Metabolic Syndrome Problematic After Liver Transplant

Metabolic Syndrome Problematic After Liver Transplant
By Crystal Phend, Senior Staff Writer, MedPage Today
Published: November 27, 2009
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner Earn CME/CE credit
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Metabolic syndrome is an "epidemic waiting to happen" among liver transplant recipients, largely as a result of their increasing likelihood of survival, a review shows.

Post-transplant metabolic syndrome prevalence was 43% to 58% after 12 to 18 months, compared with 24% in the general population, according to Arthur J. McCullough, MD, of the Cleveland Clinic, and colleagues.

The consequences also appeared more serious in liver transplant recipients, they reported online ahead of print in the December issue of Liver Transplantation.

After transplantation, patients were at a 3.07-fold (95% confidence interval 1.98 to 4.53) higher risk of cardiovascular and ischemic events than age- and sex-matched controls, according to one study consulted in the systematic review.

Transplant recipients who developed metabolic syndrome were at particular cardiovascular event risk compared with those who didn't (rate 30% versus 8%, P=0.003).

Although there is controversy over the impact of post-transplant metabolic syndrome on overall survival, the researchers noted that the same study showed 2.5 times (95% CI 1.52 to 4.05) higher relative risk of cardiovascular death in the transplant group.

There was also a significantly elevated risk of rejection and all types of infections after transplantation for those who developed metabolic syndrome.

Immunosuppressants appear to be largely to blame for the elevated risk of metabolic syndrome after liver transplantation, the investigators said.

Use of tacrolimus (Prograf)-based regimens instead of cyclosporine could help reduce metabolic syndrome risk after transplantation, as could use of lipid-lowering agents, optimal blood glucose control, and lifestyle measures, McCullough's group said.

Even before transplantation, patients should be carefully screened for diabetes, dyslipidemia, and obesity, they wrote, adding, "It is important to reiterate the importance of weight reduction before and after transplantation with a carefully constructed program including diet modification and exercise."

Dyslipidemia is a well recognized complication of liver transplantation and is also a component of the metabolic syndrome. With five-year transplant survival rates now over 70%, this problem is being increasingly recognized, the reviewers said.

In addition to overall higher metabolic syndrome rates after liver transplant, individual components of the syndrome appear more common as well. Prevalence rates at 18 months in one study were:

* 61% for diabetes after transplant compared with 13% before
* 46% for dyslipidemia, with 3% before
* 62% for hypertension, versus 10% before

Compared with general population or matched control groups, other studies have shown a 5.99 (95% CI 4.15 to 2.38) times higher prevalence of post-transplant diabetes, 3.07-fold (95% CI 2.35 to 3.93) higher prevalence of hypertension, and higher body mass index (P=0.04).

Insulin resistance, while nearly universal in patients with cirrhosis before transplantation, typically improves after transplantation significantly. But one study suggested that 41% of patients who have received a donor liver remain insulin resistant.

"It should be noted that any improvement in sensitivity post-transplant occurs despite the presence of immunosuppressive therapy, which may adversely affect insulin resistance," McCullough's group wrote.

"It is likely that this improved insulin sensitivity post-transplant is a result of an increase in peripheral glucose utilization and the correction of insulin resistance in the periphery," they added.

Differences noted between cyclosporine and tacrolimus-based regimens might have been, in part, due to the latter's steroid-sparing effect, the investigators said.

Predictors of post-transplant metabolic syndrome include higher age at transplant; rising BMI after transplant; preexisting diabetes; a history of smoking; certain immunosuppressant regimens, such as cyclosporine; and hepatitis C, alcohol, or cryptogenic cirrhosis as the indication for transplant.

The researchers provided no information on conflicts of interest.

Primary source: Liver Transplantation
Source reference:
Pagadala M, et al "Posttransplant metabolic syndrome: An epidemic waiting to happen" Liver Transpl 2009; 15: 1662-70.