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Background: Although the outcomes of living donor liver transplantation (LDLT) for pediatric acute liver failure (PALF) have improved, patient survival remains lower than in patients with chronic liver disease. We investigated whether the poor outcomes of LDLT for PALF persisted in the contemporary transplant era., Methods: We analyzed 193 patients who underwent LDLT between December 2000 and December 2020. The outcomes of patients managed in 2000-2010 (era 1) and 2011-2020 (era 2) were compared., Results: The median age at the time of LDLT was 1.2 years both eras. An unknown etiology was the major cause in both groups. Patients in era 1 were more likely to have surgical complications, including hepatic artery and biliary complications (p = 0.001 and p = 0.013, respectively). The era had no impact on the infection rate after LDLT (cytomegalovirus, Epstein-Barr virus, and sepsis). The mortality rates of patients and grafts in era one were significantly higher (p = 0.03 and p = 0.047, respectively). The 1- and 5-year survival rates were 76.4% and 70.9%, respectively, in era 1, while they were 88.3% and 81.9% in era 2 (p = 0.042). Rejection was the most common cause of graft loss in both groups. In the multivariate analysis, sepsis during the 30 days after LDLT was independently associated with graft loss (p = 0.002)., Conclusions: The survival of patients with PALF has improved in the contemporary transplant era. The early detection and proper management of rejection in patients, while being cautious of sepsis, should be recommended to improve outcomes further., (© 2024 Wiley Periodicals LLC.)

Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) are diseases with a rapidly progressive course and high mortality. Apart from treating the underlying triggers and intensive care measures, there are very limited therapeutic options for either condition. Liver transplantation is often the only life-saving treatment, but it cannot always be employed due to contraindications and severe disease progression. ACLF is characterized by underlying liver cirrhosis and typical triggers such as bacterial infections, bleeding, or alcohol binges. ALF occurs in previously healthy livers, usually as a result of purely hepatotoxic events. Disease differences are also reflected in the course and regulations of liver transplantation. Newer prognostic parameters and prioritization programs for ACLF can help improve both waiting list mortality and outcomes after transplantation., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Paediatric acute liver failure (PALF) is often characterised by its rapidity of onset and potential for significant morbidity and even mortality. Patients often develop multiorgan dysfunction/failure, including severe acute kidney injury (AKI). Whilst the management of PALF focuses on complications of hepatic dysfunction, the associated kidney impairment can significantly affect patient outcomes. Severe AKI requiring continuous kidney replacement therapy (CKRT) is a common complication of both PALF and liver transplantation. In both scenarios, the need for CKRT is a poor prognostic indicator. In adults, AKI has been shown to complicate ALF in 25-50% of cases. In PALF, the incidence of AKI is often higher compared to other critically ill paediatric ICU populations, with reports of up to 40% in some observational studies. Furthermore, those presenting with AKI regularly have a more severe grade of PALF at presentation. Observational studies in the paediatric population corroborate this, though data are not as robust-mainly reflecting single-centre cohorts. Perioperative benefits of CKRT include helping to clear water-soluble toxins such as ammonia, balancing electrolytes, preventing fluid overload, and managing raised intracranial pressure. As liver transplantation often takes 6-10 h, it is proposed that these benefits could be extended to the intraoperative period, avoiding any hiatus. Intraoperative CKRT (IoCKRT) has been shown to be practicable, safe and may help sicker recipients tolerate the operation with outcomes analogous with less ill patients not requiring IoCKRT. Here, we provide a comprehensive guide describing the rationale, practicalities, and current evidence base surrounding IoCKRT during transplantation in the paediatric population., (© 2024. The Author(s).)

Introduction: The use of natural products for therapeutic purposes is a common practice throughout the world, in part, due to the global obesity epidemic and the search for products with appetite suppression and weight loss properties, which include nutritional supplements, vitamins and minerals to herbal products. It is known that such products may be associated with various adverse health effects. Thus, the objective of this study is to report a series of cases of patients, who presented fulminant liver failure (HFI) requiring liver transplantation (LT), related to the consumption of products used for weight loss., Material and Methods: This is a retrospective cohort based on the evaluation of patients listed for LT due to IHF at the Hospital das Clínicas of the Universidade Estadual de Campinas, between 1991 and 2022, with patients who had confirmed consumption of products with the aim of loss being selected., Results: During the studied period, 92 patients were listed for HT due to IHF according to the Kings College criteria, with 5 cases being selected with proven consumption of herbal products for weight loss, and other causes that could explain the IHF were excluded. Four (80%) of the patients were female, with a mean age of 40.5 years, and 40% of the cases died., Discussion and Conclusions: Unlike traditional pharmaceutical medicines, in most countries, the commercialization of these products is not conditioned on clinical and safety evidence or prior approval by regulatory bodies. Hepatoxicity can be related to several factors, such as the presence of toxins naturally found in plants, the presence of heavy metals, contamination during obtaining or processing and the addition of substances omitted from the labels. The use of weight loss products can evolve with IHF, a fact that deserves attention, due to ease of access and growing demand, and it is important to regulate the trade of these products and raise public awareness about the risks of use without professional supervision and guidance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., (Copyright © 2023 American Association for the Study of Liver Diseases.)

In cases of uncontrollable hepatic hemorrhage or acute hepatic failure after trauma, liver transplantation can be a lifesaving procedure. Traumatic tricuspid valve injuries are rare, and symptoms can range from indolent to acute right heart failure. When concomitant, traumatic liver transplant and tricuspid injuries have significant physiologic interplay and management implications. We present a 14-year-old male injured in an all-terrain vehicle accident, who sustained a devastating disruption of the common bile duct and celiac artery injury, leading to acute hepatic failure, necessitating a two-stage liver transplantation. He was subsequently found to have a severe traumatic tricuspid injury, which required tricuspid valve replacement. At 4 years post-injury, he is without major complications. This is the first case presentation of the cooccurrence of these complex pathologies. Importantly, we demonstrate the complex decision-making surrounding traumatic liver transplantation and timing of subsequent tricuspid valve repair, weighing the complex interplay of these 2 pathologies., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Acute liver failure (ALF) is a life-threatening condition characterized by rapid liver function deterioration, necessitating a multidisciplinary approach for optimal perioperative care. This comprehensive review focuses on the critical role of the anaesthesiologist throughout the preoperative, intraoperative, and postoperative phases, addressing the unique challenges posed by ALF. The article begins with an exploration of ALF, underlining the urgency of timely referral to specialized hepatology centres. Liver transplantation emerges as a life-saving intervention, and the complex decision-making process is discussed, emphasizing the need for a multidisciplinary team to assess transplantation candidacy based on established prognostic criteria. In the preoperative phase, the review stresses the importance of early engagement with tertiary liver centres for timely referrals and identifies patients suitable for transplantation. Safe transport protocols are detailed, highlighting the meticulous planning required for the secure transfer of ALF patients between healthcare facilities. The intraoperative management section delves into the anaesthesiologist's key concerns, including neurological status, sepsis, acute kidney injury, body mass index, and preoperative fasting. Hemodynamic stability, fluid management, and coagulation balance during surgery are emphasized, with insights into anaesthesia techniques, vascular access, monitoring, and hemodynamic management tailored to the challenges posed by ALF patients. The postoperative care is thoroughly examined covering neurological, hemodynamic, metabolic, renal, and nutritional aspects. Management of ALF involves multidisciplinary team, including nephrology for continuous renal replacement therapy, transfusion medicine for plasma exchange, critical care for overall patient care, nutritionists for ensuring adequate nutrition, and hepatologists as the primary guides. In conclusion, the review recognizes the anaesthesiologist as a linchpin in the perioperative care of ALF patients. The integration of safe transport protocols and multidisciplinary approach is deemed crucial for navigating complexities of ALF, contributing to improved patient outcomes. This article serves as an invaluable resource for gastroenterologist and intensivists, enhancing their understanding of the anaesthesiologist's indispensable role in the holistic care of ALF patients in an ever-evolving healthcare landscape., (© 2024. Indian Society of Gastroenterology.)

Background: Pediatric acute liver failure (PALF) can require emergent liver transplantation (LT, >25%) or lead to death (~15%). Existing models cannot predict clinical trajectory or survival with native liver (SNL). We aimed to create a predictive model for PALF clinical outcomes based on admission variables., Methods: A retrospective, single-center PALF cohort (April 2003 to January 2022) was identified using International Classification of Disease codes, selected using National Institutes of Health PALF Study Group (PALFSG) criteria, and grouped by clinical outcome (SNL, LT, or death). Significant admission variables were advanced for feature selection using least absolute shrinkage and selection operator regression with bootstrapping (5000×). A predictive model of SNL versus LT or death was created using logistic regression and validated using PALFSG data., Results: Our single-center cohort included 147 patients (58% SNL, 32% LT, 10% expired), while the PALFSG validation cohort included 492 patients (50% SNL, 35% LT, 15% expired). Admission variables associated with SNL included albumin (odds ratio [OR], 16; P < 0.01), ammonia (OR, 2.37; P < 0.01), and total bilirubin (OR, 2.25; P < 0.001). A model using these variables predicted SNL versus LT or death with high accuracy (accuracy [0.75 training, 0.70 validation], area under the curve [0.83 training, 0.78 validation]). A scaled score (CHLA-acute liver failure score) was created that predicted SNL versus LT or death with greater accuracy (C statistic 0.83) than Pediatric End-Stage Liver Disease (C statistic 0.76) and admission liver injury unit (C statistic 0.76) scores., Conclusions: The CHLA-acute liver failure score predicts SNL versus LT or mortality in PALF using admission laboratories with high accuracy. This novel, externally validated model offers an objective guide for urgent referral to a pediatric LT center., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Acute liver failure (ALF) is characterized by an intense systemic inflammatory response, single or multiple organ system failure and high mortality. However, specific and effective treatments for ALF patients are still lacking. According to the current investigation, human umbilical cord mesenchymal stem cells (hUCMSCs) have shown remarkable potential to enhance the functional recovery of injured livers. We aimed to investigate the therapeutic effects of time-differentiated hUCMSCs administration regimens on ALF., Methods: The rat model of ALF was induced by D-galactosamine (D-gal), and hUCMSCs were administered via the tail vein 12 h before or 2 h after induction. The potential mechanisms of hUCMSCs in treatment of ALF, regulation cell subset and secretion of inflammatory factors, were verified by co-culturing with PBMCs in vitro. Liver function indicators were detected by an automatic biochemistry analyzer and inflammatory factors were obtained by ELISA detection. The distribution of hUCMSCs in rats after administration was followed by quantitative real-time fluorescence PCR., Results: The findings of the study discovered that administration of hUCMSCs 12 h prior to surgery could significantly improve the survival rate of rats, stabilize various liver function indicators in serum levels of ALT, AST, T-BIL, or ALB diminish inflammatory infiltration in liver tissue, and inhibit the secretion of inflammatory factors., Conclusion: Our data showed that pre-transplantation of hUCMSCs had a better therapeutic effect on ALF rats, providing empirical evidence for preclinical studies. Thus, the timing of hUCMSCs transplantation is necessary for the optimal clinical treatment effect., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Introduction and Objectives: Acute liver failure, also known as fulminant hepatic failure (FHF), includes a spectrum of clinical entities characterized by acute liver injury, severe hepatocellular dysfunction and hepatic encephalopathy. The objective of this study was to assess cerebral autoregulation (CA) in 25 patients (19 female) with FHF and to follow up with seventeen of these patients before and after liver transplantation., Patients and Methods: The mean age was 33.8 years (range 14-56, SD 13.1 years). Cerebral hemodynamics was assessed by transcranial Doppler (TCD) bilateral recordings of cerebral blood velocity (CBv) in the middle cerebral arteries (MCA)., Results: CA was assessed based on the static CA index (SCAI), reflecting the effects of a 20-30 mmHg increase in mean arterial blood pressure on CBv induced with norepinephrine infusion. SCAI was estimated at four time points: pretransplant and on the 1st, 2nd and 3rd posttransplant days, showing a significant difference between pre- and posttransplant SCAI (p = 0.005). SCAI peaked on the third posttransplant day (p = 0.006). Categorical analysis of SCAI showed that for most patients, CA was reestablished on the second day posttransplant (SCAI > 0.6)., Conclusions: These results suggest that CA impairment pretransplant and on the 1st day posttransplant was re-established at 48-72 h after transplantation. These findings can help to improve the management of this patient group during these specific phases, thereby avoiding neurological complications, such as brain swelling and intracranial hypertension., Competing Interests: Declaration of interests None., (Copyright © 2023 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Hepatic progenitor cell (HPC) activity and regenerative process that follows pediatric acute liver failure (PALF) is still not well understood. This clinicopathological study was thus conducted with an aim to study the correlation of liver histology and HPC activity with outcomes in PALF., Methods: All PALF patients with available hepatic histological specimens were included and specimens were analyzed for hepatocyte loss, HPC activity [using cytokeratin (CK) 7, CK19, sex-determining region Y-related high mobility group box(SOX)9 and epithelial cell adhesion molecule (EpCAM)], hepatocyte proliferation (using Ki67), and hepatocyte senescence (using p53 and p21)., Results: Ninety-four children were included: 22 (23.4%) survived with native liver (SNL) (i.e., the good outcome group) while rest (i.e., the poor outcome group) either died [33%, 35.1%] or received liver transplant (LT) [39%, 41.5%]. When compared to subjects with poor outcomes, those in the SNL group exhibited significantly less severe hepatocyte loss, fewer HPC/hpf, more proliferating hepatocytes, and less senescent hepatocytes (p < .05). Increasing severity of hepatocyte loss (adjusted OR: 9.95, 95% CI: 4.22-23.45, p < .001) was identified as an independent predictor of poor outcome. Eighty percent children with >50% native hepatocyte loss had poor outcome within 10 days of hospitalization., Conclusion: In PALF, more severe hepatocyte loss, higher number of HPC activation, lesser number of proliferating hepatocytes, and greater number of senescent hepatocytes are associated with a poor outcome. Loss of >50% hepatocytes is an independent predictor of poor outcome in PALF., (© 2023 Wiley Periodicals LLC.)

Background: Acute liver failure (ALF) is a component of multisystem organ failure that causes severe liver dysfunction in patients without underlying chronic liver disease. The patients with ALF are prone to have infections, including bacteremia. However, studies of the infectious impact for post liver transplantation (LT) in pediatric ALF are limited. We aimed to evaluate our current practice for pediatric LT cases of ALF with preoperative bacteremia., Methods: The records of all patients under 18 years old undergoing LT for ALF in our center from November 2005 to December 2021 were collected. They were divided into two groups: those with a preoperative bloodstream infection (BSI) and those without (NBSI). We compared the preoperative status and also reviewed the details of the BSI group. Intraoperative course and postoperative outcomes were also compared., Results: There were 19 BSI patients and 66 NBSI patients. One BSI case was detected on the day of LT. This patient had no changes in vital signs and general condition. After evaluation and therapeutic intervention by pediatric infectious disease specialists, LT was performed on the same day. Five cases developed septic shock at the time of detection of BSI. All BSI patients were in stable condition on the operation day with proper interventions. There were no significant differences in mortality and hospital stay between both groups., Conclusions: LT might be able to be performed for pediatric ALF even with positive blood cultures. In addition, appropriate therapeutic intervention by specialists and patient's stable condition before LT are essential., (© 2023 Wiley Periodicals LLC.)

Background: Pediatric acute liver failure (PALF) is an emergency, necessitating prompt referral and management at an experienced liver transplant center. Social determinants of health (SDOH) drive healthcare disparities and can affect many aspects of disease presentation, access to care, and ultimately clinical outcomes. Potential associations between SDOH and PALF outcomes, including spontaneous recovery (SR), liver transplant (LT) or death, are unknown. This study aims to investigate how SDOH may affect PALF and therefore identify areas for intervention to mitigate unrecognized disparities., Methods: A retrospective, single-center cohort was analyzed and then compared and validated with data from the multicenter National Institutes of Health PALF Study Group. The single-center review included 145 patients admitted with PALF using diagnostic codes. Medical records were reviewed to extract patient demographics, family structure, inpatient social worker assessments, and clinical outcomes. Data were stratified by outcome., Results: This analysis determined that level of family support (p = .02), caretaker employment (p = .02), patient age, race, and language (p = .01) may impact clinical outcomes. Specifically, the cohort of children that died had the largest proportion of non-English speaking patients with limited support systems and parents who worked full-time. Conversely, patients who underwent LT more often belonged to English-speaking families with a homemaker and extensive support systems., Conclusion: This study suggests that SDOH impact PALF outcomes and highlights patient populations facing additional challenges during an already complex healthcare emergency. These associations may indicate unconscious biases held by transplant teams when evaluating waitlist candidacy, as well as barriers to healthcare access. Strategies to better understand the broader applicability of our findings and, if confirmed, efforts to mitigate social disparities, may improve clinical outcomes in PALF., (© 2024 Wiley Periodicals LLC.)

A 24-year-old man was admitted to our hospital with abdominal distension. He was found to have acute liver failure and diagnosed with Budd-Chiari syndrome based on angiography and liver biopsy. Liver transplantation was deemed necessary when angiography showed extensive thrombotic occlusion of the hepatic veins and liver biopsy revealed submassive hepatic necrosis. The patient was found to have the JAK2V617F mutation, indicating a myeloproliferative neoplasm as the background disease. He developed hepatic encephalopathy but remained conscious on on-line hemodiafiltration. Brain-dead donor liver transplantation was performed on hospital day 30. Since then, the patient has remained well., (© 2023. Japanese Society of Gastroenterology.)

Background: Pediatric acute liver failure (PALF) is one of the most demanding emergencies in hepatology, intensive care, and for transplant team. This report describes the clinical pattern, diagnostic and therapeutic modalities in children with ALF considered at risk of death without liver transplantation, basing on a long-term experience of the pediatric transplant center., Materials and Methods: Between 1990 and 2022, 104 children aged 7 days-17 years (median 8 years), with body weight 3.1 to 77 kg (median 32 kg), were qualified for LT due to ALF, and finally 81 (78%) of them were transplanted (9% of all 899 LT performed in children in the same period)., Results: A total of 23 children were not transplanted: 15 (14.4%) died while awaiting transplantation. In 8 (7.7%) patients liver function recovered. Before transplantation 45 (43.3%) children developed circulatory failure, in 66 (63.5%) mechanical ventilation was necessary, 18 patients presented acute kidney injury (17.3%), and encephalopathy higher than stage I was present in 60 (57.7%) patients. In 63 children, various kidney/liver assist procedures were performed: CVVHD (continuous veno-venous hemodiafiltration in 22 (21.2%) patients, albumin dialysis (MARS; molecular adsorbent recirculating system) in 39 (37.5%) patients, therapeutic plasma exchange (TPE) in 13 (12.5%) patients. Twenty (24.7%) children died after LT including 15 (18.5%) in the early posttransplant period, and 5 (6.1%) in the late follow-up., Conclusions: Treatment of children with ALF in the peritransplant period is very difficult and require an experienced, multidisciplinary team. Despite continued advances in the care of children with ALF, patient survival remains lower than for elective indications for liver transplantation, and timely qualification and transplantation still are the most important factors of survival of these children., (© 2023 Wiley Periodicals LLC.)

Acetaminophen is a commonly used analgesic and antipyretic drug, which has experienced an increase in its consumption in recent years in our environment. There has also been an increase in the number of accidental and intentional overdoses that were treated by the health system. Its toxicity is dose-dependent and can cause fulminant liver failure, becoming one of the main reasons for liver transplantation in English-speaking countries. The case of a 28-year-old woman with a history of major depression and five previous suicide attempts, who deliberately ingested a significant amount of paracetamol tablets, is here presented. She developed fulminant liver failure and metabolic acidosis, for which she underwent an emergency liver transplant due to the severity of her condition, from which she evolved favorably. The decision to perform a liver transplant in serious cases like this and under a condition of severe psychiatric vulnerability is challenging and must be carefully considered. This particular case illustrates the importance of multidisciplinary care including psychiatric evaluation in patients with acetaminophen poisoning.

Background & Aims: Patients with acute liver failure (ALF) awaiting liver transplantation (LT) may develop multiorgan failure, but organ failure does not impact waitlist prioritization. The aim of this study was to examine the impact of organ failure on waitlist mortality risk and post LT outcomes in patients with ALF., Methods: We studied adults waitlisted for ALF in the United Network for Organ Sharing (UNOS) database (2002-2019). Organ failures were defined using a previously described Chronic Liver Failure modified sequential organ failure score assessment adapted to UNOS data. Regression analyses of the primary endpoints, 30-day waitlist mortality (Competing risk), and post-LT mortality (Cox-proportional hazards), were performed. Latent class analysis (LCA) was used to determine the organ failures most closely associated with 30-day waitlist mortality., Results: About 3212 adults with ALF were waitlisted, for hepatotoxicity (41%), viral (12%) and unspecified (36%) etiologies. The median number of organ failures was three (interquartile range 1-3). Having ≥3 organ failures (vs. ≤2) was associated with a sub hazard ratio (HR) of 2.7 (95%CI 2.2-3.4)) and a HR of 1.5 (95%CI 1.1-2.5)) for waitlist and post-LT mortality, respectively. LCA identified neurologic and respiratory failure as most impactful on 30-day waitlist mortality. The odds ratios for both organ failures (vs. neither) were higher for mortality 4.5 (95% CI 3.4-5.9) and lower for delisting for spontaneous survival .5 (95%CI .4-.7) and LT .6 (95%CI .5-.7)., Conclusion: Cumulative organ failure, especially neurologic and respiratory failure, significantly impacts waitlist and post-LT mortality in patients with ALF and may inform risk-prioritized allocation of organs., (© 2023 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Viral hepatitis accounts for a significant global disease burden and mortality, both in children and adults. There are significant differences in the viral etiology, epidemiology, and complications in children worldwide. Children of all ages may have devastating complications with a significant risk of mortality and long-term morbidity because of viral hepatitis. Liver transplantation is the only curative option for pediatric patients with end-stage liver disease, hepatocellular carcinoma, or acute liver failure because of viral hepatitis. The introduction of universal vaccination for hepatitis B across the world and hepatitis A in some countries had led to significant changes in the incidence of disease and the need for liver transplantation for the complications of viral hepatitis in children. The development of effective treatment with directly acting antiviral agents for hepatitis C has already transformed outcomes in adults and children and reduced the need for liver transplantation. Although newer therapy for hepatitis B is being evaluated in adults, current therapy for children is not curative, indicating the need for lifelong therapy and potential necessity for liver transplantation. The recent epidemic of acute hepatitis in children across the world has highlighted the importance of understanding the etiology of unusual causes for acute liver failure and the urgent need for liver transplantation., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Early treatment of severe acute hepatitis B virus (HBV) infection with nucleos(t)ide analogues may prevent progression to acute liver failure (ALF)., Patients and Methods: The charts of 24 patients who were treated for severe acute HBV infection (either INR ≥ 1.5 or INR≥ 1.4 and total bilirubin ≥ 20 mg/dL at the referring institution or after admission) between April 2021 and May 2023 (inclusive) were evaluated retrospectively. Twelve patients were women; median [range] age: 48 [35-68]. Entecavir (0.5 mg/day) (n = 16) or tenofovir disoproxil fumarate (245 mg/day) (n =8) were used depending on availability., Results: Two patients required liver transplant which was performed successfully in one (no suitable donor for the other). Deterioration to ALF was prevented in 22 of the 24 cases (92%); these patients could be discharged after median (range) 12 (5-24) days following initiation of the antiviral drug. There was no significant difference in efficacy between the two antiviral agents. The anti-HBsAg antibody became positive in 16 patients (73%); one other patient became HBsAg negative at 1 month after discharge but was lost to follow up. Five patients (23%) are still HBsAg positive but all except one have started treatment in the last 6 months. One of the recently treated 4 patients stopped taking the antiviral drug at his own will and one has become anti-HIV antibody positive during follow up., Conclusion: Early treatment of severe acute HBV infection with entecavir or tenofovir disoproxil fumarate prevents the need for liver transplant and consideration of living donors., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

BACKGROUND Liver transplantation is a life-saving intervention for patients with a diagnosis of acute liver failure or end-stage liver disease. Despite advances in surgical techniques and immunosuppressive therapies, primary nonfunction remains a concern, often necessitating retransplantation. In these scenarios, the anhepatic state, achieved through total hepatectomy with a temporary portacaval shunt, serves as a bridge to retransplantation. However, the challenge lies in the uncertain survival period and several potential complications associated with this procedure. CASE REPORT We present a case of a 35-year-old male patient with autoimmune hepatitis who underwent liver transplantation from a deceased donor. Seven days later, he experienced acute liver failure, leading to an urgent listing for retransplantation. To prevent the intense systemic inflammatory response, the patient underwent a total hepatectomy with a temporary portacaval shunt while awaiting another graft and endured a 57-h anhepatic state. On day 17 following retransplantation, he had cerebral death due to a hemorrhagic stroke. CONCLUSIONS This case underscores one of the most prolonged periods of anhepatic state as a bridge to retransplantation, highlighting the complexities associated with this technique. The challenges include sepsis, hypotension, coagulopathy, metabolic acidosis, renal failure, electrolyte disturbances, hypoglycemia, and hypothermia. Vigilant monitoring and careful management are crucial to improve patient outcomes. Further research is needed to optimize the duration of the anhepatic state and minimize complications for liver transplantation recipients.

Yellow phosphorus or metal phosphide (YP-MP) rodenticide poisoning has been a known cause of acute liver failure (ALF) in many countries of Asia and North and South America over the last decade. It is a highly toxic compound and is a well-known cause of intentional or accidental poisoning in both adults and children. In lower doses, it causes gastrointestinal symptoms and mild hepatic injury, and patients may spontaneously recover. In higher doses, hepatic necrosis and fatty infiltration may cause significant injury and may even lead to ALF, characterized by hepatic encephalopathy, coagulopathy, and lactic acidosis. Cardiotoxicity, rhabdomyolysis, and neutropenia are other well-documented complications. If untreated, it may lead to multi-organ dysfunction and death. Plasmapheresis and continuous renal replacement therapy (CRRT) have been used with limited success in patients who do not recover spontaneously. However, patients who develop ALF often need liver transplantation (LT). Liver transplantation has been successfully performed in ALF due to YP-MP poisoning in several countries, with good results in both adult and pediatric patients. Separate criteria for LT are important to ensure early and rapid listing of critical patients on the waiting list. The success rates of LT for ALF due to YP-MP rodenticide poisoning are very promising, provided there are no contra-indications to transplant. Plasma exchange, CRRT, or cytosorb can be used as a bridge to transplant in selected patients. In the long term, only with an increase in public awareness and sale restrictions can we prevent the intentional and accidental poisoning caused by this easily available, highly toxic compound., Competing Interests: Declaration of Competing Interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: This study aimed at studying the challenges and outcomes of live-donor liver transplantation (LDLT) for pediatric acute liver failure (PALF)., Study Design: A total of 315 patients with PALF were treated over a period of 11 years. 42 underwent LT (41 LDLT and one DDLT), constituting 38% (41/110) of all pediatric transplants during this duration. The outcomes of LDLT for PALF were analyzed., Results: All the 41 children who underwent LT met the Kings College criteria (KCC). The etiology was indeterminate in 46.3% (n = 19) children. 75.6% (n = 31) were on mechanical ventilation for grade 3/4 hepatic encephalopathy. There was presence of cerebral edema on a computed tomography scan of the brain in 50% of the children. One-third of our children required hemodynamic support with vasopressors. Systemic inflammatory response syndrome and sepsis were observed in 46.3% and 41.4% of patients, respectively. Post-LDLT 1- and 5-yr patient and graft survival were 75.6% and 70.9%, respectively. The survival in children satisfying KCC but did not undergo LT was 24% (38/161). Vascular and biliary complication rates were 2.4% and 4.8%, respectively. No graft loss occurred because of acute rejection. In multivariate analysis, pre-LT culture positivity and cerebral edema, persistence of brain edema after transplantation, and resultant pulmonary complications were significantly associated with post-LT death. Thirteen (32%) children who underwent plasmapheresis prior to LT had better post-LT neurological recovery, as evidenced by early extubation., Conclusion: LDLT for PALF is lifesaving and provides a unique opportunity to time transplantation. Good long-term survival can be achieved, despite the majority of patients presenting late for transplantation. Early referral and better selection can save more lives through timely transplantation., (© 2023. Asian Pacific Association for the Study of the Liver.)

Background: The etiology of acute liver failure (ALF) remains one of the most important factors in determining prognosis and predicting outcomes. In a significant proportion of ALF cases, however, the etiology remains unknown and is categorized as indeterminate ALF (IND-ALF). In this study, we summarize findings from patients with IND-ALF from 32 transplant centers across the United States, and we compare laboratory, prognostic, and outcome data for patients with IND-ALF., Methods: Between 1998 and 2019, 3364 adult patients with ALF or acute liver injury (ALI) from 32 liver transplant centers were enrolled in the ALFSG registry. The primary clinical outcome of interest was 21-day transplant-free survival (TFS)., Results: Of the 3364 patients enrolled in the ALFSG registry, 3.4 % (n = 114) were adjudicated as true indeterminate. On multivariate analysis, patients with a lower bilirubin, lower INR, lack of use of mechanical ventilation and no clinical features of coma at baseline had a higher odds ratio of transplant free survival. The number of deaths were similar between patients with true-IND ALF versus patients with indeterminable ALF (29.8% vs. 27.2%), with almost half of the patients requiring liver transplant (42.1% vs. 45.7%)., Conclusion: We illustrate the poor prognoses that true-IND-ALF and indeterminable ALF carry and the need for emergency liver transplantation in most cases., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To investigate whether and how experience accumulation and technical refinements simultaneously implemented in auxiliary orthotopic liver transplantation (AOLT) may impact on outcomes., Background: AOLT for acute liver failure (ALF) provides the unique chance of complete immunosuppression withdrawal after adequate native liver remnant regeneration but is a technically demanding procedure. Our department is a reference center for ALF and an early adopter of AOLT., Methods: This is a single-center retrospective before/after study of a prospectively maintained cohort of 48 patients with ALF who underwent AOLT between 1993 and 2019. In 2012, technical refinements were implemented to improve outcomes: (i) favoring the volume of the graft rather than that of the native liver, (ii) direct anastomosis of graft hepatic artery with recipient right hepatic artery instead of the use of large size vessels, (iii) end-to-side hepaticocholedocostomy instead of bilioenteric anastomosis. Early experience (1993-2011) group (n=26) and recent experience (2012-2019) group (n=22) were compared. Primary endpoint was 90-day severe morbidity rate (Clavien-Dindo≥IIIa) and secondary endpoints were overall patient survival and complete immunosuppression withdrawal rates., Results: Compared with the earlier experience group, the recent experience group was associated with a lower severe complication rate (27% vs 65%, P <0.001), as well as less biliary (18% vs 54%, P =0.017) and arterial (0% vs 15%, P =0.115) complications. The 1-, 3-, and 5-year patient survival was significantly improved (91%, 91%, 91% vs 76%, 61%, 60%, P =0.045). The rate of complete immunosuppression withdrawal increased to 94% vs 70%, ( P =0.091) with no need of long-term graft explant., Conclusion: These technical refinements favoring the liver graft and reducing morbidity may promote AOLT implementation among LT centers., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Acute liver failure is a life-threatening condition for which ABO-incompatible living donor liver transplantation (ABOi-LDLT) is sometimes the only life-saving treatment option. We reviewed a single-center experience of adult ABOi-LDLT treatment for acute liver failure (ALF)., Methods: Preoperative treatment, immune indices (B cell marker, anti-donor blood-type antibody), and postoperative outcomes were compared between ALF and non-ALF groups., Results: There were 5 and 33 patients in the ALF and non-ALF groups, respectively. The ALF group received higher doses of steroids, underwent more rounds of plasma exchange (PE), and underwent transplantation for ALF with a shorter interval following preoperative rituximab (RTx) administration (median: 2 vs 13 days; P < 0.05) than the non-ALF group. Preoperatively, CD19-positive lymphocytes in the peripheral blood were sufficiently depleted in all of the non-ALF group patients, whereas they were poorly depleted in the ALF group. Postoperatively, neither group suffered anti-donor blood-type antibody titer rebound or antibody-mediated rejection. The ALF group had a comparable 5-year survival rate to the non-ALF group (80.0% vs 77.9%)., Conclusions: Despite the delayed preoperative administration of RTx, the ALF group showed an uneventful immunological response and acceptable long-term survival rate. Thus, ABOi-LDLT seems a viable treatment option for ALF., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

In cases of acute liver failure (ALF) with hepatic coma, early liver transplantation, including ABO-incompatible (ABOi) living donor liver transplantation (LDLT), should be considered. The ABO antibody barrier can be reduced using plasma exchange (PE) and the anti-CD20 antibody rituximab. Plasma exchange is also performed for drug-induced ALF and is effective for desensitization. Rituximab treatment usually requires 14 days. There is presently no established desensitization protocol for ABOi-LDLT for ALF. Here, we report a case of drug-induced ALF with hepatic coma, which was treated with ABOi-LDLT using PE and rituximab 8 days prior to surgery. A 33-year-old female, with a history of headaches for which she was taking analgesics daily, developed drug-induced ALF with hepatic coma. Her ABOi sister desired to become a liver donor. We initiated desensitization using rituximab (500 mg) and mycophenolate mofetil (MMF, 2000 mg/day), followed by five sessions of PE. Eight days after rituximab administration, ABOi-LDLT with splenectomy was performed. Postoperatively, the patient received local infusion via portal vein for 14 days and immunosuppression with tacrolimus, methylprednisolone, and MMF. No episode of cellular or antibody-mediated rejection (AMR) was observed. The patient was discharged uneventfully 56 days after ABOi-LDLT with no problems up to 15 months after the transplant., (© 2023. Japanese Society of Gastroenterology.)

Acute liver failure (ALF) is a severe liver disease syndrome with rapid deterioration and high mortality. Liver transplantation is the most effective treatment, but the lack of donor livers and the high cost of transplantation limit its broad application. In recent years, there has been no breakthrough in the treatment of ALF, and the application of stem cells in the treatment of ALF is a crucial research field. Mesenchymal stem cells (MSCs) are widely used in disease treatment research due to their abundant sources, low immunogenicity, and no ethical restrictions. Although MSCs are effective for treating ALF, the application of MSCs to ALF needs to be further studied and optimized. In this review, we discuss the potential mechanisms of MSCs therapy for ALF, summarize some methods to enhance the efficacy of MSCs, and explore optimal approaches for MSC transplantation.

Pretransplant malignancy unrelated to hepatocellular carcinoma is a challenging condition in liver transplantation. Standard of care requires the completion of treatments and a disease-free period before the transplant. However, in the setting of a fulminant hepatic failure, these steps cannot be achieved. A 46-year-old woman with a recent diagnosis of stage 2 breast cancer presented to our center with a fulminant hepatic failure of unknown origin. Because of the rapid worsening of her clinical status, she was listed as eligible for transplant after a multidisciplinary evaluation. Because of a shortage of available donors, a deceased donor ABO-incompatible liver transplant with a synchronous mastectomy and first-level axillary lymphadenectomy was performed. To prevent antibody-mediated rejection, a triple immunosuppression therapy and a postoperative therapeutic plasmapheresis were performed. The patient remains without cancer recurrence at 18 months of follow-up. Recent studies have shown that cancer recurrence in recipients with pretransplant malignancy is considerably lower than suggested in previously published studies. However,this data is not sufficient to establish evidence-based guidelines on the indications and timing of transplant. In selected cases, the presence of a pretransplant malignancy does notrepresent a contraindication for a rescue liver transplant. Further studies are needed to stratify the risk and to help clinicians to choose the best strategy in an urgent context such as this.

Background and Aim: The prognosis of acute liver failure (ALF) remains poor, and liver transplantation is an alternative treatment option. Assessing the prognosis of ALF is important in determining treatment strategies. Here, we investigated clinical factors including serum pro-inflammatory cytokine levels that are associated with the prognosis of ALF., Methods: Sixty-six patients who developed ALF were enrolled in this study. Serum concentrations of 12 pro-inflammatory cytokines were measured on admission. The prognosis and factors associated with survival and development of hepatic coma were analyzed., Results: Of 66 patients, 4 patients underwent liver transplantation, and 49 patients were rescued without liver transplantation, while the remaining 13 patients died. Serum concentrations of interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-13, TNF, IFN -γ, IP-10, and G-CSF were significantly elevated in ALF patients. IL-4 and IL-8 levels were higher in patients who underwent liver transplantation or died than in rescued patients. Multivariable analysis identified age ≥ 55 years and IL-4 ≥ 1.2 pg/mL on admission as independent factors for mortality. Serum IL-8 levels were higher in patients with hepatic coma, and prothrombin-international normalized ratio ≥ 3.5 and IL-8 ≥ 77.2 pg/mL on admission were associated with development of hepatic coma after admission., Conclusion: Serum levels of several pro-inflammatory cytokines were elevated in ALF patients. IL-4 and IL-8 were correlated with survival and development of hepatic coma after admission, respectively. Measurement of serum pro-inflammatory cytokines seems to be useful for the management of ALF., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Auxiliary partial orthotopic liver transplant is a complex technique whereby a partial liver graft is transplanted in the orthotopic position, leaving behind a portion of the native liver. In acute liver failure, auxiliary partial orthotopic liver transplant serves as a rescue therapy and bridge for the native liver to regenerate. Auxiliary partial orthotopic liver transplant was initially considered a technically challenging procedure with inferior results versus orthotopic liver transplant. However, advancements in surgical techniques have led to improved results with auxiliary partial orthotopic liver transplant. Auxiliary partial orthotopic liver transplant is now increasingly accepted as a valid treatment option for acute liver failure. We present 2 cases of acute liver failure treated with auxiliary partial orthotopic liver transplant using an extra-small-for-size graft. The first case was a 12-year-old female patient who presented with druginduced acute liver failure and required an auxiliary partial orthotopic liver transplant with an extra-small left lobe graft (graft-to-recipient weight ratio of 0.45). The second case was a 23-year-old male patient with acute liver failure of unknown etiology who underwent an auxiliary partial orthotopic liver transplant with a small right lobe graft (graft-torecipient weight ratio of 0.5). In both cases, computed tomography liver volumetry was performed to determine the appropriate graft size for the recipient. Both patients underwent successful auxiliary partial orthotopic liver transplants, with good postoperative recovery. Follow-up examinations showed satisfactory liver function without evidence of graft failure or rejection. Auxiliary partial orthotopic liver transplant using extra-small grafts can be an effective treatment option for acute liver failure when no other suitable option exists, including as a rescue procedure for small grafts. However, careful patient selection and surgical planning are essential to ensure successful outcomes.

Drug-induced liver injury has become the main cause of acute liver failure (ALF). Injury may be dose-dependent or occur idiosyncratically. We report the case of a 37-year-old female patient admitted with grade 4 hepatic encephalopathy. Morosil use was initiated 30 days prior, and after 2 weeks, the case evolved with jaundice and diarrhea interspersed with constipation when the medication was discontinued. Morosil is a dry extract of the juice of red Moro oranges (Citrus species), grown in eastern Sicily (Italy). It is an important source of anthocyanidin pigments, which act as antioxidants and are used in the care and prevention of obesity, insulin resistance, hepatic steatosis, and cardiovascular diseases. According to the clinical picture and tests performed, the diagnosis of ALF was confirmed, by the criteria of Clichy and King's College. The patient was listed for liver transplantation as a priority, with the model for end stage liver disease (MELD) score: 41. Orthotopic liver transplantation was uneventfully performed using the Piggy-back technique. There are few reports in the literature of acute liver injury by other Citrus species, and we found no case reports of ALF related to the use of Morosil., (Copyright © 2023. Published by Elsevier Inc.)

Background: Post-hepatectomy liver failure is a severe complication after major liver resection and is associated with a high mortality rate. Nevertheless, there is no effective treatment for severe liver failure. In such a setting, rescue liver transplantation (LT) is used only in extraordinary cases with unclear results. This systematic review aims to define indication of LT in post-hepatectomy liver failure and post-LT outcomes, in terms of patient and disease-free survivals, to assess the procedure's feasibility and effectiveness., Methods: A systematic review of all English language full-text articles published until September 2022 was conducted. Inclusion criteria were articles describing patients undergoing LT for post-hepatectomy liver failure after liver resection, which specified at least one outcome of interest regarding patient/graft survival, postoperative complications, tumour recurrence and cause of death. A pseudo-individual participant data meta-analysis was performed to analyse data. Study quality was assessed with MINORS system. PROSPERO CRD42022349358., Results: Postoperative complication rate was 53.6%. All patients transplanted for benign indications survived. For malignant tumours, 1-, 3- and 5-year overall survival was 94.7%, 82.1% and 74.6%, respectively. The causes of death were tumour recurrence in 83.3% of cases and infection-related in 16.7% of LT recipients. At Cox regression, being transplanted for unconventional malignant indications (colorectal liver metastasis, cholangiocarcinoma) was a risk factor for death HR = 8.93 (95%CI = 1.04-76.63; P-value = 0.046). Disease-free survival differs according to different malignant tumours (P-value = 0.045)., Conclusions: Post-hepatectomy liver failure is an emergent indication for rescue LT, but it is not universally accepted. In selected patients, LT can be a life-saving procedure with low short-term risks. However, special attention must be given to long-term oncological prognosis before proceeding with rescue LT in an urgent setting, considering the severity of liver malignancy, organ scarcity, the country's organ allocation policies and the resource of living-related donation., Competing Interests: Declaration of Competing Interest Authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

BACKGROUND Recently, there has been a recommendation to utilize a combination of supportive extracorporeal therapies, specifically plasma exchange and continuous venovenous hemodiafiltration, in patients with acute liver failure. This 15-year retrospective study aimed to evaluate supportive extracorporeal therapy, including plasma exchange and continuous venovenous hemodiafiltration, for 114 adults with acute liver failure awaiting liver transplant. MATERIAL AND METHODS In this retrospective study, the medical records of 1288 adult patients who underwent liver transplantation and 161 adult patients who received alternative therapy were analyzed; 114 patients who received combined supportive extracorporeal therapy for acute liver failure were included in the study. Biochemical laboratory data were compared before and after therapy. RESULTS The study included 50 male and 64 female patients. The first group (34 patients) recovered with liver transplantation, and 4 patients died in the first year after liver transplantation. In the second group (80 patients), 66 patients recovered without liver transplantation, while 14 patients died within the first 2 weeks after therapy. All patients showed significant reductions in serum hepatic function tests (alanine transaminase, aspartate transaminase, and total bilirubin), ammonia, and prothrombin time/international normalized ratio after discontinuation of combined supportive extracorporeal therapy (P<0.01). There was also a significant improvement in the hemodynamic parameter. CONCLUSIONS This combined extracorporeal therapy can be used as a supportive treatment for both recovery and bridge to liver transplantation in patients with acute liver failure. In addition, treatment can be continued until liver regeneration and until a usable donor is found.

Purpose: Acute liver failure (ALF) is characterized by hepatic encephalopathy (HE) often due to intracranial hypertension (ICH). The risk/benefit-balance of intraparenchymal pressure catheter monitoring is controversial during ALF., Aims: Perform an evaluation of transcranial Doppler (TCD) use in patients with ALF listed for emergency liver transplantation., Material and Methods: Single center retrospective cohort study including all patients registered on high emergency LT list between 2012 and 2018. All TCD measurements performed during ICU stay after listing and after LT (when performed) were recorded. TCD was considered abnormal when pulsatility index (PI) was >1.2., Results: Among 106 patients with ALF, forty-seven (44%) had a TCD while on list. They had more severe liver and extrahepatic organ failure. When performed, TCD was abnormal in 51% of patients. These patients more frequently developed ICH events (45% vs. 13%, p = .02) and more frequently required increase in sedative drugs and vasopressors. While 22% of patients with normal TCD spontaneously survived, all of those with abnormal TCD died or were transplanted (p = .02). All transplanted patients who had abnormal exams normalized their TCD within 2 (1-2) days after LT., Conclusion: TCD may be a useful non-invasive tool for ICH detection and management, then guide sedation withdrawal., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Neurological impairment is not rare in infants with acute liver failure (ALF). This study aimed to investigate the perioperative risk factors for neurological impairment following liver transplantation (LT) in infantile ALF., Methods: Retrospective analysis was performed in infants who were younger than 1 year with ALF who subsequently underwent LT at our hospital between January 2005 and December 2016. Patients were considered to have neurological impairment if the Pediatric Cerebral Performance Category score was between 2 and 5 at the age of 6 years. A comparison between the groups of infants with and without neurological impairment was performed, and factors with p < .10 in the comparison were analyzed using univariate logistic regression analysis for neurological impairment., Results: Twenty-six infants survived until 6 years of age, and 31% (8/26) of them had neurological impairment. Patients with neurological impairment were significantly younger in age at ALF onset, had significantly higher pre-LT bilirubin and prothrombin time/international normalized ratio, and stayed significantly longer in the intensive care unit than those without neurological impairment. Total bilirubin (odds ratio (OR) = 1.12, 95% confidence interval (CI) 1.02-1.22, p = .012), indirect bilirubin (OR = 1.10, 95% CI 1.01-1.20, p = .025), direct bilirubin (OR = 1.22, 95% CI 1.01-1.47, p = .040), and age in month at ALF (OR = 0.76, 95% CI 0.58-0.999, p = .049) showed significant association with neurological impairment., Conclusions: High pre-LT peak bilirubin value and younger age at ALF onset can be perioperative risk factors for neurological impairment after LT in infantile ALF., (© 2023 Wiley Periodicals LLC.)

Sevoflurane is a volatile anesthetic agent that does not tend to cause clinically significant hepatotoxicity, but there are some reported hepatotoxicity cases in the literature. In the case presented here, adenotonsillectomy was performed during influenza infection, and sevoflurane was administered, after which acute fulminant hepatitis developed. At hour 24 of hospitalization after fulminant hepatic failure, liver transplant was performed in a 3.5-year-old patient without any known diseases. In such cases, etiology investigations should be planned, life support therapy should be administered, and information should be given to the patient to avoid exposure to sevoflurane in the future.

Autoimmune hepatitis is a common cause of acute liver failure. Treatment includes steroids for acute liver injury and liver transplantation in those who fail to respond or develop acute liver failure. The aim of this study is to further characterize acute liver failure secondary to autoimmune hepatitis and identify variables that predict 21-day transplant-free survival. This study included adults hospitalized with acute liver failure enrolled in the Acute Liver Failure Study Group Registry between 1998 and 2019 from 32 centers within the US. The etiology of all cases was reviewed by the Adjudication Committee, and all cases identified as autoimmune hepatitis were included. Acute liver injury was defined as an INR ≥2.0 without encephalopathy and acute liver failure as INR ≥ 1.5 with encephalopathy. Laboratory and clinical data were reviewed. Variables significantly associated with 21-day transplant-free survival were used to develop a multivariable logistic regression model.  A total of 193 cases of acute liver failure secondary to autoimmune hepatitis were identified and reviewed. There were 161 patients (83.4%) diagnosed with acute liver failure on enrollment, and 32 (16.6%) developed acute liver failure during hospitalization. At 21 days, 115 (59.6%) underwent liver transplantation, 28 (14.5%) had transplant-free survival, and 46 (23.8%) died before liver transplantation. Higher admission values of bilirubin, INR, and coma grade were associated with worse outcomes. A prognostic index incorporating bilirubin, INR, coma grade, and platelet count had a concordance statistic of 0.84. Acute liver failure secondary to autoimmune hepatitis is associated with a high short-term mortality. We developed a model specifically for autoimmune hepatitis that may be helpful in predicting 21-day transplant-free survival and early identification of patients in need of expedited liver transplant evaluation., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Acute hepatic failure is characterized by rapid deterioration of hepatic function with encephalopathy in a patient without pre-existing liver disease. Bispectral index values had a significant correlation with cerebral perfusion. Transcranial Doppler can assess changes in cerebrovascular function and has the advantages of being noteworthy and widely available. This is a case report of a hepatic encephalopathy occurring during a deceased donor liver transplant in a patient presenting fulminant hepatitis. We briefly discuss some diagnostic methods highlighting the challenges of the anesthesiologist in managing this kind of patient in the context of a major surgery., Competing Interests: DISCLOSURE All the authors declare no conflicts of interest and declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Here we present the case of a cystic fibrosis (CF) patient with preserved pulmonary function who developed acute liver failure requiring liver transplant following an episode of binge drinking and ingestion of a modest amount of acetaminophen. Cystic Fibrosis Liver Disease (CFLD) is the third most common cause of death among CF patients. The pathogenesis of CFLD is complex and still not fully understood. It is important that patients suffering from CF know about the possible dangers associated with acetaminophen and ethanol ingestion. Our case report highlights the need for more research that needs to be done to truly understand the underlying pathogenesis of CFLD and the significant risk factors that play a part in the development of acute liver failure in patients with CF.

Objective: To investigate the clinical efficacy of liver transplantation in the treatment of acute liver in children with NBAS gene deficiency disease and their outcome. Methods: This retrospective study enrolled children with NBAS gene deficiency who were admitted to the Children's Hospital of Fudan University for liver transplantation from January 2013 to June 2022. The clinical data were collected and analyzed. Medical literature published before June 2022 was searched with the keywords of "NBAS" "neuroblastoma amplified sequence recurrent" "acute liver failure" "SOPH syndrome" "short stature with optic nerve atrophy" "Pelger-Huët anomaly" in PubMed, China National Knowledge Infrastructure and Wanfang database. Results: Liver transplantation was performed in 3 patients (2 males and 1 female) with NBAS deficiency. All patients presented with fever-triggered recurrent acute liver failure. The genetic detection found compound heterozygous NBAS gene pathogenic variants in them. The total episodes of acute liver failure before liver transplantation were 11, 2, and 4 respectively, and the age at liver transplantation was 3.5, 2.3, and 2.0 years respectively. During liver transplantation, patient 1 was in the convalescent phase of acute liver failure, patient 2 was in the acute phase, presenting with hepatic encephalopathy (grade V) and respiratory failure, and patient 3 was considered to be in the acute phase. After liver transplantation, patient 1 recovered normal liver function within 1 month and had no liver transplantation-related complications. Patient 2 had secondary epilepsy, intellectual disability, movement disorder, and transiently elevated transaminases. Patient 3 died of severe infection within 1 month. There was no literature in Chinese, 6 in English, 8 NBAS-deficient patients who were treated with liver transplantation. Total 11 patients presented with fever-triggered recurrent acute liver failure. Their age at liver transplantation ranged from 0.9 to 5.0 years. Postoperative complications occurred in 3 patients. Until the last visit, they were followed up for 0.7 to 14.0 years. Total 2 patients died and the 9 surviving patients did not develop acute liver failure. Conclusions: Liver transplantation is effective for the treatment of acute liver failure associated with NBAS gene disease. However, postoperative complications of liver transplantation may occur. The timing of liver transplantation still needs further research.

Background: The occurrence of acute liver failure (ALF) in pregnant women due to an etiology unrelated to pregnancy (pregALF) that leads to liver transplantation (LT) has rarely been reported. The objective was to report the outcome of pregnant women and fetus and propose a strategy for the timing of delivery and of LT in these patients., Methods: Five consecutive pregnant patients with ALF were admitted to our center between 1986 and 2018 and underwent an LT. A systematic review of case reports concerning patients with pregALF who underwent LT was extracted from the literature., Results: Three with gestational ages (GA) at admission of 15, 22, and 31 weeks of gestation (WG) were transplanted after delivery (n = 1) or intrauterine demise (n = 2) and 2 with GA of 16 and 23 WG before delivery. One infant survived in each group. Among the 32 cases published previously, 11 (34%) had been transplanted after delivery (median GA:31 [28-33]); 10 of these 11 infants were alive at birth. The other 21 mothers were transplanted before delivery (GA:21 WG [18-22]). The median GA at delivery was 30 WG [27.75-37]. Twelve of 21 infants were alive at birth. One-year survival among the ALF patients in our series and in the literature was 100%. Overall, the perinatal survival rate was low (64.8%)., Conclusions: In pregnant patients presenting with ALF not related to the pregnancy, the LT lifesaving procedure had an excellent outcome. Overall, 65% of the infants were alive at delivery with major mortality in those fetus <22 WG despite continued pregnancy., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Neonatal acute liver failure (ALF) carries a high mortality rate; however, little data exist on its peritransplant hospital course. This project aimed to identify factors associated with outcomes in neonates with ALF using large multicenter databases. Patients with International Classification of Diseases, Ninth Revision/International Classification of Diseases, Tenth Revision codes for liver failure (2004-2018) from linked Pediatric Health Information System and Scientific Registry of Transplant Recipients databases were assigned to two groups: neonates aged ≤30 days or older infants aged 31-120 days at admission. Billing data were used to assign diagnoses and assess patient comorbidities (sepsis, extracorporeal membrane oxygenation, total parenteral nutrition, intensive care unit, and cardiac/renal/respiratory failure). Statistical analysis included Kaplan-Meier survival curve analysis and univariate and multivariate analyses with the Cox proportional hazards model. We identified 1807 neonates and 890 older infants. Neonates had significantly lower survival to 90 days ( p = 0.04) and a lower rate of liver transplantation (2.0% vs. 6.4%; p < 0.001). Common risk factors associated with death or transplant were present between groups: diagnosis, respiratory failure, cardiac failure, and renal failure. Among neonates versus older infants who received a transplant, there was no significant differences in posttransplant lengths of stay (median 38 vs. 32 days; p = 0.53), posttransplant mortality (15% vs. 11%; p = 0.66), or graft loss (9.7% vs. 8.1%; p = 0.82). We present the largest multicenter study on peritransplant outcomes in neonatal ALF and show similar risk factors for death or transplant in neonates compared with older infants. Despite lower transplantation rates, neonates demonstrate similar posttransplant outcomes as older infants. Further studies are needed to better risk stratify neonates eligible for transplant and improve outcomes., (Copyright © 2022 American Association for the Study of Liver Diseases.)

Drug-induced liver injury resulting in fulminant liver failure is a well-known condition, and many drugs have been documented in the literature as possible etiologies. However, hydralazine has seldom been reported as the offending agent. Our case report is about one such rare scenario of fulminant liver failure due to hydralazine use as an antihypertensive. A 65-year-old female patient presented with signs of fulminant liver failure 2 months after starting hydralazine for hypertension. She underwent extensive workup for the cause of acute liver failure. Other possible medications were ruled out, and workup for autoimmune and other etiologies were also negative. The patient underwent a deceased donor liver transplant and has been doing well since then. Her liver was found to be atrophic, with microscopically confirmed drug-induced liver injury. Hydralazine is used orally to treat essential hypertension and intravenously to emergently lower blood pressure. Hydralazineinduced acute liver failure is extremely rare. However, in this rare case where hydralazine-related drug-induced liver injury worsened to the extent of requiring liver transplant, we felt obliged to document and highlight this complication as a form of reminder to our colleagues of this serious outcome.