Invasive aspergillosis in patients with severe alcoholic hepatitis.
OBJECTIVE
Severe alcoholic hepatitis (AH) has a poor short-term prognosis. Although infections are frequent complications of AH, the incidence of invasive aspergillosis (IA) and its impact on outcome remain unknown.


METHODS
We prospectively followed 94 biopsy-proven severe AH episodes for 3 months. We retrospectively reviewed our diagnosis of IA based on EORTC/MSG and AspICU criteria, except for host factors.


RESULTS
Fifteen IA (6 proven, 8 probable, and 1 possible) were diagnosed after a median delay of 26 days following diagnosis of AH. The sites of infection were the lungs (n=11) and central nervous system (n=2), while IA was disseminated in 2 cases. Baseline MELD score ≥24 and ICU admission were independent risk factors for IA. Thirteen IA occurred in the context of corticosteroids, and 2 had received no specific treatment for AH. Non-response to corticosteroids at day 7 was not a risk factor for IA, but IA was associated with absence of liver improvement at day 28. Despite antifungal treatment, 3-month transplant-free survival of patients with IA was 0% compared to 53% in those without IA. IA, Lille score ≥0.45, and overt encephalopathy were independent predictors of transplant-free mortality.


CONCLUSIONS
IA is a frequent complication of severe AH and carries a very high risk of mortality. Systematic screening for IA should be recommended in these patients. Further studies are needed to identify high-risk populations requiring antifungal prophylactic treatment.
Department of Gastroenterology and Hepato-Pancreatology, Erasme Hospital, Brussels, Belgium; Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium; INSERM, U773, Centre de Recherche Biomédicale Bichat-Beaujon CRB3, Paris, France. Electronic address: tgustot@ulb.ac.be.
Thierry
T
Gustot
Department of Infectious Diseases, Erasme Hospital, Brussels, Belgium.
Evelyne
E
Maillart
Department of Gastroenterology and Hepato-Pancreatology, Erasme Hospital, Brussels, Belgium.
Massimo
M
Bocci
Department of Infectious Diseases, Erasme Hospital, Brussels, Belgium.
Rudy
R
Surin
Department of Gastroenterology and Hepato-Pancreatology, Erasme Hospital, Brussels, Belgium; Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium.
Eric
E
Trépo
Department of Gastroenterology and Hepato-Pancreatology, Erasme Hospital, Brussels, Belgium; Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium.
Delphine
D
Degré
Department of Digestive Surgery, Erasme Hospital, Brussels, Belgium.
Valerio
V
Lucidi
Department of Intensive Care Unit, Erasme Hospital, Brussels, Belgium.
Fabio Silvio
FS
Taccone
Department of Microbiology, Erasme Hospital, Brussels, Belgium.
Marie-Luce
ML
Delforge
Department of Intensive Care Unit, Erasme Hospital, Brussels, Belgium.
Jean-Louis
JL
Vincent
Department of Digestive Surgery, Erasme Hospital, Brussels, Belgium.
Vincent
V
Donckier
Department of Infectious Diseases, Erasme Hospital, Brussels, Belgium.
Frédérique
F
Jacobs
Department of Gastroenterology and Hepato-Pancreatology, Erasme Hospital, Brussels, Belgium; Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium.
Christophe
C
Moreno
D000305:Adrenal Cortex Hormones / Q000009:adverse effects; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000627:therapeutic use; D001228:Aspergillosis / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology*; D015331:Cohort Studies; D005260:Female; D005690:Galactose / Q000031:analogs & derivatives; D006519:Hepatitis, Alcoholic / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008351:Mannans / Q000097:blood; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
D000305:Adrenal Cortex Hormones; D000935:Antifungal Agents; D008351:Mannans; C012990:galactomannan; D005690:Galactose
ABIC; AH; AUROC; Age, serum Bilirubin, INR, and serum Creatinine; Alcoholic hepatitis; Aspergillosis; BAL; CSF; CT; Corticosteroids; GM; IA; ICU; INR; Infection; LT; MELD; NPV; PPV; PT; SBP; alcoholic hepatitis; area under receiver operating characteristic curve; bronchoalveolar lavage; cerebrospinal fluid; computed tomography; galactomannan; intensive care unit; international normalized ratio; invasive aspergillosis; liver transplantation; mDF; model for end-stage liver disease; modified discriminant function; negative predictive value; positive predictive value; prothrombin time; spontaneous bacterial peritonitis