Liver transplantation and obesity: Weighing the risks
The effect of obesity on graft and patient survival after liver transplantation has been a matter of debate for more than two decades. In the 1990s, large database studies suggested that patients who were morbidly obese — those with a body mass index (BMI) above 40 — had worse outcomes than did patients of normal weight. Based on this, many centers instituted strict BMI limits for liver transplant recipients.
Recent research has not supported those early findings. A 2015 meta-analysis in Liver International looked at 13 studies spanning a 13-year period and found no difference in mortality between obese patients and controls at last follow-up. There was also no observed difference in survival among subgroups with different BMI thresholds. Obese patients did, however, have worse survival compared with patients of normal weight who had similar causes of liver disease.
Another study, published in the American Journal of Transplantation in 2008, evaluated the effect of obesity on post-transplant outcomes using recipient data from a government database and Mayo Clinic. Patients were categorized according to pretransplant BMI, ranging from underweight (BMI less than 18) to Class III obese (BMI greater than 40).
Results showed that primary outcomes — patient and graft survival — were similar across all BMI categories. A 7 percent increased risk of mortality was seen for every 1 liter of fluid removed at transplant, but no risk specific to BMI.
"Survival in transplant recipients with a BMI greater than 40 or even 45 was no different from survival in patients who were less obese or normal weight," says study co-author Kymberly D. Watt, M.D., a liver transplantation specialist at Mayo Clinic's campus in Rochester, Minnesota.
Dr. Watt points out that the database studies of two decades ago failed to correct for fluid overload, which can increase weight and BMI calculations, and for other factors co-occurring with obesity, such as diabetes, heart disease and metabolic syndrome.
"These comorbidities likely have a greater effect on mortality than obesity alone, but they are all nested together in obese patients and ultimately are what affect outcomes. Studies that corrected for fluid overload and other risk cofactors found no difference in outcomes," she explains. "And although abdominal adipose tissue is associated with a higher risk of postoperative complications, it is not associated with increased mortality. Based on all the people who have gone through the work-up and are candidates for liver transplantation, obese patients have done just as well as nonobese patients."
Encouraging weight loss, preventing weight gain
Mayo Clinic does not have a set BMI cut off, opting instead to evaluate potential transplant recipients on a case-by-case basis, while also taking an aggressive approach to pretransplant weight loss. Although short- and medium-term graft and patient survival are comparable for obese and nonobese patients, risk factors associated with obesity and metabolic syndrome are known to increase perioperative morbidity and length of stay.
"A BMI of 35 is the goal in our obesity protocol," Dr. Watt says. "For patients with a BMI above 35, we have a very strict protocol of exercise and calorie restriction. We are very aggressive before transplant to maximize recovery afterward. Most of our patients lose weight because they are in a highly motivated environment with an extremely diligent dietitian team monitoring them closely. We want people to be in the best possible condition before undergoing transplant."
Of equal importance is preventing weight gain after transplantation, a common complication that occurs within the first six to 12 months. With few exceptions, patients who are overweight or obese before transplantation will continue to be so afterward, and as many as half of the normal-weight transplant recipients will become overweight or obese within three years. With increased weight comes metabolic syndrome, which is associated with cardiovascular disease and worse long-term outcomes.
A 2015 study published in Liver Transplantation retrospectively reviewed 455 recipients of liver transplants from 1999 to 2004 with an eight- to 12-year follow-up. In that study, obesity increased from close to 24 percent of recipients at four months to nearly 41 percent of recipients three years after liver transplant. Cardiovascular disease developed in 10, 20 and 30 percent of patients within one, five and eight years, respectively.
"Weight gain, diabetes, heart disease and metabolic syndrome are all intermeshed in liver transplant recipients," Dr. Watt says. "Our first goal is to help people lose weight before they get very sick and need transplant. If we can prevent liver disease from progressing, that is the ideal. If people do need to go to transplant, we want them to undergo surgery with the least possible risk and to avoid weight gain and its complications afterward."
For more information
Saab S, et al. The impact of obesity on patient survival in liver transplant recipients: A meta-analysis. Liver International. 2015;35:164.
Leonard J, et al. The impact of obesity on long-term outcomes in liver transplant patients — Results of the NIDDK liver transplant database. American Journal of Transplantation. 2008;8:667.
Fussner LA, et al. Cardiovascular disease after liver transplantation: When, what and who is at risk. Liver Transplantation. 2015;21:889.