Quantifying Sex-Based Disparities in Liver Allocation

Locke, Jayme E.; Shelton, Brittany A.; Olthoff, Kim M.; Pomfret, Elizabeth A.; Forde, Kimberly A.; Sawinski, Deirdre; Gray, Meagan; Ascher, Nancy L.

doi:10.1001/jamasurg.2020.1129

Cited by 90 publications

(150 citation statements)

References 54 publications

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“…However, the results are similar to other findings in previous publications [12], and should be a topic for future, more detailed studies. Indeed, a recent study has also shown that women are at a higher risk for death while on the transplant waiting list [23].…”

Section: Discussionmentioning

confidence: 99%

Etiologies and outcomes of cirrhosis in a large contemporary cohort

Hagström

Lindfors

Holmer

et al. 2021

Scandinavian Journal of Gastroenterology

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Background and aims: Patients with liver cirrhosis have high mortality, often estimated by the Child-Pugh or MELD scores. Etiologies of cirrhosis are rapidly shifting, and it is unclear if these scores perform similarly across subgroups of patients. Here, we describe the characteristics and outcomes of a large contemporary cohort of patients with cirrhosis. Methods: This was a cohort study with retrospectively collected data. All patients with a verified diagnosis of cirrhosis during 2004-2017 at the Karolinska University Hospital, Sweden, were identified. Data at baseline to calculate Child-Pugh, MELD and confounders for mortality was collected. Competing risk regression was used to estimate risk for outcomes, adjusted for age, sex, baseline Child-Pugh score, etiology of cirrhosis and type 2 diabetes. Results: We identified 2609 patients, with a median age of 61 years, and 68% men. Etiologies of cirrhosis shifted during the study period, with a À29% relative decrease in hepatitis C-cirrhosis and a þ 154% increase in cirrhosis due to non-alcoholic fatty liver disease. The highest overall mortality was seen in patients with alcohol-related cirrhosis. MELD and Child-Pugh scores predicted 3-month and 1 to 2-year mortality reasonably well, but with a lower predictive performance in alcohol-related cirrhosis. Men were more likely than women to receive a liver transplant (sHR ¼ 1.39, 95%CI ¼ 1.08-1.78). Conclusions: We confirm previous findings of a rapid shift in the etiologies of cirrhosis. Differences in sex in regard to access to liver transplantation deserve further attention.

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Section: Discussionmentioning

confidence: 99%

Etiologies and outcomes of cirrhosis in a large contemporary cohort

Hagström

Lindfors

Holmer

et al. 2021

Scandinavian Journal of Gastroenterology

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“…Females are more likely to die or be de-listed due to disease severity while on the liver transplant waitlist 8,10,12 . Concordantly, in our sample, females who had undergone a liver transplant had significantly more pre-transplant decompensation traits than males.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

“…After controlling for estimated liver size 12,14 or height 15 , sex disparities in transplant were reduced, but not eliminated. Likewise, controlling for geographic disparities did not ameliorate the sex disparity in receiving a liver transplant 12 . Several studies postulated that decreased body size in females leads to lower creatinine levels which in turn disadvantages females in MELD scoring 3,16,17 .…”

Section: Introductionmentioning

confidence: 94%

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Making an equal system equitable: Proposing a sex-adjusted MELDNa score for liver transplantation allocation

Sealock

Ziogas

Zhao

et al. 2021

Preprint

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Background & Aims: Liver allocation is determined by the model for end-stage liver disease (MELD), a scoring system based on four laboratory measurements. During the MELD era, sex disparities in liver transplant have increased and there are no modifications to MELD based on sex. We use data from electronic health records (EHRs) to describe sex differences in MELD labs and propose a sex adjustment. Methods: We extracted lab values for creatinine, International Normalized Ratio of prothrombin rate, bilirubin, and sodium from EHRs at Vanderbilt University Medical Center (VUMC) and the All of Us Research Project to determine sex differences in lab traits. We calculated MELDNa scores within liver transplant recipients, non-transplanted liver disease cases, and non-liver disease controls separately. To account for sex differences in lab traits in MELDNa scoring, we created a sex-adjusted MELDNa map which outputs adjusted female scores mapped to male scores of equal liver disease severity. Using waitlist data from the Liver Simulated Allocation Modeling, we conducted simulations to determine if the sex-adjusted scores reduced sex disparities. Results: All component MELDNa lab values and calculated MELDNa scores yielded significant sex differences within VUMC (n=623,931) and All of Us (n=56,715) resulting in MELDNa scoring that disadvantaged females who, despite greater decompensation traits, had lower MELDNa scores. In simulations, the sex-adjusted MELDNa score modestly increased female transplantation rate and decreased overall death. Conclusions: Our results demonstrate pervasive sex differences in all labs used in MELDNa scoring and highlight the need and utility of a sex-adjustment to the MELDNa protocol.

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“…( 41 ) In a study exploring 3 contributors to disparities in waitlist survival and LT (geography, candidate anthropometric measurements, and MELD score), size mismatch between the donor and intended recipient and incorrect assessments of liver disease severity based on the MELD score were more strongly associated with the observed sex disparity in waitlist mortality than local organ supply. ( 49 ) Defining “short stature” was the focus of a recent work by Ge et al, which showed that after adjustment for clinical and demographic characteristics, height <166 cm (5 feet, 5 inches) remained associated with an 8% increased risk of waitlist mortality (95% CI, 1.03‐1.14). ( 50 ) In a recent transplant registry–based study of gender disparities in transplantation for acute liver failure, the authors found no disparity in LT between men and women waitlisted as Status 1, suggesting that Status 1 priority may mitigate gender‐based disparities in LT. ( 51 )…”

Section: Disparities In the Lt Care Cascadementioning

confidence: 99%

Racial, Gender, and Socioeconomic Disparities in Liver Transplantation

Nephew

Serper

2021

Liver Transpl.

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Liver transplantation (LT) is a life‐saving therapy; therefore, equitable distribution of this scarce resource is of paramount importance. We searched contemporary literature on racial, gender, and socioeconomic disparities across the LT care cascade in referral, waitlist practices, allocation, and post‐LT care. We subsequently identified gaps in the literature and future research priorities. Studies found that racial and ethnic minorities (Black and Hispanic patients) have lower rates of LT referral, more advanced liver disease and hepatocellular carcinoma at diagnosis, and are less likely to undergo living donor LT (LDLT). Gender‐based disparities were observed in waitlist mortality and LT allocation. Women have lower LT rates after waitlisting, with size mismatch accounting for much of the disparity. Medicaid insurance has been associated with higher rates of chronic liver disease and poor waitlist outcomes. After LT, some studies found lower overall survival among Black compared with White recipients. Studies have also shown lower literacy and limited educational attainment were associated with increased posttransplant complications and lower use of digital technology. However, there are notable gaps in the literature on disparities in LT. Detailed population‐based estimates of the advanced liver disease burden and LT referral and evaluation practices, including for LDLT, are lacking. Similarly, little is known about LT disparities worldwide. Evidence‐based strategies to improve access to care and reduce disparities have not been comprehensively identified. Prospective registries and alternative “real‐world” databases can provide more detailed information on disease burden and clinical practices. Modeling and simulation studies can identify ways to reduce gender disparities attributed to size or inaccurate estimation of renal function. Mixed‐methods studies and clinical trials should be conducted to reduce care disparities across the transplant continuum.

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Quantifying Sex-Based Disparities in Liver Allocation

Cited by 90 publications

References 54 publications

Etiologies and outcomes of cirrhosis in a large contemporary cohort

Etiologies and outcomes of cirrhosis in a large contemporary cohort

Making an equal system equitable: Proposing a sex-adjusted MELDNa score for liver transplantation allocation

Racial, Gender, and Socioeconomic Disparities in Liver Transplantation

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