Burden of invasive fungal disease in patients with severe alcoholic hepatitis in France: a 2012-2021 national retrospective study
Résumé
Background: There is a lack of knowledge on the burden of invasive fungal disease in patients with severe alcoholic hepatitis. Methods: Among the 1,438,049 patients diagnosed with alcohol use disorders in French hospitals between 2012 and 2021, we selected individual’s with hepatic failure, portal hypertension bleeding, transjugular liver biopsy, or extrahepatic organ failure within 4 weeks following the diagnosis of alcoholic hepatitis. Our primary objective was to investigate the incidence of invasive fungal disease abd to assess the associated risk factors. We examined the 6-month mortality rate as an outcome measure. The main exposure was invasive fungal disease, while bacterial pneumonia served as the control exposure. To assess the strength of the associations, we employed multivariate logistic regression models and Cox proportional hazards models stratified by age categories, severe comorbidities, and deprivation. Results: The sample comprised 30,361 patients. Median (interquartile range) age was 55.0 (47.0-62.0) years and 73% were men. Invasive fungal disease [invasive candidosis (n=269, 0.9%); aspergillosis (n=105, 0.3%); pneumocystosis (n=47, 0.2%); cryptococcosis (n=3, 0.01%)] and bacterial pneumonia were diagnosed in 411 (1.4%) and 8,787 (10.8%) of patients, respectively. Approximately one-fifth (19.7%) of patients were documented with sepsis, and one-fourth progressed to extrahepatic organ failure. The 6-month mortality rate was ~1/4 (26.5%). Multivariate associations comprised younger ages [aOR 0.73 per decade, 95% CI (0.66-0.81) P<0.001]; sepsis [aOR 3.32, (2.63-4.21) P<0.001]; bacterial pneumonia [aOR 3.09 (2.48-3.85) P<0.001]; extrahepatic organ failure [aOR 2.19 (1.72-2.80) P<0.001]; severe comorbidities [aOR 1.14 (1.00-1.30) P<0.001]; and 6-month mortality [aOR 2.98 (2.40-3.71) P<0.001]. The probabilities of 6-month survival (95% CI) were 72.2 (71.7-72.7) and 40.5 (35.9-45.9) percent without and with invasive fungal disease, respectively (P<0.001), and 73.3 (72.8-73.9) and 63.2 (61.7-64.6) percent without and with bacterial pneumonia, respectively (P<0.001). Invasive fungal disease was associated with an independent, increased, instant, risk of 6-month death of ~80% [aHR 1.81 95% CI (1.58-2.08), P<0.001]. Bacterial pneumonia was not associated with mortality. Conclusion: Invasive fungal disease, and not bacterial pneumonia, increased the risk of 6-month mortality in patients with severe alcoholic hepatitis in France 2012-2021.