- Email: [email protected]
NASH, interfering intestinal microbiota and bile acids resorption and metabolism
POSTERS FAO disorders with oxidative stress and inflammation in subset preeclampsia syndrome. Supported by grant NNSF of China No. 81370723 and Beijing MNSF No. 71372215.
Fatty liver disease: b. Clinical P0978 A 7 DAY LOW VS HIGH GLYCAEMIC INDEX DIET REDUCES LIVER FAT CONTENT IN HEALTHY SUBJECTS: A 1 H MRS STUDY S. Bawden1,2 , M. Stephenson3 , K. Hunter4 , M. Taylor5 , P. Morris2 , L. Marciani1 , I. Macdonald6 , G. Aithal1 , P. Gowland2 . 1 NIHR Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals NHS Trust, 2 SPMIC, University of Nottingham, Nottingham, United Kingdom; 3 Agency for Science, Technology and Research, Singapore, Singapore; 4 Unilever Discover, Colworth, 5 Faculty of Human Nutrition, 6 School of Life Sciences, University of Nottingham, Nottingham, United Kingdom E-mail: [email protected] Background and Aims: Glycaemic index (GI) is a way of ranking carbohydrates according to the postprandial effect on blood glucose levels and has received increasing interest in recent years. Low glycaemic index diets have been considered potentially beneficial in a range of metabolic conditions and cohort studies have shown correlations between dietary glycaemic index and non-alcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the effects of a low (LGI) v high (HGI) glycaemic index diet on hepatic lipid stores. Methods: 1 H Magnetic resonance spectroscopy (MRS) was used to assess liver lipid levels before and after a 7 day HGI v LGI dietary intervention in a two-way randomized cross over study with >4 week washout between test visits. 8 healthy males (age 20.1±0.4 years, BMI 23.0±0.9 kg/m2 ) attended the test centre and blood glucose measurements were taken at baseline and regularly following a HGI v LGI test breakfast. MRS was acquired at baseline and end-of-day (t = 360 min) on a Philips 3T scanner using a respiratory triggered PRESS localisation sequence with varying TE for T2 correction (BW = 2 kHz, samples = 1024, TR = 5000 ms, NSA = 40, TE = 40 ms, 50 ms, 60 ms, 80 ms). Areas under the CH2 (1.3 ppm) and water (4.7 ppm) peaks were used to calculate tissue weight fat fraction.
LGI (1.6±0.7%) reaching statistical significance (two way F-test, P < 0.05) and this effect was consistent across the test day. Conclusions: This study used a simple MRS protocol to show the beneficial impact on liver lipid levels of a LGI compared with HGI diet after only 7 days. This has important applications in the design of dietary interventions to prevent and treat NAFLD as well as its metabolic consequences. Further studies should explore longer term interventions and patient groups. Acknowledgements: We wish to thank Unilever and BBSRC for funding this study. P0979 PILOT STUDY OF A NEW TREATMENT IN NAFLD/NASH, INTERFERING INTESTINAL MICROBIOTA AND BILE ACIDS RESORPTION AND METABOLISM A.M. Popescu1 . 1 Internal Medicine, Fundeni Clinical Institute, Bucharest, Romania E-mail: [email protected] Background and Aims: Intestinal microbiota plays an important role, modulating inflammation and absorption of bile acids, thus its dysfunction might trigger the NAFLD/NASH. Rifaximine (RFX) is known to eradicate intestinal bacterial overgrowth, followed by a symbiotic (SYN) that increases colonization with Bifidobacteria, exert an immunomodulatory effect, induction of tall-like receptors, increase of IL10 production and inhibition of Th1 lymphocyte generation. Ursodeoxycholic acid (UDCA) also, has been used in previous studies in NASH. Aim: Assess the efficacy of a new combined therapy consisting in RFX, followed by SYN formula and associated to UDCA in a discontinued regimen for improving NASH. Methods: 40 patients diagnosed with NASH on transaminases elevation, serological tests for NASH/fibrosis, associated diseases and liver histology, were prospectively randomized between January 2012 and September 2014 into 2 similar groups: 20 patients were treated with RFX 1200 mg/day 10 days, followed by SYN 1 bag/day, 10 days, in association with UDCA 15 mg/kg/day; 20 patients received only UDCA 15 mg/kg/day. This regimen was repeated for 3 consecutive months, 3 times/year, with final evaluation after 1 year. Results: Both groups were comparable: mean age 45–47 years; more men, 12/20 and 14/20; 16/20 in group 1 and 15/20 in group 2 were overweight, 90% with abdominal obesity; 40% group 1 and 50% group 2 had diabetes mellitus, 50% with insulin resistance; 80%, respectively 70% had hyperlipidemia; 30% vs. 50% had HTA. 90% over 80% of patients had AST/ALT ratio >1, with an increased level by 1.5×. NASH test was positive in all patients, on liver biopsies steatosis was over 60%, inflammation grade 2 to 3 and fibrosis grade 2, no liver cirrhosis. In patients treated with the combined regimen, no side effects were reported, with an improvement in bloating, abdominal pain, and diarrhea/constipation symptoms. Associated diet, change in life style, medication to correct the co-morbidities had a compliance of about 60%. After 1 year of follow-up improvements were found with regard to: weight loss of 4–10% in 70% of cases in both groups, normalization of ALT, AST and insulin sensitivity in 90% of patients from group 1, vs. 40% in group 2, decrease in steatosis infiltration by 40% and in fibrosis by 1 stage only in group 1 with combined treatment. Conclusions: Several cycles of an associated regimen with RFX+SYN+UDCA, improved significantly liver histology, steatosis and inflammation in about 60% of patients with NASH.
Results: Blood samples confirmed a high and low glycaemic response for respective test meals. On the pre diet test day, fasted liver fat fractions were consistent for both HGI and LGI arms (HGI 2.4±1.2%; LGI 2.4±1.0%; P = 0.82) and end of day lipid levels were within error of fasted levels. Following the 7 day diet, fasted liver fat fractions increased for HGI (4.7±2.0%) compared with Journal of Hepatology 2015 vol. 62 | S263–S864
S713
Fatty liver disease: b. Clinical P0978 A 7 DAY LOW VS HIGH GLYCAEMIC INDEX DIET REDUCES LIVER FAT CONTENT IN HEALTHY SUBJECTS: A 1 H MRS STUDY S. Bawden1,2 , M. Stephenson3 , K. Hunter4 , M. Taylor5 , P. Morris2 , L. Marciani1 , I. Macdonald6 , G. Aithal1 , P. Gowland2 . 1 NIHR Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals NHS Trust, 2 SPMIC, University of Nottingham, Nottingham, United Kingdom; 3 Agency for Science, Technology and Research, Singapore, Singapore; 4 Unilever Discover, Colworth, 5 Faculty of Human Nutrition, 6 School of Life Sciences, University of Nottingham, Nottingham, United Kingdom E-mail: [email protected] Background and Aims: Glycaemic index (GI) is a way of ranking carbohydrates according to the postprandial effect on blood glucose levels and has received increasing interest in recent years. Low glycaemic index diets have been considered potentially beneficial in a range of metabolic conditions and cohort studies have shown correlations between dietary glycaemic index and non-alcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the effects of a low (LGI) v high (HGI) glycaemic index diet on hepatic lipid stores. Methods: 1 H Magnetic resonance spectroscopy (MRS) was used to assess liver lipid levels before and after a 7 day HGI v LGI dietary intervention in a two-way randomized cross over study with >4 week washout between test visits. 8 healthy males (age 20.1±0.4 years, BMI 23.0±0.9 kg/m2 ) attended the test centre and blood glucose measurements were taken at baseline and regularly following a HGI v LGI test breakfast. MRS was acquired at baseline and end-of-day (t = 360 min) on a Philips 3T scanner using a respiratory triggered PRESS localisation sequence with varying TE for T2 correction (BW = 2 kHz, samples = 1024, TR = 5000 ms, NSA = 40, TE = 40 ms, 50 ms, 60 ms, 80 ms). Areas under the CH2 (1.3 ppm) and water (4.7 ppm) peaks were used to calculate tissue weight fat fraction.
LGI (1.6±0.7%) reaching statistical significance (two way F-test, P < 0.05) and this effect was consistent across the test day. Conclusions: This study used a simple MRS protocol to show the beneficial impact on liver lipid levels of a LGI compared with HGI diet after only 7 days. This has important applications in the design of dietary interventions to prevent and treat NAFLD as well as its metabolic consequences. Further studies should explore longer term interventions and patient groups. Acknowledgements: We wish to thank Unilever and BBSRC for funding this study. P0979 PILOT STUDY OF A NEW TREATMENT IN NAFLD/NASH, INTERFERING INTESTINAL MICROBIOTA AND BILE ACIDS RESORPTION AND METABOLISM A.M. Popescu1 . 1 Internal Medicine, Fundeni Clinical Institute, Bucharest, Romania E-mail: [email protected] Background and Aims: Intestinal microbiota plays an important role, modulating inflammation and absorption of bile acids, thus its dysfunction might trigger the NAFLD/NASH. Rifaximine (RFX) is known to eradicate intestinal bacterial overgrowth, followed by a symbiotic (SYN) that increases colonization with Bifidobacteria, exert an immunomodulatory effect, induction of tall-like receptors, increase of IL10 production and inhibition of Th1 lymphocyte generation. Ursodeoxycholic acid (UDCA) also, has been used in previous studies in NASH. Aim: Assess the efficacy of a new combined therapy consisting in RFX, followed by SYN formula and associated to UDCA in a discontinued regimen for improving NASH. Methods: 40 patients diagnosed with NASH on transaminases elevation, serological tests for NASH/fibrosis, associated diseases and liver histology, were prospectively randomized between January 2012 and September 2014 into 2 similar groups: 20 patients were treated with RFX 1200 mg/day 10 days, followed by SYN 1 bag/day, 10 days, in association with UDCA 15 mg/kg/day; 20 patients received only UDCA 15 mg/kg/day. This regimen was repeated for 3 consecutive months, 3 times/year, with final evaluation after 1 year. Results: Both groups were comparable: mean age 45–47 years; more men, 12/20 and 14/20; 16/20 in group 1 and 15/20 in group 2 were overweight, 90% with abdominal obesity; 40% group 1 and 50% group 2 had diabetes mellitus, 50% with insulin resistance; 80%, respectively 70% had hyperlipidemia; 30% vs. 50% had HTA. 90% over 80% of patients had AST/ALT ratio >1, with an increased level by 1.5×. NASH test was positive in all patients, on liver biopsies steatosis was over 60%, inflammation grade 2 to 3 and fibrosis grade 2, no liver cirrhosis. In patients treated with the combined regimen, no side effects were reported, with an improvement in bloating, abdominal pain, and diarrhea/constipation symptoms. Associated diet, change in life style, medication to correct the co-morbidities had a compliance of about 60%. After 1 year of follow-up improvements were found with regard to: weight loss of 4–10% in 70% of cases in both groups, normalization of ALT, AST and insulin sensitivity in 90% of patients from group 1, vs. 40% in group 2, decrease in steatosis infiltration by 40% and in fibrosis by 1 stage only in group 1 with combined treatment. Conclusions: Several cycles of an associated regimen with RFX+SYN+UDCA, improved significantly liver histology, steatosis and inflammation in about 60% of patients with NASH.
Results: Blood samples confirmed a high and low glycaemic response for respective test meals. On the pre diet test day, fasted liver fat fractions were consistent for both HGI and LGI arms (HGI 2.4±1.2%; LGI 2.4±1.0%; P = 0.82) and end of day lipid levels were within error of fasted levels. Following the 7 day diet, fasted liver fat fractions increased for HGI (4.7±2.0%) compared with Journal of Hepatology 2015 vol. 62 | S263–S864
S713