Curtis K Argo1, James T Patrie2, Carolin Lackner3, Thomas D Henry4, Eduard E de Lange4, Arthur L Weltman5, Neeral L Shah6, Abdullah M Al-Osaimi6, Patcharin Pramoonjago7, Saumya Jayakumar8, Lukas P Binder3, Winsor D Simmons-Egolf9, Sandra G Burks9, Yongde Bao10, Ann Gill Taylor11, Jessica Rodriguez12, Stephen H Caldwell13. 1. Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, VA, USA. Electronic address: cka3d@virginia.edu. 2. Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA. 3. Institute of Pathology, Medical University of Graz, Graz, Austria. 4. Department of Radiology, University of Virginia Health System, Charlottesville, VA, USA. 5. Department of Exercise Physiology, University of Virginia, Charlottesville, VA, USA. 6. Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, VA, USA. 7. Department of Pathology, University of Virginia Health System, Charlottesville, VA, USA. 8. Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, VA, USA; Division of Gastroenterology & Hepatology, University of Calgary, Calgary, Alberta, Canada. 9. Surgical Therapeutic Advancement Center, University of Virginia Health System, Charlottesville, VA, USA. 10. Biomolecular Research Facility, School of Medicine, University of Virginia, Charlottesville, VA, USA. 11. Center for the Study of Complementary and Alternative Therapies, University of Virginia, Charlottesville, VA, USA. 12. Clinical Research Unit, Metabolic Research Kitchen, University of Virginia, Charlottesville, VA, USA. 13. Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, VA, USA. Electronic address: shc5c@virginia.edu.
Abstract
BACKGROUND & AIMS: This study's aim was to assess the histological and metabolic effects of n-3 polyunsaturated fatty acids (PUFAs) vs. placebo while adjusting for the impact of age and weight change in NASH patients. (ClinicalTrials.gov: NCT00681408). METHODS:Forty-one subjects with non-cirrhotic NASH were enrolled, and 34 completed the study. 17 received n-3 fish oil 3000 mg/day and 17 received placebo daily for 1 year with typical counselling on caloric intake and physical activity for all subjects. RESULTS:N-3- and placebo-treated groups showed no significant difference for the primary end point of NASH activity score (NAS) reduction ⩾ 2 points without fibrosis progression after adjustment for known covariates (n-3, 4/17 (23.5%); placebo, 3/17, (17.6%), p = 0.99). Among subjects with increased or stable weight, n-3 subjects showed a larger decrease in liver fat content by MRI than placebo-treated subjects (p = 0.014 for 2nd quartile, p = 0.003 for 3rd quartile of weight change). N-3 treatment showed significant fat reduction on the paired analysis of image-assisted fat morphometry regardless of weight loss or gain. Exercise capacity remained markedly reduced in all subjects. No independent effects on markers of hepatocyte injury or insulin sensitivity indices were observed. CONCLUSION:N-3 PUFAs at 3000 mg/day for one year did not lead to an improvement in the primary outcome of histological activity in NASH patients (⩾ 2 point NAS reduction). N-3 led to reduced liver fat by multiple measures. Other metabolic effects were not seen, although no detrimental effects were apparent. Whether longer duration, higher dose, or different composition of n-3 therapy would lead to additional benefits is uncertain.
RCT Entities:
BACKGROUND & AIMS: This study's aim was to assess the histological and metabolic effects of n-3 polyunsaturated fatty acids (PUFAs) vs. placebo while adjusting for the impact of age and weight change in NASH patients. (ClinicalTrials.gov: NCT00681408). METHODS: Forty-one subjects with non-cirrhotic NASH were enrolled, and 34 completed the study. 17 received n-3 fish oil 3000 mg/day and 17 received placebo daily for 1 year with typical counselling on caloric intake and physical activity for all subjects. RESULTS:N-3- and placebo-treated groups showed no significant difference for the primary end point of NASH activity score (NAS) reduction ⩾ 2 points without fibrosis progression after adjustment for known covariates (n-3, 4/17 (23.5%); placebo, 3/17, (17.6%), p = 0.99). Among subjects with increased or stable weight, n-3 subjects showed a larger decrease in liver fat content by MRI than placebo-treated subjects (p = 0.014 for 2nd quartile, p = 0.003 for 3rd quartile of weight change). N-3 treatment showed significant fat reduction on the paired analysis of image-assisted fat morphometry regardless of weight loss or gain. Exercise capacity remained markedly reduced in all subjects. No independent effects on markers of hepatocyte injury or insulin sensitivity indices were observed. CONCLUSION:N-3 PUFAs at 3000 mg/day for one year did not lead to an improvement in the primary outcome of histological activity in NASH patients (⩾ 2 point NAS reduction). N-3 led to reduced liver fat by multiple measures. Other metabolic effects were not seen, although no detrimental effects were apparent. Whether longer duration, higher dose, or different composition of n-3 therapy would lead to additional benefits is uncertain.
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