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P1042 : Deregulation of de novo lipogenesis can be associated with liver damage in patients with non alcoholic fatty liver disease
POSTERS P1040 SHORT-TERM LOW-DOSE THIAZOLIDINEDIONES CAN BE A USEFUL BRIDGING THERAPY IN NASH PATIENTS WITHOUT SIDE EFFECTS S. Park1 , M. Lee1 , I.H. Moh1 , S. Shin1 . 1 Division of Gastroenterology and Hepatology, Hallym University Medical Center, Seoul, Korea, South E-mail: [email protected] Background and Aims: Thiazolidinediones (TZDs) improve insulin resistance and have shown effect in the treatment of NASH. However, only low-dose TZDs are available in non-diabetic patients in South Korea due to national health insurance reimbursement policy. Meanwhile, administration of low-dose TZDs can be used more safely while TZDs have adverse effects such as edema, fatigue, and weight gain. We assessed the effect of low-dose TZDs in nondiabetic NASH patients. Methods: We conducted a prospective study of biopsy proven NASH patients without diabetes from 2003 through 2013. Patients were treated with low-dose TZDs (rosiglitazone 4 mg or pioglitazone 15 mg, once daily) for 12 weeks. AST, ALT, ALP, total protein, albumin, total cholesterol, triglyceride, fasting blood glucose (FBS), body mass index, and HOMA-IR were measured at baseline and after 12 weeks. Data were compared with Wilcoxon Signed Rank Test. Results: Twenty-eight patients were enrolled. Ten cases were female with a mean age of 36.3±13.7 years. After 12 weeks, a significant decrease in AST (71.1±42.8 to 37.3±16.9, p < 0.01), ALT (121.7±60.1 to 59.8±34.1, p < 0.01), FBS (104.2±28.1 to 97.9±15.3, p = 0.013) and HOMA-IR (2.3±1.5 to 1.9±1.1, p = 0.039) levels was observed without weight gain or other side effects. TZDs did not affect plasma ALP, total protein, albumin, total cholesterol, and triglyceride. Conclusions: Twelve weeks administration of low-dose TZDs in non-diabetic NASH patients showed beneficial effects on liver function without side effects. Low-dose TZDs can be used as a useful bridging therapy while weight loss by dietary control and exercise takes time to be effective. P1041 RAPID IMPROVEMENT OF HEPATIC STEATOSIS AS ASSESSED BY CONTROLLED ATTENUATION PARAMETER AFTER A TWO WEEK PROTEIN-ENRICHED LOW-CALORIE DIET (HEPAFAST) A. Arslanow1 , M. Teutsch2 , H. Walle2 , F. Lammert1 , C.S. Stokes1 . 1 Department of Medicine II, Saarland University Medical Center, Homburg, 2 Bodymed AG, Kirkel, Germany E-mail: [email protected] Background and Aims: Non-alcoholic fatty liver disease (NAFLD) has become one of the most prevalent liver diseases. NAFLD increases the risk of fibrosis and cirrhosis and is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma. Previous intervention studies have been hampered by the need for liver biopsies and the lack of alternative inexpensive methods for the quantitative measurement of liver fat contents. Hence the primary aim of this study was to avail of the controlled attenuation parameter as quantitative tool for the assessment of therapeutic effects of a two-week low-calorie diet. Methods: In this prospective single center study, 59 patients with NAFLD received a 14-day low-calorie liver specific diet (HEPAFAST) containing 1000 kcal per day (41% protein, 29% carbohydrate, 24% fat and 6% fiber). The following parameters were assessed at baseline and after 14 days: hepatic fat contents using controlled attenuation parameter (CAP) during transient elastography (FibroScan); body composition with bioimpedance analysis; and serum liver function tests and lipid profiles using standard clinical-chemical assays. Results: All 59 patients (median age 55 years, range 25–78; 51% women; median BMI 31.7 kg/m2 , range 22.4–43.5) successfully completed the study. A significant reduction in hepatic steatosis (14.1%; P < 0.0001) was observed after only 2 weeks: The median CAP score S738
decreased from 293 dB/m (range 177–400) at baseline to 263 dB/m (100–353). In parallel, BMI decreased significantly (P < 0.0001), and 30.5% could be reclassified into a lower BMI category. Moreover, body and visceral fat contents were significantly (P < 0.0001) reduced by 7%. Serum triglyceride, total LDL, and the LDL/HDL index as well as g-GT activities also decreased significantly (all P < 0.001). Interestingly, 11 patients (72% women) demonstrated a CAP increase by 3% after the 2-week intervention despite improvements in body composition, thus were classified as hepatic non-responders. In contrast, a subgroup analysis of the responders revealed a decrease of 16% in median CAP scores from 308 to 261 dB/m. Conclusions: This elastography-based non-invasive study shows, for the first time, improvements in hepatic steatosis, as quantified non-invasively by CAP, after a short-term protein-enriched lowcalorie diet. The dietary intervention not only reduced body weight but improved both body and liver compositon in NAFLD. Compartment- and sex-specific HEPAFAST effects should be investigated further. P1042 DEREGULATION OF DE NOVO LIPOGENESIS CAN BE ASSOCIATED WITH LIVER DAMAGE IN PATIENTS WITH NON ALCOHOLIC FATTY LIVER DISEASE C. Rosso1 , C. Saponaro2,3 , L. Mezzabotta1 , E. Vanni1 , R. Gambino1 , F. Saba1 , R. Ibrahim Kamal Jouness1 , M. Gaggini2,4 , E. Buzzigoli2 , G.P. Caviglia1 , M.L. Abate1 , F. Salomone5 , A. Smedile1 , M. Rizzetto1 , M. Cassader1 , A. Gastaldelli2 , E. Bugianesi1 . 1 Dept. of Medical Sciences, University of Turin, Torino, 2 Cardiometabolic Risk Unit, CNR-Institute of Clinical Physiology, Pisa, 3 Dottorato Pegaso Regione Toscana in Biochimica e Biologia Molecolare, University of Siena, Siena, 4 Dept. Patologia Chirurgica, Molecolare e di Area Critica, University of Pisa, Pisa, 5 U.O.C. of Gastroenterology, Azienda Sanitaria Provinciale di Catania, Catania, Italy E-mail: [email protected] Background and Aims: Adipose tissue insulin resistance (IR) and elevated adipose free fatty acid (FFA) flux are prominent features in NAFLD. De novo lipogenesis (DNL) is up to 3-fold higher in subjects with fatty liver and is not suppressed on fasting. When DNL is stimulated, the production of saturated FAs is increased and the oxidation of FAs of any source is reduced. Both mechanisms can favor inflammation and IR. We measured FFA flux/composition and used a surrogate index of DNL (DNLi) to evaluate their relationship with histological features in a group of non-diabetic subjects with biopsy-proven NAFLD. Methods: Hepatic and adipose tissue-IR indices were derived from [2 H5 ]glycerol and [2 H2 ] glucose kinetics in a group of non-diabetic NAFLD patients in the basal state (n = 40) and after a 4 h oral glucose load test (n = 20). Gas chromatography mass spectrometry was used to assess FFAs composition. DNLi was derived as the ratio palmitic/linoleic acid. Results: Fasting plasma glucose/insulin, lipid profile, hepatic/adipose tissue IR indices and DNLi were similar in the two groups. Fasting DNLi was associated with triglycerides (TG) and FFAs levels and with adipose tissue IR (r = 0.597, r = 0.330 and r = 0.394, respectively). Among histological features, fasting DNLi significantly correlated with steatosis (r = 0.364, P = 0.02) and NAS score (r = 0.306, P = 0.05). After the glucose load, TG levels initially increased despite elevated insulin levels, suggesting a significant contribution of DNL. Accordingly, DNLi consensually increased with TG levels (r = 0.749, P < 0.005) and was significantly related to the degree of fibrosis (rs =0.514, P = 0.02). Conclusions: Oral glucose load is associated with changes in DNL and hepatic triglyceride synthesis that can favor liver fibrosis in patients with NAFLD. Funded by FP7/2007–2013 under grant agreement no. HEALTH-F22009-241762 for the project FLIP and by PRIN 2009ARYX4T.
Journal of Hepatology 2015 vol. 62 | S263–S864
decreased from 293 dB/m (range 177–400) at baseline to 263 dB/m (100–353). In parallel, BMI decreased significantly (P < 0.0001), and 30.5% could be reclassified into a lower BMI category. Moreover, body and visceral fat contents were significantly (P < 0.0001) reduced by 7%. Serum triglyceride, total LDL, and the LDL/HDL index as well as g-GT activities also decreased significantly (all P < 0.001). Interestingly, 11 patients (72% women) demonstrated a CAP increase by 3% after the 2-week intervention despite improvements in body composition, thus were classified as hepatic non-responders. In contrast, a subgroup analysis of the responders revealed a decrease of 16% in median CAP scores from 308 to 261 dB/m. Conclusions: This elastography-based non-invasive study shows, for the first time, improvements in hepatic steatosis, as quantified non-invasively by CAP, after a short-term protein-enriched lowcalorie diet. The dietary intervention not only reduced body weight but improved both body and liver compositon in NAFLD. Compartment- and sex-specific HEPAFAST effects should be investigated further. P1042 DEREGULATION OF DE NOVO LIPOGENESIS CAN BE ASSOCIATED WITH LIVER DAMAGE IN PATIENTS WITH NON ALCOHOLIC FATTY LIVER DISEASE C. Rosso1 , C. Saponaro2,3 , L. Mezzabotta1 , E. Vanni1 , R. Gambino1 , F. Saba1 , R. Ibrahim Kamal Jouness1 , M. Gaggini2,4 , E. Buzzigoli2 , G.P. Caviglia1 , M.L. Abate1 , F. Salomone5 , A. Smedile1 , M. Rizzetto1 , M. Cassader1 , A. Gastaldelli2 , E. Bugianesi1 . 1 Dept. of Medical Sciences, University of Turin, Torino, 2 Cardiometabolic Risk Unit, CNR-Institute of Clinical Physiology, Pisa, 3 Dottorato Pegaso Regione Toscana in Biochimica e Biologia Molecolare, University of Siena, Siena, 4 Dept. Patologia Chirurgica, Molecolare e di Area Critica, University of Pisa, Pisa, 5 U.O.C. of Gastroenterology, Azienda Sanitaria Provinciale di Catania, Catania, Italy E-mail: [email protected] Background and Aims: Adipose tissue insulin resistance (IR) and elevated adipose free fatty acid (FFA) flux are prominent features in NAFLD. De novo lipogenesis (DNL) is up to 3-fold higher in subjects with fatty liver and is not suppressed on fasting. When DNL is stimulated, the production of saturated FAs is increased and the oxidation of FAs of any source is reduced. Both mechanisms can favor inflammation and IR. We measured FFA flux/composition and used a surrogate index of DNL (DNLi) to evaluate their relationship with histological features in a group of non-diabetic subjects with biopsy-proven NAFLD. Methods: Hepatic and adipose tissue-IR indices were derived from [2 H5 ]glycerol and [2 H2 ] glucose kinetics in a group of non-diabetic NAFLD patients in the basal state (n = 40) and after a 4 h oral glucose load test (n = 20). Gas chromatography mass spectrometry was used to assess FFAs composition. DNLi was derived as the ratio palmitic/linoleic acid. Results: Fasting plasma glucose/insulin, lipid profile, hepatic/adipose tissue IR indices and DNLi were similar in the two groups. Fasting DNLi was associated with triglycerides (TG) and FFAs levels and with adipose tissue IR (r = 0.597, r = 0.330 and r = 0.394, respectively). Among histological features, fasting DNLi significantly correlated with steatosis (r = 0.364, P = 0.02) and NAS score (r = 0.306, P = 0.05). After the glucose load, TG levels initially increased despite elevated insulin levels, suggesting a significant contribution of DNL. Accordingly, DNLi consensually increased with TG levels (r = 0.749, P < 0.005) and was significantly related to the degree of fibrosis (rs =0.514, P = 0.02). Conclusions: Oral glucose load is associated with changes in DNL and hepatic triglyceride synthesis that can favor liver fibrosis in patients with NAFLD. Funded by FP7/2007–2013 under grant agreement no. HEALTH-F22009-241762 for the project FLIP and by PRIN 2009ARYX4T.
Journal of Hepatology 2015 vol. 62 | S263–S864