in children with acute liver failure and these patients could be considered for liver transplantation as available. Therefore, we may need to develop better predictors of pediatric acute liver failure in resource limited settings.
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Affiliation(s)
- Puja Amatya
- Department of Pediatric Critical Care, Kanchi Kamakoti CHILDS Trust Hospital, Chennai, India
| | - Sudeep Kumar Kapalavai
- Department of Pediatric Critical Care, Kanchi Kamakoti CHILDS Trust Hospital, Chennai, India
| | - Akash Deep
- Department of Pediatric Critical Care, King's College Hospital, London, United Kingdom
| | | | - Ravikumar Krupanandan
- Department of Pediatric Critical Care, Kanchi Kamakoti CHILDS Trust Hospital, Chennai, India
| | - Kalaimaran Sadasivam
- Department of Pediatric Critical Care, Kanchi Kamakoti CHILDS Trust Hospital, Chennai, India
| | - Bala Ramachandran
- Department of Pediatric Critical Care, Kanchi Kamakoti CHILDS Trust Hospital, Chennai, India
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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. 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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Anand AC, Nandi B, Acharya SK, Arora A, Babu S, Batra Y, Chawla YK, Chowdhury A, Chaoudhuri A, Eapen EC, Devarbhavi H, Dhiman R, 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. Indian National Association for the Study of the Liver Consensus Statement on Acute Liver Failure (Part 1): Epidemiology, Pathogenesis, Presentation and Prognosis. J Clin Exp Hepatol 2020; 10:339-376. [PMID: 32655238 PMCID: PMC7335721 DOI: 10.1016/j.jceh.2020.04.012] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [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 an infrequent, unpredictable, potentially fatal complication of acute liver injury (ALI) consequent to varied etiologies. Etiologies of ALF as reported in the literature have regional differences, which affects the clinical presentation and natural course. In this part of the consensus article designed to reflect the clinical practices in India, disease burden, epidemiology, clinical presentation, monitoring, and prognostication have been discussed. In India, viral hepatitis is the most frequent cause of ALF, with drug-induced hepatitis due to antituberculosis drugs being the second most frequent cause. The clinical presentation of ALF is characterized by jaundice, coagulopathy, and encephalopathy. It is important to differentiate ALF from other causes of liver failure, including acute on chronic liver failure, subacute liver failure, as well as certain tropical infections which can mimic this presentation. The disease often has a fulminant clinical course with high short-term mortality. Death is usually attributable to cerebral complications, infections, and resultant multiorgan failure. Timely liver transplantation (LT) can change the outcome, and hence, it is vital to provide intensive care to patients until LT can be arranged. It is equally important to assess prognosis to select patients who are suitable for LT. Several prognostic scores have been proposed, and their comparisons show that indigenously developed dynamic scores have an edge over scores described from the Western world. Management of ALF will be described in part 2 of this document.
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Key Words
- ACLF, acute on chronic liver failure
- AFLP, acute fatty liver of pregnancy
- AKI, Acute kidney injury
- ALF, Acute liver failure
- ALFED, Acute Liver Failure Early Dynamic
- ALT, alanine transaminase
- ANA, antinuclear antibody
- AP, Alkaline phosphatase
- APTT, activated partial thromboplastin time
- ASM, alternative system of medicine
- ASMA, antismooth muscle antibody
- AST, aspartate transaminase
- ATN, Acute tubular necrosis
- ATP, adenosine triphosphate
- ATT, anti-TB therapy
- AUROC, Area under the receiver operating characteristics curve
- BCS, Budd-Chiari syndrome
- BMI, body mass index
- CBF, cerebral blood flow
- CBFV, cerebral blood flow volume
- CE, cerebral edema
- CHBV, chronic HBV
- CLD, chronic liver disease
- CNS, central nervous system
- CPI, clinical prognostic indicator
- CSF, cerebrospinal fluid
- DAMPs, Damage-associated molecular patterns
- DILI, drug-induced liver injury
- EBV, Epstein-Barr virus
- ETCO2, End tidal CO2
- GRADE, Grading of Recommendations Assessment Development and Evaluation
- HAV, hepatitis A virus
- HBV, Hepatitis B virus
- HELLP, hemolysis
- HEV, hepatitis E virus
- HLH, Hemophagocytic lymphohistiocytosis
- HSV, herpes simplex virus
- HV, hepatic vein
- HVOTO, hepatic venous outflow tract obstruction
- IAHG, International Autoimmune Hepatitis Group
- ICH, intracerebral hypertension
- ICP, intracerebral pressure
- ICU, intensive care unit
- IFN, interferon
- IL, interleukin
- IND-ALF, ALF of indeterminate etiology
- INDILI, Indian Network for DILI
- KCC, King's College Criteria
- LC, liver cirrhosis
- LDLT, living donor liver transplantation
- LT, liver transplantation
- MAP, mean arterial pressure
- MHN, massive hepatic necrosis
- MPT, mitochondrial permeability transition
- MUAC, mid-upper arm circumference
- NAPQI, n-acetyl-p-benzo-quinone-imine
- NPV, negative predictive value
- NWI, New Wilson's Index
- ONSD, optic nerve sheath diameter
- PAMPs, pathogen-associated molecular patterns
- PCR, polymerase chain reaction
- PELD, Pediatric End-Stage Liver Disease
- PPV, positive predictive value
- PT, prothrombin time
- RAAS, renin–angiotensin–aldosterone system
- SHF, subacute hepatic failure
- SIRS, systemic inflammatory response syndrome
- SNS, sympathetic nervous system
- TB, tuberculosis
- TCD, transcranial Doppler
- TGF, tumor growth factor
- TJLB, transjugular liver biopsy
- TLR, toll-like receptor
- TNF, tumor necrosis factor
- TSFT, triceps skin fold thickness
- US, ultrasound
- USALF, US Acute Liver Failure
- VZV, varicella-zoster virus
- WD, Wilson disease
- Wilson disease (WD)
- YP, yellow phosphorus
- acute liver failure
- autoimmune hepatitis (AIH)
- drug-induced liver injury
- elevated liver enzymes, low platelets
- sALI, severe acute liver injury
- viral hepatitis
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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
| | - RadhaKrishan Dhiman
- Department of Hepatology, Post graduate 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, Post graduate 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 Medicity Hospital, 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, Cuttack, 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, Post graduate 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 Medicity Hospital, 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, Cuttack, 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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Lal BB, Sood V, Snehavardhan P, Khanna R, Pasupuleti SSR, Siloliya M, Kumar G, Alam S. A novel, bedside, etiology specific prognostic model (Peds-HAV) in hepatitis A induced pediatric acute liver failure. Hepatol Int 2020; 14:483-490. [PMID: 32372333 DOI: 10.1007/s12072-020-10050-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Accepted: 04/18/2020] [Indexed: 01/05/2023]
Abstract
BACKGROUND Hepatitis A virus (HAV) is the commonest cause of pediatric acute liver failure (PALF) in developing countries. Our objective was to develop and validate a HAV-etiology specific prognostic model in PALF. METHODS All children with HAV induced PALF (IgM HAV reactive) were included. Outcome was defined at day 28. Only those with death or native liver survival were included. The model (Peds-HAV) was derived using the independent predictors of outcome and validated in a prospective independent cohort. RESULTS Hepatitis A accounted for 131 (45.9%) of total 285 PALF. After excluding 11 children who underwent liver transplant, 120 children (74 survivors and 46 death) were included. The first 75 patients formed the derivation cohort and the next 45 patients formed the prospective validation cohort. In the derivation cohort, INR: OR 2.208, (95% CI 1.321-3.690), p = 0.003, grade of hepatic encephalopathy (HE): OR 3.078, (95% CI 1.017-9.312), p = 0.047 and jaundice-to-HE interval: OR 1.171, (95% CI 1.044-1.314), p = 0.007 were independent predictors of death. The final model comprised three criteria: (1) presence of grade 3-4 HE, (2) INR greater than 3.1, and (3) jaundice to HE interval more than 10 days. Presence of 2 or more of these criteria predicted death with 90% sensitivity, 81.4% specificity and 84.9% accuracy. Peds-HAV model was superior to existing prognostic models. In the validation cohort, Peds-HAV model predicted death with 83.3% sensitivity and 92.6% specificity. CONCLUSION Peds-HAV model is a simple, bedside, dynamic, etiology (HAV) specific prognostic model based on 3 objective parameters with optimum sensitivity and specificity, hence should be used as liver transplant listing criteria in HAV induced PALF.
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Affiliation(s)
- Bikrant Bihari Lal
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Vikrant Sood
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Pandey Snehavardhan
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Rajeev Khanna
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Manish Siloliya
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Guresh Kumar
- Department of Biostatistics, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Seema Alam
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India.
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14
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Is Time Ripe for Hepatitis A Mass Vaccination? Indian Pediatr 2019. [DOI: 10.1007/s13312-019-1630-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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15
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Singh SK, Poddar U, Mishra R, Srivastava A, Yachha SK. Ascitic fluid infection in children with liver disease: time to change empirical antibiotic policy. Hepatol Int 2019; 14:138-144. [PMID: 31290071 DOI: 10.1007/s12072-019-09968-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2019] [Accepted: 06/27/2019] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS Recent years have shown a rise in occurrence of multidrug resistant ascitic fluid infection (AFI) including resistant to third generation cephalosporins. Our aim was to find the prevalence, antibiotics resistance and outcome of AFI in children with liver disease. METHODS Children (≤ 18 years) with liver disease-related ascites were prospectively enrolled from April 2015 to October 2017. Based on the results of ascitic fluid examination and culture, patients were classified as having AFI [spontaneous bacterial peritonitis (SBP), culture negative neutrocytic ascites (CNNA) and monomicrobial non-neutrocytic bacterascites (MNB)] and no-AFI. AFI diagnosed after 48 h of index hospitalization was considered as nosocomial. RESULTS We enrolled 194 children with a median age of 85 [2-216] months. Chronic liver disease was the commonest etiology (153, 79%). AFI was present in 60 (31%) children [SBP (n = 13), CNNA (n = 39), MNB (n = 8)] of which 53% were nosocomial and resulted in high in-hospital mortality. Gram-negative bacilli dominated the ascitic fluid culture (12/21, 57%) and 10/12 (83%) of them were extended spectrum beta-lactamases (ESBL) producers. Six (60%) ESBL producers were sensitive to cefoperazone-sulbactam and 70% to carbapenems. Child-Pugh-Turcotte (CPT) score of ≥ 11 independently determined in-hospital mortality in children with AFI. CONCLUSIONS AFI was found in 31% children with liver disease and almost half of them were nosocomial resulting in high mortality. ESBL producing Gram-negative bacteria were the most frequently isolated organisms. Cefoperazone-sulbactam or carbapenems may be useful empirical antibiotics in nosocomial setting. Children with AFI and CPT score ≥ 11 should be evaluated for liver transplantation.
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Affiliation(s)
- Sumit Kumar Singh
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India
| | - Ujjal Poddar
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India.
| | - Richa Mishra
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Anshu Srivastava
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India
| | - Surender Kumar Yachha
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India
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Montrief T, Koyfman A, Long B. Acute liver failure: A review for emergency physicians. Am J Emerg Med 2018; 37:329-337. [PMID: 30414744 DOI: 10.1016/j.ajem.2018.10.032] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2018] [Revised: 10/15/2018] [Accepted: 10/17/2018] [Indexed: 02/08/2023] Open
Abstract
INTRODUCTION Acute liver failure (ALF) remains a high-risk clinical presentation, and many patients require emergency department (ED) management for complications and stabilization. OBJECTIVE This narrative review provides an evidence-based summary of the current data for the emergency medicine evaluation and management of ALF. DISCUSSION While ALF remains a rare clinical presentation, surveillance data suggest an overall incidence between 1 and 6 cases per million people every year, accounting for 6% of liver-related deaths and 7% of orthotopic liver transplants (OLT) in the U.S. The definition of ALF includes neurologic dysfunction, an international normalized ratio ≥ 1.5, no prior evidence of liver disease, and a disease course of ≤26 weeks, and can be further divided into hyperacute, acute, and subacute presentations. There are many underlying etiologies, including acetaminophen toxicity, drug induced liver injury, and hepatitis. Emergency physicians will be faced with several complications, including encephalopathy, coagulopathy, infectious processes, renal injury, and hemodynamic instability. Critical patients should be evaluated in the resuscitation bay, and consultation with the transplant team for appropriate patients improves patient outcomes. This review provides several guiding principles for management of acute complications. Using a pathophysiological-guided approach to the management of ALF associated complications is essential to optimizing patient care. CONCLUSIONS ALF remains a rare clinical presentation, but has significant morbidity and mortality. Physicians must rapidly diagnose these patients while evaluating for other diseases and complications. Early consultation with a transplantation center is imperative, as is identifying the underlying etiology and initiating symptomatic care.
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Affiliation(s)
- Tim Montrief
- University of Miami, Jackson Memorial Hospital/Miller School of Medicine, Department of Emergency Medicine, 1611 N.W. 12th Avenue, Miami, FL 33136, United States
| | - Alex Koyfman
- The University of Texas Southwestern Medical Center, Department of Emergency Medicine, 5323 Harry Hines Boulevard, Dallas, TX 75390, United States
| | - Brit Long
- Brooke Army Medical Center, Department of Emergency Medicine, 3841 Roger Brooke Dr, Fort Sam Houston, TX 78234, United States.
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Alam S, Khanna R, Sood V, Lal BB, Rawat D. Profile and outcome of first 109 cases of paediatric acute liver failure at a specialized paediatric liver unit in India. Liver Int 2017; 37:1508-1514. [PMID: 28111909 DOI: 10.1111/liv.13370] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2016] [Accepted: 01/15/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The outcome of paediatric acute liver failure largely depends on age and aetiology. The aim of this work was to study the aetiological spectrum and outcome of the paediatric acute liver failure cases. METHODS This prospective observational study included all children (<18 years age) fulfilling paediatric acute liver failure study group definition. Aetiological evaluation was done and predictive factors for poor outcome (death or liver transplantation) were analysed. RESULTS There were 109 children in total. The commonest aetiology was viral infections (50, 45.8%) followed by metabolic liver diseases (14, 13.2%) and drug-induced liver injury (12, 11%). Viral, indeterminate and drug-induced liver injury group were older in age, had higher international normalized ratio and alanine transaminases in comparison with those with metabolic liver diseases and other aetiologies (P<.05). At 90 days from presentation, 52 (47.7%) children survived with native liver. On multivariate analysis, jaundice to encephalopathy interval >7 days (adjusted OR: 9.16, 95% CI: 1.55-53) and higher paediatric/model for end-stage liver disease scores at 72 hours (adjusted OR: 1.2, 95% CI: 1.08-1.32) were associated with poor outcome. CONCLUSION Viral infections, indeterminate and drug-induced liver injury-related paediatric acute liver failure usually present in older children with higher international normalized ratio and alanine transaminases. Jaundice to encephalopathy interval >7 days and paediatric/model for end stage liver disease score >24 at 72 hours are associated with poor outcome.
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Affiliation(s)
- Seema Alam
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Rajeev Khanna
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Vikrant Sood
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Bikrant B Lal
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Dinesh Rawat
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Study of Carnitine/Acylcarnitine and Amino Acid Profile in Children and Adults With Acute Liver Failure. J Pediatr Gastroenterol Nutr 2017; 64:869-875. [PMID: 28045774 DOI: 10.1097/mpg.0000000000001510] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
OBJECTIVES Fatty acid oxidation defects (FAODs) may underlie or modify the course of acute liver failure (ALF). Overall significance of carnitine/acylcarnitine and amino acid profile in ALF is similarly undetermined. Thus, this study was undertaken to study the abnormalities in carnitine/acylcarnitine and amino acid profile in ALF. METHODS A prospective study was performed including all patients with ALF, and detailed evaluation including metabolic testing was done. RESULTS A total of 55 patients (33 pediatric and 22 adult patients) were included in the study. Three patients (a 1-year 6-month-old child, a 13-year-old adolescent, and a 21-year-old adult, ie, 5.5% of all) were identified for the study with underlying metabolic etiology, that is, carnitine palmitoyl transferase-1 deficiency, based on the abnormal carnitine/acylcarnitine profile. Almost three-fourths of patients (78%) had evidence of serum hyperaminoacidemia. Thirty-one patients (56%) had evidence of abnormal carnitine/acylcarnitine profile with predominant abnormality being low free carnitine (C0). Higher levels of serum tyrosine (P = 0.002) and lower levels of serum C0 (P = 0.032) in children and higher levels of serum phenyalanine (P = 0.047) in adults predicted poor outcome (death/liver transplant) on univariate analysis. CONCLUSIONS FAODs are not uncommon in ALF with a suggested prevalence of approximately 5.5%. FAODs can cause ALF or modify the natural course of ALF caused by other etiologies. Serum hyperaminoacidemia and low serum free carnitine may predict poor outcome in patients with acute liver failure.
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Prevalence, Clinical Profile, and Outcome of Ascitic Fluid Infection in Children With Liver Disease. J Pediatr Gastroenterol Nutr 2017; 64:194-199. [PMID: 27482766 DOI: 10.1097/mpg.0000000000001348] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
OBJECTIVES Pediatric literature on spontaneous bacterial peritonitis (SBP) is limited. We evaluated the prevalence, subtypes, clinical profile, and effect on outcome of ascitic fluid infection (AFI) in children with liver disease. METHODS Children with liver disease-related ascites and subjected to paracentesis were classified as no-AFI and AFI (SBP, culture-negative neutrocytic ascites [CNNA], and monomicrobial non-neutrocytic bacterascites). Clinical and laboratory parameters, in-hospital mortality, and outcome in follow-up were noted. RESULTS Two hundred sixty-two children (163 boys; age 84 [1-240] months, chronic liver disease [CLD, n = 173], non-CLD [n = 89]) were enrolled. A total of 28.6% (n = 75) had SBP/CNNA, more common in CLD than non-CLD (55/173 [31.7%] vs 20/89 [22.4%]; P = 0.1). A total of 50.6% SBP/CNNA cases were symptomatic for AFI. Gram-negative bacilli were isolated from 70% SBP cases. Twenty-five percent (18/72) CLD children with AFI had a poor hospital outcome, with INR, Child-Pugh score and gastrointestinal bleeding predicting outcome on multivariate analysis. Patients with CLD with SBP had higher in-hospital mortality (10/20 vs 5/35; P = 0.01) than those with CNNA, but similar Child-Pugh score (12[7-15] vs 11[7-14]; P = 0.1), recurrence of AFI (3/9 vs 6/24; P = 0.6) and mortality in follow-up (22.2% vs 25%; P = 0.1). Patients with CLD with SBP/CNNA had higher mortality over 1 year follow-up than no-AFI (24.2% [8/33] vs 12.2% [7/57]; P = 0.1) but the difference was not significant. CONCLUSIONS A total of 28.6% children with liver disease-related ascites have SBP/CNNA; 50% are symptomatic. Patients with CLD with SBP/CNNA have a mortality of 24% over 1year follow-up. CLD with SBP is similar to CNNA except for higher in-hospital mortality.
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Pediatric Acute-on-Chronic Liver Failure in a Specialized Liver Unit: Prevalence, Profile, Outcome, and Predictive Factors. J Pediatr Gastroenterol Nutr 2016; 63:400-5. [PMID: 26967824 DOI: 10.1097/mpg.0000000000001179] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES The aim of the study was to assess the prevalence, profile, outcome, and predictive factors of pediatric acute-on-chronic liver failure (ACLF). METHODS All children 3 months to 18 years satisfying the Asia Pacific Association for the Study of Liver Diseases definition of ACLF were included. Data were both extracted from records (January 2011 to December 2014) and prospectively collected (January to October 2015). Successful outcome was defined as survival with native liver at 90 days, whereas poor outcome included those who died or received liver transplantation. RESULTS Of the 499 children with chronic liver disease (CLD), 56 (11.2%) presented as ACLF, with a mean age of 9.35 (±4.39) years. Wilson disease and autoimmune hepatitis were the commonest underlying CLDs accounting for 24 (42.8%) and 18 (32.1%) cases, respectively. The most frequent events precipitating ACLF were a flare up of the underlying disease in 27 (48.2%) and acute viral hepatitis in 17 (30%). Poor outcome occurred in 22 (39.3%) children: 17 (30.4%) died and 5 (8.9%) received liver transplantation. Poor outcome was associated with grades 3 to 4 hepatic encephalopathy, bilirubin ≥17.5, international normalized ratio ≥3.5, and presence of 2 or more organ failures. On multivariate analysis, a Chronic Liver Failure-Sequential Organ Failure Assessment score ≥10 best predicted mortality (odds ratio 20.45, 95% confidence interval 3.9-106.7). CONCLUSIONS ACLF is present in 11.2% of childhood CLD, with a 90-day native liver survival of 61%. A Chronic Liver Failure-Sequential Organ Failure Assessment score of ≥10 best predicts mortality at day 90.
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Outcomes of Children With and Without Hepatic Encephalopathy From the Pediatric Acute Liver Failure Study Group. J Pediatr Gastroenterol Nutr 2016; 63:357-64. [PMID: 27367788 PMCID: PMC4992416 DOI: 10.1097/mpg.0000000000001178] [Citation(s) in RCA: 67] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Hepatic encephalopathy (HE) is challenging to identify in children with acute liver failure and was not a requirement for enrollment into the Pediatric Acute Liver Failure Study Group (PALFSG). The outcomes of PALFSG participants presenting with and without HE are presented. METHODS PALFSG participants were classified based on daily assessment of HE during the first 7 days following study enrollment: group 1-never developed HE; group 2-no HE at enrollment with subsequent HE development; and group 3-HE at study enrollment. Clinical and biochemical parameters and outcomes of death, spontaneous recovery, or liver transplantation were compared between groups. RESULTS Data from 769 PALFSG (54% boys; median age 4.2 years; range 0-17.9 years) participants were analyzed, with 277 in group 1 (36%), 83 in group 2 (11%), and 409 in group 3 (53%). Mortality occurred in 11% of all participants and was highest among group 3 participants who demonstrated persistent grade III-IV HE (55%) or showed progression of HE (26%). Eleven (4%) group 1 participants died within 21 days of enrollment. Spontaneous recovery was highest in group 1 (79%) and lowest in group 2 (25%; P < 0.001). CONCLUSIONS Mortality 21 days after enrollment was highest in participants enrolled with severe HE (grades III or IV) or demonstrating HE progression. Four percent of participants without recorded clinical HE in the 7 days after enrollment, however, died within 21 days. Improved assessment of neurological injury and pediatric acute liver failure prognostication schema are needed.
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Abstract
CONTEXT Suspecting metabolic liver disease in an infant or young child with acute liver failure, and a protocol-based workup for diagnosis is the need of the hour. EVIDENCE ACQUISITION Data over the last 15 years was searched through Pubmed using the keywords Metabolic liver disease and Acute liver failure with emphasis on Indian perspective. Those published in English language where full text was retrievable were included for this review. RESULTS Metabolic liver diseases account for 13-43% cases of acute liver failure in infants and young children. Etiology remains indeterminate in very few cases of liver failure in studies where metabolic liver diseases were recognized in large proportion. Galactosemia, tyrosinemia and mitochondrial disorders in young children and Wilsons disease in older children are commonly implicated. A high index of suspicion for metabolic liver diseases should be kept when there is strong family history of consanguinity, recurrent abortions or sibling deaths; and history of recurrent diarrhea, vomiting, failure to thrive or developmental delay. Simple dietary modifications and/or specific management can be life-saving if instituted promptly. CONCLUSION A high index of suspicion in presence of red flag symptoms and signs, and a protocol-based approach helps in timely diagnosis and prompt administration of lifesaving therapy.
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Affiliation(s)
- Seema Alam
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India. Correspondence to: Prof Seema Alam, Professor and Head, Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi 110 070, India.
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Abstract
The development of vaccination is a major achievement in modern medicine. However, children treated with immunosuppression may not at all, or only in part, receive routine immunization due to uncertainty of its risks and effect. There is a substantial lack of pediatric studies concerning the efficacy and safety of vaccination in this patient group. Experience from similar adult groups and children with HIV infection can be used as a model for other disease categories. With increasing knowledge of the immunologic basis of vaccination and how immunosuppressive drugs interfere with the immune system, improved vaccines could be tailored, and adequate, individualized guidelines issued.
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Affiliation(s)
- Thomas H Casswall
- Paediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital, Karolinska University Hospital, Sweden.
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Shen ZY, Zhang J, Song HL, Zheng WP. Bone-marrow mesenchymal stem cells reduce rat intestinal ischemia-reperfusion injury, ZO-1 downregulation and tight junction disruption via a TNF-α-regulated mechanism. World J Gastroenterol 2013; 19:3583-3595. [PMID: 23801859 PMCID: PMC3691049 DOI: 10.3748/wjg.v19.i23.3583] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2012] [Revised: 02/21/2013] [Accepted: 04/04/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effect of bone-marrow mesenchymal stem cells (BM MSCs) on the intestinal mucosa barrier in ischemia/reperfusion (I/R) injury.
METHODS: BM MSCs were isolated from male Sprague-Dawley rats by density gradient centrifugation, cultured, and analyzed by flow cytometry. I/R injury was induced by occlusion of the superior mesenteric artery for 30 min. Rats were treated with saline, BM MSCs (via intramucosal injection) or tumor necrosis factor (TNF)-α blocking antibodies (via the tail vein). I/R injury was assessed using transmission electron microscopy, hematoxylin and eosin (HE) staining, immunohistochemistry, western blotting and enzyme linked immunosorbent assay.
RESULTS: Intestinal permeability increased, tight junctions (TJs) were disrupted, and zona occludens 1 (ZO-1) was downregulated after I/R injury. BM MSCs reduced intestinal mucosal barrier destruction, ZO-1 downregulation, and TJ disruption. The morphological abnormalities after intestinal I/R injury positively correlated with serum TNF-α levels. Administration of anti-TNF-α IgG or anti-TNF-α receptor 1 antibodies attenuated the intestinal ultrastructural changes, ZO-1 downregulation, and TJ disruption.
CONCLUSION: Altered serum TNF-α levels play an important role in the ability of BM MSCs to protect against intestinal I/R injury.
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Management of acute liver failure in infants and children: Consensus statement of the pediatric gastroenterology chapter, Indian academy of pediatrics. Indian Pediatr 2013; 50:477-82. [DOI: 10.1007/s13312-013-0147-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
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Poddar B, Saigal S, Kumar A, Singh RK, Azim A, Gurjar M, Baronia A. Factors associated with outcome in acute liver failure in an intensive care unit. Indian J Gastroenterol 2013; 32:172-8. [PMID: 23054946 DOI: 10.1007/s12664-012-0252-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2012] [Accepted: 08/30/2012] [Indexed: 02/04/2023]
Abstract
AIM To study the factors associated with outcome in acute liver failure (ALF) in an intensive care unit (ICU). METHODS Consecutive patients with ALF admitted to the ICU from August 2003 to April 2010 were included. Factors associated with the primary outcome, death or survival, were compared. RESULTS Of 52 patients of median age 19 years (range 3-65), 35 (67 %) died. The etiology was viral hepatitis in 66 %, drug induced (anti-tubercular therapy) in 15 % and idiopathic in 15 %. Grades III+IV encephalopathy were found in 12 (70.6 %) survivors as against 33 (94.3 %) nonsurvivors (p = 0.019). The median admission sequential organ failure assessment (SOFA) score was eight in survivors vs. 12 in nonsurvivors (p < 0.001). Median admission prothrombin time (PT) was 42 s in survivors vs. 51 in nonsurvivors (p = 0.384); 16/17 (94.1 %) survivors had normal PT on day 4 as compared to 7/35 (20 %) nonsurvivors (p < 0.001). Median PT on day 4 was 18 s in survivors against 37 in nonsurvivors (p < 0.001). Serum bilirubin, alanine aminotransferase; and serum creatinine, sodium and phosphorus were similar in survivors and nonsurvivors. Mechanical ventilation, vasopressors and dialysis were used in 65 %, 30 %, and 12 % survivors as against 100 % (p < 0.001), 51 % and 26 % nonsurvivors. Sixteen patients had upper gastrointestinal (GI) bleed. Blood cultures were positive more often in nonsurvivors (p = 0.058). On multiple regression analysis, factors independently associated with outcome included admission SOFA score >9.5 and absolute value of PT on day 4. CONCLUSIONS Grades III and IV encephalopathy, higher SOFA score at admission and a prolonged PT which did not normalize by 4 days were associated with mortality in ALF.
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Affiliation(s)
- Banani Poddar
- Department of Critical Care Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014, India.
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Faillon S, Martinot A, Hau I, Puget A, Moulin F, Noel G, Guen CGL, Lorrot M, Callamand P, Hue V, Meritet JF, Gendrel D, Dubos F. Impact of travel on the seroprevalence of hepatitis A in children. J Clin Virol 2013; 56:46-51. [DOI: 10.1016/j.jcv.2012.10.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2012] [Revised: 09/24/2012] [Accepted: 10/10/2012] [Indexed: 12/11/2022]
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Kaur S, Kumar P, Kumar V, Sarin SK, Kumar A. Etiology and prognostic factors of acute liver failure in children. Indian Pediatr 2012; 50:677-9. [PMID: 23255683 DOI: 10.1007/s13312-013-0189-7] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2012] [Accepted: 10/26/2012] [Indexed: 01/13/2023]
Abstract
Acute liver failure (ALF) is a life-threatening condition characterized by jaundice, encephalopathy and coagulopathy leading to multiorgan failure in a patient with no prior history of liver disease. Forty three consecutive patients of ALF admitted in Pediatric ICU were studied for etiology and prognostic factors. Etiology was established in 91% cases. Viral infections were the most common cause. Mortality rate was 44%. Increasing grade of encephalopathy, >7 days interval between the onset of prodromal symptoms and encephalopathy, blood glucose <45mg/dL, serum bilirubin > 10mg/dL and pH <7.35 or >7.45 on admission were found to be associated with increased risk of mortality.
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Affiliation(s)
- Sharandeep Kaur
- Department of Pediatrics, Kalawati Saran Childrens Hospital, Lady Hardinge Medical College, New Delhi, India.
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Srivastava A, Yachha SK, Poddar U. Predictors of outcome in children with acute viral hepatitis and coagulopathy. J Viral Hepat 2012; 19:e194-201. [PMID: 22239519 DOI: 10.1111/j.1365-2893.2011.01495.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
The presence of coagulopathy in acute viral hepatitis (AVH) in children raises issues about prognosis and need for liver transplantation. We evaluated factors predicting outcome in such patients and determined the applicability of the paediatric acute liver failure study group (PALFSG) definition of acute liver failure (ALF) of coagulopathy alone in comparison with coagulopathy and encephalopathy. Children with AVH (clinical features, raised transaminases and positive viral serology) with uncorrectable coagulopathy [prothrombin time (PT) > 15 s] with or without hepatic encephalopathy (HE) were enrolled. Comparative analysis was based on (i) outcome: survivors/nonsurvivors and (ii) ALF criteria: group A coagulopathy (PT > 15 s) and encephalopathy and group B coagulopathy (PT > 20 s). We studied 130 children (86 boys, mean age 7.5 ± 4.5 years): 86 recovered and 44 died. Single virus infection was present in 96 (74%), hepatitis A being the commonest (n-69). On multiple stepwise logistic regression analysis, age <3.5 years, serum bilirubin ≥ 16.7 mg/dL, PT ≥ 40.5 s and clinical signs of cerebral oedema were independent predictors of mortality. Mortality increased from 0% with single to 100% with four risk factors. Ninety-seven cases met the PALFSG criteria: group A-79 and group B-18. Group A subjects had higher mortality (55.6%vs 0%) and poorer liver functions (bilirubin 18.1 ± 8.9 vs 13.8 ± 6.9 mg/dL, PT 63.9 ± 35.1 vs 27.2 ± 5.2 s) than group B. PT deteriorated significantly with the appearance and progression of HE. One-third of children with AVH with coagulopathy die without transplantation. Age <3.5 years, bilirubin ≥ 16.7 mg/dL, PT ≥ 40.5 s and signs of cerebral oedema are predictors of poor outcome. Children with encephalopathy and coagulopathy have a poorer outcome than those with coagulopathy alone.
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Affiliation(s)
- A Srivastava
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
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30
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Dong-Yan L, Weiguo J, Pei L. Reduction of the amount of intestinal secretory IgA in fulminant hepatic failure. Braz J Med Biol Res 2011; 44:477-82. [PMID: 21519636 DOI: 10.1590/s0100-879x2011007500051] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2010] [Accepted: 03/31/2011] [Indexed: 01/10/2023] Open
Abstract
Intestinal barrier dysfunction plays an important role in spontaneous bacterial peritonitis. In the present study, changes in the intestinal barrier with regard to levels of secretory immunoglobulin A (SIgA) and its components were studied in fulminant hepatic failure (FHF). Immunohistochemistry and double immunofluorescent staining were used to detect intestinal IgA, the secretory component (SC) and SIgA in patients with FHF (20 patients) and in an animal model with FHF (120 mice). Real-time PCR was used to detect intestinal SC mRNA in the animal model with FHF. Intestinal SIgA, IgA, and SC staining in patients with FHF was significantly weaker than in the normal control group (30 patients). Intestinal IgA and SC staining was significantly weaker in the animal model with FHF than in the control groups (normal saline: 30 mice; lipopolysaccharide: 50 mice; D-galactosamine: 50 mice; FHF: 120 mice). SC mRNA of the animal model with FHF at 2, 6, and 9 h after injection was 0.4 ± 0.02, 0.3 ± 0.01, 0.09 ± 0.01, respectively. SC mRNA of the animal model with FHF was significantly decreased compared to the normal saline group (1.0 ± 0.02) and lipopolysaccharide group (0.89 ± 0.01). The decrease in intestinal SIgA and SC induced failure of the intestinal immunologic barrier and the attenuation of gut immunity in the presence of FHF.
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Affiliation(s)
- Liu Dong-Yan
- Research Center, China Medical University Affiliated Shengjing Hospital and Key Laboratory of Congenital Malformation Research, Ministry of Health, Shenyang, China
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Honar N, Imanieh MH, Haghighat M, Dehghani SM, Zahmatkeshan M, Geramizadeh B, Badiee P, Nikeghbalian S, Kazemi K, Bahador A, Salahi H, Malek-Hosseini SA. Evaluation of Candida infection after six months of transplantation in pediatric liver recipients in iran. Int J Organ Transplant Med 2011; 2:105-7. [PMID: 25013602 PMCID: PMC4089262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Liver transplantation (LT) is the standard treatment of end-stage liver diseases (ESLD). Invasive fungal infection is one of the important causes of morbidity and mortality after transplantation. OBJECTIVE To determine the incidence of late-onset (after 6 months of LT) Candida infection in recipients. METHODS A retrospective study was conducted to evaluate 50 pediatric patients after LT for 8 years at the LT Unit of Nemazee Hospital affiliated to Shiraz University of Medical Sciences, Shiraz, Iran. We followed the patients until 6 months post-LT for episodes of Candida infection proven by culture. RESULTS One recipient (2%) developed late-onset esophageal candidiasis with improvement after intravenous amphotricin therapy but finally expired with a diagnosis of post-transplant lymphoproliferative disorder (PTLD). CONCLUSIONS The incidence of late-onset Candida infection is not significant in pediatric liver recipient, but it still remains a significant problem. Control of Candida colonization would reduce the risk of invasive fungal infections and possibly more fatal complications.
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Affiliation(s)
- N. Honar
- Gastroenterohepatology Research Center,
| | - M. H. Imanieh
- Gastroenterohepatology Research Center,,Shiraz Transplant Research Center
| | | | - S. M. Dehghani
- Gastroenterohepatology Research Center,,Shiraz Transplant Research Center,Correspondence: Seyed Mohsen Dehghani, MD, Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
E-mail:
| | | | | | - P. Badiee
- Clinical Microbiology Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
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Honar N, Imanieh MH, Dehghani SM, Haghighat M, Geramizadeh B, Yaghobi R, Alborzi A, Ziaeian M, Kazemi K, Nikeghbalian S, Bahador A, Salahi H, Malek Hosseini SA. Evaluation of cytomegalovirus infection after six months of liver transplantation in children in shiraz, southern iran. Int J Organ Transplant Med 2011; 2:20-4. [PMID: 25013590 PMCID: PMC4089245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Liver transplantation (LT) is a life-saving treatment for end-stage liver diseases (ESLD). Cytomegalovirus (CMV) infection is one of the important causes of morbidity after LT. OBJECTIVE To evaluate the incidence of late-onset (after 6 months of LT) CMV infection in pediatric recipients. METHODS A retrospective analysis was conducted to evaluate 50 pediatric patients who underwent LT for 8 years at the LT Unit of Nemazee Hospital affiliated to Shiraz University of Medical Sciences, Shiraz, Iran. We retrospectively investigated episodes of CMV infection after 6 months of LT proven by CMV antigenemia test. RESULTS Three recipients (6%) developed late-onset CMV infection. These patients finally responded to ganciclovir. CONCLUSION CMV infection is one of the most common post-LT viral infections that usually occurs in the first six months of LT. Our study shows that the incidence of late-onset CMV infection is relatively low, but it still remains a significant problem. Therefore, monitoring and management is crucial for improving the survival of children.
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Affiliation(s)
- N. Honar
- Gastroenterohepatology Research Center,
| | - M. H. Imanieh
- Gastroenterohepatology Research Center, ,Shiraz Transplant Research Center,
| | - S. M. Dehghani
- Gastroenterohepatology Research Center, ,Shiraz Transplant Research Center, ,Correspondence: Seyed Mohsen Dehghani, MD,
Associate Professor of Pediatric Gastroenterology,
Shiraz Transplant Research Center, Gastroenterohepatology Research Center, Shiraz University of Medical Sciences,
Shiraz, 71937-11351, Iran. Tel: +98 711 626 1775 Fax: +98 711 647 4298 E-mail:
| | | | | | | | - A. Alborzi
- Clinical Microbiology Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - M. Ziaeian
- Clinical Microbiology Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
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Intensive care management of children with acute liver failure. Indian J Pediatr 2010; 77:1288-95. [PMID: 20799075 DOI: 10.1007/s12098-010-0167-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2010] [Accepted: 07/30/2010] [Indexed: 12/20/2022]
Abstract
Acute liver failure is an uncommon condition associated with multi organ involvement, high morbidity and mortality. Etiology of acute liver failure varies with age and geographical location. Most cases of acute liver failure in India are due to infectious causes predominantly viral hepatitis. A significant group with indeterminate causation remains, despite careful investigation. The etiology of acute liver failure in infants is largely metabolic. The mainstay of management is supportive care in an intensive care unit. Monitoring of clinical and biochemical parameters is done frequently until the patient becomes stable. Mortality is predominantly due to raised intracranial pressure, infections and multi-organ failure. Liver transplant is an important life saving procedure for children with acute liver failure.
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Kim JE, Oh SH, Kim KM, Choi BH, Kim DY, Cho HR, Lee YJ, Rhee KW, Park SJ, Lee YJ, Lee SG. Infections after living donor liver transplantation in children. J Korean Med Sci 2010; 25:527-31. [PMID: 20357992 PMCID: PMC2844587 DOI: 10.3346/jkms.2010.25.4.527] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2009] [Accepted: 07/27/2009] [Indexed: 11/20/2022] Open
Abstract
The aim of this study was to evaluate the infectious complications after living donor liver transplantation (LDLT) in children. We enrolled 95 children (38 boys and 57 girls) who underwent LDLT from 1994 to 2004. The median age was 22 months (range, 6 months to 15 yr). We retrospectively investigated the proven episodes of bacterial, viral, and fungal infection. There occurred 150 infections in 67 (70%) of 95 patients (1.49 infections/patient); 74 in 43 patients were bacterial, 2 in 2 were fungal, and 74 in 42 were viral. The most common sites of bacterial infection were the bloodstream (33%) and abdomen (25%). Most of the bacterial infections occurred within the first month after LDLT. Bacterial and fungal infections did not result in any deaths. The most common causes of viral infection were Epstein-Barr virus in 37 patients and cytomegalovirus in 18. Seven of the 14 deaths after LDLT were associated with viral infection. Our study suggests that infection is one of the important causes of morbidity and mortality after LDLT. Especially careful monitoring and management of viral infections is crucial for improving the outcome of LDLT in children.
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Affiliation(s)
- Jeong Eun Kim
- Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
- Department of Pediatrics, Jung-Gu Community Health Center, Seoul, Korea
| | - Seak Hee Oh
- Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyung Mo Kim
- Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Bo Hwa Choi
- Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
- Department of Pediatrics, Yosuseongsim General Hospital, Yosu, Korea
| | - Dae Yeon Kim
- Department of Pediatric Surgery, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyung Rae Cho
- Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Yeoun Joo Lee
- Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Kang Won Rhee
- Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Seong Jong Park
- Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Young Joo Lee
- Division of Hepato-Biliary and Pancreas Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung Gyu Lee
- Division of Hepato-Biliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Heffron TG, Pillen T, Smallwood G, Rodriguez J, Sekar S, Henry S, Vos M, Casper K, Gupta NA, Fasola CG, Romero R. Pediatric liver transplantation for acute liver failure at a single center: a 10-yr experience. Pediatr Transplant 2010; 14:228-32. [PMID: 19519799 PMCID: PMC4380080 DOI: 10.1111/j.1399-3046.2009.01202.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Children transplanted for ALF urgently require an optimal graft and have lower post-transplant survival compared with children transplanted for chronic liver disease. Over 10 yr, 33 consecutive children transplanted for ALF were followed. Demographics, encephalopathy, intubation, dialysis, laboratory values, graft type ABOI, XL (GRWR > 5%), DDSLT, LDLT and WLT were evaluated. Complications and survival were determined. ALF accounted for 33/201 (16.4%) of transplants during this period. Twelve of 33 received ABOI, five XL grafts, 18 DDSLT, and three LDLT. Waiting time pretransplant was 2.1 days. One- and three-yr patient survival in the ALF group was 93.4% and 88.9%, and graft survivals were 86.4% and 77.7%. Median follow-up was 1452 days. ABOI one- and three yr patient and graft survival in the ALF was 91.6% and 78.6%. No difference in graft or patient survival was noted in the ALF and chronic liver disease group or the ABOI and the ABO compatible group. A combination of ABO incompatible donor livers, XL grafts, DDSLT, LDLT and WLT led to a short wait time and subsequent graft and patient survival comparable to patients with non-acute disease.
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Yachha SK, Goel A, Khanna V, Poddar U, Srivastava A, Singh U. Ascitic form of sporadic acute viral hepatitis in children: a distinct entity for recognition. J Pediatr Gastroenterol Nutr 2010; 50:184-187. [PMID: 19966578 DOI: 10.1097/mpg.0b013e3181aecb4c] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND OBJECTIVES This study looked at the frequency and differences in presentation, laboratory parameters, and outcome between ascitic acute viral hepatitis (AAVH) and nonascitic acute viral hepatitis (NAVH) in children. METHODS Diagnosis of AVH was based on clinical features, >3-fold elevation of alanine aminotransferase, viral marker positivity (IgM antihepatitis A virus, IgM antihepatitis E virus, hepatitis B surface antigen, and IgM antihepatitis B core antigen) at presentation, absence of history of liver disease, and subsequent normalization within 6 months of clinical features and liver functions including sustained resolution of ascites in AAVH on follow-up. RESULTS A total of 139 children (121 children with NAVH and 18 with AAVH, 12.9%) were studied. Children with AAVH in comparison with those with NAVH were younger (median age 4 vs 8 years), had lower frequency of prodrome (22% vs 51%), lower serum albumin (median 2.8 vs 3.7 g/dL), low total serum protein (median 6.5 vs 7.4 g/dL), and prolongation of prothrombin time (median 4.8 vs 1.05 seconds); all P < 0.03. No significant differences were found in sex, height standard deviation scores, duration of symptoms, liver span or consistency, transaminases, alkaline phosphatase, and etiology of NAVH versus AAVH. Among the AAVH group clinically detectable ascites was present in 38.9% (7/18), spontaneous bacterial peritonitis in 11%, and diuretics had to be used in 44% of cases. Ascites resolved in all of the cases in 8 weeks (94.4% cases in <4 weeks) and liver functions normalized in 17%, 50%, and 33% cases in <4, 4 to 8, and >8 weeks duration, respectively. CONCLUSIONS We report AAVH as a distinct entity that affects younger children. This subgroup has compromised biosynthetic liver functions irrespective of viral etiology with total recovery.
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Affiliation(s)
- Surender K Yachha
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
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Song HL, Lv S, Liu P. The roles of tumor necrosis factor-alpha in colon tight junction protein expression and intestinal mucosa structure in a mouse model of acute liver failure. BMC Gastroenterol 2009; 9:70. [PMID: 19772664 PMCID: PMC2761933 DOI: 10.1186/1471-230x-9-70] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2009] [Accepted: 09/22/2009] [Indexed: 01/30/2023] Open
Abstract
Background Spontaneous bacterial peritonitis (SBP) is a common clinical disease and one of the most severe complications of acute liver failure (ALF). Although the mechanism responsible for SBP is unclear, cytokines play an important role. The aim of this study was to investigate the effects of tumor necrosis factor-alpha (TNF-α) on the structure of the intestinal mucosa and the expression of tight junction (Zona Occludens 1; ZO-1) protein in a mouse model of ALF. Methods We induced ALF using D-galactosamine/lipopolysaccharide (GalN/LPS) or GalN/TNF-α and assessed the results using transmission electron microscopy, immunohistochemistry, Western blotting, ELISA and real-time quantitative PCR. The effects of administration of anti-TNF-α IgG antibody or anti-TNF-α R1 antibody before administration of GalN/LPS or GalN/TNF-α, respectively, on TNF-α were also assessed. Results Morphological abnormalities in the intestinal mucosa of ALF mice were positively correlated with serum TNF-α level. Electron microscopic analysis revealed tight junction (TJ) disruptions, epithelial cell swelling, and atrophy of intestinal villi. Gut bacteria invaded the body at sites where TJ disruptions occurred. Expression of ZO-1 mRNA was significantly decreased in both ALF models, as was the level of ZO-1 protein. Prophylactic treatment with either anti-TNF-α IgG antibody or anti-tumor necrosis factor-a receptor1 (anti-TNF-α R1) antibody prevented changes in intestinal tissue ultrastructure and ZO-1 expression. Conclusion TNF-α affects the structure of the intestinal mucosa, decreases expression of ZO-1, and affects the morphology of the colon in a mouse model of ALF. It also may participate in the pathophysiological mechanism of SBP complicated to ALF.
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Affiliation(s)
- Hong-Li Song
- Department of Infectious Diseases, The First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning Province, PR China.
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Song HL, Lv S, Liu P. The roles of tumor necrosis factor-alpha in colon tight junction protein expression and intestinal mucosa structure in a mouse model of acute liver failure. BMC Gastroenterol 2009. [PMID: 19772664 DOI: 10.1186/1471- 230x-9-70] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND Spontaneous bacterial peritonitis (SBP) is a common clinical disease and one of the most severe complications of acute liver failure (ALF). Although the mechanism responsible for SBP is unclear, cytokines play an important role. The aim of this study was to investigate the effects of tumor necrosis factor-alpha (TNF-alpha) on the structure of the intestinal mucosa and the expression of tight junction (Zona Occludens 1; ZO-1) protein in a mouse model of ALF. METHODS We induced ALF using D-galactosamine/lipopolysaccharide (GalN/LPS) or GalN/TNF-alpha and assessed the results using transmission electron microscopy, immunohistochemistry, Western blotting, ELISA and real-time quantitative PCR. The effects of administration of anti-TNF-alpha IgG antibody or anti-TNF-alpha R1 antibody before administration of GalN/LPS or GalN/TNF-alpha, respectively, on TNF-alpha were also assessed. RESULTS Morphological abnormalities in the intestinal mucosa of ALF mice were positively correlated with serum TNF-alpha level. Electron microscopic analysis revealed tight junction (TJ) disruptions, epithelial cell swelling, and atrophy of intestinal villi. Gut bacteria invaded the body at sites where TJ disruptions occurred. Expression of ZO-1 mRNA was significantly decreased in both ALF models, as was the level of ZO-1 protein. Prophylactic treatment with either anti-TNF-alpha IgG antibody or anti-tumor necrosis factor-a receptor1 (anti-TNF-alpha R1) antibody prevented changes in intestinal tissue ultrastructure and ZO-1 expression. CONCLUSION TNF-alpha affects the structure of the intestinal mucosa, decreases expression of ZO-1, and affects the morphology of the colon in a mouse model of ALF. It also may participate in the pathophysiological mechanism of SBP complicated to ALF.
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Affiliation(s)
- Hong-Li Song
- Department of Infectious Diseases, The First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning Province, PR China.
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40
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Mahadeb P, Gras J, Sokal E, Otte JB, Lerut J, Detaille T, de Cléty SC, Reding R. Liver transplantation in children with fulminant hepatic failure: The UCL experience. Pediatr Transplant 2009; 13:414-20. [PMID: 19017285 DOI: 10.1111/j.1399-3046.2008.01008.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
The outcome of pediatric LT for FHF was shown to be poor in our center. To better understand such results, recipient and transplant parameters with a putative impact on post-transplant outcome were analyzed in LT for FHF. Between March 1984 and June 2002, 33 children with FHF received a primary liver allograft. The overall results in this series were studied with respect to pre-operative demographic and metabolic variables, peri-operative events, and outcome. Five-yr patient and graft survivals were 71% and 66%, respectively, with a retransplantation rate at 18%. Incidences of perioperative hemorrhage, of HAT and PVT were 14%, 8%, and 4%, respectively. Five-yr acute rejection-free survival rate was 55%. These data confirm the worse outcome following LT for FHF when compared with LT in elective, non-malignant indications such as BA; results in FHF could not be related to surgical or immunological complications in the post-transplant period and it is hypothesized that the MOF associated with FHF contributes to early post-transplant mortality which would justify special management, including aggressive renal and hepatic support.
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Affiliation(s)
- Parikshat Mahadeb
- Pediatric Liver Transplant Program, St Luc University Clinics, Université catholique de Louvain, Brussels, Belgium
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Kirsch R, Yap J, Roberts EA, Cutz E. Clinicopathologic spectrum of massive and submassive hepatic necrosis in infants and children. Hum Pathol 2009; 40:516-26. [PMID: 19121848 DOI: 10.1016/j.humpath.2008.07.018] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2008] [Revised: 07/23/2008] [Accepted: 07/28/2008] [Indexed: 12/13/2022]
Abstract
Clinicopathologic features of 45 patients with fulminant hepatic failure due to massive or submassive hepatic necrosis were studied. Both percutaneous biopsies and liver explants were available in 23 patients, whole livers only in 11 cases, and biopsies only in 11 cases. An etiologic diagnosis was established in 16 cases (36%). A further 3 cases (7%) were associated with aplastic anemia. Established etiologies included drug reactions (n = 7); autoimmune hepatitis, type 2 (n = 3); halothane hepatitis (n = 1); ischemia/hypotension (n = 1); mushroom poisoning (n = 1); mitochondrial disorder (n = 1); hemophagocytic lymphohistiocytosis (n = 1); and adenoviral hepatitis (n = 1). The extent of necrosis on liver biopsy correlated poorly with that in liver explants (mean difference, 32% +/- 23.8%). Almost all cases could be classified into one of 2 broad patterns of necrosis, namely, (1) zonal coagulative necrosis or (2) panlobular (nonzonal) necrosis. These patterns differed significantly with respect to several clinical parameters including sex ratio, peripheral blood white cell count, serum aspartate transaminase and alanine transaminase, conjugated bilirubin, and alkaline phosphatase levels. Livers with panlobular necrosis showed a spectrum of histopathologic findings that included central venulitis (76%), lymphocytic infiltration of large duct/gallbladder epithelium (54%), and syncytial giant cell transformation (18%). These features were not seen in livers with zonal coagulative necrosis which frequently showed prominent steatosis (91%). Both patterns of necrosis frequently showed ductular proliferation (100%) and cholangiolitis (80%). The diagnostic yield of ancillary studies (histochemistry, immunohistochemistry, and electron microscopy) was very low (<1%). The small proportion of cases with etiologic diagnoses precluded correlation of clinical and histopathological parameters with specific etiologies. In summary, this study describes the spectrum of changes seen in massive and submassive necrosis in children and identifies clinical features that might differentiate between 2 broad patterns of necrosis.
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Affiliation(s)
- Richard Kirsch
- Division of Pathology, Department of Pediatric Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, M5G 1X8 Canada.
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Abstract
1. The etiology of acute liver failure in children differs from that in adults, with metabolic conditions being commoner in Europe and North America and hepatitis A being the commonest cause in Asia and South America. 2. Encephalopathy usually is a late feature and is not essential for the diagnosis. 3. Unlike adults, there are no good prognostic criteria that can predict survival without liver transplantation. 4. It is important to exclude genetic multisystem disorders before liver transplantation is considered.
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Affiliation(s)
- Anil Dhawan
- Paediatric Liver Centre, King's College London School of Medicine, King's College Hospital, London, United Kingdom.
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Minuk GY, Sun A, Sun DF, Uhanova J, Nicolle LE, Larke B, Giulivi A. Serological evidence of hepatitis E virus infection in an indigenous North American population. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2007; 21:439-42. [PMID: 17637946 PMCID: PMC2657964 DOI: 10.1155/2007/289059] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BACKGROUND Hepatitis E virus (HEV) infections are thought to be uncommon in North America. Recently, HEV transmission has been reported following the consumption of deer meat. Because deer are closely related to caribou and caribou meat is a staple of the Canadian Inuit and the American Eskimo diet, the present study explored the seroprevalence of HEV infection in an isolated Canadian Inuit community. METHODS Stored sera were thawed and tested for immunoglobulin (Ig) G and IgM anti-HEV by ELISA, and tested for HEV-RNA by reverse transcriptase polymerase chain reaction. RESULTS The study consisted of 393 sera (representing approximately 50% of the community's inhabitants). Eleven samples (3%) were IgG anti-HEV-positive. Their mean age was 29+/-8 years and three were male. Two of 11 (18%) were also IgM anti-HEV-positive. All IgG anti-HEV-positive individuals were HEV-RNA-negative. Liver biochemistry was normal in all. Seven of 11 (64%) were also positive for anti-hepatitis A virus, five (46%) were hepatitis B virus seropositive and none (0%) were positive for anti-hepatitis C virus. There were no associations between infections with HEV and other hepatropic viruses. Serological testing was negative for HEV infection in 25 caribou from an adjacent region. CONCLUSION The results of the present study showed that serological evidence of HEV infection was present in 3% of the observed Canadian Inuit population; the presence of IgM anti-HEV suggested recent infection and HEV did not appear to coinfect with other common hepatotropic viruses. The source of HEV infection in the population remains unclear. These findings are interesting but preliminary. Additional data are required to determine whether HEV infections are responsible for otherwise unexplained acute hepatitis in the Canadian Inuit population and visitors returning from northern North American communities.
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Affiliation(s)
- G Y Minuk
- Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
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Abstract
OBJECTIVE To review the incidence, etiologies, pathophysiology, and treatment of acute liver failure (ALF) in children. Emphasis will be placed on the initial management of the multiple organ system involvement of ALF. METHOD MEDLINE search from 1970 to March 2005 was performed. Search headings were as follows: acute liver failure, fulminant liver failure, pediatric liver failure, hepatic encephalopathy, and liver transplantation. Studies written in English were selected. Pediatric studies were emphasized. Adult studies were referenced if there were no pediatric studies available in regard to a specific aspect of liver failure. CONCLUSIONS Pediatric acute liver failure is a rare but life-threatening disease. The common etiologies differ for given age groups. Management includes treating specific causes and supporting multiple organ system failure. Commonly associated disorders that require initial recognition and treatment include energy production deficiencies (hypoglycemia), coagulation abnormalities, immune system dysfunctions, encephalopathy, and cerebral edema. Criteria used to determine the need for liver transplant are reviewed as well as the difficulties associated with predicting which patients will meet these criteria and how rapidly liver transplant will become the only option. Finally, experimental procedures that may provide additional time for the liver to recover are briefly reported.
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Affiliation(s)
- Joel B Cochran
- Pediatric Department, Medical University of South Carolina, Charleston, SC 29425, USA
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Kumar A, Yachha SK, Poddar U, Singh U, Aggarwal R. Does co-infection with multiple viruses adversely influence the course and outcome of sporadic acute viral hepatitis in children? J Gastroenterol Hepatol 2006; 21:1533-7. [PMID: 16928213 DOI: 10.1111/j.1440-1746.2006.04509.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND This study looked at the frequency of co-infection with multiple hepatotropic viruses and the effect of such infection on the course and outcome of acute sporadic viral hepatitis (AVH) and fulminant hepatic failure (FHF) in children. METHODS Consecutive children up to 15 years of age presenting with AVH or FHF between January 1998 and July 2002 were evaluated prospectively. The following viral markers were assessed in all children: immunoglobulin M (IgM) anti-hepatitis A virus (HAV), IgM anti-hepatitis E virus (HEV), hepatitis B surface antigen (HBsAg), IgM anti-hepatitis B core (HBc), and anti-hepatitis C virus (HCV). RESULTS A total of 149 children were included in the study, 122 with AVH and 27 with FHF. Co-infection with multiple viruses was detected in 30 (24.6%) AVH patients (A+E in 24, A+B in three, and E+B, A+C and A+E+B in one each) and seven (26%) FHF patients (A+E in five, and A+B and E+B in one each). The majority of single infections were due to HAV (AVH 70/92, FHF 14/20) followed by HEV (AVH 9/92, and FHF 5/20). HEV infection was associated with infection with another agent in 88% of patients with AVH (odds ratio 53, 95% confidence interval 15-186, P<0.0001). Frequency of anicteric state, prolonged cholestasis, relapsing hepatitis, ascites, hemolysis and mortality rates were similar in the single and multiple infection groups for both AVH and FHF patients. CONCLUSIONS Co-infection with multiple viruses is observed in one-quarter of patients with sporadic AVH in childhood. Such infection does not produce a more severe disease. HEV positivity is a strong marker for multiple infections.
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MESH Headings
- Adolescent
- Antibodies, Viral/immunology
- Child
- Child, Preschool
- Female
- Hepatitis Viruses/immunology
- Hepatitis, Viral, Human/complications
- Hepatitis, Viral, Human/epidemiology
- Hepatitis, Viral, Human/virology
- Humans
- Incidence
- Liver Failure, Acute/epidemiology
- Liver Failure, Acute/etiology
- Male
- Prospective Studies
- Risk Factors
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Affiliation(s)
- Arvind Kumar
- Department of Gastroenterology (Pediatric Gastroenterology), Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
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Abstract
Ascites is a common clinical problem in children with liver disease. The peripheral arterial vasodilation hypothesis is mostly accepted as the pathophysiological basis of ascites. The most important complication is spontaneous ascitic fluid infection in the form of spontaneous bacterial peritonitis (SBP) and its variants. Aerobic gram-negative bacteria, primarily Escherichia coli, are the most common isolates. Diagnostic paracentesis is done in patients with ascites when diagnosed first time and at the beginning of each admission to hospital. Ascitic fluid is evaluated for cell count with differential, albumin level, total protein and culture. Serum-ascites albumin gradient (SAAG) is the best single test for classifying ascites into portal hypertensive (SAAG> 1.1 g/dL) and non-portal hypertensive (SAAG < 1.1 g/dL) causes. In patients with tense ascites LVP should be performed. A neutrophil count of > 250 cells/mm3 is highly suggestive of bacterial peritonitis. Intravenous cefotaxime is the empiric antibiotic of choice. Long-term administration of oral norfloxacin 5-7.5 mg/Kg once a day in cirrhotic patients with ascitic fluid protein content of < 1g/dL or prior episode of SBP is recommended for prevention of SBP. Oral dual diuretic therapy of single morning dose of spironolactone along with furosemide in the ratio of 5:2 is recommended. While obtaining satisfactory diuretic response dual diuretic therapy can be changed over to monotherapy with spironolactone. Patients should be on sodium restricted diet. Management of ascites might ultimately require liver transplantation.
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Affiliation(s)
- Surender Kumar Yachha
- Department of Gastroenterology (Pediatric Gastroenterology), Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow - 226 014, India.
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Song HL, Lu S, Liu P. Tumor necrosis factor-alpha induces apoptosis of enterocytes in mice with fulminant hepatic failure. World J Gastroenterol 2005; 11:3701-9. [PMID: 15968724 PMCID: PMC4316020 DOI: 10.3748/wjg.v11.i24.3701] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To explore the alterations of intestinal mucosa morphology, and the effects of tumor necrosis factor α (TNFα) on enterocyte apoptosis in mice with fulminant hepatic failure (FHF).
METHODS: Liver damage was induced by lipopolysaccharide (LPS)/TNF-α in D-galactosamine (GalN) sensitized BALB/c mice. There were 40 mice in normal saline (NS)-treated group, 40 mice in LPS-treated group, 40 mice in GalN-treated group, 120 mice in GalN/ LPS-treated group and 120 mice in GalN/ TNFα-treated group. Each group was divided into five subgroups of eight mice each. Serum samples and liver, intestinal tissues were respectively obtained at 2, 6, 9, 12 and 24 h after administration. Anti-TNFα monoclonal antibody was injected intravenously into GalN/LPS-treated mice. Serum TNFα levels were determined by enzyme-linked immunosorbent assays (ELISA). Serum ALT levels were determined using an automatic analyzer. The intestinal tissues were studied under light microscope and electron microscope at 2, 6, 9, 12 and 24 h in mice with fulminant hepatic failure, respectively. Enterocyte apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method. The expression of tumor necrosis factor receptor 1 (TNFR1) in intestinal tissue was tested by immunohistochemistry Envision Two Steps.
RESULTS: Gut mucosa was morphologically normal at all time points in all groups, but typical apoptotic cells could be seen in all experimental groups under electron micro-scope. Apoptosis rate of gut mucosal epithelial cells were significantly increased at 6, 9 and 12 h, peaked at 12 h in mice with fulminant hepatic failure. TNFα induced apoptosis of enterocytes in mice with FHF. The integrated OD (IOD) levels of TNFα receptor 1 protein expressed in the intestine of mice with GalN/LPS and GalN/ TNFα-induced FHF at 2, 6, 9, 12 and 24 h after GalN/LPS and GalN/TNFα administration were 169.54±52.62/905.79±111.84, 11350.67±2133.26/28160.37±4601.67, 25781.00±2277.75/122352.30±49412.40, 5241.53±3007.24/49157.93±9804.88, 7086.13±1031.15/3283.45±127.67, respectively, compared with those in control groups (with NS, LPS and GalN administration, respectively). IOD level of TNFR1 changed significantly at 6, 9 and 12 h after GalN/LPS and GalN/TNFα administration. The expression of TNFR1 protein was significantly higher at 9 h after GalN/LPS and GalN/TNFα administration than that in control groups. Protein expression of TNFR1 was positively correlated with enterocyte apoptosis.
CONCLUSION: TNFα can induce apoptosis of enterocytes in mice with FHF. Anti-TNFα IgG can inhibit this role.
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Affiliation(s)
- Hong-Li Song
- Department of Infectious Diseases, The Second Affiliated Hospital, China Medical University, Shenyang 110004, Liaoning Province, China
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48
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Lee WS, McKiernan P, Kelly DA. Etiology, outcome and prognostic indicators of childhood fulminant hepatic failure in the United kingdom. J Pediatr Gastroenterol Nutr 2005; 40:575-81. [PMID: 15861019 DOI: 10.1097/01.mpg.0000158524.30294.e2] [Citation(s) in RCA: 144] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE To study the etiology, outcome and prognostic indicators in children with fulminant hepatic failure in the United Kingdom. DESIGN Retrospective review of all patients <17 years with fulminant hepatic failure from 1991 to 2000. Fulminant hepatic failure was defined as presence of coagulopathy (prothrombin time >24 seconds or International Normalized Ratio >2.0) with or without hepatic encephalopathy within 8 weeks of the onset of symptoms. SETTING Liver Unit, Birmingham Children's Hospital, United Kingdom. RESULTS Ninety-seven children (48 male, 49 female; median age, 27 months; range, 1 day-192.0 months) were identified with fulminant hepatic failure. The etiologies were: 22 metabolic, 53 infectious, 19 drug-induced, and 3 autoimmune hepatitis. The overall survival rate was 61%. 33% (32/97) recovered spontaneously with supportive management. Fifty-five children were assessed for liver transplantation. Four were unstable and were not listed for liver transplantation; 11 died while awaiting liver transplantation. Liver transplantation was contraindicated in 10 children. Of the 40 children who underwent liver transplantation, 27 survived. Children with autoimmune hepatitis, paracetamol overdose or hepatitis A were more likely to survive without liver transplantation. Children who had a delay between the first symptom of liver disease and the onset of hepatic encephalopathy (median, 10.5 days versus 3.5 days), higher plasma bilirubin (299 micromol/L versus 80 micromol/L), higher prothrombin time (62 seconds versus 40 seconds) or lower alanine aminotransferase (1288 IU/L versus 2929 IU/L) levels on admission were more likely to die of fulminant hepatic failure or require liver transplantation (P < 0.05). On multivariate analysis, the significant independent predictors for the eventual failure of conservative therapy were time to onset of hepatic encephalopathy >7 days, prothrombin time >55 seconds and alanine aminotransferase </=2384 IU/L on admission. CONCLUSIONS Children with fulminant hepatic failure with severe coagulopathy, lower alanine aminotransferase on admission and prolonged duration of illness before the onset of hepatic encephalopathy are more likely to require liver transplantation. Early referral to a specialized center for consideration of liver transplantation is vital.
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Affiliation(s)
- Way Seah Lee
- Department of Paediatrics, University of Malaya Medical Centre, Kuala Lumpur, Malaysia.
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49
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Thompson AE, Marshall JC, Opal SM. Intraabdominal infections in infants and children: descriptions and definitions. Pediatr Crit Care Med 2005; 6:S30-5. [PMID: 15857555 DOI: 10.1097/01.pcc.0000161963.48560.55] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To define intraabdominal infections in infants and children. DESIGN Summary of the literature with review and consensus by experts in the field. RESULTS Intraabdominal infections are common in infants and children and comprise a broad range of disorders of greatly variable severity. In addition to microbiologically mediated processes, other inflammatory disorders frequently present similar clinical syndromes. More aggressive and effective therapy for prematurity, chronic diseases of childhood, malignancies, immunodeficiencies, and organ failure, including transplantation, is likely to increase the frequency with which some of these infections are encountered. Only a limited number of processes have been clearly defined in the pediatric literature. CONCLUSIONS Criteria defining intraabdominal infection are proposed based on reports in the pediatric literature and expert opinion. Additional study of individual disorders, diagnostic criteria, and approach to management is warranted.
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Affiliation(s)
- Ann E Thompson
- Critical Care Medicine and Pediatrics, University of Pittsburgh School of Medicine, PA, USA
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50
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White FV, Dehner LP. Viral diseases of the liver in children: diagnostic and differential diagnostic considerations. Pediatr Dev Pathol 2004; 7:552-67. [PMID: 15630523 DOI: 10.1007/s10024-004-8101-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2004] [Accepted: 09/01/2004] [Indexed: 01/04/2023]
Abstract
This review summarizes the general histologic features of acute and chronic hepatitides and highlights those morphologic findings that may suggest or be diagnostic of a specific agent or etiology. The main epidemiologic, clinical, and pathologic features of the hepatotropic viruses are discussed, with an emphasis on pediatric studies and the differential diagnosis of hepatitis in childhood.
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Affiliation(s)
- Frances V White
- Department of Pathology and Immunology, Lauren V. Ackerman Laboratory of Surgical Pathology,St. Louis Children's Hospital at the Washington University Medical Center, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
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