TY - JOUR
T1 - Ammonia and urea metabolism in acute liver failure
T2 - A multicentre cohort study
AU - Cardoso, Filipe S.
AU - Toapanta, David
AU - Jimenez, Natalia
AU - Fidalgo, Pedro
AU - Figueiredo, António
AU - Valdivieso, Miriam
AU - Germano, Nuno
AU - Rule, Jody A.
AU - Lee, William M.
AU - Abraldes, Juan G.
AU - Reverter, Enric
AU - Karvellas, Constantine J.
N1 - Publisher Copyright:
© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
PY - 2024
Y1 - 2024
N2 - Background & Aims: Ammonia is metabolized into urea in the liver. In acute liver failure (ALF), ammonia has been associated with survival. However, urea variation has been poorly studied. Methods: Observational cohort including ALF patients from Curry Cabral Hospital (Lisbon, Portugal) and Clinic Hospital (Barcelona, Spain) between 10/2010 and 01/2023. The United States ALF Study Group cohort was used for external validation. Primary exposures were serum ammonia and urea on ICU admission. Primary endpoint was 30-day transplant-free survival (TFS). Secondary endpoint was explanted liver weight. Results: Among 191 ALF patients, median (IQR) age was 46 (32; 57) years and 85 (44.5%) were males. Overall, 86 (45.0%) patients were transplanted and 75 (39.3%) died. Among all ALF patients, following adjustment for age, sex, body weight, and aetiology, higher ammonia or lower urea was independently associated with higher INR on ICU admission (p <.009). Among all ALF patients, following adjustment for sex, aetiology, and lactate, higher ammonia was independently associated with lower TFS (adjusted odds ratio (95% confidence interval [CI]) = 0.991 (0.985; 0.997); p =.004). This model predicted TFS with good discrimination (area under receiver operating curve [95% CI] = 0.78 [0.75; 0.82]) and reasonable calibration (R2 of 0.43 and Brier score of 0.20) after external validation. Among transplanted patients, following adjustment for age, sex, actual body weight, and aetiology, higher ammonia (p =.024) or lower (p <.001) urea was independently associated with lower explanted liver weight. Conclusions: Among ALF patients, serum ammonia and urea were associated with ALF severity. A score incorporating serum ammonia predicted TFS reasonably well.
AB - Background & Aims: Ammonia is metabolized into urea in the liver. In acute liver failure (ALF), ammonia has been associated with survival. However, urea variation has been poorly studied. Methods: Observational cohort including ALF patients from Curry Cabral Hospital (Lisbon, Portugal) and Clinic Hospital (Barcelona, Spain) between 10/2010 and 01/2023. The United States ALF Study Group cohort was used for external validation. Primary exposures were serum ammonia and urea on ICU admission. Primary endpoint was 30-day transplant-free survival (TFS). Secondary endpoint was explanted liver weight. Results: Among 191 ALF patients, median (IQR) age was 46 (32; 57) years and 85 (44.5%) were males. Overall, 86 (45.0%) patients were transplanted and 75 (39.3%) died. Among all ALF patients, following adjustment for age, sex, body weight, and aetiology, higher ammonia or lower urea was independently associated with higher INR on ICU admission (p <.009). Among all ALF patients, following adjustment for sex, aetiology, and lactate, higher ammonia was independently associated with lower TFS (adjusted odds ratio (95% confidence interval [CI]) = 0.991 (0.985; 0.997); p =.004). This model predicted TFS with good discrimination (area under receiver operating curve [95% CI] = 0.78 [0.75; 0.82]) and reasonable calibration (R2 of 0.43 and Brier score of 0.20) after external validation. Among transplanted patients, following adjustment for age, sex, actual body weight, and aetiology, higher ammonia (p =.024) or lower (p <.001) urea was independently associated with lower explanted liver weight. Conclusions: Among ALF patients, serum ammonia and urea were associated with ALF severity. A score incorporating serum ammonia predicted TFS reasonably well.
KW - hepatitis
KW - liver regeneration
KW - necrosis
KW - nitrogen
KW - outcomes
KW - transplant
UR - http://www.scopus.com/inward/record.url?scp=85198729777&partnerID=8YFLogxK
U2 - 10.1111/liv.16043
DO - 10.1111/liv.16043
M3 - Article
AN - SCOPUS:85198729777
SN - 1478-3223
JO - Liver International
JF - Liver International
ER -