Evidence map›Paper›PMID 29333665›Full record

Trial reportAlimentary pharmacology & therapeutics2018

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

B Hameed, N A Terrault, R M Gill, R Loomba, N Chalasani, J H Hoofnagle, M L Van Natta, NASH CRN

Registry-linked trialOpen access · bronzeAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Alimentary pharmacology & therapeutics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01265498 (The Farnesoid X Receptor), which is not on this map. Cited by 30 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 2 pooled it
7.0field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01265498 phase2completednot on this map

The Farnesoid X Receptor (FXR) Ligand Obeticholic Acid in Nonalcoholic Steatohepatitis (NASH) Treatment (FLINT) Trial

TypeinterventionalSponsorNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Ran2011 to 2014Enrolled283ConditionsNonalcoholic Fatty Liver Disease (NAFLD), Nonalcoholic Steatohepatitis (NASH)Armsobeticholic acid, placebo
3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 71 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 5 institutions in 1 country.

B HameedUniversity of California San Francisco, San Francisco, CA, USA.ORCID 0000-0003-2200-8428
N A TerraultUniversity of California San Francisco, San Francisco, CA, USA.
R M GillUniversity of California San Francisco, San Francisco, CA, USA.
R LoombaUniversity of California San Diego, San Diego, CA, USA.ORCID 0000-0002-4845-9991
N ChalasaniIndiana University School, Indianapolis, IN, USA.
J H HoofnagleNational Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA.
M L Van NattaJohns Hopkins University, Baltimore, MD, USA.
NASH CRN
University of California, San Francisco · USJohns Hopkins University · USNational Institute of Diabetes and Digestive and Kidney Diseases · USUniversity of California San Diego · USUniversity School · US

Funding

Transform Dissemination and Implementation Science in CTSA ProgramsUL1TR002319 · NCATS · UNIVERSITY OF WASHINGTON · PI John K. Amory · 2017 to 2026
$100.0M
WU INSTITUTE OF CLINICAL AND TRANSLATIONAL SCIENCESUL1TR002345 · NCATS · WASHINGTON UNIVERSITY · PI William G. Powderly · 2017 to 2026
$97.8M
Engaging University of California Stakeholders for Biorespository ResearchUL1TR000004 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRANDIS, JENNIFER RUBIN · 2012 to 2015
$78.0M
Clinical and Translational Science Collaborative of ClevelandUL1TR000439 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$50.0M
Institute of Translational Health SciencesUL1TR000423 · NCATS · UNIVERSITY OF WASHINGTON · PI DISIS, MARY L. · 2012 to 2016
$49.4M
Washington University Institute of Clinical and Translational SciencesUL1TR000448 · NCATS · WASHINGTON UNIVERSITY · PI EVANOFF, BRADLEY A · 2012 to 2016
$41.4M
Pediatric Trials in Non-Alcoholic Steatohepatitis (NASH)U01DK061734 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ROHIT LOOMBA · 2002 to 2026
$24.4M
Continuation of the Non-Alcoholic Steatohepatitis Clinical Research Network (NASHU01DK061730 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI TONASCIA, JAMES A · 2002 to 2018
$23.2M
San Diego Clinical and Translational Research InstituteUL1TR000100 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S · 2012 to 2015
$19.7M
Center for Clinical and Translational ResearchUL1TR000058 · NCATS · VIRGINIA COMMONWEALTH UNIVERSITY · PI MOELLER, FREDERICK GERARD · 2012 to 2015
$12.5M
Non Alcoholic Steatohepatitis Clinical Research NetworkU01DK061732 · NIDDK · CLEVELAND CLINIC LERNER COM-CWRU · PI Srinivasan Dasarathy · 2002 to 2026
$12.2M
The Saint Louis University Component of the NASH CRNU01DK061718 · NIDDK · SAINT LOUIS UNIVERSITY · PI BRENT A NEUSCHWANDER-TETRI · 2002 to 2026
$12.0M
NCATS NIH HHS UL1 TR000006NCATS NIH HHS UL1 TR000423NCATS NIH HHS UL1 TR000439NCATS NIH HHS UL1 TR000448NCATS NIH HHS UL1 TR002319NCATS NIH HHS UL1 TR002345NIDDK NIH HHS U01 DK061713NIDDK NIH HHS U01 DK061718NIDDK NIH HHS U01 DK061728NIDDK NIH HHS U01 DK061730NIDDK NIH HHS U01 DK061731NIDDK NIH HHS U01 DK061732NIDDK NIH HHS U01 DK061734NIDDK NIH HHS U01 DK061737NIDDK NIH HHS U01 DK061738
6 · The paper itself

Abstract

backgroundIn 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.

aimsBecause 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.

methodsThe 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.

resultsWeight 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).

conclusionsOCA 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.

Indexed as

AdultAlkaline PhosphataseBiopsyBody WeightChenodeoxycholic AcidCholesterol, LDLDouble-Blind MethodFemaleHumansMaleMiddle AgedNon-alcoholic Fatty Liver DiseaseTreatment OutcomeWeight LossAlkaline PhosphataseChenodeoxycholic AcidCholesterol, LDLobeticholic acid

Identifiers

PMID29333665
PMCPMC5931362
OpenAlexW2782978792

What Socratic holds

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LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.