Post-Transplant NASH Patients Fare Worse With Older Donor Livers

Lucy Hicks

March 03, 2023

Liver transplant recipients with nonalcoholic steatohepatitis (NASH) who received grafts from older donors are at higher risk for post-transplant death, especially due to infection, according to a new study.

All-cause mortality was twice as high and death from an infectious cause was more than three times as high for patients with NASH who received liver grafts from octogenarian donors than for those who received a liver from someone younger than 50.

"The findings from this study implicate a critical need to investigate donor age as an important risk factor for poorer host and graft survival," write the authors, led by David Lee, MD, of the University of Maryland School of Medicine in Baltimore.

"Given the possibility of infectious graft complications, post–liver transplant follow-ups may need to be more comprehensive and frequent in these individuals who receive grafts from older donors," they add.

The study was published online in Digestive and Liver Disease.

Donor Age Trends

Lee and colleagues pulled data from the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research database, a national database of deidentified donor and recipient transplant data. The analysis excluded recipients younger than 18, those with a living donor, those who had hepatocellular carcinoma prior to transplant, and those who had been diagnosed with additional liver disorders apart from NASH.

The team identified 8888 recipients with NASH who received a liver transplant from 2005–2019. They stratified recipients by donor age. The 5187 patients who received livers from donors who were younger than 50 served as the reference group. The remainder were placed into four cohorts ― 1842 whose donors were in their 50s, 1290 whose donors were in their 60s, 504 whose donors were in their 70s, and 65 whose donors were in their 80s.

The researchers found that in comparison with the reference group, the average age of recipients in each donor-age cohort was progressively older. Two donor-age cohorts had significantly higher proportions of recipients with diabetes than the 46.5% in the reference group ― the sexagenarian cohort (51.7%) and the octogenarian group (66.2%).

The median follow-up time ranged from 2.35–3.61 years across all age groups.

The researchers found that for all donor-age groups excluding donors in their 60s, recipients had higher risk of all-cause mortality after transplant than the reference group. Recipients with donors in their 50s had a 16% greater risk for death (P = .01), and recipients with donors in their 70s had a 20% greater risk (P = .05). For recipients with octogenarian donors, the adjusted hazard ratio (aHR) for all-cause mortality was 2.01 (P < .001).

Only recipients in the octogenarian donor cohort were at increased risk of graft failure compared with the reference group (aHR = 3.72; P = .002).

As donor age increased, the recipient's risk of dying from sepsis and infectious causes rose compared with the reference group. Recipients' likelihood of sepsis death increased by 71% (P = .001) with donors in their 50s, 73% (P = .003) with donors in their 60s, and 76% (P = .03) with donors in their 70s. For recipients with octogenarian donors, the risk more than tripled (aHR = 3.58; P = .007). Likewise, recipients with donors in their 70s were 73% more likely to die from infectious causes. That risk nearly quadrupled among those with donors in their 80s.

Recipient Factors at Play?

While the study found a relationship between liver donor age and recipient outcomes, it is not clear whether any other recipient factors may have contributed to the higher risk of all-cause mortality, said Nancy Reau, MD, chief of the hepatology section at Rush University Medical Center in Chicago. The researchers did not parse out whether younger recipients did better with older organs than older recipients or whether older recipients fared worse with younger organs, she told Medscape Medical News.

"I wasn't convinced that they had demonstrated that the recipient may not have played a role in that," said Reau, who wasn't involved with the study.

The analysis only a found an increased risk of graft failure among recipients who received organs from octogenarian donors, so factors other than liver transplant may have contributed to all-cause mortality, she noted.

The UNOS database has some limitations, noted Timothy Pruett, MD, who directs the liver transplant program at the University of Minnesota Medical School in Minneapolis. Because the database pulls information from transplantation centers across the country, it can be difficult to standardize specific patient variables in the data.

While it's clear that a patient died, it's less certain whether an infection was the cause of death and whether that infection was somehow associated with the liver, noted Pruett, who wasn't involved in the research. For example, a patient could have had broken a hip, gone to the hospital, and contracted pneumonia, which led to their death.

"There's just not much granularity in the database, and we can't over-extrapolate what we see," Pruett told Medscape Medical News.

Knowledge Gaps

Lee agreed that more research is needed to understand what may be driving higher mortality rates among patients who receive older organs. "There are still a lot of gaps in knowledge with respect to why," he said.

Reau said she is curious as to whether certain comorbidities, such as previous infection, diabetes, or obesity, could predict worse outcomes for recipients with older organs.

"We would love to give all of our patients younger organs, but if that leads to even more disparity in need [compared] to availability and the alternative is not surviving, I think you have to place [this work] into context," she said.

The study findings shouldn't be used to deter patients with NASH from considering older organs, Reau said. More insight as to which populations might want to be choosier owing to an elevated risk would be beneficial, she added.

Lee, Pruett, and Reau report no relevant financial relationships.

Dig Liver Dis. Published online February 15, 2023. Abstract

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