Clinical characteristics and risk factors of 27 liver failure patients complicated by invasive fungal infections

doi:10.4236/health.2011.31008

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Vol.3, No.1, 39-42 (2011) Health

doi:10.4236/health.2011.31008

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: [email protected]

Received 12 October 2010; revised 28 October 2010; accepted 1 November 2010

ABSTRACT

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

1. INTRODUCTION

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

infection.

2. METHODS

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 Infection” and “th e d iagno-

sis and treatment guidelines of patients with severe inva-

sive fungal infections” which 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

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

signiﬁcant.

3. RESULTS

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

Infection

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

Patient

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-

tions.

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

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.

4. DISCUSSIO N

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

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.

5. ACKNOWLEDGE MENTS

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.

REFERENCES

[1] Zhou, H.H., De, M.T., Guo, Z.L., et al. (2010) Clinical

characteristics and therapeutic analysis of invasive fungal

infection in chronic severe hepatitis patients. Medical

Science, 35, 537-542.

[2] Liver Failure and Artificial Liver Group, Chinese Society

of Infectious Diseases, Chinese Medical Association,

Severe Liver Diseases and Artificial Liver Group, Chi-

nese Society of Hepatology, Chinese Medical Associa-

tion (2006) Diagnostic and treatment guidelines for liver

failure. Journal of Clinical Hepatology, 9, 321-324.

[3] Richardson, I.M.D. and Jones, B.L. (2003) Therapeutic

guidelines in systemic fungal infections. 3rd Edition,

Current Medical Literature, 19-20.

[4] Critical Care Medicine Branch of the Chinese Medical

Association (2007) Diagnosis and treatment guidelines of

patients with severe invasive fungal infections. Chinese

Journal of Internal Medicine, 46, 960-966.

[5] Dong, C.H., We i , J., Zhi, H., et al. (2005) Infection and

resistance of fungus. Chinese Journal of Nosocomiology,

15, 345-347.

[6] Julie, P. and William, M.L. (2005) The management of

acute liver failure. Hepatology, 41, 1179-1196.

doi:10.1002/hep.20703

[7] Zhang, X.H., Zhang, G.H., Man, C.J., et al. (2004) Clini-

cal study on the severe hepatitis with nosocomial fungal

infections and risk factors. Chinese Journal of Hepatol-

ogy, 12, 389-391.

[8] Min, X., Qiang, C. and Qian, C.F. (2007) Clinical analy-

sis of 186 severe hepatitis and cirrhosis patients with no-

socomial fungal infections. Journal of Clinical Hepatol-

ogy, 10, 24-27.

[9] Qi, F.X., Mei, L., Bing, L., et al. (2004) Risk factors of

fungal colonization in patients with chronic liver disease:

a prospective study. Chinese Journal of Nosocomiology,

14, 1344-1346.

[10] Segal, B.H., Amyroudis, N.G., Battiwalla, M., et al.

(2007) Prevention and early treatment of invasive fungal

infection in patients with cancer and neutropenia and in

stem cell transplant recipients in the era of newer broad-

spectrum antifungal agents and diagnostic adjuncts.

Clinical Infective Disease, 44, 402-409.

doi:10.1086/510677

[11] Rex, J.H. and Sobel, J.D. (2001) Prophylactic antifungal

therapy in the intensive care unit. Clinical Infective Dis-

ease, 32, 1191-1200. doi:10.1086/319763

[12] Pfaller, M.A., Jones, R.N., Messer, S.A., et al. (1998)

National surveillance of nosocomial blood stream infec-

tion due to Candida albicans: Frequency of occurrence

and antifungal susceptibility in the SCOPE Program.

Diagnostic Microbiology and Infectious Disease, 31,

327-332. doi:10.1016/S0732-8893(97)00240-X

[13] Vehreschild, J.J., Bohme, A., Reichert, D., et al. (2008)

Treatment of invasive fungal infections in clinical prac-

tice: A multi-centre survey on customary dosing, treat-

ment indications, efficacy and safety of voriconazole.

International Journal of Hematology, 87, 126-131.

doi:10.1007/s12185-008-0045-z

[14] Yi ng, J.W. (2008) Liver failure: Definitions, diagnosis

and treatment. Journal of Clinical Hepatology, 16, 725-

727.

[15] Ju, P.D. and Chun, H.L., et al. (2007) Invasive diagnosis

and treatment of fungal infections. Chinese Journal of

Infection Control, 6, 359-364.