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Cardiovascular (CV) diseases are recognized longterm causes of death after liver transplantation (LT). The objective of this multicenter study was to analyze the prevalence and the evolution of CV risk factors and CV morbidity and mortality in 1819 LT recipients along 5 years after LT. The influence of baseline variables on survival, morbidity, and mortality was studied. There was a continuous and significant increase of the prevalence of all the CV risk factors (except smoking) after LT. CV diseases were the fourth cause of mortality in the 5 years after LT, causing 12% of deaths during the follow-up. Most CV events (39%) occurred in the first year after LT. Preexisting CV risk factors such as age, pre-LT CV events, diabetes, metabolic syndrome, and hyperuricemia, and mycophenolate-free immunosuppressive therapy, increased post-LT CV morbidity and mortality. The development of new-onset CV risk factors after LT, such as dyslipidemia and obesity, independently affected late CV morbidity and mortality. Tacrolimus and steroids increased the risk of posttransplant diabetes, whereas cyclosporine increased the risk of arterial hypertension, dyslipidemia, and metabolic syndrome. In conclusion, CV complications and CV mortality are frequent in LT recipients. Preexisting CV risk factors, immunosuppressive drugs, but also the early new onset of obesity and dyslipidemia after LT play an important role on late CV complications. A strict metabolic control in the immediate post-LT period is advisable for improving CV risk of LT recipients. Liver Transplantation 23 498-509 2017 AASLD.

Chronic renal dysfunction is a frequent and severe complication in solid-organ transplant recipients. Calcineurin inhibitors (CNIs) are the main pathogenic factors of renal dysfunction. Switching from CNIs to nonnephrotoxic drugs, such as mammalian target of rapamycin inhibitors (everolimus and sirolimus), can improve renal function in these patients, but available data about the efficacy and safety of everolimus in liver transplant recipients are scarce. Twenty-one liver transplant recipients (19 males, mean age ϭ 60.6 Ϯ 7.8 years) with chronic renal dysfunction (creatinine Ն 1.5 mg/dL) were prospectively included. The basal creatinine values were 1.79 Ϯ 0.39 mg/dL (range ϭ 1.50-2.90 mg/dL). The basal creatinine clearance, evaluated with the Cockroft-Gault formula, was 54.64 Ϯ 12.47 mL/minute. Everolimus was initiated at a dosage of 0.75 mg twice daily, with target levels of 3 to 8 ng/mL. The withdrawal of CNIs was initiated after the target levels of everolimus were reached. Periodic controls of the weight, arterial pressure, liver function tests, serum creatinine, everolimus levels, proteinuria, creatinine clearance, and glomerular filtration rate at days 30, 90, 180, and 360 were made. Chronic renal dysfunction is a frequent and severe complication in solid-organ transplant recipients. Half of liver transplant patients present a variable grade of renal dysfunction, and in 8% to 28%, advanced renal failure is established. The prevalence of renal dysfunction in this population increases as the posttransplantation follow-up period lengthens. 1-5 A large study evaluating the data for 36,849 liver transplant recipients showed a 5-year accumulated incidence of chronic renal dysfunction [defined as a glomerular filtration rate (GFR) less than 29 mL/minute/m 2 ] of 18%. 6 The development of posttransplantation renal failure has a significant negative impact on the survival of liver transplant recipients.

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Serum TPS (cytokeratin-18) is elevated in patients with non-malignant liver diseases, particularly in those with prominent cytolysis. Further studies are needed to evaluate the use of TPS as a marker of liver disease.