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PANTOPRAZOLE AND RABEPRAZOLE DO NOT IMPACT THE ACTIVITY OF CYTOCHROME P450 ASSESSED BY [13 C]-AMINOPYRINE BREATH TEST IN PATIENTS WITH LIVER CIRRHOSIS
Abstracts / Digestive and Liver Disease 47S (2015) e43–e66
driving the synthesis of abnormal peptides, possibly leading to virion assembly defects and to the intracytoplasmatic accumulation of HBsAg. Conclusions Selective pressure by the immune system selects variants in the precore region that are not proportionally detectable in the periphery, possibly due to the abnormal release of defective virions. This may also have clinical implications for hepatic pathology (steatosis) and may lead to the underestimation of viral load. A better comprehension of the relationship between intrahepatic and peripheral (virological and clinical) markers may confer to these a higher diagnostic power. http://dx.doi.org/10.1016/j.dld.2015.01.136 F-43 SARCOPENIA AT FIRST DIAGNOSIS PREDICTS A REDUCED SURVIVAL IN PATIENTS AFFECTED BY HEPATOCARCINOMA G. Antonelli 1 , P. Begini 1 , E. Gigante 1 , F. Carbonetti 2 , E. Iannicelli 2 , S. Gallina 1 , A. Pellicelli 3 , L. Miglioresi 3 , G. Delle Fave 1 , M. Marignani 1 1 Digestive and Liver Diseases Dpt., Sant Andrea Hospital, School of Medicine and Psychology, Sapienza University, Rome, Italy 2 Radiology Dpt., Saint Andrew Hospital, School of Medicine and Psychology, Sapienza University, Rome, Italy 3 Liver Unit., San Camillo Forlanini Hospital, Rome, Italy
Introduction Sarcopenia is a frequent complication and an independent risk factor for mortality and clinical outcomes in patients (pts) with liver cirrhosis and in a variety of other clinical conditions. Aim of the study was to determine the prevalence of sarcopenia in a cohort of cirrhotic pts at the first diagnosis of hepatocellular carcinoma (HCC) treated in a tertiary center and its influence on survival. Methods All consecutive HCC pts treated at our outpatient clinic (years 2004-2014) undergoing abdominal computed tomography (CT) were retrospectively studied with a software analyzing the cross-sectional areas of muscles at L3 level. Data was normalized for height obtaining the Skeletal Muscle Index (SMI) to measure sarcopenia. Presence of sarcopenia was defined when SMI was ≤41 cm2/m2 for women and ≤53cm2/m2 for men with a body mass index (BMI) ≥25, and ≤43 cm2/m2 for men with BMI < 25. Results 92 HCC pts were evaluated [27F (29.4%), 65 M (70,6%]. Age at diagnosis was 71,9 years (30,7-86,4), while BMI was 24,7 (17,5-36,7). Viral infection was the cause of liver disease in most cases. Distribution by CHILD score was as follows: A = 55,4%; B = (42,4%); C = (2,2%). Median MELD score was 10 (6-18). Metastatic disease was present in 12% of cases. The distribution by BCLC was as follows: A = (41,3%);B = (25%), C = 28,3%, D = 5,4%. Overall, sarcopenia was present in 40,2%. Baseline features were similar between sarcopenic vs non sarcopenic pts. Sarcopenic pts were prevalently females (p = 0,0044) and had a reduced mean Overall Survival of 123 (95% C.I. 98 to 150) vs 66 (95% C.I. 47 to 84) weeks (p = 0,001). Multivariate analysis has shown that sarcopenia was indipendent of age (p = 0,0027). Conclusions The prevalence of Sarcopenia in HCC pts is high, with a greater frequency in female pts. Presence of Sarcopenia at diagnosis of HCC is an important predictor of a reduced survival. http://dx.doi.org/10.1016/j.dld.2015.01.137
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F-44 PANTOPRAZOLE AND RABEPRAZOLE DO NOT IMPACT THE ACTIVITY OF CYTOCHROME P450 ASSESSED BY [13 C]-AMINOPYRINE BREATH TEST IN PATIENTS WITH LIVER CIRRHOSIS A. Rocco 2 , D. Angrisani 2 , C. Rubicondo 2 , L. Staiano 1 , D. Amoruso 1 , D. Compare 2 , C. Coppola 1 , G. Nardone 2 1
Hepatology and Interventional Ultrasound Unit, Gragnano Hospital, Gragnano, Italy 2 Department of Clinical Medicine and Surgery, Gastroenterology Unit, Federico II University of Naples, Italy Introduction: Proton pump inhibitors (PPIs) are one of the most widely used drugs worldwide. Almost all PPIs undergo extensive hepatic metabolism via cytochrome (CYP)-P450 system, specifically CYP-2C19 and CYP-3A4. Pantoprazole is metabolized through the CYP-P450 system, while the primary pathway of rabeprazole metabolism is non enzymatic. In advanced liver diseases the activity of drug metabolizing enzymes is impaired, thus increasing the risk of drug accumulation, drug-drug interaction and adverse events.13 C-aminopyrine breath test (13 C-ABT) is a noninvasive, liver function test that explores CYP enzyme activity. Aim: to evaluate the effects of different PPIs on the activity of CYPs by 13 C-ABT in patients with Hepatitis C virus (HCV)-related liver cirrhosis. Material and Methods: Thirty consecutive genotype 1 HCVrelated liver cirrhosis patients, Child-Pugh A, were randomly assigned to pantoprazole (40 mg/day) or rabeprazole (20 mg/day). 13 C-ABT was performed before and 15 days after starting PPI by collecting breath samples baseline and at 30-minute intervals for 2 hours after oral administration of 13 C-aminopyrine (2 mg/Kg body weight). 13 C-enrichment of CO2 was determined by purification-isotope ratio mass spectrometer. Results were expressed as maximum percentage of 13 CO2-recovery per hour (max 13 C% dose/h) at any time (“excretion peak”) and percentage of 13 CO2-cumulative dose recovered in 2 h (%13 C cum dose at 120 min). Results: Overall, we enrolled 13 males and 17 females. Mean age was 60.9 ± 7.5 yrs. Age, gender distribution, BMI and laboratory findings did not significantly differ among pantoprazole and rabeprazole group. Baseline, 13 C-ABT results were altered in 13/30 (43%) patients (6 in pantoprazole and 7 in rabeprazole group). Fifteen days after PPIs, 13 C-ABT did not significantly changed in terms of both %dose/h and %dose/cumulative, irrespective of PPI used. Conclusion: Pantoprazole and rabeprazole do not significantly affect liver function in patients with HCV-related liver cirrhosis. Both PPIs are safe for treatment of patients with advanced liver disease. http://dx.doi.org/10.1016/j.dld.2015.01.138
driving the synthesis of abnormal peptides, possibly leading to virion assembly defects and to the intracytoplasmatic accumulation of HBsAg. Conclusions Selective pressure by the immune system selects variants in the precore region that are not proportionally detectable in the periphery, possibly due to the abnormal release of defective virions. This may also have clinical implications for hepatic pathology (steatosis) and may lead to the underestimation of viral load. A better comprehension of the relationship between intrahepatic and peripheral (virological and clinical) markers may confer to these a higher diagnostic power. http://dx.doi.org/10.1016/j.dld.2015.01.136 F-43 SARCOPENIA AT FIRST DIAGNOSIS PREDICTS A REDUCED SURVIVAL IN PATIENTS AFFECTED BY HEPATOCARCINOMA G. Antonelli 1 , P. Begini 1 , E. Gigante 1 , F. Carbonetti 2 , E. Iannicelli 2 , S. Gallina 1 , A. Pellicelli 3 , L. Miglioresi 3 , G. Delle Fave 1 , M. Marignani 1 1 Digestive and Liver Diseases Dpt., Sant Andrea Hospital, School of Medicine and Psychology, Sapienza University, Rome, Italy 2 Radiology Dpt., Saint Andrew Hospital, School of Medicine and Psychology, Sapienza University, Rome, Italy 3 Liver Unit., San Camillo Forlanini Hospital, Rome, Italy
Introduction Sarcopenia is a frequent complication and an independent risk factor for mortality and clinical outcomes in patients (pts) with liver cirrhosis and in a variety of other clinical conditions. Aim of the study was to determine the prevalence of sarcopenia in a cohort of cirrhotic pts at the first diagnosis of hepatocellular carcinoma (HCC) treated in a tertiary center and its influence on survival. Methods All consecutive HCC pts treated at our outpatient clinic (years 2004-2014) undergoing abdominal computed tomography (CT) were retrospectively studied with a software analyzing the cross-sectional areas of muscles at L3 level. Data was normalized for height obtaining the Skeletal Muscle Index (SMI) to measure sarcopenia. Presence of sarcopenia was defined when SMI was ≤41 cm2/m2 for women and ≤53cm2/m2 for men with a body mass index (BMI) ≥25, and ≤43 cm2/m2 for men with BMI < 25. Results 92 HCC pts were evaluated [27F (29.4%), 65 M (70,6%]. Age at diagnosis was 71,9 years (30,7-86,4), while BMI was 24,7 (17,5-36,7). Viral infection was the cause of liver disease in most cases. Distribution by CHILD score was as follows: A = 55,4%; B = (42,4%); C = (2,2%). Median MELD score was 10 (6-18). Metastatic disease was present in 12% of cases. The distribution by BCLC was as follows: A = (41,3%);B = (25%), C = 28,3%, D = 5,4%. Overall, sarcopenia was present in 40,2%. Baseline features were similar between sarcopenic vs non sarcopenic pts. Sarcopenic pts were prevalently females (p = 0,0044) and had a reduced mean Overall Survival of 123 (95% C.I. 98 to 150) vs 66 (95% C.I. 47 to 84) weeks (p = 0,001). Multivariate analysis has shown that sarcopenia was indipendent of age (p = 0,0027). Conclusions The prevalence of Sarcopenia in HCC pts is high, with a greater frequency in female pts. Presence of Sarcopenia at diagnosis of HCC is an important predictor of a reduced survival. http://dx.doi.org/10.1016/j.dld.2015.01.137
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F-44 PANTOPRAZOLE AND RABEPRAZOLE DO NOT IMPACT THE ACTIVITY OF CYTOCHROME P450 ASSESSED BY [13 C]-AMINOPYRINE BREATH TEST IN PATIENTS WITH LIVER CIRRHOSIS A. Rocco 2 , D. Angrisani 2 , C. Rubicondo 2 , L. Staiano 1 , D. Amoruso 1 , D. Compare 2 , C. Coppola 1 , G. Nardone 2 1
Hepatology and Interventional Ultrasound Unit, Gragnano Hospital, Gragnano, Italy 2 Department of Clinical Medicine and Surgery, Gastroenterology Unit, Federico II University of Naples, Italy Introduction: Proton pump inhibitors (PPIs) are one of the most widely used drugs worldwide. Almost all PPIs undergo extensive hepatic metabolism via cytochrome (CYP)-P450 system, specifically CYP-2C19 and CYP-3A4. Pantoprazole is metabolized through the CYP-P450 system, while the primary pathway of rabeprazole metabolism is non enzymatic. In advanced liver diseases the activity of drug metabolizing enzymes is impaired, thus increasing the risk of drug accumulation, drug-drug interaction and adverse events.13 C-aminopyrine breath test (13 C-ABT) is a noninvasive, liver function test that explores CYP enzyme activity. Aim: to evaluate the effects of different PPIs on the activity of CYPs by 13 C-ABT in patients with Hepatitis C virus (HCV)-related liver cirrhosis. Material and Methods: Thirty consecutive genotype 1 HCVrelated liver cirrhosis patients, Child-Pugh A, were randomly assigned to pantoprazole (40 mg/day) or rabeprazole (20 mg/day). 13 C-ABT was performed before and 15 days after starting PPI by collecting breath samples baseline and at 30-minute intervals for 2 hours after oral administration of 13 C-aminopyrine (2 mg/Kg body weight). 13 C-enrichment of CO2 was determined by purification-isotope ratio mass spectrometer. Results were expressed as maximum percentage of 13 CO2-recovery per hour (max 13 C% dose/h) at any time (“excretion peak”) and percentage of 13 CO2-cumulative dose recovered in 2 h (%13 C cum dose at 120 min). Results: Overall, we enrolled 13 males and 17 females. Mean age was 60.9 ± 7.5 yrs. Age, gender distribution, BMI and laboratory findings did not significantly differ among pantoprazole and rabeprazole group. Baseline, 13 C-ABT results were altered in 13/30 (43%) patients (6 in pantoprazole and 7 in rabeprazole group). Fifteen days after PPIs, 13 C-ABT did not significantly changed in terms of both %dose/h and %dose/cumulative, irrespective of PPI used. Conclusion: Pantoprazole and rabeprazole do not significantly affect liver function in patients with HCV-related liver cirrhosis. Both PPIs are safe for treatment of patients with advanced liver disease. http://dx.doi.org/10.1016/j.dld.2015.01.138