Pediatric Acute Liver Failure Research Articles

Common mechanisms in pediatric acute liver failure.

Acute liver failure (ALF) is a rare but potentially fatal disease in children. The etiology is multifactorial, including infection, autoimmune, and genetic disorders, as well as indeterminate hepatitis, which has a higher requirement for liver transplantation. Activation of the innate and adaptive immune systems leads to hepatocyte-specific injury which is mitigated by T regulatory cell activation. Recovery of the native liver depends on activation of apoptotic and regenerative pathways, including the integrated stress response (ISR; e.g., PERK), p53, and HNF4α. Loss-of-function mutations in these pathways cause recurrent ALF in response to non-hepatotropic viruses. Deeper understanding of these mechanisms will lead to improved diagnosis, management, and outcomes for pediatric ALF.

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.

Value of extracorporeal artificial liver support in pediatric acute liver failure: A single-center experience of over 10 years.

Acute liver failure (ALF) is a life-threatening disease characterized by rapid-onset liver dysfunction, coagulopathy, and encephalopathy in patients without chronic liver disease. Today, the combined application of continuous veno-venous hemodiafiltration (CVVHDF) and plasma exchange (PEX), which are forms of supportive extracorporeal therapy (SECT), with conventional liver therapy in ALF is recommended. This study aims to retrospectively analyze the effects of combined SECT in pediatric patients with ALF. We retrospectively analyzed 42 pediatric patients, followed in the liver transplantation intensive care unit. The patients had ALF and received PEX supportive therapy with combined CVVHDF. The biochemical lab values of the results for the patients before the first combined SECT and after the last combined SECT were analyzed comparatively. Of the pediatric patients included in our study, 20 were girls and 22 were boys. Liver transplantation was performed in 22 patients, and 20 patients recovered without transplantation. After the discontinuation of combined SECT, all patients had significantly lower serum liver function test results (total bilirubin, alanine transaminase, aspartate transaminase), ammonia, and prothrombin time/international normalized ratio levels than the previous levels (p < 0.01). Hemodynamic parameters (i.e., mean arterial pressure) also improved significantly. Combined CVVHDF and PEX treatment significantly improved biochemical parameters and clinical findings, including encephalopathy, in pediatric patients with ALF. PEX therapy combined with CVVHDF is a proper supportive therapy for bridging or recovery.

398 - A rare case of acute lymphocytic leukemia presenting with pediatric acute liver failure

398 - A rare case of acute lymphocytic leukemia presenting with pediatric acute liver failure

Extracorporeal Therapies in Children with Acute Liver Failure: A Single-Center Experience.

The aim of this study is to determine the indication, timing, and administration of extracorporeal therapies such as total plasma exchange and continuous renal replacement therapy in children with acute liver failure or acute-on-chronic liver failure. This study is conducted as a retrospective, single-center study. Between January 2016 and December 2021, pediatric acute liver failure or acute-on-chronic liver failure patients for whom total plasma exchange and/or continuous renal replacement therapy was performed were included in this study. Thirty-four children with acute liver failure or acute-on-chronic liver failure were included during the study period. The children comprised 14 (41.1%) males, and the median age of the patients was 54 months (5-21). Twenty-four patients (70.6%) had pediatric acute liver failure, and 10 patients (29.4%) had acute-on-chronic liver failure. Patients' median model for end-stage liver disease and pediatric end-stage liver disease scores were 24.7/23.5, respectively. Total plasma exchange therapy was performed on all patients whereas continuous renal replacement therapy was performed on 13 patients (38.2%). The median duration of continuous renal replacement therapy was 2.5 days (2-24). The median number of the total plasma exchange sessions was 3 (1-20). The median length of stay in pediatric intensive care unit was 4.5 (2-74) days. Eleven (32.5%) patients had 1 or more improvements in hepatic encephalopathy scores after extracorporeal therapy. Eleven (32.5%) patients died. There was a significant difference between the survivors and non-survivors with respect to levels of albumin, ammonia, pediatric risk of mortality scores, and pre-hepatic encephalopathy scores. Liver transplantation was performed in 4 of 24 pediatric acute liver failure patients, and all of them survived. Total plasma exchange and continuous renal replacement therapy are life-saving, and both methods may reduce morbidity and mortality, also bridging to liver transplantation.

Acute liver failure and unique challenges of pediatric liver transplantation amidst a worldwide cluster of adenovirus-associated hepatitis

Investigation into a recent cluster of acute hepatitis in children from the southeastern United States identified human adenovirus (HAdV) DNAemia in all 9 cases. Molecular genotyping in 5 of 9 (56%) children identified HAdV type 41 in all cases (100%). Importantly, 2 children from this cluster progressed rapidly to pediatric acute liver failure (PALF) and required liver transplantation. HAdV type 41, a known cause of self-limited gastroenteritis, has not previously been associated with severe cholestatic hepatitis and liver failure in healthy children. Adenovirus polymerase chain reaction assay and sequencing of amplicons performed on DNA extracted from formalin-fixed, paraffin-embedded liver tissue also identified adenovirus species F (HAdV type 40 or 41) in these 2 children with PALF. Transplant considerations and successful liver transplantation in such situations remain scarce. In this report, we describe the clinical course, laboratory results, liver pathology, and treatment of 2 children with PALF associated with HAdV type 41, one of whom developed secondary hemophagocytic lymphohistiocytosis. Their successful posttransplant outcomes demonstrate the importance of early multidisciplinary medical management and the feasibility of liver transplantation in some children with PALF and HAdV DNAemia.

Pediatric acute liver failure in Saudi Arabia: prognostic indicators, outcomes and the role of genetic testing.

The objective of this study was to determine the etiologies, outcomes, prognostic indicators and the role of genetic testing in children with acute liver failure (ALF). This retrospective study included 46 patients with pediatric acute liver failure (PALF) according to the PALF study group definition, admitted to King Fahad Specialist Hospital-Dammam, Saudi Arabia, between January 2014 and December 2021. Patients who survived with supportive therapy were designated as the recovery group, whereas those who died or underwent liver transplantation were designated as the death/transplant group. There were 26 (56.5%) patients in the recovery group and 20 (43.5%) patients in the death/transplant group. Four patients (8.7%) underwent liver transplantation. After indeterminate causes (45.6%), genetic-metabolic diseases and drug-induced liver injury (DILI) were the most common cause with 15.2 and 13%, respectively. Genetic testing had a high yield of (6/31) in identifying monogenic disease associated with ALF. Younger age, lower Glasgow Coma Scale and higher international normalized ratio (INR) on admission were predictors for poor prognosis. The death/transplant group had longer intensive care unit stay ( P < 0.001), and on admission they had more advanced hepatic encephalopathy ( P < 0.005), more prolonged prothrombin time ( P < 0.001), higher lactate ( P < 0.006), higher total and direct bilirubin ( P < 0.008) and ( P < 0.001), respectively. Genetic, metabolic and DILI causes constituted the most common cause of PALF after indeterminate causes. The use of genetic testing can improve diagnostic rates in special cases, but we could not assess the effect of genetic testing on prognosis. The overall survival rate in our study was 65.2%. Younger age, higher admission INR and lower Glasgow coma scale were indicators of poor prognosis.

Acute severe non-A-E-hepatitis of unknown origin in children – A 30-year retrospective observational study from north-west Germany

The etiology of the current acute severe non-A-E hepatitis epidemic in children remains unclear. We aimed to describe the occurrence and outcomes of acute severe hepatitis in pediatric patients in North-West Germany over a period of more than 30 years and in the context of the current epidemic. We analyzed all cases of acute severe hepatitis in childhood, as defined by the World Health Organization, at Hannover Medical School from 1990 and at the University Hospital of Essen from 2009 to 16 May 2022. We separated cases into a historic cohort (1990-2018) and a COVID-19 era cohort (2019-2022). After application of exclusion criteria, 107 patients with acute severe hepatitis were identified (2.32 cases/center/year). Annual incidence per center rose significantly from 2.2 (historic cohort until 2018) to 4.25/center/year (from 2019, p=0.002). Of all cases, 75.7% presented with jaundice, while 53.3% had clinical signs of infection. Two cases of adenovirus were proven (2004/2016), other pathogens detected were HHV-6 (4), CMV, HSV, EBV(3). Sixty-nine patients (64.5%) met the criteria of pediatric acute liver failure, with 44 requiring liver transplantation. In the current cohort, patients with infection, gastrointestinal symptoms and higher alanine aminotransferase had a better chance of transplant-free survival, whereas hepatic encephalopathy, higher international normalized ratio and bilirubin predicted a poor outcome. Twenty-five patients developed hepatitis-associated aplastic anemia and 19 patients (17.8%) died. Acute non-A-E-hepatitis in children is a rare but severe entity, often leading to acute liver failure. Clinical presentation in our current cohort resembles 2022 NAEH cases, with improved outcomes compared to historic controls. The rising incidence of NAEH in our centers since 2019, in the absence of adenoviral infection, indicates other potential triggers of similar NAEH cases. As the current epidemic of severe acute non-A-E-hepatitis cases in children highlights our limited understanding in the field, we aim to describe current cases, characterizing the presentation over time, and defining similarities and discrepancies before and during the COVID-19 pandemic. Our data show a rising incidence of non-A-E-hepatitis cases since the beginning of the COVID-19 pandemic. These cases were not associated with adenoviral infections, suggesting that the recently described accumulation of adenovirus infections in relationship to hepatitis is a new trigger for a known phenomenon, rather than a new disease entity. Therefore, the role of protective isolation and subsequent lack of contact with trivial infections in children during the pandemic should be the subject of further examinations. We expect our data to contribute to a better understanding of severe acute hepatitis in childhood, increased vigilance for this potentially lethal disease beyond the current epidemic, and ultimately improved clinical diagnosis and care.

Long-Term Survival Outcomes beyond the First Year after Liver Transplantation in Pediatric Acute Liver Failure Compared with Biliary Atresia: A Large-Volume Living Donor Liver Transplantation Single-Center Study.

Pediatric acute liver failure (PALF) is a common cause of liver transplantation (LT) but showed poor post-LT outcomes. We reviewed 36 PALF patients and 120 BA patients who underwent LT in our institution. The cause of PALF was unknown in 66.7%. PALF patients were older (6.2 vs. 2.9 years) with higher PELD scores (31.5 vs. 24.4) and shorter waitlist time (15.7 vs. 256.1 days) (p < 0.01). PALF patients showed higher rates of post-transplant renal replacement therapy (RRT) (13.9% vs. 4.2%) and hepatic artery complications (13.9% vs. 0.8%), while portal vein complications rates were lower (0% vs. 10.8%), (p < 0.05). Although PALF patients showed lower 5-year survival rates (77.8% vs. 95.0 %, p < 0.01), the 5-year survival rates of patients who lived beyond the first year were comparable (96.6% vs. 98.3%, p = 0.516). The most common cause of deaths within one year was graft failure (75.0%) in PALF patients, but infection (67.7%) in BA patients. In multivariate analysis, lower body weight, hepatic artery complications and post-transplant RRT were associated with worse survival outcomes (p < 0.05). In conclusion, physicians should be alert to monitor the immediate postoperative graft dysfunction and hepatic artery complications and patients on post-transplant RRT in order to improve survival outcomes in PALF patients.

Hepatitis A: Leading Cause of Paediatric Acute Liver Failure in Bangladesh

Background: Pediatric acute liver failure (PALF) is a multisystem disorder that gives rise to severe liver failure within days or weeks and occurs in children without pre-existing chronic liver disease. The etiology of PALF varies with age group and geographical area.&#x0D; Objectives: This study was aimed to evaluate the etiological factors of PALF in Bangladeshi children.&#x0D; Methods: This observational study was conducted at the Department of Paediatric Gastroenterology &amp; Nutrition, Bangabandhu Sheikh Mujib Medical University, Bangladesh, from 2017 to 2020. Twenty-six PALF patients were included, purposively, excluding the acute-on chronic liver failure cases. Demographic data, vaccination history, and other information regarding etiology and complications were recorded. During hospital stay following investigations were performed: Serum bilirubin, liver enzymes, prothrombin time, serum albumin, serum creatinine and electrolytes. Fisher’s exact test determined the association between etiologies of PALF and past histories along with other descriptive statistics using the open-source PSPP software.&#x0D; Results: The average age of the 26 studied patients was 8.6±3.5 years, and 73.1% belonged to 5-12 years of age group. Half of the patients had a history of taking street food or unsafe water. Only six patients had a history of ingestion of herbal medicine. None of the patients had history of vaccination against Hepatitis A. The etiology of PALF patients varied. About 54% of the studied patients had HAV infection, in 23.1% etiology was not determined. About 71.4% of the study patients with HAV infection had a history of taking street food or unsafe water, and this association was statistically significant.&#x0D; Conclusion: This study found that hepatitis A virus infection is the leading cause of paediatric acute liver failure in Bangladesh. Timely preventive measures may help in lowering fatality from liver diseases in children in Bangladesh.&#x0D; DS (Child) H J 2021; 37(2): 93-97

Therapeutic plasma exchange and continuous renal replacement therapy in pediatric dengue-associated acute liver failure: A case series from Vietnam

Background and objectivesPaediatric dengue-associated acute liver failure (PALF) is a rare and fatal complication. To date, clinical data regarding the combination of therapeutic plasma exchange (TPE) and continuous renal replacement therapy (CRRT) for the treatment of dengue-associated PALF are limited. MethodsWe conducted a single-center, retrospective study of all children with dengue-associated PALF admitted to the paediatric intensive care unit of Children Hospital No.2, Vietnam, who were treated with TPE+CRRT between January 2021 and March 2022. The main study outcomes were in-hospital survival, normalisation of hepatic function, and hepatic encephalopathy improvement. ResultsTwelve patients aged from 06 to 12 years underwent TPE+CRRT procedures. Among them, three (25 %) patients died of severe sepsis and septic shock confirmed by Enterobacteriaceae spp. haemocultures (stable on maintenance treatment of COVID-19-associated MIS-C with low dose of oral steroids on hospital admission), acute respiratory distress syndrome (ARDS), and clinically apparent intracranial haemorrhage. Nine patients (75 %) survived. The paediatric mortality risk score improved significantly at discharge compared with PICU admission (P < 0.01). Markedly, all twelve patients were diagnosed with hepatoencephalopathy of grades III and IV on PICU admission. After the combined TPE+CRRT interventions, there were substantial improvements in liver transaminases levels, coagulation profiles, and metabolic biomarkers. Normal neurological functions were observed in nine alive patients at hospital discharge. Only one patient experienced an adverse event of slightly low blood pressure, which rapidly self-resolved. Interpretation and conclusionsCombined TPE+CRRT significantly improved survival outcome, neurological status, and rapid normalisation of liver functions in dengue-associated PALF.

Long-term survival outcome beyond the 1st year of pediatric acute liver failure after liver transplantation compared with biliary atresia: a large-volume living donor liver transplantation single-center study

Sola Lee, Nam-Joon Yi, Su Young Hong, Suk Kyung Hong, YoungRok Choi, Hyung-Young Kim, Jin Soo Moon, Seong Mi Yang, Kwang-Woong Lee, Kyung-Suk Suh. Korean J Transplant 2022;36:283. https://doi.org/10.4285/ATW2022.F-4246

Acute hepatitis of unknown origin in children: A combination of factors.

On 5 April 2022, the World Health Organization was notified of 10 cases of severe acute hepatitis of unknown etiology in children under 10years of age in the United Kingdom. Although the exact cause of a proportion of pediatric acute hepatitis and acute liver failure cases was unclear, the above event has caused widespread concern worldwide. As of 14 September 2022, approximately 1,296 probable cases of acute hepatitis of unknown etiology have been reported from 37 countries/regions, of which approximately 55 required or received liver transplantation and 29 died. Although the etiology of acute hepatitis of unknown origin in children remains unclear, many hypotheses have been proposed about the disease. Instead of individual factors such as "adenovirus infection," "SARS-CoV-2 related," and "Adeno-associated virus 2 with helper virus coinfection," it is more likely due to a combination of factors. Accordingly, there is an urgent need for more data and research to clarify the disease etiology. This review aims to provide a historical perspective of acute hepatitis of unknown etiology in children in the past decades and summarize the current hypothesis and evidence on this emerging disease.

Association of duration and etiology with the effect of the artificial liver support system in pediatric acute liver failure.

We aimed to assess the efficacy of the artificial liver support system (ALSS) in pediatric acute liver failure (PALF) patients and to examine the risk factors associated with the effect of ALSS. Similar data are limited in PALF. All patients diagnosed with PALF who received ALSS from June 2011 to June 2021 in the pediatric intensive care unit of the First Hospital of Jilin University were included in this retrospective cohort analysis. The effect of ALSS was measured using difference tests before and after treatments. The risk factors associated with the effect of ALSS were evaluated according to whether the total bilirubin (TBIL) and serum ammonia decreased after ALSS (TBIL-unresponsive group vs. TBIL-responsive group, serum ammonia-unresponsive group vs. serum ammonia-responsive group). Thirty-nine patients who received ALSS during the study period were eligible for inclusion. The most common cause of PALF was undetermined causes (n = 14, 35.9%) followed by infection (n = 11, 28.2%). Four patients received pediatric liver transplantation. The overall survival rate was 76.9% (30/39). Fifteen (38.4%) patients received only one modality, whereas 61.6% patients received hybrid treatments. The most commonly used modality of ALSS was plasma exchange combined with continuous renal replacement therapy (n = 14, 35.9%). Alanine aminotransferase, TBIL, the international normalized ratio, and serum ammonia were significantly decreased after ALSS (P < 0.001). Compared with other causes, more patients with infection and toxication were observed in the TBIL-unresponsive group. A longer ALSS duration was significantly related to blood ammonia reduction. ALSS can effectively reduce serum alanine aminotransferase, TBIL, international normalized ratio, and serum ammonia and may reduce mortality. The reduction in TBIL levels after ALSS is dependent on etiology. A longer ALSS duration was associated with blood ammonia reduction. Prospective multicenter studies are needed for further validation.

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.

Immunological characteristics of severe acute hepatitis of unknown origin in a child post SARS-CoV-2 infection

Recent studies have reported that pediatric acute liver failure of unknown origin is immune-mediated, with CD8+ T cells playing a key role. Moreover, investigation of superantigen-mediated T-cell activation by the SARS-CoV-2 spike protein in pediatric severe acute hepatitis is needed in the context of the proposed mechanism of multisystem inflammatory syndrome in children (MIS-C). We investigated the immunological characteristics of a Japanese pediatric patient with severe acute hepatitis post SARS-CoV-2 infection. The patient demonstrated autoimmune hepatitis-like liver histology with CD8+ lymphocyte-predominant infiltration. There was Th1-type immune skewing, including remarkable peripheral CD8+ T-cell activation and a skewed T cell receptor repertoire. We also found elevated plasma levels of the anti-SARS-CoV-2 spike-specific IgG antibody, and the titer peaked after treatment, as seen with MIS-C. These findings support that immunological activation involving SARS-CoV-2 spike protein plays a crucial role in a pediatric patient with acute severe hepatitis post SARS-CoV-2 infection.

Etiology, outcome and prognostic indicators of acute liver failure in Asian children.

Outcome of pediatric acute liver failure (PALF) in countries with limited availability of LT is not well described. We evaluated the outcome and prognostic indicators of PALF in Malaysia where emergency LT for ALF is limited. In this retrospective review on children < 18years with PALF, we compared clinical and laboratory parameters between survival after supportive treatment and after LT or succumbed without LT. The predictive values of Liver Injury Unit (LIU; peak laboratory values for international normalized ratio [INR], ammonia, total bilirubin) and upon admission (aLIU) on outcome of PALF was evaluated using receiver operator characteristic (ROC) curves. Of 77 children (39 males [51%]; median age 2.8years) with PALF, the overall survival was 55% (n = 42); 52% (n = 40) survived with supportive management, 2.6% (n = 2) after LT. As compared to children who survived without LT, children who had LT/died had lower hemoglobin, aspartate transferase, γ-glutamyl transpeptidase (GGT), and higher serum bilirubin, alkaline phosphatase, ammonia, and serum sodium (p < 0.05). On multivariate analysis, significant independent predictor for death or LT were peak bilirubin > 452μmol/L and peak GGT < 96IU/L. The C-index of LIU and aLIU score were 0.79 and 0.68, respectively, indicating that LIU score was a good model in predicting outcome of PALF. Overall survival of PALF remained poor. High peak bilirubin and low GGT predict poor outcome of PALF. LIU score is a good model in predicting outcome of PALF and maybe useful in selecting children for emergency LT.

Screening for Wilson's disease in acute liver failure: A new scoring system in children.

BackgroundWilson’s disease (WD) is a rare cause of acute liver failure (ALF) and has a high fatality rate. Rapid and accurate diagnosis is important for ALF because of WD (ALF-WD). Our objective was to establish a simple, rapid, and accurate diagnostic test to distinguish ALF-WD from non-WD ALF (NWDALF) in children.Materials and methodsThe data from all cases with pediatric ALF were retrospectively collected and analyzed. We performed receiver operator characteristics curve (ROC) analysis and confirmed the optimum cut-off points.ResultsFifty-eight patients with pediatric ALF (12 with WD, 46 with other etiologies) were included. Older age was observed in ALF-WD compared to NWDALF (11.16 ± 2.51 years vs. 3.34 ± 3.81 years, p < 0.001). An analysis based on routine biochemical testings revealed that total bilirubin (TBil), direct bilirubin, indirect bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST:ALT ratio, alkaline phosphatase (ALP), ALP:TBil ratio, serum albumin, gamma-glutamyl transferase, cholinesterase, hemoglobin, and platelet were statistically significant between the ALF-WD and NWDALF groups. The optimum cut-off points were obtained through ROC analysis. A scoring system was formed by assigning a score of 1 or 0 to patients who met the 13 cut-off points. Using ROC analysis, we determined a cut-off point of ≥ 6.5 for ALF-WD with 91.7% sensitivity and 97.8% specificity (p < 0.0001). In addition, a best cut-off point of ≥ 1.5 based on only five variables (ALT, AST, AST:ALT ratio, ALP, and ALP:TBil ratio), had 100% sensitivity and 91.3% specificity for ALF-WD (p < 0.0001). Based on this, when age was calculated as the sixth indicator, the best cut-off value of ≥ 2.5 had 100% sensitivity and 97.8% specificity (p < 00.0001).ConclusionOur study developed a new scoring system that consists of simple laboratory tests with good sensitivity and specificity and can be used by clinicians to quickly distinguish ALF-WD from NWDALF in children.

Pediatric acute liver failure: An experience of a pediatric intensive care unit from resource limited settings.

IntroductionPediatric 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 methodsThis 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.ResultsOf 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.ConclusionPediatric 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.

335.6: Long-term Outcomes of Living Donor Versus Deceased Donor Liver Transplantation for Acute Liver Failure in United States

Introduction: Acute Liver Failure (ALF) is rarely encountered but often is associated with high morbidity and mortality. Timely Liver Transplantation is universally the only accepted rescue therapy, but not much is known about the usage of Living Donor (LDLT) versus Deceased Donor (DDLT)Liver Transplantation in the United States for this indication. Method: United Network of Organ Sharing/ Organ Procurement and Transplantation Network (UNOS/OPTN) data was reviewed from January 2002 to December 2020. Adult and pediatric recipients with diagnostic codes for ALF and listed as Status 1 were included in the study. Clinical, laboratory, and demographic characteristics were compared between LDLT and DDLT groups. In addition, Post-transplant survival rates were compared between the two groups. Results: There were a total of 246 LDLT (3.8%) and 6153 DDLT (96.2%) recipients with the diagnosis of ALF (Table 1). There was a difference in age and gender between the groups, with 93.5% of LDLT cases being for pediatric ALF cases versus 45.9% of DDLT cases being for pediatric recipients of age less than 18. There were more female gender in the DDLT group. Race was not different between the two groups. The proportion of patients waiting ≥ 3 days was 64.1% in DDLT compared to 77.2% in the LDLT group (P<0.001). There was no statistical difference between the two groups in terms of sodium, bilirubin, and INR. There were more patients with hepatic encephalopathy, and on renal replacement therapy in the DDLT group compared to LDLT group. Overall, 1, 5 and 10 year overall survival among the DDLT and LDLT groups were also similar, 87.7% vs. 85.5%, 81.1% vs. 81.1%, 74.7% vs. 79.3% (p=0.16) (Figure 1) (Log rank P=0.16). Conclusions: In the US, LDLT constitutes of only 3.8% of all liver transplants for ALF. In addition, LDLT was mostly used among pediatric recipients (93.5%), whereas DDLT was mostly used for adult recipients (54.1%). Signs of decompensation with hepatic encephlopathy, ascites, and on renal replacement therapy were more common in DDLT than LDLT group. LDLT can be carefully considered in a select group of adult ALF cases, in early phases, before further progression into renal failure and advanced encephalopathy.