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Caffeine may be protective in ethanol-induced liver damage
150
Poster Sessions
used as controls. LTA was expressed as % of cell death. Results higher than 15 were considered positive. Differences among groups were determined by the use of confidence intervals and analysis of variance. Results: LTA has positive a predictive value of 95% specificity 91%, sensitivity 89%. TNF values in females who had a positive LTA are statistically higher than in males (p < 0.05). The values of TNF alpha in DSH-LTA negative were not different form the normal population (60 pg/mL). A significant correlation (0.001) was seen between the DHS positive LTA group and higher TNF. Conclusions: There is a female predominance in HSRs to anticonvulsants. A combination of immunological markers may correlate with a positive toxicity test. Identification of critical molecular targets can lead to better tailor the therapy to the patient.
- ~ CAFFEINE MAY BE PROTECTIVE IN ETHANOL-INDUCED LIVER DAMAGE Jelenka Nikolic. Institute of Biochemistry, Medical Faculty, Nis,
Yugoslavia It is known that dietary consumption of high doses of ethanol leads to damage of various organs. Ethanol is primarily hepatotoxic agents. Alcoholic fatty liver, alcoholic hepatitis and liver cirrhosis are the most frequent diseases in alcoholics. The aim of this study is investigation of caffeine effects on liver function in alcoholic intoxication because of frequent simultaneous coffee consumption with alcoholic beverages. In this experiment we used male albino rats weighing about 200 g. Animals were divided into three groups: l- control, 2- treated with ethanol (as 15% solution), 3- treated simultaneously with caffeine (100 mg/kg bw.) and ethanol (as 15% solution). Animals were treated for ten days. Plasma levels of glucose, urea, proteins, AST and ALT levels were measured by standard biochemical analysis. The level of lipid peroxidation (MDA level) was measured by tiobarbituric acid reaction in liver homogenate. Ethanol intoxication significantly elevated tissue level of MDA (p < 0.001). Caffeine decreased MDA level in ethanol-intoxicated group (p < 0.01). Caffeine increased plasma levels of urea, glucose, proteins and plasma activities of transaminases in ethanolintoxicated animals. Dysfunction of hepatocites in alcoholic intoxication leads to hypoglycemia and hipoaibuminemia. The obtained results show that caffeine may be beneficial in respect to glucose, urea and protein concentration in the blood, but caffeine is not protective in respect to AST and ALT level.
-1-] THE MOLECULAR ADSORBENT REClRCULATING SYSTEM (MARS) IMPROVES SYSTEMIC HEMODYNAMICS AND HEPATIC ENCEPHALOPATHY IN PATIENTS WITH SEVERE ALCOHOLIC HEPATITIS
0.02). No significant changes in ammonia levels were observed. Mean arterial pressure tent to increase after each session. Baseline PAR (7.2 4- 1.7 ng/mL/h) decreased after each session and at the end of the third treatment (2.9 4- 1.3 ng/mL/h, p = 0.01). Prothrombin index and serum albumin did not change, but platelets decreased significantly after each session. Most of the beneficial effects of MARS disappeared ten days later. PAR also increased by this time although their levels were lower (5.3 4- 0.9 ng/mL/h) than baseline. Adverse effects were recorded in one patient with a severe hematoma, requiring blood transfusion, and two patients developing bacteriemia. Conclusions: Besides the known favourable effects on serum bilirubin, MARS is associated with marked relieving of hepatic encephalopathy and decreases plasma renin activity in severe alcoholic hepatitis.
42-] IRON STATUS AND HFE GENE MUTATIONS IN NON-ALCOHOLIC STEATOHEPATITIS (NASH) Mercedes Perez-Carreras l, Gregorio Castellano 1, Elena Perez I , Pilar Morales 2, Carmen Yela I , Sarbelio Rodriguez I , Jose Antonio Solis-Herruzo 1.1 Gastroenterology, Hospital '12 De Octabre',
Madrid; 21mmunology, Hospital '12 De Octubre', Madrid, Spain The aims of this study were to determine indices of iron metabolism and frequency of HFE gene mutations in Spanish patients with NASH. Methods: We measured serum iron and ferritin concentrations and transfemn saturation (TS) in 76 NASH patients. In 60 of these patients and 485 Spanish healthy controls, HFE gene mutations were tested by PCR amplification followed by digestion of PCR products with restriction enzymes Rsa I and Mbo I. Results: Increased serum iron and ferritin was found in 9% and 37%, respectively, of NASH patients, whereas, TS was elevated in only 3 % of these patients. Increased hepatic stores were present in 19% of NASH patients. We found a positive correlation between serum ferritin and severity of liver fibrosis (p = 0.04) and grade of hepatic stainable iron (p = 0.001). H63D mutation was found in 35% of patients (5% homozygous; 30% heterozygous). C282Y mutation was present as heterozygosity in only 1 patient. Homozygosity for C282Y mutation was not found. Frequency of these mutations was similar in NASH patients and control subjects. Conclusion: 1. A third of NASH patients have increased serum levels of ferritin, which correlated with the degree of fibrosis and the grade of hepatic iron stores. 2. Frequency of HFE mutations was similar in NASH patients and Spanish healthy controls.
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NON-ALCOHOLIC STEATOHEPATITIS (NASH) AND CHRONIC HEPATITIS C
Albert Pares I , Laura Cisneros l , Joan Manuel Salmer6n l, Antoni Mas l , Albert Torras 2, Joan Caballeria I , Juan Rodds 1. 1Liver Unit, Hospital
Mercedes Perez-Carreras l , Gregorio Castellano 1, Eloy Rivas 2, Francisco Colina 2, Victoria Alvarez 1, Esperanza Tomas 1, Antonio Fuertes 3, Jose Antonio Solis-Herruzo l . 1Gastroenterology,
Clinic, IDIBAPS, Barcelona; 2Departmentof Nephrology, Barcelona, Spain
Hospital '12 De Octubre', Madrid; 2pathology, Hospital '12 De Octabre', Madrid; 3Microbiology, Hospital '12 De Octubre', Madrid, Spain
The effects of MARS on liver function, hepatic encephalopathy, and systemic hemodynamics have been assessed nine patients (6 M/3 E age: 48.2 4- 2.1 years) with histologically proven severe alcoholic hepatitis Patients were treated with three 7-hour MARS sessions during three consecutive days. Liver function tests, hepatic encephalopathy score, circulating creatinine and ammonia, and systemic hemodynamics, including plasma renin activity (PRA), were measured in each patient before and after each session, and 10 days later The patients were severely jaundiced, 7 had ascites and 5 encephalopathy. The baseline serum bilirubin was 23.1 4- 2.7 mg/dl and the prothrombin index 34 4- 3%. MARS treatment was associated with a significant serum bilirubin decrease since at the end of the third session was 14.7 4- 1.1 mg/dl (p = 0.03). MARS also resulted in a conspicuous relief of encephalopathy, since it improved after each treatment, and all patients were free of encephalopathy at the end of the latest treatment (p =
The aim of this study was to analyse clinical, laboratory and histological features in NASH patients with and without chronic hepatitis C (CrHC). Methods: We study three groups of patients: Group I: 85 patients with NASH: Group II, 23 patients with CrHC without steatosis. Group III, 23 patients with both NASH and CrHC. We evaluated: age, gender, obesity, hyperlipidemia, diabetes, grade of: steatosis, inflammation and fibrosis, features of NASH, HCV viral load and genotype. Results: Age, grade of obesity and frequency of diabetes were similar in group I and III. Patients in group I were more frequently men and hyperlipidemic than group HI patients, but these patients lacked more frequently of NASH risk factors, had higher serum levels of transaminases and higher scores of inflammation and fibrosis. On the other hand, obesity, hyperlipidemia and presence of NASH risk factors were more common in group HI than in group II patients. In group III, ballooning of bepatocytes and
Poster Sessions
used as controls. LTA was expressed as % of cell death. Results higher than 15 were considered positive. Differences among groups were determined by the use of confidence intervals and analysis of variance. Results: LTA has positive a predictive value of 95% specificity 91%, sensitivity 89%. TNF values in females who had a positive LTA are statistically higher than in males (p < 0.05). The values of TNF alpha in DSH-LTA negative were not different form the normal population (60 pg/mL). A significant correlation (0.001) was seen between the DHS positive LTA group and higher TNF. Conclusions: There is a female predominance in HSRs to anticonvulsants. A combination of immunological markers may correlate with a positive toxicity test. Identification of critical molecular targets can lead to better tailor the therapy to the patient.
- ~ CAFFEINE MAY BE PROTECTIVE IN ETHANOL-INDUCED LIVER DAMAGE Jelenka Nikolic. Institute of Biochemistry, Medical Faculty, Nis,
Yugoslavia It is known that dietary consumption of high doses of ethanol leads to damage of various organs. Ethanol is primarily hepatotoxic agents. Alcoholic fatty liver, alcoholic hepatitis and liver cirrhosis are the most frequent diseases in alcoholics. The aim of this study is investigation of caffeine effects on liver function in alcoholic intoxication because of frequent simultaneous coffee consumption with alcoholic beverages. In this experiment we used male albino rats weighing about 200 g. Animals were divided into three groups: l- control, 2- treated with ethanol (as 15% solution), 3- treated simultaneously with caffeine (100 mg/kg bw.) and ethanol (as 15% solution). Animals were treated for ten days. Plasma levels of glucose, urea, proteins, AST and ALT levels were measured by standard biochemical analysis. The level of lipid peroxidation (MDA level) was measured by tiobarbituric acid reaction in liver homogenate. Ethanol intoxication significantly elevated tissue level of MDA (p < 0.001). Caffeine decreased MDA level in ethanol-intoxicated group (p < 0.01). Caffeine increased plasma levels of urea, glucose, proteins and plasma activities of transaminases in ethanolintoxicated animals. Dysfunction of hepatocites in alcoholic intoxication leads to hypoglycemia and hipoaibuminemia. The obtained results show that caffeine may be beneficial in respect to glucose, urea and protein concentration in the blood, but caffeine is not protective in respect to AST and ALT level.
-1-] THE MOLECULAR ADSORBENT REClRCULATING SYSTEM (MARS) IMPROVES SYSTEMIC HEMODYNAMICS AND HEPATIC ENCEPHALOPATHY IN PATIENTS WITH SEVERE ALCOHOLIC HEPATITIS
0.02). No significant changes in ammonia levels were observed. Mean arterial pressure tent to increase after each session. Baseline PAR (7.2 4- 1.7 ng/mL/h) decreased after each session and at the end of the third treatment (2.9 4- 1.3 ng/mL/h, p = 0.01). Prothrombin index and serum albumin did not change, but platelets decreased significantly after each session. Most of the beneficial effects of MARS disappeared ten days later. PAR also increased by this time although their levels were lower (5.3 4- 0.9 ng/mL/h) than baseline. Adverse effects were recorded in one patient with a severe hematoma, requiring blood transfusion, and two patients developing bacteriemia. Conclusions: Besides the known favourable effects on serum bilirubin, MARS is associated with marked relieving of hepatic encephalopathy and decreases plasma renin activity in severe alcoholic hepatitis.
42-] IRON STATUS AND HFE GENE MUTATIONS IN NON-ALCOHOLIC STEATOHEPATITIS (NASH) Mercedes Perez-Carreras l, Gregorio Castellano 1, Elena Perez I , Pilar Morales 2, Carmen Yela I , Sarbelio Rodriguez I , Jose Antonio Solis-Herruzo 1.1 Gastroenterology, Hospital '12 De Octabre',
Madrid; 21mmunology, Hospital '12 De Octubre', Madrid, Spain The aims of this study were to determine indices of iron metabolism and frequency of HFE gene mutations in Spanish patients with NASH. Methods: We measured serum iron and ferritin concentrations and transfemn saturation (TS) in 76 NASH patients. In 60 of these patients and 485 Spanish healthy controls, HFE gene mutations were tested by PCR amplification followed by digestion of PCR products with restriction enzymes Rsa I and Mbo I. Results: Increased serum iron and ferritin was found in 9% and 37%, respectively, of NASH patients, whereas, TS was elevated in only 3 % of these patients. Increased hepatic stores were present in 19% of NASH patients. We found a positive correlation between serum ferritin and severity of liver fibrosis (p = 0.04) and grade of hepatic stainable iron (p = 0.001). H63D mutation was found in 35% of patients (5% homozygous; 30% heterozygous). C282Y mutation was present as heterozygosity in only 1 patient. Homozygosity for C282Y mutation was not found. Frequency of these mutations was similar in NASH patients and control subjects. Conclusion: 1. A third of NASH patients have increased serum levels of ferritin, which correlated with the degree of fibrosis and the grade of hepatic iron stores. 2. Frequency of HFE mutations was similar in NASH patients and Spanish healthy controls.
~-~
NON-ALCOHOLIC STEATOHEPATITIS (NASH) AND CHRONIC HEPATITIS C
Albert Pares I , Laura Cisneros l , Joan Manuel Salmer6n l, Antoni Mas l , Albert Torras 2, Joan Caballeria I , Juan Rodds 1. 1Liver Unit, Hospital
Mercedes Perez-Carreras l , Gregorio Castellano 1, Eloy Rivas 2, Francisco Colina 2, Victoria Alvarez 1, Esperanza Tomas 1, Antonio Fuertes 3, Jose Antonio Solis-Herruzo l . 1Gastroenterology,
Clinic, IDIBAPS, Barcelona; 2Departmentof Nephrology, Barcelona, Spain
Hospital '12 De Octubre', Madrid; 2pathology, Hospital '12 De Octabre', Madrid; 3Microbiology, Hospital '12 De Octubre', Madrid, Spain
The effects of MARS on liver function, hepatic encephalopathy, and systemic hemodynamics have been assessed nine patients (6 M/3 E age: 48.2 4- 2.1 years) with histologically proven severe alcoholic hepatitis Patients were treated with three 7-hour MARS sessions during three consecutive days. Liver function tests, hepatic encephalopathy score, circulating creatinine and ammonia, and systemic hemodynamics, including plasma renin activity (PRA), were measured in each patient before and after each session, and 10 days later The patients were severely jaundiced, 7 had ascites and 5 encephalopathy. The baseline serum bilirubin was 23.1 4- 2.7 mg/dl and the prothrombin index 34 4- 3%. MARS treatment was associated with a significant serum bilirubin decrease since at the end of the third session was 14.7 4- 1.1 mg/dl (p = 0.03). MARS also resulted in a conspicuous relief of encephalopathy, since it improved after each treatment, and all patients were free of encephalopathy at the end of the latest treatment (p =
The aim of this study was to analyse clinical, laboratory and histological features in NASH patients with and without chronic hepatitis C (CrHC). Methods: We study three groups of patients: Group I: 85 patients with NASH: Group II, 23 patients with CrHC without steatosis. Group III, 23 patients with both NASH and CrHC. We evaluated: age, gender, obesity, hyperlipidemia, diabetes, grade of: steatosis, inflammation and fibrosis, features of NASH, HCV viral load and genotype. Results: Age, grade of obesity and frequency of diabetes were similar in group I and III. Patients in group I were more frequently men and hyperlipidemic than group HI patients, but these patients lacked more frequently of NASH risk factors, had higher serum levels of transaminases and higher scores of inflammation and fibrosis. On the other hand, obesity, hyperlipidemia and presence of NASH risk factors were more common in group HI than in group II patients. In group III, ballooning of bepatocytes and