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Introduction
Quentin M. Anstee is an Academic Hepatologist in the Faculty of Medical Sciences, Newcastle University. A practising clinician, he is also an Honorary Consultant Hepatologist in the Liver Unit at the Freeman Hospital, Newcastle.
His primary research interest is the study of genetic and epigenetic modifiers of progressive liver disease with particular focus on the pathogenesis, diagnosis and treatment of Non-Alcoholic Fatty Liver Disease (NAFLD/NASH) and Hepatic Fibrosis.
Current institution
Additional affiliations
August 2016 - present
September 2010 - present
September 2010 - August 2016
Publications
Publications (575)
The role of adaptive immunity in early cancer development is controversial. Here we show that chronic inflammation and fibrosis in humans and mice with non-alcoholic fatty liver disease is accompanied by accumulation of liver-resident immunoglobulin-A-producing (IgA⁺) cells. These cells also express programmed death ligand 1 (PD-L1) and interleukin...
Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition, strongly associated with the metabolic syndrome, that can lead to progressive hepatic fibrosis, cirrhosis and hepatic failure. Subtle inter-patient genetic variation and environmental factors combine to determine variation in disease progression. A common non-synonymous...
Subtle inter-patient genetic variation and environmental factors combine to determine disease progression in non-alcoholic fatty liver disease (NAFLD). Carriage of the PNPLA3 rs738409 c.444C>G minor allele (encoding the I148M variant) has been robustly associated with advanced NAFLD. Although most hepatocellular carcinoma (HCC) is related to chroni...
NAFLD is a spectrum of progressive liver disease that encompasses simple steatosis, NASH, fibrosis and, ultimately, cirrhosis. NAFLD is recognized as the hepatic component of the metabolic syndrome, as these conditions have insulin resistance as a common pathophysiological mechanism. Therefore, NAFLD is strongly associated with type 2 diabetes mell...
There remains uncertainty about the natural history of non-alcoholic fatty liver disease (NAFLD). The spectrum of NAFLD includes non-alcoholic fatty liver (NAFL; steatosis without hepatocellular injury) and steatohepatitis (NASH; steatosis with hepatocyte ballooning degeneration +/- fibrosis). Our aim was to assess the histological severity of NAFL...
Background
The continuum of metabolic syndrome encompasses a spectrum of dysfunctions impacting obesity‐linked insulin resistance, glucose homeostasis, lipid metabolism and pro‐inflammatory immune responses. The global prevalence of metabolic diseases, including diabetes, chronic liver disease, cardiometabolic disease and kidney disease, has surged...
Background and Aims
The performance of non‐invasive liver tests (NITs) is known to vary across settings and subgroups. We systematically evaluated whether the performance of three NITs in detecting advanced fibrosis in patients with metabolic dysfunction‐associated steatotic liver disease (MASLD) varies with age, sex, body mass index (BMI), type 2...
Spatial transcriptomics (ST) has the potential to provide unprecedented insights into gene expression across tissue architecture, but existing analytical methods often overlook the full complexity of the spatial dimension. We present STExplorer, an R package that adapts well-established computational geography (CG) methods to explore the micro-geog...
Metabolic dysfunction-associated steatohepatitis (MASH) is a major cause of liver-related morbidity and mortality, yet treatment options are limited. Manual scoring of liver biopsies, currently the gold standard for clinical trial enrollment and endpoint assessment, suffers from high reader variability. This study represents the most comprehensive...
Metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) are associated with a high prevalence of type 2 diabetes (T2D). Individuals with MASLD exhibit insulin resistance (IR) and hyperglycemia, but it is unclear whether hepatic glucose production (HGP) is increased with MASLD severity. We evaluated HGP in a cohor...
LINKED CONTENT
This article is linked to McPherson et al papers. To view these articles, visit https://doi.org/10.1111/apt.18061 and https://doi.org/10.1111/apt.18171.
LINKED CONTENT
This article is linked to McPherson et al papers. To view these articles, visit https://doi.org/10.1111/apt.18061 and https://doi.org/10.1111/apt.18176
Although metabolic dysfunction-associated steatohepatitis (MASH) is rapidly becoming a leading cause of cirrhosis worldwide, therapeutic options are limited and the number of clinical trials in MASH-related compensated cirrhosis is low as compared to those conducted in earlier disease stages. Moreover, designing clinical trials in MASH cirrhosis pr...
Background
The EU Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) project (IMI2-853966) aimed to develop tools to establish integrated research platforms (IRP) for conducting adaptive-design trials in various diseases, including metabolic-dysfunction associated steatohepatitis (MASH). One essential component of a successful MASH IRP is a robust...
Introduction
Liver disease disproportionately affects the most economically disadvantaged, exacerbating health inequalities. In the United Kingdom, the prevalence of food insecurity (FI) has increased by 230% since 2021, affecting an estimated 17% of the general population. Evidence indicates a paradox wherein FI contributes to both obesity and com...
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, encompasses steatosis and metabolic dysfunction-associated steatohepatitis (MASH), leading to cirrhosis and hepatocellular carcinoma. Preclinical MASLD research is mainly performed in rodents; however, the model that best recapit...
Background:
Dual agonism of glucagon receptor and glucagon-like peptide-1 (GLP-1) receptor may be more effective than GLP-1 receptor agonism alone for treating metabolic dysfunction-associated steatohepatitis (MASH). The efficacy and safety of survodutide (a dual agonist of glucagon receptor and GLP-1 receptor) in persons with MASH and liver fibro...
Metabolic-dysfunction associated steatohepatitis (MASH) is a major cause of liver-related morbidity and mortality, yet treatment options are limited. Manual scoring of liver biopsies, currently the gold standard for clinical trial enrollment and endpoint assessment, suffers from high reader variability. This study represents the most comprehensive...
Background
It is unclear what biopsychosocial factors influence the impact of NAFLD on health-related quality of life (HRQoL), and if these factors are equally important predictors between different nationalities.
Methods
HRQoL (CLDQ) was measured in both Southern European (Spain, n = 513) and Northern European (United Kingdom -UK-, n = 224) cohor...
Background & Aims
There is a need to reduce the screen failure rate (SFR) in metabolic dysfunction‐associated steatohepatitis (MASH) clinical trials (MASH+F2‐3; MASH+F4) and identify people with high‐risk MASH (MASH+F2‐4) in clinical practice. We aimed to evaluate non‐invasive tests (NITs) screening approaches for these target conditions.
Methods...
Background & Aims
Robust performance of non-invasive tests (NITs) across ages is critical to assess liver disease among patients with metabolic dysfunction-associated liver disease (MASLD). We evaluated the impact of age on the performance of NIS2+™ vs. other NITs.
Methods
An analysis cohort (N = 1,926) with biopsy-proven MASLD was selected among...
Aims: Overlapping asymmetric data sets are where a large cohort of observations have a small amount of information recorded, and within this group there exists a smaller cohort which have extensive further information available. Missing imputation is unwise if cohort size differs substantially; therefore, we aim to develop a way of modelling the sm...
Aims
Metabolic dysfunction Associated Steatotic Liver Disease (MASLD) outcomes such as MASH (metabolic dysfunction associated steatohepatitis), fibrosis and cirrhosis are ordinarily determined by resource-intensive and invasive biopsies. We aim to show that routine clinical tests offer sufficient information to predict these endpoints.
Methods
Usi...
Background
The Fibrosis-4 Index (FIB-4) is used as a non-invasive tool for the presence of advanced liver fibrosis in metabolic dysfunction-associated steatotic liver disease and type 2 diabetes. However, evidence for an association between FIB-4 and risk of mortality and/or liver-related clinical outcomes is limited. The aim of this study was to i...
Background
Liver histopathologic assessment is the accepted surrogate endpoint in NASH trials; however, the scoring of NASH Clinical Research Network (CRN) histologic parameters is limited by intraobserver and interobserver variability. We designed a consensus panel approach to minimize variability when using this scoring system. We assessed agreem...
Background
Currently, assessment of candidate pharmacotherapies in patients with non-alcoholic steatohepatitis (NASH) involves invasive liver biopsy. Non-invasive scores, such as the FibroScan-aspartate aminotransferase (FAST) score, are used to identify candidates for therapy, but their ability to assess disease progression or treatment effect is...
Background
Non‐alcoholic steatohepatitis (NASH) is a progressive form of non‐alcoholic fatty liver disease (NAFLD) associated with steatosis, hepatocellular injury, inflammation and fibrosis. In a Phase 2 trial in adults with NASH (NCT02912260), resmetirom, an orally administered, liver‐targeted thyroid hormone receptor‐β selective agonist, signifi...
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 en...
Introduction
Application of at least two non-invasive tests (NITs) for fibrosis is recommended by international guidelines to stage liver fibrosis in primary/secondary care. Generally, NITs differentiate advanced fibrosis (F3–4) from milder stages (F0–2) with reasonable accuracy, providing a high negative predictive value. Many clinicians do not em...
Unlike for advanced liver fibrosis, the practical rules for the early non-invasive diagnosis of cirrhosis in NAFLD remain not well defined. Here, we report the derivation and validation of a stepwise diagnostic algorithm in 1568 patients with NAFLD and liver biopsy coming from four independent cohorts. The study algorithm, using first the elastogra...
Background:
Early identification of those with NAFLD activity score ≥ 4 and significant fibrosis (≥F2) or "at-risk MASH" is a priority as these patients are at increased risk for disease progression and may benefit from therapies. We developed and validated a highly specific metabolomics-driven score to identify at-risk MASH.
Methods:
We include...
Background:
Standardized measures for evaluating patients' experiences with nonalcoholic steatohepatitis (NASH) and their perceived changes with treatment in clinical trials have been limited. To meet this need, a patient-reported outcome (PRO) measure, NASH-CHECK, was developed to evaluate symptoms and health-related quality of life for patients...
Background & aims:
Obeticholic acid (OCA) is a first-in-class farnesoid X receptor agonist and antifibrotic agent in development for treating pre-cirrhotic liver fibrosis due to nonalcoholic steatohepatitis (NASH). We aimed to validate the original 18-month liver biopsy analysis from the phase 3 REGENERATE trial of OCA for treatment of NASH with a...
Background aims:
Fatty liver disease is a major public health threat due to its very high prevalence and related morbidity and mortality. Focused and dedicated interventions are urgently needed to target disease prevention, treatment, and care.
Approach results:
We developed an aligned, prioritized action agenda for the global fatty liver diseas...
Unlabelled:
The principal limitations of the terms nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favour of a change in nomenclature a...
Unlabelled:
The principal limitations of the terms nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favour of a change in nomenclature a...
Background:
Histologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD.
Met...
Background & aims
An estimated 38% of adults worldwide have NAFLD. From individual impacts to widespread public health and economic consequences, the implications of this disease are profound. This study aimed to develop an aligned, prioritised research agenda for the global fatty liver disease community of practice.
Methods
Nine co-chairs drafted...
Unlabelled:
The principal limitations of the terms nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favour of a change in nomenclature a...
Background aims:
With distinct mechanisms of action, the combination of tropifexor (TXR) and cenicriviroc (CVC) may provide an effective treatment for non-alcoholic steatohepatitis. This randomized, multicenter, double-blind, phase 2b study assessed the safety and efficacy of TXR and CVC combination, compared with respective monotherapies.
Approa...
Background & aims:
Non-alcoholic fatty liver disease (NAFLD) is a complex disease, resulting from the interplay between environmental determinants and genetic variations. Single nucleotide polymorphism (SNP) rs738409 C>G in the patatin-like phospholipase domain-containing 3 (PNPLA3) gene is associated with hepatic fibrosis and with higher risk of...
Background & aims:
NIS4® is a blood-based non-invasive test (NIT) designed to effectively rule in/rule out at-risk non-alcoholic steatohepatitis (NASH), defined as non-alcoholic fatty liver disease (NAFLD) activity score ≥4 and significant fibrosis (stage ≥2), among patients with metabolic risk factors. Robustness of NIT scores across characterist...
Background & aims:
The progression of nonalcoholic steatohepatitis (NASH) to fibrosis and hepatocellular carcinoma (HCC) is aggravated by auto-aggressive T cells. The gut-liver axis contributes to NASH, but the mechanisms involved and the consequences for NASH-induced fibrosis and liver cancer remain unknown. We investigated the role of gastrointe...
Non-alcoholic fatty liver disease (NAFLD) is a common, progressive liver disease strongly associated with the metabolic syndrome. It is unclear how progression of NAFLD towards cirrhosis translates into systematic changes in circulating proteins. Here, we provide a detailed proteo-transcriptomic map of steatohepatitis and fibrosis during progressiv...
Objectives:
The Glucokinase Regulatory Protein GKRP, encoded by GCKR, enables acute regulation of liver glucokinase to support metabolic demand. The common human GCKR rs1260326:P446>L variant within a large linkage disequilibrium region associates with pleiotropic traits, lower Type 2 diabetes risk and raised blood triglycerides and cholesterol. W...
Background & aims:
Cenicriviroc (CVC) is a novel, orally administered, chemokine receptor type 2 and 5 antagonist that showed antifibrotic potential in preclinical and phase IIb studies of nonalcoholic steatohepatitis (NASH). Herein, we report efficacy and safety results from the phase III study.
Methods:
AURORA was a phase III, randomized, doub...
Background & aims:
We conducted an individual patient data (IPD) meta-analysis to establish stiffness cut-off values for Magnetic Resonance Elastography (MRE) in staging liver fibrosis and to assess potential confounding factors.
Methods:
A systematic review of the literature identified studies reporting MRE data in patients with non-alcoholic f...
Chronic liver disease (CLD) and its associated complications (cirrhosis and liver cancer) cause significant mortality, morbidity, and economic burden. Published data from the World Health Organization (WHO) and/or the Global Burden of Disease (GBD) show that the burden of CLD is large and growing primarily due to the increasing burden of nonalcohol...
Background aims:
Detecting non-alcoholic steatohepatitis (NASH) remains challenging, while at-risk NASH (steatohepatitis and F≥ 2) tends to progress and is of interest for drug development and clinical application. We developed prediction models by supervised machine learning (ML) techniques, with clinical data and biomarkers to stage and grade no...
Background:
We evaluated the diagnostic accuracy of simple non-invasive tests(NITs) in NAFLD patients with type 2 diabetes(T2D).
Methods:
This was an individual patient data meta-analysis of 1780 patients with biopsy-proven NAFLD and T2D. The index tests of interest were FIB-4, NAFLD Fibrosis Score(NFS), APRI, liver stiffness measurement(LSM) by...
Background and aims:
Non-alcoholic steatohepatitis (NASH) constitutes a significant unmet medical need with a burgeoning field of clinical research and drug development. Platform trials (PT) might help accelerate drug development while lowering overall costs and creating a more patient-centric environment. This review provides a comprehensive and...
Background:
The reference standard for detecting non-alcoholic steatohepatitis (NASH) and staging fibrosis-liver biopsy-is invasive and resource intensive. Non-invasive biomarkers are urgently needed, but few studies have compared these biomarkers in a single cohort. As part of the Liver Investigation: Testing Marker Utility in Steatohepatitis (LI...
