Obese Transplant Recipients Fare Worse With Fatty Livers

Laird Harrison

November 11, 2018

SAN FRANCISCO — The fat in a donor liver and the fat in the recipient increase risk for death after transplant, according to results from a new study.

This does not mean that obese patients should be denied liver transplants, or that high-macrosteatosis livers should be thrown away, said Patrick Northup, MD, from the University of Virginia School of Medicine in Charlottesville.

Rather, he said, these results support the practice of selecting leaner livers for fatter recipients and vice versa.

"Some people would look at this and say, 'this is what we already do.' I think our paper helps quantify the risk," he told Medscape Medical News.

The finding also has implications for the way patients are ranked on the national liver transplantation waiting list.

That ranking was devised when hepatitis C was the predominant liver disease, Northup explained. But the incidence of hepatitis C peaked in 1989, dropped steadily until 2006, and only recently began to increase again. At the same time, obesity rates have soared, increasing the prevalence of nonalcoholic steatohepatitis.

These trends have changed the characteristics of both the liver donor and the recipient, said Northup. In addition, patients with liver disease are living longer.

"Transplant has changed a lot over the past 15 or so years. It's been our impression that patients are sicker going into transplant," he said. "And just about every organ we use these days has some risks associated with it. The data we go by to determine which organs go into which patients are pretty outdated, frankly."

In the past, Northup remembers imposing a cutoff body mass index (BMI) of 35 kg/m2 for liver transplant eligibility. "We made patients lose weight before they could get a transplant," he said. But the threshold for liver transplantation has steadily crept up, sometimes reaching a 40 kg/m2.

In their own clinic, Northup and his colleagues noticed that obese liver recipients and recipients of highly macrosteatotic livers fared worse than normal-weight recipients and recipients of livers with macrosteatosis in the normal range.

High-Macrosteatosis Grafts in High-BMI Recipients

So the team analyzed 23,504 liver donors and recipients who underwent graft biopsy before successful transplantation. Grafts were defined as highly macrosteatotic livers if the steatosis was at least 30% on biopsy. Obesity was defined as a BMI above 35 kg/m² after adjustment for ascites volume.

The cases were divided into four cohorts: high-macrosteatosis grafts in high-BMI recipients; normal grafts in high-BMI recipients; high-macrosteatosis grafts in normal-BMI recipients; and normal grafts in normal-BMI recipients.

Overall, 2675 of the liver recipients had a high BMI and 2002 of the livers were highly macrosteatotic.

There were no clinical differences in the cohorts for age, model for end-stage liver disease (MELD) score, serum sodium at transplant, or time spent on the waiting list.

In the high-macrosteatosis, high-BMI cohort, grafts were slightly lower risk than in the other cohorts, aside from the macrosteatosis (donor risk index, 1.827 vs 1.909; = .002).

High BMI in recipients was an independent predictor of post-transplant mortality at 30 days (hazard ratio [HR], 1.78; 95% confidence interval [CI], 1.47 - 2.16; < .0001) and at 365 days (HR, 1.18; 95% CI, 1.04 - 1.34; = .009) after adjustment for recipient age, additional donor risk factors, recipient disease etiology, and MELD score at transplant.

High macrosteatosis of the graft was the strongest independent predictor of mortality at 30 days (HR, 2.05, 95% CI, 1.66 - 2.53; < .0001). This effect diminished but persisted at 365 days (HR, 1.27; 95% CI, 1.10 - 1.46; = .001).

At all time points after transplantation, mortality was the highest in the high-macrosteatosis, high-BMI cohort and lowest in the normal-graft, lower-BMI cohort.

Table. Liver Transplant Survival Rates
Cohort 30-Day Survival, % 90-Day Survival, % 365-Day Survival, %
High macrosteatosis, high BMI 93.1 90.4 87.0
Low macrosteatosis, high BMI 95.4 93.2 89.6
High macrosteatosis, normal BMI 95.1 93.6 89.4
Low mascrosteatosis, normal BMI 97.6 95.7 90.9

The differences between the high-macrosteatosis, high-BMI cohort and the other cohorts were statistically significant at all time points. The differences between the low-macrosteatosis, high-BMI and the high-macrosteatosis, normal-BMI cohorts were not significantly different.

"A liver graft that has fat in it put into an obese patient has the worst outcome," said Northup. "The best outcomes are a normal liver into normal patient."

But, he pointed out, the overall survival rate was reasonably high. "The grafts, especially in patients who have moderate MELD scores, who don't have a lot of metabolic difficulty, end up doing well with many different types of donors."

Northup hopes that regulatory agencies and insurers will take note of these findings when assessing the performance of transplant centers. "When you're from an area of the country with a lot of obese patients, your numbers should acknowledge that you're dealing with a high-risk population," he said.

The finding should give pause to anyone involved in matching donors and recipients for liver transplants, said Kimberly Brown, MD, from the Liver Transplant Program at the Henry Ford Health System in Detroit.

"At some point, this, as well as other data, may redefine for us who is an acceptable transplant risk," she told Medscape Medical News.

"If we're going to accept patients who are morbidly obese, we have to be very selective about the organs they receive," she added.

Northup has disclosed no relevant financial relationships. Brown reports financial relationships with Gilead, Merck, and Pfizer.

The Liver Meeting 2018: American Association for the Study of Liver Diseases (AASLD). Presented November 11, 2018.

Follow Medscape Gastroenterology on Twitter @MedscapeGastro and Laird Harrison @LairdH

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