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316 ACUTE GASTROINTESTINAL BLEEDING PROLONGS QT INTERVAL IN CIRRHOSIS
02B. CIRRHOSIS AND COMPLICATIONS – B) CLINICAL ASPECTS 315 CIPROFLOXACIN VS. CEFTRIAXONE IN THE PREVENTION OF BACTERIAL INFECTION IN PATIENTS WITH ADVANCED CIRRHOSIS AND GASTROINTESTINAL HEMORRHAGE J.W. Yun, B.I. Kim, J.H. Park, H.J. Kim, D.I. Park, Y.K. Cho, C.I. Shon, W.K. Jeon. Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea E-mail: [email protected] Background and Aims: Up to recently, oral norfloxacin is the standard of therapy in the prevention of bacterial infection in cirrhosis with gastrointestinal hemorrhage. However, the prevalence of quinolone-resistant bacteria or gram-positive bacteria has been increased constantly during the last years. The purpose of our randomized controlled study was to compare the effectiveness of oral ciprofloxacin versus intravenous ceftriaxone for prevention of bacterial infection in advanced cirrhosis with gastrointestinal hemorrhage. Also, we investigated the influence of intestinal permeability and endotoxin in bacterial infection development. Methods: Of 29 patients who had advanced cirrhosis and hemorrhage, 12 were randomly assigned to receive oral ciprofloxacin (500 mg twice daily for 7 days) and 17 to receive intravenous ceftriaxone (2.0g/day for 7 days). The primary outcome was the prevention of bacterial infection within 10 days after treatment. The secondary outcome included the clinical parameters for association of bacterial infection. Serum endotoxin level was measured by kinetic turbidimetric assay (Microplate reader, Charles River Endosafe® , USA). Also, Intestinal permeability was assessed by measurement of urinary polyethylene glycol (PEG) after oral ingestion of PEG. Results: Clinical characteristics of enrolled patients were comparable between two groups. The rate of proved and possible infection was significantly higher in ciprofloxacin group than ceftriaxone group (n = 5, 41.7% vs. n = 1, 5.9%, p = 0.011). There was no proved infection in ceftriaxone group. The mode of infection in ciprofloxacin group included bacteremia (n = 2, 16.7%), spontaneous bacterial peritonitis (n = 1, 8.3%) and urinary tract infection (n = 2, 16.7%). The isolated organisms were gram-positive cocci in 3 patients and gram-negative bacilli in 2 patients in ciprofloxacin group. Serum endotoxin level and intestinal permeability were more increased in bacterial infection group than non-infection group (23.69±36.34 EU/mL vs. 0.15±0.15 EU/mL and 1.41±1.23% vs. 0.58±0.92%). But, there were no statistically significant differences between two groups. Conclusions: The prevalence of bacterial infection is significantly lower in intravenous ceftriaxone group than oral ciprofloxacin group in advanced cirrhosis with gastrointestinal hemorrhage. Thus we would expect the therapeutic efficacy for prophylaxis of bacterial infection. 316 ACUTE GASTROINTESTINAL BLEEDING PROLONGS QT INTERVAL IN CIRRHOSIS A. Zambruni, A. Di Micoli, E. Bracci, K. Fontana, P. Caraceni, M. Domenicali, F. Mirici-Cappa, V. Santi, G. Magini, R. Casadio, M. Frigerio, M. Bernardi, F. Trevisani. Dipartimento di Medicina Interna Cardioangiologia Epatologia, Universita’ degli Studi di Bologna, Policlinico S.Orsola-Malpighi, Bologna, Italy E-mail: [email protected] Background and Aims: QT interval prolongation in cirrhosis may trigger ventricular arrhythmias, which have been reported during acute gastrointestinal (GI) bleeding. Our aim was to monitor the length of ventricular repolarisation during acute GI bleeding in cirrhosis. Methods: 61 cirrhotics (age: 60.7±13.0 yrs, Child-Pugh class: A/B/C: 19/23/19) experiencing GI haemorrhage and 15 non-cirrhotic controls (age: 75.5±3.0 yrs) were enrolled. Patients were evaluated at the time of bleeding (T1) and, in survivors (42 cirrhotics and all controls), after recovery (2−15 days: T2). As baseline (T0), we utilized data available from the last hospitalisation (1−16 months before). Cirrhotics
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were treated with vasoconstrictors (16), endoscopy alone (24) or with vasoconstrictors (12) and laparotomic variceal ligation + vasoconstrictors (9). QT interval was corrected for heart rate by the “cirrhosis specific” formula (QTc = QT/RR^1/3.02) in cirrhotics, and the Fridericia formula (QTc = QT/RR^1/3) in controls (normal value <452 ms). Results (mean±SD): in cirrhotics, bleeding leads to an haemoglobin (T0: 11.7±1.8, T1: 8.3±1.7 g/dl; p < 0.0001) and mean arterial pressure (MAP) (T0: 88.0±9.4, T1: 72.7±12.5 mmHg; p < 0.0001) drop, while heart rate increased (T0: 78.1±14.7, T1: 94.1±21.0 bpm; p < 0.0001). QTc interval prolonged in 51 (84%) cases (T0: 414.0±36.8, T1: 453.8±36.3 msec, p < 0.0001). In the 42 survivors, QTc interval shortened after bleeding (T1: 445.7±5.3, T2: 425.8±36.3 msec; p < 0.0001). No correlation was found between QTc lengthening and haemoglobin/MAP drop. The Child-Pugh score significantly worsened during bleeding (T0: 8.3±2.5, T1: 10.0±2.4; p < 0.0001), remaining unchanged thereafter (T2: 9.3±2.2; p = 0.53). QTc interval at T1 was significantly longer in patients who died compared to survivors (471.8±8.0 vs. 445.7±5.3; p = 0.012). In controls, bleeding caused an haemoglobin (T0: 14.6±1.7, T1: 8.9±2.6 g/dl; p = 0.04) and MAP (T0: 106.7±18.9, T1: 85.4±21.5 mmHg; p = 0.021) drop, and a heart rate increase (T0: 75.3±11.9, T1: 87.1±22.3 bpm; p = 0.07) which were comparable to those observed in cirrhotics. QTc interval tended to prolong during bleeding but the increase did not reach the statistical significance (T0: 407.4±22.0, T1: 449.0±18.9, T2 431.0±25.7 msec, p = 0.083). Conclusions: in cirrhotic patients QT interval increases during acute bleeding. Moreover, a prolonged QT interval heralds a poor prognosis. A monitoring of QT interval in cirrhotic patients during acute bleeding is warranted. 317 PROGNOSTIC INDICATORS OF SURVIVAL IN COMPENSATED AND DECOMPENSATED STAGES OF LIVER CIRRHOSIS: VALIDATION OF A 4-STAGE CLASSIFICATION A. Zipprich1 , M.M. Dollinger1 , G. Garcia-Tsao2 , S. Rogowski1 , W.E. Fleig1 . 1 Martin-Luther-University Halle-Wittenberg, First Department of Medicine, Halle/Saale, Germany; 2 Yale University, School of Medicine, New Haven, USA E-mail: [email protected];[email protected] Background: Four different stages of cirrhosis with increasing one-year mortality were recently defined based on an untreated patient cohort (J Hepatol 2006;44:217). Within compensated cirrhosis, stages 1 (1% mortality) and 2 (3% mortality) were classified according to the absence or presence of varices, within decompensated cirrhosis according to the presence of ascites without variceal hemorrhage (VH) (stage 3, 20% mortality) or VH with or without ascites (stage 4, 57% mortality). Our aim was to evaluate long-term survival using this new system in a large single-center cohort of patients (pts) receiving standard therapy. Methods: 729 consecutive pts with suspected cirrhosis admitted in our center between 12/1995 and 12/2004 received full clinical and hemodynamic assessment including determination of CTP/MELD score and the hepatic venous pressure gradient [HVPG]. Patients were followed for a median of 47 months (IQ 10−80). Survival was calculated using the KaplanMeier method (cut-off 31/11/2006), a multivariate Cox regression model was used to examine independent predictors of survival in compensated and decompensated cirrhosis. Results: 458 pts met inclusion criteria (confirmed cirrhosis/no malignancy/no TIPS). Survival was significantly different between the two stages (S1 vs. S2; *p = 0.024) in compensated pts but not between the two stages (S3 vs. S4) in decompensated pts (table). In contrast, when pts in stage 4 were divided by the absence or presence of ascites, two different survival groups could be identified (median survival 48 vs. 31 months, p = 0.05). The strongest independent predictor of survival in compensated pts was HVPG >10 mmHg, while in decompensated pts it was the MELD score. Conclusion: The new classification confirms its prognostic significance in our cohort of patients. However, in decompensated patients the sub-staging
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were treated with vasoconstrictors (16), endoscopy alone (24) or with vasoconstrictors (12) and laparotomic variceal ligation + vasoconstrictors (9). QT interval was corrected for heart rate by the “cirrhosis specific” formula (QTc = QT/RR^1/3.02) in cirrhotics, and the Fridericia formula (QTc = QT/RR^1/3) in controls (normal value <452 ms). Results (mean±SD): in cirrhotics, bleeding leads to an haemoglobin (T0: 11.7±1.8, T1: 8.3±1.7 g/dl; p < 0.0001) and mean arterial pressure (MAP) (T0: 88.0±9.4, T1: 72.7±12.5 mmHg; p < 0.0001) drop, while heart rate increased (T0: 78.1±14.7, T1: 94.1±21.0 bpm; p < 0.0001). QTc interval prolonged in 51 (84%) cases (T0: 414.0±36.8, T1: 453.8±36.3 msec, p < 0.0001). In the 42 survivors, QTc interval shortened after bleeding (T1: 445.7±5.3, T2: 425.8±36.3 msec; p < 0.0001). No correlation was found between QTc lengthening and haemoglobin/MAP drop. The Child-Pugh score significantly worsened during bleeding (T0: 8.3±2.5, T1: 10.0±2.4; p < 0.0001), remaining unchanged thereafter (T2: 9.3±2.2; p = 0.53). QTc interval at T1 was significantly longer in patients who died compared to survivors (471.8±8.0 vs. 445.7±5.3; p = 0.012). In controls, bleeding caused an haemoglobin (T0: 14.6±1.7, T1: 8.9±2.6 g/dl; p = 0.04) and MAP (T0: 106.7±18.9, T1: 85.4±21.5 mmHg; p = 0.021) drop, and a heart rate increase (T0: 75.3±11.9, T1: 87.1±22.3 bpm; p = 0.07) which were comparable to those observed in cirrhotics. QTc interval tended to prolong during bleeding but the increase did not reach the statistical significance (T0: 407.4±22.0, T1: 449.0±18.9, T2 431.0±25.7 msec, p = 0.083). Conclusions: in cirrhotic patients QT interval increases during acute bleeding. Moreover, a prolonged QT interval heralds a poor prognosis. A monitoring of QT interval in cirrhotic patients during acute bleeding is warranted. 317 PROGNOSTIC INDICATORS OF SURVIVAL IN COMPENSATED AND DECOMPENSATED STAGES OF LIVER CIRRHOSIS: VALIDATION OF A 4-STAGE CLASSIFICATION A. Zipprich1 , M.M. Dollinger1 , G. Garcia-Tsao2 , S. Rogowski1 , W.E. Fleig1 . 1 Martin-Luther-University Halle-Wittenberg, First Department of Medicine, Halle/Saale, Germany; 2 Yale University, School of Medicine, New Haven, USA E-mail: [email protected];[email protected] Background: Four different stages of cirrhosis with increasing one-year mortality were recently defined based on an untreated patient cohort (J Hepatol 2006;44:217). Within compensated cirrhosis, stages 1 (1% mortality) and 2 (3% mortality) were classified according to the absence or presence of varices, within decompensated cirrhosis according to the presence of ascites without variceal hemorrhage (VH) (stage 3, 20% mortality) or VH with or without ascites (stage 4, 57% mortality). Our aim was to evaluate long-term survival using this new system in a large single-center cohort of patients (pts) receiving standard therapy. Methods: 729 consecutive pts with suspected cirrhosis admitted in our center between 12/1995 and 12/2004 received full clinical and hemodynamic assessment including determination of CTP/MELD score and the hepatic venous pressure gradient [HVPG]. Patients were followed for a median of 47 months (IQ 10−80). Survival was calculated using the KaplanMeier method (cut-off 31/11/2006), a multivariate Cox regression model was used to examine independent predictors of survival in compensated and decompensated cirrhosis. Results: 458 pts met inclusion criteria (confirmed cirrhosis/no malignancy/no TIPS). Survival was significantly different between the two stages (S1 vs. S2; *p = 0.024) in compensated pts but not between the two stages (S3 vs. S4) in decompensated pts (table). In contrast, when pts in stage 4 were divided by the absence or presence of ascites, two different survival groups could be identified (median survival 48 vs. 31 months, p = 0.05). The strongest independent predictor of survival in compensated pts was HVPG >10 mmHg, while in decompensated pts it was the MELD score. Conclusion: The new classification confirms its prognostic significance in our cohort of patients. However, in decompensated patients the sub-staging