PREDICTIVE FACTORS THAT INFLUENCE THE SURVIVAL RATES IN LIVER CIRRHOSIS PATIENTS WITH SPONTANEOUS BACTERIAL PERITONITIS

PEI CHUAN TSUNG ET AL DIVISION OF GASTROENTEROLOGY, DEPARTMENT OF INTERNAL MEDICINE, INJE UNIVERSITY SEOUL PAIK HOSPITAL, INJE UNIVERSITY COLLEGE OF MEDICINE, SEOUL, KOREA

REZA NUGRAHA YULISAR

Narasumber : dr. Arnold Harahap, SpPD KGEH

INTRODUCTION
Cirrhosis is defined as a diffuse hepatic process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules. Spontaneous bacterial peritonitis (SBP) : a bacterial infection of the ascitic fluid, diagnosed based on: Positive ascites fluid culture And / or > 250 neutrophils in ascitic fluid, Not associated with surgery or an intraabdominal origin of infection in liver cirrhosis patients

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

CIRRHOSIS ASSOCIATED IMMUNE DISFUNCTION SYNDROME

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

TATALAKSANA SBP

Antibiotik
Empiris : Cefotaxime 2x2 gr IV for 5 days or ciprofloxacin 2x200 mg IV for 7 days

Albumin
1.5 gr/kgBB at time of diagnosis, and 1 gr/kgBB day 3

JOURNAL READING

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%.

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 and appropriate use of antibiotics to high risk patients of SBP The recent growing percentage of antibiotic-resistant strains remains a serious medical problem, particularly Gram negative organisms resistant to quinolones and that produce the extended spectrum B lactamase

1. 2.

Pinzello G, Simonetti RG, Craxi A, et al. Spontaneous bacterial peritonitis: a prospective investigation in predominantly nonalcoholic cirrhotic patients. Hepatology 1983;3:5459. Evans LT, Kim WR, Poterucha JJ, et al. Spontaneous bacterial peritonitis in asymptomatic outpatients with cirrhotic ascites. Hepatology 2003;37:897901.

AIM
Investigate whether the cultured bacteria species are associated with the poor outcome in liver cirrhosis patients with SBP and also other predictive factors for mortality in cirrhotic patients with SBP.

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 peritoneal infection, systemic signs of infection, such as fever or leukocytosis, or clinical deterioration without any obvious precipitating factors

 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 disease 4. Evidence of severe immunosuppression 5. Other malignancies except HCC

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 <250 cells/mm3.

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 hrs after the treatment when compared with that from the first tapped ascites.

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 of vancomycin and carbapenem (meropenem)

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 liver disease) 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), laboratory findings of ascitic fluid, and presence of recurrence of SBP were used on multivariate analysis.

BASELINE CHARACTERISTICS

ISOLATION OF CULTURED ORGANISM

Microorganisms in ascitic fluid were isolated in 39 patients (41.1%) and a total of 47 species of microorganisms were isolated.

RESULTS

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 than the Western studies (~60%).1 Only 12-18% of organisms were Gram positive in the 1990s and increased to 24.1% in 2007 in Korea. Similarly, in Western studies, the proportion was 1934%, 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 study compared 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. Taehan Kan Hakhoe Chi 2002;8:61-70.

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

Tandon and Garcia reviewed 18 prognostic studies for in hospital and 1 month mortalities in adult SBP, renal dysfunction was the most important predictor for mortality, followed by MELD score. Heo J et all performed a multi center retrospective study in Korea: ESBL producing organisms-induced SBP and combined HCC were associated with poor prognosis in SBP patients. Bacteremia, higher MELD score, and no microbiological response were prognostic factors for a poor outcome in SBP patients

Child-Pugh score 10 showed lower survival rates than patients with Child -Pugh score <10. MELD score higher than or equal to 20 was associated with high mortality. However, both higher Child-Pugh and MELD score were not significant independent predictors of survival in SBP patients. The presence of HCC at the time of diagnosis of SBP, higher serum bilirubin levels, the prolonged serum prothrombin time (INR), renal dysfunction at the diagnosis of SBP, and lower glucose levels in ascitic fluid were the independent predictive factors of overall survival rates in cirrhotic patients with SBP.

LIMITATIONS OF THE STUDY

1. 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 followup 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 characteristic of this study. 5. In hospital mortality was high, may be influenced by high percentage of HCC patients.

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 isolated microorganisms did not influence the survival rate Presence of HCC, and lab findings at the time of diagnosis (bilirubin serum, PT, renal dysfunction, lower glucose level in ascitic fluid) were the independent factors of mortality.

THANK YOU

VALIDITY
Are the result of this prognosis study valid ? 1.Was a defined, representative sample of patients assembled at a common (usually early) point in the course of their disease ? 2. Was patient follow up sufficiently long and complete? 3. Were objective outcome criteria applied in a blind fashion? 4. If subgroups with different prognoses are identified, was there adjustment for important prognosis factors? 5. How precise are the prognostic estimated? UNCLEAR

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

YES

See table 4