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BACKGROUND & AIMS: In experimental models, alcohol induces acute changes in lipid metabolism that cause hepatocyte lipoapoptosis and inflammation. Here we study human hepatic lipid turnover during controlled alcohol intoxication. METHODS: We studied 39 participants with 3 distinct hepatic phenotypes: alcohol-related liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), and healthy controls. Alcohol was administrated via nasogastric tube over 30 min. Hepatic and systemic venous blood was sampled simultaneously at 3 time points: baseline, 60, and 180 min after alcohol intervention. Liver biopsies were sampled 240 min after alcohol intervention. We used ultra-high performance liquid chromatography mass spectrometry to measure levels of more than 250 lipid species from the blood and liver samples. RESULTS: After alcohol intervention, the levels of blood free fatty acid (FFA) and lysophosphatidylcholine (LPC) decreased, while triglyceride (TG) increased. FFA was the only lipid class to decrease in NAFLD after alcohol intervention, whereas LPC and FFA decreased and TG increased after intervention in ALD and healthy controls. Fatty acid chain uptake preference in FFAs and LPCs were oleic acid, linoleic acid, arachidonic acid, and docosahexaenoic acid. Hepatic venous blood FFA and LPC levels were lower when compared with systemic venous blood levels throughout the intervention. After alcohol intoxication, liver lipidome in ALD was similar to that in NAFLD. CONCLUSIONS: Alcohol intoxication induces rapid changes in circulating lipids including hepatic turnaround from FFA and LPC, potentially leading to lipoapoptosis and steatohepatitis. TG clearance was suppressed in NAFLD, possibly explaining why alcohol and NAFLD are synergistic risk factors for disease progression. These effects may be central to the pathogenesis of ALD. CLINICAL TRIALS REGISTRATION: The study is registered at Clinicaltrials.gov (NCT03018990). LAY SUMMARY: We report that alcohol induces hepatic extraction of free unsaturated fatty acids and lysophosphatidylcholines, hepatotoxic lipids which have not been previously associated with alcohol-induced liver injury. We also found that individuals with non-alcoholic fatty liver disease have reduced lipid turnover during alcohol intoxication when compared with people with alcohol-related fatty liver disease. This may explain why alcohol is particularly more harmful in people with non-alcoholic fatty liver and why elevated BMI and alcohol have a synergistic effect on the risk of liver-related death.
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Introducción: Se conoce que la leucocitosis y la hiperglucemia se correlacionan a corto plazo con peor pronóstico en pacientes con síndrome coronario agudo, pero su novel relación, denominada índice leucoglucémico (ILG), se ha evaluado escasamente. Objetivos: Analizar el valor pronóstico del ILG en pacientes con infarto agudo de miocardio con elevación del segmento ST (IAMCEST) y su valor agregado a los puntajes de riesgo clásicos. Material y métodos: Se analizaron los pacientes con diagnóstico de IAMCEST del Registro Multicéntrico SCAR (Síndromes Coronarios Agudos en Argentina). El punto final analizado fue la muerte o Killip Kimball 3-4 (KK 3-4) en el período hospitalario. Se analizó el ILG tanto como variable continua como en cuartiles según los valores de los percentiles 25, 50 y 75. Resultados: Se analizaron 405 de 476 pacientes con diagnóstico final de IAMCEST. La presencia del punto final fue significativamente creciente por cuartiles de ILG: 0%, 7,60%, 9,30% y 30,60% (p < 0,0001). El área bajo la curva ROC del ILG para el punto final combinado fue de 0,77 [(IC 95% 0,71-0,88); p = 0,0001]; el mejor valor de corte pronóstico fue de 1.000. La presencia de muerte o KK 3-4 fue del 0% y del 13% en los IAMCEST con ILG menor o mayor de 1.000, respectivamente. En un modelo de regresión logística multivariado, el ILG se asoció independientemente con muerte o KK 3-4. El área bajo la curva ROC del puntaje TIMI para IAMCEST fue de 0,58. El agregado del ILG incrementó su capacidad discriminatoria a 0,66 (p = 0,001). Conclusiones: El ILG demostró que es un predictor independiente de mala evolución en el IAMCEST (muerte o KK 3-4), con valor aditivo al puntaje TIMI.
Background: Leukocytosis and hyperglycemia correlate with worse short-term prognosis in patients with acute coronary syndrome, but their new relationship, called leuko-glycemic index (LGI), has been scarcely evaluated. Objectives: The aim of this study was to analyze the prognostic value of LGI in patients with ST-segment-elevation acute myocardial infarction (STEMI) and its added value to classical risk scores. Methods: Patients diagnosed with STEMI from the SCAR (Acute Coronary Syndromes in Argentina) Multicenter Registry were analyzed. The final endpoint was death or in-hospital Killip-Kimball 3-4 (KK 3-4). The LGI was analyzed as a continu-ous variable and in quartiles according to 25, 50 and 75 percentile values. Results: The study evaluated 405 out of 476 patients with final STEMI diagnosis. Presence of the primary endpoint significantly increased per LGI quartile: 0%, 7.60%, 9.30% and 30.60% (p < 0.0001). The LGI area under the ROC curve for the composite endpoint was 0.77 [(95% CI 0.71-0.88); p = 0.0001]; the best prognostic cut-off value was 1000. Presence of death or KK 3-4 was 0% and 13% in STEMI patients with LGI below or above 1000, respectively In a multivariate logistic regression model, LGI was independently associated with death or KK 3-4. The area under the ROC curve of the TIMI risk score for STEMI was 0.58. The addition of LGI increased its discriminatory capacity to 0.66 (p = 0.001). Conclusions: The LGI was an independent predictor of adverse outcome in STEMI patients (death or KK 3-4), adding prognostic value to the TIMI risk score.
