Liver Transplantation For Fulminant Hepatic Failure Research Articles

2233 Emergent Living Donor Liver Transplantation for Fulminant Hepatic Failure Secondary to Wilson’s Disease

INTRODUCTION: Liver transplantation (LT) is indicated for patients with Wilson’s disease (WD) who present with either fulminant hepatic failure (FHF) or end-stage liver disease. However, there is very limited information regarding emergent LDLT in adult patients with WD presenting with FHF. Here we report a case of FHF due to decompensated WD in an adult treated with emergent LDLT. CASE DESCRIPTION/METHODS: A 25-year-old female with no prior medical history presented with jaundice and fatigue. At presentation, lab tests showed: Br 14.8 mg/dL, ALT 42 U/L, AST 165 U/L, ALP 65 IU/L, INR 3.2. Serum ceruloplasmin level was low: 70 (Range 190-390) and 24 hour urine copper was markedly elevated at 7269 μg /24 Hr (Range 5–50). Subsequent clinical course was characterized by progressive encephalopathy and coagulopathy. Lab tests 4 days later revealed: Br 36.42, ALT 30, ALT 217, ALP 30, Cr 2.75 mg/dL, INR 5.8 (MELD > 40). She was diagnosed with FHF due to WD and underwent emergent LDLT utilizing a left lobe graft from her 33-year-old brother, who had a normal screening ceruloplasmin. Explant revealed a cirrhotic liver with necrosis, cholestasis and positive copper immunostain (Figures 1 and 2). Quantitative hepatic copper content was 2119 mcg/g (Range 10−35). Recipient genetic testing revealed c.2930C>T p. (Thr977Met) variant in homozygosity in the ATP7B gene. Donor was heterozygous. The patient gradually improved and continues to do well 8 months later with normal ceruloplasmin and 24 hour urinary copper excretion. DISCUSSION: WD is an autosomal recessive disorder of copper metabolism caused by a mutation in the ATP7B gene on chromosome 13. It affects one in 30 000 individuals with a reported carrier frequency of one in 90. LT is the only effective option in WD presenting with FHF and corrects the underlying hepatic metabolic defect. The overwhelming majority of reported cases of emergent LT for FHF secondary to WD in adults utilized deceased donor LT, with a few reported cases of LDLT in children. Given the narrow window of opportunity for LT in FHF and concerns related to heterozygosity in donors, emergent LDLT is rarely performed in this setting. In recipients with cirrhosis secondary to WD, LT using heterozygous donors for the WD gene has been shown to have outcomes comparable to that from a deceased, unrelated donor. Given the scarcity of deceased donor organs, LDLT may be a viable option for patients with decompensated WD presenting with FHF, even if the donor could potentially be heterozygous for the WD mutation.

The different etiology of fulminant hepatic failure (FHF) in Korea and prognostic factors in patients undergoing liver transplantation for FHF

The prognosis of fulminant hepatic failure (FHF) depends on the etiology and reversibility. In this study, we identified the etiological difference of FHF in Korea and analyzed the prognostic factors after liver transplantation (LT) for FHF. We retrospectively reviewed 42 patients with FHF who underwent LT from April 1999 to April 2011 at Samsung Medical Center, Seoul, Korea. The patients were categorized into two groups according to the short-term result of LT, and perioperative profiles were compared to identify the short-term poor prognostic factors. Unlike Western countries, there was no paracetamol-related FHF but herbal/folk medicines were the most frequent causes of FHF (26.2%). HAV-related FHF increased significantly and comprised the main portion of FHF with Herbal/folk medicines after 2005. Encephalopathy grade, onset time, pre-transplantation need of renal replacement, and ventilator treatment were significantly different between groups in univariate analysis. In multivariate analysis, pre-transplantation renal replacement treatment and hepatic encephalopathy grade IV were the independent prognostic factors after LT. The etiologies of FHF in Korea were different compared with Western reports. The requirement of renal replacement treatment and hepatic encephalopathy grade IV were identified as independent poor prognostic factors after LT for FHF in this study.

Liver transplantation for children with Wilson disease: comparison of outcomes between children and adults

Liver transplantation (LT) is lifesaving for patients with Wilson disease (WD) presenting with fulminant hepatic failure (FHF) or chronic liver disease (CLD) unresponsive to treatment. To determine the outcome of LT in pediatric and adult patients with WD. United Network for Organ Sharing data on LT from 1987 to 2008 were analyzed. Outcomes were compared for patients requiring LT for FHF and CLD after 2002. Multivariate logistic regression was used to determine risk factors for death and graft loss. Of 90,867 patients transplanted between 1987 and 2008, 170 children and 400 adults had WD. The one- and five-yr patient survival of children was 90.1% and 89% compared to 88.3% and 86% for adults, p = 0.53, 0.34. After 2002, 103 (41 children) were transplanted for FHF and 67 (10 children) for CLD. One- and five-yr patient survival was higher in children transplanted for CLD compared to FHF; 100%, 100% vs. 90%, 87.5% respectively, p = 0.30, 0.32. One- and five-yr patient survival was higher in adults transplanted for CLD compared to FHF; 94.7%, 90.1% vs. 90.3%, 89.7%, respectively, p = 0.36, 0.88. Encephalopathy, partial graft, and ventilator use were risk factors for death by logistic regression. LT is an excellent treatment option for patients with WD. Patients transplanted for CLD had higher patient survival rates than patients with FHF.

Fulminant Hepatic Failure in Children

Death occurs in half of all children with fulminant hepatic failure (FHF). Although liver transplantation (LT) is potentially life-saving, there are only a few published series with limited experience. The aim was to examine predictors of survival after LT for FHF. Between 1984 and 2008, all LT for FHF performed in recipients less than or equal to 18 years of age were analyzed from a prospectively maintained database using 35 demographic, laboratory, and operative variables. Unique calculated variables included creatinine clearance (cCrCl) and Pediatric End-Stage Liver Disease score (PELD). Study end-points were patient and death censored graft survival. Median follow-up was 98 months. Statistical analysis involved the log-rank test and Cox proportional hazards model. A total of 122 children underwent 159 LTx. Cryptogenic was the primary etiology (70%) and the median age was 53 months. The significant (P < 0.05) univariate predictors of worse graft survival were: recipient age <24 months, cCrCl <60 mL/min/1.73m, PELD >25 points, and warm ischemia time >60 minutes. The significant (P < 0.05) univariate predictors of worse patient survival were: recipient African-American and Asian race, recipient age <24 months, cCrCl <60 mL/min/1.73m, and time from onset jaundice to encephalopathy <7 days. On multivariate analysis, survival was significantly impacted by 4 variables: cCrCl <60 mL/min/1.73m (GRAFT and PATIENT), PELD >25 points (GRAFT), recipient age <24 months (GRAFT), and time from onset jaundice to encephalopathy <7 days (PATIENT). While overall 5- and 10-year survival was 73% and 72% (GRAFT) and 77% and 73% (PATIENT), these were significantly worse when a combination of multivariate risk-factors were present. This data from a large, single-center experience demonstrates that LT is the treatment of choice for FHF and results in durable survival. Analysis revealed 4 novel outcome predictors. Young children with rapid onset acute liver failure are a high-risk subpopulation. Unique to this study, cCrCl and PELD accurately predicted the end-points. This analysis identifies patient subpopulations requiring early aggressive intervention with LT.

Is It Right to Promote Living Donor Liver Transplantation for Fulminant Hepatic Failure in Pediatric Recipients?

Good clinical results are currently achieved in elective pediatric liver transplantation (LT) with living-related donors. However, the question whether such therapeutic approach may also be promoted in case of fulminant hepatic failure (FHF) remains a matter of debate. This work briefly reviews the ethical background and overall medical results of living-related donation in pediatric LT. When considering FHF, success is essentially conditioned by the availability of a suitable organ donor before the onset of irreversible brain damage and death of the transplant candidate on the waiting list. Accordingly, living donor LT provides several advantages for patients with FHF, including the short waiting time and the access to a transplant with reduced ischemic injury and optimal graft quality; however, living donation is also characterized by several drawbacks to be carefully considered, particularly the possibility of coercion to the recipient's family as well as the operative risks of the emergency donor hepatectomy. The ethical soundness of living parental donor LT for FHF is discussed, with emphasis to the type of medical context, with or without access to an efficient emergency postmortem organ sharing system.

P0264 RISK FACTORS PREDICTING MORTALITY IN FULMINANT HEPATIC FAILURE IN CHILDREN ??? 17 YEARS RETROSPECTIVE ANALYSIS

Introduction: Spontaneous recovery of fulminant hepatic failure (FHF) remains unpredictable, especially in children. The successful use of orthotopic liver transplantation in FHF has created a need for early prognostic indicators to select the patients most likely to benefit at a time when liver transplantation is still feasible. Methods: We retrospectively reviewed the medical records of all 38 pediatric patients under 18 years old presenting with FHF who were seen and admitted from January 1986 to December 2002 to Children’s Hospital of Cheng-Gung Medical Center in Kaohsiung, Taiwan. The patients were subdivided into two groups by whether they later died or not and were further analyzed by comparing their demographic data, past or personal history, biochemical parameters at admission and the initial time when encephalopathy occurred, clinical manifestations, ultrasonographic findings, and hospital course to access the predicting factors for mortality in FHF children. Statistical tools used to compare variables between groups were Students t-test and chi-square test. Values were expressed as mean(??′SD) and P<0.05 was considered significant. Results: Mean age of the 38 patients was 4.22(±5.49) years old (range: 5 days to 17 years old). Males are more predominant than females (24 v.s. 14). Viral hepatitis revealed the commonest etiology where viral agent(s) other than hepatitis A to D corresponded the most common (23.1%). The mortality rate was 55.3%(21 of 38 patients dead). Non-survivors had significantly higher WBC (17460±10440/cm2 v.s. 11040±4460/cm2), lower GPT (934.22±1637.19 U/L v.s. 2994.60±2413.59 U/L), higher direct (10.18±6.47 mg/dl v.s. 5.19±3.69 mg/dl) and total bilirubin (25.17±14.89 mg/dl v.s. 9.89±7.41 mg/dl) at the day when encephalopathy occurred, longer time interval between the onset of jaundice and encephalopathy (11.75±8.20 days v.s. 1.50±0.71 days), and higher incidence of splenomegaly and transfusion than the survivors (P<0.05). Conclusion: Our study provides the clues for predicting the mortality of FHF in pediatric patients at the onset of encephalopathy that were rarely mentioned in children before. This prediction is valuable because it may be useful to reverse the unfavorable outcome with appropriate therapy, including intensive management and emergent orthotopic liver transplantation, in early stage.

Analyzing liver transplantation for fulminant hepatic failure at UCLA: a retrospective look at 18 years' experience.

Objective To analyze outcomes after liver transplantation (LT) in patients with fulminant hepatic failure (FHF) with emphasis on pretransplant variables that can potentially help predict posttransplant outcome. Summary background data FHF is a formidable clinical problem associated with a high mortality rate. While LT is the treatment of choice for irreversible FHF, few investigations have examined pretransplant variables that can potentially predict outcome after LT. Methods A retrospective review was undertaken of all patients undergoing LT for FHF at a single transplant center. The median follow-up was 41 months. Thirty-five variables were analyzed by univariate and multivariate analysis to determine their impact on patient and graft survival. Results Two hundred four patients (60% female, median age 20.2 years) required urgent LT for FHF. Before LT, the majority of patients were comatose (76%), on hemodialysis (16%), and bound for intensive care. The 1- and 5-year survival rates were 73% and 67% (patient) and 63% and 57% (graft). The primary cause of patient death was sepsis, and the primary cause of graft failure was primary graft nonfunction. Univariate analysis of pre-LT variables revealed that 19 variables predicted survival. From these results, multivariate analysis determined that the serum creatinine was the single most important prognosticator of patient survival. Conclusions This study, representing one of the largest published series on LT for FHF, demonstrates a long-term survival of nearly 70% and develops a clinically applicable and readily measurable set of pretransplant factors that determine posttransplant outcome. (Ann Surg 2003;237:666–676.)

Liver transplantation for fulminant hepatic failure: experience with more than 200 patients over a 17-year period.

To analyze outcomes after liver transplantation (LT) in patients with fulminant hepatic failure (FHF) with emphasis on pretransplant variables that can potentially help predict posttransplant outcome. FHF is a formidable clinical problem associated with a high mortality rate. While LT is the treatment of choice for irreversible FHF, few investigations have examined pretransplant variables that can potentially predict outcome after LT. A retrospective review was undertaken of all patients undergoing LT for FHF at a single transplant center. The median follow-up was 41 months. Thirty-five variables were analyzed by univariate and multivariate analysis to determine their impact on patient and graft survival. Two hundred four patients (60% female, median age 20.2 years) required urgent LT for FHF. Before LT, the majority of patients were comatose (76%), on hemodialysis (16%), and ICU-bound. The 1- and 5-year survival rates were 73% and 67% (patient) and 63% and 57% (graft). The primary cause of patient death was sepsis, and the primary cause of graft failure was primary graft nonfunction. Univariate analysis of pre-LT variables revealed that 19 variables predicted survival. From these results, multivariate analysis determined that the serum creatinine was the single most important prognosticator of patient survival. This study, representing one of the largest published series on LT for FHF, demonstrates a long-term survival of nearly 70% and develops a clinically applicable and readily measurable set of pretransplant factors that determine posttransplant outcome.

Liver Transplantation for Fulminant Hepatic Failure

Fulminant hepatic failure (FHF) is the clinical syndrome associated with acute massive necrosis of the liver that has been functioning normally before the onset of illness. It is characterized by increasing jaundice, decrease in the size of the liver, fetor hepaticus, coagulopathy, renal failure, hepatic encephalopathy, and eventual death. The mortality rate for FHF when associated with grade IV coma is 80 to 95%.1,2 The symptoms of hepatic failure (especially encephalopathy) develop within eight weeks from the onset of illness. Various modalities of medical treatment have been applied for FHF, but none of these has had a significant impact on the lethal prognosis.3–5 With the significant improvement in the results of liver transplantation over the past several years,6,7 liver replacement has become a practical therapeutic option for advanced FHF.8,9 We report here our experience with liver transplantation for FHF in 42 patients under the cyclosporine (CsA)/steroid immunosuppressive therapy.