Outcome Of Acute Liver Failure Research Articles

Current status of etiology and outcomes of acute liver failure in India-A multicentre study from tertiary centres.

Acute liver failure (ALF) is a medical emergency and liver transplantation (LT) may be required as definitive therapy. The etiology varies across geographical locations and is mostly viral dominant in India. We aimed at evaluating the spectrum, impact of interventions (plasma exchange [PLEx], continuous renal replacement therapy [CRRT]) and outcomes of ALF in India in recent times. A multicentre retrospective study across four major tertiary care centres. As many as 183ALF patients (median age, 23years; females, 43.1%; model for end-stage liver disease [MELD], 32.7) from January 2021 to December 2023 were included. Nineteen percent had infection and 40.4% of patients satisfied King's College criteria (KCC) at admission. Most common cause for ALF was hepatitis A virus (HAV) (44.2%) followed by rodenticide poisoning (10.3%). Approximately 35% of patients each received either PLEx or CRRT. The 7, 14 and 21-day transplant-free survival probability was 65.5%, 60.1%, and 57.3%, respectively. Only 3.8% of patients underwent liver transplantation. On multivariable Cox regression analysis, hemoglobin (HR, 0.74 [0.63-0.87]), lactate (HR, 1.14 [1.03-1.26]), advanced hepatic encephalopathy (HE) (HR, 4.87 [1.89-12.5]) and fulfilling KCC [HR, 10.04 [4.57-22.06]) at admission were the independent predictors of mortality. A model including KCC + lactate + HE ≥ 3 with or without hemoglobin had an AUROC of 0.81-0.84 to predict mortality. In those who underwent PLEx, advanced HE (HR, 4.13 [1.75-9.7]), procalcitonin (HR, 1.18 [1.07-1.30]) and KCC (HR, 4.6 [1.6-13.1), while for those who received CRRT, lactate (HR, 1.37 [1.22-1.54]) and KCC (HR, 6.4 [2.5-15.8]) independently predicted mortality. Hepatitis A virus is currently the most common cause for ALF in India, emphasizing the need for universal vaccination programmes. Spontaneous survival in tertiary care centres is 57%. LT rates were low.

FRI-327-YI Plasma multi-omic reveals dysregulated gut arbitrated increase in bacterial peptides and metabolites predictive of poor outcomes in acute liver failure

FRI-327-YI Plasma multi-omic reveals dysregulated gut arbitrated increase in bacterial peptides and metabolites predictive of poor outcomes in acute liver failure

Clinical characteristics and outcomes of acute liver failure in neonates: a retrospective cohort in China.

Neonatal acute liver failure (NALF), as a rare disease with high mortality, has limited relevant literature reports in China. We attempted to analyze a NALF cohort to improve the prognosis of this disease. We included all patients diagnosed with NALF at our institution between 2016 and 2021 and retrospectively reviewed their electronic records. NALF was defined as an INR ≥ 2.0 due to liver disease 28days after birth. Comparisons were made according to etiology and outcome. The Kaplan-Meier method was used to estimate survival. Fifty-eight patients were included in this study. Etiologies included hypoxic/ischemic injury (29.3%), infection (27.6%), gestational alloimmune liver disease with neonatal hemochromatosis (GALD-NH) (10.3%), inherited metabolic diseases (5.2%), hemophagocytic lymphohistiocytosis (1.7%), other etiologies (12.1%), and unidentified causes (13.8%). Enteroviruses constituted 87.5% of the viral infections, whereas herpes simplex virus accounted for no infections. The median INR was significantly lower in the infection group than in the GALD-NH group (P < 0.05 for multiple comparisons). At the last follow-up, none of the patients had undergone liver transplantation, and the overall mortality rate was 50%. Liver function completely recovered in 31% of the patients, all of whom survived. The overall median survival time was 48days; 26days for hypoxic/ischemic injury and 43days for GALD-NH. The incidence of cholestasis was significantly greater among surviving patients (P = 0.018). Conclusion: Hypoxic/ischemic injury and infection are the predominant etiologies of NALF in China. The overall prognosis of NALF is poor, but its short-term prognosis is determined by the etiology. What is Known: • Neonatal acute liver failure (NALF) is a rare disorder with limited cohort studies, especially in China. • Gestational alloimmune liver disease, viral infections (especially herpes simplex virus), metabolic diseases and ischemic insults are common etiologies of NALF, which are significantly different from other populations. • There are no reliable biochemical markers to predict the outcome of NALF. What is New: • In this first report on a Chinese NALF cohort, we demonstrate that hypoxic/ischemic injury and infection (excluding herpes simplex virus) are the predominant etiologies of NALF. • The overall prognosis of NALF is poor, and its etiology determines the short-term outcome.

Acute kidney injury in acute liver failure: A narrative review.

Acute kidney injury (AKI) is a frequent complication of acute liver failure (ALF) and it worsens the already worse prognoses of ALF. ALF is an uncommon disease, with varying etiologies and varying definitions in different parts of the world. There is limited literature on the impact of AKI on the outcome of ALF with or without transplantation. The multifaceted etiology of AKI in ALF encompasses factors such as hemodynamic instability, systemic inflammation, sepsis and direct nephrotoxicity. Indications of renal replacement therapy (RRT) for AKI in ALF patients extend beyond the conventional criteria for dialysis and continuous renal replacement therapy (CRRT) may have a role in transplant-free survival or bridge to liver transplantation (LT). LT is a life-saving option for ALF, so despite somewhat lower survival rates of LT in ALF patients with AKI, LT is not usually deferred. In this review, we will discuss the guidelines' recommended definition and classification of AKI in ALF, the impact of AKI in ALF, the pathophysiology of AKI and the role of CRRT and LT in ALF patients with AKI.

Liver transplantation from donation after circulatory death donors in acute liver failure outcomes in the USA

Liver transplantation from donation after circulatory death donors in acute liver failure outcomes in the USA

Peripheral Injection of hUC-MSCs in the Treatment of Acute Liver Failure: A Pre-Clinical Cohort Study in Rhesus Monkeys.

Using a toxin-induced lethal acute liver failure (ALF) monkey model, we have recently shown that early peripheral infusion of human umbilical cord mesenchymal stem cells (hUC-MSCs) can alleviate liver damage and improve animal survival by suppressing the activation of circulating monocytes and the subsequent cytokine storm. Here, we explored whether the administration of hUC-MSCs could still improve ALF when the cytokine storm is fully developed. We treated ALF monkeys with peripheral delivery of hUC-MSCs at 48 hr after toxin challenge. Liver indices, histology, imaging, and animal survival were recorded and analyzed. In our cohort study, we conducted and demonstrated that the infusion of hUC-MSCs significantly improved liver histology, effectively controlled inflammatory cytokine storms, and increased survival rates. Additionally, the administration of a higher dose of hUC-MSCs (2 × 107/monkey) yielded superior outcomes compared to a lower dose (1 × 107/monkey). Treatment of hUC-MSCs can significantly improve the pathological and survival outcomes of ALF even when the cytokine storm has been fully developed, indicating a promising clinical solution for ALF.

Waitlist and posttransplant outcomes of pregnancy-related acute liver failure in the United States.

Data on the liver transplant (LT) outcomes of women with acute liver failure (ALF) due to liver diseases unique to pregnancy (P-ALF) are limited. Using United Network of Organ Sharing (UNOS) data (1987-2021), we analyzed waitlist and post-LT outcomes of ALF in women of childbearing age comparing P-ALF versus ALF due to liver diseases not unique to pregnancy. Baseline characteristics were compared between groups at the time of listing for LT. Of 3542 females aged 16-43 years and listed for LT for ALF, 84 (2%) listed for P-ALF were less likely to be Black (11 vs. 21%, p =0.033), have lower international normalized ratio (2.74 vs. 4.53 p <0.002), but more likely to have respiratory failure (56% vs. 41%, p <0.005), be on pressors (58% vs. 43%, p <0.005), and require dialysis (23% vs. 10%, p <0.001). The cumulative 90-day waitlist mortality (WLM) was lower in P-ALF vs. ALF due to liver diseases not unique to pregnancy (7.4 vs. 16.6%, p <0.001). Posttransplant survival rates at 5 years were similar (82% vs. 79%, p =0.89). In a Fine and Gray regression model controlled for listing year and Model for End-Stage Liver Disease score, 90-day WLM was lower in P-ALF with a sub-HR of 0.42 (95% CI: 0.19-0.94, p =0.035). Of 84 women with P-ALF and listed for LT, 45 listed for hemolysis-elevated liver enzymes-low platelets (HELLP) versus 39 for acute fatty liver of pregnancy had higher 90-day WLM (19.3% vs. 5.7% p <0.005). The 90-day WLM was about 10-fold higher in HELLP versus acute fatty liver of pregnancy with a sub-HR of 9.97 (95% CI: 1.64-60.55, p =0.013). In this UNOS database analysis of ALF among women of childbearing age, the waitlist outcome is better in women with P-ALF compared to women with ALF due to liver diseases not unique to pregnancy. Among women with P-ALF, the 90-day WLM is worse for HELLP versus acute fatty liver of pregnancy. Further studies are needed to improve the management of HELLP and prevent the development of ALF in this subgroup population.

Single-center experience in 127 adult patients, mono or dual artificial liver support therapy, in patients with acute liver failure.

Acute liver failure (ALF) is a serious condition characterized by sudden liver dysfunction, jaundice and hepatic encephalopathy. Its mortality rate of approximately 80% underscores the urgent need for effective treatments. Supportive extracorporeal therapies (SET), which temporarily support liver function and remove toxins, have shown promise in improving outcomes in acute liver failure (ALF). The aim of this study was to compare the outcomes of dual supportive extracorporeal therapy (SET) and mono supportive extracorporeal therapy in patients with acute liver failure. A total of 127 patients with acute liver failure were included in this retrospective, single-center study. Of these, 62 patients received dual supportive extracorporeal therapy and 65 patients received mono supportive extracorporeal therapy. Primary endpoints were survival without the need for liver transplantation and mortality. Secondary endpoints included resolution of encephalopathy and normalization of International Normalized Ratio (INR). In the dual supportive extracorporeal therapy group, 59.6% of patients survived without the need for liver transplantation, while 27.4% achieved recovery with liver transplantation. The mortality rate in this group was 12.9%. Significant regression of encephalopathy grade was observed in 87% of patients, and the 1 year mortality rate for liver transplant recipients was 10.7%. In the mono supportive extracorporeal therapy group, 61.5% of patients experienced a successful recovery without the need for liver transplantation, with a mortality rate of 29.2%. Significant improvement in the grade of encephalopathy was observed in 70.7% of patients. Both dual supportive extracorporeal therapy (CVVHDF and PE) and mono supportive extracorporeal therapy (PE) were associated with significant improvements in renal and hepatic biochemical parameters, blood ammonia levels, and neurological status in patients with acute liver failure associated with grade III-IV hepatic encephalopathy. In particular, dual support was associated with improved hemodynamic stability, lactic acidosis and acid-base balance. Survival in acute liver failure in our retrospective cohort using a protocolized approach to extracorporeal therapies is higher compared to previously published large ALF studies. This protocolized approach warrants further prospective studies.

Etiology and Outcome of Adult and Pediatric Acute Liver Failure in Europe.

Acute liver failure (ALF) is rare but life-threatening. Common causes include intoxications, infections, and metabolic disorders. Indeterminate etiology is still frequent. No systematic data on incidence, causes, and outcome of ALF across Europe are available. Via an online survey we reached out to European Reference Network Centers on rare liver diseases. Numbers and etiology of ALF cases during 2020 were retrieved and diagnostic and treatment availabilities assessed. In total, 455 cases (306 adult, 149 pediatric) were reported from 36 centers from 20 countries. Intoxication was the most common cause in adult and pediatric care. The number of cases with indeterminate etiology is low. Diagnostic tools and specific treatment options are broadly available within this network. This is the first approach to report on etiology and outcome of ALF in the pediatric and adult population in Europe. High diagnostic yield and standard of care reflects the expert status of involved centers.

Prognostic Scores in Acute Liver Failure Due to Viral Hepatitis.

Viral infections are among the major causes of acute liver failure (ALF) worldwide. While the role of agents such as hepatitis A, B, C, D and E viruses in precipitating ALF are well known, improvements in serological assays have led to the detection of viral agents such as Epstein Barr virus, cytomegalovirus etc. as atypical causes of ALF. Despite the plethora of literature available on viral hepatitis and ALF, there is very limited large-scale epidemiologic data on the prevalence, risk factors of progression and outcomes in ALF of viral causes. This is important as viral infections remain the leading cause of ALF in the East and in developing countries, while the impact of viral ALF in the West has largely been ameliorated by effective vaccination and sanitization programs. This review focuses specifically on the available prognostic scores that aid in the management of ALF of viral etiologies while also briefly reviewing the current literature on newer viral agents known to cause ALF, risk factors of progression, outcomes and how management algorithms can be developed by incorporation of prognostic scoring systems for referral and transplant listing.

FRI022 - Novel strategies required to further improve outcomes in acute liver failure

FRI022 - Novel strategies required to further improve outcomes in acute liver failure

Drug-induced autoimmune hepatitis: A minireview.

Drug-induced autoimmune hepatitis (DIAIH) is a specific phenotype of drug-induced liver injury that may lead to the devastating outcome of acute liver failure requiring liver transplantation. Drugs implicated in DIAIH include antimicrobials such as nitrofurantoin and minocycline, non-steroidal anti-inflammatory drugs, statins as well as anti-tumor necrosis agents. The clinical features of drug-induced liver injury are indistinguishable from idiopathic autoimmune hepatitis (AIH) as both may have positive AIH-related autoantibodies, elevated immunoglobulin G, as well as similar histopathological findings. In patients who show no clinical improvement, or there is progressive liver injury despite cessation of the suspected drug, a liver biopsy should be considered, whereby the presence of advance fibrosis on histology favors the diagnosis of idiopathic AIH. Empirical treatment with corticosteroids may be required in patients with non-resolving liver injury. A typical clinical scenario supportive of DIAIH includes a history of drug exposure with spontaneous resolution of liver injury after drug withdrawal and the absence of relapse after rapid steroid taper. In this article we report two cases of DIAIH secondary to Sorafenib and Atorvastatin along with a review of currently available literature. Early identification and treatment often lead to a favorable outcome in DIAIH.

Application of Bone Marrow Mesenchymal Stem Cells Effectively Eliminates Endotoxemia to Protect Rat from Acute Liver Failure Induced by Thioacetamide

Background:Endotoxemia is related to worse clinical outcomes in acute liver failure (ALF), but its management remains unsatisfactory. In this study, we aimed to assess whether the application of bone marrow mesenchymal stem cells (BMSCs) could eliminate endotoxemia and protect rats against ALF induced by thioacetamide (TAA).Methods:BMSCs were isolated from rats and identified by the specific morphology, differentiation potential, and surface markers. The optimal dose of TAA for this study was explored and TAA-induced ALF rats were randomized to three groups: the normal control group (Saline), ALF group (TAA + Saline), and BMSCs-treated group (TAA + BMSCs). The intestinal migration and differentiation of BMSCs was tracked in vivo, and intestinal permeability, endotoxin and inflammatory cytokines, histology, and mortality were analyzed. Moreover, we added the inhibitor of the PI3K/AKT/mTOR signaling pathway into the co-culture system of BMSCs with enterocytes and then performed CK and Villin expression experiments to assess the role of PI3K/AKT/mTOR signal pathway in the intestinal differentiation of BMSCs.Results:BMSCs migrated to the intestinal injury sites and differentiated into enterocytes, intestinal permeability was decreased compared with the ALF group. The higher expression of endotoxin and inflammatory cytokines were reversed after BMSCs transplantation in rats with ALF. Mortality and intestinal lesion were significantly decreased. Blocking the PI3K/AKT/mTOR signal pathway inhibited BMSCs’ intestinal differentiation in vitro.Conclusion:BMSCs can eliminate endotoxemia and reduce mortality in rats with ALF, and the PI3K/AKT/mTOR signal pathway is involved in intestinal differentiation. BMSCs transplantation could be a potential candidate for the treatment of endotoxemia in ALF.

The Role of Predictive Models in the Assessment of the Poor Outcomes in Pediatric Acute Liver Failure.

Objectives: In children, acute liver failure (ALF) is a severe condition with high mortality. As some patients need liver transplantation (LT), it is essential to predict the fatal evolution and to refer them early for LT if needed. Our study aimed to evaluate the prognostic criteria and scores for assessing the outcome in children with ALF. Methods: Data of 161 children with ALF (54.66% female, mean age 7.66 ± 6.18 years) were analyzed based on final evolution (32.91% with fatal evolution or LT) and etiology. We calculated on the first day of hospitalization the PELD score (109 children), MELD, and MELD-Na score (52 children), and King’s College Criteria (KCC) for all patients. The Nazer prognostic index and Wilson index for predicting mortality were calculated for nine patients with ALF in Wilson’s disease (WD). Results: PELD, MELD, and MELD-Na scores were significantly higher in patients with fatal evolution (21.04 ± 13.28 vs. 13.99 ± 10.07, p = 0.0023; 36.20 ± 19.51 vs. 20.08 ± 8.57, p < 0.0001; and 33.07 ± 8.29 vs. 20.08 ± 8.47, p < 0.0001, respectively). Moreover, age, bilirubin, albumin, INR, and hemoglobin significantly differed in children with fatal evolution. Function to etiology, PELD, MELD, MELD-Na, and KCC accurately predicted fatal evolution in toxic ALF (25.33 vs. 9.90, p = 0.0032; 37.29 vs. 18.79, p < 0.0001; 34.29 vs. 19.24, p = 0.0002, respectively; with positive predicting value 100%, negative predicting value 88.52%, and accuracy 89.23% for King’s College criteria). The Wilson index for predicting mortality had an excellent predictive strength (100% sensibility and specificity), better than the Nazer prognostic index. Conclusions: Prognostic scores may be used to predict the fatal evolution of ALF in children in correlation with other parameters or criteria. Early estimation of the outcome of ALF is essential, mainly in countries where emergency LT is problematic, as the transfer to a specialized center could be delayed, affecting survival chances.

Follistatin-controlled activin-HNF4α-coagulation factor axis in liver progenitor cells determines outcome of acute liver failure.

In patients with acute liver failure (ALF) who suffer from massive hepatocyte loss, liver progenitor cells (LPCs) take over key hepatocyte functions, which ultimately determines survival. This study investigated how the expression of hepatocyte nuclear factor 4α (HNF4α), its regulators, and targets in LPCs determines clinical outcome of patients with ALF. Clinicopathological associations were scrutinized in 19 patients with ALF (9 recovered and 10 receiving liver transplantation). Regulatory mechanisms between follistatin, activin, HNF4α, and coagulation factor expression in LPC were investigated in vitro and in metronidazole-treated zebrafish. A prospective clinical study followed up 186 patients with cirrhosis for 80months to observe the relevance of follistatin levels in prevalence and mortality of acute-on-chronic liver failure. Recovered patients with ALF robustly express HNF4α in either LPCs or remaining hepatocytes. As in hepatocytes, HNF4α controls the expression of coagulation factors by binding to their promoters in LPC. HNF4α expression in LPCs requires the forkhead box protein H1-Sma and Mad homolog 2/3/4 transcription factor complex, which is promoted by the TGF-β superfamily member activin. Activin signaling in LPCs is negatively regulated by follistatin, a hepatocyte-derived hormone controlled by insulin and glucagon. In contrast to patients requiring liver transplantation, recovered patients demonstrate a normal activin/follistatin ratio, robust abundance of the activin effectors phosphorylated Sma and Mad homolog 2 and HNF4α in LPCs, leading to significantly improved coagulation function. A follow-up study indicated that serum follistatin levels could predict the incidence and mortality of acute-on-chronic liver failure. These results highlight a crucial role of the follistatin-controlled activin-HNF4α-coagulation axis in determining the clinical outcome of massive hepatocyte loss-induced ALF. The effects of insulin and glucagon on follistatin suggest a key role of the systemic metabolic state in ALF.

Liver transplantation in acute liver failure: Dilemmas and challenges.

Acute liver failure (ALF) refers to a state of severe hepatic injury that leads to altered coagulation and sensorium in the absence of pre-existing liver disease. ALF has different causes, but the clinical characteristics are strikingly similar. In clinical practice, however, inconsistency in the definition of ALF worldwide and confusion regarding the existence of pre-existing liver disease raise diagnostic dilemmas. ALF mortality rates used to be over 80% in the past; however, survival rates on medical treatment have significantly improved in recent years due to a greater understanding of pathophysiology and advances in critical care management. The survival rates in acetaminophen-associated ALF have become close to the post-transplant survival rates. Given that liver transplantation (LT) is an expensive treatment that involves a major surgical operation in critically ill patients and lifelong immunosuppression, it is very important to select accurate patients who may benefit from it. Still, emergency LT remains a lifesaving procedure for many ALF patients. However, there is a lack of consistency in current prognostic models that hampers the selection of transplant candidates in a timely and precise manner. The other problems associated with LT in ALF are the shortage of graft, development of contraindications on the waiting list, vaguely defined delisting criteria, time constraints for pre-transplant evaluation, ethical concerns, and comparatively poor post-transplant outcomes in ALF. Therefore, there is a desperate need to establish accurate prognostic models and explore the roles of evolving adjunctive and alternative therapies, such as liver support systems, plasma exchange, stem cells, auxiliary LT, and so on, to enhance transplant-free survival and to fill the void created by the graft shortage

Diagnostic Dilemma and Treatment Outcome in Acute Liver Failure Due to Wilson's Disease.

BackgroundWilson’s disease (WD) manifesting as acute liver failure (ALF) is a life-threatening condition, and spontaneous recovery is rare. Diagnostic scores like the alkaline phosphatase elevation/total bilirubin elevation ratio and aspartate aminotransferase/alanine aminotransferase ratio can distinguish WD from other ALF etiologies. Liver transplantation plays a major role in treating these patients, and the revised Wilson Index is useful in patient selection for this procedure. The aim of this study was to evaluate diagnostic scores, treatments, and outcomes of a large cohort of patients with WD-ALF.Material/MethodsTwenty adult patients of a historical cohort admitted from January 2001 to December 2017 were prospectively observed. Demographic, clinical, laboratory, and radiology data, and treatment, time on the waiting list for liver transplantation, and outcomes were recorded.ResultsNo diagnostic laboratory scores were 100% positive in patients with WD-ALF. Cut-off values for the alkaline phosphatase/total bilirubin ratio and aspartate aminotransferase/alanine aminotransferase ratio were met by 65.0% and 80.0% of patients, respectively. All patients met at least 1 criterion for high risk of death (Nazer or revised Wilson Index) and qualified for liver transplantation. In 9 patients, albumin dialysis was used before surgery. Survival after liver transplantation was 85.0% and 74.4% after 1 month and 1 year, respectively.ConclusionsFurther research on a novel diagnostic score in WD-ALF is warranted. Adult patients suspected to have WD as the cause of ALF should be treated in the referral liver transplantation unit. Liver transplantation makes long-term survival possible for patients with this critical illness.

A STUDY ON ETIOLOGY, CLINICAL FEATURES, MANAGEMENT AND OUTCOME OF ACUTE LIVER FAILURE IN PAEDIATRIC INTENSIVE CARE UNIT OF BURDWAN MEDICAL COLLEGE

Introduction: In the present study, etiology, important clinical features, management and outcome of acute liver failure in children admitted in Pediatric Intensive Care Unit (PICU) of BURDWAN MEDICALCOLLEGE, WB are studied. Aims and objectives:To study different clinical features among those children having acute liver failure. I. To study the management and outcome of those children with acute liver failure in the Pediatric Intensive Care Unit. Material and methods: Pediatric Intensive Care Unit of BURDWAN MEDICALCOLLEGE, WB. 1 Year [December 2019 to November 2020]. Patients from 3months of age to 12years of age are eligible for enrolment if they meet the following criteria. Conclusion: Present study showed that cerebral edema was signicantly associated with mortality whereas AKI and spontaneous bacterial peritonitis were not signicantly related with mortality. Mean TSB and Prothrobin Time were higher but mean serum albumin was lower in those cases that had died.

Etiology and Outcome of Acute Liver Failure in Children—The Experience of a Single Tertiary Care Hospital from Romania

Background: Acute liver failure (ALF) is a rare disease, associated with high mortality, despite optimal medical therapy without emergency liver transplantation. Knowing the possible cause of ALF plays a vital role in the management, as the child could benefit from effective specific therapies in emergencies. Methods: We have analyzed the etiology and outcome of ALF in children followed-up in a tertiary care hospital between January 2012–December 2018. The patients were grouped into different age categories: neonates (0–1 month), infants (1–12 months), children (1–14 years), and teenagers (14–18 years). Results: 97 children (46 males, 47.42%, the mean age of 7.66 ± 8.18 years) were admitted with ALF. The most important causes of ALF were in neonates and infants, infections (72.72%), and metabolic disorders (43.47%), in children and adolescents were the toxic causes (60% and 79.41%). The mortality rate was 31.95% (31 patients), mainly in ALF due to infections or metabolic disorders. Conclusions: In neonates and infants, the main causes of ALF were infections and metabolic diseases, while in older children and teenagers, were toxin-induced liver injuries. The mortality among neonates and infants was significantly higher than in other ages. Early recognition and immediate therapeutic intervention could improve the outcome of these patients.

Transplant center experience influences spontaneous survival and waitlist mortality in acute liver failure: An analysis of the UNOS database.

Transplant centers coordinate complex care in acute liver failure (ALF), for which liver transplant (LT) can be lifesaving. We studied associations between waitlist outcomes and center (1) ALF waitlist volume (low: <20; medium: 20-39; high: 40+ listings) and (2) total LT volume (<600, 600-1199, 1200+ LTs) in a retrospective cohort of 3248 adults with ALF listed for LT at 92 centers nationally from 2002 to 2019. Predicted outcome probabilities (LT, died/too sick, spontaneous survival [SS]) were obtained with multinomial regression, and observed-to-expected ratios were calculated. Median center outcome rates were 72.6% LT, 18.2% died/too sick, and 6.1% SS. SS was significantly higher with greater center ALF volume (median 0% for low-, 5.9% for medium-, and 8.6% for high-volume centers; P=.039), while waitlist mortality was highest at low-volume centers (median 21.4%, IQR: 16.1%-26.7%; P=.042). Significant heterogeneity in center performance was observed for waitlist mortality (observed-to-expected ratio range: 0-4.1) and particularly for SS (0-6.4), which persisted despite accounting for recipient case mix. This novel study demonstrates that increased center experience is associated with greater SS and reduced waitlist mortality for ALF. More-focused management pathways are needed to improve ALF outcomes at less-experienced centers and to identify opportunities for improvement at large.