Aug. 17, 2021

Weight loss is associated with improvements in patients with nonalcoholic steatohepatitis (NASH) and other favorable outcomes in the general population, and it can enhance eligibility for liver transplantation among patients with cirrhosis and morbid obesity. But finding a weight-loss strategy that is safe and effective for these patients can be challenging.

In a review article published in Hepatology in 2021, Kymberly D. Watt, M.D., and co-authors discuss the use of four Food and Drug Administration (FDA)-approved weight-loss medications and three alternative medicine treatments in patients with cirrhosis and in liver transplant recipients. Dr. Watt is a hepatologist at Mayo Clinic in Rochester, Minnesota, and serves as medical director for liver transplantation at the William J. von Liebig Center for Transplantation and Clinical Regeneration.

Background

NASH has become the most common indication for liver transplantation in women and the second most common indication in men. The association between obesity and the development of NASH is well established. In a recent analysis of national registry data, researchers noted that 35.9% of adult liver transplant recipients were obese at the time of transplant. And three years after liver transplantation, the prevalence of obesity among these individuals increased to 40.8%.

Medical therapy for weight loss — including dietary adjustments, exercise and pharmacotherapy — is typically recommended for patients with a body mass index (BMI) of 30 to 40. Surgical and endoscopic bariatric procedures are typically considered for patients with a BMI greater than 40, or for patients with metabolic comorbidities and a BMI greater than 35. However, some patients with BMIs that fall within the ranges suggested for bariatric procedures have additional risk factors and may not be good candidates for this approach. In patients with cirrhosis who are at increased risk of perioperative decompensation and mortality and in liver transplant recipients, a medical approach to weight loss may be preferred.

FDA-approved pharmacological therapies for obesity

The four weight-loss medications currently approved by the FDA for treatment of obesity are orlistat, phentermine-topiramate, naltrexone-bupropion and liraglutide. Although some society guidelines have endorsed the use of these medications in patients with cirrhosis or in liver transplant recipients, they have not yet been widely used in this population.

Dr. Watt and co-authors note that data related to the use of these medications in patients with cirrhosis and in post-transplant settings is scarce. In their article, the authors review the mechanism of action and the available safety and efficacy data for orlistat, phentermine-topiramate, naltrexone-bupropion and liraglutide and for three alternative therapies (cardamom, curcumin and carnitine) and translate this for the cirrhosis and transplant populations. Their overarching conclusion is that the FDA-approved agents can be used in patients with well-compensated liver disease and in transplant recipients, but they may not be appropriate for patients with decompensated liver disease. The alternative agents did not appear to provide significant weight-loss benefit, limiting their use.

Dr. Watt and co-authors describe the beneficial effects of weight-loss medications and alternative medicines on weight and other metabolic surrogates, and they outline a proposed care pathway for weight-loss pharmacotherapy in patients with obesity and cirrhosis. The care pathway begins with an evaluation that identifies the patient's Child-Pugh score (CPS), need and eligibility for transplantation, current medications, and comorbidities. There are separate care pathways for patients with a class A and class B CPS and for patients with a class C CPS. In addition, the authors provide an algorithmic approach to these agents in the transplant population, focusing on first line use of glucagon-like peptide 1 (GLP-1) agonists due to their additional benefits in glucose management.

Guidance for using weight-loss medications

The review also summarizes guidance for the use of weight-loss medications or alternative medications in patients with cirrhosis and in liver transplant recipients. For each of the agents discussed, a table lists pretransplant use (based on Child-Pugh class), post-transplant use, any dose adjustments based on renal status and common adverse events.

Summary

All four FDA-approved medications for weight loss appear to have various metabolic benefits that may affect both obesity and metabolic disease in select patients. According to Dr. Watt and co-authors, the choice of weight-loss medications for patients with cirrhosis and for liver transplant recipients should be tailored to each patient's clinical profile, and the choice requires careful follow-up.

Dr. Watt acknowledges that the small data pool obtained from patients with advanced liver disease and from liver transplant recipients means that additional studies are needed to provide more-definitive data on the clinical impact of these agents in these populations. However, this review answers some questions about the safety and potential impact of weight-loss pharmacotherapy in these populations, which may help future studies.

"We know that for patients in these populations who need to lose weight, the mainstay is still diet and exercise. When used in conjunction with a diet and exercise regimen, these agents can help patients achieve modest weight-loss benefits. We are hopeful that future research collaboration will help answer more questions related to how best to help these patients achieve weight loss," says Dr. Watt.

For more information

Brown SA, et al. Pharmacotherapy for weight loss in cirrhosis and liver transplantation: Translating the data and underused potential. Hepatology. 2021;73:2051.