Evidence map›Paper›PMID 34977519›Full record

ArticleJHEP reports : innovation in hepatology2022

Pegbelfermin selectively reduces secondary bile acid concentrations in patients with non-alcoholic steatohepatitis.

Yi Luo, Benjamin E Decato, Edgar D Charles, Diane E Shevell, Colleen McNaney, Petia Shipkova, Abraham Apfel, Giridhar S Tirucherai, Arun J Sanyal

2 registry-linked trialsOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JHEP reports : innovation in hepatology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.6field-weighted citation impact, top 10% 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.

NCT02413372 phase2completednot on this map

A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multiple Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamic Effects of BMS-986036 in Adults With Non-alcoholic Steatohepatitis

TypeinterventionalSponsorBristol-Myers SquibbRan2015 to 2017Enrolled184ConditionsNon-Alcoholic SteatohepatitisArmsBMS-986036, Placebo
NCT03198182 phase1completednot on this map

A Randomized, Parallel, Placebo-Controlled, Multiple Dose Study to Evaluate the Safety to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BMS-986036 in Healthy Japanese and Non-Japanese Subjects

TypeinterventionalSponsorBristol-Myers SquibbRan2017 to 2017Enrolled63ConditionsMetabolicsArmsPlacebo, BMS-986036
3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 22 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Yi LuoBristol Myers Squibb, Princeton, NJ, USA.
Benjamin E DecatoBristol Myers Squibb, Princeton, NJ, USA.
Edgar D CharlesBristol Myers Squibb, Princeton, NJ, USA.
Diane E ShevellBristol Myers Squibb, Princeton, NJ, USA.
Colleen McNaneyBristol Myers Squibb, Princeton, NJ, USA.
Petia ShipkovaBristol Myers Squibb, Princeton, NJ, USA.
Abraham ApfelBristol Myers Squibb, Princeton, NJ, USA.
Giridhar S TirucheraiBristol Myers Squibb, Princeton, NJ, USA.
Arun J SanyalDepartment of Internal Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, Richmond, VA, USA.
Bristol-Myers Squibb (United States) · USVirginia Commonwealth University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

aimsIncreased serum bile acids (BAs) have been observed in patients with non-alcoholic steatohepatitis (NASH). Pegbelfermin (PGBF), a polyethylene glycol-modified (PEGylated) analogue of human fibroblast growth factor 21 (FGF21), significantly decreased hepatic steatosis and improved fibrosis biomarkers and metabolic parameters in patients with NASH in a phase IIa trial. This exploratory analysis evaluated the effect of PGBF on serum BAs and explored potential underlying mechanisms.

methodsSerum BAs and 7α-hydroxy-4-cholesten-3-one (C4) were measured by HPLC-mass spectrometry (MS) using serum collected in studies of patients with NASH (NCT02413372) and in overweight/obese adults (NCT03198182) who received PGBF. Stool samples were collected in NCT03198182 to evaluate faecal BAs by liquid chromatography (LC)-MS and the faecal microbiome by metagenetic and metatranscriptomic analyses.

resultsSignificant reductions from baseline in serum concentrations of the secondary BA, deoxycholic acid (DCA), and conjugates, were observed with PGBF, but not placebo, in patients with NASH; primary BA concentrations did not significantly change in any arm. Similar effects of PGBF on BAs were observed in overweight/obese adults, allowing for an evaluation of the effects of PGBF on the faecal microbiome and BAs. Faecal transcriptomic analysis showed that the relative abundance of the gene encoding choloylglycine hydrolase, a critical enzyme for secondary BA synthesis, was reduced after PGBF, but not placebo, administration. Furthermore, a trend of reduction in faecal secondary BAs was observed.

conclusionsPGBF selectively reduced serum concentrations of DCA and conjugates in patients with NASH and in healthy overweight/obese adults. Reduced choloylglycine hydrolase gene expression and decreased faecal secondary BA levels suggest a potential role for PGBF in modulating secondary BA synthesis by gut microbiome. The clinical significance of DCA reduction post-PGBF treatment warrants further investigation. LAY SUMMARY: Pegbelfermin (PGBF) is a hormone that is currently being studied in clinical trials for the treatment of non-alcoholic fatty liver disease. In this study, we show that PGBF treatment can reduce bile acids that have previously been shown to have toxic effects on the liver. Additional studies to understand how PGBF regulates bile acids may provide additional information about its potential use as a treatment for fatty liver.

Indexed as

ALT, alanine aminotransferaseApoA1, apolipoprotein A1AST, aspartate aminotransferaseBA, bile acidbaiCD, 7α-hydroxy-3-oxo-delta4-cholenoic acid oxidoreductasebaiH, 7β-hydroxy-3-oxo-delta4-cholenoic acid oxidoreductaseBile salt hydrolaseBiomarkersBSH, bile salt hydrolaseC4C4, 7α-hydroxy-4-cholesten-3-oneCA, cholic acidCDCA, chenodeoxycholic acidCYP7A1, cytochrome P450 7A1DCA, deoxycholic acidDeoxycholic acidFGF21FGF21, fibroblast growth factor 21FXR, farnesoid X receptorGCA, glyco-cholic acidGCDCA, glyco-chenodeoxycholic acidGDCA, glyco-deoxycholic acidGUDCA, glyco-ursodeoxycholic acidHbA1c, glycated haemoglobinhdhA, 7-alpha-hydroxysteroid dehydrogenaseHFF, hepatic fat fractionLCA, lithocholic acidLC, liquid chromatographyMicrobiomeMS, mass spectrometryNAFLD, non-alcoholic fatty liver diseaseNASH, non-alcoholic steatohepatitisPEGylated, polyethylene glycol-conjugatedPGBF, pegbelferminPRO-C3, N-terminal type III collagen propeptideQD, once dailyQW, once weeklyT2DM, type 2 diabetes mellitusTCA, tauro-cholic acidTCDCA, tauro-chenodeoxycholic acidTDCA, tauro-deoxycholic acidUDCA, ursodeoxycholic acid

Identifiers

PMID34977519
PMCPMC8689226
OpenAlexW3212396009

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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 OpenQuestion graph.