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

for the NASH CRN

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)645-656
Number of pages12
JournalAlimentary Pharmacology and Therapeutics
Volume47
Issue number5
DOIs
StatePublished - Mar 1 2018

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Fatty Liver
Weight Loss
Weights and Measures
Placebos
Histology
Therapeutics
Alkaline Phosphatase
6-ethylchenodeoxycholic acid
Placebo Effect
Liver
Transaminases
Serum
LDL Cholesterol
Blood Glucose
Randomized Controlled Trials
Clinical Trials
Lipids
Biopsy

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Clinical and metabolic effects associated with weight changes and obeticholic acid in non-alcoholic steatohepatitis. / for the NASH CRN.

In: Alimentary Pharmacology and Therapeutics, Vol. 47, No. 5, 01.03.2018, p. 645-656.

Research output: Contribution to journalArticle

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title = "Clinical and metabolic effects associated with weight changes and obeticholic acid in non-alcoholic steatohepatitis",
abstract = "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.",
author = "{for the NASH CRN} and B. Hameed and Terrault, {N. A.} and Gill, {R. M.} and R. Loomba and Naga Chalasani and Hoofnagle, {J. H.} and {Van Natta}, {M. L.} and Daniela Allende and Srinivasan Dasarathy and {J. McCullough}, Arthur and Revathi Penumatsa and Jaividhya Dasarathy and {E. Lavine}, Joel and {F. Abdelmalek}, Manal and Mustafa Bashir and Stephanie Buie and {Mae Diehl}, Anna and Cynthia Guy and Christopher Kigongo and Mariko Kopping and David Malik and Dawn Piercy and Naga Chalasani and Samer Gawrieh and Samer Gawrieh and Kumar Sandrasegaran and Raj Vuppalanchi and Raj Vuppalanchi and {M. Brunt}, Elizabeth and Theresa Cattoor and Danielle Carpenter and Janet Freebersyser and Debra King and Jinping Lai and {A. Neuschwander-Tetri}, Brent and Joan Siegner and Susan Stewart and Susan Torretta and Kristina Wriston and {Cardona Gonzalez}, Maria and Jodie Davila and Manan Jhaveri and {V. Kowdley}, Kris and Nizar Mukhtar and Erik Ness and Michelle Poitevin and Brook Quist and Sherilynn Soo and Brandon Ang and Cynthia Behling",
year = "2018",
month = "3",
day = "1",
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language = "English (US)",
volume = "47",
pages = "645--656",
journal = "Alimentary Pharmacology and Therapeutics",
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}

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, Naga

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 - Chalasani, Naga

AU - Gawrieh, Samer

AU - Gawrieh, Samer

AU - Sandrasegaran, Kumar

AU - Vuppalanchi, Raj

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 - Quist, Brook

AU - Soo, Sherilynn

AU - Ang, Brandon

AU - Behling, Cynthia

PY - 2018/3/1

Y1 - 2018/3/1

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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