Pharmacotherapy for Weight Loss in Cirrhosis and Liver Transplantation: Translating the Data and Underused Potential

Abstract

BaCKgRoUND aND aIMS: Thirty percent of patients with cirrhosis are obese and the prevalence of obesity increases after transplant to >40% post-transplant. There are currently four weight loss medications approved by the FDA for treatment of obesity (orlistat, phentermine-topiramate, naltrexone-bupropion, and liraglutide). The aim of this review was to investigate the data on the use of these weight loss medications and alternative medicines in patients with cirrhosis and in liver transplant recipients (LTRs). appRoaCH aND ReSUltS: While there is paucity of data for these medications in patients with cirrhosis and LTRs, Liraglutide appears to be generally safe in view of its pharmacokinetic properties. Phentermine-topiramate seems to have the highest weight loss potential but special consideration should be given to neuropsychiatric disorders, cardiovascular comorbidities, and drug interactions. There are emerging data on use of alternative medicines for weight loss but more data are needed. CoNClUSIoNS:The use of weight loss medications is feasible in this patient population but the decision of which medication to prescribe should be individualized based on the degree of renal and hepatic impairment, other co-morbidities, and concomitant medications. (Hepatology 2021;73:2051-2062.O besity is estimated to affect 40% of the United States population and is associated with hepatic, metabolic and cardiovascular morbidities as well as certain cancers and premature death. (1,2) Thirty percent of patients with cirrhosis are obese, while 40% are overweight, and recent analysis of national registry data revealed that 35.9% of adult liver-transplant recipients (LTRs) were obese at the time of transplant. (2,3) In a retrospective study, obesity increased from 23.8% at 4 months to 40.8% 3 years after transplant. (4) Obesity and other components of metabolic syndrome are closely associated with development of NASH, which has become the most common indication for transplantation in women and the second most common indication in men. (5,6) About half of LTRs meet the criteria for metabolic syndrome, placing them at significant risk for long-term cardiovascular and metabolic complications. (7) Weight loss is associated with improvement in NASH and portal hypertension as well as longterm favorable outcomes in general population. (8)(9)(10) Weight loss may enhance future transplant eligibility of patients with cirrhosis and morbid obesity. The parallel increase in prevalence of NASH cirrhosis and obesity highlights the importance of finding a weight-loss strategy that is safe and effective in cirrhosis and LTRs. The data for weight loss-related

Management of metabolic syndrome after liver transplant

“…Glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide, could potentially be a good option pending future studies in LT recipients. [10] CONCLUSIONS…”

“…Several oral weight loss agents have been shown to be effective in patients with advanced liver disease, but data on the post-LT population is limited. Glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide, could potentially be a good option pending future studies in LT recipients 10 …”

Genetic and Life Style Risk Factors for Recurrent Non-alcoholic Fatty Liver Disease Following Liver Transplantation

“…Orlistat should be given at least 3 h before or after calcineurin inhibitors and levels should be monitored closely. There are no recorded interactions with antimetabolites or mammalian target of rapamycin (mTOR) inhibitors (26).…”

“…There are no data specific to the benefit of naltrexone-bupropion in the post-transplant setting, but there is no established interaction with post-transplant immunosuppressive medication. However, bupropion is a strong CYP2D6 inhibitor and can elevate the serum concentration of many drugs (26).…”

Utility of glucagon-like peptide 1 receptor agonists as anti-obesity medications in liver transplant recipients

“…To the editor, Obesity occurs in >40% of liver transplant recipients (LTRs) and causes metabolic derangements that increase mortality. [1] In recent years, glucagon-like peptide 1 receptor agonists (GLP-1RA) have emerged as a novel pharmacologic class. While these agents were shown to effectively treat obesity in the general population, [2] their utility is unknown in LTRs, where metabolism is significantly altered by immunosuppressive agents, among other factors.…”