Invasive Pulmonary Aspergillosis in Patients with Acute-On-Chronic Liver Failure
Z WU
0
1
Z LING
0
1
F SHAO
0
1
J SHENG
0
1
L LI
0
1
0
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University
, Hangzhou, Zhejiang,
China
1
Professor Lanjuan Li State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University
, Hangzhou, Zhejiang 310003,
China
-
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Invasive Pulmonary Aspergillosis in
Patients with Acute-on-chronic Liver
Failure
OBJECTIVE: Patients with acute-on-chronic
liver failure (AoCLF) are prone to various
infections, including invasive pulmonary
aspergillosis (IPA). This retrospective study
investigated the relationship between
AoCLF and IPA in a large patient cohort.
METHODS: Twenty-nine out of 470 patients
with AoCLF, who were diagnosed with
definite or probable IPA by clinical and
laboratory parameters and were treated
with voriconazole, were analysed for
predisposing factors for IPA and clinical
outcome. RESULTS: Imaging findings, such
as the halo sign and increased white blood
cell count, contributed to the early
diagnosis of IPA. Patients with AoCLF and
IPA experienced fever, cough and chest
pain and, despite treatment with
antifungal therapy, most (25/29 patients)
died within 7 days. Possible risk factors for
IPA included prolonged antibiotic therapy
and dexamethasone exposure.
CONCLUSIONS: AoCLF with prolonged
antibiotic therapy and dexamethasone
exposure carries a high risk for IPA. AoCLF
patients with IPA involved in this study
exhibited fever, cough, chest pain and
increased white blood cell count, and their
imaging findings were useful for the early
diagnosis of IPA.
Aspergillus spp. cause a wide spectrum of
lung diseases, and are commonly isolated
from soil, plant debris and indoor
environments, including hospitals. Invasive
pulmonary aspergillosis (IPA) is a potentially
severe and frequently fatal early
complication in certain
immunocompromised and immunosuppressed
aZ Wu and Z Ling contributed equally to this work.
patients, such as transplant recipients and
chemotherapy patients, with a mortality rate
exceeding 90% in these patients.1 4 Chronic
necrotizing pulmonary aspergillosis and
Aspergillus spp. pneumonia, often with
dissemination, are two well-known forms of
this invasive disease.5,6 IPA mainly occurs in
patients with malignancy who experience
deep and prolonged neutropenia, but there
are other established risk factors (such as
high-dose, long-term corticosteroid therapy
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or advanced forms of acquired
immunodeficiency syndrome).7 Patients with
liver disease, especially liver failure, are
often immunocompromised and are also
prone to various infections including
bacterial, viral and fungal infections such as
IPA.8 12 Prodanovic et al.13 reported four
cases of IPA in patients with Child-Pugh class
C liver cirrhosis in a critical care setting,
which is considered a possible risk factor for
IPA. The diagnosis of IPA can be elusive
because the fungus is difficult to isolate; in
addition, its symptoms and signs are not
specific, and the effects of antifungal agents
and duration of treatment for IPA remain
inadequate. Together, these are major
complicating factors for
immunocompromised patients and might be
associated with increased mortality rates.
Although IPA is the major factor associated
with poor prognosis, there has been no
largescale analysis of IPA in patients with liver
disease, especially acute-on-chronic liver
failure (AoCLF), which denotes an acute
deterioration of known or unknown chronic
liver disease or a gradual decompensation of
end-stage liver disease.
The current study determined the clinical
presentation, predisposing factors and
outcome of IPA in patients with AoCLF.
Possible risk factors for IPA and treatment
regimens were analysed in these patients, in
an effort to determine the basis for the high
mortality rate observed.
Patients and methods
STUDY POPULATION
This retrospective study included patients
with AoCLF who were admitted to the State
Key Laboratory for Diagnosis and Treatment
of Infectious Diseases, Department of
Infectious Diseases, The First Affiliated
Hospital, College of Medicine, Zhejiang
University, China, between July 2007 and
December 2010. Patients with acute
deterioration in liver function over 2 4
weeks with a defined inflammation-related
precipitant (infection or alcoholic hepatitis),
leading to: severe progressive clinical
deterioration despite > 48 h supportive care;
increasing jaundice (serum bilirubin > 100
mol/l); evidence of abnormal coagulation
(defined as an international normalized
ratio [INR] 1.5); and either encephalopathy
(grade 2) or hepatorenal syndrome (HRS)
in those with clinical, radiological,
biochemical and histological evidence of
cirrh (...truncated)