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Clinical and metabolic effects associated with weight changes and obeticholic acid in non‐alcoholic steatohepatitis
Journal article   Open access   Peer reviewed

Clinical and metabolic effects associated with weight changes and obeticholic acid in non‐alcoholic steatohepatitis

Nonalcoholic Steatohepatitis Clinical Research Network (NASH), B Hameed, N A Terrault, R M Gill, R Loomba, N Chalasani, J H Hoofnagle, Mark L Van Natta and Mariana Lazo
Alimentary Pharmacology & Therapeutics, v 47(5), pp 645-656
01 Mar 2018
DOI: https://doi.org/10.1111/apt.14492
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1111/apt.14492View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze),  Open

Abstract

6.1 Pharmaceuticals Adult Alkaline Phosphatase Biomedical and Clinical Sciences Biopsy Body Weight Cardiovascular Chenodeoxycholic Acid Clinical Research Clinical Sciences Clinical Trials and Supportive Activities Complementary and Integrative Health Digestive Diseases Double-Blind Method Evaluation of treatments and therapeutic interventions Female Gastroenterology & Hepatology Humans LDL Liver Disease Male Middle Aged NASH CRN Non-alcoholic Fatty Liver Disease Nutrition Oral and gastrointestinal Pharmacology and Pharmaceutical Sciences Treatment Outcome Weight Loss Cholesterol Hepatitis
Background In a 72-week, randomised controlled trial of obeticholic acid (OCA) in non-alcoholic steatohepatitis (NASH), OCA was superior to placebo in improving serum ALT levels and liver histology. OCA therapy also reduced weight. Aims Because weight loss by itself can improve histology, to perform a post hoc analysis of the effects of weight loss and OCA treatment in improving clinical and metabolic features of NASH. Methods The analysis was limited to the 200 patients with baseline and end-of-treatment liver biopsies. Weight loss was defined as a relative decline from baseline of 2% or more at treatment end. Results Weight loss occurred in 44% (45/102) of OCA and 32% (31/98) of placebo-treated patients (P = 0.08). The NAFLD Activity score (NAS) improved more in those with than without weight loss in both the OCA- (-2.4 vs -1.2, P<0.001) and placebo-treated patients (-1.2 vs -0.5, P = 0.03). ALT levels also improved in those with vs without weight loss in OCA- (-43 vs -34 U/L, P = 0.12) and placebo-treated patients (-29 vs -10 U/L, P = 0.02). However, among those who lost weight, OCA was associated with opposite effects from placebo on changes in alkaline phosphatase (+21 vs -12 U/L, P<0.001), total (+13 vs -14 mg/dL, P = 0.02) and LDL cholesterol (+18 vs -12 mg/dL, P = 0.01), and HbA1c (+0.1 vs -0.4%, P = 0.01). Conclusions OCA leads to weight loss in up to 44% of patients with NASH, and OCA therapy and weight loss have additive benefits on serum aminotransferases and histology. However, favourable effects of weight loss on alkaline phosphatase, lipids and blood glucose seen in placebo-treated patients were absent or reversed on OCA treatment. These findings stress the importance of assessing concomitant metabolic effects of new therapies of NASH. Clinical trial number: NCT01265498.

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UN Sustainable Development Goals (SDGs)

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#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
Web of Science research areas
Gastroenterology & Hepatology
Pharmacology & Pharmacy
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