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. 2023 Sep;79(3):717-727.
doi: 10.1016/j.jhep.2023.05.028. Epub 2023 Jun 12.

The novel SALT-M score predicts 1-year post-transplant mortality in patients with severe acute-on-chronic liver failure

Ruben Hernaez  1 , Constantine J Karvellas  2 , Yan Liu  3 , Sophie-Caroline Sacleux  4 , Saro Khemichian  5 , Lance L Stein  6 , Kirti Shetty  7 , Christina C Lindenmeyer  8 , Justin R Boike  9 , Douglas A Simonetto  10 , Robert S Rahimi  11 , Prasun K Jalal  12 , Manhal Izzy  13 , Michael S Kriss  14 , Gene Y Im  15 , Ming V Lin  16 , Janice H Jou  17 , Brett E Fortune  18 , George Cholankeril  12 , Alexander Kuo  19 , Nadim Mahmud  20 , Fasiha Kanwal  21 , Faouzi Saliba  22 , Vinay Sundaram  19 , Thierry Artzner  23 , Rajiv Jalan  24 ; Multi-Organ Dysfunction and Evaluation for Liver Transplantation (MODEL) Consortium
Collaborators, Affiliations

The novel SALT-M score predicts 1-year post-transplant mortality in patients with severe acute-on-chronic liver failure

Ruben Hernaez et al. J Hepatol. 2023 Sep.

Abstract

Background & aims: Twenty-eight-day mortality ranges from 30-90% in patients with acute-on-chronic liver failure grades 2/3 (severe ACLF). Though liver transplantation (LT) has demonstrated a survival benefit, the scarcity of donor organs and uncertainty regarding post-LT mortality among patients with severe ACLF may cause hesitancy. We developed and externally validated a model to predict 1-year post-LT mortality in severe ACLF, called the Sundaram ACLF-LT-Mortality (SALT-M) score, and estimated the median length of stay (LoS) after LT (ACLF-LT-LoS).

Methods: In 15 LT centers in the US, we retrospectively identified a cohort of patients with severe ACLF transplanted between 2014-2019, followed up to Jan'2022. Candidate predictors included demographics, clinical and laboratory values, and organ failures. We selected predictors in the final model using clinical criteria and externally validated them in two French cohorts. We provided measures of overall performance, discrimination, and calibration. We used multivariable median regression to estimate LoS after adjusting for clinically relevant factors.

Results: We included 735 patients, of whom 521 (70.8%) had severe ACLF (120 ACLF-3, external cohort). The median age was 55 years, and 104 with severe ACLF (19.9%) died within 1-year post-LT. Our final model included age >50 years, use of 1/≥2 inotropes, presence of respiratory failure, diabetes mellitus, and BMI (continuous). The c-statistic was 0.72 (derivation) and 0.80 (validation), indicating adequate discrimination and calibration based on the observed/expected probability plots. Age, respiratory failure, BMI, and presence of infection independently predicted median LoS.

Conclusions: The SALT-M score predicts mortality within 1-year after LT in patients with ACLF. The ACLF-LT-LoS score predicted median post-LT stay. Future studies using these scores could assist in determining transplant benefits.

Impact and implications: Liver transplantation (LT) may be the only life-saving procedure available to patients with acute-on-chronic liver failure (ACLF), but clinically instability can augment the perceived risk of post-transplant mortality at 1 year. We developed a parsimonious score with clinically and readily available parameters to objectively assess 1-year post-LT survival and predict median length of stay after LT. We developed and externally validated a clinical model called the Sundaram ACLF-LT-Mortality score in 521 US patients with ACLF with 2 or ≥3 organ failure(s) and 120 French patients with ACLF grade 3. The c-statistic was 0.72 in the development cohort and 0.80 in the validation cohort. We also provided an estimation of the median length of stay after LT in these patients. Our models can be used in discussions on the risks/benefits of LT in patients listed with severe ACLF. Nevertheless, the score is far from perfect and other factors, such as patient's preference and center-specific factors, need to be considered when using these tools.

Keywords: ACLF; liver transplantation; prognosis; risk score.

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Conflict of interest statement

Conflicts of interest

Rajiv Jalan is the inventor of OPA, which has been patented by UCL and licensed to Mallinckrodt Pharma. He is also the founder of Yaqrit Discovery, a spin out company from University College London, Hepyx Limited and Cyberliver. He had research collaborations with Yaqrit Discovery. All other authors declare no conflict of interests.

Please refer to the accompanying ICMJE disclosure forms for further details.

Figures

Fig. 1.
Fig. 1.
Proportion of causes of deaths in the MODEL Consortium (n = 521).
Fig. 2.
Fig. 2.. Discriminatory prediction of different models used in liver transplant candidates to predict 1-year post-liver transplantation.
Discriminative ability of the SALT-M score compared to the MELD-Na score, the change in MELD from ICU to transplantation over time (Delta-MELD), donor MELD-Na, the CLIF-C ACLF score and BAR score. BAR, balance of risk; CLIF-C ACLF, Chronic Liver Failure-Consortium acute-on-chronic liver failure; ICU, intensive care unit; MELD(-Na), model for end-stage liver disease-(sodium); SALT-M, Sundaram-ACLF-LT-Mortality. (This figure appears in color on the web.)
Fig. 3.
Fig. 3.. Calibration plots showing observed vs. predicted probability 1-year mortality and median length of stay between LT and first hospital discharge.
ACLF, acute-on-chronic liver failure; LoS, length of stay; LT, liver transplantation.
Fig. 4.
Fig. 4.. Example to illustrate how to use the SALT-M and ACLF-LT-LoS scores clinically.
LT, liver transplantation; MDRB, multi-drug resistant bacteria; RRT, renal replacement therapy; WBC, white blood cell count.
See this image and copyright information in PMC

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