Obesity, hyperlipidemia, and metabolic syndrome.
ABSTRACT 1. Obesity is increasingly common among liver transplantation (LT) recipients and donors. Outcomes following LT for selected patients with class I-III obesity are similar to those for nonobese recipients. In patients who are otherwise satisfactory candidates for LT, a high body mass index, as long as it does not present a technical barrier, should not be considered to be an absolute contraindication to LT. 2. The most common causes of death beyond the first year of LT are, in descending order of frequency, graft failure (especially secondary to hepatitis C virus recurrence), malignancy, cardiovascular disease, infections, and renal failure. Metabolic syndrome is an important risk factor for each of these etiologies of posttransplant death. Posttransplant diabetes, posttransplant hypertension, and an original diagnosis of cryptogenic cirrhosis, which is commonly associated with metabolic syndrome, are all associated with an increased risk of post-LT mortality. Features of metabolic syndrome should be screened for and treated in LT recipients. 3. Because of the physiological mechanism of post-LT hypertension, which includes renal arteriolar constriction secondary to calcineurin inhibition, calcium channel blocking agents are a good pharmacological treatment modality and have been shown to be effective in renal protection in randomized controlled trials of posttransplant hypertension. 4. It is rare for dietary changes and weight reduction to result in normalization of the lipid profile. Statins should thus be initiated early in the course of management of post-LT dyslipidemia. Forty milligrams of simvastatin per day, 40 mg of atorvastatin per day, and 20 mg of pravastatin per day are reasonable starting doses for post-LT hypercholesterolemia. It is important to remember that the effects of statin therapy are additive to those of a controlled diet (eg, a Mediterranean diet rich in omega-3 fatty acids, fruits, vegetables, and dietary fiber). 5. Nonalcoholic steatohepatitis, an increasingly common etiology of cirrhosis and liver failure, recurs commonly after LT and may also arise de novo. Treatment should be directed at managing obesity and complications of metabolic syndrome. Optimal immunosuppression in patients with nonalcoholic steatohepatitis is still evolving but should include steroid minimization.
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ABSTRACT: The European Liver Transplant Registry (ELTR) currently allows for the analysis of 44,286 liver transplantations (LTs) performed on 39,196 patients in a 13-year period. After an exponential increase, the number of LTs is plateauing due to a lack of organs. To cope with this, alternatives to cadaveric LT, such as split LT, domino LT, or living-related LT (LRLT) are being used increasingly. They now account for 11% of all procedures. One of the most important findings in the evolution of LT is the considerable improvement of results along time with, for the mean time, a one-year survival of 83%, all indications confounded. The improvement is particularly significant for cancers. This improvement is mainly represented by hepatocellular carcinoma, with a gain of 17% for 5-year survival rate from 1990 to 2000. Increasingly, older donors are used to augment the donor pool and older recipients are transplanted due to improved results and a better selection of patients. More than two thirds of deaths and three quarters of retransplantations occurred within the first year of transplantation. Retransplantation is associated with much less optimal results than first LT. One of the prominent features of recent years is the development of LRLT. LRLT is now performed by almost half of the European centers. As with split LT or domino LT, LRLT aims to provide more patients to be transplanted. Special attention is paid to reducing the risk for the donor, which is now estimated to be 0.5% mortality and 21% postoperative morbidity.Liver Transplantation 01/2004; 9(12):1231-43. · 3.94 Impact Factor
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ABSTRACT: Studies assessing morbidity and mortality in obese patients undergoing orthotopic liver transplantation (OLT) have produced conflicting results, mainly because of the small sample size. The objective of our study was to determine graft and patient survival in obese adults receiving OLT in the U.S. between 1988 through 1996 using the United Network for Organ Sharing (UNOS) database. Among the 23,675 transplantations performed during the 9-year study period, 18,172 (75%) patients fulfilled the inclusion criteria. Of these, 8,382 (46%) were nonobese (body mass index [BMI] < 25 kg/m(2)), 5,913 (33%) were overweight (BMI, 25.1-30 kg/m(2)), 2,611 (14%) were obese (BMI, 30.1-35 kg/m(2)), 911 (5%) were severely obese (BMI, 35.1-40 kg/m(2)), and 355 (2%) were morbidly obese (BMI, 40.1-50 kg/m(2)). The outcome measures assessed were immediate (30-day), 1-, 2-, and 5-year patient survival. Obese groups had a higher proportion of women, a greater prevalence of cryptogenic cirrhosis (P <.05) and diabetes (P <.05), and a higher serum creatinine. Primary graft nonfunction, and immediate, 1-year, and 2-year mortality were significantly higher in the morbidly obese group (P <.05). Five-year mortality was significantly higher both in the severely and morbidly obese subjects (P <.05), mostly as a result of adverse cardiovascular events. Kaplan-Meier survival was significantly lower in morbidly obese patients, and morbid obesity was an independent predictor of mortality. Obesity is associated with a significant increase in long-term mortality, mostly as a result of cardiovascular events. Weight loss should be recommended for all patients awaiting a liver transplantation, especially if their BMI is more than 35 kg/m(2).Hepatology 01/2002; 35(1):105-9. · 12.00 Impact Factor
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ABSTRACT: Many subjects with cryptogenic cirrhosis have underlying nonalcoholic steatohepatitis (NASH). The natural history of NASH-related cryptogenic cirrhosis after orthotopic liver transplantation (OLT) is not well defined. A primarily retrospective study of patients with the clinical histological phenotype of NASH-related cirrhosis undergoing OLT was performed. Data were compared with 2 sets of age- and weight-matched controls with (1) primary biliary cirrhosis or primary sclerosing cholangitis or (2) alcoholic liver disease. After OLT, all patients were managed by a standard immunosuppressive protocol. Liver biopsies were performed at 6 and 12 months after OLT and at 1- to 2-year intervals thereafter, as well as when liver enzyme levels were elevated enough to warrant diagnostic biopsy. Twenty-seven subjects with cryptogenic cirrhosis and a clinical histological phenotype of NASH and 3 patients with a long-standing diagnosis of NASH before OLT were included. The 30-day perioperative mortality was 1 in 30 patients. During a median follow-up of 3.5 +/- 2.7 years, 2 additional patients died of sepsis. There was a time-dependent increase in the risk for allograft steatosis that approached 100% by 5 years compared with only an approximately 25% incidence of steatosis in the control groups (P <.009, log-rank test). On multivariate analysis, only the cumulative steroid dose correlated with time to development of allograft steatosis. Three patients developed histological progression from hepatic steatosis to steatohepatitis. Of these, 1 patient developed progressive fibrosis. Four patients experienced at least 1 episode of acute cellular rejection; however, no patient developed chronic rejection or graft failure. In conclusion, nonalcoholic fatty liver disease occurs frequently after OLT in patients with the phenotype of NASH-related cirrhosis. Despite the frequent histological recurrence of disease, clinical outcomes are similar to those of other groups of patients undergoing OLT.Liver Transplantation 04/2001; 7(4):363-73. · 3.94 Impact Factor