Vol.3, No.1, 39-42 (2011) Health
Copyright © 2011 SciRes. Openly accessible at htt p://www.scirp.org/journal/HEALTH/
Clinical characteristics an d risk factors of 27 liver failure
patients complicated by invasive fungal infections
Longfeng Jiang, Jun Li*, Yaping Han, Yuan Liu, Youde Yan, Nian Chen, Li Dong,
Donghui Zhou, Ruiyun Wang
Department of Infectious Disease, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
*Corresponding Author: dr-lijun@vip.sina.com
Received 12 October 2010; revised 28 October 2010; accepted 1 November 2010
To investigate the clinical feature, risk factors
and outcome of treatment in patients with liver
failure complicated by invasive fungal infec-
tions. Retrospective analysis of the clinical data
and related factors of 27 patients with liver fail-
ure complicated by invasive fungal infections
was performed. These patients were admitted
from January 2007 to August 2009 in our de-
partment. Among them, Candida albicans ac-
counted for 17cases (54.84% ), albicans tropic als
for 4 cases (12.90%). Fungal infection in respi-
ratory tract and alimentary tract accounted for
58.06% and 11% respectively. 81.25% of them
had fever fluctuating from 37.4oC to 40oC.
81.25% had elevated white blood cell counts .All
had the usage of broad-spectrum of antibiotics,
whereas some of them used cor ticosteroid s and
had invasive medical manipulation for the
treatment. Most patients deteriorated after inva-
sive fungal infections. 21 cases accepted with
the treatment of antifungal drugs and mortality
rate was 63.00%. It was found that the invasive
fungal infection possibility of patients with liver
failure significantly increased. To prevent the
occurrence of invasive fungal infection, promptly
early treatment of liver failure, proper use of
antibiotics, cautious use or disuse of corticos-
teroids, reduction of invasive medical manipu-
lation should be well done. Early detection and
treatment of fungal infection are vital to de-
crease in mortality rate.
Keywords: Fungus Diseases; Immunity;
Liver Failure; Clinical Feature; Aspergillus
With the widespread use of broad-spectrum of anti-
biotics and invasive medical manipulation for the treat-
ment in clinical, the incidence of invasive fungal infec-
tions enhanced and candida albicans and aspergllus were
the main infection strain s [1]. Due to low immunity, the
patients with liver failure are prone to micro-ecological
unbalance. As conditional pathogenic bacteria, fungi
could increase rapidly. Therefore patients with liver fail-
ure can easily merge invasive fungal infections which
would lead to high mortality rate. In this study, the clin-
ical data and related factors of 27 patients are retrospec-
tively analyzed, who are treated in our department be-
cause of liver failure complicated by invasive fungal
2.1. Study Object
27 patients with liver failure complicated by invasive
fungal infections were admitted from January 2007 to
August 2009 in our department. The clinical data and
related factors of them were retrospective analyzed,
There are male 19 cases, female 8 cases. Their age
ranged from 33 to 82. Etiology: hepatitis B virus infec-
tion 16 cases, drug-induced hepatitis 3 cases, hepatitis C
virus infection 1case, autoimmune hepatitis 2 cases, al-
coholic hepatitis 2 cases, hepatitis B with hepatocellular
carcinoma 3 cases.
2.2. Diagnostic Criteria
Diagnostic criteria of liver failure are in accordance with
2006 liver failure treatment guidelines ” [2]. Diagnosis of
invasive fungal infection refers to 2003 Therapeutic
Guidelines in Systemic Fungal Infectionandth e d iagno-
sis and treatment guidelines of patients with severe inva-
sive fungal infectionswhich was developed by Critical
Care Medic ine Br anc h of th e Chinese Medical Association
in 2007 [3,4].
2.3. Fungi Cultivation and Identification
The cultivation of fungi was d etected using the BAC-
L.F. Jiang et al. / Health 3 (2011) 39-42
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TEC29210 training apparatus (BD). Identification used
fungal identification card (YBC) .
2.4. Record and Anal ysis
Records of patients include 1) sex, age, hospitalization
days, history of past illness, clinical features and com-
plications; 2) fungal infections: Use of antibiotics and
hormones, fungal infection time and type, location , pe-
ripheral blood white blood cell count, liver function,
invasi ve operation freque nc y a nd s o on.
2.5. Statistical Analysis
Data are expressed as mean ± standard error of the
mean. Differences between any two groups were deter-
mined by t test; P < 0.05 was considered statistically
3.1. The Fungal Infection Type and Proportion
There were 31 fu ngi isolated in 27 patients (Table 1).
3.2. The Fungal Infection location Distribution
31 fungi located in various parts, including 18 respi-
ratory tract infection (58.06%), intestinal infection 11
(35.48%), fungal blood culture positive 2 (6.45%) (Ta-
ble 2).
3.3. The C linical Featur es of Invasi ve Fun gal
Temperature: 22 cases (81.25%) showed fever and
temperature fluctuated from 37.4˚C to 40˚C; clinical
manifestation s: Symptoms of respiratory system in-
fection in clud ing throat discomfort, cough, sputum,
chest tightness, shortness of breath, etc.; critical cases all
had high fever and severe toxemia; principal symptoms
of digestive system infection were abdominal distension,
abdominal pain and diarrhea; fungal septicemia 2 cases
occurred severe h igh fever and gradually de terioration in
constitutional symptom, one of them emerged skin
Table 1. 31 fungal type and proportion.
type count proportion
Candida albicans 17 54.84%
Candida tropicalis 3 9.68%
Smooth Candida mycoderma 1 3.23%
Monilia krusei 5 16.13%
Other Candida 1 3.23%
Aspergillus 4 12.90%
Tab le 2. The fungal infection location distribution.
location cases proportion
respiratory tract infection 18 58.06%
intestinal infection 11 35.48%
fungal blood culture positive 2 6.45%
mucous membrane petechia and ecchymosis; Peripheral
blood cells: There are 17 cases whose values increased
(62.96%) and neutrophil ratio increased (75%); liver
function: Jaundice deepened 22 cases (81.48%), pro-
thrombin time prolongation 20 cases (74.07%). The
white blood cell (WBC), serum bilirubin (TBIL), proth-
rombin time (PT) were analyzed before and after fungal
infection in patient with liver failure. As a result, there
was statistical difference (Table 3).
3.4. Relationship between the Length of Stay
in Hospital and the Fungal Infection in
Among 27 patients ,the length of hospit aliza tio n
time is 5-76 days, average 36 ± 29 days, fungal infec-
tions occu rred 6-55 days after hospitaliz ation , average
18 ± 13 days;
Hormone usage: 11 cases used hormone inside or out-
side hospital, most of them were applied with hydrocorti-
sone 25 mg-50 mg each time to prevent nosocomial
transfusion reaction, yet 2 patients outside the hospital
used a larg e high dose of methylprednisolone. Antibiotic s
usage: 2 cases administered one type of broad-spectrum
antibiotic (7.4%), more than two types of broad-spectrum
antibiotics that included the third generation or fourth
generation cephalosporins, quinolones, penicillins and so
on. Invasive medical manipulation: abdominal paracente-
sis 23 case-times, deep venous catheterization 19
case-times, urinary tract intubation 5 case-times, lumbar
puncture 1case-time, some patients were operated with
two or more than two kinds invasive medical manipula-
3.5. Treatment and Outcome
In addition to positive treatment in primary diseases
among 27 liver failure patients complicated by invasive
fungal infection , 21 patients were also given fluconazole,
itraconazole, voriconazole, caspofungin, allicin and
Table 3. Laboratory index was analyzed (x ± s)before and after
fungal infection.
index before fungal infection after fungal infection P
WBC(10^9/L) 4.25 ± 4.49 9.82 ± 6.27 0.042
TB(umol/L) 165.39 ± 242.50 379.87 ± 242.29 0.046
L.F. Jiang et al. / Health 3 (2011) 39-42
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PT(S) 22.43 ± 6.02 32.38 ± 10.08 0.045
other anti-fungal treatment, and some of them even used
combined drug therapy. Result: Among 27 liver failure
patients complicated by invasive fungal infection, mor-
tality rate was 63.00%, which included auto-discharged
patients. 3 patients suffered from fungal pneumonia and
1 case having fungal sepsis died.
Fungi are widespread in nature as conditional patho-
gen, which exist in skin or mucous membrane and cause
infection by invasion when organism is in low immunity
[5]. Because of long time hospitalization, liver failure
patients were easy to show various complications such
as ascites, water-electrolyte imbalance and so on. Con-
ducted many kinds of invasive medical manipulation
which include abdominal paracentesis, deep venous ca-
theterization etc. Long term use of broad-spectrum anti-
biotics. Due to above factors, the opportunity of invasive
fungal infections significantly increases. Liver failure
patients would be further aggravate in liver damaged,
even lead to death if complicated by infection [6].
The pathogenic fungi of 27 liver failure patients with
invasive fungal infection were mainly Candida, which
was consistent with the results reported by Zhang Xu-
ehai, etc. [7] and Xie Min et al. [8]. This result illu-
strated that Candida were widely distributed in nature
and stronger pathogenicity in organism. Aspergillus in-
fection was once considered uncommon in the past [9],
but aspergillus infection rate in this group was 12.90%
(4/27), all for lung infection, and mortality rate was 75%.
The infection sites’ constitution ratios were respiratory
tract infections (58.06%), intestinal tract infections
(35.48%). The above summary indicated that spectrum
of fungal infection in severe hepatitis patients was ex-
panding with the improvement of diagnosis. The disease
severity was more complex and more emphasis should
be laid.
Liver failure patients combined with invasive fungal
infection were not obvious and specific clinical manife-
stations. It was not easy to identify the sym ptoms of liv-
er failure itself. After fungal infections, the majority of
patients would be exacerbated. The white blood cell
(WBC), serum bilirubin (TBIL), prothrombin time (PT)
were analyzed before and after fungal infection in pa-
tient with liver failure, there was statistically differ-
ent .These patients occurred conditions ( i.e., unexplained
fever, deteriorated disease progress, aggravated systemic
symptoms, poor effect of application broad spectrum
antibiotics) should be highly vigilant against invasive
fungal infection. Routine fungal examination should be
carried out to facilitate early diagnosis and give antifun-
gal treatment on time.
In this group, 27 cases with fungal infections occurred
in 6-55 days after adm is sion, al l exi sted in br oad-spectrum
antibiotic usage and invasive operation. Part of them used
hormone inside or outside hospital .According to the re-
port by Xie Min et al. [8], application of broad-spectrum
antibiotics, invasive operation, hormone usage, and dis-
eases severity etc., were closely related to liver failure
complicat ed by funga l i nfe cti ons.
Because of the complexity of fungal infection, multi-
tiered treatment were advocated in current treatment,
including preventive therapy, empirical therapy, preemp-
tive therapy and targeted therapy [4], specific fungus
preventive treatment in clinical work for high-risk pa-
tients could reduce incidence of invasive fungal infection
[10]. Amphotericin B, fluconazole, itraconazole, and vo-
riconazole are main therapeutical drugs for IFI now.
Amphotericin B has obvious adverse reaction, and most
patients are hard to tolerate. It has been reported that flu-
conazole had good anti-fungus effect [11]. The antimi-
crobial spectrum of fluconazole is nar row, and it is mai n-
ly sensitive to candida albicans, but not valid for
non-candida albicans and aspergillus. Furthermore, can-
didal drug resistance obviously increases after long-term
use [12]. Itraconazole has certain hepatotoxicity, so it is
cautiously used in severe hepatitis patients. Voriconazole
is a type of broad spectrum antifungal agent, and it has
good safety. Antifungus spectrum of voriconazole covers
main pathomycete such as candida, aspergillus, Crypto-
coccus and it is now a good choice for IFI therapy [12].
Therefore, even though most patients were executed an-
ti-fungal treatment, mortality was 63.00%, according to
report Xie Min et al. [7]. The mortality of liver failure
patients without complicated by fungal infections was
37.78%. This indicated that invasive fungal infection
would make liver failure more serious and increase the
mortality rate sig n ifican tly f urth er aggravated the original
liver failure an d increased the mortality ra te sign ificantly
in liver failure patients.
Currently the patients with liver failure do not have
specific treatment, but only early diagnosis and early
treatment; actively to prevent liver cell necrosis and
promote liver regeneration, positively treat etiology and
prevent complications [14]. For the liver failure patients,
according to clinical data analysis of invasive fungal in-
fection in this paper, we believe that some clinical work
should be paid attentation to, including 1) treat primary
disease, strengthen nutritional support , stabilize internal
environment, enhance body resistance; 2) rational use of
antibiotics, avoidance of the abuse in broad-spectrum
antibiotics and careful use of hormones; 3) reduction of
invasive operation as far as possible, strict implementa-
L.F. Jiang et al. / Health 3 (2011) 39-42
Copyright © 2011 SciRes. Openly accessible at htt p://www. scirp.org/journa l/HEALTH/
tion of the aseptic operation, intensive care etc., which
will be helpful to decrease the incidence of fungal infec-
tion in liver failure patients; 4) for liver failure patients,
closely monitor the changes of clinical manifestations in
the course of treatment, if situations appear such as the
new symptoms or signs unexplained original disease,
sudden deterioration of stable condition , invalidity of
antibiotic therapy. We should be highly vigilant against
the occurrence of fungal infection, retaining appropriate
specimens for etiology isolation, identification and ac-
quisition of drug susceptibility results as soon as possi-
ble, in order to achieve early diagnosis in fungal infec-
tion. Moreover, a number of new rapid detection me-
thods included fungal cell wall compounds and fungal
genes DNA etc. were increasingly concerned [15]. Com-
bination of Various diagnostic methods was beneficial to
the early diagnosis of invasive fungal, and provided evi-
dence for the early and effective treatment of fungal in-
fections, thus further improving the survival rate of liver
failure patients.
This study was supported by the National Natural Science Founda-
tion, the funding for Jiangsu Province Key Laboratory and key medical
personnel in Infectious Diseas es and the funding for Guiding Research
Projects of Health Departmen t of Jiangsu Province, China.
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