Women With HCC Less Likely to Receive Liver Transplant, More Likely to Die Than Men

Women with hepatocellular carcinoma (HCC) were less likely to receive a liver transplant and more likely to die while wait-listed compared with men, with these disparities mostly, but not entirely, explained by the smaller size of female candidates, according to a retrospective cohort study.

The analysis of more than 30,000 transplant candidates with HCC found that women had a lower 1-year cumulative incidence of deceased-donor liver transplant compared with men (50.8% vs 54%, P<0.001) and a higher 1-year cumulative incidence of death or delisting due to health deterioration (16.2% vs 15%, P=0.002), reported Heidi Yeh, MD, of Massachusetts General Hospital in Boston, and colleagues in JAMA Surgery.

After adjusting for patient factors (with the exception of size), female sex was associated with a lower incidence of deceased-donor liver transplant (subdistribution HR [SHR] 0.92, 95% CI 0.89-0.95, P<0.001). However, when height and weight were added to the model for adjustment, female sex was not associated with transplant (SHR 0.97, 95% CI 0.93-1.02, P=0.27).

The same pattern held true in the case of death and waiting-list removal. After adjusting for candidate factors, but without adjusting for size, female sex was associated with a higher incidence of death or delisting (SHR 1.06, 95% CI 1.00-1.13, P=0.04), but after adjusting for height and weight, this changed (SHR 0.96, 95% CI 0.89-1.04, P=0.28).

While the disparities between women and men described in the study are mostly explained by candidate size, Yeh and colleagues noted that a comparison of short women and short men indicated that women were still less likely to receive a transplant (HR 0.93, 95% CI 0.88-0.99, P=0.03).

“Among patients with HCC, sex-based differences in transplant candidate size may be the predominant, but not the only, explanation for differences in access to [deceased-donor liver transplant] and waiting list outcomes,” the authors wrote. “This disparity may be largely explained by the smaller size of female candidates, which limits the number of suitable donors. Therefore, additional solutions to the sex-based disparity should include efforts to improve access to size-appropriate donor livers for smaller candidates regardless of sex.”

In a commentary accompanying the study, Mohamad El Moheb, MD, and Allan Tsung, MD, both of the University of Virginia in Charlottesville, called the implications of the study “broad-reaching,” since they could extend beyond disparities related to sex.

“Nation of origin could be a crucial factor for receiving a [deceased-donor liver], particularly for immigrants from countries with shorter-statured males,” they suggested. “This demographic is largely understudied and may experience fewer transplants and increased mortality due to size disadvantages potentially compounding on other factors like language barriers.”

As to how to address these disparities, Yeh and colleagues said there are several “realistic” possible policies that could be implemented.

For example, they referred to a recent analysis showing that allocating the smallest 10% of donors to the smallest 15% of candidates could overcome the size disparity. Or, additional Model for End-Stage Liver Disease (MELD) exception points could be extended to smaller patients.

“Splittable liver grafts, which are underused, could also be preferentially allocated to shorter patients,” they suggested.

For this study, Yeh and colleagues identified 31,725 adult wait-listed liver transplant candidates who received exception scores for HCC between January 2010 and March 2023. Mean age at receipt of exception was 61, and 76.3% were men.

Of these candidates, fewer women than men received a transplant (60% vs 62.2%), more women died while on the waiting list (6.7% vs 5.4%), and similar proportions were removed for being too sick (13.3% vs 13%).

Women also spent more days on the waiting list than men before reaching these endpoints, and had improved post-transplant survival compared with men.

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