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REZA NUGRAHA YULISAR

PREDICTIVE FACTORS THAT INFLUENCE

THE SURVIVAL RATES IN LIVER CIRRHOSIS

PATIENTS WITH SPONTANEOUS BACTERIAL

PERITONITIS

PEI CHUAN TSUNG ET ALDIVISION OF GASTROENTEROLOGY, DEPARTMENT OF INTERNAL MEDICINE, INJE

UNIVERSITY SEOUL PAIK HOSPITAL, INJE UNIVERSITY COLLEGE OF MEDICINE, SEOUL,KOREA

Narasumber : dr. Arnold Harahap, SpPD KGEH


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INTRODUCTION Cirrhosis is defined as a diffuse hepatic process characterized by fibrosis and

the conversion of normal liver architecture into structurally abnormalnodules.

Spontaneous bacterial peritonitis ( SBP) : a bacterial infection of the asciticfluid, diagnosed based on:

Positive ascites fluid culture

And / or > 250 neutrophils in ascitic fluid,

Not associated with surgery or an intraabdominal origin of infection inliver cirrhosis patients

Clin Gastroenterol Hepatol. 2011;9(9):727-738.


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CIRRHOSIS ASSOCIATED IMMUNE DISFUNCTIONSYNDROME


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GEJALA KLINIS SBP Local symptoms: abdominal pain, nausea vomitus, diarhea, ileus Systemic inflammation : fever, leucositosis, tachycardia, tachypnea Worsening liver function Hepatic encephalopathy Shock Renal failure Asymptomatic


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TATALAKSANA SBP

Antibiotik Empiris : Cefotaxime

2x2 gr IV for 5 daysor ciprofloxacin 2x200mg IV for 7 days

Albumin 1.5 gr/kgBB at time of

diagnosis, and 1gr/kgBB day 3


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JOURNAL READING


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INTRODUCTION

Cirrhosis, is one of the leading causes of morbidity and mortality in and ranked

the 8th most common cause of death in 2007. SBP, occurring in about 9% of cases

Prognosis was extremely poor , with in-hospital mortality rate reaching 100%.


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In-hospital mortality for the first episode of SBP ranges from 10% to 50%,depending on various risk factors. 1

One-year mortality after a first episode of SBP has been reported to be 31%and 93%. 2

Outcome of SBP has improved due to the introduction of effective andappropriate use of antibiotics to high risk patients of SBP

The recent growing percentage of antibiotic-resistant strains remains aserious medical problem, particularly Gram negative organisms resistant to

quinolones and that produce the extended spectrum B lactamase

1. Pinzello G, Simonetti RG, Craxi A,et al . Spontaneous bacterial peritonitis: a prospective investigation in predominantly nonalcoholic cirrhotic patients.Hepatology 1983;3:545 9.2. Evans LT, Kim WR, Poterucha JJ,et al . Spontaneous bacterial peritonitis in asymptomatic outpatients with cirrhotic ascites.Hepatology 2003;37:897 901.


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AIM Investigate whether the cultured bacteria species

are associated with the poor outcome in livercirrhosis patients with SBP and also other

predictive factors for mortality in cirrhoticpatients with SBP.


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STUDY DESIGN AND PATIENT POPULATION Patients data collected retrospectively from medical records (January 2003

December 2010) in one center.

SBP was diagnosed based on:

1. Ascitic fluid PMN count >250 cells/mm 3

2. Absence of any clinical and radiologic findings of secondary peritonitis Ascitic fluid culture using diagnostic paracentesis was performed in all

patients with ascites who developed local symptoms or signs of peritonealinfection, systemic signs of infection, such as fever or leukocytosis, orclinical deterioration without any obvious precipitating factors


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Exclusion criteria :

1. A sign of free air in the abdominal X-ray

2. Had a recent surgery or trauma

3. Severe cardiopulmonary or cardiovascular disease4. Evidence of severe immunosuppression

5. Other malignancies except HCC


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TREATMENT RESPONSE The empirical antibiotic was administered immediately when SBP

was diagnosed. Follow up ascitic fluid tapping was performed if the signs and

symptoms of SBP failed to disappear after 48 hours of initial

empirical antibiotics therapy. The resolution of SBP was defined as a fading of all signs and

symptoms of SBP or PMN count in ascitic fluid had reduced to


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TREATMENT RESPONSE Treatment failure was defined

Persistent or worsening of the signs and symptoms of SBP or

Less than 25% decreased of PMN count in the ascitic fluid tapped 48 hrsafter the treatment when compared with that from the first tapped

ascites.


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ANTIBIOTICS USED The initial empirical antibiotic used : third-generation cephalosporin

(cefotaxime). When initial treatment failed, antibiotic therapy changed based on

the susceptibility of the cultured organisms to the antibiotics. When initial antibiotic treatments had failed + ascitic fluid culture (-),

switched antibiotics from cefotaxime to a combination ofvancomycin and carbapenem (meropenem)


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ANALYSIS Cumulative survival rates were calculated using Kaplan-Meier analysis and the

difference was determined by the log-rank test.

Cause of liver cirrhosis, Child-Pugh grade, MELD (model for end-stage liverdisease) score, serum laboratory findings including serum prothrombin time(INR), bilirubin, and albumin levels, cultured bacteria (isolated microorganisms,

Gram stain of cultured bacteria, numbers of cultured bacteria), laboratoryfindings of ascitic fluid, and presence of recurrence of SBP were used onmultivariate analysis.


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BASELINE CHARACTERISTICS


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Microorganisms in ascitic fluid wereisolated in 39 patients (41.1%) and atotal of 47 species of microorganisms

were isolated.

ISOLATION OF CULTURED ORGANISM


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RESULTS


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DISCUSSIONS The microorganisms were isolated in 39 of 95 patients (41.1%). The result was

similar to the previous studies conducted in Korea (39-41%) which is lower thanthe Western studies (~60%). 1

Only 12-18% of organisms were Gram positive in the 1990s and increased to24.1% in 2007 in Korea. Similarly, in Western studies, the proportion was 19-

34%, in this study, 40.7% Eschericia coli (12 of the 47 cases, 25.5%), Klebsiella species (9 cases, 19.1%) and

Streptococcus species (9 cases, 19.1%) were still the most common organisms,Enterococcus species (6 cases, 12.8%) was noticeably higher in our studycompared to the previous studies in Korea and Western countries.

1. Song HG, Lee HC, Joo YH, Jung S, Park YH, Ryu SH, et al. Clinical and microbiological characteristics of spontaneous bacterial peritonitis (SBP) in a recent five year period. TaehanKan Hakhoe Chi 2002;8:61-70.


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DISCUSSIONS Data showed that the types of cultured bacterial organisms did not

affect the survival rates of cirrhotic patients with SBP. No statistical significances were found between the presence and

absence of the bacteria, the positivity of bacterial Gram stain, the

number of isolated microorganisms, and the mortality rates High mortality rates were seen in the patients with a high MELD

score


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Tandon and Garcia reviewed 18 prognostic studies for in hospital and 1 monthmortalities in adult SBP, renal dysfunction was the most important predictor formortality, followed by MELD score.

Heo J et all performed a multi center retrospective study in Korea: ESBLproducing organisms-induced SBP and combined HCC were associated with poor

prognosis in SBP patients. Bacteremia, higher MELD score, and nomicrobiological response were prognostic factors for a poor outcome in SBPpatients


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Child-Pughscore 10 showed lower survival rates than patients with Child-Pugh score


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LIMITATIONS OF THE STUDY1. Single center study : unlikely reflects all of the characteristics of isolated organisms in

Korea.

2. The number of patients involved in this study was relatively small.

3. The follow-up periods after diagnosis of SBP were short; we even failed to obtain follow-up records of 10 patients for sufficiently long duration.

4. Thus journal could not have the assessment of treatment response in many patients,which was not available in multivariate analysis, owing to the retrospective characteristicof this study.

5. In hospital mortality was high, may be influenced by high percentage of HCC patients.


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CONCLUSION The proportion of Gram positive organisms, especially Enterococcus species, is

increasing. The bacterial factors including the presence or absence of the bacteria, the types of

isolated microorganism, the positivity of bacterial Gram stain and the number of isolatedmicroorganisms did not influence the survival rate

Presence of HCC, and lab findings at the time of diagnosis (bilirubin serum, PT, renaldysfunction, lower glucose level in ascitic fluid) were the independent factors of mortality.


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THANK YOU


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VALIDITY

Are the result of this prognosis study valid ?

1.Was a defined, representative sample ofpatients assembled at a common (usuallyearly) point in the course of their disease ?

UNCLEAR

2. Was patient follow up sufficiently longand complete?

No, the follow up period were short and 10patients lost to follow up

3. Were objective outcome criteria appliedin a blind fashion?

NO

4. If subgroups with different prognoses areidentified, was there adjustment for

important prognosis factors?

YES

5. How precise are the prognosticestimated?

See table 4

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