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 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.     

Liver transplantation for metabolic liver disease in adulthood

The clinical presentation of metabolic liver disease is highly variable, covering acute liver failure, liver cirrhosis, hepatic cancer and various extrahepatic manifestations. Both natural course and prognosis after liver transplantation are substantially influenced by extrahepatic manifestations. In many types of metabolic liver disease, timely diagnosis allows for successful medical treatment. However, progressive liver failure and severe extrahepatic damage can be the indication for liver transplantation. In general, standard transplantation criteria also apply for metabolic liver disease. They have to be modified by disease-specific criteria, and extrahepatic damage may necessitate multiorgan transplantation. The overall prognosis after liver transplantation for metabolic liver disease is favorable. Furthermore, several metabolic defects are phenotypically cured by liver transplantation. Alternative treatments like hepatocyte transplantation or gene therapy are still in the experimental stage.     

Liver transplantation for metabolic liver diseases

Liver transplantation has become an accepted treatment for several metabolic liver diseases. With advances in organ transplantation and immunosuppressive strategies, survival rates following liver transplantation are generally excellent. When the primary metabolic defect is hepatic in origin, liver transplantation not only replaces the dysfunctional organ but also cures the underlying metabolic defect. For conditions in which the primary metabolic defect is extrahepatic, liver transplantation is usually performed for hepatic complications, although disease recurrence may occur. This article reviews common metabolic liver diseases treated with liver transplantation in the adult population.     

Adult live donor liver transplantation

The increasing awareness of liver diseases and their early detection have led to an increase in the number of transplant waiting list candidates over the past decade. This need has not been matched by the actual number of orthotopic liver transplantations performed. Live donor liver transplantation (LDLT) is an innovative surgical technique intended to expand the available organ donor pool. Although LDLT offers definite advantages to the recipient, it offers none to the donor except for the possibility of psychological well-being. Clinical research studies aimed at the prospective collection of data for donors and recipients need to be conducted.     

De novo and recurrence of metabolic dysfunction-associated fatty liver disease after liver transplantation

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new acronym adopted from the consensus of international experts. Given the increasing prevalence of MAFLD in pre-transplant settings, de novo and recurrent graft steatosis/MAFLD are common in post-transplant settings. The impact of graft steatosis on long-term outcomes is unclear. The current knowledge of incidence rate, risk factors, diagnosis, long-term outcomes, and management of graft steatosis (both de novo and recurrent) is discussed in this review.     

Orthotopic liver transplantation for alcoholic liver disease

Alcohol abuse is the most common cause of end-stage liver disease in the United States, but many transplant centers are unwilling to accept alcoholic patients because of their supposed potential for recidivism, poor compliance with the required immunosuppression regimen and resulting failure of the allograft. There is also concern that alcohol-induced injury in other organs will preclude a good result. From July 1, 1982, to April 30, 1988, 73 patients received orthotopic liver transplants at the University of Pittsburgh for end-stage alcoholic liver disease. Fifty-two (71%) of these were alive at 25 +/- 9 mo (mean +/- S.D.) after transplantation, when a phone survey of these patients, their wives/husbands, and their physicians was performed to evaluate their subsequent use of alcohol, current medical condition and employment. Data obtained were compared with those for nonalcoholic patients selected as transplant controls. The recidivism rate has been 11.5%, with most patients drinking only socially. Fifty-four percent of the survivors are employed, 21% classify themselves as homemakers and only 11 (21%) are unable to work. Twenty-one patients died after transplantation; the most frequent cause of death was sepsis (43%), and intraoperative death was the next most common cause (28.6%). These data demonstrate that alcoholic patients can be transplanted successfully and achieve good health not significantly different from that of individuals transplanted for other causes. Thus orthotopic liver transplantation is a therapeutic option that should be considered for individuals with end-stage alcoholic liver disease who desire such therapy.     

Liver transplantation for pediatric inherited metabolic liver diseases

Liver transplantation(LT) remains the gold standard treatment for end stage liver disease in the pediatric population. For liver based metabolic disorders(LBMDs),the decision for LT is predicated on a different set of paradigms. With improved outcomes post-transplantation, LT is no longer merely life saving, but has the potential to also significantly improve quality of life. This review summarizes the clinical presentation, medical treatment and indications for LT for some of the common LBMDs. We also provide a practical update on the dilemmas and controversies surrounding the indications for transplantation, surgical considerations and prognosis and long terms outcomes for pediatric LT in LBMDs. Important progress has been made in understanding these diseases in recent years and with that we outline some of the new therapies that have emerged.     

Liver transplantation in metabolic liver diseases

Abstract   Two types of metabolic disorders are treated with transplantation: those associated with severe liver damage, like alpha-1 antitrypsin deficiency, progressive familial cholestatic syndromes, tyrosinaemia, glycogen storage diseases, or cystic fibrosis; and those in which the liver is structurally normal, but is genetically unable to produce an essential protein, usually an enzyme, with consequent lethal systemic disease, like Crigler-Najjar syndrome, familial hypercholesterolaemia, propionic acidaemia, or urea cycle defects. The first group of diseases, among which the most common is alpha-1 antitrypsin deficiency, are treated by substitution of the whole liver with the donor liver, while the second group can be treated by auxiliary transplantation, to provide sufficient production of the deficient protein by the donor liver segment, while the native liver provides a safety net should the transplant fail and remains available for possible future gene therapy. In recent years, attempts have been made to treat these conditions by isolated human hepatocyte transplantation, with temporary success.     

Liver transplantation for alcoholic liver disease

Patients with end-stage alcoholic liver disease should be considered for liver transplantation. A careful pretransplant evaluation must be undertaken to assess for both medical and psychiatric factors that will continue to require attention following transplantation. Although most programs require at least 6 months of ethanol abstinence before consideration of liver transplantation, there is little evidence that this conclusively predicts a reduction in recidivism. Most programs continue to exclude those with alcoholic hepatitis. Postoperatively, attention to psychiatric issues, recidivism, compliance, and assessment for tumors, especially squamous cell carcinomas, should be undertaken.     

Liver transplantation for alcoholic liver disease

Alcoholism is a disease of remission and relapse. A lapse in abstinence tends to be viewed as a failure to commit to abstinence, and an acknowledged relapse may lead to the patient's removal from the liver transplant list; however, such a relapse may actually offer insight into alcoholism. Liver transplant physicians should consider recognizing lapses in abstinence as slips that indicate a need for treatment of alcoholism. Further research should address which alcoholic liver patients suffer relapses and how alcohol relapse affects the ability to maintain abstinence before or after transplantation.     

Liver transplantation for cholestatic liver disease

Opinion statement Liver transplantation is an effective form of therapy for patients with end-stage cholestatic disease that improves both survival and quality of life. Liver transplantation is very effective for the treatment of intractable pruritus but less effective for the treatment of lethargy. Survival rates are good (more than 70% at 5 years); these patients are at greater risk of developing acute and chronic rejection and are more likely to require long-term immunosuppression. Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) recur in the graft. Recurrent PSC may be difficult to differentiate from secondary sclerosing cholangitis, but it recurs in up to 60% of patients at 5 years and may reduce graft survival. PBC recurrence, noted in up to 40% of patients at 10 years, has little effect on graft survival with respect to cancers. Patients with PSC are at greater risk of both colonic cancer (which may be reduced by ursodeoxycholic acid) and cholangiocarcinoma. Diagnosis of cholangiocarcinoma before transplantation usually contraindicates transplantation. The main challenges facing liver transplantation are the need to expand the donor pool and the need to find immunosuppressive regimens with fewer long-term toxicities.     

Liver transplantation for alcoholic liver disease

Alcoholic liver disease(ALD) is the second commonest indication for liver transplantation after viral hepatitis in the United States and Europe.Controversies surround the indications and allocation of scarce and expensive resource for this so called self inflicted disease.Controversies stem from the apprehension that alcoholic recipients are likely to relapse and cause damage to the graft.There is a need to select those candidates with lower risk for relapse with the available predictive factors and scores....