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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)
Preprint / 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.

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.

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.-H., …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.

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, 72(2), 381-391. 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.

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.