Disease Etiology Matters: Divergent Post-Transplant Outcomes in ACLF Across Primary Liver Diseases - 04/02/26
, Youngjae Cha 1, Mohammed Rifat Shaik 1, Ashton Harmacinski 1, Kimberly Schuster 2, Sarah Yang 1, Hyuk Joon Kwon 1, Mohamed Refaat 3, Abdul Yousaf 3, Nishat Anjum Shaik 1, Sarah Sandlow 1, Zainab Mujahid 1, Gregory Hongyuan Fan 2, Raza Malik 4
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Highlights |
• | Post-liver transplant outcomes in acute-on-chronic liver failure vary significantly by underlying liver disease etiology. |
• | Increasing ACLF severity is associated with higher post-transplant mortality across most etiologies. |
• | Alcohol-associated liver disease, hepatitis C, and MASLD demonstrated increased post-transplant mortality even at lower ACLF grades. |
• | Higher ACLF grades are associated with increased infectious, respiratory, septic, and cardiac causes of death across etiologies. |
• | These findings support etiology-specific risk stratification and individualized post-transplant counseling. |
Abstract |
Background & Aims |
Acute-on-chronic liver failure (ACLF) is associated with high short-term mortality. Liver transplantation remains the only definitive therapy; however, persistent organ scarcity emphasizes the need to better identify patients most likely to benefit. The long-term post-transplant prognosis of ACLF patients across different underlying liver disease etiologies remains poorly characterized.
Methods |
This study included data from the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research (STAR) Database, encompassing liver transplant (LT) recipients spanning from 2005 to 2019. Patients were segmented into distinct groupings: those without ACLF (control) and those with ACLF grades 1, 2, and 3 (exposures), as per the EASL-CLIF criteria. Primary outcomes encompassed post-transplant graft failure and all-cause mortality. Secondary outcomes included mortality attributed to specific organ system failures.
Results |
Among 36,748 liver transplant recipients, increasing ACLF severity was associated with higher post-LT all-cause mortality across most liver disease etiologies. Alcohol-associated liver disease (ALD), hepatitis C, and metabolic dysfunction–associated steatotic liver disease (MASLD) exhibited increased all-cause mortality across all ACLF grades. Autoimmune hepatitis (AIH) and hepatitis B demonstrated increased mortality primarily in advanced ACLF (AIH G3: aHR 1.53, 95% CI 1.25–1.86, p<0.001; hepatitis B G3 aHR 1.95, 95% CI 1.45–2.62, p<0.001), while hereditary liver disease showed no significant differences in all-cause mortality. Furthermore, ALD (aHR 1.72, 95%CI 1.23-2.41, p=0.002) and hepatitis C (aHR 1.48, 95%CI 1.19-1.55, p<0.001) with Grade 3 ACLF were associated with increased incidence of post-LT graft failure. Across etiologies, higher ACLF grades were associated with increased infectious, respiratory, septic, and cardiac causes of death.
Conclusion |
Our findings demonstrate etiology-specific differences in post-transplant mortality across ACLF grades. Alcohol-associated liver disease, hepatitis C, and MASLD were associated with increased mortality across all ACLF grades, while hepatitis B showed higher mortality in ACLF grades 1 and 3. Further prospective studies are warranted to clarify etiology-specific transplant benefit.
Le texte complet de cet article est disponible en PDF.Keywords : UNOS-STAR, post-transplant prognosis, post-transplant complications, etiologies of liver disease
Plan
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