Transplantation For Acute Liver Failure Research Articles

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.

Pediatric living-donor liver transplantation for acute liver failure: analysis of 57 cases

We reviewed 57 pediatric patients admitted with acute liver failure to Kyoto University Hospital in Japan over a period of 15 years to compare the etiology and the long-term outcome of infants and children after living donor liver transplantation (LDLT). Patients were divided into two groups according to age at the time of liver transplantation, infants group (<1 year, n = 20), and children group (1-18 years, n = 37). The overall survival rates were 73.6%, 69.5% and 67.2% at 1, 5, and 10 years after LDLT respectively. Age of recipients at the time of LDLT had a strong impact on their outcome, Children had significantly better outcome than infants (P = 0.001). Surgical complications were comparable between both groups. Infants had higher rates of acute cellular rejection (ACR), which was associated with features of hepatitis in many cases. Refractory ACR was the leading cause of death in eight out of 12 infants, while it resulted in loss of one child only. Cox's proportional hazard regression model was used to examine potential risk factors for graft loss and it shows that age <1 year was associated with high risk of graft loss [hazard ratio (HR) = 11.393; CI = 1.961-76.1763] (P < 0.05). In conclusion, Infants had poorer prognosis than children and refractory ACR was the leading cause of death. Using additional immunosuppressant for cases with severe and atypical rejections is recommended.

Auxiliary Liver Transplantation for Acute Liver Failure in Children

The aim of this study is to present the largest experience of auxiliary liver transplantation for acute liver failure (ALF) in children over the past 19 years. Between 1990 and 2009, a total of 128 liver transplants were performed on children with ALF. Of these, 20 received auxiliary liver transplants (19 were cadaveric and 1 living graft). The recipient median age was 12 years (range: 1 -16). Indications for auxiliary partial orthotopic liver transplantation were seronegative non-A non-B hepatitis in 16 children, drug induced in 2, and 1 autoimmune hepatitis and 1 mushroom poisoning. The median waiting time for transplantation was 2 days (range: 1-9). After native liver partial hepatectomy, 20 grafts were implanted orthotopically and included 8 right lobes, 8 left lateral segments, 3 left lobes, and 1 whole liver. Regeneration of the native liver was assessed by radiologic, nuclear medicine imaging, and histology. Follow-up imaging and biopsies were performed at intervals of 3 to 6 months and yearly. Patient survival was 85% at 1, 5, and 10 years. There were 3 deaths at a median of 9 days (range: 8-52) post-transplantation. There was 1 retransplant for chronic rejection 15 months post-transplantation. There were no biliary or vascular complications. Of 17 survivors, 14 (82%) have successfully regenerated their native liver and so far 11 children (65% of the survivors) have been withdrawn from immunosuppression at a median time of 23 months (range: 4-106) after transplantation. Auxiliary partial orthotopic liver transplantation should be considered in children presenting with ALF who fulfill criteria for liver transplantation.

Chilean Experience in Liver Transplantation for Acute Liver Failure in Children

Background Acute liver failure (ALF) in children is a life-threatening condition, associated with high mortality, and in almost one third of the cases, with no other therapeutic option than orthotopic liver transplant (OLT). The aim of this study was to present our experience with OLT for ALF in pediatric patients in Chile. Patients fulfilling the criteria for ALF who were transplanted in our centers were prospectively included in an excel Microsoft database. We analyzed demographics, etiology, surgical techniques, complications, and long-term results. Patients and Methods Between 1994 and 2009, we transplanted 52 pediatric patients with ALF. The most frequent known etiology was acute hepatitis A in 9 cases (18%), but in 26 cases (50%) it was impossible to determine the etiology. Thirty- one patients were males (63%). The overall mean age was 7.5 years and the mean weight, 28.1 kg. Thirty-five (67%) received a cadaveric graft. Among them in 18 cases (34%) the liver had to be reduced but 17 (33%) received whole livers. There were 17 (33%) recipients of living-related livers. Twenty-two patients needed reoperation, including 13 due to surgical complications (59%) and 9 (41%) as planned interventions. Ten patients were retransplanted. Results Actuarial survival of patients at 1 year was 80% and at 5 and 10 years, 72%. Graft survival at 1 year was 79%, at 5 years 69%, and at 10 years 50%. Conclusion We have reported a series of pediatric liver transplant patients due to ALF whose results were comparable to other reported series. Living donor transplantation for ALF should be considered and offers a low morbidity rate without mortality.

Long-term outcomes of emergency liver transplantation for acute liver failure

Acute liver failure continues to be associated with a high mortality rate, and emergency liver transplantation is often the only life-saving treatment. The short-term outcomes are decidedly worse in comparison with those for nonurgent cases, whereas the long-term results have not been reported as extensively. We report our center's experience with urgent liver transplantation, long-term survival, and major complications. From 1994 to 2007, 60 patients had emergency liver transplantation for acute liver failure. The waiting list mortality rate was 6%. The mean waiting time was 2.7 days. Post-transplantation, the perioperative mortality rate was 15%, and complications included neurological problems (13%), biliary problems (10%), and hepatic artery thrombosis (5%). The 5- and 10-year patient survival rates were 76% and 69%, respectively, and the graft survival rates were 65% and 59%. Recipients of blood group-incompatible grafts had an 83% retransplantation rate. Univariate analysis by Cox regression analysis found that cerebral edema and extended criteria donor grafts were associated with worse long-term survival. Severe cerebral edema on a computed tomography scan pre-transplant was associated with either early mortality or permanent neurological deficits. The keys to long-term success and continued progress in urgent liver transplantation are the use of good-quality whole grafts and a short waiting list time, both of which depend on access to a sufficient pool of organ donors. Severe preoperative cerebral edema should be a relative contraindication to transplantation.

Liver transplantation for acute liver failure due to toxic agent ingestion in children

ALF is characterized by sudden onset, impaired liver function, jaundice and encephalopathy, without previous liver disease. We analyzed the patients who underwent LT due to toxic agent induced ALF to raise community awareness about preventing the toxic agent induced ALF. Five children (three boys, two girls) underwent LT due to toxic agent ingestion. Toxic agents were mushroom poisoning (n = 2), Datura stramonium (n = 1), yellow phosphorous (n = 1) and INH (n = 1). On admission, one patient had stage IV, two had stage III and two had stage II hepatic encephalopathy but worsened during the follow-up. One patient had renal failure, and three patients required mechanical ventilation. Three patients underwent LRLT and others from a DD. Post-operative complications were managed by supportive managements successfully, and overall all the patients are alive (100% survival) without any organ sequelae. Although outcome of these patients are excellent, ALF may be prevented in these cases by educating the public about consuming mushrooms and toxic effects of wild plants, prohibiting fireworks and serial liver enzyme measurements after initiating INH.

Emergency Adult-to-Adult Living-Donor Liver Transplantation for Acute Liver Failure in A Hepatitis B Virus Endemic Area

The outcomes of patients with acute liver failure (ALF) vary greatly according to etiology. Emergency adult-to-adult living-donor liver transplantation (adult LDLT) would help address the shortage of available organs for patients with ALF, especially in hepatitis B virus (HBV)-endemic areas. We analyzed a prospective database of 110 consecutive adult patients with ALF. ALF was defined as sudden development of severe coagulopathy and encephalopathy within 26 weeks of onset of symptoms. In about 90% of patients, ALF was caused by etiologies that usually result in poor outcomes, including HBV infection (37%). Three cases (3%) were associated with acetaminophen overdose. Of the 99 patients listed for emergency liver transplantation, four (4%) underwent deceased-donor liver transplantation (DDLT), and 40 (40%) underwent adult LDLT. The 1-year survival rate of adult LDLT patients was 85%. Of the 55 patients listed but not transplanted, 45 (82%) died within a median of 7 days (range, 1-90 days). Multivariate analysis showed that adult LDLT (hazard ratio [HR] 0.10, P < 0.01) and DDLT (HR 0.12, P = 0.04) were associated with decreased mortality, whereas older age (HR 1.03, P = 0.01) and higher Model for End-stage Liver Disease (MELD) (HR 1.03, P = 0.04) was associated with increased mortality of patients. There was no living donor mortality. Eight (17.8%) and three (6.7%) living donors experienced grade 1 and 2 complications, respectively. Emergency adult LDLT can be performed expeditiously and safely for patients with ALF, and greatly improves the survival rate. As the window during which transplantation is possible is limited, emergency adult LDLT should be considered one of the first-line treatment options in patients with ALF, especially in regions in which ALFs are caused by etiologies associated with poor outcome and the supply of organs is severely limited.

Pediatric liver transplantation for acute liver failure at a single center: a 10-yr experience.

Children transplanted for ALF urgently require an optimal graft and have lower post-transplant survival compared with children transplanted for chronic liver disease. Over 10 yr, 33 consecutive children transplanted for ALF were followed. Demographics, encephalopathy, intubation, dialysis, laboratory values, graft type ABOI, XL (GRWR > 5%), DDSLT, LDLT and WLT were evaluated. Complications and survival were determined. ALF accounted for 33/201 (16.4%) of transplants during this period. Twelve of 33 received ABOI, five XL grafts, 18 DDSLT, and three LDLT. Waiting time pretransplant was 2.1 days. One- and three-yr patient survival in the ALF group was 93.4% and 88.9%, and graft survivals were 86.4% and 77.7%. Median follow-up was 1452 days. ABOI one- and three yr patient and graft survival in the ALF was 91.6% and 78.6%. No difference in graft or patient survival was noted in the ALF and chronic liver disease group or the ABOI and the ABO compatible group. A combination of ABO incompatible donor livers, XL grafts, DDSLT, LDLT and WLT led to a short wait time and subsequent graft and patient survival comparable to patients with non-acute disease.

Living‐related Liver Transplantation for Acute Liver Failure

Living‐related Liver Transplantation for Acute Liver Failure

Feasibility of adult-to-adult living donor liver transplantation for acute liver failure

Feasibility of adult-to-adult living donor liver transplantation for acute liver failure

Outcome after wait-listing for emergency liver transplantation in acute liver failure: A single centre experience

Though emergency liver transplantation (ELT) is an established treatment for severe acute liver failure (ALF), outcomes are inferior to elective surgery. Despite prioritization, many patients deteriorate, becoming unsuitable for ELT. We examined a single-centre experience of 310 adult patients with ALF registered for ELT over a 10-year period to determine factors associated with failure to transplant, and in those patients undergoing ELT, those associated with 90-day mortality. One hundred and thirty-two (43%) patients had ALF resulting from paracetamol and 178 (57%) from non-paracetamol causes. Seventy-four patients (24%) did not undergo surgery; 92% of these died. Failure to transplant was more likely in patients requiring vasopressors at listing (hazard ratio 1.9 (95% CI 1.1-3.6)) paracetamol aetiology (2.5 (1.4-4.6)) but less likely in blood group A (0.5 (0.3-0.9)). Post-ELT survival at 90-days and one-year increased from 66% and 63% in 1994-1999 to 81% and 79% in 2000-2004 (p<0.01). Four variables were associated with post-ELT mortality; age >45 years (3 (1.7-5.3)), vasopressor requirement (2.2 (1.3-3.8), transplantation before 2000 (1.9 (1.1-3.3)) and use of high-risk grafts (2.3 (1.3-4.2). The data indicate improved outcomes in the later era, despite higher level patient dependency and greater use of high-risk grafts, through improved graft/recipient matching.

Indication criteria for liver transplantation for acute liver failure in Japan

In Japan, patients with hepatitis are diagnosed as having fulminant hepatitis and late-onset hepatic failure (LOHF) when grade II or more severe hepatic encephalopathy develops within 8 weeks and between 8 and 24 weeks, respectively, of the disease onset, with a prothrombin time of less than 40% of the standardized value. Fulminant hepatitis patients are classified into the acute and subacute types, in which the encephalopathy occurs within 10 days and later than 11 days, respectively. According to the nation-wide survey by the Intractable Liver Disease Study Group of Japan, liver transplantation was performed in 14% and 26% of the patients with the acute and subacute types, respectively, and in 19% with LOHF between 1998 and 2003. Survival rate of these patients was 77%, which was greater than those of the patients treated without liver transplantation; 54%, 24% and 12% in the acute and subacute types and LOHF, respectively. The indications for liver transplantation in fulminant hepatitis patients are currently determined according to the Guideline of the Acute Liver Failure Study Group of Japan in 1996, which is based on assessment of the prognosis of the patients at the onset of hepatic encephalopathy and reassessed 5 days later. Predictive accuracy of the Guideline, assessed in the patients between 1998 and 2003, were 68% and 78% among the cases with the acute and subacute types, respectively, of fulminant hepatitis. Liver transplantation was considered in most of LOHF patients at 8 or more days before encephalopathy development. Although liver transplantation improved the prognosis of patients with acute liver failure, the Guideline should be modified to improve the accuracy for fulminant hepatitis patients, and the new criteria should be made for LOHF patients.

Auxiliary transplantation for acute liver failure: Histopathological study of native liver regeneration

Auxiliary liver transplantation (ALT) permits the serial assessment of regeneration in livers of patients with acute liver failure (ALF). Forty-nine ALF patients [32 adults (median age, 23 years; range, 16-40 years) and 17 children (median age, 12 years; range, 1-15 years)] underwent ALT between 1994 and 2004 at King's College Hospital. Twenty-four patients had seronegative liver failure, 15 had acetaminophen toxicity, 4 had hepatitis B virus (HBV) infection, 3 had drug-induced liver failure, 2 had autoimmune hepatitis, and 1 had mushroom poisoning. Nine patients without post-ALT native liver histology were excluded from review. All acetaminophen-induced, HBV, and drug-related patients had diffuse injury. Twelve seronegative patients and the autoimmune hepatitis patient had a map-like injury. On follow-up, 9 acetaminophen-induced patients, 9 seronegative patients, 2 drug-induced ALF patients, 3 HBV patients, and the autoimmune patient recovered to a near-normal native liver with inconsequential scarring. The hepatocyte proliferative rate in diffuse necrosis was 27.4% (range, 3.1%-69.4%) at hepatectomy and sharply decreased after 8 days post-ALT, being minimal months and years after ALT. In conclusion, in patients undergoing ALT for ALF with a diffuse pattern of liver injury-mainly acetaminophen toxicity-hepatocyte proliferation occurs in the native liver within a few days of transplantation. If the injury is map-like (most cases of seronegative ALF), regeneration seems to involve variable hepatocellular proliferation and potential ductular hepatopoiesis, but sequential assessment is difficult because of sampling variation. The likelihood of histological recovery appears to be minimal in livers with total hepatocyte loss at the time of ALT.

Liver transplantation for acute liver failure: a 5 years experience

Fulminant hepatic failure carries a high morbidity and mortality. Liver transplantation has markedly improved the prognosis of patients with fulminant hepatic failure. To evaluate the outcome of 20 patients with acute liver failure and indication for liver transplantation. A retrospective review of 20 patients with acute liver failure and indication for liver transplantation was performed. Patients were divided into two groups: group A with 12 patients who underwent liver transplantation and group B with 8 patients who did not receive liver transplantation. Both groups were analyzed according to age, sex, ABO blood type, etiology of acute liver failure, time on list until transplantation or death, and survival rates. Group A patients were additionally analyzed according to preoperative INR, AST, and ALT peak values and MELD (Model for End-stage Liver Disease) scores; intraoperative red blood cells and plasma transfusion and cold ischemia time; postoperative lenght of intensive care unit and hospital stay, and needed for dialysis. Group A: there were four men and eight women with an average age of 24.6 years. The average liver waiting time period was 3.4 days and MELD score 36. Seven patients are alive with good hepatic function at a medium follow-up of 26.2 months. The actuarial survival rate was 65.2% at 1 year. Group B: There were two men and six women with an average age of 30.9 years. The mean waiting time on list until death was 7.4 days. All patients died while waiting for a liver donor. Despite the improvements in intensive care management, most patients with acute liver failure and indication for liver transplantation ca not survive long without transplant. Liver transplantation is potentially the only curative modality and has markedly improved the prognosis of those patients.

Liver transplantation for acute liver failure: Not too early but never too late

Liver transplantation for acute liver failure: Not too early but never too late

Outcomes of living donor liver transplantation for acute liver failure: The adult-to-adult living donor liver transplantation cohort study

For acute liver failure (ALF), living donor liver transplantation (LDLT) may reduce waiting time and provide better timing compared to deceased donor liver transplantation (DDLT). However, there are concerns that a partial graft would result in reduced survival of critically ill LDLT recipients and that the rapid evolution of ALF would lead to selection of inappropriate donors. We report outcomes for ALF patients (and their donors) evaluated for LDLT between 1998 and April 2007 from the Adult-to-Adult Living Donor Liver Transplantation Cohort. Of the 1201 potential LDLT recipients, 14 had ALF, only 6 of whom had an identified cause. The median time from listing to first donor evaluation was 1.5 days, and the median time from evaluation to transplantation was 1 day. One patient recovered without liver transplant, 3 of 10 LDLT recipients died, and 1 of 3 DDLT recipients died. Five of the 10 living donors had a total of 7 posttransplant complications. In conclusion, LDLT is rarely performed for ALF, but in selected patients it may be associated with acceptable recipient mortality and donor morbidity.

Role of Liver Transplantation in Acute Liver Failure

Orthotopic liver transplantation is employed as salvage therapy for individuals who are unable to recover from acute liver failure. Prognostic models are helpful but not entirely accurate in predicting those who will eventually require liver transplantation. There are specific criteria for United Network for Organ Sharing category 1a (urgent) listing of these patients. Unfortunately, clinical deterioration develops rapidly and many require removal from the waiting list prior to transplantation. With advances in critical care management and surgical technique, 1-year post-transplant survival rates have improved to 60 to 80%. Alternatives to conventional orthotopic liver transplantation include living donor liver transplantation, ABO-incompatible grafts, and auxiliary liver transplantation. There are many ethical and psychosocial issues inherent to transplanting these sick patients due to the urgent nature of acute liver failure. Fortunately, the long-term survival and quality of life in these transplant recipients is good.

Rapid evolution of congenital hepatic fibrosis after liver transplantation for acute liver failure: The potential role of extrahepatic factors

A 9-year-old male underwent deceased donor liver transplantation for idiopathic fulminant hepatic failure. In the postoperative period, a review of perioperative biopsies of the donor liver revealed mild features of congenital hepatic fibrosis. Over the ensuing year, the recipient developed severe complications of congenital hepatic fibrosis including multiple episodes of cholangitis and progressive portal hypertension. After a second transplant, the patient had no further episodes of cholangitis and/or features of portal hypertension. Examination of the explanted liver revealed remarkable progression of the congenital hepatic fibrosis, suggesting that the phenotype of this disease may be dependent in part on extrahepatic factors.

Right Hepatic Trisectionectomy for Hepatobiliary Diseases

To assess the results of 275 patients undergoing right hepatic trisectionectomy and to clarify its current role. Right hepatic trisectionectomy is considered one of the most extensive liver resections, and few reports have described the long-term results of the procedure. Short- and long-term outcomes of 275 consecutive patients who underwent right hepatic trisectionectomy from January 1993 to January 2006 were analyzed. Of the 275 patients, 160 had colorectal metastases, 49 had biliary tract cancers, 20 had hepatocellular carcinomas, 20 had other metastatic tumors, and 12 had benign diseases. Fourteen of the 275 patients underwent right hepatic trisectionectomy as part of auxiliary liver transplantation for acute liver failure and were excluded. Concomitant procedures were carried out in 192 patients: caudate lobectomy in 45 patients, resection of tumors from the liver remnant in 57 patients, resection of the extrahepatic biliary tree in 45 patients, and lymphadenectomy in 45 patients. One-, 3-, 5-, and 10-year survivals were 74%, 54%, 43%, and 36%, respectively. Overall hospital morbidity and 30-day and in-hospital mortalities were 41%, 7%, and 8%, respectively. Survivals for individual tumor types were acceptable, with 5-year survivals for colorectal metastasis and cholangiocarcinoma being 38% and 32%, respectively. Multivariate analysis disclosed the amount of intraoperative blood transfusion to be the sole independent predictor for the development of hospital morbidity. Age over 70 years, preoperative bilirubin levels, and the development of postoperative renal failure were found to be independent predictors of long-term survival. Right hepatic trisectionectomy remains a challenging procedure. The outcome is not influenced by additional concomitant resection of tumors from the planned liver remnant. Caution must be taken when considering patients older than 70 years for such resections.

Liver Transplantation for Acute Liver Failure: Trying to Define When Transplantation Is Futile

Background Recently, the model of end-stage liver disease (MELD) index has been used to select patients with acute liver failure (ALF) or transplantation. By the time the indication for orthotopic liver transplantation (OLT) is defined, the patient’s clinical status may worsen. Objective In this study, MELD was used to define patients beyond OLT. Methods Among adult patients ALF was responsible for 17 OLT. Their medical records were reviewed to calculate the MELD score just before the OLT. MELD of the deceased patients after OLT (group 1, n = 8), was compared with the MELD score of living recipients (group 2, n = 9). Creatinine level, need for dialysis, use of vasoactive amines, and mechanical ventilation before OLT were also analyzed in these groups. A significant difference was defined when P < .05. Results The mean MELD score ± SD was 51.86 ± 12.3 for group 1, and 38.47 ± 7.1 for group 2 ( P = .02). There was no difference between the creatinine values for patients in the 2 groups ( P = .20). Also, the use of vasoactive amines or the need of dialysis before OLT were not different ( P = .12 and P = .25, respectively). Group 1 was more frequently under mechanical ventilation, and showed a 4.29 relative risk for death after OLT. Conclusion MELD score could be useful to define the prognosis of OLT among patients with ALF.