John C Martin Foundation.

No abstract

Cardiac and cerebral vascular diseases are leading causes of morbidity and death in solid organ transplant recipients. Immunosuppressant drugs are associated with dyslipidemia, hypertension, and hyperglycemia, which along with obesity are the main features of metabolic syndrome. In the nontransplant population, metabolic syndrome is associated with increased risk for major vascular complications. We postulated that metabolic syndrome is common post-liver transplantation and plays a significant role leading to cardiac and cerebrovascular events. Our Multi-Organ Transplant Program database was reviewed for all liver transplant recipients between January 1998 and June 2004 with follow-up until December 2005. We adapted the 2001 National Cholesterol Education Program-Adult Treatment Panel III Guidelines to define posttransplantation metabolic syndrome (PTMS) as the presence at least 3 of the following: 1) obesity (body mass index Ͼ30 kg/m 2 ); 2) serum triglyceride level Ն1.7 mmol/L; 3) high density lipoprotein level Ͻ1 mmol/L in men and Ͻ1.3 mmol/L in women; 4) hypertension; and 5) fasting plasma glucose Ն5.6 mmol/L. A total of 118 patients were included. Among them, 69 patients (58%) had PTMS. The mean (Ϯ standard deviation) time from transplant was 59 Ϯ 21 months (no significant difference in patients with or without metabolic syndrome). Overall, patients with metabolic syndrome had a significantly higher average age, posttransplantation body mass index, fasting glucose, high-density lipoprotein levels, and serum triglycerides. There was no difference in creatinine, hemoglobin, or prednisone average dose between the 2 groups. There were 25 major vascular events affecting 21% of patients. There were significantly more vascular events in patients with metabolic syndrome posttransplantation than in those without (30% vs. 8%; P ϭ 0.003) during the study period. In conclusion, the prevalence of metabolic syndrome post-liver transplant is significantly higher than that estimated in the general population. Metabolic syndrome appears to be associated with an increased risk of major vascular events in our liver transplant population.

Liver transplantation is the only effective therapeutic option for patients with end-stage liver disease due to primary sclerosing cholangitis (PSC). In this study, we analyzed a single center's experience with 150 consecutive PSC patients who received 174 liver allografts. Mean follow-up was 55 months. Actuarial patient survival at 1, 2, 5, and 10 years was 93.7%, 92.2%, 86.4%, and 69.8%, respectively, whereas graft survival was 83.4%, 83.4%, 79.0%, and 60. 5%, respectively. The main indication for retransplantation was hepatic artery thrombosis, and the major cause of death was severe infection. Patients with PSC had a higher incidence of acute cellular and chronic ductopenic rejection compared to a non-PSC control group. Chronic ductopenic rejection adversely affected patient and graft survival. Biliary strictures, both anastomotic and nonanastomotic, were frequent and occurred in 16.2% and 27.2% of patients, respectively. The incidence of recurrent PSC was 20%. A negative impact on patient survival was not seen in patients with either postoperative biliary strictures or recurrence of PSC. Six patients (4%) had cholangiocarcinoma and 1 patient died related to recurrence of malignant disease. Seventy-eight percent of PSC patients had associated inflammatory bowel disease, most commonly chronic ulcerative colitis, which did not adversely impact patient outcome posttransplantation. Nine patients required proctocolectomy after liver transplantation; 5 because of intractable symptoms related to inflammatory bowel disease and 4 due to the development of colorectal carcinoma/high-grade dysplasia. Our data show that liver transplantation provides excellent long-term patient and graft survival for patients with end-stage PSC.

Recurrence of primary sclerosing cholangitis (PSC) following liver transplantation has been suggested; however, it has not been fully defined because of numerous complicating factors and the lack of diagnostic criteria. In the present study, we investigated the recurrence of PSC by developing strict criteria and applying them to a large cohort of PSC patients who underwent liver transplantation. Between March 1985 and June 1996, 150 PSC patients underwent liver transplantation at the Mayo Clinic; mean follow up was 55 months. The incidence of nonanastomotic biliary strictures and hepatic histologic findings suggestive of PSC were compared between patients transplanted for PSC and a non-PSC transplant control group. Our definition of recurrent PSC was based on characteristic cholangiographic and histologic findings that occur in nontransplant PSC patients. By using strict criteria, 30 patients with other known causes of posttransplant nonanastomotic biliary strictures were excluded leaving 120 patients for analysis of recurrence of PSC. We found evidence of PSC recurrence after liver transplantation in 24 patients (20%). Of these, 22 out of 24 patients showed characteristic features of PSC on cholangiography and 11 out of 24 had compatible hepatic histologic abnormalities with a mean time to diagnosis of 360 and 1,350 days, respectively. Both cholangiographic and hepatic histologic findings suggestive of PSC recurrence were seen in nine patients. The higher incidence and later onset of nonanastomotic biliary strictures in patients with PSC compared with a non-PSC control group is supportive of the fact that PSC does recur following liver transplantation. We were unable to identify specific clinical risk factors for recurrent PSC, and the overall patient and graft survival in patients with recurrent PSC was similar to those without evidence of recurrence. Our observations provide convincing evidence that PSC frequently recurs in the hepatic allograft using strict inclusion and exclusion criteria. (HEPATOLOGY