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Using a machine learning model to risk stratify for the presence of significant liver disease in a primary care population (2023)
Journal Article
Bennett, L., Mostafa, M., Hammersley, R., Purssell, H., Patel, M., Street, O., …Guha, I. N. (2023). Using a machine learning model to risk stratify for the presence of significant liver disease in a primary care population. Journal of Medical Artificial Intelligence, 6, Article 27. https://doi.org/10.21037/jmai-23-35

Background: Current strategies for detecting significant chronic liver disease (CLD) in the community are based on the extrapolation of diagnostic tests used in secondary care settings. Whilst this approach provides clinical utility, it has limitatio... Read More about Using a machine learning model to risk stratify for the presence of significant liver disease in a primary care population.

An integrated gene-to-outcome multimodal database for metabolic dysfunction-associated steatotic liver disease (2023)
Journal Article
Kendall, T. J., Jimenez-Ramos, M., Turner, F., Ramachandran, P., Minnier, J., McColgan, M. D., …Fallowfield, J. A. (2023). An integrated gene-to-outcome multimodal database for metabolic dysfunction-associated steatotic liver disease. Nature Medicine, 29, 2939–2953. https://doi.org/10.1038/s41591-023-02602-2

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the commonest cause of chronic liver disease worldwide and represents an unmet precision medicine challenge. We established a retrospective national cohort of 940 histologically defi... Read More about An integrated gene-to-outcome multimodal database for metabolic dysfunction-associated steatotic liver disease.

Development, validation, and prognostic evaluation of a risk score for long-term liver-related outcomes in the general population: a multicohort study (2023)
Journal Article
Serra-Burriel, M., Juanola, A., Serra-Burriel, F., Thiele, M., Graupera, I., Pose, E., …Wildsmith, T. (2023). Development, validation, and prognostic evaluation of a risk score for long-term liver-related outcomes in the general population: a multicohort study. Lancet, 402(10406), https://doi.org/10.1016/s0140-6736%2823%2901174-1

Background: Liver cirrhosis is a major cause of death worldwide. Cirrhosis develops after a long asymptomatic period of fibrosis progression, with the diagnosis frequently occurring late, when major complications or cancer develop. Few reliable tools... Read More about Development, validation, and prognostic evaluation of a risk score for long-term liver-related outcomes in the general population: a multicohort study.

Mortality rates among patients successfully treated for hepatitis C in the era of interferon-free antivirals: population based cohort study (2023)
Journal Article
Hamill, V., Wong, S., Benselin, J., Krajden, M., Hayes, P. C., Mutimer, D., …Innes, H. (2023). Mortality rates among patients successfully treated for hepatitis C in the era of interferon-free antivirals: population based cohort study. BMJ, 382, Article e074001. https://doi.org/10.1136/bmj-2022-074001

Objectives To quantify mortality rates for patients successfully treated for hepatitis C in the era of interferon-free, direct acting antivirals and compare these rates with those of the general population. Design Population based cohort study.... Read More about Mortality rates among patients successfully treated for hepatitis C in the era of interferon-free antivirals: population based cohort study.

Circadian Disruption Primes Myofibroblasts for Accelerated Activation as a Mechanism Underpinning Fibrotic Progression in Non-Alcoholic Fatty Liver Disease (2023)
Journal Article
Jokl, E., Llewellyn, J., Simpson, K., Adegboye, O., Pritchett, J., Zeef, L., …Piper Hanley, K. (2023). Circadian Disruption Primes Myofibroblasts for Accelerated Activation as a Mechanism Underpinning Fibrotic Progression in Non-Alcoholic Fatty Liver Disease. Cells, 12(12), Article 1582. https://doi.org/10.3390/cells12121582

Circadian rhythm governs many aspects of liver physiology and its disruption exacerbates chronic disease. CLOCKΔ19 mice disrupted circadian rhythm and spontaneously developed obesity and metabolic syndrome, a phenotype that parallels the progression... Read More about Circadian Disruption Primes Myofibroblasts for Accelerated Activation as a Mechanism Underpinning Fibrotic Progression in Non-Alcoholic Fatty Liver Disease.

SteatoSITE: an Integrated Gene-to-Outcome Data Commons for Precision Medicine Research in NAFLD (2023)
Working Paper
Fallowfield, J., Kendall, T., Jimenez-Ramos, M., Turner, F., Ramachandran, P., Minnier, J., …Guha, I. SteatoSITE: an Integrated Gene-to-Outcome Data Commons for Precision Medicine Research in NAFLD

Nonalcoholic fatty liver disease (NAFLD) is the commonest cause of chronic liver disease worldwide and a growing healthcare burden. The pathobiology of NAFLD is complex, disease progression is variable and unpredictable, and there are no qualified pr... Read More about SteatoSITE: an Integrated Gene-to-Outcome Data Commons for Precision Medicine Research in NAFLD.

PRO-C3 is a predictor of clinical outcomes in distinct cohorts of patients with advanced liver disease (2023)
Journal Article
Nielsen, M. J., Dolman, G. E., Harris, R., Frederiksen, P., Chalmers, J., Grove, J. I., …Guha, I. N. (2023). PRO-C3 is a predictor of clinical outcomes in distinct cohorts of patients with advanced liver disease. JHEP Reports, 5(6), Article 100743. https://doi.org/10.1016/j.jhepr.2023.100743

Background & Aims: Fibroblast activity is a key feature of fibrosis progression and organ function loss, leading to liver-related complications and mortality. The fibrogenesis marker, PRO-C3, has been shown to have prognostic significance in relation... Read More about PRO-C3 is a predictor of clinical outcomes in distinct cohorts of patients with advanced liver disease.

Delivery of biannual ultrasound surveillance for individuals with cirrhosis and cured hepatitis C in the UK (2023)
Journal Article
Hamill, V., Gelson, W., MacDonald, D., Richardson, P., Ryder, S. D., Aldersley, M., …Innes, H. (2023). Delivery of biannual ultrasound surveillance for individuals with cirrhosis and cured hepatitis C in the UK. Liver International, 43(4), 917-927. https://doi.org/10.1111/liv.15528

Background: Previous studies show the uptake of biannual ultrasound (US) surveillance in patients with cirrhosis is suboptimal. Here, our goal was to understand in broader terms how surveillance is being delivered to cirrhosis patients with cured hep... Read More about Delivery of biannual ultrasound surveillance for individuals with cirrhosis and cured hepatitis C in the UK.

Comparing magnetic resonance liver fat fraction measurements with histology in fibrosis: the difference between proton density fat fraction and tissue mass fat fraction (2022)
Journal Article
Bawden, S. J., Hoad, C., Kaye, P., Stephenson, M., Dolman, G., James, M. W., …Aithal, G. P. (2023). Comparing magnetic resonance liver fat fraction measurements with histology in fibrosis: the difference between proton density fat fraction and tissue mass fat fraction. Magnetic Resonance Materials in Physics, Biology and Medicine, 36(4), 553-563. https://doi.org/10.1007/s10334-022-01052-0

Objective: Magnetic resonance spectroscopy (MRS) provides a powerful method of measuring fat fraction. However, previous studies have shown that MRS results give lower values compared with visual estimates from biopsies in fibrotic livers. This study... Read More about Comparing magnetic resonance liver fat fraction measurements with histology in fibrosis: the difference between proton density fat fraction and tissue mass fat fraction.

Low Accuracy of FIB-4 and NAFLD Fibrosis Scores for Screening for Liver Fibrosis in the Population (2022)
Journal Article
Graupera, I., Thiele, M., Serra-Burriel, M., Caballeria, L., Roulot, D., Wong, G. L., …Krag, A. (2022). Low Accuracy of FIB-4 and NAFLD Fibrosis Scores for Screening for Liver Fibrosis in the Population. Clinical Gastroenterology and Hepatology, 20(11), 2567-2576.e6. https://doi.org/10.1016/j.cgh.2021.12.034

Background & Aims Fibrosis-4 (FIB-4) and the nonalcoholic fatty liver disease fibrosis score (NFS) are the 2 most popular noninvasive blood-based serum tests proposed for widespread fibrosis screening. We therefore aimed to describe the accuracy o... Read More about Low Accuracy of FIB-4 and NAFLD Fibrosis Scores for Screening for Liver Fibrosis in the Population.

Variability of noninvasive MRI and biological markers in compensated cirrhosis: insights for assessing disease progression (2022)
Journal Article
Bradley, C. R., Cox, E. F., Palaniyappan, N., Aithal, G. P., Francis, S. T., & Guha, I. N. (2022). Variability of noninvasive MRI and biological markers in compensated cirrhosis: insights for assessing disease progression. European Radiology Experimental, 6(1), Article 52. https://doi.org/10.1186/s41747-022-00303-y

Abstract: Background: We annually monitored stable compensated cirrhosis (CC) patients to evaluate serial variation in blood serum, liver stiffness, and multiparametric magnetic resonance imaging (mpMRI) measures to provide reference change values (R... Read More about Variability of noninvasive MRI and biological markers in compensated cirrhosis: insights for assessing disease progression.

Liver blood marker testing in UK primary care: a UK wide cohort study, 2004-2016 (2022)
Journal Article
Scutt, P., Ban, L., Card, T., Crooks, C. J., Guha, N., West, J., & Morling, J. R. (2022). Liver blood marker testing in UK primary care: a UK wide cohort study, 2004-2016. BMJ Open, 12(9), e058967. https://doi.org/10.1136/bmjopen-2021-058967

OBJECTIVE: We aimed to determine (1) the temporal trends of liver enzyme testing in UK general practice and (2) how these vary among different subgroups at risk of chronic liver disease (CLD). DESIGN: Retrospective cohort study. SETTING: UK primary c... Read More about Liver blood marker testing in UK primary care: a UK wide cohort study, 2004-2016.

Genetic variation in TERT modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: Results from a genome-wide case-control study (2022)
Journal Article
Buch, S., Innes, H., Lutz, P. L., Nischalke, H. D., Marquardt, J. U., Fischer, J., …Stickel, F. (2022). Genetic variation in TERT modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: Results from a genome-wide case-control study. Gut, https://doi.org/10.1136/gutjnl-2022-327196

Objective: Hepatocellular carcinoma (HCC) often develops in patients with alcohol-related cirrhosis at an annual risk of up to 2.5%. Some host genetic risk factors have been identified but do not account for the majority of the variance in occurrence... Read More about Genetic variation in TERT modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: Results from a genome-wide case-control study.

Performance of routine risk scores for predicting cirrhosis-related morbidity in the community (2022)
Journal Article
Innes, H., Morling, J. R., Buch, S., Hamill, V., Stickel, F., & Guha, I. N. (2022). Performance of routine risk scores for predicting cirrhosis-related morbidity in the community. Journal of Hepatology, 77(2), 365-376. https://doi.org/10.1016/j.jhep.2022.02.022

BACKGROUND & AIMS: Models predicting an individual’s ten-year risk of cirrhosis complications have not been developed for a community setting. Our objectives were to assess the performance of existing risk scores – both with and without genetic data... Read More about Performance of routine risk scores for predicting cirrhosis-related morbidity in the community.

Transient Elastography in Community Alcohol Services: Can It Detect Significant Liver Disease and Impact Drinking Behaviour? (2022)
Journal Article
Subhani, M., Harman, D. J., Scott, R. A., Bennett, L., Wilkes, E. A., James, M. W., …Guha, I. N. (2022). Transient Elastography in Community Alcohol Services: Can It Detect Significant Liver Disease and Impact Drinking Behaviour?. Biomedicines, 10(2), Article 477. https://doi.org/10.3390/biomedicines10020477

Introduction: Alcohol is the leading cause of cirrhosis in Western populations. The early identification of high-risk drinkers followed by intervention is an effective way to reduce harm. We aim to assess the feasibility of integrating transient elas... Read More about Transient Elastography in Community Alcohol Services: Can It Detect Significant Liver Disease and Impact Drinking Behaviour?.

Comprehensive Comparative Analysis of Standard Validated, Genetic, and Novel Biomarkers to Enhance Prognostic Risk-Stratification in Patients With Hepatitis C Virus Cirrhosis (2022)
Journal Article
Innes, H., Walker, A. J., Benselin, J., Grove, J. I., Pedergnana, V., Azim Ansari, M., …Guha, I. N. (2022). Comprehensive Comparative Analysis of Standard Validated, Genetic, and Novel Biomarkers to Enhance Prognostic Risk-Stratification in Patients With Hepatitis C Virus Cirrhosis. Clinical and Translational Gastroenterology, 13(3), Article e00462. https://doi.org/10.14309/ctg.0000000000000462

INTRODUCTION: Risk-stratifying patients with hepatitis C virus (HCV) cirrhosis according to medium-term prognosis will inform clinical decision-making. It is unclear which biomarkers/models are optimal for this purpose. We quantified the discriminati... Read More about Comprehensive Comparative Analysis of Standard Validated, Genetic, and Novel Biomarkers to Enhance Prognostic Risk-Stratification in Patients With Hepatitis C Virus Cirrhosis.

Health Technology Adoption in Liver Disease: Innovative Use of Data Science Solutions for Early Disease Detection (2022)
Journal Article
Bennett, L., Purssell, H., Street, O., Piper Hanley, K., Morling, J. R., Hanley, N. A., …ID-LIVER Consortium. (2022). Health Technology Adoption in Liver Disease: Innovative Use of Data Science Solutions for Early Disease Detection. Frontiers in Digital Health, 4, Article 737729. https://doi.org/10.3389/fdgth.2022.737729

Chronic liver disease (CLD) is an ignored epidemic. Premature mortality is considerable and in the United Kingdom (UK) liver disease is in the top three for inequitable healthcare alongside heart and respiratory disease. Fifty percentage of patients... Read More about Health Technology Adoption in Liver Disease: Innovative Use of Data Science Solutions for Early Disease Detection.

The rs429358 Locus in Apolipoprotein E Is Associated With Hepatocellular Carcinoma in Patients With Cirrhosis (2021)
Journal Article
Innes, H., Nischalke, H. D., Guha, I. N., Weiss, K. H., Irving, W., Gotthardt, D., …Buch, S. (2022). The rs429358 Locus in Apolipoprotein E Is Associated With Hepatocellular Carcinoma in Patients With Cirrhosis. Hepatology Communications, 6(5), 1213-1226. https://doi.org/10.1002/hep4.1886

The host genetic background for hepatocellular carcinoma (HCC) is incompletely understood. We aimed to determine if four germline genetic polymorphisms, rs429358 in apolipoprotein E (APOE), rs2642438 in mitochondrial amidoxime reducing component 1 (M... Read More about The rs429358 Locus in Apolipoprotein E Is Associated With Hepatocellular Carcinoma in Patients With Cirrhosis.

Population screening for liver fibrosis: Toward early diagnosis and intervention for chronic liver diseases (2021)
Journal Article
Ginès, P., Castera, L., Lammert, F., Graupera, I., Serra‐Burriel, M., Allen, A. M., …Krag, A. (2022). Population screening for liver fibrosis: Toward early diagnosis and intervention for chronic liver diseases. Hepatology, 75(1), 219-228. https://doi.org/10.1002/hep.32163

Cirrhosis, highly prevalent worldwide, develops after years of hepatic inflammation triggering progressive fibrosis. Currently, the main etiologies of cirrhosis are non-alcoholic fatty liver disease and alcohol-related liver disease, although chronic... Read More about Population screening for liver fibrosis: Toward early diagnosis and intervention for chronic liver diseases.

Performance of models to predict hepatocellular carcinoma risk among UK patients with cirrhosis and cured HCV infection (2021)
Journal Article
Innes, H., Jepsen, P., McDonald, S., Dillon, J., Hamill, V., Yeung, A., …Guha, I. N. (2021). Performance of models to predict hepatocellular carcinoma risk among UK patients with cirrhosis and cured HCV infection. JHEP Reports, 3(6), Article 100384. https://doi.org/10.1016/j.jhepr.2021.100384

Background & Aims: Hepatocellular carcinoma (HCC) prediction models can inform clinical decisions about HCC screening provided their predictions are robust. We conducted an external validation of 6 HCC prediction models for UK patients with cirrhosis... Read More about Performance of models to predict hepatocellular carcinoma risk among UK patients with cirrhosis and cured HCV infection.

Characterizing the risk interplay between alcohol intake and body mass index on cirrhosis morbidity (2021)
Journal Article
Innes, H., Crooks, C. J., Aspinall, E., Card, T. R., Hamill, V., Dillon, J., …Morling, J. R. (2022). Characterizing the risk interplay between alcohol intake and body mass index on cirrhosis morbidity. Hepatology, 75(2), 369-378. https://doi.org/10.1002/hep.32123

Background and Aims: It is thought that alcohol intake and body mass index (BMI) interact supra-additively to modulate the risk of cirrhosis, but evidence for this phenomenon is limited. We investigated the interrelationship between alcohol and BMI o... Read More about Characterizing the risk interplay between alcohol intake and body mass index on cirrhosis morbidity.

Reliable computational quantification of liver fibrosis is compromised by inherent staining variation (2021)
Journal Article
Astbury, S., Grove, J. I., Dorward, D. A., Guha, I. N., Fallowfield, J. A., & Kendall, T. J. (2021). Reliable computational quantification of liver fibrosis is compromised by inherent staining variation. Journal of Pathology: Clinical Research, 7(5), 471-481. https://doi.org/10.1002/cjp2.227

Biopsy remains the gold standard measure for staging liver disease, both to inform prognosis and to assess the response to a given treatment. Semiquantitative scores such as the Ishak fibrosis score are used for evaluation. These scores are utilised... Read More about Reliable computational quantification of liver fibrosis is compromised by inherent staining variation.

Addition of hyaluronic acid to the FIB-4 liver fibrosis score improves prediction of incident cirrhosis and hepatocellular carcinoma in Type 2 diabetes: The Edinburgh Type 2 Diabetes Study (2021)
Journal Article
Grecian, S. M., McLachlan, S., Fallowfield, J. A., Hayes, P. C., Guha, I. N., Morling, J. R., …Strachan, M. W. (2021). Addition of hyaluronic acid to the FIB-4 liver fibrosis score improves prediction of incident cirrhosis and hepatocellular carcinoma in Type 2 diabetes: The Edinburgh Type 2 Diabetes Study. Obesity Science and Practice, 7(5), 497-508. https://doi.org/10.1002/osp4.484

Background: Type 2 diabetes is associated with increased risk of progression to cirrhosis and hepatocellular carcinoma (HCC) in people with chronic liver diseases, particularly non-alcoholic fatty liver disease (NAFLD). However, the absolute risk of... Read More about Addition of hyaluronic acid to the FIB-4 liver fibrosis score improves prediction of incident cirrhosis and hepatocellular carcinoma in Type 2 diabetes: The Edinburgh Type 2 Diabetes Study.

Acceptability of chronic liver disease screening in a UK primary care setting: a qualitative evaluation (2020)
Journal Article
Knight, H., Harman, D., Morling, J. R., Aithal, G., Card, T., Guha, I. N., & Bains, M. (2020). Acceptability of chronic liver disease screening in a UK primary care setting: a qualitative evaluation. BMJ Open, 10(11), https://doi.org/10.1136/bmjopen-2020-041574

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. OBJECTIVES: The increasing incidence of chronic liver disease (CLD) in the UK may be attributed to a rise in... Read More about Acceptability of chronic liver disease screening in a UK primary care setting: a qualitative evaluation.

In severe alcoholic hepatitis, serum cytokeratin-18 fragments are diagnostic, prognostic and theragnostic biomarkers (2020)
Journal Article
Atkinson, S. R., Grove, J. I., Liebig, S., Astbury, S., Vergis, N., Goldin, R., …Aithal, G. P. (2020). In severe alcoholic hepatitis, serum cytokeratin-18 fragments are diagnostic, prognostic and theragnostic biomarkers. American Journal of Gastroenterology, 115(11), 1857-1868. https://doi.org/10.14309/ajg.0000000000000912

INTRODUCTION: Up to 40% of patients with severe alcoholic hepatitis (AH) die within 6 months of presentation, making prompt diagnosis and appropriate treatment essential. We determined the associations between serum keratin-18 (K18) and histologi... Read More about In severe alcoholic hepatitis, serum cytokeratin-18 fragments are diagnostic, prognostic and theragnostic biomarkers.

Late diagnosis of chronic liver disease in a community cohort (UK biobank): determinants and impact on subsequent survival (2020)
Journal Article
Innes, H., Morling, J., Aspinall, E. A., Goldberg, D. J., Hutchinson, S. J., & Guha, I. N. (2020). Late diagnosis of chronic liver disease in a community cohort (UK biobank): determinants and impact on subsequent survival. Public Health, 187, 165-171. https://doi.org/10.1016/j.puhe.2020.07.017

BACKGROUND: Chronic liver disease (CLD) is frequently diagnosed at a late stage when prognosis is poor. We aimed to determine the patient factors associated with a late CLD diagnosis and its subsequent impact on survival in order to support early dia... Read More about Late diagnosis of chronic liver disease in a community cohort (UK biobank): determinants and impact on subsequent survival.

Health related quality of life in individuals at high risk of chronic liver disease: Impact of a community diagnostic pathway (2020)
Journal Article
Tildesley, Z., Chalmers, J., Harris, R., West, J., Guha, I. N., & Morling, J. R. (2020). Health related quality of life in individuals at high risk of chronic liver disease: Impact of a community diagnostic pathway. Public Health In Practice, 1, https://doi.org/10.1016/j.puhip.2020.100033

Objectives: There is a lack of understanding of health related quality of life (HRQoL) in chronic liver disease (CLD). With the rising prevalence of alcohol and obesity driven CLD, and the increasing ability to screen for fibrosis, it is important to... Read More about Health related quality of life in individuals at high risk of chronic liver disease: Impact of a community diagnostic pathway.

Non?invasive risk scores do not reliably identify future cirrhosis or hepatocellular carcinoma in Type 2 diabetes: The Edinburgh type 2 diabetes study (2020)
Journal Article
Grecian, S. M., McLachlan, S., Fallowfield, J. A., Kearns, P. K., Hayes, P. C., Guha, I. N., …Strachan, M. W. (2020). Non‐invasive risk scores do not reliably identify future cirrhosis or hepatocellular carcinoma in Type 2 diabetes: The Edinburgh type 2 diabetes study. Liver International, 40(9), 2252-2262. https://doi.org/10.1111/liv.14590

Background The incidence of cirrhosis and hepatocellular carcinoma (HCC) is increased in Type 2 diabetes, primarily secondary to non‐alcoholic fatty liver disease (NAFLD). European guidelines recommend screening for NAFLD in Type 2 diabetes. America... Read More about Non?invasive risk scores do not reliably identify future cirrhosis or hepatocellular carcinoma in Type 2 diabetes: The Edinburgh type 2 diabetes study.

aMAP risk score predicts hepatocellular carcinoma development in patients with chronic hepatitis (2020)
Journal Article
Fan, R., Papatheodoridis, G., Sun, J., Innes, H., Toyoda, H., Xie, Q., …Hou, J. (2020). aMAP risk score predicts hepatocellular carcinoma development in patients with chronic hepatitis. Journal of Hepatology, 73(6), 1368-1378. https://doi.org/10.1016/j.jhep.2020.07.025

© 2020 European Association for the Study of the Liver Background & Aims: Hepatocellular carcinoma (HCC) is the leading cause of death in patients with chronic hepatitis. In this international collaboration, we sought to develop a global universal HC... Read More about aMAP risk score predicts hepatocellular carcinoma development in patients with chronic hepatitis.

Inter- and Intra-individual Variation, and Limited Prognostic Utility, of Serum Alkaline Phosphatase in a Trial of Patients With Primary Sclerosing Cholangitis (2020)
Journal Article
Trivedi, P. J., Muir, A. J., Levy, C., Bowlus, C. L., Manns, M. P., Lu, X., …Hirschfield, G. M. (2021). Inter- and Intra-individual Variation, and Limited Prognostic Utility, of Serum Alkaline Phosphatase in a Trial of Patients With Primary Sclerosing Cholangitis. Clinical Gastroenterology and Hepatology, 19(6), 1248-1257. https://doi.org/10.1016/j.cgh.2020.07.032

Background & Aims Serum alkaline phosphatase (ALP) and the enhanced liver fibrosis (ELF) score are used as endpoints in trials of patients with primary sclerosing cholangitis (PSC). We aimed to quantify inter- and intra-individual variation in level... Read More about Inter- and Intra-individual Variation, and Limited Prognostic Utility, of Serum Alkaline Phosphatase in a Trial of Patients With Primary Sclerosing Cholangitis.

Non-invasive risk scores do not reliably identify future cirrhosis or hepatocellular carcinoma in Type 2 diabetes: The Edinburgh Type 2 Diabetes Study (2020)
Journal Article
Grecian, S. M., McLachlan, S., Fallowfield, J. A., Kearns, P. K., Hayes, P. C., Guha, N. I., …Strachan, M. W. (2020). Non-invasive risk scores do not reliably identify future cirrhosis or hepatocellular carcinoma in Type 2 diabetes: The Edinburgh Type 2 Diabetes Study. Liver International, 40(9), 2252-2262. https://doi.org/10.1111/liv.14590

Background The incidence of cirrhosis and hepatocellular carcinoma (HCC) is increased in Type 2 diabetes, primarily secondary to non‐alcoholic fatty liver disease (NAFLD). European guidelines recommend screening for NAFLD in Type 2 diabetes. America... Read More about Non-invasive risk scores do not reliably identify future cirrhosis or hepatocellular carcinoma in Type 2 diabetes: The Edinburgh Type 2 Diabetes Study.

Genome-wide Association Study for Alcohol-related Cirrhosis Identifies Risk Loci in MARC1 and HNRNPUL1. (2020)
Journal Article
Innes, H., Buch, S., Hutchinson, S., Guha, I. N., Morling, J. R., Barnes, E., …Stickel, F. (2020). Genome-wide Association Study for Alcohol-related Cirrhosis Identifies Risk Loci in MARC1 and HNRNPUL1. Gastroenterology, 159(4), 1276-1289.e7. https://doi.org/10.1053/j.gastro.2020.06.014

Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved. BACKGROUND & AIMS: Little is known about genetic factors that affect development of alcohol-related cirrhosis. We performed a genome-wide association study (GWAS) of samp... Read More about Genome-wide Association Study for Alcohol-related Cirrhosis Identifies Risk Loci in MARC1 and HNRNPUL1..

FibroScan-AST (FAST) score for the non-invasive identification of patients with non-alcoholic steatohepatitis with significant activity and fibrosis: a prospective derivation and global validation study (2020)
Journal Article
Newsome, P. N., Sasso, M., Deeks, J. J., Paredes, A., Boursier, J., Chan, W., …Harrison, S. A. (2020). FibroScan-AST (FAST) score for the non-invasive identification of patients with non-alcoholic steatohepatitis with significant activity and fibrosis: a prospective derivation and global validation study. The Lancet Gastroenterology & Hepatology, 5(4), 362-373. https://doi.org/10.1016/S2468-1253%2819%2930383-8

Background The burden of non-alcoholic fatty liver disease (NAFLD) is increasing globally, and a major priority is to identify patients with non-alcoholic steatohepatitis (NASH) who are at greater risk of progression to cirrhosis, and who will be ca... Read More about FibroScan-AST (FAST) score for the non-invasive identification of patients with non-alcoholic steatohepatitis with significant activity and fibrosis: a prospective derivation and global validation study.

Obesity is the most common risk factor for chronic liver disease: Results from risk stratification pathway using transient elastography (2019)
Journal Article
Harris, R., Card, T. R., Delahooke, T., Aithal, G. P., & Guha, I. N. (2019). Obesity is the most common risk factor for chronic liver disease: Results from risk stratification pathway using transient elastography. American Journal of Gastroenterology, 114(11), 1744-1752. https://doi.org/10.14309/ajg.0000000000000357

Introduction Obesity has been associated with liver fibrosis yet guidelines do not emphasise it as an independent risk factor in which to have a high index of suspicion of advanced disease. We aimed to elucidate the effect of a raised body mass inde... Read More about Obesity is the most common risk factor for chronic liver disease: Results from risk stratification pathway using transient elastography.

Transient elastography for screening of liver fibrosis: cost-effectiveness analysis from six prospective cohorts in Europe and Asia (2019)
Journal Article
Serra-Burriel, M., Graupera, I., Torán, P., Thiele, M., Roulot, D., Wai-Sun Wong, V., …Lammert, F. (2019). Transient elastography for screening of liver fibrosis: cost-effectiveness analysis from six prospective cohorts in Europe and Asia. Journal of Hepatology, 71(6), 1141-1151. https://doi.org/10.1016/j.jhep.2019.08.019

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) pose an important challenge to current clinical healthcare pathways due to a large number of at-risk patients. Therefore, we aimed to explore the cost-effec... Read More about Transient elastography for screening of liver fibrosis: cost-effectiveness analysis from six prospective cohorts in Europe and Asia.

Development and implementation of a commissioned pathway for the identification and stratification of liver disease in the community (2019)
Journal Article
Chalmers, J., Wilkes, E., Harris, R., Kent, L., Kinra, S., Aithal, G., …Guha, I. N. (2020). Development and implementation of a commissioned pathway for the identification and stratification of liver disease in the community. Frontline Gastroenterology, 11(2), 86-92. https://doi.org/10.1136/flgastro-2019-101177

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ. Objective: To describe the development of the Nottingham liver disease stratification pathway, present a 12-month evaluation of uptake and stratification results... Read More about Development and implementation of a commissioned pathway for the identification and stratification of liver disease in the community.

Validation of a model for identification of patients with compensated cirrhosis at high risk of decompensation (2019)
Journal Article
Guha, I., Harris, R., Berhane, S., Dillon, A., Coffey, L., James, M., …Johnson, P. (2019). Validation of a model for identification of patients with compensated cirrhosis at high risk of decompensation. Clinical Gastroenterology and Hepatology, 17(11), 2330-2338.e1. https://doi.org/10.1016/j.cgh.2019.01.042

Background & Aims: It is important to rapidly identify patients with advanced liver disease. Routine tests to assess liver function and fibrosis provide data that can be used to determine patients’ prognoses. We tested the validated the ability of co... Read More about Validation of a model for identification of patients with compensated cirrhosis at high risk of decompensation.

Accuracy of FibroScan Controlled Attenuation Parameter and Liver Stiffness Measurement in Assessing Steatosis and Fibrosis in Patients With Nonalcoholic Fatty Liver Disease (2019)
Journal Article
Tsochatzis, E., Eddowes, P. J., Sasso, M., Allison, M., Tsochatzis, E., Anstee, Q. M., …Newsome, P. N. (2019). Accuracy of FibroScan Controlled Attenuation Parameter and Liver Stiffness Measurement in Assessing Steatosis and Fibrosis in Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology, 156(6), 1717-1730. https://doi.org/10.1053/j.gastro.2019.01.042

Background & Aims: We estimated the accuracy of FibroScan vibration-controlled transient elastography controlled attenuation parameter (CAP) and liver stiffness measurements (LSMs) in assessing steatosis and fibrosis in patients with suspected NAFLD.... Read More about Accuracy of FibroScan Controlled Attenuation Parameter and Liver Stiffness Measurement in Assessing Steatosis and Fibrosis in Patients With Nonalcoholic Fatty Liver Disease.

The effects of terlipressin and direct portacaval shunting on liver hemodynamics following 80% hepatectomy in the pig (2019)
Journal Article
Hammond, J. S., Godtliebsen, F., Steigen, S., Guha, I. N., Wyatt, J., Revhaug, A., …Mortensen, K. E. (2019). The effects of terlipressin and direct portacaval shunting on liver hemodynamics following 80% hepatectomy in the pig. Clinical Science, 133(1), 153-166. https://doi.org/10.1042/CS20180858

Liver failure is the major cause of death following liver resection. Post-resection portal venous pressure (PVP) predicts liver failure, is implicated in its pathogenesis and when PVP is reduced, rates of liver dysfunction decrease. The aim of this s... Read More about The effects of terlipressin and direct portacaval shunting on liver hemodynamics following 80% hepatectomy in the pig.

SOX9 regulated matrix proteins are increased in patients serum and correlate with severity of liver fibrosis (2018)
Journal Article
Athwal, V. S., Pritchett, J., Martin, K., Llewellyn, J., Scott, J., Harvey, E., …Hanley, K. P. (2018). SOX9 regulated matrix proteins are increased in patients serum and correlate with severity of liver fibrosis. Scientific Reports, 8(1), Article 17905. https://doi.org/10.1038/s41598-018-36037-4

Extracellular matrix (ECM) deposition and resultant scar play a major role in the pathogenesis and progression of liver fibrosis. Identifying core regulators of ECM deposition may lead to urgently needed diagnostic and therapetic strategies for the d... Read More about SOX9 regulated matrix proteins are increased in patients serum and correlate with severity of liver fibrosis.

Short-term changes observed in multi-parametric liver MRI following therapy with direct acting antivirals in chronic hepatitis C virus patients (2018)
Journal Article
Bradley, C., Scott, R., Cox, E., Palaniyappan, N., Thompson, B., Ryder, D., …Francis, S. (2019). Short-term changes observed in multi-parametric liver MRI following therapy with direct acting antivirals in chronic hepatitis C virus patients. European Radiology, 29(6), 3100–3107. https://doi.org/10.1007/s00330-018-5788-1

Methods: We applied multiparametric MRI to assess changes in liver composition, perfusion and blood flow in 17 patients before DAA therapy and after treatment completion (within 12 weeks of last DAA tablet swallowed). Results: We observed changes in... Read More about Short-term changes observed in multi-parametric liver MRI following therapy with direct acting antivirals in chronic hepatitis C virus patients.

Time to endoscopy for acute upper gastrointestinal bleeding: results from a prospective multicentre trainee-led audit (2018)
Journal Article
Siau, K., Hodson, J., Ingram, R., Baxter, A., Widlak, M. M., Sharratt, C., …Major, G. (2018). Time to endoscopy for acute upper gastrointestinal bleeding: results from a prospective multicentre trainee-led audit. United European Gastroenterology Journal, https://doi.org/10.1177/2050640618811491

Background: Endoscopy within 24 hours of admission (early endoscopy) is a quality standard in acute upper gastrointestinal bleeding (AUGIB). We aimed to audit time to endoscopy outcomes and identify factors affecting delayed endoscopy (>24h of admiss... Read More about Time to endoscopy for acute upper gastrointestinal bleeding: results from a prospective multicentre trainee-led audit.

MRI assessment of altered dynamic changes in liver haemodynamics following a meal challenge in compensated cirrhosis (2018)
Journal Article
Cox, E. F., Palaniyappan, N., Aithal, G. P., Guha, I. N., & Francis, S. T. (2018). MRI assessment of altered dynamic changes in liver haemodynamics following a meal challenge in compensated cirrhosis. European Radiology Experimental, 2, Article 26. https://doi.org/10.1186/s41747-018-0056-3

Background: To use magnetic resonance imaging (MRI) to dynamically assess postprandial changes in hepatic and collateral blood flow, liver perfusion and oxygenation in healthy participants and patients with liver disease with compensated cirrhosis (C... Read More about MRI assessment of altered dynamic changes in liver haemodynamics following a meal challenge in compensated cirrhosis.

Using MRI to study the alterations in liver blood flow, perfusion and oxygenation in response to physiological stress challenges: meal, hyperoxia and hypercapnia (2018)
Journal Article
Cox, E. F., Palaniyappan, N., Aithal, G. P., Guha, I. N., & Francis, S. T. (in press). Using MRI to study the alterations in liver blood flow, perfusion and oxygenation in response to physiological stress challenges: meal, hyperoxia and hypercapnia. Journal of Magnetic Resonance Imaging, ISSN 1053-1807

Background: Non-invasive assessment of dynamic changes in liver blood flow, perfusion and oxygenation using magnetic resonance imaging (MRI) may allow detection of subtle haemodynamic alterations in cirrhosis. Purpose: To assess the feasibility of... Read More about Using MRI to study the alterations in liver blood flow, perfusion and oxygenation in response to physiological stress challenges: meal, hyperoxia and hypercapnia.

ADAPT: an algorithm incorporating PRO-C3 accurately identifies patients with NAFLD and advanced fibrosis (2018)
Journal Article
Daniels, S. J., Leeming, D. J., Eslam, M., Hashem, A. M., Nielsen, M. J., Krag, A., …George, J. (2019). ADAPT: an algorithm incorporating PRO-C3 accurately identifies patients with NAFLD and advanced fibrosis. Hepatology, 69(3), 1075-1086. https://doi.org/10.1002/hep.30163

Given the high global prevalence of nonalcoholic fatty liver disease (NAFLD), the need for relevant noninvasive biomarkers and algorithms to accurately stage disease severity is a critical unmet medical need. Identifying those with advanced fibrosis... Read More about ADAPT: an algorithm incorporating PRO-C3 accurately identifies patients with NAFLD and advanced fibrosis.

Multi-organ assessment of compensated cirrhosis patients using quantitative magnetic resonance imaging (2018)
Journal Article
Bradley, C. R., Cox, E. F., Scott, R. A., James, M. W., Kaye, P., Aithal, G. P., …Guha, I. N. (2018). Multi-organ assessment of compensated cirrhosis patients using quantitative magnetic resonance imaging. Journal of Hepatology, 69(5), 1015-1024. https://doi.org/10.1016/j.jhep.2018.05.037

© 2018 European Association for the Study of the Liver Background & Aims: Advancing liver disease results in deleterious changes in a number of critical organs. The ability to measure structure, blood flow and tissue perfusion within multiple organs... Read More about Multi-organ assessment of compensated cirrhosis patients using quantitative magnetic resonance imaging.

The XL probe: a luxury or a necessity? risk stratification in an obese community cohort using transient elastography (2018)
Journal Article
Harris, R., Card, T. R., Delahooke, T., Aithal, G. P., & Guha, I. N. (2018). The XL probe: a luxury or a necessity? risk stratification in an obese community cohort using transient elastography. United European Gastroenterology Journal, 6(9), 1372-1379. https://doi.org/10.1177/2050640618772944

Background: Transient elastography is a non-invasive tool which can stratify patients at risk of chronic liver disease. However, a raised body mass index has been independently associated with a failed or unreliable examination. Objective: The pur... Read More about The XL probe: a luxury or a necessity? risk stratification in an obese community cohort using transient elastography.

Analysis of genotyping for predicting liver injury marker, Procollagen III in persons at risk of non-alcoholic fatty liver disease (2018)
Journal Article
Grove, J. I., Thiagarajan, P., Astbury, S., Harris, R., Delahooke, T., Guha, I. N., & Aithal, G. P. (2018). Analysis of genotyping for predicting liver injury marker, Procollagen III in persons at risk of non-alcoholic fatty liver disease. Liver International, 38(10), 1832-1838. https://doi.org/10.1111/liv.13733

Background & Aims Chronic liver disease presents a major global public health challenge. Stratification of asymptomatic, at-risk patients in primary care using non-invasive methods has the potential to address this by identifying those likely to pr... Read More about Analysis of genotyping for predicting liver injury marker, Procollagen III in persons at risk of non-alcoholic fatty liver disease.

Hepatic elastin content is predictive of adverse outcome in advanced fibrotic liver disease (2018)
Journal Article
Kendall, T., Dolman, G., Duff, C., Paish, E. C., Zaitoun, A., Irving, W. L., …Guha, I. N. (2018). Hepatic elastin content is predictive of adverse outcome in advanced fibrotic liver disease. Histopathology, 73(1), 90-100. https://doi.org/10.1111/his.13499

Aims. Needle biopsy remains essential for diagnosis in assessment of liver disease, although there remains associated risk. Examination is largely limited to subjective evaluation and biopsies are not exploited to provide personalised prognostic info... Read More about Hepatic elastin content is predictive of adverse outcome in advanced fibrotic liver disease.

Obesity and type 2 diabetes are important risk factors underlying previously undiagnosed cirrhosis in general practice: a cross-sectional study using Transient Elastography (2017)
Journal Article
Harman, D. J., Ryder, S. D., James, M. W., Wilkes, E. A., Card, T. R., Aithal, G. P., & Guha, I. N. (2018). Obesity and type 2 diabetes are important risk factors underlying previously undiagnosed cirrhosis in general practice: a cross-sectional study using Transient Elastography. Alimentary Pharmacology and Therapeutics, 47(4), 504-515. https://doi.org/10.1111/apt.14463

Background: Rising cirrhosis incidence and mortality in the United Kingdom has been attributed predominantly to excess alcohol consumption. However, metabolic risk factors such as type 2 diabetes and obesity may also be important. Aim: To screen at-... Read More about Obesity and type 2 diabetes are important risk factors underlying previously undiagnosed cirrhosis in general practice: a cross-sectional study using Transient Elastography.

SOX9 predicts progression towards cirrhosis in patients while its loss protects against liver fibrosis (2017)
Journal Article
Athwal, V. S., Pritchett, J., Llewellyn, J., Martin, K., Camacho, E., Raza, S. M., …Hanley, K. P. (in press). SOX9 predicts progression towards cirrhosis in patients while its loss protects against liver fibrosis. EMBO Molecular Medicine, 9(12), https://doi.org/10.15252/emmm.201707860

Fibrosis and organ failure is a common endpoint for many chronic liver diseases. Much is known about the upstream inflammatory mechanisms provoking fibrosis and downstream potential for tissue remodeling. However, less is known about the transcriptio... Read More about SOX9 predicts progression towards cirrhosis in patients while its loss protects against liver fibrosis.

Economic evaluation of a community-based diagnostic pathway to stratify adults for non-alcoholic fatty liver disease: a Markov model informed by a feasibility study (2017)
Journal Article
Tanajewski, L., Harris, R., Harman, D. J., Aithal, G. P., Card, T. R., Gkountouras, G., …Elliott, R. (in press). Economic evaluation of a community-based diagnostic pathway to stratify adults for non-alcoholic fatty liver disease: a Markov model informed by a feasibility study. BMJ Open, 7(6), https://doi.org/10.1136/bmjopen-2016-015659

Objectives: To assess the long-term cost-effectiveness of a risk stratification pathway, compared with standard care, for detecting non-alcoholic fatty liver disease (NAFLD) in primary care. Setting: Primary care general practices in England. P... Read More about Economic evaluation of a community-based diagnostic pathway to stratify adults for non-alcoholic fatty liver disease: a Markov model informed by a feasibility study.

Prevalence of clinically significant liver disease within the general population, as defined by non-invasive markers of liver fibrosis: a systematic review (2017)
Journal Article
Harris, R., Harman, D. J., Card, T. R., Aithal, G. P., & Guha, I. N. (2017). Prevalence of clinically significant liver disease within the general population, as defined by non-invasive markers of liver fibrosis: a systematic review. The Lancet Gastroenterology & Hepatology, 2(4), 288-297. https://doi.org/10.1016/S2468-1253%2816%2930205-9

As of 2016, there is no evidence-based pathway to stratify the risk of chronic liver disease in a general population setting. Non-invasive tests of liver fibrosis might provide a mechanism for earlier diagnosis. These tests have been extensively vali... Read More about Prevalence of clinically significant liver disease within the general population, as defined by non-invasive markers of liver fibrosis: a systematic review.

Non-invasive assessment of portal hypertension using quantitative magnetic resonance imaging (2016)
Journal Article
Palaniyappan, N., Cox, E., Bradley, C., Scott, R., Austin, A., O’Neill, R., …Aithal, G. P. (2016). Non-invasive assessment of portal hypertension using quantitative magnetic resonance imaging. Journal of Hepatology, 65(6), 1131-1139. https://doi.org/10.1016/j.jhep.2016.07.021

Background & Aims Hepatic venous pressure gradient (HVPG) measurement is currently the only validated technique to accurately evaluate changes in portal pressure. In this study, we evaluate the use of non-contrast quantitative magnetic resonance i... Read More about Non-invasive assessment of portal hypertension using quantitative magnetic resonance imaging.

Direct targeting of risk factors significantly increases the detection of liver cirrhosis in primary care: a cross-sectional diagnostic study utilising transient elastography (2015)
Journal Article
Harman, D. J., Ryder, S. D., James, M. W., Jelpke, M., Ottey, D. S., Wilkes, E. A., …Guha, I. N. (2015). Direct targeting of risk factors significantly increases the detection of liver cirrhosis in primary care: a cross-sectional diagnostic study utilising transient elastography. BMJ Open, 5(4), Article e007516. https://doi.org/10.1136/bmjopen-2014-007516

OBJECTIVES: To assess the feasibility of a novel diagnostic algorithm targeting patients with risk factors for chronic liver disease in a community setting. DESIGN: Prospective cross-sectional study. SETTING: Two primary care practices (adult... Read More about Direct targeting of risk factors significantly increases the detection of liver cirrhosis in primary care: a cross-sectional diagnostic study utilising transient elastography.

A study of T1 relaxation time as a measure of liver fibrosis and the influence of confounding histological factors (2015)
Journal Article
Hoad, C. L., Palaniyappan, N., Kaye, P., Chernova, Y., James, M. W., Costigan, C., …Aithal, G. P. (2015). A study of T1 relaxation time as a measure of liver fibrosis and the influence of confounding histological factors. NMR in Biomedicine, 28(6), 706-714. https://doi.org/10.1002/nbm.3299

Liver biopsy is the standard test for the assessment of fibrosis in liver tissue of patients with chronic liver disease. Recent studies have used a non‐invasive measure of T1 relaxation time to estimate the degree of fibrosis in a single slice of the... Read More about A study of T1 relaxation time as a measure of liver fibrosis and the influence of confounding histological factors.

?-Glutamyltransferase, but not markers of hepatic fibrosis, is associated with cardiovascular disease in older people with type 2 diabetes mellitus: the Edinburgh Type 2 Diabetes Study (2015)
Journal Article
Morling, J. R., Fallowfield, J. A., Williamson, R. M., Robertson, C. M., Glancy, S., Guha, I. N., …Price, J. F. (2015). γ-Glutamyltransferase, but not markers of hepatic fibrosis, is associated with cardiovascular disease in older people with type 2 diabetes mellitus: the Edinburgh Type 2 Diabetes Study. Diabetologia, 58(7), 1484-1493. https://doi.org/10.1007/s00125-015-3575-y

© 2015, The Author(s). Aims/hypothesis: We examined the association of prevalent and incident cardiovascular disease (CVD) with chronic liver disease in a cohort of community-based people with type 2 diabetes, in order to clarify the relationship bet... Read More about ?-Glutamyltransferase, but not markers of hepatic fibrosis, is associated with cardiovascular disease in older people with type 2 diabetes mellitus: the Edinburgh Type 2 Diabetes Study.

Multiplex protein analysis to determine fibrosis stage and progression in patients with chronic hepatitis C. (2014)
Journal Article
Patel, K., Remlinger, K. S., Walker, T. G., Leitner, P., Lucas, J. E., Gardner, S. D., …Guha, I. N. (2014). Multiplex protein analysis to determine fibrosis stage and progression in patients with chronic hepatitis C. Clinical Gastroenterology and Hepatology, 12(12), 2113-2120.e3. https://doi.org/10.1016/j.cgh.2014.04.037

Background & Aims: Noninvasive tests cannot differentiate between adjacent stages of fibrosis, which limits assessment of disease progression and regression during therapy. We investigated whether levels of cytokines and extracellular matrix proteins... Read More about Multiplex protein analysis to determine fibrosis stage and progression in patients with chronic hepatitis C..

Using non-invasive biomarkers to identify hepatic fibrosis in people with type 2 diabetes mellitus: The Edinburgh type 2 diabetes study (2013)
Journal Article
Morling, J. R., Fallowfield, J. A., Guha, I. N., Nee, L. D., Glancy, S., Williamson, R. M., …Price, J. F. (2014). Using non-invasive biomarkers to identify hepatic fibrosis in people with type 2 diabetes mellitus: The Edinburgh type 2 diabetes study. Journal of Hepatology, 60(2), 384-391. https://doi.org/10.1016/j.jhep.2013.10.017

Background & Aims It is difficult to determine the different stages of non-alcoholic fatty liver disease without the use of invasive liver biopsy. In this study we investigated five non-invasive biomarkers used previously to detect hepatic fibrosis... Read More about Using non-invasive biomarkers to identify hepatic fibrosis in people with type 2 diabetes mellitus: The Edinburgh type 2 diabetes study.