JHEP reports : innovation in hepatology · 2026
Liver transplantation at the extreme: Analysis of outcomes and predictors of futility in patients with acute-on-chronic liver failure grade 3 on maximal life support.
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Melehy Andrew, Thepbunchonchai Asara, Tran Benjamin V, Hernaez Ruben, Amara Dominic, Ebaid Samer, Markovic Daniela, Kaldas Fady M, Barjaktarevic Igor, Xia Victor, Karvellas Constantine J, Khemichian Saro, Stein Lance L, Shetty Kirti, Lindenmeyer Christina C, Boike Justin R, Simonetto Douglas A, Rahimi Robert S, Jalal Prasun K, Izzy Manhal, Kriss Michael S, Im Gene Y, Lin Ming V, Jou Janice H, Fortune Brett E, Cholankeril George, Kuo Alexander, Sundaram Vinay, Multi-Organ Dysfunction and Evaluation for Liver Transplantation (MODEL) Consortium, Busuttil Ronald W, Farmer Douglas G, Agopian Vatche G
Аннотация
BACKGROUND & AIMS: Although patients with grade 3 acute-on-chronic liver failure (ACLF-3), have high mortality, there is a subset requiring maximal life support. We report post liver transplant (LT) outcomes and identify factors associated with futility in extreme ACLF-3 (eACLF-3) recipients, all requiring intubation, vasopressors, and dialysis at LT.
METHODS: We identified adult eACLF-3 LT recipients between January 2010 and December 2021. Pre-LT characteristics were compared among eACLF-3 recipients with and without the futile outcome (1-year or in-hospital mortality), predictors of futility were identified, and a logistic regression model was evaluated using fivefold cross-validation. Findings were validated using the Multi-Organ Dysfunction and Evaluation for Liver Transplantation (MODEL) Consortium.
RESULTS: Of 1,608 adult LT recipients at our center, 177 (11%) were eACLF-3. Thirty-five (20%) eACLF-3 recipients experienced futility. Predictors of futility were previous upper abdominal surgery (odds ratio [OR] = 4.6, p = 0.002), sepsis within 14 days before LT (OR = 5.9, p = 0.013), intubation because of pneumonia or acute respiratory distress syndrome (OR = 3.5, p = 0.010), worsening PaO2:FiO2 ratio (OR = 3.9, p = 0.008), and pre-LT base deficit (OR = 1.27, p = 0.007). Futility was predicted with an AUROC of 0.74 (SD 0.15). When compared with the MODEL Consortium, our cohort had improved 3-, 6-, and 12-month survivals of 89%, 85%, and 80%, compared with 83%, 79%, and 70%, respectively (p = 0.048); however overall 5-year survival was similar (63% vs. 59%, p = 0.14).
CONCLUSIONS: We report the largest single-center experience of LT for patients with eACLF-3, demonstrating acceptable survival despite high acuity, validated in the MODEL Consortium dataset. Prospective validation of the predictive model and identified risk factors is necessary, and may aid in appropriate selection of patients with ACLF-3 requiring maximal life support before LT.
IMPACT AND IMPLICATIONS: There has been persistent interest in the liver transplant community regarding transplant for acute-on-chronic liver failure grade 3 (ACLF-3) recipients. In this work, we report on a large single-center experience transplanting ACLF-3 recipients, specifically investigating an extreme subset of these patients who were all mechanically ventilated, receiving vasopressors, and receiving hemodialysis at time of transplant. We characterized their outcomes, identifying clear risk factors associated with futility in this hyperacute subgroup and demonstrating that with appropriate selection, even patients in this extreme subgroup can experience acceptable 5-year post-transplant survival. Although we could not externally validate our model because of data availability, the obtained external patient cohort of patients with extreme ACLF-3 broadly validates our findings. We feel that these results represent an important contribution to the liver transplant community given concerns about transplanting this hyperacute subpopulation. These results may help guide physicians in selecting appropriate candidates for transplant.
METHODS: We identified adult eACLF-3 LT recipients between January 2010 and December 2021. Pre-LT characteristics were compared among eACLF-3 recipients with and without the futile outcome (1-year or in-hospital mortality), predictors of futility were identified, and a logistic regression model was evaluated using fivefold cross-validation. Findings were validated using the Multi-Organ Dysfunction and Evaluation for Liver Transplantation (MODEL) Consortium.
RESULTS: Of 1,608 adult LT recipients at our center, 177 (11%) were eACLF-3. Thirty-five (20%) eACLF-3 recipients experienced futility. Predictors of futility were previous upper abdominal surgery (odds ratio [OR] = 4.6, p = 0.002), sepsis within 14 days before LT (OR = 5.9, p = 0.013), intubation because of pneumonia or acute respiratory distress syndrome (OR = 3.5, p = 0.010), worsening PaO2:FiO2 ratio (OR = 3.9, p = 0.008), and pre-LT base deficit (OR = 1.27, p = 0.007). Futility was predicted with an AUROC of 0.74 (SD 0.15). When compared with the MODEL Consortium, our cohort had improved 3-, 6-, and 12-month survivals of 89%, 85%, and 80%, compared with 83%, 79%, and 70%, respectively (p = 0.048); however overall 5-year survival was similar (63% vs. 59%, p = 0.14).
CONCLUSIONS: We report the largest single-center experience of LT for patients with eACLF-3, demonstrating acceptable survival despite high acuity, validated in the MODEL Consortium dataset. Prospective validation of the predictive model and identified risk factors is necessary, and may aid in appropriate selection of patients with ACLF-3 requiring maximal life support before LT.
IMPACT AND IMPLICATIONS: There has been persistent interest in the liver transplant community regarding transplant for acute-on-chronic liver failure grade 3 (ACLF-3) recipients. In this work, we report on a large single-center experience transplanting ACLF-3 recipients, specifically investigating an extreme subset of these patients who were all mechanically ventilated, receiving vasopressors, and receiving hemodialysis at time of transplant. We characterized their outcomes, identifying clear risk factors associated with futility in this hyperacute subgroup and demonstrating that with appropriate selection, even patients in this extreme subgroup can experience acceptable 5-year post-transplant survival. Although we could not externally validate our model because of data availability, the obtained external patient cohort of patients with extreme ACLF-3 broadly validates our findings. We feel that these results represent an important contribution to the liver transplant community given concerns about transplanting this hyperacute subpopulation. These results may help guide physicians in selecting appropriate candidates for transplant.