Toggle Main Menu Toggle Search

Open Access padlockePrints

Serum levels of fibrogenesis biomarkers reveal distinct endotypes predictive of response to weight loss in advanced nonalcoholic fatty liver disease

Lookup NU author(s): Dr Kate HallsworthORCiD, Jadine Scragg, Dr Leah Avery, Laura HaighORCiD, Dr Olivier GovaereORCiD, Dr Guy Taylor, Dr Sophie Cassidy, Professor Stuart McPhersonORCiD, Professor Quentin AnsteeORCiD

Downloads


Licence

This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2023 Lippincott Williams and Wilkins. All rights reserved.Background: NAFLD is associated with activation of fibroblasts and hepatic fibrosis. Substantial patient heterogeneity exists, so it remains challenging to risk-stratify patients. We hypothesized that the amount of fibroblast activity, as assessed by circulating biomarkers of collagen formation, can define a "high-risk, high-fibrogenesis" patient endotype that exhibits greater fibroblast activity and potentially more progressive disease, and this endotype may be more amendable to dietary intervention. Methods: Patients with clinically confirmed advanced NAFLD were prescribed a very low-calorie diet (VLCD) intervention (800 kcal/d) to induce weight loss, achieved using total diet replacement. Serum markers of type III (PRO-C3) and IV collagen (PRO-C4) fibrogenesis were assessed at baseline every second week until the end of the VLCD, and 4 weeks post-VLCD and at 9 months follow-up. Results: Twenty-six subjects had a mean weight loss of 9.7% with VLCD. This was associated with significant improvements in liver biochemistry. When stratified by baseline PRO-C3 and PRO-C4 into distinct fibrosis endotypes, these predicted substantial differences in collagen fibrogenesis marker dynamics in response to VLCD. Patients in the high activity group (PRO-C3 11.4 ng/mL and/or PRO-C4 236.5 ng/mL) exhibited a marked reduction of collagen fibrogenesis, ranging from a 40%-55% decrease in PRO-C3 and PRO-C4, while fibrogenesis remained unchanged in the low activity group. The biochemical response to weight loss was substantially greater in patients a priori exhibiting a high fibroblast activity endotype in contrast to patients with low activity. Conclusions: Thus, the likelihood of treatment response may be predicted at baseline by quantification of fibrogenesis biomarkers.


Publication metadata

Author(s): Karsdal MA, Hallsworth K, Scragg J, Leeming DJ, Villesen IF, Avery L, Haigh L, Govaere O, Wichmann S, Taylor G, Cassidy S, McPherson S, Anstee QM

Publication type: Article

Publication status: Published

Journal: Hepatology Communications

Year: 2023

Volume: 7

Issue: 10

Print publication date: 01/10/2023

Acceptance date: 21/06/2023

Date deposited: 09/04/2024

ISSN (electronic): 2471-254X

Publisher: Lippincott Williams and Wilkins

URL: https://doi.org/10.1097/HC9.0000000000000254

DOI: 10.1097/HC9.0000000000000254

PubMed id: 37756043


Altmetrics

Altmetrics provided by Altmetric


Funding

Funder referenceFunder name
777377European Commission
EFPIA
CL-2013-04-010
Innovative Medicines Initiative 2 Joint Undertaking
European Union Horizon 2020 Research and Innovation Programme
National Institute for Health Research
Newcastle NIHR Biomedical Research Centre

Share