ObjectiveTo determine the long-term results of liver transplantation for hepatocellular carcinoma (HCC) measuring 5 cm or larger treated in a multimodality adjuvant protocol. Summary Background DataTransplant has been established as a viable treatment of HCC measuring less than 5 cm, but the results for larger tumors have been disappointing. Several studies have shown promising preliminary results when combining transplant with preoperative transarterial chemoembolization and/or perioperative systemic chemotherapy in the treatment of advanced HCC that is not amenable to resection. However, follow-up in the studies has been limited and the number of patients has been small. MethodsBeginning in October 1991, all patients with unresectable HCC measuring 5 cm or larger, as measured by computed tomography, were considered for enrollment in the authors' multimodality protocol. Entry criteria required that all patients be free of extrahepatic disease based on computed tomography scans of the chest and abdomen and bone scan and have a patent main portal vein and major hepatic veins on duplex ultrasonography. Patients received subselective arterial chemoembolization with mitomycin C, doxorubicin, and cisplatin at the time of diagnosis, repeated as necessary based on tumor response. Patients received a single systemic intraoperative dose of doxorubicin (10 mg/m 2 ) before revascularization of the new liver and systemic doxorubicin (50 mg/m 2 ) every 3 weeks as tolerated, for a total of six cycles, beginning on the sixth postoperative week. ResultsEighty patients were enrolled; 37 were eventually excluded, due mainly to disease progression while on the waiting list, and 43 underwent liver transplant. Mean pathologic tumor diameter was 5.8 Ϯ 2.7 cm. Median follow-up of surviving transplanted patients was 55.1 Ϯ 24.9 months. There were two (4.7%) perioperative deaths. Median overall survival was significantly longer in transplanted patients (49.9 Ϯ 10.42 months) than in those who were excluded (6.83 Ϯ 1.34 months). Overall and recurrence-free survival rates in transplanted patients at 5 years were 44% and 48%, respectively. A tumor size larger than 7 cm and the presence of vascular invasion correlated significantly with recurrence. Recurrencefree survival at 5 years was significantly higher for the 32 patients with tumors measuring 5 to 7 cm (55%) than the 12 patients with tumors larger than 7 cm (34%). ConclusionsA significant proportion of patients with HCC measuring 5 cm or larger can achieve long-term survival after liver transplantation in the context of multimodal adjuvant therapy. Patients with tumors measuring 5 to 7 cm have significantly longer recurrence-free survival compared with those with larger tumors.

Liver transplantation is being performed with excellent 5-year survival. Significant comorbidities exist, however, which appear to be related to long-term immunosuppression.

Decompensated liver disease associated with chronic hepatitis C virus (HCV) infection is the most common indication for liver transplantation. It was shown previously that greater pretransplantation HCV titers are associated with relatively poor patient and graft survival. The tolerability and efficacy of antiviral therapy in patients with decompensated liver disease are not known. We conducted a pilot study to determine the likely tolerability and efficacy of pretransplantation antiviral therapy with interferon alfa-2b, with or without ribavirin. HCV RNApositive patients at or near the top of their respective waiting lists were randomly assigned to one of three treatment regimens until the time of liver transplantation: (1) group A, interferon alfa-2b, 1 ؋ 10 6 U/d; (2) group B, interferon alfa-2b, 3 ؋ 10 6 U three times weekly; or (3) group C, interferon alfa-2b, 1 ؋ 10 6 U/d, plus ribavirin, 400 mg twice daily. Less than half the patients screened met entry criteria, with thrombocytopenia and leukopenia the most common reasons for exclusion. Fifteen patients were administered antiviral therapy; three patients in group A and six patients each in groups B and C. Loss of detectable HCV RNA was seen in 33% of patients, whereas 55% had a decrease in viral titers on therapy. Twenty-three adverse events occurred, including 20 serious adverse events. Thrombocytopenia was the most common adverse event. Two infectious complications occurred; one of these had a fatal outcome. We conclude that although pretransplantation antiviral therapy may reduce HCV titers in a minority of patients who meet treatment initiation criteria, adverse events associated with therapy are frequent and often severe in patients with Child's class B and C cirrhosis. C hronic hepatitis C virus (HCV) infection is the most common indication for liver transplantation in the United States. 1 Although patients undergoing liver transplantation for HCV have been reported to have similar overall patient and graft survival to most other indications, 2-6 recurrence of HCV is a substantial source of morbidity, mortality, and graft loss. 2,4,7-10 To date, meaningful data regarding posttransplantation follow-up in HCV-infected recipients are only available for a mean of 3 to 5 years. [2][3][4][5][6] In the nontransplantation setting, it is estimated that the mean time from infection to the development of cirrhosis is 20 years. 11,12 In liver transplant recipients, the course of HCV-induced liver injury is accelerated, with HCV recurrence apparent histologically in approximately 50% of HCVinfected transplant recipients and HCV-associated allograft failure leading to death or graft loss in approximately 10% of transplant recipients by the fifth postoperative year. 2,3,7,10,[13][14][15][16][17] Greater pretransplantation levels of viremia have been associated with attenuated patient and allograft survival among HCV-infected liver transplant recipients. 7 The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Liver Transplant Database report...

ObjectiveTo summarize the evolution of a living donor liver transplant program and the authors' experience with 109 cases. Summary Background DataThe authors' institution began to offer living donor liver transplants to children in 1993 and to adults in 1998. MethodsDonors were healthy, ages 18 to 60 years, related or unrelated, and ABO-compatible (except in one case). Donor evaluation was thorough. Liver biopsy was performed for abnormal lipid profiles or a history of significant alcohol use, a body mass index more than 28, or suspected steatosis. Imaging studies included angiography, computed tomography, endoscopic retrograde cholangiopancreatography, and magnetic resonance imaging. Recipient evaluation and management were the same as for cadaveric transplant. ResultsAfter ABO screening, 136 potential donors were evaluated for 113 recipients; 23 donors withdrew for medical or personal reasons. Four donor surgeries were aborted; 109 transplants were performed. Fifty children (18 years or younger) received 47 left lateral segments and 3 left lobes; 59 adults received 50 right lobes and 9 left lobes. The average donor hospital stay was 6 days. Two donors each required one unit of banked blood. Right lobe donors had three bile leaks from the cut surface of the liver; all resolved. Another right lobe donor had prolonged hyperbilirubinemia. Three donors had small bowel obstructions; two required operation. All donors are alive and well. The most common indications for transplant were biliary atresia in children (56%) and hepatitis C in adults (40%); 35.6% of adults had hepatocellular carcinoma. Biliary reconstructions in all children and 44 adults were with a Roux-en-Y hepaticojejunostomy; 15 adults had duct-to-duct anastomoses. The incidence of major vascular complications was 12% in children and 11.8% in adult recipients. Children had three bile leaks (6%) and six (12%) biliary strictures. Adult patients had 14 (23.7%) bile leaks and 4 (6.8%) biliary strictures. Patient and graft survival rates were 87.6% and 81%, respectively, at 1 year and 75.1% and 69.6% at 5 years. In children, patient and graft survival rates were 89.9% and 85.8%, respectively, at 1 year and 80.9% and 78% at 5 years. In adults, patient and graft survival rates were 85.6% and 77%, respectively, at 1 year. ConclusionLiving donor liver transplantation has become an important option for our patients and has dramatically changed our approach to patients with liver failure. The donor surgery is safe and can be done with minimal complications. We expect that living donor liver transplants will represent more than 50% of our transplants within 3 years.The shortage of cadaveric organs for liver transplantation has limited our ability to provide this life-saving therapy.