Bacterial Infection in Cirrhotic Patientsand Its Relationship With AlcoholHeitor Rosa, M.D., Ame´rico O. Silverio, M.D., Rafael F. Perini, M.D., and Cla´udia B. Arruda, M.D.Department of Gastroenterology and Hepatology, Federal University of Goia´s, School of Medicine, Goiaˆnia,Goias, Brazil

OBJECTIVE: Infections are regarded as a major complicationand an important cause of death in cirrhotics. Alcohol is apredisposing factor to infections in such patients. This studywas undertaken to compare the frequency and evolution ofbacterial infection among alcoholic and nonalcoholic cir-rhotics.

METHODS: To observe this relationship, we retrospectivelystudied a cohort of 382 cirrhotic inpatients, 201 of whomwere alcoholic (alcohol intake$80 g/day for$10 yr) and181 of whom were nonalcoholic.

RESULTS: A total of 128 (33.5%) patients presented withinfection upon hospitalization, 78 of whom were alcoholicand 50 of whom were nonalcoholic (p 5 0.02). A total of157 cases of infection were diagnosed, with spontaneousbacterial peritonitis as the most prevalent one (54.1%),followed by pneumonia (18.5%), infection of the soft parts(10.8%), and urinary tract infection (7.0%). Infection anddeaths were more frequent in patients with Child-Pugh Cthan in those with Child-Pugh A/B (p 5 0.003,p 5 0.0002respectively). Alcoholic patients with Child-Pugh A/B weremore susceptible to infection compared to nonalcoholicpatients (p 5 0.02), although no difference was noted as tothe number of deaths (p 5 0.1). With regard to patients withChild-Pugh C, no statistical difference was found in theinfections or deaths among alcoholics and nonalcoholics(p 5 0.8, p 5 0.8).

CONCLUSIONS: Our findings suggest that, despite the factthat bacterial infections are more common in cirrhotic al-coholics, its seems that the mortality rate is associated morewith the severity than with the etiology of the hepaticdisease. (Am J Gastroenterol 2000;95:1290–1293. © 2000by Am. Coll. of Gastroenterology)

INTRODUCTION

The liver plays an important role in the removal of endo-toxins and bacteria from the bloodstream (1). Patients withchronic liver disease show a decrease in the capability ofremoval because of such immune response abnormalities asa reduction in the complement levels in both serum andascitic liquid (2, 3), a decrease in the phagocytosis capabilityof the hepatic reticuloendothelial system (4, 5), an alteration

in the function of neutrophils (6), and a reduction of theopsonic activity of the ascitic liquid (7).

Hepatic cirrhosis may be considered one of the mostcommon causes of acquired immunodeficiency (8). As aconsequence of this multifactorial immunodeficiency, theincidence of bacterial infection is higher in cirrhotic patientswhen compared to that in the general population (3). Itshould be noted that this is a major complication and animportant cause of death in the natural history of cirrhosis(9–14).

Acute and chronic alcohol abuse fosters an increase in thepermeability of the intestinal mucosa, facilitating the ab-sorption of endotoxins (15), and inhibits the activity ofKupffer cells (16, 17), causing a double dysfunction thatfavors the development of endotoxemia in patients withalcohol-induced hepatic disease (18). In fact, the prevalenceof endotoxemia is higher in alcoholic cirrhotics when com-pared to nonalcoholics (19).

Besides having an important role in the onset and aggra-vation of the hepatic lesion, endotoxins are also responsiblefor such extrahepatic events as hypotension, alteration of therenal function, consumption coagulopathy, and the produc-tion of cytokines (18, 20). The facts described here allow forthe supposition that such infections may be more frequentand more severe in cirrhotic alcoholic patients.

This study aimed to compare the frequency and evolutionof bacterial infection between the groups of cirrhotic alco-holics and that of nonalcoholics.

MATERIALS AND METHODS

The medical records of 382 cirrhotic patients hospitalized atthe Service of Gastroenterology and Hepatology of theHospital of Clinics of the Medical School of the FederalUniversity of Goias, Brazil, were retrospectively reviewedbetween January 1986 and May 1998. The collected datawere entered in the Databank Arago dBxl2.1 program(WordTech Systems, Inc., CA).

Patients were divided into two groups according to theetiology of cirrhosis. Group I consisted of patients withalcohol-related cirrhosis with no other causes of chronicliver disease; group II consisted of patients with non–alco-hol-related cirrhosis. Alcohol was considered to be the cause

THE AMERICAN JOURNAL OF GASTROENTEROLOGY Vol. 95, No. 5, 2000© 2000 by Am. Coll. of Gastroenterology ISSN 0002-9270/00/$20.00Published by Elsevier Science Inc. PII S0002-9270(00)00818-2

of cirrhosis when the daily intake was$80 g for malepatients and$60 g for female patients for a duration of$10 yr.

The diagnosis for cirrhosis was established through he-patic biopsy in 141 patients (37.0%) or was based on un-equivocal clinical data, which usually included hepatomeg-aly or splenomegaly, jaundice or ascites, spider angiomas,and the correlation between laboratory findings and imagingwhen biopsy could not be performed for either clinical ortechnical reasons (21). The Child-Pugh index was used toassess the severity of cirrhosis (22).

Data related to gender, age, number of times of hospital-ization, clinical follow-up, time and amount (in grams) ofalcohol consumption, presence and site of infection, resultof cultures of blood, ascitic liquid, as well as other biolog-ical tissues and serum leukocytes counts were consideredfor the analysis.

The ascitic fluid was studied in all patients with ascites.Spontaneous bacterial peritonitis (SBP) was diagnosedwhen cytological examination showed counts of polymor-phonuclear leukocytes$250 cells/mm3, irrespective of theculture result, in the absence of an intra-abdominal source ofinfection.

Urinary tract infection (UTI) was diagnosed through theisolation of .106 bacteria/mm3 or through clinical symp-toms and leukocyturia. Bronchopneumonia (BCP) was di-agnosed through both clinical and radiological examina-tions. Other infections in different sites were diagnosedthrough specific methods according to the infectious pro-cess.

The statistical analysis was carried out using the Epinfo6.0 (Centers for Disease Control Epidemiology ProgramOffice, Atlanta, GA). Either the Kruskal-Wallis or thex2

test of association was used with the purpose of comparingthe averages between the two samples, with correctionthrough the test of Yates or the exact test of Fisher (bicau-dal) whenever appropriate. Results are expressed as average6 SD. The level of significance for all tests was set at 5%.

The Committee of Ethics of the Institution approved thecurrent study.

RESULTS

A total of 260 male patients (68.1%) and 122 female pa-tients (31.9%) were studied. Their ages averaged 45.9614.8 yr (range, 11–82 yr). All of these 382 patients ac-counted for 737 hospitalizations in our service, correspond-ing to an average of 1.9 hospitalizations per patient.

Group I (alcoholic cirrhotics) consisted of 201 patients(52.6%), 162 (80.6%) of whom were male, and the averageage was 46.56 12.4 yr (range, 16–82 yr). The averagenumber of hospitalizations was 1.8 per patient. Group II(nonalcoholic cirrhotics) consisted of 181 patients (47.4%),98 (54.1%) of whom were male, and the average age was45 6 17.0 yr (range,11–80 yr). When the two groups werecompared, no statistically significant differences were foundamong the number of patients, the age average and theaverage number and length of hospitalization (Table 1).

A total of 128 (33.5%) patients presented with bacterialinfection, totaling 157 infectious processes. The most fre-quent infection was SBP, which accounted for 85 episodesof infections (54.1%), followed by 29 (18.5%) cases ofpneumonia, 17 (10.8%) cases of infection of the soft parts,and 11 (7.0%) cases of UTI. When the patients weregrouped separately, it was noted that 78 (38.8%) of those ingroup I and 50 (27.6%) of those in group II (p 5 0.02)presented with infections. Of the 78 patients with bacterialinfection in group I, 25 (32.0%) died, compared to 22(44.0%) of the 50 patients in group II (p 5 0.2) (Table 1).

The Child-Pugh classification was applicable in 347(90.8%) patients, distributed as follows: 87 (25.1%) Child-Pugh A, 176 (50.7%) Child-Pugh B and 84 (24.2%) Child-Pugh C. Of 84 patients with Child-Pugh C, 41 (49.0%) hadinfection, compared to 80 of 263 cirrhotic patients withChild-Pugh A or B (30.0%) (p 5 0.003) (Table 2). Of 41(60.9%) patients with Child-Pugh C who had infection, 25died, compared to 20 of 80 (25.0%) patients with Child-Pugh A or B with infection (p 5 0.0002).

Of 141 (36.9%) patients from group I with Child-Pugh Aor B, 52 developed infection, compared with 28 of 122(22.9%) patients of group II with the same Child-Pugh score

Table 1. Profile of 382 Cirrhotic Patients Distributed in Groups According to the Use of Alcohol

Profile

Group

Total p ValueGroup I

(Alcoholics)Group II

(Nonalcoholics)

n (%) 201 (52.6) 181 (47.4) 382 (100.0) NSMen (%) 162 (62.3) 98 (37.7) 260 (68.1) ,0.05Women (%) 39 (32.0) 83 (68.0) 122 (31.9) ,0.05Age (x 6 SD) 46.56 12.4 45.06 17.0 45.86 14.8 NSChild-Pugh A/B 141 (70.1) 122 (67.4) 263 (75.8) NSChild-Pugh C 51 (26.6) 33 (21.3) 84 (24.2) NSTimes of hospitalization (media/patient) 1.8 2.0 1.9 NSDays of hospitalization per patient (X6 SD) 20.06 13.0 27.06 26.0 23.06 20.0 NSWith infection (%) 78 (38.8) 50 (27.6) 128 (33.5) ,0.05

Deaths (%) 25/78 (32.0) 22/50 (44.0) 47/128 (38.0) NS

1291AJG – May, 2000 Bacterial Infections in Alcoholic Cirrhotics

(p 5 0.02) (Table 2). However, no statistically significantdifference was found between the two groups in the numberof deaths among patients with infection: 10 patients in groupI (19.2%), and 10 in group II (35.7%) (p 5 0.1).

With regard to Child-Pugh C patients, 25 of 51 (49.0%)from group I and 16 out of 33 (48.5%) from group II hadinfection, respectively (p 5 0.8) (Table 2). Likewise, nostatistically significant difference was found in the mortalityrate of 60.0% (n5 15) in group I and 62.5% (n5 10) ingroup II (p 5 0.8).

DISCUSSION

Patients with chronic liver disease are more susceptible tobacterial infection. In addition to immune alterations ob-served in the serum and ascitic fluid (2–7), other factorssuch as alcohol ingestion, malnutrition, digestive bleeding,stasis of the portal system, and an alteration in the perme-ability of the intestinal mucosa have also been considered toexplain this higher predisposition to bacterial infections (l,17, 19, 23, 25–27).

Approximately 14.5–61.0% of cirrhotics present withbacterial infection upon hospitalization or develop it duringhospitalization (9, 10, 14, 23, 24). A high index of suspicionfor bacterial infection and a low threshold for performingsurveillance cultures is required to initiate an aggressivetreatment approach, because untreated bacterial infectioncan have a serious impact on the survival of cirrhotic pa-tients (8–11). In the present study of 382 cirrhotics, 128(33.5%) patients presented with bacterial infection, totaling157 infectious processes observed upon hospitalization.

Alcohol abuse predisposes to transient endotoxemia, evenin patients with no signs of chronic hepatitis (19), and theprevalence of endotoxemia is higher in alcoholic cirrhoticsthan in nonalcoholic ones (28). Furthermore, acute orchronic alcoholism brings about an increase in the perme-ability of the intestinal mucosa, facilitating the absorption ofendotoxins (15), and also inhibits the activity of Kupffercells (16, 17), favoring the development of endotoxemia inpatients with alcohol-induced hepatic disease (18).

Suarezet al. (24) observed a higher prevalence of infec-tions in patients with cirrhosis of alcoholic etiology

(80.3%), when compared with the postnecrotic cirrhoticpatients (45.4%) and the cryptogenic ones (33.3%). Accord-ing to the authors, the depression of the reticuloendothelialand, most importantly, the alcohol-induced decrease in thechemotaxic activity of granulocytes could explain their find-ings (24).

A higher prevalence of bacterial infection in alcoholiccirrhotics in comparison with nonalcoholic cirrhotics wasalso found in this study (p 5 0.02). However, the clinicalevolution did not seem to have been influenced by the use ofalcohol, given that there was no statistically significantdifference in the number of deaths between the two groupsof patients 25 (32.0%) and 22 (44.0%), respectively (p 50.2).

It has been reported that the incidence and mortalityresulting from bacterial infections are directly related to theseverity of the hepatic disease (9, 14, 23, 24, 29). In fact, ahigher susceptibility to infection in the Child-Pugh C pa-tients in comparison to the Child-Pugh A or B patients (p 50.003) was observed, and a greater proportion of Child-Pugh C patients died (p 5 0.0002).

Although the Child-Pugh A or B alcoholic patients aremore susceptible to infection than the nonalcoholic patients(p 5 0.02), no statistical difference in the number of deathsbetween the two groups was found (p 5 0.1). With regardto patients with Child-Pugh C, no significant difference ineither the frequency of infection or the mortality rate be-tween groups I and II was found (p 5 0.8 andp 5 0.8,respectively).

Our findings suggest that, despite the fact that bacterialinfections are more common in cirrhotic alcoholics, it seemsthat the mortality rate is associated more with the severitythan with the etiology of hepatic disease.

Reprint requests and correspondence:Heitor Rosa, M.D., Rua126, n. 21, Setor Sul, 74093–080, Goiaˆnia-GO, Brazil.

Received May 3, 1999; accepted Oct. 28, 1999.

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Table 2. Prevalence of Infection in the 347 Cirrhotic PatientsAccording to the Child-Pugh Index Regarding the Use ofAlcohol

Etiology

Child-Pugh A/B Child-Pugh C

InfectionNo

Infection InfectionNo

Infection

Group I(Alcoholics) 52* 89 25† 26

Group II(Nonalcoholics) 28* 94 16† 17

Total 80‡ 183 41‡ 43

* p 5 0.02.† p 5 0.8.‡ p 5 0.003.

1292 Rosa et al. AJG – Vol. 95, No. 5, 2000

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