Development and validation of the Gender-Equity Model for Liver Allocation (GEMA) to prioritise candidates for liver transplantation: a cohort study

Research areas:

• Uncategorized

Year:

2023

Type of Publication:

Article

Authors:

• Rodríguez-Perálvarez, Manuel Luis
• Gómez-Orellana, Antonio Manuel
• Majumdar, Avik
• Bailey, Michael
• McCaughan, Geoffrey W
• Gow, Paul
• Guerrero, Marta
• Taylor, Rhiannon
• Guijo-Rubio, David
• Hervás-Martínez, César
• Tsochatzis, Emmanuel A

Journal:

The Lancet Gastroenterology & Hepatology

Volume:

8

Number:

3

Pages:

242-252

Month:

March

ISSN:

2468-1253

BibTex:

@article{GEMA_Liver_transplant_cohort_study_2022, author = "Manuel Luis Rodr{\'i}guez-Per{\'a}lvarez and Antonio Manuel G{\'o}mez-Orellana and Avik Majumdar and Michael Bailey and Geoffrey W McCaughan and Paul Gow and Marta Guerrero and Rhiannon Taylor and David Guijo-Rubio and C{\'e}sar Herv{\'a}s-Mart{\'i}nez and Emmanuel A Tsochatzis", abstract = "The Model for End-stage Liver Disease (MELD) and its sodium-corrected variant (MELD-Na) have created gender disparities in accessing liver transplantation. We aimed to derive and validate the Gender-Equity Model for liver Allocation (GEMA) and its sodium-corrected variant (GEMA-Na) to amend such inequities. In this cohort study, the GEMA models were derived by replacing creatinine with the Royal Free Hospital glomerular filtration rate (RFH-GFR) within the MELD and MELD-Na formulas, with re-fitting and re-weighting of each component. The new models were trained and internally validated in adults listed for liver transplantation in the UK (2010–20; UK Transplant Registry) using generalised additive multivariable Cox regression, and externally validated in an Australian cohort (1998–2020; Royal Prince Alfred Hospital [Australian National Liver Transplant Unit] and Austin Hospital [Victorian Liver Transplant Unit]). The study comprised 9320 patients: 5762 patients for model training, 1920 patients for internal validation, and 1638 patients for external validation. The primary outcome was mortality or delisting due to clinical deterioration within the first 90 days from listing. Discrimination was assessedby Harrell’s concordance statistic 449 (5·8%) of 7682 patients in the UK cohort and 87 (5·3%) of 1638 patients in the Australian cohort died or were delisted because of clinical deterioration within 90 days. GEMA showed improved discrimination in predicting mortality or delisting due to clinical deterioration within the first 90 days after waiting list inclusion compared with MELD (Harrell’s concordance statistic 0·752 [95% CI 0·700–0·804] vs 0·712 [0·656–0·769]; p=0·001 in the internal validation group and 0·761 [0·703–0·819] vs 0·739 [0·682–0·796]; p=0·036 in the external validation group), and GEMA-Na showed improved discrimination compared with MELD-Na (0·766 [0·715–0·818] vs 0·742 [0·686–0·797]; p=0·0058 in the internal validation group and 0·774 [0·720–0·827] vs 0·745 [0·690–0·800]; p=0·014 in the external validation group). The discrimination capacity of GEMA-Na was higher in women than in the overall population, both in the internal (0·802 [0·716–0·888]) and external validation cohorts (0·796 [0·698–0·895]). In the pooled validation cohorts, GEMA resulted in a score change of at least 2 points compared with MELD in 1878 (52·8%) of 3558 patients (25·0% upgraded and 27·8% downgraded). GEMA-Na resulted in a score change of at least 2 points compared with MELD-Na in 1836 (51·6%) of 3558 patients (32·3% upgraded and 19·3% downgraded). In the whole cohort, 3725 patients received a transplant within 90 days of being listed. Of these patients, 586 (15·7%) would have been differently prioritised by GEMA compared with MELD; 468 (12·6%) patients would have been differently prioritised by GEMA-Na compared with MELD-Na. One in 15 deaths could potentially be avoided by using GEMA instead of MELD and one in 21 deaths could potentially be avoided by using GEMA-Na instead of MELD-Na. GEMA and GEMA-Na showed improved discrimination and a significant re-classification benefit compared with existing scores, with consistent results in an external validation cohort. Their implementation could save a clinically meaningful number of lives, particularly among women, and could amend current gender inequities in accessing liver transplantation.", awards = "JCR(2023): 30.9, Position: 2/143 (Q1) Category: GASTROENTEROLOGY {\&}amp; HEPATOLOGY", comments = "JCR(2023): 30.9, Position: 2/143 (Q1) Category: GASTROENTEROLOGY {\&}amp; HEPATOLOGY", doi = "10.1016/S2468-1253(22)00354-5", issn = "2468-1253", journal = "The Lancet Gastroenterology {\&}amp; Hepatology", month = "March", note = "JCR(2023): 30.9, Position: 2/143 (Q1) Category: GASTROENTEROLOGY {\&}amp; HEPATOLOGY", number = "3", pages = "242--252", title = "{D}evelopment and validation of the {G}ender-{E}quity {M}odel for {L}iver {A}llocation ({GEMA}) to prioritise candidates for liver transplantation: a cohort study", url = "doi.org/10.1016/S2468-1253(22)00354-5", volume = "8", year = "2023", }

Note:

JCR(2023): 30.9, Position: 2/143 (Q1) Category: GASTROENTEROLOGY & HEPATOLOGY

Abstract:

The Model for End-stage Liver Disease (MELD) and its sodium-corrected variant (MELD-Na) have created gender disparities in accessing liver transplantation. We aimed to derive and validate the Gender-Equity Model for liver Allocation (GEMA) and its sodium-corrected variant (GEMA-Na) to amend such inequities. In this cohort study, the GEMA models were derived by replacing creatinine with the Royal Free Hospital glomerular filtration rate (RFH-GFR) within the MELD and MELD-Na formulas, with re-fitting and re-weighting of each component. The new models were trained and internally validated in adults listed for liver transplantation in the UK (2010–20; UK Transplant Registry) using generalised additive multivariable Cox regression, and externally validated in an Australian cohort (1998–2020; Royal Prince Alfred Hospital [Australian National Liver Transplant Unit] and Austin Hospital [Victorian Liver Transplant Unit]). The study comprised 9320 patients: 5762 patients for model training, 1920 patients for internal validation, and 1638 patients for external validation. The primary outcome was mortality or delisting due to clinical deterioration within the first 90 days from listing. Discrimination was assessedby Harrell’s concordance statistic 449 (5·8%) of 7682 patients in the UK cohort and 87 (5·3%) of 1638 patients in the Australian cohort died or were delisted because of clinical deterioration within 90 days. GEMA showed improved discrimination in predicting mortality or delisting due to clinical deterioration within the first 90 days after waiting list inclusion compared with MELD (Harrell’s concordance statistic 0·752 [95% CI 0·700–0·804] vs 0·712 [0·656–0·769]; p=0·001 in the internal validation group and 0·761 [0·703–0·819] vs 0·739 [0·682–0·796]; p=0·036 in the external validation group), and GEMA-Na showed improved discrimination compared with MELD-Na (0·766 [0·715–0·818] vs 0·742 [0·686–0·797]; p=0·0058 in the internal validation group and 0·774 [0·720–0·827] vs 0·745 [0·690–0·800]; p=0·014 in the external validation group). The discrimination capacity of GEMA-Na was higher in women than in the overall population, both in the internal (0·802 [0·716–0·888]) and external validation cohorts (0·796 [0·698–0·895]). In the pooled validation cohorts, GEMA resulted in a score change of at least 2 points compared with MELD in 1878 (52·8%) of 3558 patients (25·0% upgraded and 27·8% downgraded). GEMA-Na resulted in a score change of at least 2 points compared with MELD-Na in 1836 (51·6%) of 3558 patients (32·3% upgraded and 19·3% downgraded). In the whole cohort, 3725 patients received a transplant within 90 days of being listed. Of these patients, 586 (15·7%) would have been differently prioritised by GEMA compared with MELD; 468 (12·6%) patients would have been differently prioritised by GEMA-Na compared with MELD-Na. One in 15 deaths could potentially be avoided by using GEMA instead of MELD and one in 21 deaths could potentially be avoided by using GEMA-Na instead of MELD-Na. GEMA and GEMA-Na showed improved discrimination and a significant re-classification benefit compared with existing scores, with consistent results in an external validation cohort. Their implementation could save a clinically meaningful number of lives, particularly among women, and could amend current gender inequities in accessing liver transplantation.

Comments:

JCR(2023): 30.9, Position: 2/143 (Q1) Category: GASTROENTEROLOGY & HEPATOLOGY