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591 Clinical and histologic spectrum of nonalcoholic fatty liver disease in patients treated by gastroplasty
Category 9: Alcoholic Liver Disease, NAFLD and Drug-Induced Liver Disease Animals were injected with either subcutaneous or intraduodenal (0.5-50.0 mg/kg) histamine injection followed by LPS (0.5 mg/kg, ip). PBS was used for vehicle and control and sham surgeries were performed for comparison. Animals were sacrificed over a 24 h period post LPS administration. Serum transaminase and cytokine liver mRNA levels were determined. Results: A time-dependent increase in ALT/AST over baseline was seen up to 4 h (89±13, 174±32 U/l; p<0.001) and remained elevated through 6 h while then normalizing by 24 h following LPS. Histamine pre-treatment at all doses subcutaneously prevented this increase over the 24 h period and in a dose-dependent manner intestinally, with complete protection at 5.0 mg/kg (0±9, 10±15 U/l; p<0.05). LPS induced TNF-alpha and IL-6 mRNA levels which peaked at 1 and 4 h, respectively (both 150-250fold). By both routes, histamine dose-dependently decreased the cytokine messages, but this down-regulation was independent of the normalization of transaminase levels. Conclusion: Regardless of the route of administration, histamine protects against LPS-induced liver injury in rats primed by ethanol exposure, however this protective effect appears to be independent of TNF-alpha and IL-6 regulation.
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Patients and methods: Seventy eight patients had gastroplsty (surgical restriction of storage capacity of the stomach) as a treatment of morbid obesity. There were 50 nfemales and 28 males, aged between 25 -58 years of age. At entry and in each following month in each patient assessed basic clinical tests, BMI, blood level of liver enzymes ALT and AST, lipids, sugar. The patients were followed for the next 2 years. Liver wedge biopsy was taken from 50 patients, repeated in 6 patients after several months and had morphological examination, particulary for steatosis, steatohepatitis and fibrosis. Results and conclusion: The prevalence of metabolic syndrome reached 100%. There were no statistically significant differences of blood liver enzymes, lipids, sugar and hypertensive disease between patients of different sexes, age and duration of obesity. Hepatic steatosis of various degree was present in 90% of examined histologically samples, 10% had features of NASH and fibrosis. No cirrhotic transformation was found. Level of ALT and AST was related to the degree of hepatic steatosis and to the BMI. Gradual loss of weight, improvement of laboratory tests and histological hepatic lesions noted in all patients followed up.
592 CHOLESTATIC HEPATITIS – MANIFESTATION OF TICLOPIDIN 590 PROGNOSTIC FACTORS OF HEPATORENAL SYNDROME (HRS) TYPE 1 IN ACUTE ALCOHOLIC HEPATITIS
P. Jarcuska 1 , E. Veseliny 1 , B. Bodnarova 1 , A. Kovacova 2 , M. Hancova 3 . 1 1st Dpt of Internal Medicine, University Hospital, Kosice, Slovakia; 2 Dpt of Clinical Biochemistry, University Hospital, Kosice, Slovakia; 3 Institute of Mathematics, Faculty of Science, Safarik University, Kosice, Slovakia Aim of study: To find prognostic factors of mortality in HRS in acute alcoholic hepatitis. Material and methods: From February 1998 to October 2003, 20 patients with acute alcoholic hepatitis complicated by HRS type 1 had been treated with continual terlipressin infusion (1-2 mg daily) in combination with albumin plasmaexpansion (20-60 g daily). Patients had been divided into 2 groups: group A: patients died during hospitalization (8 patients, age: 46,13±15,79 years), group B: patients improved during hospitalization (12 patients, age: 48,25±13,09 years). Results: There were no significant differences between both groups in serum creatinine, bilirubine and in Child-Pugh score before treatment, but patients in group A had at the end of the therapy higher serum creatinine levels (257,75±97,47 resp. 161,17±70,90 umol/l, p=0,047), bilirubine levels (384,50±203,85 resp. 101,81±92,06 umol/l, p=0,003) and Child-Pugh score (13,13±0,78 resp. 10,58±2,02, p=0,0024) than patients in group B. We observed that serum creatinine decreased (at least 20%) in 6/8 patients in group A and in all patients in group B (NS), but normalisation of serum creatinine was found only in 6 patients in group B (p=0,042). Patients in group A had higher number of infection complications (3,25±0,83 resp. 2,25±1,01, p=0,037) and higher grade of hepatic encephalopathy (3,50±0,71 resp. 1,42±1,11, p=0,0015) than patients in group B. Conclusion: Progression of hepatic failure is more important for prognosis of patients with HRS type 1 in acute alcoholic hepatitis than laboratory parameters before the start of therapy.
591 CLINICAL AND HISTOLOGIC SPECTRUM OF NONALCOHOLIC FATTY LIVER DISEASE IN PATIENTS TREATED BY GASTROPLASTY
K. Jaskiewicz 1 , S. Raczynska 2 , R. Rzepko 1 . 1 Department of Pathology, Medical University of Gdansk, Gdansk, Poland; 2 Department of General Surgery, Medical University of Gdansk, Gdansk, Poland NAFLD has been recently recognised to be one of the heading causes of chronic liver disease. The purpose of this work is to evaluate the relationship of steatohepatitis with the metabolic syndrome (obesity, insulin resistance, dyslipidemia and hypertension) and effects of surgical treatment of obesity.
INDUCED LIVER INJURY- NEW INSIGTS INTO MECHANISM OF LIVER DAMAGE
I. Kraslova 1,2 , L. Muchova 1,2 , L. Vitek 1,2 , R. Bruha 2 , J. Stritesky 3 , J. Svatosova 3 , T. Svestka 2 , A. Novotny 2 . 1 Laboratory of Hepatology, Institute of Clinical Biochemistry and Laboratory Diagnostics, General University Hospital, Prague, Czech Republic; 2 4th Department of Internal Medicine, General University Hospital, Prague, Czech Republic; 3 Institute of Pathology, General University Hospital, Prague, Czech Republic Background: Cholestatic hepatitis is a rare complication of the antiplatelet agent ticlopidin. The mechanism of ticlopidin induced liver damage remains unknown, but the role of immune system in its pathogenesis is suggested. Aim: To evaluate the role of the immune system in pathogenesis of ticlopidin induced liver damage. Patients: Three patients with cholestatic hepatitis with ticlopidin related liver injury, 3 patients with obstructive jaundice due to choledocholithiasis and 3 healthy individuals were studied. The diagnosis of ticlopidine induced cholestatic hepatitis was established in patients who developed prolonged cholestatic hepatitis 2-12 weeks after receiving ticlopidin following percutaneous coronary angioplasty. Other causes of liver injury and cholestasis were excluded. Methods: The serum levels of INF-g, IL-2, IL-4, sFas (CD95+), sFas-L (CD95+Ligand) and TNF-a were measured by ELISA. The immunostaining for anti-CD4+, CD8+ and CD95+ cells and the TUNEL assay to evaluate the grade of apoptosis was performed in liver tissue of patients with cholestatic hepatitis. Results: The serum levels of sFas, sFas-L and TNF-a were substantially higher among patients with cholestatic hepatitis in comparison to patients from other groups. There were no statistically different changes in serum levels of IL-4 and IFN-g among these three groups. The high proportion of CD8+ and CD95+ cells and positive reaction in TUNEL assay suggests the role of enhanced apoptosis in the pathogenesis. Conclusion: Cholestatic hepatitis is a rare adverse effect of ticlopidin treatment that may be immune mediated. The results of the present study suggest the key role of apoptotic pathways in drug induced liver damage.
173
Patients and methods: Seventy eight patients had gastroplsty (surgical restriction of storage capacity of the stomach) as a treatment of morbid obesity. There were 50 nfemales and 28 males, aged between 25 -58 years of age. At entry and in each following month in each patient assessed basic clinical tests, BMI, blood level of liver enzymes ALT and AST, lipids, sugar. The patients were followed for the next 2 years. Liver wedge biopsy was taken from 50 patients, repeated in 6 patients after several months and had morphological examination, particulary for steatosis, steatohepatitis and fibrosis. Results and conclusion: The prevalence of metabolic syndrome reached 100%. There were no statistically significant differences of blood liver enzymes, lipids, sugar and hypertensive disease between patients of different sexes, age and duration of obesity. Hepatic steatosis of various degree was present in 90% of examined histologically samples, 10% had features of NASH and fibrosis. No cirrhotic transformation was found. Level of ALT and AST was related to the degree of hepatic steatosis and to the BMI. Gradual loss of weight, improvement of laboratory tests and histological hepatic lesions noted in all patients followed up.
592 CHOLESTATIC HEPATITIS – MANIFESTATION OF TICLOPIDIN 590 PROGNOSTIC FACTORS OF HEPATORENAL SYNDROME (HRS) TYPE 1 IN ACUTE ALCOHOLIC HEPATITIS
P. Jarcuska 1 , E. Veseliny 1 , B. Bodnarova 1 , A. Kovacova 2 , M. Hancova 3 . 1 1st Dpt of Internal Medicine, University Hospital, Kosice, Slovakia; 2 Dpt of Clinical Biochemistry, University Hospital, Kosice, Slovakia; 3 Institute of Mathematics, Faculty of Science, Safarik University, Kosice, Slovakia Aim of study: To find prognostic factors of mortality in HRS in acute alcoholic hepatitis. Material and methods: From February 1998 to October 2003, 20 patients with acute alcoholic hepatitis complicated by HRS type 1 had been treated with continual terlipressin infusion (1-2 mg daily) in combination with albumin plasmaexpansion (20-60 g daily). Patients had been divided into 2 groups: group A: patients died during hospitalization (8 patients, age: 46,13±15,79 years), group B: patients improved during hospitalization (12 patients, age: 48,25±13,09 years). Results: There were no significant differences between both groups in serum creatinine, bilirubine and in Child-Pugh score before treatment, but patients in group A had at the end of the therapy higher serum creatinine levels (257,75±97,47 resp. 161,17±70,90 umol/l, p=0,047), bilirubine levels (384,50±203,85 resp. 101,81±92,06 umol/l, p=0,003) and Child-Pugh score (13,13±0,78 resp. 10,58±2,02, p=0,0024) than patients in group B. We observed that serum creatinine decreased (at least 20%) in 6/8 patients in group A and in all patients in group B (NS), but normalisation of serum creatinine was found only in 6 patients in group B (p=0,042). Patients in group A had higher number of infection complications (3,25±0,83 resp. 2,25±1,01, p=0,037) and higher grade of hepatic encephalopathy (3,50±0,71 resp. 1,42±1,11, p=0,0015) than patients in group B. Conclusion: Progression of hepatic failure is more important for prognosis of patients with HRS type 1 in acute alcoholic hepatitis than laboratory parameters before the start of therapy.
591 CLINICAL AND HISTOLOGIC SPECTRUM OF NONALCOHOLIC FATTY LIVER DISEASE IN PATIENTS TREATED BY GASTROPLASTY
K. Jaskiewicz 1 , S. Raczynska 2 , R. Rzepko 1 . 1 Department of Pathology, Medical University of Gdansk, Gdansk, Poland; 2 Department of General Surgery, Medical University of Gdansk, Gdansk, Poland NAFLD has been recently recognised to be one of the heading causes of chronic liver disease. The purpose of this work is to evaluate the relationship of steatohepatitis with the metabolic syndrome (obesity, insulin resistance, dyslipidemia and hypertension) and effects of surgical treatment of obesity.
INDUCED LIVER INJURY- NEW INSIGTS INTO MECHANISM OF LIVER DAMAGE
I. Kraslova 1,2 , L. Muchova 1,2 , L. Vitek 1,2 , R. Bruha 2 , J. Stritesky 3 , J. Svatosova 3 , T. Svestka 2 , A. Novotny 2 . 1 Laboratory of Hepatology, Institute of Clinical Biochemistry and Laboratory Diagnostics, General University Hospital, Prague, Czech Republic; 2 4th Department of Internal Medicine, General University Hospital, Prague, Czech Republic; 3 Institute of Pathology, General University Hospital, Prague, Czech Republic Background: Cholestatic hepatitis is a rare complication of the antiplatelet agent ticlopidin. The mechanism of ticlopidin induced liver damage remains unknown, but the role of immune system in its pathogenesis is suggested. Aim: To evaluate the role of the immune system in pathogenesis of ticlopidin induced liver damage. Patients: Three patients with cholestatic hepatitis with ticlopidin related liver injury, 3 patients with obstructive jaundice due to choledocholithiasis and 3 healthy individuals were studied. The diagnosis of ticlopidine induced cholestatic hepatitis was established in patients who developed prolonged cholestatic hepatitis 2-12 weeks after receiving ticlopidin following percutaneous coronary angioplasty. Other causes of liver injury and cholestasis were excluded. Methods: The serum levels of INF-g, IL-2, IL-4, sFas (CD95+), sFas-L (CD95+Ligand) and TNF-a were measured by ELISA. The immunostaining for anti-CD4+, CD8+ and CD95+ cells and the TUNEL assay to evaluate the grade of apoptosis was performed in liver tissue of patients with cholestatic hepatitis. Results: The serum levels of sFas, sFas-L and TNF-a were substantially higher among patients with cholestatic hepatitis in comparison to patients from other groups. There were no statistically different changes in serum levels of IL-4 and IFN-g among these three groups. The high proportion of CD8+ and CD95+ cells and positive reaction in TUNEL assay suggests the role of enhanced apoptosis in the pathogenesis. Conclusion: Cholestatic hepatitis is a rare adverse effect of ticlopidin treatment that may be immune mediated. The results of the present study suggest the key role of apoptotic pathways in drug induced liver damage.