Transplantation For Acute Liver Failure Research Articles

TEMPORARY REMOVAL: A novel scoring system to predict short-term mortality after living donor liver transplantation for acute liver failure

Liver transplantation is often the only lifesaving option for acute liver failure (ALF); however, the predictors of short-term mortality (death within one year) after living donor liver transplantation (LDLT) for ALF have yet to be defined. We retrospectively collected patients ≥18 years old who underwent LDLT for ALF between 2010 and 2020 at 35 centers in Asia. Univariate and multivariate logistic regression analyses were conducted to identify the clinical variables related to short-term mortality and establish a novel scoring system. The Kaplan-Meier method was performed to explore the association between the score and overall survival. Of the 339 recipients, 46 (13.6%) died within 1 year after LDLT. Multivariate analyses revealed 4 independent risk factors for death: use of vasopressors or mechanical ventilation, the higher model for end-stage liver disease score, and a lower graft-to-recipient weight ratio. The internally validated c-statistic of the short-term mortality after transplant (SMT) score derived from these 4 variables was 0.80 (95% confidence interval: 0.74-0.87). The SMT score successfully stratified recipients into low-, intermediate-, and high-risk groups with 1-year overall survival rates of 96%, 80%, and 50%, respectively. In conclusion, our novel SMT score based on 4 predictors will guide ALF recipient and living donor selection.

Living donor liver transplantation for a patient with acute liver failure following thyroid storm: a case report

BackgroundThyroid storm can be complicated by liver dysfunction, which may occasionally progress to acute liver failure. We herein report a case of acute liver failure following thyroid storm that was treated with living donor liver transplantation after resuscitation from cardiopulmonary arrest.Case reportThe patient was a woman in her 40 s who had been diagnosed with an abnormal thyroid function. She suffered from fatigue and vomiting, and was found to have consciousness disorder, a fever, and tachycardia with a neck mass. She was diagnosed with thyroid storm and was referred to our hospital. After arrival, she went into cardiopulmonary arrest and veno-arterial extracorporeal membrane oxygenation was initiated. In addition to treatment for thyroid storm with antithyroid drugs, steroids, and plasma exchange, extracorporeal life support was required for 5 days. However, despite improvements in her thyroid function, her liver function deteriorated. We planned living donor liver transplantation for acute liver failure after ensuring the recovery and control of the thyroid function following total thyroidectomy. The donor was her husband who donated the right lobe of his liver. Although she experienced acute cellular rejection after surgery, and other complications—including intra-abdominal hemorrhaging and ischemic changes in the intestine—her liver function and general condition gradually improved. One year after living donor liver transplantation, the patient was in a good condition with a normal liver function.ConclusionsTo our knowledge, this is the first report of living donor liver transplantation in a patient with acute liver failure following thyroid storm. Liver transplantation should be recognized as an effective treatment for acute liver failure following thyroid storm.

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.

Liver Transplantation for Acute Liver Failure During Pregnancy: Case Report and Literature Review

Liver failure during pregnancy is a rare and highly fatal condition frequently resulting from the patient's pre-existing chronic liver disease. There is no established protocol for managing this condition, and physicians tend to adopt a conservative approach due to concerns about the impact of liver transplantation on fetal development. However, conservative treatment may exacerbate the condition, increasing the risk of fetal and miscarriage deaths. In this study, we present a case of acute-on-chronic liver failure resulting from chronic hepatitis during the 19th week of gestation. Despite undergoing conservative treatment, the fetus tragically died, but the patient achieved an excellent clinical outcome after emergency liver transplantation. We also conducted a systematic review of the literature on liver transplantation during pregnancy from the last decade, examining the causes of liver failure and transplantation during pregnancy. Our research complied with the principles outlined in the Declaration of Helsinki and the Istanbul Declaration.

Liver support systems and liver transplantation in acute liver failure.

Acute liver failure (ALF) results in a multitude of complications that result in multi-organ failure. This review focuses on the pathophysiological processes and how to manage with these with artificial liver support and liver transplantation (LT). The pathophysiological sequence of events behind clinical deterioration in ALF comes down to two profound consequences of the failing liver. The first is the development of hyperammonemia, as the liver can no longer synthesize urea. The result is that the splanchnic system instead of removing ammonia becomes an ammonia-producing organ system that causes hepatic encephalopathy (HE) and cerebral oedema. The second complication is caused by the necrotic liver cells that release large molecules that originate from degrading proteins, that is damage associated molecular patterns (DAMPs) which causes inflammatory activation of intrahepatic macrophages and an overflow of DAMPs molecules into the systemic circulation resulting in a clinical picture that resembles septic shock. In this context the combined use of continuous renal replacement therapy (CRRT) and plasma exchange are rational and simple ways to remove ammonia and DAMPS molecules. This combination improve survival for ALF patients deemed not appropriate for LT, despite poor prognostic criteria, but also ensure a better stability of vital organs while awaiting LT. The combination of CRRT with albumin dialysis tends to have a similar effect. Currently, the selection criteria for LT for non-paracetamol cases appear robust while the criteria for paracetamol-intoxicated patients have become more unreliable and now consist of more dynamic prognostic systems. For patients that need LT for survival, a tremendous improvement in the post-LT results has been achieved during the last decade with a survival that now reach merely 90% which is mirroring the results seen after LT for chronic liver disease.

Outcomes of adult living donor liver transplantation for acute liver failure: A 15-year experience in a single center

Geunhyeok YANG, Young-In YOON*, Deok-Bog MOON, Dong-Hwan JUNG, Gi-Won SONG, Tae-Yong HA, Gil-Chun PARK, Rak-kyun OH, Hyo Jung KO, Sung-Gyu LEE. Ann Hepatobiliary Pancreat Surg 2023;27:S204. https://doi.org/10.14701/ahbps.2023S1.LV-PP-6-4

Long-term outcomes following ABO-incompatible living donor liver transplantation for acute liver failure: a single-center experience of over 20years.

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). Preoperative treatment, immune indices (B cell marker, anti-donor blood-type antibody), and postoperative outcomes were compared between ALF and non-ALF groups. 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 13days; 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%). 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.

THU-407 - Liver transplantation in acute liver failure in Slovenia

THU-407 - Liver transplantation in acute liver failure in Slovenia

Long-term outcomes of pediatric liver transplantation in acute liver failure vs end-stage chronic liver disease: A retrospective observational study.

Children with acute liver failure (ALF) who meet the criteria are eligible for super-urgent transplantation, whereas children with end-stage chronic liver disease (ESCLD) are usually transplanted electively. Pediatric liver trans plantation (PLT) in ALF and ESCLD settings has been well described in the literature, but there are no studies comparing the outcomes in these two groups. To determine if there is a difference in post-operative complications and survival outcomes between ALF and ESCLD in PLT. This was a retrospective observational study of all primary PLTs performed at a single center between 2000 and 2019. ALF and ESCLD groups were compared for pretransplant recipient, donor and operative parameters, and post-operative outcomes including graft and patient survival. Over a 20-year study period, 232 primary PLTs were performed at our center; 195 were transplanted for ESCLD and 37 were transplanted for ALF. The ALF recipients were significantly older (median 8 years vs 5.4 years; P = 0.031) and heavier (31 kg vs 21 kg; P = 0.011). Living donor grafts were used more in the ESCLD group (34 vs 0; P = 0.006). There was no difference between the two groups concerning vascular complications and rejection, but there were more bile leaks in the ESCLD group. Post-transplant patient survival was significantly higher in the ESCLD group: 1-, 5-, and 10-year survival rates were 97.9%, 93.9%, and 89.4%, respectively, compared to 78.3%, 78.3%, and 78.3% in the ALF group (P = 0.007). However, there was no difference in 1-, 5-, and 10-year graft survival between the ESCLD and ALF groups (90.7%, 82.9%, 77.3% vs 75.6%, 72.4%, and 66.9%; P = 0.119). Patient survival is inferior in ALF compared to ESCLD recipients; the main reason is death in the 1st year post-PLT in ALF group. Once the ALF children overcome the 1st year after transplant, their survival stabilizes, and they have good long-term outcomes.

Role of liver transplantation in acute liver failure due to exertional heat stroke

Background: Exertional heat stroke is a life-threatening condition characterized by hyperthermia and multisystem organ failure. This includes central nervous system dysfunction, rhabdomyolysis and renal failure, disseminated intravascular coagulation and acute liver failure. It is well established that liver transplantation is a lifesaving procedure for patients with acute liver failure however standard criteria has not been established for transplanting patients with acute liver failure in the setting of exertional heat stroke. Herein we report a series of four patients presenting with acute liver failure in the setting of exertional heat stroke of which three underwent liver transplantation. Our aim is to define the profile of patients to be considered for liver transplantation, timing to surgery and predictors of morbidity and mortality following transplantation. This will allow for improved selection of patients who may benefit from liver transplantation in the setting of exertional heat stroke.

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

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

FRI027 - Trends in liver transplantation for acute liver failure. A Spanish multicenter study

FRI027 - Trends in liver transplantation for acute liver failure. A Spanish multicenter study

Quick preparation of ABO-incompatible living donor liver transplantation for acute liver failure.

Acute liver failure is life-threatening and has to be treated by liver transplantation urgently. When deceased donors or ABO-compatible living donors are not available, ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) becomes the only choice. How to prepare ABO-I LDLT urgently is an unsolved issue. A quick preparation regimen was designed, which was consisted of bortezomib (3.5mg) injection to deplete plasma cells and plasma exchange to achieve isoagglutinin titer ≤ 1: 64 just prior to liver transplantation and followed by rituximab (375mg/m2 ) on post-operative day 1 to deplete B-cells. Eight patients received this quick preparation regimen to undergo ABO-I LDLT for acute liver failure from 2012 to 2019. They aged between 50 and 60years. The median MELD score was 39 with a range from 35 to 48. It took 4.75 ± 1.58 days to prepare such an urgent ABO-I LDLT. All the patients had successful liver transplantations, but one patient died of antibody-mediated rejection at post-operative month 6. The 3-month, 6-month, and 1-year graft/patient survival were 100%, 87.5%, and 75%, respectively. In conclusion, this quick preparation regimen can reduce isoagglutinin titers quickly and make timely ABO-I LDLT feasible for acute liver failure.

Liver transplantation in acute liver failure: a challenging scenario

Acute liver failure is a critical medical condition defined as rapid development of hepatic dysfunction associated with encephalopathy. The prognosis in these patients is highly variable and depends on the etiology, interval between jaundice and encephalopathy, age, and the degree of coagulopathy. Determining the prognosis for this population is vital. Unfortunately, prognostic models with both high sensitivity and specificity for prediction of death have not been developed. Liver transplantation has dramatically improved survival in patients with acute liver failure. Still, 25% to 45% of patients will survive with medical treatment. The identification of patients who will eventually require liver transplantation should be carefully addressed through the combination of current prognostic models and continuous medical assessment.

Graft Reduction for Size and High GRWR in Pediatric Living Donor Liver Transplantation

Introduction: Large graft size is a commonly encountered problem in infants undergoing liver transplantation. Various graft reduction techniques have been described- anatomical vs non-anatomical, in vivo vs ex situ, and hyper-reduced grafts. We present our experience of using graft reduction techniques for pediatric liver transplantation. Methods: Two patients 6 and 7 months old weighing 7.5 kgs and 4.1 kgs underwent living donor liver transplantation for acute liver failure and cryptogenic cirrhosis respectively. For the first patient, mother was the donor for left lateral segment (LLS), with a GRWR of 3.5. Based on the pre-operative imaging, in-situ graft reduction was done in view of the bigger size of the graft relative to child’s abdominal cavity. Second patient received LLS from her mother and had a GRWR of 8. In-situ graft reduction was done till mono-segment 2. However, because of high GRWR, non-anatomical graft reduction was done on the back table making it a hyper-reduced graft. Graft reduction was done using CUSA. Results: Liver grafts in both the recipients could be accommodated well without any signs of poor portal blood flow. The resultant GRWR was 1.5 and 2.3 for the first and second patient. Post-operatively, first patient developed chylous ascites which settled with conservative management over 3 weeks and was discharged. Second patient succumbed to sepsis and expired. However, there was no sign of graft dysfunction. Conclusion: Graft reduction technique are safe, effective and easily reproducible technique and is an important part of the armamentarium of a Pediatric Liver Transplantation Center.

Collagen and elastic fibres in acute and chronic liver injury

The histological distinction between acute and chronic liver injury is a challenging aspect of liver histopathology. It is traditionally based on the interpretation of morphological changes to the extracellular matrix (ECM) at sites of hepatocyte loss using histochemical stains. Our aim was to investigate whether immunohistochemistry and multiplexing for collagen type (I & III) and elastic fibres and a modified Victoria blue method could be helpful. We studied 43 livers removed at transplantation for acute liver failure (ALF, 20 cases) or cirrhosis (23) plus 8 normal controls. In ALF the periportal ECM was normal in 2 cases, contained mainly collagen I associated with a ductular reaction in 6 cases, and delicate elastic strands in 11 cases. Periportal deposition of mainly collagen I and mature elastic fibres was observed in cirrhosis. In ALF the perisinusoidal ECM was intact in 4 cases, collapsed or condensed but of normal composition (predominantly collagen III) in 2 cases, and collapsed and condensed containing mostly collagen I in 17 cases (7 including delicate immature elastic strands). In contrast, bridging fibrous septa of cirrhosis contained abundant collagen 1 and bundles of mature elastin. We propose the use of a scale and the use of immunohistochemistry and multiplexing in additional to histochemical stains to characterise the ECM changes in acute and chronic liver injury.

Auxiliary liver transplantation for acute liver failure

Contents 1. What is auxiliary LT (ALT)? 2. When does ALT need? 3. What are issues of ALT for acute liver failure (ALF)? 4. Who can be a good candidate for ALT? 5. How to carve out a niche of technical challenges 6. How to manage Post-ALT patients 7. A SNUH case: A video clip 8. Reappraisal of ALT for ALF for Expanding Organ Utility. An APOLT (auxiliary partial orthtopic liver transplantation) for ALF has a benefit of immunosuppressant discontinuation in 60%-100% without compromising patients' survival outcome. This can also provide to expand the donor pool in some aspect. However, it's technically challenging as well as graft function and native liver regeneration is usually unpredictable. Thus, selection of good candidates (young, biopsy guided, hemodyenamically stable) and delicate surgical modification are important to lead a successful APOLT for ALF. In addition, this should be supported by careful postoperative monitoring and slow/steady immunosuppressant withdrawal after confirmation of native liver function restoration.

Liver transplantation in acute liver failure: Dilemmas and challenges.

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

Auxiliary Partial Orthotopic Liver Transplantation for Acute Liver Failure: Not Supportive Enough?

Auxiliary Partial Orthotopic Liver Transplantation for Acute Liver Failure: Not Supportive Enough?

Transplanted hepatocytes rescue mice in acetaminophen-induced acute liver failure through paracrine signals for hepatic ATM and STAT3 pathways.

Acute liver failure constitutes a devastating condition that needs novel cell and molecular therapies. To elicit synergisms in cell types of therapeutic interest, we studied hepatocytes and liver sinusoidal endothelial in mice with acetaminophen-induced acute liver failure. The context of regenerative signals was examined by transplants in peritoneal cavity because it possesses considerable capacity and allows soluble signals to enter the systemic circulation. Whereas transplanted hepatocytes and liver sinusoidal endothelial cells engrafted in peritoneal cavity, only the former could rescue mice in liver failure by improving injury outcomes, activating hepatic DNA damage repair, and inducing liver regeneration. The cytokines secreted by donor hepatocytes or liver sinusoidal endothelial cells differed and in hepatocytes from mice undergoing acetaminophen toxicity major cytokines were even rendered deficient (eg, G-CSF, VEGF, and others). Significantly, recapitulating hepatotoxicity-related DNA damage response in cultured cells identified impairments in ATM and JAK/STAT3 intersections since replacing cytokines produced less from injured hepatocytes restored these pathways to avoid acetaminophen hepatotoxicity. Similarly, hepatocyte transplantation in acute liver failure restored ATM and JAK/STAT3 pathways to advance DNA damage/repair and liver regeneration. The unexpected identification of novel hepatic G-CSF receptor expression following injury allowed paradigmatic studies of G-CSF supplementation to confirm the centrality of this paracrine ATM and STAT3 intersection. Remarkably, DNA damage/repair and hepatic regeneration directed by G-CSF concerned rebalancing of regulatory gene networks overseeing inflammation, metabolism, and cell viability. We conclude that healthy donor hepatocytes offer templates for generating specialized cell types to replace metabolic functions and regenerative factors in liver failure.