TY - JOUR
T1 - Clinical and metabolic effects associated with weight changes and obeticholic acid in non-alcoholic steatohepatitis
AU - for the NASH CRN
AU - Hameed, B.
AU - Terrault, N. A.
AU - Gill, R. M.
AU - Loomba, R.
AU - Chalasani, N.
AU - Hoofnagle, J. H.
AU - Van Natta, M. L.
AU - Allende, Daniela
AU - Dasarathy, Srinivasan
AU - J. McCullough, Arthur
AU - Penumatsa, Revathi
AU - Dasarathy, Jaividhya
AU - E. Lavine, Joel
AU - F. Abdelmalek, Manal
AU - Bashir, Mustafa
AU - Buie, Stephanie
AU - Mae Diehl, Anna
AU - Guy, Cynthia
AU - Kigongo, Christopher
AU - Kopping, Mariko
AU - Malik, David
AU - Piercy, Dawn
AU - W. Cummings, Oscar
AU - Gawrieh, Samer
AU - Ragozzino, Linda
AU - Sandrasegaran, Kumar
AU - Vuppalanchi, Raj
AU - M. Brunt, Elizabeth
AU - Cattoor, Theresa
AU - Carpenter, Danielle
AU - Freebersyser, Janet
AU - King, Debra
AU - Lai, Jinping
AU - A. Neuschwander-Tetri, Brent
AU - Siegner, Joan
AU - Stewart, Susan
AU - Torretta, Susan
AU - Wriston, Kristina
AU - Cardona Gonzalez, Maria
AU - Davila, Jodie
AU - Jhaveri, Manan
AU - V. Kowdley, Kris
AU - Mukhtar, Nizar
AU - Ness, Erik
AU - Poitevin, Michelle
AU - M. Clark, Jeanne
AU - Lazo, Mariana
AU - Sternberg, Alice
AU - Tonascia, James
AU - Yates, Katherine
N1 - Publisher Copyright:
© 2018 John Wiley & Sons Ltd
PY - 2018/3
Y1 - 2018/3
N2 - 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.
AB - 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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U2 - 10.1111/apt.14492
DO - 10.1111/apt.14492
M3 - Article
C2 - 29333665
AN - SCOPUS:85040659151
SN - 0269-2813
VL - 47
SP - 645
EP - 656
JO - Alimentary Pharmacology and Therapeutics
JF - Alimentary Pharmacology and Therapeutics
IS - 5
ER -