Non-overweight NAFLD patients have poor liver transplant outcomes

Non-overweight patients with non-alcoholic fatty liver disease (NAFLD) have an elevated risk of all-cause mortality following liver transplant and are also more likely to be removed from the liver transplant waitlist compared with obese/overweight patients, according to a study presented at The Liver Meeting Digital Experience™.

“Our study suggests that non-overweight individuals with NAFLD cirrhosis have higher rates of waitlist removal due to clinical deterioration, as well as worse post-transplant survival compared with their overweight and obese counterparts,” said lead researcher Dr Pedro Ochoa-Allemant from the Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, US.

Using the United Network of Organ Sharing (UNOS) database, Ochoa-Allemant and co-researchers identified 24,127 patients with NAFLD who were scheduled to undergo liver transplant between February 27, 2002 and June 30, 2020. Of these, 6.8 percent were classified as non-overweight (BMI 18.5–24.9 kg/m²), while 93.2 percent were classified as overweight or obese (BMI ≥25.0 kg/m²).

On the waitlist, there were more women in the non-overweight vs the overweight/obese group. Those in the non-overweight group were also older and were more likely to have public insurance. Non-overweight patients had worse functional status, and a higher prevalence of ascites, hepatic encephalopathy, and transjugular intrahepatic portosystemic shunt at baseline compared with those in the overweight/obese group.

Compared with patients who were overweight/obese, non-overweight patients had a higher likelihood of being removed from the liver transplant waitlist due to death before liver transplant or clinical deterioration (hazard ratio [HR], 1.14, 95 percent confidence interval [CI], 1.03–1.27; p=0.01). [The Liver Meeting Digital Experience™, abstract 1505]

Non-overweight patients were also at greater risk of all-cause mortality after liver transplant compared with overweight/obese patients (HR, 1.50, 95 percent CI, 1.27–1.76; p<0.001).

Non-overweight patients with diabetes were at a higher risk of waitlist removal than overweight/obese patients without diabetes (HR, 1.29, 95 percent CI, 1.12–1.48; p<0.001), and were at a greater risk of all-cause mortality post-transplant (HR, 1.95, 95 percent CI, 1.57–2.42; p<0.001).

Multivariable analysis showed that non-overweight patients with diabetes had a significantly greater risk of liver transplant waitlist removal (HR, 1.18, 95 percent CI, 1.03–1.36; p=0.02). Compared with overweight/obese patients, all-cause mortality following liver transplant was greater in non-overweight patients, both in those with diabetes (HR, 1.84, 95 percent CI, 1.48–2.28; p<0.001) and without diabetes (HR, 1.47, 95 percent CI, 1.25–1.73; p<0.001).

“[T]he combination of low/normal BMI and [diabetes] was most strongly associated with waitlist removal and all-cause mortality after liver transplant,” noted the researchers.

“NAFLD is one of the leading aetiologies of liver disease among adults awaiting liver transplantation, and non-overweight individuals with NAFLD represent a subset of patients with a distinct risk factor profile characterized by increased visceral adipose tissue, underlying insulin resistance, and genetic predisposition,” said Ochoa-Allemant.

“Despite an apparent healthy status with lower BMI, these patients have increased cardiometabolic risk factors, such as diabetes, that are associated with subsequent worse outcomes throughout the transplant process,” he continued.

The researchers pointed out that compared with overweight patients without diabetes, non-overweight patients with diabetes “needed better nutritional counselling and healthy lifestyle interventions to help them lower their risk of severe outcomes” during their time on the waitlist as well as post-transplant.

“Therefore, it is crucial to identify these individuals at higher risk for adverse outcomes and effectively intervene by enhancing nutritional support, promoting physical activity, and investigating other potential metabolic interventions to minimize risk before and after liver transplantation,” Ochoa-Allemant highlighted.