- Email: [email protected]
1365 METABOLIC ALTERATIONS OF LIPID KINETICS IN NAFLD PATIENTS AND THEIR CONTRIBUTION TO LIVER DAMAGE
POSTERS advanced disease (b = 0.12, p = 0.001) independent of age (b = 0.04, p = 0.004), gender (b = 0.58, p < 0.04), alcohol consumption (p = 0.27) and waist circumference (p = 0.34). In patients younger than 40 with HOMA <2, advanced disease was exceedingly rare (1/44, 2.3%). Conclusion: In a large European population of NAFLD patients, IR was strongly associated with hepatic inflammation and fibrosis. Low levels of IR (HOMA <2) are associated with reduced risk of advanced disease, especially in younger patients, even if overweight, with high ALT and steatohepatitis.
1366 BENEFICIAL INFLUENCE OF POLYUNSATURATED PHOSPHATIDYLCHOLINE ENHANCES FUNCTIONAL LIVER CONDITION AND LIVER STRUCTURE IN PATIENTS WITH NONALCOHOLIC STEATOHEPATITIS. RESULTS OF PROLONGED RANDOMIZED BLINDED PROSPECTIVE CLINICAL STUDY E. Sas1 , V. Grinevich2 , O. Efimov2 , N. Shcherbina2 . 1 Department of Therapy Postgraduate, 2 Military-Medical Academy, Saint Petersburg, Russia E-mail: [email protected]
1365 METABOLIC ALTERATIONS OF LIPID KINETICS IN NAFLD PATIENTS AND THEIR CONTRIBUTION TO LIVER DAMAGE C. Rosso1 , E. Vanni1 , L. Mezzabotta1 , R. Gambino1 , S. Carenzi1 , F. Saba1 , E. Buzzigoli2 , M. Gaggini2 , G.P. Caviglia1 , M. Cassader1 , A. Smedile1 , M. Rizzetto1 , A. Gastaldelli2 , E. Bugianesi1 . 1 Medical Sciences Dept., University of Turin, Turin, 2 Cardiometabolic Risk Unit, Institute of Clinical Physiology, CNR, Pisa, Italy E-mail: [email protected]
From 1998 to 2012 in our prolonged randomized prospective, blinded clinical trial we studied the effect of polyunsaturated phosphatidylcholine – PUPC (Essentiale® forte N, produced by A. Nattermann & Cie.GmbH) in diabetic patients with NASH. 215 patients with type 2 diabetes of not-complicated course, which was adequately controlled by diet and metformin intake, were recruited for the study. All patients followed the basic treatment scheme included dietary and physical regimen and metformin, daily dosage – 1000 mg. 178 patients of investigational group (IG) additionally were treated by PUPC, daily dosage contained 1368 mg Phosphatidilcholine. Altogether 152 (85.4%) patients of IG and 37 patients of Control Group (CG) were available for follow up. In a subsequent for the remaining patients in the study during above seven years (long-term investigational group (LIG) 114–64.0%), liver function markers and ultrasound studies were measured at least twice per year. A significant reduction of all the liver enzymes was observed after treatment by PUPC, viz. baseline vs. six months after treatment: ALT: 56.5±28.6 IU/L vs. 35.2±18.4 IU/L, p = 0.02, AST: 39.0±9.0 IU/L vs. 26.5±7.2 IU/L, p = 0.04, GGT: 38.2±11.4 IU/L vs. 27.5±8.6 IU/L, p = 0.03). Ultrasound studies were performed on the basis of liver attenuation value assessment and revealed the hepatic echo-texture had become significantly improved after PUPC treatment in 101/152 (66.4%) of patients (p = 0.02), while there was no change in 7/152 (4.6%) individuals. In the group of patients LIG further dynamics of the liver enzymes had no statistically significant differences from CG, but sonographics signs of fatty liver statistically decreased in 93/114 (81.6%) and became more effective control of diabetes in 98/114 (86.0%) patients (significant reduction in HBc). The results of liver biopsy (histological examination) and Fibromax test showed, that in patients with NAFLD additionally treated by PUPC, the progress of hepatic fibrosis was significantly slowly, then in CG (Fibromax test result: F2 vs. F3) (p = 0.03). In addition after of treatment we found significant increase of steatosis in long-term CG, and its reduction in LIG (p = 0.02). The study results suggest that polyunsaturated phosphatidilcholine improves liver function and structures, also help glucose control in diabetic sufferers with NASH.
Background and Aims: It has been hypothesized that excessive lipids availability contributes to the necro-inflammatory processes and to fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). The purpose of this study was to evaluate the impact of whole body lipolysis, circulating NEFA levels/composition and insulin resistance (either basally and after a fat challenge) in the pathogenesis of liver damage in NAFLD. Methods: [2H5]glycerol kinetics and plasma levels of Fatty acids (FA), triglycerides (TG) and VLDL-TG, saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) were determined in 15 non-obese, normolipidaemic, non-diabetic patients with biopsy-proven NAFLD and 6 control subjects during the basal state and after an oral fat load (200 ml dairy cream and egg yolk). FA composition was assessed by high performance liquid chromatography. Total and incremental post-load area under the curve (AUC and IAUC) of lipids and hormones were calculated. Whole body lipolysis and Adipose tissue IR index were derived from glycerol Ra. Results: In NAFLD patients post-load TG, VLDL-TG and FA plasma concentrations were increased at all curve time-points (TG p = 0.029, VLDL-TG p = 0.038 and FA p = 0.036; NAFLD vs controls). Similarly, the corresponding IAUCs resulted increased 2-fold (p = 0.024 for TG and VLDL-TG, p = 0.022 for NEFA). NAFLD patients had similar levels of SFA, MUFA and PUFA in the basal state, but increased SFA (lauric and myristic acids, p = 0.009 and 0.031) and MUFA (oleic acid, p = 0.023) after load. Basal glycerol Ra and Adipo-IR were significantly increased (p < 0.03 and p < 0.001 respectively vs CT). Among all parameters, higher BMI (p = 0.007), IAUC insulin (p = 0.038), IAUC C-peptide (p = 0.013) and Adipo-IR (p = 0.033 for basal and 0.007 for post-load) were significantly associated with severe fibrosis. However, only BMI (p = 0.05), IAUC insulin (p = 0.05) and IAUC C-peptide (p = 0.027) were associated with a NAS score ≥5. Conclusions: NAFLD patients present multiple qualitative and quantitative alterations in lipid metabolism even in the absence of overt metabolic derangements. Adipose tissue insulin resistance is one of the main determinants of liver fibrosis, but an important contribution is provided by insulin levels and secretion per se. Funding from the EU’s Seventh Framework Programme (FP7/2007– 2013) under grant agreement no. HEALTH-F2–2009–241762 for the project FLIP.
1367 INCREASED GUT PERMEABILITY IN METABOLIC SYNDROME IS NOT ASSOCIATED WITH CHANGES IN BILE ACID PROFILE B. Leber1 , N. Tripolt1 , S. Lemesch2 , A. Horvath2 , T. Stojakovic3 , G. Fauler3 , R. Stauber2 , P. Fickert2 , H. Sourji1 , V. Stadlbauer2 . 1 Department of Internal Medicine, 2 Department of Internal Medicine, Division of Gastroenterology and Hepatology, 3 Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria E-mail: [email protected] Background: High fat diet can lead to metabolic syndrome (MetS) and is associated with changes in gut microbiota. Gut microbiota composition impacts on gut permeability and bile acid composition. The aim of this study was to investigate whether patients with MetS show increased gut permeability, whether this is associated with changes in serum bile acid composition and whether consumption of a probiotic affects gut permeability and serum bile acids. Methods: Patients with MetS were randomized to receive trice daily 6.5x109 CFU Lactobacillus casei Shirota (LcS) (probiotic group)
Journal of Hepatology 2013 vol. 58 | S409–S566
S549
1366 BENEFICIAL INFLUENCE OF POLYUNSATURATED PHOSPHATIDYLCHOLINE ENHANCES FUNCTIONAL LIVER CONDITION AND LIVER STRUCTURE IN PATIENTS WITH NONALCOHOLIC STEATOHEPATITIS. RESULTS OF PROLONGED RANDOMIZED BLINDED PROSPECTIVE CLINICAL STUDY E. Sas1 , V. Grinevich2 , O. Efimov2 , N. Shcherbina2 . 1 Department of Therapy Postgraduate, 2 Military-Medical Academy, Saint Petersburg, Russia E-mail: [email protected]
1365 METABOLIC ALTERATIONS OF LIPID KINETICS IN NAFLD PATIENTS AND THEIR CONTRIBUTION TO LIVER DAMAGE C. Rosso1 , E. Vanni1 , L. Mezzabotta1 , R. Gambino1 , S. Carenzi1 , F. Saba1 , E. Buzzigoli2 , M. Gaggini2 , G.P. Caviglia1 , M. Cassader1 , A. Smedile1 , M. Rizzetto1 , A. Gastaldelli2 , E. Bugianesi1 . 1 Medical Sciences Dept., University of Turin, Turin, 2 Cardiometabolic Risk Unit, Institute of Clinical Physiology, CNR, Pisa, Italy E-mail: [email protected]
From 1998 to 2012 in our prolonged randomized prospective, blinded clinical trial we studied the effect of polyunsaturated phosphatidylcholine – PUPC (Essentiale® forte N, produced by A. Nattermann & Cie.GmbH) in diabetic patients with NASH. 215 patients with type 2 diabetes of not-complicated course, which was adequately controlled by diet and metformin intake, were recruited for the study. All patients followed the basic treatment scheme included dietary and physical regimen and metformin, daily dosage – 1000 mg. 178 patients of investigational group (IG) additionally were treated by PUPC, daily dosage contained 1368 mg Phosphatidilcholine. Altogether 152 (85.4%) patients of IG and 37 patients of Control Group (CG) were available for follow up. In a subsequent for the remaining patients in the study during above seven years (long-term investigational group (LIG) 114–64.0%), liver function markers and ultrasound studies were measured at least twice per year. A significant reduction of all the liver enzymes was observed after treatment by PUPC, viz. baseline vs. six months after treatment: ALT: 56.5±28.6 IU/L vs. 35.2±18.4 IU/L, p = 0.02, AST: 39.0±9.0 IU/L vs. 26.5±7.2 IU/L, p = 0.04, GGT: 38.2±11.4 IU/L vs. 27.5±8.6 IU/L, p = 0.03). Ultrasound studies were performed on the basis of liver attenuation value assessment and revealed the hepatic echo-texture had become significantly improved after PUPC treatment in 101/152 (66.4%) of patients (p = 0.02), while there was no change in 7/152 (4.6%) individuals. In the group of patients LIG further dynamics of the liver enzymes had no statistically significant differences from CG, but sonographics signs of fatty liver statistically decreased in 93/114 (81.6%) and became more effective control of diabetes in 98/114 (86.0%) patients (significant reduction in HBc). The results of liver biopsy (histological examination) and Fibromax test showed, that in patients with NAFLD additionally treated by PUPC, the progress of hepatic fibrosis was significantly slowly, then in CG (Fibromax test result: F2 vs. F3) (p = 0.03). In addition after of treatment we found significant increase of steatosis in long-term CG, and its reduction in LIG (p = 0.02). The study results suggest that polyunsaturated phosphatidilcholine improves liver function and structures, also help glucose control in diabetic sufferers with NASH.
Background and Aims: It has been hypothesized that excessive lipids availability contributes to the necro-inflammatory processes and to fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). The purpose of this study was to evaluate the impact of whole body lipolysis, circulating NEFA levels/composition and insulin resistance (either basally and after a fat challenge) in the pathogenesis of liver damage in NAFLD. Methods: [2H5]glycerol kinetics and plasma levels of Fatty acids (FA), triglycerides (TG) and VLDL-TG, saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) were determined in 15 non-obese, normolipidaemic, non-diabetic patients with biopsy-proven NAFLD and 6 control subjects during the basal state and after an oral fat load (200 ml dairy cream and egg yolk). FA composition was assessed by high performance liquid chromatography. Total and incremental post-load area under the curve (AUC and IAUC) of lipids and hormones were calculated. Whole body lipolysis and Adipose tissue IR index were derived from glycerol Ra. Results: In NAFLD patients post-load TG, VLDL-TG and FA plasma concentrations were increased at all curve time-points (TG p = 0.029, VLDL-TG p = 0.038 and FA p = 0.036; NAFLD vs controls). Similarly, the corresponding IAUCs resulted increased 2-fold (p = 0.024 for TG and VLDL-TG, p = 0.022 for NEFA). NAFLD patients had similar levels of SFA, MUFA and PUFA in the basal state, but increased SFA (lauric and myristic acids, p = 0.009 and 0.031) and MUFA (oleic acid, p = 0.023) after load. Basal glycerol Ra and Adipo-IR were significantly increased (p < 0.03 and p < 0.001 respectively vs CT). Among all parameters, higher BMI (p = 0.007), IAUC insulin (p = 0.038), IAUC C-peptide (p = 0.013) and Adipo-IR (p = 0.033 for basal and 0.007 for post-load) were significantly associated with severe fibrosis. However, only BMI (p = 0.05), IAUC insulin (p = 0.05) and IAUC C-peptide (p = 0.027) were associated with a NAS score ≥5. Conclusions: NAFLD patients present multiple qualitative and quantitative alterations in lipid metabolism even in the absence of overt metabolic derangements. Adipose tissue insulin resistance is one of the main determinants of liver fibrosis, but an important contribution is provided by insulin levels and secretion per se. Funding from the EU’s Seventh Framework Programme (FP7/2007– 2013) under grant agreement no. HEALTH-F2–2009–241762 for the project FLIP.
1367 INCREASED GUT PERMEABILITY IN METABOLIC SYNDROME IS NOT ASSOCIATED WITH CHANGES IN BILE ACID PROFILE B. Leber1 , N. Tripolt1 , S. Lemesch2 , A. Horvath2 , T. Stojakovic3 , G. Fauler3 , R. Stauber2 , P. Fickert2 , H. Sourji1 , V. Stadlbauer2 . 1 Department of Internal Medicine, 2 Department of Internal Medicine, Division of Gastroenterology and Hepatology, 3 Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria E-mail: [email protected] Background: High fat diet can lead to metabolic syndrome (MetS) and is associated with changes in gut microbiota. Gut microbiota composition impacts on gut permeability and bile acid composition. The aim of this study was to investigate whether patients with MetS show increased gut permeability, whether this is associated with changes in serum bile acid composition and whether consumption of a probiotic affects gut permeability and serum bile acids. Methods: Patients with MetS were randomized to receive trice daily 6.5x109 CFU Lactobacillus casei Shirota (LcS) (probiotic group)
Journal of Hepatology 2013 vol. 58 | S409–S566
S549