Is Weight Protective for NAFLD Patients Undergoing Transplant?

For patients with non-alcoholic fatty liver disease (NAFLD) and cirrhosis awaiting a liver transplant, those without overweight or obesity were more likely to either be removed from the waitlist or die after transplantation, a researcher said.

In an analysis of over 24,000 NAFLD patients awaiting a liver, patients without overweight or obesity were 14% more likely to be removed from the waitlist (subdistribution HR 1.14, 95% CI 1.03-1.27, P=0.01) and 50% more likely to die after transplant (HR 1.50, 95% CI 1.27-1.76, P<0.001) compared to those with overweight or obesity, reported Pedro Ochoa-Allemant, MD, of the Yale School of Medicine in New Haven, Connecticut.

Among the subset of patients with diabetes, higher risk for waitlist removal (subdistribution HR 1.29, 95% CI 1.12-1.48, P<0.001) and post-transplant death (HR 1.95, 95% CI 1.57-2.42, P<0.001) were also observed in those without overweight or obesity, he said at a poster presentation at the virtual American Association for the Study of Liver Diseases annual meeting.

“Usually clinicians would associate NAFLD with overweight and obese patients, but there is also a significant amount of patients that are non-overweight and also have NAFLD, and this subset of patients have a very particular pathophysiology,” Ochoa-Allemant said at a press conference, noting that data are limited in this particular group of patients.

She told MedPage Today that these patients have “a distinct risk factor profile characterized by increased visceral adipose tissue, underlying insulin resistance, and genetic predisposition.”

“This report is timely given NAFLD continues to grow, not only as a leading chronic global liver disease, but also a leading reason for liver transplantation,” said Jonathan G. Stine, MD, MSc, of Penn State Liver Center in Hershey, who was not involved in this study. “Given the continued inequity in liver transplantation where the demand for donor organs greatly outweighs the supply from the available donor pool, this often leads to longer waiting-list times.”

Ochoa-Allemant’s group evaluated United Network of Organ Sharing (UNOS) data on 24,127 NAFLD patients on the liver transplant waiting list from 2002 to 2020. Patients were grouped into two categories: non-overweight (BMI 18.5-24.9; 6.8% of participants) and those with overweight or obese (BMI of 25 or above; 93.2%).

The primary outcome assessed waitlist removal due to death or deterioration, and the secondary outcome was all-cause mortality after transplant.

Patients in the non-overweight group were more likely to be women, older, on public health insurance, and have worse functional status. Compared to patients with overweight or obesity, they had more hepatic encephalopathy, ascites, and transjugular intrahepatic portosystemic shunts at listing.

Multivariable analysis confirmed an association between diabetes and risk for waitlist removal in the non-overweight group (subdistribution HR 1.18, 95% CI 1.03-1.36, P=0.02). As well as for the higher risk of post-transplant mortality in non-overweight patients both with (HR 1.47, 95% CI 1.25-1.73, P<0.001) and without diabetes (HR 1.84, 95% CI 1.48-2.28, P<0.001).

“Poorly controlled diabetes pre-transplant is also an independent predictor of poor outcomes,” noted Sudha Kodali, MD, MSPH, of the Houston Methodist Hospital, who was also not involved with the research. “Hence the combination of both — as shown in this abstract — was not a surprise, but corroborates findings of previous studies and also highlights the importance of aggressive management of diabetes and importance of nutrition and optimum BMI in waitlisted patients,”

The analysis had limitations, researchers acknowledged, including the small percentage of patients without overweight or obesity.

Shine told MedPage Today that there were several other “important factors” that would not be available in a UNOS database analysis, such as sarcopenia and frailty, which could affect liver transplant outcomes.

“Further studies are needed, especially prospective cohorts, to better characterize the clinical trajectory of non-overweight individuals with NAFLD,” Ochoa-Allemant said.