Liver Failure In Children Research Articles

Paracetamol is both a friend and a foe: What should a pediatrician know? A clinical case

One of the most common drug-related side effects is hepatotoxicity. The most common cause of severe drug-induced liver injury is acetaminophen (paracetamol), as it is an over-the-counter drug. Paracetamol is safe and effective in children and adolescents at therapeutic doses; however, it is the leading cause of acute liver failure in children (21% of cases) and adults (40%) with overdose. The clinical presentation of toxic liver damage depends on the time elapsed after taking paracetamol and its dose. Symptoms of liver damage are not always obvious but can develop rapidly from day 2 to day 5 after poisoning. The article presents a clinical case of an unintentional overdose of paracetamol in a teenage girl due to non-compliance with the dose and regimen.

Drug Acute Liver Failure in Children Caused by Anthelmintic Agents (Albendazole): Treatment Strategy.

Drug-induced liver injury accounts for numerous clinically significant events each year and can cause severe injury, resulting in a need for liver transplant or fatality. Liver injury triggered by albendazole is relatively common, resulting in mild to moderate changes in liver enzymes and affecting ~16% of patients who use this medication. Albendazole-induced liver injury and jaundice have been previously documented, but a case of fulminant hepatic failure requiring liver transplant has not yet been described. Acute liver failure is a clinical syndrome that is potentially reversible. About 2% of liver transplants are performed because of acute liver failure. We reviewed drug-induced fulminant and subfulminant hepatic failures among pediatric patients transferred to the Batumi Center for Liver Diseases and Transplantation in Georgia. The 6 cases were children aged 2 to 14 years who were diagnosed in Georgia between 2018 and 2023. Of 6 children, patients N1 and N2 had reversible acute liver failure and treatment ended with recovery, patients N3 and N4 had successful transplant procedures performed at the peak of disease development, and patients N5 and N6 did not receive transplant procedures because of presence of irreversible brain damage. Although the Model for End-Stage Liver Disease Score (the model score for patients with end-stage liver disease) is useful for patients with chronic hepatocytic failure, the score does not apply for patients with acute liver failure. On the basis of our study, at the first signs of disease development, patients should be referred to the transplant center and the preparation of a living donor should be started immediately, so that organ transplant can be performed without a long elapse of time.

Clinico-etiological profile of acute liver failure in children in a tertiary care hospital of northernmost India

Clinico-etiological profile of acute liver failure in children in a tertiary care hospital of northernmost India

Etiology and clinical management progress of acute liver failure in children

Etiology and clinical management progress of acute liver failure in children

The role of microRNA in the development of liver diseases. Part 1

The scientific review shows the role of miRNA in the development of liver diseases, namely: acute liver failure, non-alcoholic fatty liver disease. To write the article, information was searched using the databases Scopus, Web of Science, MedLine, PubMed, Google Scholar, EMBASE, Global Health, The Cochrane Library, CyberLeninka. The authors indicate the importance of some miRNAs in the development of liver diseases. It was established that the development of acute liver failure is associated with a significant increase in the concentration of miR-21, miR-122, miR-221 and miR-192 in blood serum. The authors present the features of changes in miRNA content in acute liver failure in children. It is stated that drug-induced acute liver failure is accompanied by an increase in the concentration level of miR-122, miR-1246, miR-4270, miR-4433, miR-4463, miR-4484, miR-4532, pre-miR-4767 and a decrease in the concentration level miR-455-3p, miR-1281 and pre-miR-4274 in serum. MicroRNAs miR-224-5p, miR-320a, miR-449a and miR-877-5p regulate the process of metabolizing acetaminophen by inhibiting enzymes (CYP3A4, HNF1A, HNF4A and NR1I2). The authors demonstrated that transfection of exogenous miR-224-5p, miR-320a, miR-449a and miR-877-5p into HepaRG cells protects them from the toxic effect of acetaminophen. The scientists demonstrated that patients with non-alcoholic steatohepatitis had more than two-fold increased concentrations of miR-19a and miR-19b, miR-122, miR-125b, miR-192 and miR-375 in their blood serum. It is emphasized that overexpression of miR-122 is associated with high activity of alanine aminotransferase. Thus, the association of micro-RNA generation with the development of liver diseases has become the goal of research by scientists around the world in recent years. The development of acute liver failure is associated with a significant increase in the concentration of miR-21, miR-122, miR-221 and miR-192 in blood serum. A high level of miR-27b-3p, miR-122-5p, miR-192-5p, miR-1290 in blood serum is a highly diagnostic marker of non-alcoholic fatty liver disease. Therefore, microRNAs play an important role in the development of acute liver failure and non-alcoholic fatty liver disease and can be used as diagnostic and prognostic criteria, which, in the future, may contribute to increasing the effectiveness of therapy.

May 2022 acute hepatitis outbreak, is there a role for COVID-19 and other viruses?

There has been an increasing number of reported cases of acute hepatitis of unknown origin in previously healthy children since first reported on March 31, 2022. This clinical syndrome is identified by jaundice and markedly elevated liver enzymes with increased aspartate transaminase and/or alanine aminotransaminase (greater than 500 IU/L). We conducted an inclusive literature review with respect to acute hepatitis outbreaks in children using the search terms acute hepatitis, outbreak, children, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease 2019 (COVID-19), and adenovirus. According to the cumulative data presented in four main studies, the median age is 4 years, with a male predominance (1.3:1). Jaundice was the most common clinical manifestation (69%), followed by vomiting (63%), anorexia (52.9%), diarrhea (47.2%), abdominal pain (39%), pyrexia (33.3%), pale stool (30%), and dark urine (30%). Coryza and lethargy were reported in 16.6%, while pruritus was reported in 2% of cases. Acute liver failure was observed in 25% of cases. The exact mechanism of this acute hepatitis outbreak is still not entirely clear. Adenoviruses and SARS-CoV-2 were detected in a significant number of patients. Coinfection with adenovirus and SARS-CoV-2 could be a possible underlying mechanism. However, other possible infections and mechanisms must be considered in the pathogenesis of this condition. Acute hepatitis of unknown origin in children has been a serious problem since the start of the COVID-19 pandemic but has not yet been sufficiently addressed. Many questions remain regarding the underlying mechanisms leading to acute liver failure in children, and it is likely that extensive future research is needed.

Outbreak of indeterminate acute liver failure in children with adenoviraemia – Not a new disease

In the year 2022, an outbreak of indeterminate acute hepatitis and indeterminate paediatric acute liver failure (ID-PALF) in association with adenoviraemia in immunocompetent children was reported in the UK. We postulate that this association is not a new disease in immunocompetent children. Children with acute hepatitis during the outbreak who were referred to King's College Hospital, London for advice and management were included in the study. Data on the frequency of ID-PALF in 2022, as well as transplantation rates and the association with adenovirus infection, were obtained from electronic health records. The clinical presentation, histology and outcomes of children with ID-PALF and adenoviraemia in 2017-2021 were compared with those in2022. From January to June 2022, 65 patients with acute hepatitis were referred. Ten children were admitted with ID-PALF. ID-PALF constituted 26% of all PALF cases in 2017-2021, in contrast to 58.8% during the 2022 outbreak. During the outbreak, adenoviraemia was present in 52% of children with acute hepatitis without liver failure (in whom adenoviraemia test results were available) and in 100% of ID-PALF cases. Adenoviraemia was seen in immunocompetent children in 6/13 (46%) of all ID-PALF cases between 2017-2019, with a clear absence of adenoviraemia in the 6 ID-PALF cases during 2020-2021. Compared to ID-PALF with adenoviraemia in 2017-2019 (n= 6), ID-PALF with adenoviraemia during the outbreak (n= 10) was associated with more frequent hepatic encephalopathy, hypotension requiring vasoactive medications and higher plasma ammonia levels (admission and peak), with similar native liver survival. The recent outbreak of ID-PALF with adenoviraemia in immunocompetent children does not appear to be a new disease, contrary to perception and other reports. The frequency of such cases over the years could be linked to background rates of adenovirus infections. Indeterminate paediatric acute liver failure (ID-PALF) associated with adenoviraemia in immunocompetent children is not a new disease specific to 2022. The exclusive role of human adenovirus infection in the causation of this outbreak of acute hepatitis seems unlikely. Indeed, we provide histological data from explants in transplanted patients that do not support direct viral cytotoxicity. The disease is probably mediated by immunological injury directed towards adenovirus infection and/or adeno-associated virus-2.

Duration of Invasive Mechanical Ventilation Post-Liver Transplantation: Does One Size Fit All?

Duration of Invasive Mechanical Ventilation Post-Liver Transplantation: Does One Size Fit All?

Neonatal Hepatic Myeloid Progenitors Expand and Propagate Liver Injury in Mice.

Biliary atresia (BA) is a progressive pediatric inflammatory disease of the liver that leads to cirrhosis and necessitates liver transplantation. The rapid progression from liver injury to liver failure in children with BA suggests that factors specific to the perinatal hepatic environment are important for disease propagation. Hematopoietic stem and progenitor cells (HSPCs) reside in the fetal liver and are known to serve as central hubs of inflammation. We hypothesized that HSPCs are critical for the propagation of perinatal liver injury (PLI). Newborn BALB/c mice were injected with rhesus rotavirus (RRV) to induce PLI or with PBS as control. Livers were compared using histology and flow cytometry. To determine the effects of HSPCs on PLI, RRV-infected neonatal mice were administered anti-CD47 and anti-CD117 to deplete HSPCs. PLI significantly increased the number of common myeloid progenitors and the number of CD34+ hematopoietic progenitors. Elimination of HSPCs through antibody-mediated myeloablation rescued animals from PLI and significantly increased survival (RRV+isotype control 36.4% vs. RRV+myeloablation 77.8%, Chi-test = 0.003). HSPCs expand as a result of RRV infection and propagate PLI. Targeting of HSPCs may be useful in preventing and treating neonatal inflammatory diseases of the liver such as BA.

Etiology, Outcome and Factors Predicting Native Liver Survival In Acute Liver Failure In Children: Experience From A Tertiary Care Centre

Etiology, Outcome and Factors Predicting Native Liver Survival In Acute Liver Failure In Children: Experience From A Tertiary Care Centre

Transplantation in Pediatrics Liver Failure Associated with Acute Hepatitis of Unknown Etiology

Introduction. On 5th April 2022, some cases of severe acute hepatitis of unknown etiology in children were reported in the United Kingdom. Since then, the number has increased rapidly, with 650 probable cases identified worldwide. This review focuses on available information about managing acute liver failure (ALF) in pediatrics with acute hepatitis of unknown etiology through the perspective of hepatobiliary surgery. Method. A literature review proceeded on some databases, namely PubMed and Google Scholar. Epidemiological data and technical policy were obtained from World Health Organization and some government institutions. Results. Severe acute hepatitis can progressively develop into acute liver failure, thus requiring a liver transplantation procedure immediately. There are about 30 patients have received a liver transplant. Fourteen patients reported had died. Liver transplantation is necessary to treat acute liver failure in children with acute hepatitis of unknown etiology. The need for a liver transplant can be avoided if ALF is prevented. Conclusion. The decision to perform or not to perform a liver transplant procedure may consider indications, contraindications, possible outcomes, patient status, availability of donors, and access to transplant centers' facilities and resources.

Acute Liver Failure in Children: Clinical Presentation and Management

Introduction: Acute liver failure (ALF) is an uncommon condition in which rapid deterioration of liver functions results in coagulopathy, usually with an international randomized ratio (INR) of greater than 1.5 which is not corrected by a single dose of vitamin K, the condition associated with encephalopathy or INR 2 or more and is not corrected by a single dose of vitamin K without encephalopathy. Acute liver failure (ALF) is a life-threatening condition characterized by jaundice, encephalopathy and coagulopathy leading to multi-organ failure in a patient with no prior history of liver disease and carries a very high mortality rate. Objective: To study the clinical presentation and management of acute liver failure (ALF) among children admitted to Jaffer Ibn Oaf Teaching Hospital in Khartoum, Sudan during the year 2019. Methods: A descriptive cross sectional and hospital-based study conducted in all children presented to Jaffer Ibn Oaf Teaching Hospital in Khartoum, Sudan with acute liver failure during January to December 2019. The study sample was calculated by total coverage of all patients. Study questionnaires captured mainly quantitative data. The data was reviewed and analyzed into descriptive and inferential statistics by using computerized software package for window statistical package for social science (SPSS) version 21. Results: 47 children had acute liver failure were included. The prevalence of pediatric ALF in the studied hospital was 8.95%. The majority of participants were males and were 2 months to 14 years of age. All patients (100%) presented with jaundice, 38 (80.9%) had weakness and fatigue, 23 (48.9%) developed encephalopathy, mainly grade-I, 19 (40.0%) had nausea, 16 (34%) had ascites and 7 (14.8%) had seizures. INR was prolonged in all patients. Most patients had abnormal liver function tests. Almost all patient received vitamin K injection. Many patients needed pressure and circulation support and special treatment based on the underline cause. The mortality rate was 34% and 29.8% of the patients were recovered without liver transplantation. Statistically significant best outcome associated with elder age and hepatic encephalopathy grade-1. Poor outcome was significantly frequent among patients with anemia, thrombocytopenia, leukocytosis, hypokalemia and high liver enzymes. Conclusion: Pediatric acute liver failure mainly presented with jaundice, weakness and fatigue, grade-I encephalopathy, nausea, ascites and seizures. Treatment was mainly supportive with some patient needed treatment for the underlying causes. Poor outcome associated with anemia, thrombocytopenia, leukocytosis, hypokalemia and high liver enzymes.

Expert symposium on severe acute hepatitis of unknown cause in children, a paradigm of exchanges and sharing between Chinese and Western medicine professionals.

Expert symposium on severe acute hepatitis of unknown cause in children, a paradigm of exchanges and sharing between Chinese and Western medicine professionals.

Ratio of aspartate aminotransferase to alanine aminotransferase and alkaline phosphatase to total bilirubin in Wilsonian acute liver failure in children.

Acute liver failure (ALF) caused by Wilson disease (WD) is always fatal. Therefore, a quick diagnosis of WD is needed to start immediate management. This study aims to determine the ratio of aspartate aminotransferase to alanine aminotransferase (AST/ALT) and the ratio of alkaline phosphatase to total bilirubin (ALP/TB) in diagnosing Wilsonian acute liver failure (WALF) in children. Sixty children with acute liver failure were included in this study, of whom40 had WALF and 20 had a non-Wilsonian acute liver failure (non-WALF). The serum ALT, AST, alkaline phosphatase, and total bilirubin of each blood sample were measured. We evaluated the sensitivity and specificity of AST/ALT ratio and ALP/TB ratio in WALF diagnosis. Consanguinity and Kayser-Fleischer (K-F) rings were found in 32.5% and 72.5% of WALF cases, respectively. The mean hemoglobin, median ALT, median alkaline phosphatase, and mean ceruloplasmin of children with WALF were lower than those in the non-WALF group. In WALF cases, the median AST/ALT ratio was higher than in non-WALF cases. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of the ratio of AST to ALT were 70%, 95%, 96.5%, 61.3% and 78.3%, respectively. However, when the cutoff value is ≥ 1.85, the maximum sensitivity produced by the AST/ALT ratio is 77.5% and the specificity is 95%. The sensitivity, specificity, PPV, NPV, and diagnostic accuracy of the ratio of ALP/TB < 4 were 32.5%, 100%, 100%, 42.5%, and 55%, respectively. The overall mortality rate was 50%, while the WALF mortality was60%. A positive AST/ALT and ALP/TB ratio strongly suggest WALF, but a negative result does not exclude WALF. We cannot use these ratios as a diagnostic tool for children with WALF. In WALF cases, the mortality rate is remarkably high, and the high score of the new Wilson index predicts the mortality rate without liver transplantation.

Diagnosis and treatment of fever-related recurrent acute liver failure in children

Diagnosis and treatment of fever-related recurrent acute liver failure in children

Diagnosis and treatment of acute liver failure in children with Wilson’s disease

Diagnosis and treatment of acute liver failure in children with Wilson’s disease

Proceedings of ESPGHAN Monothematic Conference 2020: "Acute Liver Failure in Children": Diagnosis and Initial Management.

The Hepatology Committee of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) aims to educate pediatric gastroenterologists, members of ESPGHAN and professionals from other specialties promoting an exchange of clinical expertise in the field of pediatric hepatology. Herewith we have concentrated on detailing the recent advances in acute liver failure in infants and children. The 2020 ESPGHAN monothematic three-day conference on pediatric hepatology disease, entitled "acute liver failure" (ALF), was organized in Athens, Greece. ALF is a devastating disease with high mortality and most cases remain undiagnosed. As knowledge in diagnosis and treatment of ALF in infants and children has increased in the past decades, the objective was to update physicians in the field with the latest research and developments in early recognition, curative therapies and intensive care management, imaging techniques and treatment paradigms in these age groups. In the first session, the definition, epidemiology, various causes of ALF, in neonates and older children and recurrent ALF (RALF) were discussed. The second session was dedicated to new aspects of ALF management including hepatic encephalopathy (HE), coagulopathy, intensive care interventions, acute on chronic liver failure, and the role of imaging in treatment and prognosis. Oral presentations by experts in various fields are summarized highlighting key learning points. The current report summarizes the major learning points from this meeting. It also identifies areas where there is gap of knowledge, thereby identifying the research agenda for the near future.

Proceedings of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition Monothematic Conference, 2020: "Acute Liver Failure in Children": Treatment and Directions for Future Research.

The Hepatology Committee of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) aims to educate pediatric gastroenterologists, members of ESPGHAN and professionals from other specialties promoting an exchange of clinical expertise in the field of pediatric hepatology. The 2020 single topic ESPGHAN monothematic 3-day conference on pediatric liver disease, was organized in Athens, Greece and was entitled " Acute Liver Failure" (ALF). ALF is a devastating disease with high mortality and in a considerable fraction of patients, the cause remains unresolved. As knowledge in diagnosis and treatment of ALF in infants and children has increased in the past decades, the objective was to update physicians in the field with developments in medical therapy and indications for liver transplantation (LT) and to identify areas for future research in clinical and neurocognitive outcomes in ALF. We recently reported the epidemiology, diagnosis, and initial intensive care management issues in separate manuscript. Herewith we report on the medical treatment, clinical lessons arising from pediatric studies, nutritional and renal replacement therapy (RRT), indications and contraindications for LT, neurocognitive outcomes, new techniques used as bridging to LT, and areas for future research. Oral presentations by experts in various fields are summarized highlighting key learning points. The current report summarizes the current insights in medical treatment of pediatric ALF and the directions for future research.

Acute-on-chronic liver failure in children.

Although various complex definitions of acute-on-chronic liver failure (ACLF) have been suggested in relation to adult patients, there is currently no universal definition of the syndrome in pediatric patients. In simplified terms, ACLF is characterized by the acute deterioration of the liver functions due to the effects of a precipitating factor on the basis of a chronic liver disease. Acute events and underlying liver diseases are very different in children from those seen in adults. Moreover, acute events and underlying chronic liver diseases vary among geographical regions, although it seems that the most common such diseases and acute events are autoimmune hepatitis, Wilson’s disease, and their flares. ACLF is associated with a poor prognosis. While no scoring systems have been developed to predict the prognosis for children with ACLF, modified versions of the Asian Pacific Association for the Study of the liver’s acute-on-chronic liver failure scoring system and the Chronic Liver Failure-Sequential Organ Failure Assessment criteria can be used in children until specific and validated scoring systems are available. Aside from liver transplantation, there is no proven treatment for ACLF. Thus, the early recognition of ACLF prior to the development of extrahepatic organ failure is important.

Clinical characteristics of acute liver failure associated with hepatitis A infection in children in Mogadishu, Somalia: a hospital-based retrospective study

BackgroundHepatitis A is one of the most common infectious causes of acute hepatitis, and currently, a neglected global public health problem necessitating an urgent response in Somalia. Hepatitis A infection and its rare complication of acute liver failure in children are largely based on very limited data. The aim of the study was therefore to investigate the Hepatitis A infection and its rare complication of acute liver failure in children in Somalia.MethodsThis retrospective study was conducted on children aged 0–18 years who were admitted to the pediatric departments of the Somalia Mogadishu-Turkey Training and Research Hospital, Somali, from June 2019 and December 2019. Patients who were tested for hepatitis A infection during the study period and had complete data were included. Children with chronic disease, primary or secondary immunodeficiency, blood transfusion history, and missing data were excluded. ed data including patients' demographics, clinical presentation, laboratory results, ultrasonographic findings, length of hospital stay, clinical course and outcome were retrieved from the hospital database system.ResultsOf the 13,047 children, 219 were analyzed. Of the 219 Hepatitis A cases, 25 (11%) were diagnosed with pediatric acute liver failure (PALF). The mean age of children with Hepatitis A was 6.7 years. The majority of cases were reported in the 5–9 (39.7%) year age range. Hepatic encephalopathy, length of hospital stay, levels of albumin, and values of PT, aPPT, and INR were significantly higher in children with acute live failure. The presence of cholecystitis and cholecystitis with ascites in the sonographic evaluation were poor prognostic markers for acute liver failure.ConclusionsThis study revealed hepatitis A virus infection and its related acute liver failure among hospitalized children in Somalia of which 11% had PALF. Hence, the introduction of Hepatitis A vaccination, which is the main public health tool, into the national immunization program, the improvement of hygiene conditions, raising awareness of the disease, and increasing health literacy are necessary to prevent the consequence of the Hepatitis A virus in children.