- Email: [email protected]
447 PROSPECTIVE VALIDATION OF CLINICAL PROGNOSTIC INDICATORS IN ACUTE LIVER FAILURE
01b: LIVER TRANSPLANTATION/SURGERY/ACUTE LIVER FAILURE − b) CLINICAL rapamycin influence on HCV replication in comparison with calcineurin inhibitor in LT patients. We aimed to study the effect of rapamycin on HCV replication vs calcineurin inhibitors in LT subjects. Patients and Methods: From December 2005 to March 2008 14 LT patients with HCV (decompensated cirrhosis or HCC) started rapamycin in substitution of calcineurin inhibitors, at least 24 weeks after LT. RNAHCV (by Taqman) and ALT/AST levesl were assessed at days −30, 0, +30, +90, +180 and 365 of rapamycin. Results: 71% were male (n = 10 males); mean age 61±7 years. 93% (n = 13) were infected with HCV-genotype 1b. LT was due to HCC in 71% (n = 10). The indications for rapamycin were HCC (8 cases, 57%), serum creatinine >1.5 mg/ml (5, 36%), and extrahepatic cancer (n = 1, 7%). Rapamycin replaced tacrolimus in 12 cases (86%) and cyclosporine in 2 (14%). The mean time from LT to rapamycin use was 32±31 months (range 7−95), and the median time on rapamycin was 41 weeks (4–147). Evolution of HCV viraemia and AST/ALT levels during rapamycin are shown in table 1. Table 1
HCV (×106 IU/mL) AST (U/L) ALT (U/L)
Day 0 (n = 14)
Day 30 (n = 14)
Day 90 (n = 12)
Day 180 (n = 9)
Day 365 (n = 8)
53±28 80±100 71±100
32±35 42±71 48±77
23±39 108±74 108±72
16±16 63±96 52±96
11±12 86±104 67±96
Rapamycin was withdrawn in 5 patients (36%), due to pneumonitis in 4 (80%). There were no significant changes in HCV-RNA or serum AST/ALT level during follow-up. Conclusion: The use of rapamycin after calcineurin inhibitors did not have a significant impact on HCV-RNA or serum AST/ALT levels. The most frequent reason for rapamycin withdrawal was pneumonitis. 446 CYSTATIN C CONCENTRATION AS A PREDICTOR OF DEATH AND CARDIOVASCULAR EVENTS AFTER LIVER TRANSPLANTATION V. Bernal1 , I. Pascual2 , P. Esquivias3 , A. Garc´ıa-Gil4 , C. Fern´andez2 , ´ Sim´on1 . 1 Hepatology & I. Lacambra2 , M.T. Serrano1 , M.A. Gastroenterology, 2 Cardiology, 3 Research Unit CIBERehd, 4 Liver Transplant Unit, Lozano Blesa University Hospital, Zaragoza, Spain E-mail: [email protected] Background and Aims: Diagnosis of renal failure is essential in cirrhosis. Serum creatinine concentration (Cr) presents a poor sensibility to detect early renal impairment. Cardiac dysfunction may also be present in these patients. Recently, cystatin C (Cys) has been suggested not only as a sensitive marker of renal function but also as a stronger predictor of the risk of death and cardiovascular events. To date no study has explored this fact in cirrhotic. The aims of this study were: 1. To investigate the value of plasma Cys concentration for the detection of moderate impaired renal function. 2. To correlate Cys levels with markers of severity of cirrhosis and cardiac function. 3. To evaluate whether Cys concentrations are associated with mortality and cardiovascular events among cirrhotic after LT. Methods: Clinical and biochemical data, echocardiography, heart hemodynamic measurements and Cys levels were analyzed in 100 cirrhotic candidates to LT. Cardiovascular events were recorded including: congestive heart failure, myocardial infarction, serious arrhythmias or stroke. Results: 1. Receiver-operator characteristics curves (ROC) showed a similar efficiency to detect creatinine clearance less than 60 ml/min/1.73m2 (Cys = 0.753; Cr = 0.799; GFR, Glomerular filtration rate, CockcroftGault formula = 0.842; Urea = 0.823; p = 0.001). However, at cut off concentrations of 1.3 mg/dl, Cr showed a great specificity (96%) but a poor sensibility (13%). Sensitivity of Cys was superior (83%) with a moderate specificity (55%) at cut off of 1400 ng/ml.
S169
2. Cys levels were not related to right heart hemodynamic measurements. In the regression analysis, Cys was significantly related to Child score, fractional shortening (echocardiographic parameter of systolic dysfunction) and creatinine. 3. Over a median follow-up of 2.7 years, 14 patients developed some cardiovascular events. Of these, 13 had high levels of Cys (>1400 ng/ml) before LT, with significant differences (p < 0.05). In the Kaplan–Meier analysis Cys discriminated significantly between survivors and nonsurvivors (p < 0.05), better than MELD. Conclusions: Cystatin C determination could be a valuable tool for early diagnosis of renal dysfunction in cirrhotic. Furthermore, it could be a predictor of the risk of death and cardiovascular events after LT.
447 PROSPECTIVE VALIDATION OF CLINICAL PROGNOSTIC INDICATORS IN ACUTE LIVER FAILURE A. Bhalla1 , C. Rao2 , R.K. Dhiman3 , N. Sharma1 , S. Mahi1 , V. Suri1 , Y. Chawla3 . 1 Internal Medicine, 2 PGIMER, 3 Hepatology, PGIMER, Chandigarh, India E-mail: [email protected] Background and Aims: Acute liver failure is a complex multisystem illness and carries a mortality of 70–800%. In a retrospective study, we at our centre had identified 5 clinical prognostic indicators (CPI) i.e. age >50 yrs, jaundice encephalopathy interval >7 days, cerebral edema, Serum creatinine >1.5 mg/dl and prothrombin time >35 seconds. These compared well with MELD score and King’s college criterion. Our aim was to validate these indicators in a prospective study. Methods: This prospective study was carried out at the Nehru Hospital attached to the post Graduate Institute of Medical Education and Research at Chandigarh between July 2006 to July 2007. All the patients presenting to the emergency with acute liver failure (O Grady’s criterion) were included. Detailed clinical history, with clinical parameters, were noted and laboratory parameters were studied at admission and at 48 hours interval till the patient recovered or died. All the patients received conservative therapy and no liver transplants were offered. MELD score was calculated using online calculator and CPI was calculated based on the clinical + laboratory criterion. Each criterion was given a single point and a cumulative score was calculated. The data analysis was performed using SPSS software. Results: A total of 81 patients were screened and 41 fulfilled the inclusion criterion. 92.68% patients had hyperacute liver failure at presentation. Mean age was 28.54±13.32 years. 34.2% patients survived and all belonged to hyper acute liver failure group. Mean score amongst the survivors was 1.38±0.96 and amongst the patients dying early was 3.25±1.03. Presence of any 3 criterion (score of 3) had a specificity of 92.31% and a Positive predictive value of 93.75% in predicting adverse outcome. MELD score in survivors was 28.85±5.89 and amongst non survivors was 32.63±7.97. MELD of >33 had a specificity of 61% and positive predictive value of 80.76%. when both were compared by ROC curve, area under the curve for any 3 CPI was higher than MELD score of >33. Conclusion: Clinical prognostic indicator is a simple tool for prediction of mortality in patients with acute liver failure. In our study population it fared better than MELD score. 448 PROGNOSTIC VALUE OF TRANSIENT ELASTOGRAPHY FOR THE OUTCOME OF ACUTE LIVER FAILURE (ALF) A. Dechˆene1 , A. El Fouly1 , M. Schlattjan1 , R.K. Gieseler1 , F. Saner2 , A. Paul2 , G. Gerken1 , A.E. Canbay1 . 1 Gastroenterology and Hepatology, 2 General, Visceral and Transplantation Surgery, University Clinic of Essen, Essen, Germany E-mail: [email protected] Background: Transient elastography [FibroScan® (FS)] has been validated for the evaluation of liver stiffness in chronic hepatopathy. By correlation with well-established markers of hepatic fibrosis, the present prospective
HCV (×106 IU/mL) AST (U/L) ALT (U/L)
Day 0 (n = 14)
Day 30 (n = 14)
Day 90 (n = 12)
Day 180 (n = 9)
Day 365 (n = 8)
53±28 80±100 71±100
32±35 42±71 48±77
23±39 108±74 108±72
16±16 63±96 52±96
11±12 86±104 67±96
Rapamycin was withdrawn in 5 patients (36%), due to pneumonitis in 4 (80%). There were no significant changes in HCV-RNA or serum AST/ALT level during follow-up. Conclusion: The use of rapamycin after calcineurin inhibitors did not have a significant impact on HCV-RNA or serum AST/ALT levels. The most frequent reason for rapamycin withdrawal was pneumonitis. 446 CYSTATIN C CONCENTRATION AS A PREDICTOR OF DEATH AND CARDIOVASCULAR EVENTS AFTER LIVER TRANSPLANTATION V. Bernal1 , I. Pascual2 , P. Esquivias3 , A. Garc´ıa-Gil4 , C. Fern´andez2 , ´ Sim´on1 . 1 Hepatology & I. Lacambra2 , M.T. Serrano1 , M.A. Gastroenterology, 2 Cardiology, 3 Research Unit CIBERehd, 4 Liver Transplant Unit, Lozano Blesa University Hospital, Zaragoza, Spain E-mail: [email protected] Background and Aims: Diagnosis of renal failure is essential in cirrhosis. Serum creatinine concentration (Cr) presents a poor sensibility to detect early renal impairment. Cardiac dysfunction may also be present in these patients. Recently, cystatin C (Cys) has been suggested not only as a sensitive marker of renal function but also as a stronger predictor of the risk of death and cardiovascular events. To date no study has explored this fact in cirrhotic. The aims of this study were: 1. To investigate the value of plasma Cys concentration for the detection of moderate impaired renal function. 2. To correlate Cys levels with markers of severity of cirrhosis and cardiac function. 3. To evaluate whether Cys concentrations are associated with mortality and cardiovascular events among cirrhotic after LT. Methods: Clinical and biochemical data, echocardiography, heart hemodynamic measurements and Cys levels were analyzed in 100 cirrhotic candidates to LT. Cardiovascular events were recorded including: congestive heart failure, myocardial infarction, serious arrhythmias or stroke. Results: 1. Receiver-operator characteristics curves (ROC) showed a similar efficiency to detect creatinine clearance less than 60 ml/min/1.73m2 (Cys = 0.753; Cr = 0.799; GFR, Glomerular filtration rate, CockcroftGault formula = 0.842; Urea = 0.823; p = 0.001). However, at cut off concentrations of 1.3 mg/dl, Cr showed a great specificity (96%) but a poor sensibility (13%). Sensitivity of Cys was superior (83%) with a moderate specificity (55%) at cut off of 1400 ng/ml.
S169
2. Cys levels were not related to right heart hemodynamic measurements. In the regression analysis, Cys was significantly related to Child score, fractional shortening (echocardiographic parameter of systolic dysfunction) and creatinine. 3. Over a median follow-up of 2.7 years, 14 patients developed some cardiovascular events. Of these, 13 had high levels of Cys (>1400 ng/ml) before LT, with significant differences (p < 0.05). In the Kaplan–Meier analysis Cys discriminated significantly between survivors and nonsurvivors (p < 0.05), better than MELD. Conclusions: Cystatin C determination could be a valuable tool for early diagnosis of renal dysfunction in cirrhotic. Furthermore, it could be a predictor of the risk of death and cardiovascular events after LT.
447 PROSPECTIVE VALIDATION OF CLINICAL PROGNOSTIC INDICATORS IN ACUTE LIVER FAILURE A. Bhalla1 , C. Rao2 , R.K. Dhiman3 , N. Sharma1 , S. Mahi1 , V. Suri1 , Y. Chawla3 . 1 Internal Medicine, 2 PGIMER, 3 Hepatology, PGIMER, Chandigarh, India E-mail: [email protected] Background and Aims: Acute liver failure is a complex multisystem illness and carries a mortality of 70–800%. In a retrospective study, we at our centre had identified 5 clinical prognostic indicators (CPI) i.e. age >50 yrs, jaundice encephalopathy interval >7 days, cerebral edema, Serum creatinine >1.5 mg/dl and prothrombin time >35 seconds. These compared well with MELD score and King’s college criterion. Our aim was to validate these indicators in a prospective study. Methods: This prospective study was carried out at the Nehru Hospital attached to the post Graduate Institute of Medical Education and Research at Chandigarh between July 2006 to July 2007. All the patients presenting to the emergency with acute liver failure (O Grady’s criterion) were included. Detailed clinical history, with clinical parameters, were noted and laboratory parameters were studied at admission and at 48 hours interval till the patient recovered or died. All the patients received conservative therapy and no liver transplants were offered. MELD score was calculated using online calculator and CPI was calculated based on the clinical + laboratory criterion. Each criterion was given a single point and a cumulative score was calculated. The data analysis was performed using SPSS software. Results: A total of 81 patients were screened and 41 fulfilled the inclusion criterion. 92.68% patients had hyperacute liver failure at presentation. Mean age was 28.54±13.32 years. 34.2% patients survived and all belonged to hyper acute liver failure group. Mean score amongst the survivors was 1.38±0.96 and amongst the patients dying early was 3.25±1.03. Presence of any 3 criterion (score of 3) had a specificity of 92.31% and a Positive predictive value of 93.75% in predicting adverse outcome. MELD score in survivors was 28.85±5.89 and amongst non survivors was 32.63±7.97. MELD of >33 had a specificity of 61% and positive predictive value of 80.76%. when both were compared by ROC curve, area under the curve for any 3 CPI was higher than MELD score of >33. Conclusion: Clinical prognostic indicator is a simple tool for prediction of mortality in patients with acute liver failure. In our study population it fared better than MELD score. 448 PROGNOSTIC VALUE OF TRANSIENT ELASTOGRAPHY FOR THE OUTCOME OF ACUTE LIVER FAILURE (ALF) A. Dechˆene1 , A. El Fouly1 , M. Schlattjan1 , R.K. Gieseler1 , F. Saner2 , A. Paul2 , G. Gerken1 , A.E. Canbay1 . 1 Gastroenterology and Hepatology, 2 General, Visceral and Transplantation Surgery, University Clinic of Essen, Essen, Germany E-mail: [email protected] Background: Transient elastography [FibroScan® (FS)] has been validated for the evaluation of liver stiffness in chronic hepatopathy. By correlation with well-established markers of hepatic fibrosis, the present prospective