Cardiovascular diseases after liver transplantation—a still emerging and unsolved problem!

Abstract

The outcome of adult liver transplantation (LT) recipients has improved incrementally over the last 4 decades with patient survival rates of approximately 90% at 1 year and 70%-80% at 5 to 10 years. The greatest progress has been mainly achieved in the early postoperative period because of improved selection criteria, advances in surgical techniques, and improvements in immunosuppressive and anti-infective drug therapies. The survival rates beyond 1 year, however, have remained relatively stagnant during the same time period. This fact as well as the growing number of long-term survivors has increased the importance of understanding the underlying mechanisms and risk factors for intermediate and late post-LT complications and death attributed to medical complications. Beside de novo malignancies, cardiovascular diseases (CVDs) have emerged as one the leading causes of non-graftrelated morbidity and mortality in LT recipients, accounting for 12%-16% of deaths. 1Several studies have shown that LT recipients have a significantly increased risk of cardiovascular (CV) events and deaths compared to an age-and sexmatched general population. This elevated CVD rate ranges from 9% at 5 years to up to 25% at 10 years. 2The high prevalence of metabolic syndrome (MS) and its clinical features, in particular insulin-resistant (type 2) diabetes, obesity (body mass index >30 kg/ m 2 ), dyslipidemia, and arterial hypertension, either alone or in combination, are the main contributors to the high risk of CVD in the post-LT period. It has been shown that patients with post-LT MS are approximately 4 times more likely to have a CV event than recipients without MS. In addition, recent studies have reported a significantly higher post-LT prevalence of MS ranging from 40% to 58% at 1 year compared to the general population. 3,4 Interestingly, the higher incidence of MS in LT recipients is not only seen in patients transplanted for nonalcoholic fatty liver disease (NAFLD) but also in patients transplanted for other indications.NAFLD, the hepatic manifestation of MS, is the leading cause of abnormal liver function tests in the Western world. Fatty liver disease leads to a spectrum of liver diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), fibrosis, and ultimately liver cirrhosis. End-stage liver disease secondary to NASH cirrhosis has become the second most common cause for LT and presumably will be the leading indication in the next decade. This is of further importance as current studies have shown that CVDs are especially overrepresented in patients with NASH-related liver disease, 5 independent of common underlying risk factors, such as MS and diabetes. 6 Several studies have determined the cumulative risk of CVD after LT. Independent predictive factors of CVD are older age at transplantation, male sex, preexisting cardiac disease, and components of the MS. [7][8][9]

Hospitalizations for Cardiovascular Disease After Liver Transplantation in the United States†

“…Numerous studies have demonstrated significant CV morbidity and mortality after liver transplantation . However, these outcomes vary across reports.…”

Metabolic Disorders in Liver Transplant Recipients: The State of the Art

“…The prevalence of MetS has increased over the years, both in the general adult population [82] and in specific subpopulations, such as patients undergoing LT [83]. Approximately half of the patients undergoing LT develop MetS within 3 years post LT [83], and the mortality rate in post-LT patients with MetS is four times higher than in those without MetS [84]. The development of MetS in these patients is attributed to factors such as pre-LT weight, age, the presence of diabetes, and triglyceride levels.…”