TY - JOUR
T1 - Biomarker-assisted identification of sepsis-related acute liver impairment
T2 - A frequent and deadly condition in critically ill patients
AU - Jensen, Jens Ulrik Stæhr
AU - Peters, Lars
AU - Itenov, Theis S.
AU - Bestle, Morten
AU - Thormar, Katrin M.
AU - Mohr, Thomas T.
AU - Lundgren, Bettina
AU - Grarup, Jesper
AU - Lundgren, Jens D.
PY - 2019
Y1 - 2019
N2 - The prognostic impact of mild/moderate liver impairment among critically ill patients is not known. We aimed to determine whether acute liver impairment, as measured by several biomarkers, (i) is frequent, (ii) influences prognosis and (iii) to determine whether such an effect is specific for infected critically ill patients. A biomarker and clinical cohort study based on a randomized controlled trial. All-cause mortality was the primary endpoint. Biomarkers hyaluronic acid (HA), bilirubin, albumin, alkaline phosphatase and the international normalized ratio (INR) were determined. Multivariable statistics were applied to estimate risk increase according to liver biomarker increase at baseline and the model was adjusted for age, APACHE II, severe sepsis/septic shock vs. milder infection, chronic alcohol abuse Charlson's co-morbidity index, cancer disease, surgical or medical patient, body mass index, sex, estimated glomerular filtration rate, mechanical ventilation and the other biomarkers. Time-to-event graphs were used. The patients were critically ill patients (n = 1096) from nine mixed medical/surgical intensive care units without known hepatobiliary disease. HA levels differed between infected patients (median 210.8 ng/mL [IQR: 93.2-556.6]) vs. the non-infected (median 56.8 ng/mL [IQR: 31.9-116.8], p < 0.001). Serum HA quartiles 2, 3 and 4 were independent predictors of 90-day all-cause mortality for the entire population (infected and non-infected). However, the signal was driven by the infected patients (positive interaction test, no signal in non-infected patients). Among infected patients, HA quartiles corresponded directly to the 90-day risk of dying: 1st quartile: 57/192 = 29.7%, 2nd quartile: 84/194 = 43.3%, 3rd quartile: 90/193 = 46.6%, 4th quartile: 101/192 = 52.3 %, p for trend: <0.0001. This finding was confirmed in adjusted analyses: hazard ratio vs. 1st quartile: 2nd quartile: 1.3 [0.9-1.8], p = 0.14, 3rd quartile: 1.5 [1.1-2.2], p = 0.02, 4th quartile: 1.9 [1.3-2.6], p < 0.0001). High bilirubin was also an independent predictor of mortality. Among infected critically ill patients, subtle liver impairment, (elevated HA and bilirubin), was associated with a progressive and highly increased risk of death for the patient; this was robust to adjustment for other predictors of mortality. HA can identify patients at high risk.
AB - The prognostic impact of mild/moderate liver impairment among critically ill patients is not known. We aimed to determine whether acute liver impairment, as measured by several biomarkers, (i) is frequent, (ii) influences prognosis and (iii) to determine whether such an effect is specific for infected critically ill patients. A biomarker and clinical cohort study based on a randomized controlled trial. All-cause mortality was the primary endpoint. Biomarkers hyaluronic acid (HA), bilirubin, albumin, alkaline phosphatase and the international normalized ratio (INR) were determined. Multivariable statistics were applied to estimate risk increase according to liver biomarker increase at baseline and the model was adjusted for age, APACHE II, severe sepsis/septic shock vs. milder infection, chronic alcohol abuse Charlson's co-morbidity index, cancer disease, surgical or medical patient, body mass index, sex, estimated glomerular filtration rate, mechanical ventilation and the other biomarkers. Time-to-event graphs were used. The patients were critically ill patients (n = 1096) from nine mixed medical/surgical intensive care units without known hepatobiliary disease. HA levels differed between infected patients (median 210.8 ng/mL [IQR: 93.2-556.6]) vs. the non-infected (median 56.8 ng/mL [IQR: 31.9-116.8], p < 0.001). Serum HA quartiles 2, 3 and 4 were independent predictors of 90-day all-cause mortality for the entire population (infected and non-infected). However, the signal was driven by the infected patients (positive interaction test, no signal in non-infected patients). Among infected patients, HA quartiles corresponded directly to the 90-day risk of dying: 1st quartile: 57/192 = 29.7%, 2nd quartile: 84/194 = 43.3%, 3rd quartile: 90/193 = 46.6%, 4th quartile: 101/192 = 52.3 %, p for trend: <0.0001. This finding was confirmed in adjusted analyses: hazard ratio vs. 1st quartile: 2nd quartile: 1.3 [0.9-1.8], p = 0.14, 3rd quartile: 1.5 [1.1-2.2], p = 0.02, 4th quartile: 1.9 [1.3-2.6], p < 0.0001). High bilirubin was also an independent predictor of mortality. Among infected critically ill patients, subtle liver impairment, (elevated HA and bilirubin), was associated with a progressive and highly increased risk of death for the patient; this was robust to adjustment for other predictors of mortality. HA can identify patients at high risk.
KW - biomarkers
KW - infection
KW - liver impairment
KW - mortality
U2 - 10.1515/cclm-2018-1350
DO - 10.1515/cclm-2018-1350
M3 - Journal article
C2 - 30951497
AN - SCOPUS:85064138883
VL - 57
SP - 1422
EP - 1431
JO - Clinical Chemistry and Laboratory Medicine
JF - Clinical Chemistry and Laboratory Medicine
SN - 1434-6621
IS - 9
ER -