High Urgency Liver Transplantation Research Articles

Liver Transplantation After Organ Donation Due to Hydrogen Sulfide Intoxication: Report of the First Case.

The discrepancy of patients on the waiting list and the availability of organs suitable for transplantation continues to represent a relevant problem in transplantation medicine. Regarding liver transplantation, the increasing use of organs from donors with so-called extended criteria meanwhile has become daily practice in many countries.1 Consequently, every potential donor reported is carefully evaluated for suitability for organ donation. When a liver from a young brain-dead donor after hydrogen sulfide (H2S) intoxication was offered for a high-urgency listed patient, research of the literature did not provide any help for decision making in organ allocation. Herewith, we want to share our experience following the successful use of this donor liver for transplantation. A 60-y-old female patient with acute liver failure caused by an autoimmune hepatitis was transferred to our center and eventually listed for high-urgency liver transplantation following biopsy-proven diagnosis and rapid worsening of the clinical condition despite thorough intensive medical treatment (see Figure 1). Within 5 h after approval of high-urgency status, we were offered a liver from a 19-y-old female brain-dead donor following H2S intoxication in suicidal intent. Apart from depression, the donor was in excellent general condition before intoxication and had no other known illnesses. Despite recently promoted organ protective effects in experimental studies,2 inhalation of H2S in higher concentrations is highly toxic and eventually led to cardiac arrest in this patient.3 Following a short period of resuscitation, the donor was admitted to an intensive care unit and eventually diagnosed brain dead. Within 24 h, severe lung edema and subsequently respiratory failure developed as signs of multiorgan failure. Regarding the liver, apart from an initial peak of transaminases (peak AST and ALT levels of 357 and 438 U/L, respectively), the laboratory findings were all unremarkable. Because of the severe condition of our recipient with severe hepatic encephalopathy, we thus accepted the organ after intense interdisciplinary discussion despite the lack of any data on successful use of organs for transplant under these conditions. Upon arrival of the organ at our center, histological work-up of the liver by frozen section was performed despite excellent macroscopic appearance, which did not reveal any signs of acute liver injury or chronic alterations‚ such as steatosis or fibrosis (see Figure 2). Subsequent liver transplantation was completely uneventful. The patient’s clinical condition improved rapidly, with discharge at day 15 after transplantation (see Figure 1). During follow-up of 6 mo, no irregularities were observed, with excellent graft function and medical condition of the recipient at last visit. In conclusion, to our knowledge‚ this is the first report of a liver transplant from a brain-dead donor after hydrogen sulfide intoxication. Based on this single-case experience, potential donors after hydrogen sulfide intoxication should be carefully evaluated and considered for organ donation. Particularly evaluation of potential grafts applying normothermic machine perfusion might represent another valuable option in case of less urgent conditions of the recipients.4FIGURE 1.: Course of laboratory parameters (AST, ALT [both U/L], bilirubin [µmol/L], and INR) of the recipient before and after LTx, with time points of liver biopsy, PE and steroid therapy‚ and day of transplantation indicated by gray bars. ALT, alanine aminotransferase; AST, aspartate aminotransferase; INR, international normalized ratio; LTx, liver transplantation; PE, plasmapheresis.FIGURE 2.: Histopathology of liver wedge biopsy: hematoxylin and eosin staining shows no steatosis, fibrosis, or cirrhosis ([A] ×40 magnification and [B] ×100 magnification), and Elastica van Gieson staining highlights absence of fibrosis within the liver parenchyma ([C] ×40 magnification and [D] ×100 magnification).

Recipient-Specific Risk Factors Impairing Patient and Graft Outcome after Pediatric Liver Transplantation—Analysis of 858 Transplantations in 38 Years

(1) Background and Aim: Despite excellent long-term results in pediatric liver transplantation (pLTx), mortality and graft loss still are to be diminished. We aim to describe time-dependent changes and long-term outcome of a large single-center pLTx cohort and to identify independent recipient-related risk factors impairing patient and graft survival. (2) Methods: This is a retrospective single-center study analyzing all pediatric liver transplants from 1983–2020. Risk factors for mortality and graft loss were identified by univariable and multi-linear regression analysis. (3) Results: We analyzed 858 liver transplantations in 705 pediatric patients. Five-year patient/graft survival increased from 60.9%/48.0% (1983–1992) to 97.5%/86.5% (OR = 12.5; p < 0.0001/OR = 6.5; p < 0.0001) (2014–2020). Indications changed significantly over time, with a higher proportion of patients being transplanted for malignancies and metabolic disease and indications of PFIC and α1AT-deficiency declining. The era of transplantation (log7.378/9.657; p < 0.0001) and indication of acute liver failure (log = 1.944/2.667; HR = 2.015/1.772; p = 0.0114/0.002) impairs patient/graft survival significantly in the multivariate analysis. Furthermore, patient survival is worsened by re-transplantation (log = 1.755; HR = 1.744; p = 0.0176) and prolonged waiting times in high-urgency status (log = 2.588; HR = 1.073; p = 0.0026), whereas the indication of biliary atresia improved outcome (log = 1.502; HR = 0.575; p = 0.0315). Graft survival was additionally impaired by pre-existing portal vein thrombosis (log = 1.482; HR = 2.016; p = 0.0330). (4) Conclusions: Despite more complex indications, patient and graft survival after pLTx continue to improve.. Acute liver failure remains the indication with poorest outcome, and listing for high urgency liver transplantation should be considered carefully and early to keep waiting time on HU list short. Furthermore, pre-transplant portal vein thrombosis should be prevented whenever possible to improve graft survival.

Analysis of the Trend Over Time of High-Urgency Liver Transplantation Requests in Italy in the 4-Year Period 2014-2017

BackgroundThe national protocol for the handling of high-urgency (HU) liver organ procurement for transplant is administered by the Italian National Transplant Center. In recent years, we have witnessed a change in requests to access the program. We have therefore evaluated their temporal trend, the need to change the access criteria, the percentage of transplants performed, the time of request satisfaction, and the follow-up. MethodsWe analyzed all the liver requests for the HU program received during the 4-year period of 2014 to 2017 for adult recipients (≥18 years of age): all the variables linked to the recipient or to the donor and the organ transplants are registered in the Informative Transplant System as established by the law 91/99. In addition, intention to treat (ITT) survival rates were compared among 4 different groups: (1) patients on standard waiting lists vs (2) patients on urgency waiting lists, and (3) patients with a history of transplant in urgency vs (4) patients with a history of transplant not in urgency. ResultsOut of the 370 requests included in the study, 291 (78.7%) were satisfied with liver transplantation. Seventy-nine requests (21.3%) have not been processed, but if we consider only the real failures, this percentage falls to 13.1% and the percentage of satisfied requests rises to 86.9%. The average waiting period for liver transplantation (LT) is 1.7 days and most requests (74%) are met in less than 24 hours, if we consider the hours between the registration of the request and the donor reporting . The percentage of late retransplantations is 2.1%. The clinical indication for HU-LT that appears to improve over time is hepatic artery thrombosis (82.5%). The overall 1-year patient survival is 68.3%. The overall 1-year graft survival, performed on all the patients, is 89% and all the indications for HU-LT appear to go well over time with an average survival rate greater than 85%. ConclusionsThe indications for HU-LT are changing according to the changes in the hepatologic field in recent years. The centralized management of requests has proven to be successful in optimizing responses. Urgent LT is confirmed to be lifesaving in its timeliness.

Evaluating twenty-years of follow-up after orthotopic liver transplantation, best practice for donor-recipient matching: What can we learn from the past era?

AIMTo characterize major determinants of 20-year survival after liver transplantation (LT).METHODSThis longitudinal single-institution study includes 313 consecutive patients who received a LT between 1988 and 1992. Pretransplant clinical characteristics and laboratory values were assessed and compared between 20-year survivors and non-survivors. Particular attention was paid to the Model for End-Stage Liver Disease (labMELD)-score and the Eurotransplant Donor Risk Index (ET-DRI) to unravel their impact on 20-year survival after LT.RESULTSTwenty-year survivors were significantly younger (44 vs 50 years, P = 0.001), more likely to be female (49% vs 36%, P = 0.03) and less likely to be obese at the time of LT (19% vs 32%, P = 0.011). Mean labMELD-score (P = 0.156), rate of high-urgency LT (P = 0.210), cold-ischemia time (P = 0.994), rate of retransplantation (P = 0.12) and average donor age (28 vs 33 years, P = 0.099) were not statistically different. The mean estimated glomerular filtration rate was higher among survivors (P = 0.007). ET-DRI > 1.4 (P = 0.020) and donor age ≥ 30 years (P < 0.022) had significant influence on 20-year survival. The overall survival was not significantly impacted by labMELD-score categories (P = 0.263).CONCLUSIONLT offers excellent long-term results in case of optimal donor and recipient conditions. However, mainly due to the current organ shortage, these ideal circumstances are rarely given; thus algorithms for donor-recipient matching need to be refined, in order to enable a maximum benefit for the recipients of high quality as well as marginal organs.

Application of the Liver Maximum Function Capacity Test in Acute Liver Failure: A Helpful Tool for Decision-Making in Liver Transplantation?

Background. Despite aggressive intensive medical management acute liver failure (ALF) may require high-urgency liver transplantation (LTx). Available prognostic scores do not apply for all patients; reliable tools to identify individuals in need of LTx are highly required. The liver maximum function capacity test (LiMAx) might represent an appropriate option. Referring to a case of ALF after Amanita phalloides-intoxication the potential of the LiMAx-test in this setting is discussed. Presentation of Case. LiMAx was performed in a 27-year-old patient prior to and after high-urgency LTx. In accordance with clinical appearance of hepatic encephalopathy, coagulopathy, and acute kidney failure, the LiMAx-test constituted a fulminant course of ALF with hardly any detectable metabolic activity. Following LTx with a marginal donor organ (95% hepatosteatosis), uptake of liver function was demonstrated by postoperative increase of the LiMAx-value. The patient was discharged from hospital on postoperative day 26. Discussion. ALF often is associated with a critical state of the patient that requires almost immediate decision-making regarding further therapy. Application of a noninvasive liver function test might help to determine the prognosis of ALF and support decision-making for or against LTx as well as acceptance of a critical donor organ in case of a critically ill patient.

Experience with molecular adsorbent recirculating system treatment in 20 children listed for high-urgency liver transplantation.

For more than 10 years, children at our national center for pediatric liver transplantation (LT) have been treated with Molecular Adsorbent Recirculating System (MARS) liver dialysis as a bridging therapy to high-urgency LT. Treatment was reserved for 20 patients with the highest degrees of hepatic encephalopathy (HE; median grade = 3.5). Death from neurological sequelae was considered imminent for these patients, and this was further reflected in significantly higher international normalized ratios and ammonia levels and worse prognostic liver indices (Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease scores and liver injury units) in comparison with 32 wait-listed patients who did not receive MARS dialysis. MARS therapy was generally well tolerated, with a reduction in thrombocytes and hemorrhaging as the most common side effects. HE improvement was documented in 30% of the treated patients, but progression to grade IV encephalopathy occurred in 45% of the patients despite the treatment. Serum ammonia, bilirubin, bile acid, and creatinine levels significantly decreased during treatment. Eighty percent of MARS-treated patients survived to undergo LT, and their survival was equivalent to that of non-MARS-treated patients with severe liver failure (69%, P = 0.52). The heterogeneity between MARS-treated patients and non-MARS-treated patients in our cohort precluded a statistical evaluation of a benefit from MARS for patient survival. Our data demonstrate the safety of MARS even in the most severely ill patients awaiting LT, but strategies that promote the more rapid and widespread availability of high-quality donor organs remain of critical importance for improving patient survival in cases of severe acute liver failure.

Spontaneous Hepatic Rupture in Amyloidosis – Report of a Case

In systemic amyloidosis spontaneous rupture of the liver is a rare complication. Here we report on a patient with unrecognized systemic amyloidosis who presented to an outside hospital with unspecific abdominal pain. Under the signs of a hemorrhagic shock, distended abdomen and intraabdominal bleeding a laparotomy was performed. Due to uncontrollable hemorrhage of the ruptured right liver lobe a packing was performed. After being transferred to the reporting institution a CT scan was performed showing a grade IV laceration of the right liver. Therefore a transarterial embolization of the right hepatic artery was carried out. The following day an infection of the abdominal cavity and the abdominal wall with gas-producing bacteria was noticed and a relaparotomy, necrectomy and repacking due to diffuse bleeding were performed. The situation deteriorated and at the second relaparotomy the following day an almost completely necrotic liver was found. The patient deceased the following day. Life-threatening spontaneous liver rupture due to systemic amyloidosis might only successfully be cured by high urgency liver transplantation as presented in the literature. However, in two published cases interventional therapy by embolization of bleeding vessels has saved patients' life.

Seltene Ursache eines akuten Leberversagens

A rare cause of acute liver failure is adult onset Still's disease (AOSD), a systemic inflammatory disorder. We present the case of a 24-year-old woman who presented with acute liver failure necessitating high urgency liver transplantation. The diagnosis of AOSD was established in accordance with the Yamaguchi classification criteria, including arthralgia, fever, sore throat, rash and hepatosplenomegaly. The early detection and therapy of AOSD can possibly avoid the development of liver failure with a poor prognosis.

Prediction of outcome and selection of the liver transplantat candidate in acute liver failure.

Acute liver failure (ALF) is characterized by a sudden and severe deterioration of liver function, typically mirrored by a marked increase of the international normalized ratio (INR) and hepatic encephalopathy (HE). Due to various possible causes hepatocytes get damaged via either apoptotic or necrotic pathways. Anticipating the natural prognosis of a patient with ALF is one of the most challenging tasks in hepatology critical care. Important factors that influence the chance of spontaneous recovery are the underlying etiology of acute liver failure, the acuity of disease, and the severity of HE. Once an estimation of the prognosis in the individual patient has been made, this quickly has to be integrated in the discussion whether high-urgency liver transplantation is necessary and justifiable. This decision has to cover several medical, social, and organizational issues. Well organized liver transplantation programs around the world have achieved an impressive improvement of the 1 year survival rate in ALF from around 40% without transplantation up to nearly 80% with transplantation. The recent debate on whether severe acute alcoholic hepatitis could represent a new candidate eligible for high-urgency liver transplantation shows that the topic is still open for discussion.

High urgency liver transplantation in ornithine transcarbamylase deficiency presenting with acute liver failure

OTCD can present with ALF at any age. Under adequate therapy symptoms resolve quickly. We report a three-yr-old girl with the manifestation of an OTCD as ALF. Despite adequate pharmacotherapy and protein restriction, the patient deteriorated and developed hepatic encephalopathy. A high urgency liver transplantation was performed and the patient recovered completely. We conclude that in patients with ALF urea cycle defects in general and OTCD in particular should be considered as differential diagnosis. Patients should be managed in a center that has the capacity for an emergency liver transplantation.

Extracorporeal liver support with multipass albumin dialysis or plasmapheresis and filtering systems in acute liver failure

Acute liver failure is a very complex type of disease with a mortality of up to 90%, leading to numerous severe disturbances of the whole organism. Bleeding because of absent synthesis of various coagulation factors and disseminated intravascular coagulation, acute kidney failure, circulatory failure with vasopressor dependence, respiratory failure with adult respiratory distress syndrome, neurological failure up to coma because of hepatic encephalopathy, and a very high risk of infection and sepsis frequently result from the initial state of isolated liver failure. High urgency liver transplantation is a highly efficient therapy if performed in time. However, increasing the rate of spontaneous recovery of the patients' own liver, and reducing the need for liver transplantation is preferable and would further improve the outcome of acute liver failure. Extracorporeal liver support by multipass albumin dialysis or plasmapheresis and filtering systems may offer a possibility to fulfill these aims of therapy. A prospective study in 88 patients with acute liver failure has shown a nonsignificant trend in improvement of survival after acute liver failure by multipass albumin dialysis and filtering. Other retrospective studies have shown benefits in improving hepatic encephalopathy and brain oedema. Further, an increase in the rate of spontaneous recovery of liver function has been described. With regional citrate anticoagulation for multipass albumin dialysis and filtering, the need for systemic anticoagulation - a potentially very harmful measure in these patients - can be eliminated and the rate of filter clotting can extremely effectively be reduced.

Continuous veno-venous single-pass albumin hemodiafiltration in children with acute liver failure*

To investigate the applicability, efficacy, and safety of single-pass albumin dialysis in children. Retrospective data review of uncontrolled clinical data. University-based pediatric intensive care unit collaborating with a local center for liver transplantation. Nine children, aged 2 to 15 yrs, who were treated with single-pass albumin dialysis for acute liver failure of various origins under a compassionate-use protocol between 2000 and 2006. All patients met high-urgency liver transplantation criteria. Single-pass albumin dialysis was performed as rescue therapy for children with acute liver failure. The decrease in hepatic encephalopathy (grades 1-4) and the serum levels of bilirubin, bile acids, and ammonium were measured to assess the efficacy of detoxification. As a measure of liver synthesis function, thromboplastin time and fibrinogen were analyzed. The safety of the procedure was assessed by documenting adverse effects on mean arterial blood pressure, platelet count, and clinical course. Seven out of nine patients were bridged successfully to either native organ recovery (n = 1) or liver transplantation (n = 6), one of them twice. Six out of nine patients undergoing single-pass albumin dialysis (ten treatments) survived. In six patients, hepatic encephalopathy could be reduced at least by one degree. Ammonium, bilirubin, and bile acid levels decreased in all patients. One patient had an allergic reaction to albumin. In childhood acute liver failure, treatment with single-pass albumin dialysis was generally well tolerated and seems to be effective in detoxification and in improving blood pressure, thus stabilizing the critical condition of children before liver transplantation and facilitating bridging to liver transplantation. It may be beneficial in avoiding severe neurologic sequelae after acute liver failure and thereby improve survival. Single-pass albumin dialysis is an inexpensive albumin-based detoxification system that is easy to set up and requires little training. Whether and to what extent single-pass albumin dialysis can support children with acute liver failure until native liver recovery remains unclear.

Hepatic tumorigenesis in acute hepatic failure

We report on a 59-year-old woman and a 31-year-old man with no previous medical history of liver disease presenting with acute liver failure probably caused by drug toxicity. High urgency liver transplantation was performed 30 and 51 days after the onset of symptoms, respectively. Histomorphological evaluation of the explanted livers revealed incidental dysplastic nodules and hepatocellular carcinoma of up to 8 mm in diameter. Up to now only a few cases of metastatic liver disease and even fewer cases of primary liver cancer presenting as acute liver failure have been described. Our cases indicate hepatic tumorigenesis not as a cause of hepatic failure but either as an event taking place in parallel or as a process being induced by progressive liver failure.

Major bile duct injuries after laparoscopic cholecystectomy: a tertiary center experience.

Bile duct injury is a severe and potentially life-threatening complication of laparoscopic cholecystectomy. Several series have described a 0.5% to 1.4% incidence of bile duct injuries during laparoscopic cholecystectomy. The aim of this study was to report on an institutional experience with the management of complex bile duct injuries and outcome after surgical repair. Data were collected prospectively from 40 patients with bile duct injuries referred for surgical treatment to our center between April 1998 and December 2003. Prior to referral, 35 patients (87.5%) underwent attempts at surgical reconstruction at the primary hospital. In 77.5% of the patients, complex type E1 or type E2 BDI was found. Concomitant with bile duct injury, seven patients had vascular injuries. Roux-en-Y hepaticojejunostomy was carried out in 33 patients. In two patients, Roux-en-Y hepaticojejunostomy and vascular reconstruction were necessary. Five patients, one with primary nondiagnosed Klatskin tumor, required right hepatectomy. Two patients, both with bile duct injuries and vascular damage, died postoperatively. Because of progressive liver insufficiency, one of them was listed for high-urgency liver transplantation but died prior to intervention. At the median follow-up of 589 days, 82.5% of the patients are in excellent general condition. Seven patients have signs of chronic cholangitis. Major bile duct injuries remain a significant cause of morbidity and even death after laparoscopic cholecystectomy. Because they present a considerable surgical challenge, early referral to an experienced hepatobiliary center is recommended.