- Email: [email protected]
200 EFFECT OF DIFFERENT SEDATION ON CRITICAL FLICKER FREQUENCY, A DIAGNOSTIC TOOL FOR MINIMAL ENCEPHALOPATHY
POSTERS 15) out of 294 hospitalized cirrhotic patients. The main site of infection were: urinary tract infection (40%), pneumonia (20%), spontaneous bacterial peritonitis (17%). Multidrug resistant bacteria were isolated in 51% of the cases. Patients who developed a nosocomial infection were more likely to show a worse liver function (MELD 15±8 vs 12±4; p < 0.01), to bear a TIPS (20% vs 7%; p = 0.05), to have less available space in the hospital room (44% vs 27%; p < 0.001) and to have undergone a higher number of invasive procedures (2.7±2 vs 1.7±1.1; p = 0.01). The hospital stay was longer in patients with nosocomial infection even if the time before the diagnosis of the infection was considered (15±12 vs 8±10; p < 0.01). At multivariate analysis hospitalization in a room with an additional bed (p = 0.004; OR 2.5; IC 1.1–5), the number of invasive procedures (p = 0.002; OR 6; IC 2.6–14), and a longer hospital stay (p = 0.05; OR 1.9; IC 1.02–1.2) were selected as independent predictors for the development of nosocomial infections. Conclusions: A large number of invasive procedures, a longer hospital stay and an inadequate room in hospital are factors significantly related to the development of nosocomial infections in cirrhotic patients. 198 TRANSIENT ELASTOGRAPHY IS A USEFUL CLINICAL TOOL TO DETECT MINIMAL HEPATIC ENCEPHALOPATHY IN A COHORT OF COMPENSATED CIRRHOTIC PATIENTS Z. Galvin, M.T. O’Neill, D. Lowry, S. Stewart. Centre for Liver Diseeases, Mater Misericordiae University Hospital, Dublin, Ireland E-mail: [email protected] Introduction: Minimal hepatic encephalopathy (mHE) is a common cause of neurocognitive dysfunction in patients with cirrhosis. It is associated with falls, impaired driving skills, the later development of overt HE and reduced overall survival. Treatment has been shown to improve psychometric performance, enhance qualityof-life parameters and reduce the risk of progression to overt HE. The diagnosis is based on psychometric and/or neuro-physiological tests. These tests can be time consuming, expensive and may require experienced personnel and therefore are not widely used outside of the research setting. Transient elastography (TE) is an established non-invasive tool to determine the severity of hepatic fibrosis. Aim: The aim of this study was to investigate if TE could be used in a population with compensated cirrhosis to identify patients most likely to have mHE. Methods: All compensated, biopsy-proven, cirrhotic patients attending the outpatient department were included in the study. Patients with any clinical evidence of neuropsychiatric disturbance were excluded. Each patient completed the Psychometric Hepatic Encephalopathy Score (PHES) and had TE performed on the same day. PHES raw data was compared to UK normative data and a score of two or more standard deviations below the mean diagnosed mHE. TE was performed using Fibroscan (Echosens) and the median value of ten valid acquisitions gave the liver stiffness measurement (LSM) in kPa. Statistical analysis was done using SPSS version 18. The diagnostic performance of LSM was assessed by using receiver operating characteristics (ROC) curves. The optimal cut-off value for LSM was chosen to maximise the sum of sensitivity and specificity. Results: 29/86 patients (34%) had mHE on PHES. LSM was significantly higher in those with mHE than in those without mHE (median 38.6 kPa v 17.3 kPa; p = 0.002). Based on the ROC curve a cut-off of 20.8 kPa had a sensitivity of 79% and a specificity of 67% to detect mHE (AUROC = 0.785, p = 0.001). Conclusion: TE can be used to risk stratify patients for the presence of mHE. All patients with a LSM >20.8 kPa should either be tested for mHE or empirically treated. Sincere thanks to Dr Marsha Morgan for facilitating the use of UK PHES normative data.
199 PERIBILIARY GLAND DILATATION: MORPHOMETRIC AND CLINICAL CORRELATION IN 74 PATIENTS N. Goossens1 , L. Rubbia-Brandt2 , E. Giostra1 , L. Spahr1 . 1 Gastroenterology & Hepatology, 2 Pathology, Geneva University Hospital, Geneva, Switzerland E-mail: [email protected] Background and Aims: Peribiliary glands (PBG) are found adjacent to large intra and extra-hepatic ducts, however their function remains uncertain. Recently, multipotent stem/progenitor cells have been described in these glands suggesting a possible role in regeneration. PBG cystic dilatation has previously been described in association with cirrhosis however its natural history, clinical associations and pathophysiology remain unclear. Our aim was to better characterise the prevalence, histological and clinical findings of PBG dilatation in a retrospective cohort of patients undergoing liver transplantation (LT) for end-stage liver disease. Methods: Explants of patients undergoing LT between October 2006 and October 2011 were included; exclusion criteria included paediatric patients, biliary pathology, acute liver failure (ALF) or insufficient clinical data. We performed a morphometric analysis of the PBG by measuring their maximal diameter in the hilar region. PBGs were judged to be dilated when their luminal diameter exceeded 1000 mm. We correlated this data to clinical and biological information. Results: 74 patients were included in this cohort (exclusion (n): paediatric=20, ALF=9, biliary=11, other=8, insufficient data=46). Clinical characteristics were as follows: average age: 52 years, mean MELD: 14, men: 52%, alcoholic cirrhosis: 48%, viral cirrhosis: 54%, HCC: 53%, ascites: 52%. 30% of patients had histologically proven PBG dilatation. In univariate analysis PBG dilatation was associated with a higher MELD (20.6 vs 12.5, p = 0.007), higher Child–Pugh score (10.3 vs 8.01, p = 0.003) higher bilirubin (212 vs 84.3, p = 0.035) higher INR (2.1 vs 1.4, p = 0.024) and less frequent viral aetiology to the cirrhosis (29% vs 61%, p = 0.063). Sex, age, presence of ascites, alkaline phosphatase level and alcoholic aetiology were not associated with PBG dilatation. In multivariate analysis, MELD (OR = 1.11 per unit increase in MELD score, 95% CI 1.03–1.17, p = 0.005) was the only significant factor associated with PBG dilatation. Conclusions: PBG dilatation is a frequent finding in cirrhotic patients undergoing liver transplantation. In our cohort of patients transplanted for advanced liver disease it was significantly correlated to the degree of liver failure. Further studies should attempt to characterise this finding more fully and assess whether PBG dilatation is associated with proliferation of multipotent stem cells found in PBGs. 200 EFFECT OF DIFFERENT SEDATION ON CRITICAL FLICKER FREQUENCY, A DIAGNOSTIC TOOL FOR MINIMAL ENCEPHALOPATHY F. Grunhage, ¨ A. Seegmuller, ¨ F. Lammert. Medical Department II, Saarland University Medical Center, Homburg, Germany E-mail: [email protected] Introduction: Critical flicker frequency measurements are a valid tool for assessing early stages of cerebral dysfunction in patients with acute and chronic liver diseases. However, it may also serve as a tool for assessing the fitness of these patients after specific diagnostic or therapeutic interventions. Driving after sedation for endoscopic procedures is a matter of debate, in particular since recent results from a large study (Horiuchi et al. Am J Gastroenterol 2009) have suggested that driving home after propofol sedation might be safe. We used CFF analysis to asses the time-dependent effect of different sedation methods on brain function in the endoscopy unit of a tertiary referral centre.
Journal of Hepatology 2013 vol. 58 | S63–S227
S87
POSTERS Methods: In total, 83 patients were included in the study. All patients received a CFF analysis before, 30, 60, 90 and 120 min after the endoscopy. CFF results were correlated to sedation methods. Differences in the CFF between groups and within groups were tested by non-parametric Mann–Whitney U or paired t-tests comparisons as appropriate. Results: Overall, 33.7% of patients received no sedation, 26.5% were sedated with propofol (P) alone, and 38.6% of patients received a combination of propofol with midazolam (P/M). While in the control group no changes in CFF results were detected, patients with sedation experienced a clear drop in CFF results at 30 min. This drop was more pronounced in patients P/M-sedation as compared to P-mono sedation (30 min CFF: 37.6 Hz vs. 42.2 Hz). In addition the effect of sedation was detectable for >120min in P/M sedated patients, while CFF results in patients with P-mono sedation recovered to baseline values after 60min. Discussion/Conclusion: Our study clearly shows that the use of CFF assessment may be beyond testing for hepatic encephalopathy. We here show that the combination of propofol with midazolam leads to long lasting effects on CFF, which may affect driving capability, whereas sedation with propofol wares off within one hour. CFF analysis may be an easy to use tool to asses driving ability in this setting. 201 LONG-TERM EFFECT OF PROPRANOLOL ON PORTAL HYPERTENSION IN PATIENTS WITH CIRRHOSIS: A SINGLE CENTRE PROSPECTIVE EXPERIENCE S. Heebøll1 , H. Vilstrup1 , S. Keiding1,2 . 1 Department of Hepatology and Gastroenterology, 2 Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark E-mail: [email protected] Background and Aims: Portal hypertension in patients with cirrhosis is usually treated with non-selective b-blockade using propranolol as primary or secondary prophylaxis against variceal bleeding. However, a significant fraction of the patients do not obtain the hemodynamic effect and these patients are at risk of side effects to b-blockade without the targeted risk reduction. Here, we aimed to investigate the response rate at our institution and identify markers of response/non-response.
Figure 1. Relationship between difference in HVPG with and without propranolol 80 mg daily and native HVPG in 124 patients with cirrhosis. Negative values denote a positive treatment response. Regression line is shown (P < 0.001). Individual values are shown for patients with complete response, i.e. reduction of HVPG to ≤12 mmHg (solid circles); partial response, i.e. reduction of HVPG by ≥20% (triangles); and no response (open circles). S88
Methods: In 124 patients with cirrhosis, the hepatic venous pressure gradient (HVPG) was measured with and without propranolol on a daily dose of 80 mg, and consecutive HVPG data were registered in a prospective database along with clinical data. Results: Overall, 41% responded to treatment. The relationship between change in HVPG and native HVPG showed that the HVPG reduction was larger for higher native HVPG values (P < 0.001) (Fig. 1) and multivariate analysis showed that the native HVPG was the only clinical variable that predicted a positive treatment effect (P = 0.002). Interestingly, presence of gastric varices was associated with lack of adequate treatment effect (P = 0.04). There was no significant relation between the reductions in heart rate and HVPG (P = 0.4). Conclusions: Our results support the clinical practice of measuring HVPG with and without treatment to minimize meaningless treatment. The significant association between a high native HVPG and propranolol induced HVPG reduction indicates a potential pharmacological treatment benefit also for patients with advanced portal hypertension. 202 VON WILLEBRAND FACTOR – A MARKER FOR HEPATOPULMONARY SYNDROME T. Horvatits, A. Drolz, A. Ferlitsch, C. Mueller, P. Schenk, V. Fuhrmann. Department of Internal Medicine 3, Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria E-mail: [email protected] Background: Hepatopulmonary syndrome (HPS) occurs in 20–30% of patients with liver cirrhosis and is associated with a >2fold increased mortality. Pulmonary angiogenesis and endothelial dysfunction seem to play a central role in its pathogenesis. von Willebrand factor antigen (vWF-Ag), a marker of endothelial dysfunction, is significantly elevated in patients with liver cirrhosis and portal hypertension. vWF levels are associated with increased pulmonary angiogenesis in a rat model of HPS. Single nucleotide polymorphisms (SNPs) in the vWF-gene are associated with HPS. Therefore we aimed to evaluate the role of vWF-Ag in patients with HPS. Methods: 128 patients (94 male, 34 female; mean age: 56 years) with liver cirrhosis were included in this prospective study. vWFAg was assessed by ELISA. All patients were screened for presence of clinically significant HPS according to established consensus guidelines (presence of cirrhosis, AaDO2 >15 mmHg & PaO2 <80 mmHg, intrapulmonary vasodilatation in contrast enhanced echocardiography). Results: Criteria of HPS were fulfilled in 27 patients. Liver cirrhosis was caused mainly by alcoholic liver disease (63%), chronic hepatitis C (24%) and others (13%). vWF-Ag level was significantly higher in patients with HPS compared to patients without HPS (483±123% versus 331±100%; p < 0.05). vWF-Ag correlated significantly with gas exchange abnormalities in the total cohort by means of AaDO2 (r = 0.47; p < 0.05) and PaO2 (r = 0.4; p < 0.05). ROCAUC of vWF-Ag for detection of HPS was 0.825. The best cut off with maximal sensitivity was 327% (sensitivity of 100% and specificity of 51.5%; positive predictive value: 34.2%, 95% CI: 23.9–45.7%; negative predictive value: 100%, 95% CI: 92.7–100%). vWF-Ag levels were significantly associated with HPS (OR: 1.016, 95% CI: 1.009–1.023, p < 0.05) and remained significantly associated with HPS after correction for sex, age, MELD score and hepatic venous pressure gradient (OR: 1.019, 95% CI: 1.002–1.036, p < 0.05). Conclusion: vWF-Ag is a significant predictor for presence of HPS, independently of severity of cirrhosis. vWF-Ag using a cut-off level >327% may help to identify HPS in patients with cirrhosis.
Journal of Hepatology 2013 vol. 58 | S63–S227
199 PERIBILIARY GLAND DILATATION: MORPHOMETRIC AND CLINICAL CORRELATION IN 74 PATIENTS N. Goossens1 , L. Rubbia-Brandt2 , E. Giostra1 , L. Spahr1 . 1 Gastroenterology & Hepatology, 2 Pathology, Geneva University Hospital, Geneva, Switzerland E-mail: [email protected] Background and Aims: Peribiliary glands (PBG) are found adjacent to large intra and extra-hepatic ducts, however their function remains uncertain. Recently, multipotent stem/progenitor cells have been described in these glands suggesting a possible role in regeneration. PBG cystic dilatation has previously been described in association with cirrhosis however its natural history, clinical associations and pathophysiology remain unclear. Our aim was to better characterise the prevalence, histological and clinical findings of PBG dilatation in a retrospective cohort of patients undergoing liver transplantation (LT) for end-stage liver disease. Methods: Explants of patients undergoing LT between October 2006 and October 2011 were included; exclusion criteria included paediatric patients, biliary pathology, acute liver failure (ALF) or insufficient clinical data. We performed a morphometric analysis of the PBG by measuring their maximal diameter in the hilar region. PBGs were judged to be dilated when their luminal diameter exceeded 1000 mm. We correlated this data to clinical and biological information. Results: 74 patients were included in this cohort (exclusion (n): paediatric=20, ALF=9, biliary=11, other=8, insufficient data=46). Clinical characteristics were as follows: average age: 52 years, mean MELD: 14, men: 52%, alcoholic cirrhosis: 48%, viral cirrhosis: 54%, HCC: 53%, ascites: 52%. 30% of patients had histologically proven PBG dilatation. In univariate analysis PBG dilatation was associated with a higher MELD (20.6 vs 12.5, p = 0.007), higher Child–Pugh score (10.3 vs 8.01, p = 0.003) higher bilirubin (212 vs 84.3, p = 0.035) higher INR (2.1 vs 1.4, p = 0.024) and less frequent viral aetiology to the cirrhosis (29% vs 61%, p = 0.063). Sex, age, presence of ascites, alkaline phosphatase level and alcoholic aetiology were not associated with PBG dilatation. In multivariate analysis, MELD (OR = 1.11 per unit increase in MELD score, 95% CI 1.03–1.17, p = 0.005) was the only significant factor associated with PBG dilatation. Conclusions: PBG dilatation is a frequent finding in cirrhotic patients undergoing liver transplantation. In our cohort of patients transplanted for advanced liver disease it was significantly correlated to the degree of liver failure. Further studies should attempt to characterise this finding more fully and assess whether PBG dilatation is associated with proliferation of multipotent stem cells found in PBGs. 200 EFFECT OF DIFFERENT SEDATION ON CRITICAL FLICKER FREQUENCY, A DIAGNOSTIC TOOL FOR MINIMAL ENCEPHALOPATHY F. Grunhage, ¨ A. Seegmuller, ¨ F. Lammert. Medical Department II, Saarland University Medical Center, Homburg, Germany E-mail: [email protected] Introduction: Critical flicker frequency measurements are a valid tool for assessing early stages of cerebral dysfunction in patients with acute and chronic liver diseases. However, it may also serve as a tool for assessing the fitness of these patients after specific diagnostic or therapeutic interventions. Driving after sedation for endoscopic procedures is a matter of debate, in particular since recent results from a large study (Horiuchi et al. Am J Gastroenterol 2009) have suggested that driving home after propofol sedation might be safe. We used CFF analysis to asses the time-dependent effect of different sedation methods on brain function in the endoscopy unit of a tertiary referral centre.
Journal of Hepatology 2013 vol. 58 | S63–S227
S87
POSTERS Methods: In total, 83 patients were included in the study. All patients received a CFF analysis before, 30, 60, 90 and 120 min after the endoscopy. CFF results were correlated to sedation methods. Differences in the CFF between groups and within groups were tested by non-parametric Mann–Whitney U or paired t-tests comparisons as appropriate. Results: Overall, 33.7% of patients received no sedation, 26.5% were sedated with propofol (P) alone, and 38.6% of patients received a combination of propofol with midazolam (P/M). While in the control group no changes in CFF results were detected, patients with sedation experienced a clear drop in CFF results at 30 min. This drop was more pronounced in patients P/M-sedation as compared to P-mono sedation (30 min CFF: 37.6 Hz vs. 42.2 Hz). In addition the effect of sedation was detectable for >120min in P/M sedated patients, while CFF results in patients with P-mono sedation recovered to baseline values after 60min. Discussion/Conclusion: Our study clearly shows that the use of CFF assessment may be beyond testing for hepatic encephalopathy. We here show that the combination of propofol with midazolam leads to long lasting effects on CFF, which may affect driving capability, whereas sedation with propofol wares off within one hour. CFF analysis may be an easy to use tool to asses driving ability in this setting. 201 LONG-TERM EFFECT OF PROPRANOLOL ON PORTAL HYPERTENSION IN PATIENTS WITH CIRRHOSIS: A SINGLE CENTRE PROSPECTIVE EXPERIENCE S. Heebøll1 , H. Vilstrup1 , S. Keiding1,2 . 1 Department of Hepatology and Gastroenterology, 2 Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark E-mail: [email protected] Background and Aims: Portal hypertension in patients with cirrhosis is usually treated with non-selective b-blockade using propranolol as primary or secondary prophylaxis against variceal bleeding. However, a significant fraction of the patients do not obtain the hemodynamic effect and these patients are at risk of side effects to b-blockade without the targeted risk reduction. Here, we aimed to investigate the response rate at our institution and identify markers of response/non-response.
Figure 1. Relationship between difference in HVPG with and without propranolol 80 mg daily and native HVPG in 124 patients with cirrhosis. Negative values denote a positive treatment response. Regression line is shown (P < 0.001). Individual values are shown for patients with complete response, i.e. reduction of HVPG to ≤12 mmHg (solid circles); partial response, i.e. reduction of HVPG by ≥20% (triangles); and no response (open circles). S88
Methods: In 124 patients with cirrhosis, the hepatic venous pressure gradient (HVPG) was measured with and without propranolol on a daily dose of 80 mg, and consecutive HVPG data were registered in a prospective database along with clinical data. Results: Overall, 41% responded to treatment. The relationship between change in HVPG and native HVPG showed that the HVPG reduction was larger for higher native HVPG values (P < 0.001) (Fig. 1) and multivariate analysis showed that the native HVPG was the only clinical variable that predicted a positive treatment effect (P = 0.002). Interestingly, presence of gastric varices was associated with lack of adequate treatment effect (P = 0.04). There was no significant relation between the reductions in heart rate and HVPG (P = 0.4). Conclusions: Our results support the clinical practice of measuring HVPG with and without treatment to minimize meaningless treatment. The significant association between a high native HVPG and propranolol induced HVPG reduction indicates a potential pharmacological treatment benefit also for patients with advanced portal hypertension. 202 VON WILLEBRAND FACTOR – A MARKER FOR HEPATOPULMONARY SYNDROME T. Horvatits, A. Drolz, A. Ferlitsch, C. Mueller, P. Schenk, V. Fuhrmann. Department of Internal Medicine 3, Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria E-mail: [email protected] Background: Hepatopulmonary syndrome (HPS) occurs in 20–30% of patients with liver cirrhosis and is associated with a >2fold increased mortality. Pulmonary angiogenesis and endothelial dysfunction seem to play a central role in its pathogenesis. von Willebrand factor antigen (vWF-Ag), a marker of endothelial dysfunction, is significantly elevated in patients with liver cirrhosis and portal hypertension. vWF levels are associated with increased pulmonary angiogenesis in a rat model of HPS. Single nucleotide polymorphisms (SNPs) in the vWF-gene are associated with HPS. Therefore we aimed to evaluate the role of vWF-Ag in patients with HPS. Methods: 128 patients (94 male, 34 female; mean age: 56 years) with liver cirrhosis were included in this prospective study. vWFAg was assessed by ELISA. All patients were screened for presence of clinically significant HPS according to established consensus guidelines (presence of cirrhosis, AaDO2 >15 mmHg & PaO2 <80 mmHg, intrapulmonary vasodilatation in contrast enhanced echocardiography). Results: Criteria of HPS were fulfilled in 27 patients. Liver cirrhosis was caused mainly by alcoholic liver disease (63%), chronic hepatitis C (24%) and others (13%). vWF-Ag level was significantly higher in patients with HPS compared to patients without HPS (483±123% versus 331±100%; p < 0.05). vWF-Ag correlated significantly with gas exchange abnormalities in the total cohort by means of AaDO2 (r = 0.47; p < 0.05) and PaO2 (r = 0.4; p < 0.05). ROCAUC of vWF-Ag for detection of HPS was 0.825. The best cut off with maximal sensitivity was 327% (sensitivity of 100% and specificity of 51.5%; positive predictive value: 34.2%, 95% CI: 23.9–45.7%; negative predictive value: 100%, 95% CI: 92.7–100%). vWF-Ag levels were significantly associated with HPS (OR: 1.016, 95% CI: 1.009–1.023, p < 0.05) and remained significantly associated with HPS after correction for sex, age, MELD score and hepatic venous pressure gradient (OR: 1.019, 95% CI: 1.002–1.036, p < 0.05). Conclusion: vWF-Ag is a significant predictor for presence of HPS, independently of severity of cirrhosis. vWF-Ag using a cut-off level >327% may help to identify HPS in patients with cirrhosis.
Journal of Hepatology 2013 vol. 58 | S63–S227