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Oral bile acid administration reduces endotoxemia and bacterial translocation (BT) in ascitic cirrhotic rats
Category 2: Cirrhosis and its complications, pathophysiology and clinical aspects ~
ETIOLOGY OF LIVER CIRRHOSIS: AN HISTOLOGICAL APPRAISAL
Susana Lopes, Pedro Moutinho Ribeiro, Guilherme Macedo, Tome Ribeiro. Gastroenterology Unit, H.S. Joao, Porto, Portugal Introduction and Aim: Knowing the etiology of chronic liver disease and cirrhosis in a particular setting, may give some clues about the relative strenght of the hepatotoxic factors and may allow the establishment of some epidemiologic priorities for investigation and clinical practice. Hepatocellular carcinoma screening strategies may be substantially modified if there is evidence of a significant prevalence of risk factors for its development. Material and Methods: We have evaluated the histological diagnosis presented in the Pathology Department registry, corresponding to all the knew cirrhotic patients diagnosed in a 40 month period in a Central Hospital. Results: We have studied 241 cases of cirrhosis, from 173 male patients (and 68 females), with the etiology distributed as follows: alcoholic in 91 (38%), viral in 64 (27%) - related to HBV infection in 28 patients and to HCV in 36 patients. Hemochromatosis and variable degrees of iron overload was observed in 13 patients (5%) and 16 (6%) respectively. In 8 patients (3%) we found hepatocellular carcinoma; autoimmune cirrhosis was diagnosed in 8 patients (3%), Wilson's in 7 (3%), alphal antitrypsin deficiency in 5 (2%), primary biliary cirrhosis in 2 patients (1%) like primary sclerosing cholangitis and secondary biliary cirrhosis (1%). In 39 cases (16%) there was no histological identification of etiology. Conclusion: Alcoholic liver disease is still the leading cause of cirrhosis and HCV was more prevalent than HBV cirrhosis. In a significative number of patients (16%), histology was not enough to elucidate the etiology of cirrhosis, suggesting that toxic or metabolic not yet identifiable factors may be important in a group of patients.
7 ~ - ] ORAL BILE ACID ADMINISTRATION REDUCES ENDOTOXEMIA AND BACTERIAL TRANSLOCATION (BT) IN ASCITIC CIRRHOTIC RATS Vicente Lorenzo Zunigal, Ramon Bartoli 1, Ramon Planas I , Marco Antonio Alvarez 1, Belen Vinado I , Josep Mane t , Lee Hagey 2, Alan F. Hofmann 2, Miguel Angel Gassull I . 1Hospital Universitari Germans
Trias i Pujol, Badalona, Spain; 2University of California, San Diego, USA In cirrhosis there is a decrease in intraluminal bile acid concentrations which can favour endotoxin absorption and BT. Aim: To assess the effect of the administration of a deconjugation resistant bile acid (cholylsarcosine: Cs) and a deconjugable bile acid (cholylglycine: Cg) upon endotoxemia and the incidence of BT in ascitic cirrhotic rats. Methods: 45 S-D rats with orogastric CC14-induced cirrhosis and ascites were randomized to be treated with oral Cs, Cg or placebo (P) (70 mg/kg body weight dally) for 2 weeks. Three groups of 5 healthy rats receiving the same doses of Cs, Cg or P were used as control groups. Results: In placebo treated rats, secretion of bile was significantly lower in cirrhotic than in healthy rats (11.3 4- 2.73 vs 20.26 4- 1.38 ul/min; p < 0.05). The administration of Cs and Cg to cirrhotic rats normalized bile secretion (21 4- 3.12 and 24.46 4- 2.73 ul/min), and bile secretion become enriched in Cs and in cholylconjugates, respectively. Endotoxemia was significantly higher in cirrhotic rats receiving P (0.282 4- 0.124 Ul/ml) than in those treated with Cs or Cg (0.098 4- 0.002 and 0.101 4- 0.007; p < 0.001). The incidence of death and/or BT was significantly higher in cirrhotic rats receiving P (10/15: 66%) than in those treated with Cs or Cg (5/15: 33% and 4/15: 26%; p < 0.05). Conclusions: The administration of conjugated bile acids to ascitic cirrhotic rats causes increased bile acid secretion, that is associated with decreased endotoxemia, decreased BT, and decreased mortality. These results suggest that oral conjugated bile acids may be useful in preventing BT and SBP in cirrhotic patients.
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205
ENDOSCOPIC BAND LIGATION VERSUS ENDOSCOPIC INJECTION SCLEROTHERAPY OF OESOPHAGEAL VARICES - A COMPARATIVE STUDY
Mario Markov. Clinic of Internal Medicine, Hospital 'St Anna', Sofia,
Bulgaria Aim and Methods: we have examined 30 patients with oesophageal varices and active bleeding for three-year period according to terminate the active bleeding, rebleeding, complications and side-effects. 15 patients were treated with sclerotherapy (First group) and other 15 with band ligation (Second group). Results: we stopped active bleeding for 73.3 per cent from the First group and 93.3 per cent from the Second group. 46.6 per cent from First group and 0 per cent from Second group are received rebleeding for 6 monthsperiod. We observed mucosal ulceration appearance in 26.6 per cent from First group and 6.6 per cent from Second group and oesophageal strictures in 20 per cent from First group and 6.6 per cent from the Second. We did not find oesophageal perforation, systemic complications like peritonitis, pneumonia and septicaemia. We have found short-term disphagia in 60 per cent and 33.3 per cent, retrosternal pain in 73.3 per cent and 40 per cent, transient fever in 46.7 per cent and 20 per cent respectively from First and Second group. Conclusions: band ligation is more effective than sclerotherapy for control of active bleeding and the incidences of rebleeding are considerable lower. Furthermore the band ligation is related to lower frequency of complications and side-effects. Our data demonstrate advantages fro using band ligation in preference to sclerotherapy and so band ligation should be considered the endoscopic treatment of choise in treatment of bleeding oesophageal varices.
~ - ~ - ] PRELIMINARY RESULTS OF A RANDOMISED CONTROLLED TRIALS IN THE PREVENTION OF EARLY POST-TIPS HEPATIC ENCEPHALOPATHY: A COMPARISON BETWEEN RIFAXlMIN AND LACTITOL Andrea Masini, Francesca Nicolao, Cesare Efrati, Manuela Merli, Adolfo Francesco Attili, Oliviero Riggio. Dipartimento di Medicina Clinica,
Divisione di Gastroenterologia, Universitgt di Roma, La Sapienza, Rome, Italy The incidence of post-TIPS hepatic encephalopathy (HE) in cirrhotics is 29-54% at one year, with a maximum during the first month. There is no consensus about the opportunity to treat patients submitted to TIPS for the prevention of HE. Aim of this study was to test the efficacy of lactitol (L) 60 g/day, rifaximine (R) 1200 mg/day and no treatment (NT) in the prevention of early post-TIPS HE. Thirty nine consecutive cirrhotics (age 57 4- 11, Child-Pugh class 9A, 21B, 9C) submitted to TIPS were enrolled. Etiology of liver cirrhosis was alcoholic in 12. Patients were evaluated before TIPS and 7-14-21-30 days after TIPS by clinical examination, psychometric tests and plasma ammonia (NH3). The 3 groups were comparable for age, Child-Pugh class, etiology, porto-caval pressure gradient after TIPS, preTIPS NH3, trail making test performance and previous episodes of HE. Twelve patients developed HE in the study period (30.7%); 5 in the lactitol group, 4 in the rifaximine group and 3 in the no treatment group. The incidence of HE was similar in the three groups (log rank test; p = 0.62). In the patients who did not developed HE, venous blood ammonia levels (L = 124 4- 52 vs R = 114 -4- 16.5 vs NT = 137 4- 77 mcg/dl; p = 0.76), trail making test performance (L -- 61 4- 30 vs R = 48 4- 7 vs NT = 58 4- 33 sec; p = 0.68) and PSE index (L = 0.16 vs R = 0.14 vs NT = 0.15; p = 0.44) were similar one month after TIPS in the three groups. Our data show that the treatment with lactitol or rifaximin do neither yield a lower incidence of HE, nor improve NH3 or psychometric test during the first month after TIPS placement.
ETIOLOGY OF LIVER CIRRHOSIS: AN HISTOLOGICAL APPRAISAL
Susana Lopes, Pedro Moutinho Ribeiro, Guilherme Macedo, Tome Ribeiro. Gastroenterology Unit, H.S. Joao, Porto, Portugal Introduction and Aim: Knowing the etiology of chronic liver disease and cirrhosis in a particular setting, may give some clues about the relative strenght of the hepatotoxic factors and may allow the establishment of some epidemiologic priorities for investigation and clinical practice. Hepatocellular carcinoma screening strategies may be substantially modified if there is evidence of a significant prevalence of risk factors for its development. Material and Methods: We have evaluated the histological diagnosis presented in the Pathology Department registry, corresponding to all the knew cirrhotic patients diagnosed in a 40 month period in a Central Hospital. Results: We have studied 241 cases of cirrhosis, from 173 male patients (and 68 females), with the etiology distributed as follows: alcoholic in 91 (38%), viral in 64 (27%) - related to HBV infection in 28 patients and to HCV in 36 patients. Hemochromatosis and variable degrees of iron overload was observed in 13 patients (5%) and 16 (6%) respectively. In 8 patients (3%) we found hepatocellular carcinoma; autoimmune cirrhosis was diagnosed in 8 patients (3%), Wilson's in 7 (3%), alphal antitrypsin deficiency in 5 (2%), primary biliary cirrhosis in 2 patients (1%) like primary sclerosing cholangitis and secondary biliary cirrhosis (1%). In 39 cases (16%) there was no histological identification of etiology. Conclusion: Alcoholic liver disease is still the leading cause of cirrhosis and HCV was more prevalent than HBV cirrhosis. In a significative number of patients (16%), histology was not enough to elucidate the etiology of cirrhosis, suggesting that toxic or metabolic not yet identifiable factors may be important in a group of patients.
7 ~ - ] ORAL BILE ACID ADMINISTRATION REDUCES ENDOTOXEMIA AND BACTERIAL TRANSLOCATION (BT) IN ASCITIC CIRRHOTIC RATS Vicente Lorenzo Zunigal, Ramon Bartoli 1, Ramon Planas I , Marco Antonio Alvarez 1, Belen Vinado I , Josep Mane t , Lee Hagey 2, Alan F. Hofmann 2, Miguel Angel Gassull I . 1Hospital Universitari Germans
Trias i Pujol, Badalona, Spain; 2University of California, San Diego, USA In cirrhosis there is a decrease in intraluminal bile acid concentrations which can favour endotoxin absorption and BT. Aim: To assess the effect of the administration of a deconjugation resistant bile acid (cholylsarcosine: Cs) and a deconjugable bile acid (cholylglycine: Cg) upon endotoxemia and the incidence of BT in ascitic cirrhotic rats. Methods: 45 S-D rats with orogastric CC14-induced cirrhosis and ascites were randomized to be treated with oral Cs, Cg or placebo (P) (70 mg/kg body weight dally) for 2 weeks. Three groups of 5 healthy rats receiving the same doses of Cs, Cg or P were used as control groups. Results: In placebo treated rats, secretion of bile was significantly lower in cirrhotic than in healthy rats (11.3 4- 2.73 vs 20.26 4- 1.38 ul/min; p < 0.05). The administration of Cs and Cg to cirrhotic rats normalized bile secretion (21 4- 3.12 and 24.46 4- 2.73 ul/min), and bile secretion become enriched in Cs and in cholylconjugates, respectively. Endotoxemia was significantly higher in cirrhotic rats receiving P (0.282 4- 0.124 Ul/ml) than in those treated with Cs or Cg (0.098 4- 0.002 and 0.101 4- 0.007; p < 0.001). The incidence of death and/or BT was significantly higher in cirrhotic rats receiving P (10/15: 66%) than in those treated with Cs or Cg (5/15: 33% and 4/15: 26%; p < 0.05). Conclusions: The administration of conjugated bile acids to ascitic cirrhotic rats causes increased bile acid secretion, that is associated with decreased endotoxemia, decreased BT, and decreased mortality. These results suggest that oral conjugated bile acids may be useful in preventing BT and SBP in cirrhotic patients.
~
205
ENDOSCOPIC BAND LIGATION VERSUS ENDOSCOPIC INJECTION SCLEROTHERAPY OF OESOPHAGEAL VARICES - A COMPARATIVE STUDY
Mario Markov. Clinic of Internal Medicine, Hospital 'St Anna', Sofia,
Bulgaria Aim and Methods: we have examined 30 patients with oesophageal varices and active bleeding for three-year period according to terminate the active bleeding, rebleeding, complications and side-effects. 15 patients were treated with sclerotherapy (First group) and other 15 with band ligation (Second group). Results: we stopped active bleeding for 73.3 per cent from the First group and 93.3 per cent from the Second group. 46.6 per cent from First group and 0 per cent from Second group are received rebleeding for 6 monthsperiod. We observed mucosal ulceration appearance in 26.6 per cent from First group and 6.6 per cent from Second group and oesophageal strictures in 20 per cent from First group and 6.6 per cent from the Second. We did not find oesophageal perforation, systemic complications like peritonitis, pneumonia and septicaemia. We have found short-term disphagia in 60 per cent and 33.3 per cent, retrosternal pain in 73.3 per cent and 40 per cent, transient fever in 46.7 per cent and 20 per cent respectively from First and Second group. Conclusions: band ligation is more effective than sclerotherapy for control of active bleeding and the incidences of rebleeding are considerable lower. Furthermore the band ligation is related to lower frequency of complications and side-effects. Our data demonstrate advantages fro using band ligation in preference to sclerotherapy and so band ligation should be considered the endoscopic treatment of choise in treatment of bleeding oesophageal varices.
~ - ~ - ] PRELIMINARY RESULTS OF A RANDOMISED CONTROLLED TRIALS IN THE PREVENTION OF EARLY POST-TIPS HEPATIC ENCEPHALOPATHY: A COMPARISON BETWEEN RIFAXlMIN AND LACTITOL Andrea Masini, Francesca Nicolao, Cesare Efrati, Manuela Merli, Adolfo Francesco Attili, Oliviero Riggio. Dipartimento di Medicina Clinica,
Divisione di Gastroenterologia, Universitgt di Roma, La Sapienza, Rome, Italy The incidence of post-TIPS hepatic encephalopathy (HE) in cirrhotics is 29-54% at one year, with a maximum during the first month. There is no consensus about the opportunity to treat patients submitted to TIPS for the prevention of HE. Aim of this study was to test the efficacy of lactitol (L) 60 g/day, rifaximine (R) 1200 mg/day and no treatment (NT) in the prevention of early post-TIPS HE. Thirty nine consecutive cirrhotics (age 57 4- 11, Child-Pugh class 9A, 21B, 9C) submitted to TIPS were enrolled. Etiology of liver cirrhosis was alcoholic in 12. Patients were evaluated before TIPS and 7-14-21-30 days after TIPS by clinical examination, psychometric tests and plasma ammonia (NH3). The 3 groups were comparable for age, Child-Pugh class, etiology, porto-caval pressure gradient after TIPS, preTIPS NH3, trail making test performance and previous episodes of HE. Twelve patients developed HE in the study period (30.7%); 5 in the lactitol group, 4 in the rifaximine group and 3 in the no treatment group. The incidence of HE was similar in the three groups (log rank test; p = 0.62). In the patients who did not developed HE, venous blood ammonia levels (L = 124 4- 52 vs R = 114 -4- 16.5 vs NT = 137 4- 77 mcg/dl; p = 0.76), trail making test performance (L -- 61 4- 30 vs R = 48 4- 7 vs NT = 58 4- 33 sec; p = 0.68) and PSE index (L = 0.16 vs R = 0.14 vs NT = 0.15; p = 0.44) were similar one month after TIPS in the three groups. Our data show that the treatment with lactitol or rifaximin do neither yield a lower incidence of HE, nor improve NH3 or psychometric test during the first month after TIPS placement.