Sex-based disparities in liver allocation driven by organ size mismatch, MELD score

Addressing local supply constraints may be insufficient to improve poorer outcomes among women who need a liver transplant, based on a large retrospective analysis.

Sex-based disparities in liver allocation were more strongly associated with liver size mismatch and MELD (Model for End-stage Liver Disease) score than geographic factors, reported lead author Jayme E. Locke, MD, of the University of Alabama at Birmingham, and colleagues.

“Currently, the transplant community is considering geographic redistribution ... to redefine local organ supply by replacing donor service areas with fixed concentric circles around donor hospitals,” the investigators wrote in JAMA Surgery. “However, newly proposed geographic models rely on the same metric for medical urgency, the MELD score, and offer no solution for candidates with small body stature who may appear at the top of the match run yet are routinely skipped secondary to discrepancies in donor-recipient size.”

To further investigate the driving forces behind sex-based disparities, the investigators conducted the first national study of its kind, involving 81,357 adults who were wait-listed for liver transplant. Primary outcomes included deceased donor liver transplant and wait list mortality. Using multivariate regression models and inverse odds ratio weighting, the investigators determined proportions of disparity shared across MELD score, candidate anthropometric and liver measurements, and geographic location.

Compared with men, women were 14.4% less likely to receive a transplant, and 8.6% more likely to die on the wait list.

The only geographic factor significantly associated with the increased disparity between female sex and wait list mortality was organ procurement organization, which was associated with a 22% increase. The disparity between rates of transplant receipt was not linked with any geographic factors.

In contrast, MELD score accounted for increases in disparity of 10.3% and 50.1% for organ receipt and wait list mortality, respectively. Candidate anthropometric and liver measurements played an even greater role, raising disparity by 49.0% for organ receipt and 125.8% for wait list mortality.

“Size mismatch between the donor and intended recipient and incorrect assessments of liver disease severity were more strongly associated with the observed sex disparity in wait list mortality than local supply of organs,” the investigators wrote.

Dr. Locke and colleagues noted that ongoing debates about geographic disparity hinge upon the assumption that the MELD score accurately measures disease severity, despite known shortcomings, including reliance upon serum creatinine level, which is influenced by muscle mass and therefore overestimates kidney function in women, and sex-based differences in size, which the MELD score does not incorporate whatsoever.

As such, the investigators suggested that addressing issues with the MELD score and organ size mismatch should be part of a more comprehensive approach to fixing sex-based disparities among candidates for liver transplant.

“Although geographic factors matter, examining geographic access alone may be insufficient,” they concluded.

James F. Markmann, MD, PhD, chief of the division of transplantation at Massachusetts General Hospital, Boston, who has previously published research in support of geographic redistribution, said in an interview that the study by Dr. Locke and colleagues “highlights a well-known problem in the liver transplant field.”

“The cause of this disparity is nicely illustrated by Dr. Locke’s work, which shows multiple contributing factors,” Dr. Markmann said.

While Dr. Markmann agreed with Dr. Locke and colleagues’ proposal that estimated glomerular filtration rate, instead of creatinine, could be used to more accurately measure renal function across sexes, he suggested that the disparities uncovered by their analysis are more likely driven by body size than sex.

“A more impactful factor and one obvious to those performing transplants is that on average the smaller body habitus of females makes more organs unsuitable due to size mismatch,” Dr. Markmann said. “In general, it is technically much less of a barrier to put a small liver into a large patient, than a large liver in a small patient. But, the same disparity in access almost certainly applies to small males; unfortunately, the authors did not examine this point. If allocation changes are envisioned to gain greater fairness in organ access, at least for the recipient size issue, it should be a size issue and not a sex issue.”

Dr. Markmann went on to explain that steps are currently being taken to make liver access more equitable.

“As of February 4th of this year, a broader sharing program for deceased donor livers was implemented,” he said. “This will make more organs available to those in greatest need. It will also potentially increase the number of liver offers to sick patients with a small body habitus and will hopefully reduce the excess morbidity and mortality they suffer.”

According to Willscott E. Naugler, MD and Susan L. Orloff, MD, of Oregon Health & Science University, Portland, novel clinical strategies need to be reinforced with a broader mindset in order to close the gap between men and women.

“A change in the MELD score is unlikely to fix this problem,” they wrote in an accompanying JAMA Surgery editorial, “but it is not hard to think of solutions; one could imagine, for example, allowing women of small stature to access pediatric livers while ramping up liver splits to increase contributions to the pediatric pool.”

Dr. Naugler and Dr. Orloff went on to suggest that barriers to equity may be culturally insidious.

“It is likely that the same unconscious biases that lead us to pay women surgeons less account for the lack of will to make these simple changes,” they wrote. “Not mentioned are multiple sociocultural elements that favor men over women in organ transplant. ... These realities cannot be fixed with changes to the MELD score, and we must be mindful not to let such notions distract from the essential hard work of creating long-lasting cultural changes that underpin a true path forward.”

The investigators disclosed relationships with Sanofi, Hansa Medical, Natera, and others.

SOURCE: Locke JE et al. JAMA Surg. 2020 May 20. doi: 10.1001/jamasurg.2020.1129.

Addressing local supply constraints may be insufficient to improve poorer outcomes among women who need a liver transplant, based on a large retrospective analysis.

Sex-based disparities in liver allocation were more strongly associated with liver size mismatch and MELD (Model for End-stage Liver Disease) score than geographic factors, reported lead author Jayme E. Locke, MD, of the University of Alabama at Birmingham, and colleagues.

“Currently, the transplant community is considering geographic redistribution ... to redefine local organ supply by replacing donor service areas with fixed concentric circles around donor hospitals,” the investigators wrote in JAMA Surgery. “However, newly proposed geographic models rely on the same metric for medical urgency, the MELD score, and offer no solution for candidates with small body stature who may appear at the top of the match run yet are routinely skipped secondary to discrepancies in donor-recipient size.”

To further investigate the driving forces behind sex-based disparities, the investigators conducted the first national study of its kind, involving 81,357 adults who were wait-listed for liver transplant. Primary outcomes included deceased donor liver transplant and wait list mortality. Using multivariate regression models and inverse odds ratio weighting, the investigators determined proportions of disparity shared across MELD score, candidate anthropometric and liver measurements, and geographic location.

Compared with men, women were 14.4% less likely to receive a transplant, and 8.6% more likely to die on the wait list.

The only geographic factor significantly associated with the increased disparity between female sex and wait list mortality was organ procurement organization, which was associated with a 22% increase. The disparity between rates of transplant receipt was not linked with any geographic factors.

In contrast, MELD score accounted for increases in disparity of 10.3% and 50.1% for organ receipt and wait list mortality, respectively. Candidate anthropometric and liver measurements played an even greater role, raising disparity by 49.0% for organ receipt and 125.8% for wait list mortality.

“Size mismatch between the donor and intended recipient and incorrect assessments of liver disease severity were more strongly associated with the observed sex disparity in wait list mortality than local supply of organs,” the investigators wrote.

Dr. Locke and colleagues noted that ongoing debates about geographic disparity hinge upon the assumption that the MELD score accurately measures disease severity, despite known shortcomings, including reliance upon serum creatinine level, which is influenced by muscle mass and therefore overestimates kidney function in women, and sex-based differences in size, which the MELD score does not incorporate whatsoever.

As such, the investigators suggested that addressing issues with the MELD score and organ size mismatch should be part of a more comprehensive approach to fixing sex-based disparities among candidates for liver transplant.

“Although geographic factors matter, examining geographic access alone may be insufficient,” they concluded.

James F. Markmann, MD, PhD, chief of the division of transplantation at Massachusetts General Hospital, Boston, who has previously published research in support of geographic redistribution, said in an interview that the study by Dr. Locke and colleagues “highlights a well-known problem in the liver transplant field.”

“The cause of this disparity is nicely illustrated by Dr. Locke’s work, which shows multiple contributing factors,” Dr. Markmann said.

While Dr. Markmann agreed with Dr. Locke and colleagues’ proposal that estimated glomerular filtration rate, instead of creatinine, could be used to more accurately measure renal function across sexes, he suggested that the disparities uncovered by their analysis are more likely driven by body size than sex.

“A more impactful factor and one obvious to those performing transplants is that on average the smaller body habitus of females makes more organs unsuitable due to size mismatch,” Dr. Markmann said. “In general, it is technically much less of a barrier to put a small liver into a large patient, than a large liver in a small patient. But, the same disparity in access almost certainly applies to small males; unfortunately, the authors did not examine this point. If allocation changes are envisioned to gain greater fairness in organ access, at least for the recipient size issue, it should be a size issue and not a sex issue.”

Dr. Markmann went on to explain that steps are currently being taken to make liver access more equitable.

“As of February 4th of this year, a broader sharing program for deceased donor livers was implemented,” he said. “This will make more organs available to those in greatest need. It will also potentially increase the number of liver offers to sick patients with a small body habitus and will hopefully reduce the excess morbidity and mortality they suffer.”

According to Willscott E. Naugler, MD and Susan L. Orloff, MD, of Oregon Health & Science University, Portland, novel clinical strategies need to be reinforced with a broader mindset in order to close the gap between men and women.

“A change in the MELD score is unlikely to fix this problem,” they wrote in an accompanying JAMA Surgery editorial, “but it is not hard to think of solutions; one could imagine, for example, allowing women of small stature to access pediatric livers while ramping up liver splits to increase contributions to the pediatric pool.”

Dr. Naugler and Dr. Orloff went on to suggest that barriers to equity may be culturally insidious.

“It is likely that the same unconscious biases that lead us to pay women surgeons less account for the lack of will to make these simple changes,” they wrote. “Not mentioned are multiple sociocultural elements that favor men over women in organ transplant. ... These realities cannot be fixed with changes to the MELD score, and we must be mindful not to let such notions distract from the essential hard work of creating long-lasting cultural changes that underpin a true path forward.”

The investigators disclosed relationships with Sanofi, Hansa Medical, Natera, and others.

SOURCE: Locke JE et al. JAMA Surg. 2020 May 20. doi: 10.1001/jamasurg.2020.1129.

Addressing local supply constraints may be insufficient to improve poorer outcomes among women who need a liver transplant, based on a large retrospective analysis.

Sex-based disparities in liver allocation were more strongly associated with liver size mismatch and MELD (Model for End-stage Liver Disease) score than geographic factors, reported lead author Jayme E. Locke, MD, of the University of Alabama at Birmingham, and colleagues.

“Currently, the transplant community is considering geographic redistribution ... to redefine local organ supply by replacing donor service areas with fixed concentric circles around donor hospitals,” the investigators wrote in JAMA Surgery. “However, newly proposed geographic models rely on the same metric for medical urgency, the MELD score, and offer no solution for candidates with small body stature who may appear at the top of the match run yet are routinely skipped secondary to discrepancies in donor-recipient size.”

To further investigate the driving forces behind sex-based disparities, the investigators conducted the first national study of its kind, involving 81,357 adults who were wait-listed for liver transplant. Primary outcomes included deceased donor liver transplant and wait list mortality. Using multivariate regression models and inverse odds ratio weighting, the investigators determined proportions of disparity shared across MELD score, candidate anthropometric and liver measurements, and geographic location.

Compared with men, women were 14.4% less likely to receive a transplant, and 8.6% more likely to die on the wait list.

The only geographic factor significantly associated with the increased disparity between female sex and wait list mortality was organ procurement organization, which was associated with a 22% increase. The disparity between rates of transplant receipt was not linked with any geographic factors.

In contrast, MELD score accounted for increases in disparity of 10.3% and 50.1% for organ receipt and wait list mortality, respectively. Candidate anthropometric and liver measurements played an even greater role, raising disparity by 49.0% for organ receipt and 125.8% for wait list mortality.

“Size mismatch between the donor and intended recipient and incorrect assessments of liver disease severity were more strongly associated with the observed sex disparity in wait list mortality than local supply of organs,” the investigators wrote.

Dr. Locke and colleagues noted that ongoing debates about geographic disparity hinge upon the assumption that the MELD score accurately measures disease severity, despite known shortcomings, including reliance upon serum creatinine level, which is influenced by muscle mass and therefore overestimates kidney function in women, and sex-based differences in size, which the MELD score does not incorporate whatsoever.

As such, the investigators suggested that addressing issues with the MELD score and organ size mismatch should be part of a more comprehensive approach to fixing sex-based disparities among candidates for liver transplant.

“Although geographic factors matter, examining geographic access alone may be insufficient,” they concluded.

James F. Markmann, MD, PhD, chief of the division of transplantation at Massachusetts General Hospital, Boston, who has previously published research in support of geographic redistribution, said in an interview that the study by Dr. Locke and colleagues “highlights a well-known problem in the liver transplant field.”

“The cause of this disparity is nicely illustrated by Dr. Locke’s work, which shows multiple contributing factors,” Dr. Markmann said.

While Dr. Markmann agreed with Dr. Locke and colleagues’ proposal that estimated glomerular filtration rate, instead of creatinine, could be used to more accurately measure renal function across sexes, he suggested that the disparities uncovered by their analysis are more likely driven by body size than sex.

“A more impactful factor and one obvious to those performing transplants is that on average the smaller body habitus of females makes more organs unsuitable due to size mismatch,” Dr. Markmann said. “In general, it is technically much less of a barrier to put a small liver into a large patient, than a large liver in a small patient. But, the same disparity in access almost certainly applies to small males; unfortunately, the authors did not examine this point. If allocation changes are envisioned to gain greater fairness in organ access, at least for the recipient size issue, it should be a size issue and not a sex issue.”

Dr. Markmann went on to explain that steps are currently being taken to make liver access more equitable.

“As of February 4th of this year, a broader sharing program for deceased donor livers was implemented,” he said. “This will make more organs available to those in greatest need. It will also potentially increase the number of liver offers to sick patients with a small body habitus and will hopefully reduce the excess morbidity and mortality they suffer.”

According to Willscott E. Naugler, MD and Susan L. Orloff, MD, of Oregon Health & Science University, Portland, novel clinical strategies need to be reinforced with a broader mindset in order to close the gap between men and women.

“A change in the MELD score is unlikely to fix this problem,” they wrote in an accompanying JAMA Surgery editorial, “but it is not hard to think of solutions; one could imagine, for example, allowing women of small stature to access pediatric livers while ramping up liver splits to increase contributions to the pediatric pool.”

Dr. Naugler and Dr. Orloff went on to suggest that barriers to equity may be culturally insidious.

“It is likely that the same unconscious biases that lead us to pay women surgeons less account for the lack of will to make these simple changes,” they wrote. “Not mentioned are multiple sociocultural elements that favor men over women in organ transplant. ... These realities cannot be fixed with changes to the MELD score, and we must be mindful not to let such notions distract from the essential hard work of creating long-lasting cultural changes that underpin a true path forward.”

The investigators disclosed relationships with Sanofi, Hansa Medical, Natera, and others.

SOURCE: Locke JE et al. JAMA Surg. 2020 May 20. doi: 10.1001/jamasurg.2020.1129.