Liver transplantation and surgery : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society最新文献

Hepatic allograft rejection has been divided into humoral (or hyperacute), acute (or cellular), and chronic (or ductopenic) forms. Humoral rejection is extremely uncommon in the liver and is not graded. Acute rejection will occur in approximately 50% of liver allografts, is more common in the first few weeks posttransplantation, and is defined by Snover's triad of portal hepatitis, endothelialitis (or endotheliitis), and lymphocytic cholangitis. This form of rejection is generally reversible, either spontaneously or with additional immunosuppressive therapy, and can be reliably graded using a system with categories of mild, moderate, and severe rejection, associated with 37%, 48%, and 75% unfavorable shortterm and 1%, 12%, and 14% unfavorable long-term outcomes, respectively. Chronic rejection is characterized histologically by progressive duct loss and a lipid-rich vasculopathy that can be difficult to diagnose in early phases. Chronic rejection typically occurs several months to a year posttransplantation, although exceptions exist.

Nonsurgical therapy provides some benefit to patients with advanced hepatocellular carcinoma, although surgical options, including transplantation, remain the only chance for cure. Careful patient selection is required; patients with small nodular tumors may be considered for PEI therapy, whereas patients with larger tumors may be considered for TACE. Regardless of the treatment modality, the likelihood of survival is usually directly associated with the degree of hepatic dysfunction. Randomized, controlled trials of these treatment modalities are limited in number and design; therefore, it is difficult to assess their true impact on patient survival and quality of life. Secondary chemoprophylaxis against recurrent disease with vitamin A analogues is a promising adjunctive measure to both surgical and nonsurgical treatments for hepatocellular carcinoma.

The advances made in surgical technique, postoperative care, and immunosuppression during the 1980s have permitted orthotopic liver transplantation (OLT) to evolve into an effective and widely accepted therapy for infants and children with end-stage liver disease. Biliary atresia, a progressive, obliterative disease of the bile ducts, is the most common indication for OLT in children, accounting for approximately 50% of cases. Metabolic liver disease (MLD) accounts for 20% to 25%; other common indications for OLT include fulminant hepatic failure (FHF) and forms of intrahepatic cholestasis. The principal problem associated with the increasing application of OLT is the burden placed on resources, particularly the availability of donor organs. The limited pool of size-matched donor organs has led to the application of a variety of alternatives to address the needs of the pediatric recipient; these include (1) reduced-size liver transplantation, (2) "split-liver" transplantation, and (3) use of living-related organ donors. In view of the impact on overall organ availability, the use of nontransplant options, including liver cell transplantation, especially for FHF and MLD, deserves broader application. Despite the success of transplantation, major challenges in childhood liver transplantation remain, including (1) improved preoperative management to ensure adequate growth, (2) more precise posttransplant management of immunosuppression to ensure graft viability and avoidance of lymphoproliferative disease, (3) earlier recognition of cytomegalovirus and Epstein-Barr virus infection, and (4) provision of services in a more cost-effective manner. The ultimate solution is to prevent liver disease through vaccination and research.

Liver transplantation is a highly effective treatment for patients with advanced primary biliary cirrhosis and primary sclerosing cholangitis. Transplantation is indicated when the patient's survival with transplantation is better than without or, earlier than this, if the patient's quality of life is intolerable from intractable fatigue or pruritus. Medical therapies for chronic cholestatic liver diseases are very limited. Ursodeoxycholic acid therapy in primary biliary cirrhosis reduces cholestasis and prolongs transplant-free survival; no other drugs are of proven efficacy in primary biliary cirrhosis, and none have any benefit on the disease progression of primary sclerosing cholangitis. Aggressive endoscopic therapy may produce symptomatic and biochemical improvement in primary sclerosing cholangitis but should be done without the expectation of retarding disease progression. Bilirubin is one of five criteria of the Child-Turcotte-Pugh score, which is necessary for the United Network for Organ Sharing listing for orthotopic liver transplantation. In addition, it is a major prognostic indicator in all the predictive models for primary biliary cirrhosis. Bilirubin reduction with ursodeoxycholic acid therapy in primary biliary cirrhosis appears to parallel disease severity, and prognostic models utilizing bilirubin retain their predictive power for survival even in treated patients. In summary, medical therapies for chronic cholestatic liver disease have very little effect on disease progression and, subsequently, on the timing or selection for transplantation. Liver transplantation is the only definitive therapy for primary biliary cirrhosis and primary sclerosing cholangitis.