Liver Transplantation For Metabolic Disease Research Articles

Living Donor-Initiated Domino Split-Liver Transplantation in Pediatric Setup: A Case Report With Literature Review

In patients undergoing liver transplantation for metabolic diseases, removing the patient's liver for transplantation to another recipient is called "domino liver transplantation." The extracted liver can be divided and transplanted into 2 recipients, which is called domino split-liver transplantation in the literature. However, in our study, the domino liver was obtained from a pediatric patient. A patient with maple syrup urine disease (MSUD) underwent a living donor liver transplant, and the explanted liver was divided in situ into right and left lobes and transplanted to 2 separate patients. Demographic data, surgical techniques, postoperative period, and patient follow-ups were evaluated. The father's left lobe liver graft was transplanted into a 12-year-old boy with MSUD. The removed liver was divided in situ into right and left lobes. The left lobe was transplanted to a 14-year-old male patient, whereas the right lobe was transplanted to a 67-year-old male patient. The donor and the first recipient were discharged on postoperative days 5 and 22. The second pediatric patient who underwent domino split-left lobe transplantation was discharged on postoperative day 23. The adult patient who underwent domino split-right lobe transplantation died on postoperative day 12 owing to massive esophageal variceal bleeding. Patients who underwent liver transplantation due to MSUD are among the best donor choices for domino liver transplantation. If the extracted liver has a sufficient volume and anatomic features for a split, it can be used in "selected cases."

Liver transplant for inherited metabolic disease among siblings.

Liver transplantation is a successful option for inherited metabolic disease yet little is published on the outcome among siblings. We report outcomes of siblings who have undergone liver transplantation for metabolic disease in a single program. Seventy-one siblings (35 males) from 33 individual families underwent liver transplantation since 1982. Outcomes were compared over three consecutive eras. Twenty-eight families had two siblings, four had three siblings, and one had four siblings. In half of families where dates of listing were known, siblings were listed simultaneously. Mean (SD) age at listing for the oldest and second sibling was 13.2 (7.1) and 9.8 (5.7) years, respectively (p<.01). In 18/33 families, the oldest sibling underwent transplantation first. Mean (SD) age at transplant fell from the oldest to second sibling from 12.9 (7.2) to 9.5 (6.3) years, respectively (p<.001). Ten-year patient survival was 83.5% which improved over the eras: era 1 (1982-1994) 65.0%, era 2 (1995-2007) 87.5%, and era 3 (2008-2019) 93.8%: p<.03. Sex, age at transplant, order of transplant, and presence of structural liver disease did not significantly impact survival. When siblings undergo liver transplant for inherited metabolic disease, later siblings are listed and transplanted at a significantly younger age.

Evolving Trends in Liver Transplant for Metabolic Liver Disease in the United States.

Indications for liver transplantation (LT) in metabolic disease are evolving. We reviewed the US experience with primary LT for metabolic disease in the Scientific Registry for Transplant Recipients (October 1987 to June 2017) to determine the following: temporal changes in indications, longterm outcomes, and factors predicting survival. Patients were grouped by the presence of structural liver disease (SLD) and whether the defect was confined to the liver. There were 5996 patients who underwent LT for metabolic disease, 2354 (39.3%) being children. LT for metabolic disease increased in children but not in adults. Children experienced a 6-fold increase in LT for metabolic disease without SLD. Indications for LT remained stable in adults. Living donor liver transplantation increased between era 1 and era 3 from 5.6% to 7.6% in children and 0% to 4.5% in adults. Patient and graft survival improved with time. The latest 5-year patient survival rates were 94.5% and 81.5% in children and adults, respectively. Outcomes were worse in adults and in those with extrahepatic disease (P<0.01), whereas SLD did not affect outcomes. Survival improved with younger age at LT until age<2 years. On multivariate analysis, diagnostic category, inpatient status, age at LT, and transplant era significantly predicted outcomes in all ages with male sex predicting survival in childhood only. Children without structural disease were less likely to die awaiting LT and had improved post-LT survival compared with children with chronic liver disease. In conclusion, LT for metabolic disease is increasingly used for phenotypic correction in children; extrahepatic manifestations significantly impact survival at all ages; where indicated, transplantation should not be unnecessarily delayed; and the development of new allocation models may be required.

PS-048 - 30 years of liver transplantation for metabolic disease in the United States

PS-048 - 30 years of liver transplantation for metabolic disease in the United States

Liver transplantation in metabolic diseases: A single center experience

Liver transplantation in metabolic diseases: A single center experience

Recent advances in liver transplantation for metabolic disease.

The indications and outcomes of liver transplantation for metabolic disease have been reviewed recently and this short review concentrates on recent developments and advances. Recently recognized metabolic causes of acute liver failure are reviewed and their implications for transplantation discussed. Newly described indications for liver transplantation in systemic metabolic diseases are described and an update is given on the role of auxiliary and domino liver transplantation.

Liver transplantation in metabolic diseases: Clinical data in Rome

Liver transplantation in metabolic diseases: Clinical data in Rome

Liver transplantation and cell therapies for inborn errors of metabolism

Liver transplantation is now very successful with >85% long term survival into adult life. When considering the impact of liver transplantation for metabolic disease two independent factors need to be considered; whether or not the defect causes liver disease and whether or not it is confined to the liver. When considering transplantation many factors need to be considered including the local success of transplantation, the impact of the metabolic disease on the patient and family and the potential for future therapeutic developments. Where transplantation is undertaken for a liver based defect there is a lifelong complete correction of the defect. Where there is a residual extrahepatic defect this will have an impact on the outcome of liver transplantation and the severity of this defect must be considered as part of the transplant assessment process. Access to a multi-disciplinary team with expertise in metabolic disease, liver disease and other relevant organ based specialists is crucial. Most children will receive transplantation from cadaveric donor but living related transplantation from a heterozygote parent is usually safe and effective. Auxiliary liver transplantation has a small but useful role where partial correction of the defect is helpful and there is a future prospect of gene therapy. The first-generation of hepatocyte transplants have shown proof of principle but to date have had a rather modest and temporary metabolic effect. Stem cells may have the potential to produce a more sustained and significant metabolic correction, but must be shown to be effective in controlled trials.

Liver transplantation for metabolic liver diseases in adults: indications and outcome

Orthotopic liver transplantation is the preferred treatment for many patients with complications of end-stage liver disease. For metabolic liver diseases liver transplantation does not only replace the diseased organ, but also can potentially correct the metabolic defect. Results of liver transplantation for metabolic diseases have been encouraging. In Wilson's disease liver transplantation is considered an effective treatment for the fulminant form and for end-stage liver disease, associated with an excellent long-term outcome. However, it is still a matter of controversy whether liver transplantation should be considered in Wilson's disease patients with severe neurological impairment. Liver transplantation for hereditary haemochromatosis is relatively uncommon and is associated with a decreased post-transplantation patient survival, most likely due to infections and cardiac complications. Reduction of iron overload prior to liver transplantation in patients with hereditary haemochromatosis might be associated with a better outcome.

Pediatric liver transplantation for metabolic diseases

Pediatric liver transplantation for metabolic diseases

Comparison of Outcome between Pediatric Liver Transplantation for Metabolic Diseases and Biliary Atresia.

773 Children with metabolic diseases (MD) have a defined enzyme deficiency in an often normal liver. MD are, after biliary atresia (BA) the second largest indication for liver transplantation (LT) in children. Cure of the disease and prevention of secondary damage to other organs or malignant degeneration in the liver are the main goals for treatment. Most MD patients have a normal liver function and no signs of portal hypertension. Furthermore, pretransplant abdominal surgery in MD patients is uncommon. The outcome of LT in patients with MD is considered to be superior to that for other indications. The aim of this study was to compare the outcome of LT in terms of patient survival, graft survival, and morbidity in MD and BA patients. From November 1982 to June 1997 24 children were transplanted for MD and 52 for BA. The mean (SD) Child-Pugh score in MD patients was 8.3 (3.2) and 9.8 (2.1) in BA patients (p<0.05). All but two BA patients (96%) had previous abdominal surgery compared to only five (24%) of the MD patients (p<0.001). Median follow-up in the MD patients was 3.5 year (range 1-9.3) and 4.2 year (range 0.3-14.1) in BA patients. One and five year patient survival in the MD patients was 96% and 84% compared to 84% and 70% for BA patients (p=ns). One and five year graft survival in the MD patients was 75% and 58% compared to 75% and 64% in BA patients (p=ns). During follow up three patients (13%) in the MD group died compared to 15 (29%) in the BA group (p=ns). The percentage of patients who experienced postoperative bleeding, gastrointestinal, biliary, vascular, infectious, and neurological complications or rejections was not different between both groups. Furthermore, there was no difference observed in ICU stay, days on the ventilator, complication rate, and intervention rate. Seven (29%) children of the MD group were retransplanted compared to 11 (21%) of the BA group (p=ns). Conclusion: Despite their better pretransplant condition the outcome after LT for MD is not different from that after LT for BA.

ADULT LIVER TRANSPLANTATION FOR METABOLIC LIVER DISEASE

Liver replacement provides an effective method of replacing a failing liver, and corrects the underlying defect in many metabolic conditions. Results of liver transplantation for metabolic diseases have been encouraging, with the exception of hereditary hemochromatosis, in which infectious and for which cardiac complications appear to increase posttransplant mortality. An improved understanding of the underlying genetic and molecular defect will lead to advances in medical therapy and perhaps will decrease the need for liver replacement. The prospects of gene therapy are being pursued for many metabolic disorders, however until this research leads to direct clinical application, liver transplantation remains the only effective option for many patients with metabolic liver disease.

LIVER TRANSPLANTATION FOR HEMOCHROMATOSIS, WILSON'S DISEASE, AND OTHER METABOLIC DISORDERS

Liver transplantation provides an effective means for replacing a failing liver, in addition to correcting the underlying abnormality in many metabolic disorders. Results of liver transplantation for metabolic diseases have been generally encouraging, with the exception of hereditary hemochromatosis, in which infectious and cardiac complications appear to increase post-transplant mortality. Better pretransplant diagnosis of hemochromatosis, utilizing the recently identified putative gene, may help reduce post-transplant complications. In metabolic diseases, improved understanding of the underlying genetic and molecular defects will lead to advances in medical therapy and perhaps a decreased need for liver transplantation. NTBC therapy for hereditary tyrosinemia and purified glucocerebroside therapy for Gaucher disease are two such examples. The prospects of gene therapy are being actively pursued for many metabolic diseases, such as CF, hemophilia, and familial hypercholesterolemia. Until such investigation leads directly to clinical practice, however, liver transplantation remains an effective option for therapy for a wide range of metabolic diseases.

Auxiliary liver transplantation for metabolic diseases

Auxiliary liver transplantation for metabolic diseases

Liver Transplantation for Metabolic Disease of the Liver

Hepatic transplantation for metabolic or genetic diseases of the liver produces a definite cure of the liver disease and also effectively cures the underlying metabolic abnormalities of the genetic disease in question. Liver transplantation is highly likely to become the current treatment of choice for a wide variety of metabolic disorders based predominantly in the liver. This is true not only for those that produce grossly evident hepatic disease with cirrhosis, but also for those that are free of obvious hepatocellular injury but are based either predominantly or exclusively within the liver.