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1. Designing clinical trials to address alcohol use and alcohol-associated liver disease: an expert panel Consensus Statement

Author

Lee, Brian P., Witkiewitz, Katie, Mellinger, Jessica, Anania, Frank A., Bataller, Ramon, Cotter, Thomas G., Curtis, Brenda, Dasarathy, Srinivasan, DeMartini, Kelly S., Diamond, Ivan, Diazgranados, Nancy, DiMartini, Andrea F., Falk, Daniel E., Fernandez, Anne C., German, Margarita N., Kamath, Patrick S., Kidwell, Kelley M., Leggio, Lorenzo, Litten, Raye, Louvet, Alexandre, Lucey, Michael R., McCaul, Mary E., Sanyal, Arun J., Singal, Ashwani K., Sussman, Norman L., Terrault, Norah A., Thursz, Mark R., Verna, Elizabeth C., Radaeva, Svetlana, Nagy, Laura E., and Mitchell, Mack C.

Published
2024
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2. Phenogrouping heart failure with preserved or mildly reduced ejection fraction using electronic health record data

Author

Soltani, Fardad, Jenkins, David A., Kaura, Amit, Bradley, Joshua, Black, Nicholas, Farrant, John P., Williams, Simon G., Mulla, Abdulrahim, Glampson, Benjamin, Davies, Jim, Papadimitriou, Dimitri, Woods, Kerrie, Shah, Anoop D., Thursz, Mark R., Williams, Bryan, Asselbergs, Folkert W., Mayer, Erik K., Herbert, Christopher, Grant, Stuart, Curzen, Nick, Squire, Iain, Johnson, Thomas, O’Gallagher, Kevin, Shah, Ajay M., Perera, Divaka, Kharbanda, Rajesh, Patel, Riyaz S., Channon, Keith M., Lee, Richard, Peek, Niels, Mayet, Jamil, and Miller, Christopher A.

Published
2024
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4. Author Correction: Defective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis

Author

Argemi, Josepmaria, Latasa, Maria U., Atkinson, Stephen R., Blokhin, Ilya O., Massey, Veronica, Gue, Joel P., Cabezas, Joaquin, Lozano, Juan J., Van Booven, Derek, Bell, Aaron, Cao, Sheng, Vernetti, Lawrence A., Arab, Juan P., Ventura-Cots, Meritxell, Edmunds, Lia R., Fondevila, Constantino, Stärkel, Peter, Dubuquoy, Laurent, Louvet, Alexandre, Odena, Gemma, Gomez, Juan L., Aragon, Tomas, Altamirano, Jose, Caballeria, Juan, Jurczak, Michael J., Taylor, D. Lansing, Berasain, Carmen, Wahlestedt, Claes, Monga, Satdarshan P., Morgan, Marsha Y., Sancho-Bru, Pau, Mathurin, Philippe, Furuya, Shinji, Lackner, Carolin, Rusyn, Ivan, Shah, Vijay H., Thursz, Mark R., Mann, Jelena, Avila, Matias A., and Bataller, Ramon

Published
2023
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5. Multi-tissue profiling of oxylipins reveal a conserved up-regulation of epoxide:diol ratio that associates with white adipose tissue inflammation and liver steatosis in obesity

Author

Hateley, Charlotte, Olona, Antoni, Halliday, Laura, Edin, Matthew L., Ko, Jeong-Hun, Forlano, Roberta, Terra, Ximena, Lih, Fred B., Beltrán-Debón, Raúl, Manousou, Penelopi, Purkayastha, Sanjay, Moorthy, Krishna, Thursz, Mark R., Zhang, Guodong, Goldin, Robert D., Zeldin, Darryl C., Petretto, Enrico, and Behmoaras, Jacques

Published
2024
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6. Dysregulated anti-oxidant signalling and compromised mitochondrial integrity negatively influence regulatory T cell function and viability in liver disease

Author

Vaikunthanathan, Trishan, Landmann, Emmanuelle, Correa, Diana Marin, Romano, Marco, Trevelin, Silvia Cellone, Peng, Qi, Crespo, Elena, Corrado, Mauro, Lozano, Juan-José, Pearce, Erika L., Perpinan, Elena, Zoccarato, Anna, Siew, Leonard, Edwards-Hicks, Joy, Khan, Reenam, Luu, Nguyet-Thin, Thursz, Mark R., Newsome, Philip N., Martinez-Llordella, Marc, Shah, Naina, Lechler, Robert I., Shah, Ajay M., Sanchez-Fueyo, Alberto, Lombardi, Giovanna, and Safinia, Niloufar

Published
2023
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10. Derivation and validation of the BIMAST score for predicting the presence of fibrosis due to Metabolic dysfunction-associated steatotic liver disease among diabetic patients in the community.

Author

Forlano, Roberta, Stanic, Tijana, Jayawardana, Sahan, Mullish, Benjamin H., Yee, Michael, Mossialos, Elias, Goldin, Robert D., Petta, Salvatore, Tsochatzis, Emmanouil, Thursz, Mark R., and Manousou, Pinelopi

Subjects
TYPE 2 diabetes, QUALITY-adjusted life years, COST effectiveness, LIVER function tests, BODY mass index, ASPARTATE aminotransferase
Abstract

Background & aims: Current screening pathways, developed from tertiary care cohorts, underestimate the presence of Metabolic-dysfunction associated steatotic liver disease (MASLD) in patients with type 2 diabetes mellitus (T2DM) in the community. We developed, validated, and assessed cost-effectiveness of a new score for screening the presence of fibrosis due to MASLD in primary care. Methods: Consecutive T2DM patients underwent screening for liver diseases with transient elastography (TE). Based on predictors of significant/advanced fibrosis, we generated the BIMAST score (based on aspartate aminotransferase (AST) and body mass index (BMI)) and validated it internally and externally (Royal Free Hospital, London and Palermo Hospital). For cost-effectiveness analysis, 6 screening strategies were compared against standard of care: BIMAST score, ultrasound plus abnormal liver function tests, FIB-4, NAFLD fibrosis score, ELF and transient elastography (TE). A Markov model was built based on fibrosis status. Cost per quality-adjusted life year (QALY) gained and the incremental cost-effectiveness ratio (ICER) were estimated over a lifetime. Results: Among 300 patients enrolled, 64% (186) had MASLD and 10% (28) other causes of liver disease. In the whole population, patients with significant fibrosis, advanced fibrosis, and cirrhosis due to MASLD were 17% (50/287), 11% (31/287), and 3% (8/287), respectively. In primary care, BIMAST performed better than other non-invasive markers at predicting significant and advanced fibrosis. Moreover, BIMAST reduced false negatives from 54% (ELF) and 38% (FIB-4) to 10%. In both validation cohorts, BIMAST performance was as good as FIB-4. In the cost-utility analysis, ICER was £2,337.92/QALY for BIMAST. Conclusion: The BIMAST predicts the presence of significant fibrosis in the community, reduces false negatives and is cost-effective. The BIMAST score should be included in the holistic assessment of diabetic patients. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Association of troponin level and age with mortality in 250 000 patients : cohort study across five UK acute care centres

Author

Kaura, Amit, Panoulas, Vasileios, Glampson, Benjamin, Davies, Jim, Mulla, Abdulrahim, Woods, Kerrie, Omigie, Joe, Shah, Anoop D, Channon, Keith M, Weber, Jonathan N, Thursz, Mark R, Elliott, Paul, Hemingway, Harry, Williams, Bryan, Asselbergs, Folkert, O’Sullivan, Michael, Kharbanda, Rajesh, Lord, Graham M, Melikian, Narbeh, Patel, Riyaz S, Perera, Divaka, Shah, Ajay M, Francis, Darrel P, and Mayet, Jamil

Published
2019

15. Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes

Author

Pazoki, Raha, Vujkovic, Marijana, Elliott, Joshua, Evangelou, Evangelos, Gill, Dipender, Ghanbari, Mohsen, van der Most, Peter J., Pinto, Rui Climaco, Wielscher, Matthias, Farlik, Matthias, Zuber, Verena, de Knegt, Robert J., Snieder, Harold, Uitterlinden, André G., Lynch, Julie A., Jiang, Xiyun, Said, Saredo, Kaplan, David E., Lee, Kyung Min, Serper, Marina, Carr, Rotonya M., Tsao, Philip S., Atkinson, Stephen R., Dehghan, Abbas, Tzoulaki, Ioanna, Ikram, M. Arfan, Herzig, Karl-Heinz, Järvelin, Marjo-Riitta, Alizadeh, Behrooz Z., O’Donnell, Christopher J., Saleheen, Danish, Voight, Benjamin F., Chang, Kyong-Mi, Thursz, Mark R., and Elliott, Paul

Published
2021
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18. Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits

Author

Zhou, Hang, Sealock, Julia M., Sanchez-Roige, Sandra, Clarke, Toni-Kim, Levey, Daniel F., Cheng, Zhongshan, Li, Boyang, Polimanti, Renato, Kember, Rachel L., Smith, Rachel Vickers, Thygesen, Johan H., Morgan, Marsha Y., Atkinson, Stephen R., Thursz, Mark R., Nyegaard, Mette, Mattheisen, Manuel, Børglum, Anders D., Johnson, Emma C., Justice, Amy C., Palmer, Abraham A., McQuillin, Andrew, Davis, Lea K., Edenberg, Howard J., Agrawal, Arpana, Kranzler, Henry R., and Gelernter, Joel

Published
2020
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20. Corticosteroids Reduce Risk of Death Within 28 Days for Patients With Severe Alcoholic Hepatitis, Compared With Pentoxifylline or Placebo—a Meta-analysis of Individual Data From Controlled Trials

Author

Louvet, Alexandre, Thursz, Mark R., Kim, Dong Joon, Labreuche, Julien, Atkinson, Stephen R., Sidhu, Sandeep Singh, O’Grady, John G., Akriviadis, Evangelos, Sinakos, Emmanouil, Carithers, Robert L., Jr., Ramond, Marie-José, Maddrey, Willis C., Morgan, Timothy R., Duhamel, Alain, and Mathurin, Philippe

Published
2018
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21. Mortality risk prediction of high-sensitivity C-reactive protein in suspected acute coronary syndrome: A cohort study

Author

Kaura, Amit, Hartley, Adam, Panoulas, Vasileios, Glampson, Ben, Shah, Anoop S. V., Davies, Jim, Mulla, Abdulrahim, Woods, Kerrie, Omigie, Joe, Shah, Anoop D., Thursz, Mark R., Elliott, Paul, Hemmingway, Harry, Williams, Bryan, Asselbergs, Folkert W., O'Sullivan, Michael, Lord, Graham M., Trickey, Adam, Sterne, Jonathan AC, Haskard, Dorian O., Melikian, Narbeh, Francis, Darrel P., Koenig, Wolfgang, Shah, Ajay M., Kharbanda, Rajesh, Perera, Divaka, Patel, Riyaz S., Channon, Keith M., Mayet, Jamil, and Khamis, Ramzi

Subjects
Mortality -- Risk factors, Acute coronary syndrome -- Prognosis -- Patient outcomes, C-reactive protein -- Measurement -- Health aspects, Biological sciences
Abstract

Background There is limited evidence on the use of high-sensitivity C-reactive protein (hsCRP) as a biomarker for selecting patients for advanced cardiovascular (CV) therapies in the modern era. The prognostic value of mildly elevated hsCRP beyond troponin in a large real-world cohort of unselected patients presenting with suspected acute coronary syndrome (ACS) is unknown. We evaluated whether a mildly elevated hsCRP (up to 15 mg/L) was associated with mortality risk, beyond troponin level, in patients with suspected ACS. Methods and findings We conducted a retrospective cohort study based on the National Institute for Health Research Health Informatics Collaborative data of 257,948 patients with suspected ACS who had a troponin measured at 5 cardiac centres in the United Kingdom between 2010 and 2017. Patients were divided into 4 hsCRP groups ( Following the exclusion criteria, there were 102,337 patients included in the analysis (hsCRP 15 mg/L makes it unlikely that sepsis was a major contributor. Conclusions These multicentre, real-world data from a large cohort of patients with suspected ACS suggest that mildly elevated hsCRP (up to 15 mg/L) may be a clinically meaningful prognostic marker beyond troponin and point to its potential utility in selecting patients for novel treatments targeting inflammation. Trial registration ClinicalTrials.gov - NCT03507309, Author(s): Amit Kaura 1,2, Adam Hartley 1,2, Vasileios Panoulas 1,2, Ben Glampson 2, Anoop S. V. Shah 1,2,3, Jim Davies 4, Abdulrahim Mulla 2, Kerrie Woods 4, Joe Omigie 5, [...]

Published
2022
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23. Defective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis

Author

Argemi, Josepmaria, Latasa, Maria U., Atkinson, Stephen R., Blokhin, Ilya O., Massey, Veronica, Gue, Joel P., Cabezas, Joaquin, Lozano, Juan J., Van Booven, Derek, Bell, Aaron, Cao, Sheng, Vernetti, Lawrence A., Arab, Juan P., Ventura-Cots, Meritxell, Edmunds, Lia R., Fondevila, Constantino, Stärkel, Peter, Dubuquoy, Laurent, Louvet, Alexandre, Odena, Gemma, Gomez, Juan L., Aragon, Tomas, Altamirano, Jose, Caballeria, Juan, Jurczak, Michael J., Taylor, D. Lansing, Berasain, Carmen, Wahlestedt, Claes, Monga, Satdarshan P., Morgan, Marsha Y., Sancho-Bru, Pau, Mathurin, Philippe, Furuya, Shinji, Lackner, Carolin, Rusyn, Ivan, Shah, Vijay H., Thursz, Mark R., Mann, Jelena, Avila, Matias A., and Bataller, Ramon

Published
2019
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24. Acceptability and feasibility of a screen-and-treat programme for hepatitis B virus infection in The Gambia: the Prevention of Liver Fibrosis and Cancer in Africa (PROLIFICA) study

Author

Lemoine, Maud, Shimakawa, Yusuke, Njie, Ramou, Taal, Makie, Ndow, Gibril, Chemin, Isabelle, Ghosh, Sumantra, Njai, Harr F, Jeng, Adam, Sow, Amina, Toure-Kane, Coumba, Mboup, Souleymane, Suso, Penda, Tamba, Saydiba, Jatta, Abdullah, Sarr, Louise, Kambi, Aboubacar, Stanger, William, Nayagam, Shevanthi, Howell, Jessica, Mpabanzi, Liliane, Nyan, Ousman, Corrah, Tumani, Whittle, Hilton, Taylor-Robinson, Simon D, D'Alessandro, Umberto, Mendy, Maimuna, and Thursz, Mark R

Published
2016
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25. PD-1 blockade improves Kupffer cell bacterial clearance in acute liver injury

Author

Triantafyllou, Evangelos, Gudd, Cathrin L.C., Mawhin, Marie-Anne, Husbyn, Hannah C., Trovato, Francesca M., Siggins, Matthew K., O'Connor, Thomas, Kudo, Hiromi, Mukherjee, Sujit K., Wendon, Julia A., Bernsmeier, Christine, Goldin, Robert D., Botto, Marina, Khamri, Wafa, McPhail, Mark J.W., Possamai, Lucia A., Woollard, Kevin J., Antoniades, Charalambos G., and Thursz, Mark R.

Subjects
Cell death -- Genetic aspects -- Health aspects, Gene expression -- Health aspects, Immune response -- Genetic aspects, Cellular proteins -- Health aspects, Liver diseases -- Genetic aspects -- Development and progression -- Care and treatment, Health care industry
Abstract

Patients with acute liver failure (ALF) have systemic innate immune suppression and increased susceptibility to infections. Programmed cell death 1 (PD-1) expression by macrophages has been associated with immune suppression during sepsis and cancer. We therefore examined the role of the programmed cell death 1/programmed death ligand 1 (PD-1/PD-L1) pathway in regulating Kupffer cell (KC) inflammatory and antimicrobial responses in acetaminophen-induced (APAP-induced) acute liver injury. Using intravital imaging and flow cytometry, we found impaired KC bacterial clearance and systemic bacterial dissemination in mice with liver injury. We detected increased PD-1 and PD-L1 expression in KCs and lymphocyte subsets, respectively, during injury resolution. Gene expression profiling of [PD-1.sup.+] KCs revealed an immune-suppressive profile and reduced pathogen responses. Compared with WT mice, [PD-1.sup.-]deficient mice and anti-[PD-1.sup.-]treated mice with liver injury showed improved KC bacterial clearance, a reduced tissue bacterial load, and protection from sepsis. Blood samples from patients with ALF revealed enhanced PD-1 and PD-L1 expression by monocytes and lymphocytes, respectively, and that soluble PD-L1 plasma levels could predict outcomes and sepsis. PD-1 in vitro blockade restored monocyte functionality. Our study describes a role for the PD-1/PD-L1 axis in suppressing KC and monocyte antimicrobial responses after liver injury and identifies anti-PD-1 immunotherapy as a strategy to reduce infection susceptibility in ALF., Introduction Acute liver failure (ALF) is a rare clinical syndrome in which coagulopathy, jaundice, and hepatic encephalopathy arise in the context of acute hepatic injury without preexisting chronic liver disease [...]

Published
2021
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26. Immune Checkpoint Inhibitor-Induced Liver Injury.

Author

Gudd, Cathrin L.C., Sheth, Roosey, Thursz, Mark R., Triantafyllou, Evangelos, and Possamai, Lucia A.

Subjects
IMMUNE checkpoint proteins, LIVER injuries, COMBINATION drug therapy, IPILIMUMAB, IMMUNE system
Abstract

Checkpoint inhibitors (CPIs) are immunotherapy drugs used to treat cancer by boosting the immune system, but they can cause side effects, including liver damage. This document provides an overview of CPI-induced liver injury and how to manage it. Combination therapy with certain drugs carries a higher risk of adverse events. The document also discusses risk factors, diagnosis, and treatment guidelines for checkpoint inhibitor hepatitis (CPI-H). Further research is needed to identify definitive risk factors and refine treatment guidelines. The article emphasizes the importance of biomarkers and diagnostic tools to personalize treatment strategies. [Extracted from the article]

Published
2023
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27. Clinical utility of HCV core antigen detection and quantification using serum samples and dried blood spots in people who inject drugs in Dar-es-Salaam, Tanzania

Author

Mohamed, Zameer, Mbwambo, Jessie, Shimakawa, Yusuke, Poiteau, Lila, Chevaliez, Stephane, Pawlotsky, Jean-Michel, Rwegasha, John, Bhagani, Sanjay, Taylor-Robinson, Simon D., Makani, Julie, Thursz, Mark R., and Lemoine, Maud

Subjects
Blood serum -- Health aspects, Hepatitis C virus -- Health aspects -- Research, Antiretroviral agents -- Dosage and administration, Health, World Health Organization
Abstract

Introduction: A lack of access to hepatitis C virus (HCV) diagnostics is a significant barrier to achieving the World Health Organization 2030 global elimination goal. HCV core antigen (HCVcAg) quantification and dried blood spot (DBS) are appealing alternatives to conventional HCV serology and nucleic acid testing (NAT) for resource-constraint settings, particularly in difficult-to-reach populations. We assessed the accuracy of serum and DBS HCVcAg testing in people who inject drugs in Tanzania using HCV NAT as a reference. Method: Between May and July 2015, consecutive HCV-seropositive patients enrolled in the local opioid substitution treatment centre were invited to participate in the study. All had HCV RNA detection (Roche Molecular Systems, Pleasanton, CA, USA), genotyping (NS5B gene phylogenetic analysis) and HCVcAg on blood samples and DBS (Architect assay; Abbott Diagnostics, Chicago, IL, USA). Results: Out of 153 HCV-seropositive individuals, 65 (42.5%) and 15 (9.8%) were co-infected with HIV (41 (63%) were on anti-retroviral therapy (ARVs)) and hepatitis B respectively. In total, 116 were viraemic, median viral load of 5.7 (Interquartile range (IQR); 4.0-6.3) log iU/ml (75 (68.2%) were genotype 1a, 35 (31.8%) genotype 4a). The median alanine transaminase (ALT) (iU/l), aspartate transaminase (AST) (iU/l) and gamma-glutamyl transferase (GGT) (iU/l) were 35 (IQR; 23-51), 46 (32-57) and 69 (35-151) respectively. For the quantification of HCV RNA, serum HCVcAg had a sensitivity at 99.1% and a specificity at 94.1%, with an area under the receiver operating curve (AUROC) at 0.99 (95% CI 0.98-1.00). DBS HCVcAg had a sensitivity of 76.1% and a specificity of 97.3%, with an AUROC of 0.87 (95% CI 0.83-0.92). HCVcAg performance did not differ by HIV co-infection or HCV genotype. Conclusions: Our study suggests that HCVcAg testing in serum is an excellent alternative to HCV polymerase chain reaction in Africa. Although HCVcAg detection and quantification in DBS has a reduced sensitivity, its specificity and accuracy are good and it could therefore be used for scaling up HCV testing and care in resource-limited African settings. Keywords: people who inject drugs; hepatitis C virus (HCV); dried blood spot; HCV core antigen; screening; Africa, Introduction An estimated 80 million people are chronically infected with hepatitis C virus (HCV) worldwide and about 700,000 annual deaths are attributable to HCV [1-3]. The World Health Organization (WHO) [...]

Published
2017
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28. MerTK expressing hepatic macrophages promote the resolution of inflammation in acute liver failure

Author

Triantafyllou, Evangelos, Pop, Oltin T, Possamai, Lucia A, Wilhelm, Annika, Liaskou, Evaggelia, Singanayagam, Arjuna, Bernsmeier, Christine, Khamri, Wafa, Petts, Gemma, Dargue, Rebecca, Davies, Scott P, Tickle, Joseph, Yuksel, Muhammed, Patel, Vishal C, Abeles, Robin D, Stamataki, Zania, Curbishley, Stuart M, Ma, Yun, Wilson, Ian D, Coen, Muireann, Woollard, Kevin J, Quaglia, Alberto, Wendon, Julia, Thursz, Mark R, Adams, David H, Weston, Chris J, and Antoniades, Charalambos G

Published
2018
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29. Rifaximin in non‐alcoholic steatohepatitis: An open‐label pilot study

Author

Cobbold, Jeremy F.L., Atkinson, Stephen, Marchesi, Julian R., Smith, Ann, Wai, Sann N., Stove, Julie, Shojaee‐Moradie, Fariba, Jackson, Nicola, Umpleby, A. Margot, Fitzpatrick, Julie, Thomas, E. Louise, Bell, Jimmy D., Holmes, Elaine, Taylor‐Robinson, Simon D., Goldin, Robert D., Yee, Michael S., Anstee, Quentin M., and Thursz, Mark R.

Published
2018
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33. THU-247-YI Multi-tissue profiling of oxylipins reveal a conserved upregulation of epoxide: diol ratio that associates with white adipose tissue inflammation and liver steatosis in obesity

Author

Hateley, Charlotte, Olona, Antoni, Halliday, Laura, Edin, Matthew, Ko, Jeong-Hun, Forlano, Roberta, Terra, Ximena, Lih, Fred, Beltran-Debon, Raul, Manousou, Pinelopi, Purkayastha, Sanjay, Moorthy, Krishna, Thursz, Mark R, Zhang, Guodong, Goldin, Robert D., Zeldin, Darryl, Petretto, Enrico, and Behmoaras, Jacques

Published
2024
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35. FRI-215-YI MASL-B registry: results from a european cohort of patients with chronic hepatitis B and metabolic dysfunction-associated steatotic liver disease

Author

Forlano, Roberta, Martinez-Gili, Laura, Lacey, Madeleine, Sigon, Giordano, Mullish, Benjamin H., Mallet, Vincent, Parlati, Lucia, Richardson, Paul, Forde, Niamh, Serviddio, Gaetano, Villani, Rosanna, Lens, Sabela, Buti, Maria, Viganò, Mauro, Loglio, Alessandro, Lampertico, Pietro, D'Ambrosio, Roberta, Monico, Sara, Maffi, Gabriele, Lombardi, Rosa, Fracanzani, Anna Ludovica, De Luca, Chiara, Ingiliz, Patrick, Mangia, Alessandra, Leserre, Federica, Piazzolla, Valeria, Russo, Francesco Paolo, Raimondo, Giovanni, Papatheodoridis, George, Papatheodoridi, Margarita, Samonakis, Dimitrios N., Barnes, Eleanor, O'Donnell, Denise, O'Donoghue, Jennifer, Abeles, R. Daniel, Pugliese, Nicola, Aghemo, Alessio, Lemoine, Maud, Thursz, Mark R., Brown, Ashley, and Manousou, Pinelopi

Published
2024
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36. TOP-553 Deciphering the immunological dynamics of flares following nucleos (t)ide analogue (NA) cessation in HBeAg negative chronic hepatitis B in a large, longitudinal, phase II multi-centred clinical trial (NUC-B study)

Author

Phillips, Sandra, Mistry, Sameer, Harris, Nicola, Zope, Dimple, Moore, Celia, Hahn, Gareth, Rosario, Michelle, Carr-Smith, Camilla, Carrillo, Maria Cortes, Elangovan, Lavanya, Agarwal, Kosh, Hand, James, Sivell, Chris, Kennedy, Patrick, Congreave, Susan, Barnes, Mathew, Ryder, Stephen D., Habib, Mariam, Thursz, Mark R., and Chokshi, Shilpa

Published
2024
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38. SAT-274 Serum proteomic analyses reveal elevated HGFand IL-8 in patients with alcohol-related hepatitis compared to decompensated alcohol-related cirrhosis and can differentiate patients with AH at risk of infection from those at risk of acute kidney injury

Author

Tyson, Luke D., Atkinson, Stephen R., Patel, Vishal C., Allison, Michael, Austin, Andrew, Dear, James W., Forrest, Ewan H., Hunter, RobertW., Liu, Tong, Masson, Steven, McPhail, Mark J.W., Nunes, Joao, Richardson, Paul, Ryder, Stephen D., Wright, Mark, Holmes, Elaine, Thursz, Mark R., and Vergis, Nikhil

Published
2024
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40. THU-317 Alcohol-related hepatitis is associated with a distinctive pattern of disordered bile acid metabolism and reduced bile acid transporter expression

Author

Tyson, Luke D., Atkinson, Stephen R., Mullish, Benjamin H., Pechlivanis, Alexandros, Allison, Michael, Austin, Andrew, Chappell, Katie, Forbes, Stuart J., Forrest, Ewan H., Kilpatrick, Alastair M., Martinez-Gili, Laura, Masson, Steven, McPhail, Mark J.W., Richardson, Paul, Torres, Daniel Rodrigo, Ryder, Stephen D., Wright, Mark, Patel, Vishal C., Vergis, Nikhil, Holmes, Elaine, and Thursz, Mark R.

Published
2024
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42. LBO-003 Results of a phase 2b multicenter randomized trial of larsucosterol for the treatment of severe alcohol-associated hepatitis (AHFIRM trial)

Author

Shiffman, Mitchell, Da, Ben, Stein, Lance, Moreno, Christophe, Mehta, Ashwini, Louvet, Alexandre, Nicoll, Amanda, Goel, Aparna, Kwong, Allison, Flamm, Steven, Satapathy, Sanjaya, Kuo, Alexander, Pyrsopoulos, Nikolaos T., Ganger, Daniel, Aloman, Costica, Strasser, Simone, Tse, Edmund, Russo, Mark, Rockey, Don, Gray, Meagan, Mitchell, Mack, Thursz, Mark R., Krebs, William, Scott, Deborah, Blevins, Christina, Brown, James, Lin, WeiQi, and Sussman, Norman

Published
2024
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43. Genome-wide association study and replication of liver enzyme loci

Author

Pazoki, Raha, Vujkovic, Marijana, Elliott, Joshua, Evangelou, Evangelos, Gill, Dipender, Ghanbari, Mohsen, Van der Most, Peter J., Pinto, Rui Climaco, Wielscher, Matthias, Farlik, Matthias, Zuber, Verena, de Knegt, Robert J., Snieder, Harold, Uitterlinden, Andre G., Lynch, Julie A., Jiang, Xiyun, Said, Saredo, Kaplan, David E., Lee, Kyung Min, Serper, Marina, Carr, Rotonya M., Tsao, Philip S., Atkinson, Stephen R., Dehghan, Abbas, Tzoulaki, Ioanna, Ikram, Arfan, Herzig, Karl-Heinz, Jarvelin, Marjo-Riitta, Alizadeh, Behrooz Z., O'Don-Nell, Christopher J., Saleheen, Danish, Voight, Benjamin F., Chang, Kyong-Mi, Thursz, Mark R., Elliott, Paul, Life Course Epidemiology (LCE), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)

Published
2022

45. Defective monocyte oxidative burst predicts infection in alcoholic hepatitis and is associated with reduced expression of NADPH oxidase

Author

Vergis, Nikhil, Khamri, Wafa, Beale, Kylie, Sadiq, Fouzia, Aletrari, Mina O, Moore, Celia, Atkinson, Stephen R, Bernsmeier, Christine, Possamai, Lucia A, Petts, Gemma, Ryan, Jennifer M, Abeles, Robin D, James, Sarah, Foxton, Matthew, Hogan, Brian, Foster, Graham R, O’Brien, Alastair J, Ma, Yun, Shawcross, Debbie L, Wendon, Julia A, Antoniades, Charalambos G, and Thursz, Mark R

Published
2017
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46. A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers

Author

Whitfield, John B., Schwantes-An, Tae Hwi, Darlay, Rebecca, Aithal, Guruprasad P., Atkinson, Stephen R., Bataller, Ramon, Botwin, Greg, Chalasani, Naga P., Cordell, Heather J., Daly, Ann K., Day, Christopher P., Eyer, Florian, Foroud, Tatiana, Gleeson, Dermot, Goldman, David, Haber, Paul S., Jacquet, Jean Marc, Liang, Tiebing, Liangpunsakul, Suthat, Masson, Steven, Mathurin, Philippe, Moirand, Romain, McQuillin, Andrew, Moreno, Christophe, Morgan, Marsha Y., Mueller, Sebastian, Nagy, Laura E., Nahon, Pierre, Nalpas, Bertrand, Naveau, Sylvie, Perney, Pascal, Pirmohamed, Munir, Seitz, Helmut K., Soyka, Michael, Stickel, Felix, Thompson, Andrew, Thursz, Mark R., Tre?po, Eric, Morgan, Timothy R., and Seth, Devanshi

Subjects
genome wide association, Hepatocellular carcinoma, single nucleotide polymorphism, coffee, risk stratification, chronic alcohol use
Abstract

Background & Aims: Only a minority of excess alcohol drinkers develop cirrhosis. We developed and evaluated risk stratification scores to identify those at highest risk. Methods: Three cohorts (GenomALC-1: n = 1,690, GenomALC-2: n = 3,037, UK Biobank: relevant n = 6,898) with a history of heavy alcohol consumption (≥80 g/day (men), ≥50 g/day (women), for ≥10 years) were included. Cases were participants with alcohol-related cirrhosis. Controls had a history of similar alcohol consumption but no evidence of liver disease. Risk scores were computed from up to 8 genetic loci identified previously as associated with alcohol-related cirrhosis and 3 clinical risk factors. Score performance for the stratification of alcohol-related cirrhosis risk was assessed and compared across the alcohol-related liver disease spectrum, including hepatocellular carcinoma (HCC). Results: A combination of 3 single nucleotide polymorphisms (SNPs) (PNPLA3:rs738409, SUGP1-TM6SF2:rs10401969, HSD17B13:rs6834314) and diabetes status best discriminated cirrhosis risk. The odds ratios (ORs) and (95% CIs) between the lowest (Q1) and highest (Q5) score quintiles of the 3-SNP score, based on independent allelic effect size estimates, were 5.99 (4.18–8.60) (GenomALC-1), 2.81 (2.03–3.89) (GenomALC-2), and 3.10 (2.32–4.14) (UK Biobank). Patients with diabetes and high risk scores had ORs of 14.7 (7.69–28.1) (GenomALC-1) and 17.1 (11.3–25.7) (UK Biobank) compared to those without diabetes and with low risk scores. Patients with cirrhosis and HCC had significantly higher mean risk scores than patients with cirrhosis alone (0.76 ± 0.06 vs. 0.61 ± 0.02, p = 0.007). Score performance was not significantly enhanced by information on additional genetic risk variants, body mass index or coffee consumption. Conclusions: A risk score based on 3 genetic risk variants and diabetes status enables the stratification of heavy drinkers based on their risk of cirrhosis, allowing for the provision of earlier preventative interventions. Lay summary: Excessive chronic drinking leads to cirrhosis in some people, but so far there is no way to identify those at high risk of developing this debilitating disease. We developed a genetic risk score that can identify patients at high risk. The risk of cirrhosis is increased >10-fold with just two risk factors – diabetes and a high genetic risk score. Risk assessment using this test could enable the early and personalised management of this disease in high-risk patients.

Published
2022

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