- Email: [email protected]
197 BACTERIAL DNA DETECTION BY REAL-TIME PCR AND 16s RDNA GENE SEQUENCING IN SPONTANEOUS BACTERIAL PERITONITIS
POSTERS 196 PROCALCITONIN IS THE BEST DIAGNOSTIC AND PROGNOSTIC MARKER OF SEPSIS IN DECOMPENSATED CIRRHOTIC PATIENTS F. Schepis1 , M. Bianchini1 , I. Ferretti1 , M. Marino1 , S. Bonfreschi1 , G. Dattomo1 , F. Agnello1 , M.L. Wratten2 , N. De Maria1 , E. Villa1 . 1 Azienda Ospedaliero – Universitaria di Modena, Modena, 2 BRAHMS Italia, Milan, Italy E-mail: fi[email protected] Background and Aims: Almost 50% of hospitalized cirrhotics are septic. At the admission, no clear-cut clinical and biochemical features are helpful in diagnosing and prognostically stratifying ascitic patients with suspected bacterial infection. We evaluated procalcitonin (PCT) as a diagnostic and prognostic tool in decompensated cirrhotics with suspected sepsis. Patients and Methods: All cirrhotic patients admitted to our Unit for decompensation were eligible. Exclusion criteria were ongoing antibiotic therapy, recent hospitalization, and HCC out of Milan criteria. At admission signs of SIRS and blood test including PCT and C reactive protein (CRP) were recorded. In all patients, cell count of ascites, blood and urine cultures, and chest ray were performed. Sepsis was defined as the presence of 2 or more signs of SIRS plus demonstrated bacterial infection or SBP. In patients who started antibiotic treatment, all tests were repeated after 48 hours. Results: A total of 108 consecutive admission of 75 patients were analyzed (age: 60.7±13; Meld score: 18.12±7.2; Child–Pugh score: 9.7±1.9; HCC: 24%). Sepsis was present in 43 patients (39.8%; SBP: 29.6%). At univariate analysis, Meld score (21±9.52 Vs 16.7±5.6; p = 0.001), Child–Pugh score (10.5±2.1Vs 9.6±1.9; p = 0.029), CRP (5.03±4.85 Vs 2.05±1.85; p = 0.0001) and PCT levels (3.86±6.98 Vs 0.38±0.37 p = 0.0001) were higher in septic patients than in non septic. Multivariate analysis identified PCT as the only variable independently related to sepsis (p = 0.0001). ROC curve for PCT showed an AUC of 0.803 (best cut-off = 0.49 ng/ml). At admission, a PCT value >0.49 ng/ml was significantly related to inpatient mortality (p = 0.005). Antibiotic treated patients (n = 48; 44%), who kept normal or normalized PCT within 48 h of treatment showed significantly higher survival (p = 0.009) than remaining patients. Conclusion: PCT is both the best marker of ongoing sepsis and the strongest prognostic indicator in hospitalized cirrhotic patients with ascites. 197 BACTERIAL DNA DETECTION BY REAL-TIME PCR AND 16s RDNA GENE SEQUENCING IN SPONTANEOUS BACTERIAL PERITONITIS G. Soriano1 , O. Esparcia2 , M. Montemayor2 , C. Guarner-Argente1 , R. Pericas2 , X. Torras1 , N. Calvo3 , E. Roman ´ 1 , F. Navarro2 , C. Guarner1 , P. Coll2 . 1 Department of Gastroenterology, CIBERehd, 2 Department of Microbiology, 3 Department of Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain E-mail: [email protected] Background: Despite of inoculation into blood culture bottles, ascitic fluid culture is negative in 50% of cases of spontaneous bacterial peritonitis (SBP). AIM. To determine whether 16S rDNA gene detection by real-time PCR and sequencing increases the efficacy of culture in microbiological diagnosis of SBP. Patients and Methods: We included all cirrhotic patients with SBP (ascitic fluid neutrophil count ≥250/mm3 , n = 55): culture was positive in 25 (SBP+C) and negative in 30 (SBP-C). We also included a group of cirrhotic patients with sterile ascites (SA, ascitic fluid neutrophil count <250/mm3 and negative culture, n = 20), and another group of patients with neoplasic ascites (NA, n = 27). Bedside inoculation into blood culture bottles and real-time PCR and sequencing of 16S rDNA gene were performed in ascitic fluid. Results: Bacterial DNA was detected in 23/25 (92%) cases from SBP+C group, 16/30 (53%) in SBP-C (p = 0.004 respect to SBP+C),
12/20 (60%) in SA (p = 0.01 respect to SBP+C and pNS respect to SBP-C) and 0/27 in NA (p < 0.001 respect to other groups). Sequencing identified 12 cases from SBP+C group to genus or species level (8 agreed with culture, 4 did not), 6 in SBP-C and 6 in SA. In the remaining cases with positive PCR, sequencing did not yield a definitive bacterial identification. Analyzing all SBP episodes (n = 55) and comparing patients with positive (n = 39) and negative bacterial DNA (n = 16), the former showed worse liver function (Child–Pugh AB/C 19/20 vs 13/3, p = 0.03), a trend to a higher inflammatory response (blood leukocyte count 11,880±9235 vs 6588±2713/mm3 , p = 0.002; SIRS 48.7% vs 18.7%, p = 0.06; ascitic fluid neutrophil count 7214±12,854 vs 2649±4183/mm3 , pNS) and a trend to higher in-hospital mortality (25.6% vs 6.2%, pNS) and 3-month probability of mortality (31% vs 6%, p = 0.058). Conclusions: 1. Bacterial DNA was not detected in almost half negative culture SBP episodes, questioning the bacterial etiology in these cases. 2. Characteristics and clinical course in these patients differed from SBP patients with positive bacterial DNA. 3. Methodology used did not always identify amplified bacterial DNA; this could be due to presence of polymicrobial DNA as a consequence of previous polymicrobial translocations and require further studies. 198 RENIN-ANGIOTENSIN-ALDOSTERONE INHIBITORS FOR THE REDUCTION OF PORTAL PRESSURE: A META-ANALYSIS AND SYSTEMATIC REVIEW P. Tandon, J.G. Abraldes, A. Berzigotti, J.C. Garcia-Pagan, ´ J. Bosch. Hospital Clinic de Barcelona, Barcelona, Spain E-mail: [email protected] Background: Renin-angiotensin-aldosterone antagonists [ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), aldosterone antagonists (AA)] have been identified as potential therapies for portal pressure reduction, predominantly by reducing intrahepatic resistance. Trials in patients with cirrhosis have demonstrated discordant hemodynamic results and safety profiles, especially due to the risk of systemic hypotension in patients with decompensated disease. This meta-analysis evaluated the efficacy and safety of RAAS inhibitors in reducing the hepatic venous pressure gradient (HVPG). Methods: After a comprehensive literature search, English language full-text controlled trials in adult patients with portal hypertension and cirrhosis on ACEi, ARB or AA were included. The primary outcome was the mean change in HVPG between treatment and control groups. Two independent reviewers performed trial selection and quality assessment. Results: From 193 citations, 19 controlled trials (n = 678) were included (7 ACEi/ARB vs placebo, 4 ACEi/ARB vs beta-blockers (BB), 1 ARB + BB vs BB and 7 AA vs control). When compared to placebo, ACEi/ARB resulted in a significant HVPG reduction (weighted mean difference −3.8 mmHg;95% CI: −5.9 to −1.8). The best quality trials were those comparing ACEi/ARB to BB. Individual patient data (n = 125) was available for 3 out of 4 of these trials. Pooled data showed that BB caused a greater reduction in HVPG than ACEi/ARB (p = 0.01). Notably, in those patients with Child PughA cirrhosis, the reduction in HVPG with ACEi/ARB (n = 34) (−17%; 95% CI: −6 to −28), was similar to that of BB (n = 25) (−21%;95% CI: −9 to −32). Due to significant variation in the comparison groups of the AA trials, we were unable to pool these studies. There was no difference in adverse events or withdrawals in any of the treatment and control group comparisons, but selected studies did note adverse hemodynamic and renal effects in decompensated patients on ACEi/ARB. Conclusions: ACEi/ARB’s reduce portal pressure in patients with Child PughA cirrhosis, with minimal adverse events. The efficacy
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12/20 (60%) in SA (p = 0.01 respect to SBP+C and pNS respect to SBP-C) and 0/27 in NA (p < 0.001 respect to other groups). Sequencing identified 12 cases from SBP+C group to genus or species level (8 agreed with culture, 4 did not), 6 in SBP-C and 6 in SA. In the remaining cases with positive PCR, sequencing did not yield a definitive bacterial identification. Analyzing all SBP episodes (n = 55) and comparing patients with positive (n = 39) and negative bacterial DNA (n = 16), the former showed worse liver function (Child–Pugh AB/C 19/20 vs 13/3, p = 0.03), a trend to a higher inflammatory response (blood leukocyte count 11,880±9235 vs 6588±2713/mm3 , p = 0.002; SIRS 48.7% vs 18.7%, p = 0.06; ascitic fluid neutrophil count 7214±12,854 vs 2649±4183/mm3 , pNS) and a trend to higher in-hospital mortality (25.6% vs 6.2%, pNS) and 3-month probability of mortality (31% vs 6%, p = 0.058). Conclusions: 1. Bacterial DNA was not detected in almost half negative culture SBP episodes, questioning the bacterial etiology in these cases. 2. Characteristics and clinical course in these patients differed from SBP patients with positive bacterial DNA. 3. Methodology used did not always identify amplified bacterial DNA; this could be due to presence of polymicrobial DNA as a consequence of previous polymicrobial translocations and require further studies. 198 RENIN-ANGIOTENSIN-ALDOSTERONE INHIBITORS FOR THE REDUCTION OF PORTAL PRESSURE: A META-ANALYSIS AND SYSTEMATIC REVIEW P. Tandon, J.G. Abraldes, A. Berzigotti, J.C. Garcia-Pagan, ´ J. Bosch. Hospital Clinic de Barcelona, Barcelona, Spain E-mail: [email protected] Background: Renin-angiotensin-aldosterone antagonists [ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), aldosterone antagonists (AA)] have been identified as potential therapies for portal pressure reduction, predominantly by reducing intrahepatic resistance. Trials in patients with cirrhosis have demonstrated discordant hemodynamic results and safety profiles, especially due to the risk of systemic hypotension in patients with decompensated disease. This meta-analysis evaluated the efficacy and safety of RAAS inhibitors in reducing the hepatic venous pressure gradient (HVPG). Methods: After a comprehensive literature search, English language full-text controlled trials in adult patients with portal hypertension and cirrhosis on ACEi, ARB or AA were included. The primary outcome was the mean change in HVPG between treatment and control groups. Two independent reviewers performed trial selection and quality assessment. Results: From 193 citations, 19 controlled trials (n = 678) were included (7 ACEi/ARB vs placebo, 4 ACEi/ARB vs beta-blockers (BB), 1 ARB + BB vs BB and 7 AA vs control). When compared to placebo, ACEi/ARB resulted in a significant HVPG reduction (weighted mean difference −3.8 mmHg;95% CI: −5.9 to −1.8). The best quality trials were those comparing ACEi/ARB to BB. Individual patient data (n = 125) was available for 3 out of 4 of these trials. Pooled data showed that BB caused a greater reduction in HVPG than ACEi/ARB (p = 0.01). Notably, in those patients with Child PughA cirrhosis, the reduction in HVPG with ACEi/ARB (n = 34) (−17%; 95% CI: −6 to −28), was similar to that of BB (n = 25) (−21%;95% CI: −9 to −32). Due to significant variation in the comparison groups of the AA trials, we were unable to pool these studies. There was no difference in adverse events or withdrawals in any of the treatment and control group comparisons, but selected studies did note adverse hemodynamic and renal effects in decompensated patients on ACEi/ARB. Conclusions: ACEi/ARB’s reduce portal pressure in patients with Child PughA cirrhosis, with minimal adverse events. The efficacy
Journal of Hepatology 2010 vol. 52 | S59–S182
S85