Acute liver failure.

ABSTRACT: Acute liver failure, commonly caused by acetaminophen overdose, is associated with numerous systemic complications including cerebral edema, hypotension, acute kidney injury, and infection. Management is primarily supportive, with an emphasis on excellent neurocritical care. Although some antidotes and targeted treatments exist, the only definitive treatment remains orthotopic liver transplant.

Assessing the clinical efficacy of low-volume therapeutic plasma exchange in achieving recovery from acute liver failure induced by yellow phosphorous poisoning.

BACKGROUND: Acute liver failure (ALF) following yellow phosphorous (YP) ingestion is similar to acetaminophen-induced ALF and it has become a public concern in our region. This study assessed low volume therapeutic plasma exchange (LV-TPE) efficacy in improving the transplant free survival in YP poisoning. METHODS: Adult patients with toxicology reports of YP and ALF requiring critical care were included in the study. LV-TPE was planned for three consecutive days and three more if required. Performed 1.3 to 1.5 plasma volume replacing with 0.9% normal saline, 5% human albumin solution, and fresh frozen plasma based on ASFA 2019 criteria. MELD score, laboratory parameters, LV-TPE details were captured. The study end point was clinical outcome of the patients. RESULTS: Among 36 patients, 19 underwent LV-TPE and 17 opted out of LV-TPE and they were included as a control arm. The MELD score was 32.64 ± 8.05 and 37.83 ± 9.37 in both groups. There were 13 survivors in LV-TPE group leading to a 68.42% reduction in mortality. The coagulation and biochemical parameters showed a significant percentage change after LV-TPE. Refractory shock, delay in initiating procedure and acidosis were independent predictors of mortality. CONCLUSION: A well-timed LV-TPE improves the survival of patients with ALF due to YP poisoning.

Cryopreserved cGMP-compliant human pluripotent stem cell-derived hepatic progenitors rescue mice from acute liver failure through rapid paracrine effects on liver cells.

BACKGROUND: Liver transplantation remains the only curative treatment for end-stage liver diseases. Unfortunately, there is a drastic organ donor shortage. Hepatocyte transplantation emerged as a viable alternative to liver transplantation. Considering their unique expansion capabilities and their potency to be driven toward a chosen cell fate, pluripotent stem cells are extensively studied as an unlimited cell source of hepatocytes for cell therapy. It has been previously shown that freshly prepared hepatocyte-like cells can cure mice from acute and chronic liver failure and restore liver function. METHODS: Human PSC-derived immature hepatic progenitors (GStemHep) were generated using a new protocol with current good manufacturing practice compliant conditions from PSC amplification and hepatic differentiation to cell cryopreservation. The therapeutic potential of these cryopreserved cells was assessed in two clinically relevant models of acute liver failure, and the mode of action was studied by several analytical methods, including unbiased proteomic analyses. RESULTS: GStemHep cells present an immature hepatic phenotype (alpha-fetoprotein positive, albumin negative), secrete hepatocyte growth factor and do not express major histocompatibility complex. A single dose of thawed GStemHep rescue mice from sudden death caused by acetaminophen and thioacetamide-induced acute liver failure, both in immunodeficient and immunocompetent animals in the absence of immunosuppression. Therapeutic biological effects were observed as soon as 3 h post-cell transplantation with a reduction in serum transaminases and in liver necrosis. The swiftness of the therapeutic effect suggests a paracrine mechanism of action of GStemHep leading to a rapid reduction of inflammation as well as a rapid cytoprotective effect with as a result a proteome reprograming of the host hepatocytes. The mode of action of GStemHep relie on the alleviation of inhibitory factors of liver regeneration, an increase in proliferation-promoting factors and a decrease in liver inflammation. CONCLUSIONS: We generated cryopreserved and current good manufacturing practice-compliant human pluripotent stem cell-derived immature hepatic progenitors that were highly effective in treating acute liver failure through rapid paracrine effects reprogramming endogenous hepatocytes. This is also the first report highlighting that human allogeneic cells could be used as cryopreserved cells and in the absence of immunosuppression for human PSC-based regenerative medicine for acute liver failure.

Preclinical efficacy and safety of encapsulated proliferating human hepatocyte organoids in treating liver failure.

Alginate-encapsulated hepatocyte transplantation is a promising strategy to treat liver failure. However, its clinical application was impeded by the lack of primary human hepatocytes and difficulty in controlling their quality. We previously reported proliferating human hepatocytes (ProliHHs). Here, quality-controlled ProliHHs were produced in mass and engineered as liver organoids to improve their maturity. Encapsulated ProliHHs liver organoids (eLO) were intraperitoneally transplanted to treat liver failure animals. Notably, eLO treatment increased the survival of mice with post-hepatectomy liver failure (PHLF) and ameliorated hyperammonemia and hypoglycemia by providing liver functions. Additionally, eLO treatment protected the gut from PHLF-augmented permeability and normalized the increased serum endotoxin and inflammatory response, which facilitated liver regeneration. The therapeutic effect of eLO was additionally proved in acetaminophen-induced liver failure. Furthermore, we performed assessments of toxicity and biodistribution, demonstrating that eLO had no adverse effects on animals and remained non-tumorigenic.

[Advancements in the diagnosis and treatment of pediatric acute liver failure]. / 儿童急性肝衰竭的诊治进展.

Pediatric acute liver failure (PALF) is a rare and rapidly progressive clinical syndrome with a poor prognosis and significant mortality. The etiology of PALF is complex, and it presents with diverse and atypical clinical manifestations. Accurate diagnosis based on age-related factors, early recognition or prevention of hepatic encephalopathy, and precise supportive treatment targeting the underlying cause are crucial for improving outcomes and prognosis. This article provides a comprehensive review of recent research on the diagnosis and treatment of PALF, aiming to offer guidance for clinical practice.

Hypoxia preconditioning of human amniotic mesenchymal stem cells enhances proliferation and migration and promotes their homing via the HGF/C-MET signaling axis to augment the repair of acute liver failure.

BACKGROUND: Transplantation of mesenchymal stem cells (MSCs) is a newly developed strategy for treating acute liver failure (ALF). Nonetheless, the low survival rate of MSCs after transplantation and their poor homing to damaged tissues limit the clinical application of MSCs. The research assessed whether hypoxic preconditioning (HPC) can improve the biological activity of human amniotic mesenchymal stem cells (hA-MSCs), promote their homing ability to the liver of mice with ALF, and influence liver tissue repair. METHODS: Flow cytometry, CCK8, Transwell, and Western blotting assays were conducted to assess the effects of hypoxic preconditioning on the phenotype, proliferation, and migration of hA-MSCs and the changes in the c-Met and CXCR4 gene expression levels were studied. To evaluate the effects of the transplantation of hypoxic preconditioning of hA-MSCs on the homing and repair of D-galactosamine (D-GalN)/LPS-induced ALF, the mechanism was elucidated by adding c-Met, CXCR4-specific blockers (SU11274 and AMD3100). RESULTS: After hypoxia pretreatment (1% oxygen volume fraction), hA-MSCs maintained the morphological characteristics of adherence and vortex colony growth and showed high CD44, CD90, and CD105 and low CD31, CD34, and CD45 expression levels. Hypoxic preconditioning of hA-MSCs significantly increased their proliferation and migration and highly expressed the c-Met and CXCR4 genes. In vivo and in vitro, this migration-promoting effect was suppressed by the c-Met specific blocker SU11274. In the acute liver failure mouse model, the HGF expression level was considerably elevated in the liver than that in the serum, lungs and kidneys. The transplantation of hypoxic preconditioned hA-MSCs introduced a remarkable improvement in the liver function and survival rate of mice with ALF and enhanced the anti-apoptosis ability of liver cells. The anti-apoptotic enhancing effect of hypoxic preconditioning was suppressed by the c-Met specific blocker SU11274. Hypoxic hA-MSCs administration was observed to have considerably increased the fluorescent cells in the liver than that recorded after administering normal oxygen-hA-MSCs. The number of hepatic fluorescent cells decreased remarkably after adding the c-Met inhibitor SU11274, compared to that recorded after hypoxic pretreatment, whereas the effect of c-Met inhibitor SU11274 on normal oxygen-hA-MSCs was not significant. CONCLUSIONS: Hypoxic preconditioning depicted no impact on the morphology and phenotype features of the human amniotic mesenchymal stem cells, but it can promote their proliferation, migration, anti-apoptotic effect, and homing rate and improve the repair of acute liver failure, which might be mediated by the HGF/c-Met signaling axis.

Pre-administration of human umbilical cord mesenchymal stem cells has better therapeutic efficacy in rats with D-galactosamine-induced acute liver failure.

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.

Stem Cell-Based Strategies: The Future Direction of Bioartificial Liver Development.

Acute liver failure (ALF) results from severe liver damage or end-stage liver disease. It is extremely fatal and causes serious health and economic burdens worldwide. Once ALF occurs, liver transplantation (LT) is the only definitive and recommended treatment; however, LT is limited by the scarcity of liver grafts. Consequently, the clinical use of bioartificial liver (BAL) has been proposed as a treatment strategy for ALF. Human primary hepatocytes are an ideal cell source for these methods. However, their high demand and superior viability prevent their widespread use. Hence, finding alternatives that meet the seed cell quality and quantity requirements is imperative. Stem cells with self-renewing, immunogenic, and differentiative capacities are potential cell sources. MSCs and its secretomes encompass a spectrum of beneficial properties, such as anti-inflammatory, immunomodulatory, anti-ROS (reactive oxygen species), anti-apoptotic, pro-metabolomic, anti-fibrogenesis, and pro-regenerative attributes. This review focused on the recent status and future directions of stem cell-based strategies in BAL for ALF. Additionally, we discussed the opportunities and challenges associated with promoting such strategies for clinical applications.

Continuous renal replacement therapy and survival in acute liver failure: A systematic review and meta-analysis.

OBJECTIVE: Acute liver failure (ALF) is a rare syndrome leading to significant morbidity and mortality. An important cause of mortality is cerebral edema due to hyperammonemia. Different therapies for hyperammonemia have been assessed including continuous renal replacement therapy (CRRT). We conducted a systematic review and meta-analysis to determine the efficacy of CRRT in ALF patients. MATERIALS AND METHODS: We searched MEDLINE, EMBASE, Cochrane Library, and Web of Science. Inclusion criteria included adult patients admitted to an ICU with ALF. Intervention was the use of CRRT for one or more indications with the comparator being standard care without the use of CRRT. Outcomes of interest were overall survival, transplant-free survival (TFS), mortality and changes in serum ammonia levels. RESULTS: In total, 305 patients underwent CRRT while 1137 patients did not receive CRRT. CRRT was associated with improved overall survival [risk ratio (RR) 0.83, 95% confidence interval (CI) 0.70-0.99, p-value 0.04, I2 = 50%] and improved TFS (RR 0.65, 95% CI 0.49-0.85, p-value 0.002, I2 = 25%). There was a trend towards higher mortality with no CRRT (RR 1.24, 95% CI 0.84-1.81, p-value 0.28, I2 = 37%). Ammonia clearance data was unable to be pooled and was not analyzable. CONCLUSION: Use of CRRT in ALF patients is associated with improved overall and transplant-free survival compared to no CRRT.

Human umbilical cord mesenchymal stem cells protect against ferroptosis in acute liver failure through the IGF1-hepcidin-FPN1 axis and inhibiting iron loading.

Acute liver failure (ALF) is a significant global issue with elevated morbidity and mortality rates. There is an urgent and pressing need for secure and effective treatments. Ferroptosis, a novel iron-dependent regulation of cell death, plays a significant role in multiple pathological processes associated with liver diseases, including ALF. Several studies have demonstrated that mesenchymal stem cells (MSCs) have promising therapeutic potential in the treatment of ALF. This study aims to investigate the positive effects of MSCs against ferroptosis in an ALF model and explore the underlying molecular mechanisms of their therapeutic function. Our results show that intravenously injected MSCs protect against ferroptosis in ALF mouse models. MSCs decrease iron deposition in the liver of ALF mice by downregulating hepcidin level and upregulating FPN1 level. MSCs labelled with Dil are mainly observed in the hepatic sinusoid and exhibit colocalization with the macrophage marker CD11b fluorescence. ELISA demonstrates a high level of IGF1 in the CCL 4+MSC group. Suppressing the IGF1 effect by the PPP blocks the therapeutic effect of MSCs against ferroptosis in ALF mice. Furthermore, disruption of IGF1 function results in iron deposition in the liver tissue due to impaired inhibitory effects of MSCs on hepcidin level. Our findings suggest that MSCs alleviate ferroptosis induced by disorders of iron metabolism in ALF mice by elevating IGF1 level. Moreover, MSCs are identified as a promising cell source for ferroptosis treatment in ALF mice.

Fractionated plasma separation and adsorption integrated with continuous veno-venous hemofiltration in patients with acute liver failure: A single center experience from China.

OBJECTIVE: To evaluate the clinical efficacy and safety of fractionated plasma separation and adsorption integrated with continuous veno-venous hemofiltration (FPSA-CVVH) treatment in patients with acute liver failure (ALF). METHODS: In this retrospective study, we enrolled patients with ALF (serum total bilirubin >10 mg/dL or Model for End-Stage Liver Disease [MELD] Score >18) hospitalized between August 2017 and August 2022. All patients had at least two sessions of FPSA-CVVH. The primary measure of treatment efficacy was the reduction ratios (RRs) of bilirubin after each session of FPSA-CVVH. RESULTS: Seventy-eight patients with ALF were enrolled. The MELD score at baseline was 22.9 ± 7.5. The mean total bilirubin was 22.05 ± 5.94 mg/dL, direct bilirubin was 16.33 ± 4.60 mg/dL and indirect bilirubin was 3.43 ± 1.60 mg/dL. One hundred and eighty seven sessions of FPSA-CVVH treatment lasting 8 hours each were performed. After a single session, serum total bilirubin, direct bilirubin and indirect bilirubin were significantly decreased. RRs were 52.0% ± 7.6% for total bilirubin, 59.4% ± 13.0% for direct bilirubin and 36.9% ± 15.4% for indirect bilirubin. Twenty nine patients (37.2%) survived and were discharged from the hospital, 12 of them recovered their liver function while the remaining 17 patients needed intermittent artificial liver support therapy. CONCLUSION: FPSA-CVVH therapy is an effective artificial liver support therapy in patients with ALF. It may be considered as a "bridge technique" to the recovery of liver function in critical ill patients with ALF.

Microfluidic Fabrication of MicroRNA-Induced Hepatocyte-Like Cells/Human Umbilical Vein Endothelial Cells-Laden Microgels for Acute Liver Failure Treatment.

Acute liver failure (ALF) is a critical life-threatening disease that occurs due to a rapid loss in hepatocyte functions. Hepatocyte transplantation holds great potential for ALF treatment, as it rapidly supports liver biofunctions and enhances liver regeneration. However, hepatocyte transplantation is still limited by renewable and ongoing cell sources. In addition, intravenously injected hepatocytes are primarily trapped in the lungs and have limited efficacy because of the rapid clearance in vivo. Here, we designed a Y-shaped DNA nanostructure to deliver microRNA-122 (Y-miR122), which could induce the hepatic differentiation and maturation of human mesenchymal stem cells. mRNA sequencing analysis revealed that the Y-miR122 promoted important hepatic biofunctions of the induced hepatocyte-like cells including fat and lipid metabolism, drug metabolism, and liver development. To further improve hepatocyte transplantation efficiency and therapeutic effects in ALF treatment, we fabricated protective microgels for the delivery of Y-miR122-induced hepatocyte-like cells based on droplet microfluidic technology. When cocultured with human umbilical vein endothelial cells in microgels, the hepatocyte-like cells exhibited an increase in hepatocyte-associated functions, including albumin secretion and cytochrome P450 activity. Notably, upon transplantation into the ALF mouse model, the multiple cell-laden microgels effectively induced the restoration of liver function and enhanced liver regeneration. Overall, this study presents an efficient approach from the generation of hepatocyte-like cells to hepatocyte transplantation in ALF therapy.

Efficacy of therapeutic plasma exchange in pediatric cases of acute liver failure as an extracorporeal liver support system.

BACKGROUND: Acute liver failure in the pediatric population is often accompanied by deranged metabolism, severe encephalopathy and coagulopathy. A liver transplant is the most viable option for the management of such patients. Therapeutic plasma exchange (TPE) is helpful in improving the liver biochemistry profile, thereby, increasing their likelihood of undergoing a liver transplant METHOD: The study was conducted over a period of 3 years (January 2018 to December 2021). Indications mainly consisted of ALF with hepatic encephalopathy, worsening liver parameters in spite of medical management, and candidacy for undergoing a liver transplant. Plasma exchange was performed daily or alternatively until the patient recovered, succumbed, or was stable enough to undergo a transplant. Biochemical parameters serum bilirubin, ALT, AST serum ammonia serum urea, serum creatinine were recorded before and after TPE sessions. RESULTS: The study group comprised 14 patients of which a total of 28 TPE was performed. There were a total of 5 cases of cryptogenic ALF, 4 of Wilson disease, 2 cases each of infection-related ALF and autoimmune hepatitis, and a single case of drug-induced hepatitis. A total of 5 out of 14 patients underwent a liver transplant and amongst the 9 who did not undergo a transplant, 4 patients expired due to septic shock syndrome; the remaining 5 were discharged in a stable condition following TPE sessions. The disease-free survival was 78.9% and the transplant-free survival was 35.71%. CONCLUSION: TPE plays a crucial role in improving the biochemistry profile of the liver in children with liver failure.

Acute liver failure and aplastic crisis due to anorexia nervosa in an adolescent girl: a case report.

Anorexia nervosa (AN) has a high mortality rate due to the widespread organ dysfunction caused by the underlying severe malnutrition. Malnutrition-induced hepatitis is common among individuals with AN especially as body mass index decreases, while acute liver failure and aplastic crisis related to coagulation disease and encephalopathy rarely occur in AN patients. The supervised increase of caloric intake can quickly improve the elevated aminotransferases caused by starvation and aplastic crisis. This current case report describes a 12-year-old adolescent girl who was admitted with a 3-month history of weight loss. Within 3 months, she had lost 10 kg of weight. The girl was diagnosed with AN, acute liver failure, severe malnutrition with emaciation, electrolyte disorder, bradycardia and aplastic crisis. She was gradually supplemented with vitamins and enteral nutrition to avoid refeeding syndrome. After treatment, her liver function and haematopoietic function returned to normal. In conclusion, acute liver failure and aplastic crisis are rare but potentially life-threatening complications of AN, which could be improved by supervised feeding and timely rehydration. AN should be considered as the potential aetiology of acute liver failure and aplastic crisis.

Combined Age with Mean Decrease Rates of Total Bilirubin and MELD Score as a Novel and Simple Clinical Predictor on 90-Day Transplant-Free Mortality in Adult Patients with Acute Liver Failure Undergoing Plasma Exchange: A Single-Center Retrospective Study.

Background: Acute liver failure (ALF), previously known as fulminant hepatic failure, has become a common, rapidly progressive, and life-threatening catastrophic hepatic disease in intensive care unit (ICU) due to the continuous increase in drug abuse, viral infection, metabolic insult, and auto-immune cause. At present, plasma exchange (PE) is the main effective alternative treatment for ALF in ICU clinical practice, and high-volume plasma exchange (HVP) has been listed as a grade I recommendation for ALF management in the American Society for Apheresis (ASFA) guidelines. However, no existing models can provide a satisfactory performance for clinical prediction on 90-day transplant-free mortality in adult patients with ALF undergoing PE. Our study aims to identify a novel and simple clinical predictor of 90-day transplant-free mortality in adult patients with ALF undergoing PE. Methods: This retrospective study contained adult patients with ALF undergoing PE from the Medical ICU (MICU) in the Second Affiliated Hospital of Harbin Medical University between January 2017 and December 2020. Baseline and clinical data were collected and calculated on admission to ICU before PE, including gender, age, height, weight, body mass index (BMI), etiology, total bilirubin, direct bilirubin, indirect bilirubin, prothrombin activity, model for end-stage liver disease (MELD) score, and sequential organ failure assessment (SOFA) score. Enrolled adult patients with ALF undergoing PE were divided into a survival group and a death group at discharge and 90 days on account of medical records and telephone follow-up. After each PE, decreased rates of total bilirubin and MELD score and increased rates of prothrombin activity were calculated according to the clinical parameters. In clinical practice, different patients underwent different times of PE, and thus, mean decrease rates of total bilirubin and MELD score and mean increase rate of prothrombin activity were obtained for further statistical analysis. Results: A total of 73 adult patients with ALF undergoing 204 PE were included in our retrospective study, and their transplant-free mortality at discharge and 90 days was 6.85% (5/73) and 31.51% (23/73), respectively. All deaths could be attributed to ALF-induced severe and life-threatening complications or even multiple organ dysfunction syndrome (MODS). Most of the enrolled adult patients with ALF were men (76.71%, 56/73), with a median age of 48.77 years. Various hepatitis virus infections, unknown etiology, auto-immune liver disease, drug-induced liver injury, and acute pancreatitis (AP) accounted for 75.34%, 12.33%, 6.85%, 4.11%, and 1.37% of the etiologies in adult patients with ALF, respectively. Univariate analysis showed a significant difference in age, mean decrease rates of total bilirubin and MELD score mean increase rate of prothrombin activity, decrease rates of total bilirubin and MELD score, and increase rate of prothrombin activity after the first PE between the death group and survival group. Multivariate analysis showed that age and mean decrease rates of total bilirubin and MELD score were closely associated with 90-day transplant-free mortality in adult patients with ALF undergoing PE. The 90-day transplant-free mortality was 1.081, 0.908, and 0.893 times of the original value with each one-unit increase in age and mean decrease rates of total bilirubin and MELD score, respectively. The areas under the receiver operatingcharacteristic (ROC) curve of age, mean decrease rates of total bilirubin and MELD score, and the three combined were 0.689, 0.225, 0.123, and 0.912, respectively. The cut-off values of age, mean decrease rates of total bilirubin and MELD score, and the three combined were 61.50, 3.12, 1.21, and 0.33, respectively. The specificity and sensitivity of combined age with mean decrease rates of total bilirubin and MELD score for predicting 90-day transplant-free mortality in adult patients with ALF undergoing PE were 87% and 14%. Conclusion: Combined age with mean decrease rates of total bilirubin and MELD score as a novel and simple clinical predictor can accurately predict 90-day transplant-free mortality in adult patients with ALF undergoing PE, which is worthy of application and promotion in clinical practice, especially in the identification of potential transplant candidates.

Liver Transplantation for Acute Liver Failure Due to Yellow Phosphorus Poisoning - A Comprehensive Review.

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.

The Effect of Molecular Adsorbent Recirculating System in Patients With Liver Failure: A Case Series of 44 Patients.

BACKGROUND: Liver failure is associated with a high mortality rate, with many patients requiring transplant for definitive treatment. The Molecular Adsorbent Recirculating System (MARS) is a nonbiologic system that provides extracorporeal support. Literature on MARS therapy is mixed: outcomes support MARS therapy for patients with isolated acute liver failure, but data on patients with chronic disease is varied. Several case studies report success using MARS as a bridging treatment for patients awaiting transplant. The purpose of this case series is to present the outcomes of 44 patients who underwent MARS therapy for liver failure, 19 of whom used MARS therapy as a bridging therapy to transplant. METHODS: This study retrospectively identified 44 patients who underwent MARS therapy for liver failure at Mayo Clinic, Jacksonville, between January 2014 and April 2021. Variables of interest included changes in laboratory markers of hepatic functioning, number and length of MARS therapy sessions, transplantation status, and mortality. RESULTS: Following MARS therapy, there were improvements in mean serum bilirubin, ammonia, urea, creatinine, International Normalized Ratio, alanine aminotransferase, and aspartate aminotransferase levels. Twenty-seven patients (61.36%) survived the hospital stay; 17 (38.63%) died in the hospital. The majority of surviving patients (n = 19; 73.07%) received liver transplant. Six did not require transplant (22.22%). All but 1 patient who received MARS as a bridging treatment to transplant survived the follow-up period (n = 18; 94.74%). CONCLUSIONS: Outcomes of these 44 cases suggest that MARS improves liver failure-associated laboratory parameters and may be effective therapy as a bridge to liver transplant.

Acute Fulminant Hepatic Failure in 23-Year-Old Female Taking Homeopathic Remedy.

Homeopathic remedies made primarily from eggshells, and therefore calcium, can be marketed for treatment of back pain and vaginal discharge. We present a case of a 23-year-old otherwise healthy woman who presented with acute liver failure (ALF) ultimately requiring liver transplantation as a result of taking increased doses of a homeopathic product with the primary ingredient of eggshells. Although relatively uncommon compared with medications such as acetaminophen, herbal supplements have been reported to cause drug-induced liver injury (DILI), thought to be primarily due to contaminants. This is the first known report of DILI resulting from a homeopathic product with the primary ingredient of eggshells, and it demonstrates the importance of early ALF recognition and treatment, as well as the importance of practicing caution when using homeopathic supplements.

Therapeutic plasma exchange for neonatal hepatic failure.

We report a case of therapeutic plasma exchange in a neonate with fulminant liver failure. A six-day old, 2800-gram baby was referred to our medical center for evaluation and treatment of fulminant hepatic failure. The working diagnosis at admission was gestational alloimmune liver disease, and therapeutic plasma exchange was proposed. A double volume plasma exchange was successfully performed, using the Spectra Optia apheresis system, primed with packed red blood cells. Access was obtained via a radial artery catheter and a peripheral intravenous line. On hospital D-14 a diagnosis of E3 deficiency was confirmed, and disease-specific therapy was started. Automated TPE using peripheral arterial and venous catheters may be safely performed in neonates, and should be considered in the treatment of a variety of disorders including neonatal fulminant hepatic failure.