Liver Transplantation For Acute Liver Failure Research Articles

Recipient Survival among Living Donor vs. Deceased Donor Liver Transplants for Acute Liver Failure in the United States.

Objectives: Acute liver failure (ALF) is associated with high morbidity and mortality. Timely liver transplantation (LT) is the only universally accepted therapy for ALF that is non-responsive to medical therapy. Data regarding the use of living donor LT (LDLT) for this indication in the US is scarce. Materials and Methods: United Network of Organ Sharing/Organ Procurement and Transplantation Network (UNOS/OPTN) data from January 2002 to December 2020 were reviewed. Adult and pediatric recipients listed as status 1 were included. Demographics, clinical and laboratory data, and post-LT survival rates were compared for LDLT vs. DDLT recipients. Results: There were 180 LDLT (3.6%) and 4779 DDLT (96.4%) recipients with a diagnosis of ALF. The majority of recipients in the LDLT group were pediatric (n = 164, 91%) compared to the DDLT group (n = 1455, 30%), p < 0.001. In the pediatric-only group, post-LT survival was comparable between LDLT and DDLT recipients (p = 0.15). Five-year post-LT survival was higher for pediatric recipients compared to adults in the LDLT group (84.2% vs. 62.5%, respectively, p < 0.001) and the DDLT group (82.8% vs. 78.7%, respectively, p < 0.001). Adults had a higher hazard of death compared to pediatric recipients in the LDLT group (HR = 3.560, 95% CI 1.612-7.844, p = 0.002) and the DDLT group (HR = 1.472, 95% CI 1.290-1.679, p < 0.001). In multivariate analysis results, the type of LT and age group were not associated with higher post-LT mortality. Conclusions: In the US, LDLT constitutes 3.6% of LTs for ALF. In the pediatric-only group, post-LT survival was comparable between LDLT and DDLT recipients. Overall, there were superior post-LT outcomes for pediatric recipients compared to adults for LDLT and DDLT.

Impact of preoperative bloodstream infection on outcomes of pediatric liver transplant recipients treated for acute liver failure.

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. 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. 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. 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.

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.

Kidney injury and status 1 liver transplantation: Outcomes, kidney function, and listing for kidney transplantation.

Effects of kidney injury (KI) at the time of liver transplantation (LT) for acute liver failure (ALF) remain poorly described. We hypothesized that patients with ALF and KI who undergo LT have persistent post-transplant KI, inferior survival, and increased rate of kidney transplantation (KT). The US Scientific Registry of Transplant Recipients database was queried for patients transplanted with status 1 listing for LT between 2002 and 2021. KI was defined as estimated glomerular filtration rate (eGFR)≤30mL/min/1.73m2 or dialysis in the week prior to LT. Outcomes evaluated were post-LT eGFR, listing for subsequent KT, and overall survival (OS) after LT. A total of 2984 patients underwent LT for ALF with 1241 (41.6%) having KI. KI patients had lower eGFR at 6months post-LT (57.8 vs. 68.7, p<.001) that persisted out to 5years (59.9 vs. 69.7, p<.001). KI patients were more likely to be listed for KT (4.3% vs. 1.9%, p<.001) and undergo listing sooner after LT (.8 vs. 3.7years, p<.001). Patients without KI had higher adjusted post-transplant OS compared to those with KI (HR .75, p<.001). KI in the setting of ALF portends a worse prognosis for both kidney recovery and OS.

A look into hemostatic characteristics during pediatric liver transplantation using the thromboelastometry (ROTEM® ) test.

There is a paucity of evidence about the coagulation profile regarding the complexity of children undergoing liver transplantation (LT). This study aimed to investigate intraoperative hemostatic changes during pediatric LT according to the etiology for LT and examine the ability of rotational thromboelastometry (ROTEM® , TEM International GmbH, Munich, Germany) as a point-of-care monitoring method. We evaluated 106 patients aged 3months to 17years undergoing LT for acute liver failure (ALF) and chronic liver disease, which consists of patients with cholestatic disease, metabolic/genetic disease, and cancer. A total of 731 ROTEM® measurements, including 301 ellagic acid to initiate clotting via the intrinsic pathway, 172 tissue factor to initiate the extrinsic clotting cascade (EXTEM), and 258 cytochalasin D to inhibit platelet activity reflecting fibrinogen (FIBTEM), were analyzed at predetermined time points (the preanhepatic, anhepatic, and postreperfusion phases). We simultaneously conducted conventional coagulation tests. In children with ALF, preanhepatic measurements of conventional coagulation tests and ROTEM® showed a more hypocoagulable state than other diseases. During LT, the coagulation profile was deranged, with a prolonged clotting time and reduced clot firmness, changes that were more profound in the cholestatic disease group. Maximum clot firmness (MCF) on EXTEM and FIBTEM were well correlated with the platelet count and fibrinogen concentration (r=0.830, p<0.001 and r=0.739, p<0.001, respectively). On the EXTEM, MCF with 30mm predicted a platelet count <30,000/mm3 (area under the curve, 0.985), and 6mm predicted a fibrinogen concentration <100mg/dl on the FIBTEM (area under the curve, 0.876). However, the activated partial thromboplastin time and prothrombin time were significant but only weakly correlated with the clotting time on the ROTEM® . In children undergoing LT, coagulation profiles depend on the etiology for LT. During LT, ROTEM® parameters could help detect thrombocytopenia and hypofibrinogenemia and guide transfusion therapy as a point-of-care monitoring method.

Comparison of Clinical Outcomes of Induction Regimens in Patients Undergoing Liver Transplantation for Acute Liver Failure.

Spontaneous survival rates in acute liver failure (ALF) are vastly improved by liver transplantation (LT). However, the value of induction agents beyond steroids continues to be debated. To understand the potential benefit of different induction regimens in the ALF population, we compared overall survival of recipients undergoing LT in the United States for ALF. Using the Scientific Registry of Transplant Recipients, we assessed the impact of induction immunosuppression (IS) in a cohort of 3754 first-time LT recipients with a diagnosis of ALF from 2002 to 2018. Induction IS therapy was grouped into steroid-only induction, use of antithymocyte globulin (ATG), or interleukin 2 receptor antibody. Other regimens were excluded from analysis. Survival analysis was estimated via Cox proportional hazards models and expressed as hazard ratios (HRs). In LT for ALF, the use of induction agents beyond steroids is increasingly frequent over the last 2 decades. The use of ATG is associated with worse overall survival, even after adjusting for donor and recipient factors, with HR of 1.24 (95% confidence interval, 1.00-1.53; P = 0.05). An elevated serum creatinine, recipient and donor age, and Black ethnicity, were all associated with reduced survival, whereas maintenance IS with calcineurin inhibitors (CNIs) was associated with improved survival. Although adjunct induction therapy has become more common, our analysis shows that compared with a steroid-only induction regimen, the addition of ATG is associated with worse overall survival after LT for ALF. CNI maintenance was highly protective, suggesting that an IS strategy focusing on corticosteroid-only induction followed by CNI maintenance may offer the best overall survival rate.

Liver Transplant in Acute Liver Failure – Looking Back Over 10 Years

Acute liver failure (ALF) is the leading cause for emergency liver transplantation (LT) all over the world. We looked at the profile of cases who required LT for ALF from a single centre to identify the possible predictors of poor outcomes. During the 10-year period starting from 2007, 320 cases of ALF were treated at our institution, of which 70 (median age 24 years, Male:Female 1:2) underwent LT. Retrospective analyses of these 70 patients were performed. Etiology was identifiable in 73% (n=51) of cases (yellow phosphorous [YP] poisoning [n= 16], Hepatitis A virus [HAV] [n= 15], Hepatitis B virus [HBV] [n= 5], Hepatitis E virus [HEV] [n= 1], anti-tubercular therapy [ATT] induced [n=6], acute Wilson's [n= 3], and autoimmune [n= 5]]. Upon meeting King's College Hospital criteria, 69 had live donor LT (61 right lobe grafts, three left lobe grafts, five leftlateral segment grafts) and one had deceased donor LT. Among these, there were five auxiliary partial orthotopic grafts and four ABO-incompatible transplants. Overall, 90-day mortality was 35.7% (n= 25), predominantly due to sepsis. Significant risk factors for mortality on multivariate analysis included indeterminate etiology, pre-op renal dysfunction, and Grade IV hepatic encephalopathy (HE). Cumulative 10-year survival of the remaining survivors was 95.6% (n= 45). LT for ALF carries high perioperative mortality (35.7%) in those presenting with indeterminate etiology, pre-op renal dysfunction, and Grade IV HE. Nevertheless, if they survive the perioperative period, long-term survival is excellent.

Outcomes of liver transplantation for acute fatty liver disease of pregnancy.

Acute fatty liver of pregnancy (AFLP) often resolves after pregnancy delivery but can progress to acute liver failure necessitating liver transplantation. We performed a retrospective review of the national Scientific Registry of Transplant Recipients (SRTR) data to identify all women in the United States undergoing liver transplantation (LT) for acute liver failure (ALF) from AFLP from 1991 to 2015, and compared to outcomes in women of childbearing age undergoing transplant for ALF from acetaminophen and ALF from other etiologies. Women with AFLP were likely to be on life support at time of LT and had high rates of renal dysfunction (median Cr 2.1, IQR 1.2-2.3), and hyperbilirubinemia (median bilirubin 17.1, IQR 11.0, 19.9). Although their early and late LT survival outcomes were comparable to the other indications for LT, cumulative 5-year graft survival was numerically lower among AFLP patients (54%, 95% CI, 27-76) compared to APAP (70%, 95% CI, 63-77) and "Other ALF" (76%, 95% CI, 72-80) groups. In conclusion, although AFLP is a rare indication for LT, AFLP patients were as sick or sicker than other women of childbearing age undergoing LT for ALF. Worsened graft survival may be related to higher rates of rejection in the AFLP group.

45. Liver Transplant in Acute Liver Failure – Looking Back

Background and Aims: Acute liver failure (ALF) although relatively uncommon, tends to affect young individuals and is the leading cause for emergency liver transplantation (LT) the world over. We carried out this study to look at the disease spectrum and to identify the possible predictors of poor outcomes after LT. Methods: We analyzed retrospectively data of 70 cases (median age 24yrs, M:F 1:2) of LT performed for ALF at our institution from April 2007 to April 2017 (out of total of 560 (12%)). Results: The etiology was identified in 53 cases [HAV (n = 15), HBV(n = 5), HEV (n = 1), ATT induced n= (6), Acute Wilson's (n = 3), Autoimmune (n = 5) and Yellow Phosphorous (YP), rodenticide poisoning (n = 16)] and remaining 17 cases were of indeterminate etiology. Etiology differed between adults (>12 years, n = 61) and children (n = 9). Whilst the most common etiology in adults were indeterminate followed by HAV and YP poisoning, equal incidence of indeterminate, acute Wilson's and ATT induced liver failure were seen among children. Upon meeting King's College criteria, 69 had live donor LT (55 Right lobe grafts, 3 left lobe grafts, 4 lefts lateral segment grafts and 5 cases were APOLT) and 1 deceased donor LT. Post-operative morbidity seen were bile leak (23%), sepsis (17.3%), ACR (14.4%), AKI (13%), graft dysfunction (5%), HAT (2.8%) and PVT (1.4%). Overall mortality was 36% (50% in the pediatric and 34% in adults), vast majority of which (92%) occurred within 30 days of transplant. The major cause of mortality was sepsis with MODS. Risk factors for mortality on univariate analysis included donor age >35yrs, pre-transplant renal dysfunction, Grade 4 encephalopathy and hepatitis A, YP poisoning and seronegative etiology. However, on multivariate analysis, only grade IV HE was a significant risk factor for post-transplant mortality. Over a median follow up of 6.17yrs, 60.2% of perioperative survivors are leading a normal life. Most of these mortalities (81.2%) occurred in the immediate post-operative period (within 30 days). Conclusions: LT for ALF carry high mortality (36%) in those presenting with Grade 4 encephalopathy. Nevertheless, if they survive the perioperative period, long term survival is excellent. The authors have none to declare.

Neurological Complications Occurring After Liver Transplantation: Role of Risk Factors, Hepatic Encephalopathy, and Acute (on Chronic) Brain Injury.

Orthotopic liver transplantation (LT) remains the only way to definitively cure patients with the most severe liver diseases. Because the survival rate is now fairly high, important questions about neurological sequelae or quality of life after LT have emerged. Indeed, LT represents a peculiar situation because up to 30% of patients present with neurological symptoms after LT compared with only 4% after cardiac transplant and 0.5% after renal transplant. These postoperative neurological symptoms have long been interpreted as sequelae of hepatic encephalopathy (HE). However, postoperative decompensation of an unknown cerebral condition due to the pathophysiology of cirrhosis or undiagnosed neurodegenerative disorders or aging constitute other possibilities that are underrecognized. Some patients who undergo LT for acute liver failure and patients with cirrhosis without episodes of HE and without any previous cerebral alteration also display post-LT neurological symptoms. This latter situation speaks in favor of a direct adverse effect of either general anesthesia, the surgical procedure, or factors related to the postoperative intensive care unit (ICU) environment. The role of inflammation, which has been described in the ICU setting, could also be a crucial determinant. In this review, we will discuss the neurological complications associated with LT, the neurocognitive complications after LT, and how to assess the LT-related neurological or neurocognitive complications. Furthermore, we will review the various hypotheses surrounding post-LT neurocognitive impairment and will conclude with recommendations for future directions.

Liver Transplantation and Auxiliary Partial Orthotopic Transplantation Outcomes in Wilson’s Disease

Introduction Liver transplantation (LT) is an effective option for Wilson's disease (WD) patients with neurologic symptoms, acute liver failure and with advance decompansated liver disease. In this retrospective study we aimed to review our LT results for WD patients. Materials and Methods Between December 1988 and October 2017 we performed 580 LT procedures at our center (age range, 6 months-64 years). We performed 53 LT in WD (45 living donor LT, 8 deceased donor LT) and after discharge we followed them for 12-350 months. We evaluated the regression of neurologic symptoms and reported survival, graft function of WD patients after LT. Results We performed LT for acute liver failure in 7 WD patients and for end stage liver failure in 41 WD patients. Five patients had LT for neurological WD. One of these neurological WD patients had auxiliary partial orthotopic LT (APOLT) due to neurological WD without hepatic failure (child A). After APOLT he is doing well with normal liver functions and ceruloplasmin levels. All neurologic symptoms were regressed in all of these 5 neurological WD patients. Four of these 53 WD patients had retransplantation (due to 1 primary non-function and 3 chronic rejections) and 3 retransplant patients are doing well with normal liver functions. Thirteen of 53 WD patients died; 6 patients died in early postoperative period, 7 patients died during their follow up due to complications unconnected to WD. The remaining 40 patients have normal liver functions in their follow up (range 12-350 months). Our long term survival is 85%. Conclusion Liver transplantation for WD with end stage liver failure and neurological WD has good outcomes. We may also consider auxiliary partial orthotopic LT for progressive neurological WD patients with no hepatic insufficiency.

Living Donor Liver Transplantation in Acute Liver Failure Patients with Grade IV Encephalopathy: Is Deep Hepatic Coma Still an Absolute Contraindication? A Successful Single-Center Experience

BackgroundThe prognosis of the patients of acute liver failure (ALF) with onset of hepatic coma is often dismal. ALF is a well-accepted indication for liver transplantation (LT) and has markedly improved the prognosis of these patients. However, its role in ALF patients with onset of hepatic coma has never been elucidated before. The aim of our study was to analyze the outcome in patients of ALF with hepatic coma who underwent LT.Material/MethodsFrom January 2002 to December 2015, a total of 726 liver transplantations were done at China Medical University Hospital, Taiwan. The hospital database of 59 recipients that underwent LT for ALF was analyzed. Eleven ALF patients with the onset of hepatic coma (grade IV encephalopathy) requiring mechanical ventilatory support were retrospectively analyzed. The patients were sub-grouped in 2 groups depending on the timing of LT after the onset of hepatic coma: Group A had LT within 48 h of onset of coma (n=7) and Group B had LT after 48 h of onset of coma (n=4).ResultsThe study cohort (group A and B) comprised 8 males and 3 females, with an average age of 39.63±13.95 years (range, 13 to 63). Ten patients received living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) was done in 1 recipient. All the patients in group A had complete neurological recovery and were extubated within 48 h after LT, whereas extubation was delayed for various reasons for group B patients. At a mean follow up of 36 months (range, 20 to 76 months), the overall survival of all the recipients (group A and B) was 72%. Three-year survival for Group A (n=7) was 85% and for Group B (n=4) it was 50%. There were no acute rejection episodes.ConclusionsLT is an acceptable modality of treatment for patients of ALF with new onset of hepatic coma. Neurological recovery is expected in all patients if LT can be done within 48 h of onset of hepatic coma without increasing the risk of morbidity. Due to shortage of deceased donor organs in Asia, LDLT can be used proactively, with a success rate comparable to that of non-ALF patients undergoing LT.

Live donor liver transplantation for acute liver failure: A single center experience.

Acute liver failure (ALF) is an indication for emergency liver transplantation (LT). Although centers performing only deceased donor liver transplants (DDLT) have shown improved outcomes in this situation, they still have relatively long waiting lists. An alternative would be living donor liver transplantation (LDLT), which has shown equivalent outcomes in the elective situation but there is limited evidence of its results in ALF. The purpose of this study was to assess the outcomes in patients with ALF undergoing emergency LDLT in our center in Delhi, India. We prospectively collected data on 479 patients who underwent LT in our hospital between January 2009 and December 2015 to evaluate the outcomes of those with ALF. The ALF patients were listed for transplantation after they met the Kings' College criteria and rapid evaluation was done following a protocol consisting of three phases. Patients with grade III/IV encephalopathy were put on mechanical ventilation. Data regarding their postoperative course, morbidity, and mortality were analyzed. Thirty-six (7.5%) out of the 479 patients underwent emergency LT for ALF. Their mean age was 27.5years (range 4-59years) and the male to female ratio of 2:3. Preoperative intubation was required in 15 of 25 patients who had encephalopathy. Wilson's disease was the most common cause of ALF in children while in adults, it was acute viral hepatitis. The time interval between listing and transplantation was a mean of 36 ± 12.4h. The mean graft to recipient weight ratio (GRWR) was 1.06 ± 0.3. The recipients were extubated postoperatively after a mean period of 2.6days and their mean ICU stay was 6.3days. Postoperative infection was the most common complication and required upgradation of antifungal and antibiotic treatments. Neurological complications occurred in five patients. Thirty-one of 36 (86.1%) patients survived and progressive cerebral edema and sepsis were the most common causes of mortality. Patients who died had higher model for end-stage liver disease scores, longer cold ischemia time (CIT), and higher grades of encephalopathy (though 80% patients with encephalopathy survived). There was no donor mortality. At long-term follow up of a median of 56months, 29 (80.5%) of 36 patients were still alive. In our experience, LDLT is an alternative procedure to DDLT in patients with ALF and is associated with good outcomes even in patients with high grades of encephalopathy.

Liver transplantation for bile duct injury after open and laparoscopic cholecystectomy

BackgroundBile duct injury (BDI) after cholecystectomy is a serious complication. In a small subset of patients with BDI, failure of surgical or non-surgical management might lead to acute or chronic liver failure. The aim of this study was to review the indications and outcome of liver transplantation (LT) for BDI after open and laparoscopic cholecystectomy.MethodsPatients with BDI after cholecystectomy who were on the waiting list for LT between January 1987 and December 2010 were identified from LT centres in Spain. A standardized questionnaire was sent to each unit for extraction of data on diagnosis, previous treatments, indication and outcome of LT for BDI.ResultsSome 27 patients with BDI after cholecystectomy in whom surgical and non-surgical management for BDI failed were scheduled for LT over the 24-year interval. Emergency LT for acute liver failure was indicated in seven patients, all after laparoscopic cholecystectomy. Two patients died while on the waiting list and only one patient survived more than 30 days after LT. Elective LT for secondary biliary cirrhosis after a failed hepaticojejunostomy was performed in 13 patients after open and seven after laparoscopic cholecystectomy. One patient from the elective transplantation group died within 30 days of LT. The estimated 5-year overall survival rate was 68 per cent.ConclusionEmergency LT for acute liver failure was more common in patients with BDI after laparoscopic cholecystectomy, and associated with a poor outcome.

Perioperative risk factors for prolonged mechanical ventilation after liver transplantation due to acute liver failure

BackgroundAcute liver failure (ALF) is a rapidly progressing and fatal disease for which liver transplantation (LT) is the only treatment. Posttransplant mechanical ventilation tends to be more prolonged in patients with ALF than in other LT patients. The present study examined the clinical effects of prolonged posttransplant mechanical ventilation (PMV), and identified risk factors for PMV following LT for ALF.MethodsWe reviewed data of patients undergoing LT for ALF between January 2005 and June 2011. After grouping patients according to administration of PMV (≥ 24 h), donor and recipient perioperative variables were compared between the groups with and without PMV. Potentially significant factors (P < 0.1) from the univariate intergroup comparison were entered into a multivariate logistic regression to establish a predictive model for PMV.ResultsTwenty-four (25.3%) of 95 patients with ALF who received PMV had a higher mortality rate (29.2% vs 11.3%, P = 0.038) and longer intensive care unit stay (12.9 ± 10.4 vs 7.1 ± 2.7 days, P = 0.012) than patients without PMV. The intergroup comparisons revealed worse preoperative hepatic conditions, more supportive therapy, and more intraoperative fluctuations in vital signs and less urine output in the with- compared with the without-PMV group. The multivariate analysis revealed that preoperative hepatic encephalopathy (≥ grade III), intraoperative blood pressure fluctuation, and oliguria (< 0.5 ml/kg/h) were independent risk factors for PMV.ConclusionsPMV was associated with deleterious outcomes. Besides care for known risk factors including hepatic encephalopathy, meticulous attention to managing intraoperative hemodynamic circulatory status is required to avoid PMV and improve the posttransplant prognosis in ALF patients.

Outcomes after living donor liver transplantation for acute liver failure in Japan: Results of a nationwide survey

Nationwide surveys of acute liver failure (ALF) are conducted annually in Japan, and 20% of patients with ALF undergo liver transplantation (LT). We extracted data for 212 patients who underwent LT for ALF from the nationwide survey database of the Intractable Liver Diseases Study Group of Japan. After the exclusion of 3 patients who underwent deceased donor LT, 209 recipients of living donor liver transplantation (LDLT) were analyzed. ALF patients were placed into 3 subgroups according to the time from the onset of the disease to the occurrence of encephalopathy: patients who presented with encephalopathy within 10 days of the disease's onset were classified as having acute ALF, patients who presented within 11 to 56 days were classified as having subacute ALF, and patients who presented within 9 to 24 weeks were classified as having late-onset hepatic failure (LOHF). Long-term follow-up data were obtained from the registry of the Japanese Liver Transplantation Society. The 2 data sets were merged, and descriptive and survival data were analyzed. A Cox regression analysis was performed to define factors predicting overall mortality, short-term mortality (≤90 days after LT), and long-term mortality (>90 days after LT). One hundred ninety of the analyzed patients (91%) were adults (age ≥ 18 years); 70 patients (34%) were diagnosed with acute ALF, 124 (59%) were diagnosed with subacute ALF, and 15 (7%) were diagnosed with LOHF. Hepatitis B virus was the most common cause of acute ALF (61%), whereas autoimmune hepatitis (14%) and drug allergy-induced hepatitis (14%) were more frequent in patients with subacute ALF or LOHF. The cumulative patient survival rates 1, 5, and 10 years after LT were 79%, 74%, and 73%, respectively. Patient age was associated with short- and long-term mortality after LT, whereas ABO incompatibility affected short-term mortality, and donor age affected long-term mortality. In conclusion, the long-term outcomes of LDLT for ALF in this study were excellent, regardless of the etiology or classification. The majority of the donors were living donors. Increasing the deceased donor pool might be an urgent necessity.

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Genetic, immunological and clinical risk factors for biliary strictures following liver transplantation

Biliary strictures after liver transplantation (LT) are a major cause of morbidity and reduced graft survival. The purpose of this study was to investigate genetic, immunological and clinical risk factors for the occurrence of post-LT ischaemic type biliary lesions (ITBLs) and biliary anastomotic strictures (AS). Clinical and laboratory data, chemokine receptor (CCR) genotypes, chemotactic cytokines and anti-major-histocompatibility complex antibodies in serum were investigated in 162 LT patients. In the univariate analysis, older donor and recipient age, partial LT, high peak aspartate aminotransaminase (AST) levels and CC chemokine receptor 5 delta32 loss-of-function mutation (CCR5Δ32) were associated with ITBL, whereas LT for acute liver failure (ALF), ABO-compatible non-identical LT, presence of donor-specific anti-human leucocyte antigen (HLA) class II antibodies and fractalkine receptor (CX3CR1)-249II allele were associated with AS. In the multivariate analysis, CCR5Δ32 was an independent risk factor for ITBL, whereas LT for ALF, ABO-compatible non-identical LT, and CX3CR1-249II allele remained predictive for AS. Serum levels of interferon-gamma and interleukin (IL)-6 as well as IL-10 were significantly increased in patients with biliary strictures. Specific chemokine receptor polymorphisms of the recipient are associated with development of post-LT biliary strictures. Altered cytokine profile may contribute to enhanced fibrotic tissue remodelling and biliary stricture formation. Screening of anti-HLA antibodies might be useful for early identification of at-risk patients who could benefit from closer surveillance and tailored immunosuppressive regimen. Our findings may have relevance for prediction and management of post-LT biliary strictures.

Liver Transplantation for Acute Liver Failure: A Spanish Perspective

The Spanish characteristics of organ donation (high accessibility to a transplant) and the different proportion in the etiologies of acute liver failure (ALF), namely, the very low incidence of paracetamol overdose causing this syndrome in contrast with other Western countries, are the causes of some specific features of emergency liver transplantation for ALF. The most relevant are the short time between the need for a graft and effective urgent liver transplant, and the high proportion of patients who undergo this therapy. This paper analyzes these characteristics and provides information about the use of biological and nonbiological extracorporeal liver support devices in acute liver failure, suggesting that these systems should be tested in countries with a long waiting times for urgent liver transplantation, or in patients with ALF and contraindications for transplantation.

Treatment of antibody-mediated rejection with high-dose immunoglobulins in ABO-incompatible liver transplant recipient

ABO-incompatible liver transplantation (LT) entails high risk of antibody-mediated rejection (AMR) and poor graft survival. Different treatment modalities have been reported, but none with use of a 2-week course of high-dose polyclonal i.v. immunoglobulins (IVIg) associated with plasmapheresis without the use of steroid pulses or monoclonal antibody. A 60-year-old male patient with blood-group O, Caucasian, underwent urgent LT for acute liver failure after hepatectomy for HCV-related hepatocellular carcinoma. He was grafted with a 66-year-old, blood-group A, HCV-positive liver graft. Pretransplant conditioning consisted of plasmapheresis and immunosuppression was triple with tacrolimus (TAC), steroids, and mycophenolate mofetil with anti-IL2-R monoclonal antibodies, plasmapheresis if hemagglutinin level >1:8, and extracorporeal photopheresis. After reduction of liver function tests to baseline, the patient presented a tenfold increase in alanine aminotransferases (ALT) levels 7 days post-transplantation. AMR was confirmed on histology. Treatment consisted of IVIg (1.5 g/Kg/daily for the first 7 days, and 1 g/Kg/daily from day 8 to 14) with a 14-day course of plasmapheresis. No side effect was observed and daily blood IgG levels ranged between 24.4 and 36.4 g/l. At the end of the scheduled course ALT returned to baseline. A control liver biopsy 55 days after LT showed no rejection and replacement of necrosis with fibrous strands. This case may support the role of high-dose IVIg for treatment and/or prophylaxis of severe AMR.