Imperial College London

ProfessorMarkThursz

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Professor of Hepatology. Head of Department
 
 
 
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Contact

 

+44 (0)20 3312 1903m.thursz

 
 
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Assistant

 

Ms Dawn Campbell +44 (0)20 3312 6454

 
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Location

 

Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

624 results found

Forlano R, Mullish BH, Roberts LA, Thursz MR, Manousou Pet al., 2022, The Intestinal Barrier and Its Dysfunction in Patients with Metabolic Diseases and Non-Alcoholic Fatty Liver Disease, International Journal of Molecular Sciences, ISSN: 1422-0067

Journal article

Mohamed Z, Scott N, Nayagam S, Rwegasha J, Mbwambo J, Thursz MR, Brown AS, Hellard M, Lemoine Met al., 2022, Cost effectiveness of simplified HCV screening-and-treatment interventions for people who inject drugs in Dar-es-Salaam, Tanzania, International Journal of Drug Policy, Vol: 99, ISSN: 0955-3959

Journal article

Singal AK, Kwo P, Kwong A, Liangpunsakul S, Louvet A, Mandrekar P, McClain C, Mellinger J, Szabo G, Terrault N, Thursz M, Winder GS, Kim WR, Shah VHet al., 2021, Research methodologies to address clinical unmet needs and challenges in alcohol-associated liver disease, HEPATOLOGY, ISSN: 0270-9139

Journal article

Vergis N, Patel V, Bogdanowicz K, Czyzewska-Khan J, Fiorentino F, Day E, Cross M, Foster N, Lord E, Goldin R, Forrest E, Thursz Met al., 2021, IL-1 Signal Inhibition In Alcoholic Hepatitis (ISAIAH): a study protocol for a multicentre, randomised, placebo controlled trial to explore the potential benefits of canakinumab in the treatment of alcoholic hepatitis, Trials, Vol: 22, Pages: 1-16, ISSN: 1745-6215

Background: Alcohol consumption causes a spectrum of liver abnormalities and leads to over 3 million deaths per year. Alcoholic hepatitis (AH) is a florid presentation of alcoholic liver disease characterized by liver failure in the context of recent and heavy alcohol consumption. The aim of this study is to explore the potential benefits of the IL-1β antibody, Canakinumab, in the treatment of AH.Methods: This is multicentre, double-blind, randomised placebo-controlled trial. Participants will be diagnosed with AH using clinical criteria. Liver biopsy will then confirm that all histological features of AH are present. Up to 58 participants will be recruited into two groups from 15 centres in the United Kingdom. Patients will receive an infusion of Canakinumab or matched placebo by random 1:1 allocation. The primary outcome is reduction in lobular inflammation, comparing histological appearances at baseline with appearances at 28 days. Patients with evidence of ongoing disease activity will receive a second infusion of Canakinumab or placebo. Participants will be followed up for 90 days. Secondary outcomes include mortality and change in MELD score at 90 days. Discussion: This phase II study will explore the benefits of the IL-1β antibody, canakinumab, in the treatment of AH to provide proof of concept that inhibition of IL-1β signaling may improve histology and survival for patients with AH. Trial registration: Prospectively registered with EudraCT 2017-003724-79.

Journal article

Whitfield JB, Schwantes-An T-H, Darlay R, Aithal GP, Atkinson SR, Bataller R, Botwin G, Chalasani NP, Cordell HJ, Daly AK, Day CP, Eyer F, Foroud T, Gleeson D, Goldman D, Haber PS, Jacquet J-M, Liang T, Liangpunsakul S, Masson S, Mathurin P, Moirand R, McQuillin A, Moreno C, Morgan MY, Mueller S, Müllhaupt B, Nagy LE, Nahon P, Nalpas B, Naveau S, Perney P, Pirmohamed M, Seitz HK, Soyka M, Stickel F, Thompson A, Thursz MR, Trépo E, Morgan TR, Seth D, GenomALC Consortiumet al., 2021, A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers., J Hepatol

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 (Q2) 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, all

Journal article

Innes AJ, Mullish BH, Ghani R, Szydlo RM, Apperley JF, Olavarria E, Palanicawandar R, Kanfer EJ, Milojkovic D, McDonald JAK, Brannigan ET, Thursz MR, Williams HRT, Davies FJ, Marchesi JR, Pavlu Jet al., 2021, Fecal microbiota transplant mitigates adverse outcomes in patients colonized with multidrug-resistant organisms undergoing allogeneic hematopoietic cell transplantation, Frontiers in Cellular and Infection Microbiology, Vol: 11, Pages: 1-8, ISSN: 2235-2988

The gut microbiome can be adversely affected by chemotherapy and antibiotics prior to hematopoietic cell transplantation (HCT).This affects graft success and increases susceptibility to multidrug-resistant organism (MDRO) colonization and infection. Weperformed an initial retrospective analysis of our use of fecal microbiota transplantation (FMT) from healthy donors as therapy forMDRO-colonized patients with hematological malignancy. FMT was performed on eight MDRO-colonized patients pre-HCT (FMT-MDROgroup), and outcomes compared with 11 MDRO colonized HCT patients from the same period. At 12 months, survival wassignificantly higher in the FMT-MDRO group (70% versus 36% p = 0.044). Post-HCT, fewer FMT-MDRO patients required intensivecare (0% versus 46%, P = 0.045) or experienced fever (0.29 versus 0.11 days, P = 0.027). Intestinal MDRO decolonization occurred in25% of FMT-MDRO patients versus 11% non-FMT MDRO patients. Despite the significant difference and statistically comparablepatient/transplant characteristics, as the sample size was small, a matched-pair analysis to non-MDRO colonized control cohorts(2:1 matching) was performed. At 12 months, the MDRO group who did not have an FMT had significantly lower survival (36.4%versus 61.9% respectively, p=0.012), and higher non relapse mortality (NRM; 60.2% versus 16.7% respectively, p=0.009) than theirpaired non-colonized cohort. There was no difference in survival (70% versus 43.4%, p=0.14) or NRM (12.5% versus 31.2%respectively, p=0.24) between the FMT-MDRO group and their paired cohort. Negative outcomes, including mortality associatedwith MDRO colonization, may be ameliorated by pre-HCT FMT, despite lack of intestinal decolonization. Further work is needed toexplore the observed benefit.

Journal article

Khamri W, Gudd C, Liu T, Nathwani R, Krasniqi M, Azam S, Barbera T, Trovato FM, Possamai LA, Triantafyllou E, Castro Seoane R, Lebosse F, Singanayagam A, Kumar N, Bernsmeier C, Mukherjee S, McPhail MJW, Weston CJ, Antoniades CG, Thursz MRet al., 2021, Suppressor CD4+ T cells expressing HLA-G are expanded in the peripheral blood from patients with acute decompensation of cirrhosis, Gut, ISSN: 0017-5749

Journal article

Forlano R, Harlow C, Mullish BH, Thursz MR, Manousou P, Yee Met al., 2021, Binge-eating disorder is associated with an unfavourable body mass composition in patients with Non-alcoholic fatty liver disease, International Journal of Eating Disorders, Vol: 54, Pages: 2025-2030, ISSN: 0276-3478

The interaction between eating disorders and non-alcoholic fatty liver disease (NAFLD) remains unexplored, especially with regards to binge-eating disorder (BED). Our team conducted a service evaluation project in order to assess risk factors for the presence of BED among patients with NAFLD and the impact of BED on body mass composition. The overall prevalence of patients screening positive to BED Screener-7 (BEDS-7) was 28.4%, while a previous diagnosis of depression and marital status (as single or separated) were independently associated with positive BED. Furthermore, patients with positive BEDS-7 had higher BMI, with greater visceral component and overall lower muscle mass. There was no difference in terms of liver disease severity as assessed by noninvasive markers of fibrosis. However, as body mass composition and sarcopenia have been shown to be associated to disease progression in patients with NAFLD, further studies are required to ascertain the long-term impact of BED in these patients. Moreover, further work is warranted to identify to implement multidisciplinary approach within clinical psychology for the management of patients with BED, who may be particularly challenging in terms of achieving lifestyle modifications. As a hepatology community, we should address NAFLD with a more holistic approach.

Journal article

Gustot T, Stadlbauer V, Laleman W, Alessandria C, Thursz Met al., 2021, Transition to decompensation and acute-on-chronic liver failure: Role of predisposing factors and precipitating events, JOURNAL OF HEPATOLOGY, Vol: 75, Pages: S36-S48, ISSN: 0168-8278

Journal article

Lemoine M, Cooke GS, Thursz M, Matthews PCet al., 2021, Cuts to UK official development assistance budget jeopardise global viral hepatitis elimination goals., Lancet Gastroenterol Hepatol, Vol: 6, Pages: 527-528

Journal article

Possamai L, Gudd C, Au L, Triantafyllou E, Shum B, Liu T, Nathwani R, Kumar N, Mukherjee S, Dhar A, Woollard K, Yone Y, Pinato D, Thursz M, Goldin R, Gore M, Larkin J, Khamri W, Antoniades C, Turajlic Set al., 2021, Activation and transcriptional profile of monocytes and CD8+ T cells are altered in checkpoint inhibitor-related hepatitis, Journal of Hepatology, Vol: 75, Pages: 177-189, ISSN: 0168-8278

Background & Aims: Checkpoint inhibitor-related hepatitis (CPI-Hep) is an emerging clinical challenge. We aimed to gain insights into the immunopathology of CPI-Hep by comprehensively characterising myeloid and lymphoid subsets.Methods: CPI-treated patients with or without related hepatitis (CPI-Hep; n = 22 and CPI-noHep; n = 7) were recruited. Phenotypic and transcriptional profiling of peripheral immune subsets was performed and compared with 19 healthy controls (HCs). In vitro monocyte-derived macrophages (MoMFs) were assessed for activation and cytokine production. CD163, CCR2, CD68, CD3, CD8 and granzyme B expression was assessed using immunohistochemistry/immunofluorescence (n = 4).Results: A significant total monocyte depletion was observed in CPI-Hep compared with HCs (p = 0.04), along with a proportionate increase in the classical monocyte population (p = 0.0002) and significant upregulation of CCR2, CD163 and downregulation of CCR7. Soluble CD163 levels were significantly elevated in CPI-Hep compared with HCs (p <0.0001). In vitro MoMFs from CPI-Hep showed enhanced production of pro-inflammatory cytokines. CD8+ T cells demonstrated increased perforin, granzyme B, ICOS and HLA-DR expression in CPI-Hep. Transcriptional profiling indicated the presence of activated monocyte and enhanced effector CD8+ T cell populations in CPI-Hep. Immunohistochemistry demonstrated co-localisation of CD8+/granzyme B+ T cells with CD68+CCR2+/CD68+CD163+ macrophages in CPI-Hep liver tissue.Conclusions: CPI-Hep is associated with activation of peripheral monocytes and an enhanced cytotoxic, effector CD8+ T cell phenotype. These changes were reflected by liver inflammation composed of CD163+/CCR2+ macrophages and CD8+ T cells.Lay summary: Some patients who receive immunotherapy for cancer develop liver inflammation, which requires cessation of cancer treatment. Herein, we describe ways in which the white blood cells of patients who develop liver inflammation differ from tho

Journal article

Post G, Howell J, Sow A, Ndow G, Chemin I, Lo G, Cessay A, Cohen D, Njie R, Toure S, Diop M, Sombie R, Nana J, Leroy V, Lacombe K, Bojang L, Tacke F, Toure-Kane C, Ka M, Mendy M, Mboup S, Thursz M, Shimakawa Y, Ingiliz P, Lemoine Met al., 2021, Clinical utility of quantifying hepatitis B surface antigen in African patients with chronic hepatitis B, JOURNAL OF VIRAL HEPATITIS, Vol: 28, Pages: 1003-1010, ISSN: 1352-0504

Journal article

Pazoki R, Elliott J, Evangelou E, Gill D, Pinto R, Zuber V, Said S, Dehghan A, Tzoulaki I, Jarvelin MR, Thursz M, Elliott Pet al., 2021, Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes, Nature Communications, Vol: 12, ISSN: 2041-1723

Serum concentration of hepatic enzymes are linked to liver dysfunction, metabolic and cardiovascular diseases. We perform genetic analysis on serum levels of alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) using data on 437,438 UK Biobank participants. Replication in 315,572 individuals from European descent from the Million Veteran Program, Rotterdam Study and Lifeline study confirms 517 liver enzyme SNPs. Genetic risk score analysis using the identified SNPs is strongly associated with serum activity of liver enzymes in two independent European descent studies (The Airwave Health Monitoring study and the Northern Finland Birth Cohort 1966). Gene-set enrichment analysis using the identified SNPs highlights involvement in liver development and function, lipid metabolism, insulin resistance, and vascular formation. Mendelian randomization analysis shows association of liver enzyme variants with coronary heart disease and ischemic stroke. Genetic risk score for elevated serum activity of liver enzymes is associated with higher fat percentage of body, trunk, and liver and body mass index. Our study highlights the role of molecular pathways regulated by the liver in metabolic disorders and cardiovascular disease.

Journal article

Ghani R, Mullish BH, McDonald JAK, Ghazy A, Williams HRT, Brannigan ET, Mookerjee S, Satta G, Gilchrist M, Duncan N, Corbett R, Innes AJ, Pavlu J, Thursz MR, Davies F, Marchesi JRet al., 2021, Disease prevention not decolonization – a model for fecal microbiota transplantation in patients colonized with multidrug-resistant organisms, Clinical Infectious Diseases, Vol: 72, Pages: 1444-1447, ISSN: 1058-4838

Fecal microbiota transplantation (FMT) yields variable intestinal decolonization results for multidrug-resistant organisms (MDROs). This study showed significant reductions in antibiotic duration, bacteremia and length of stay in 20 patients colonized/ infected with MDRO receiving FMT (compared to pre-FMT history, and a matched group not receiving FMT), despite modest decolonization rates.

Journal article

Vergis N, Phillips R, Cornelius V, Katsarou A, Youngstein T, Cook L, Willicombe M, Pilay C, Shturova T, Almonte M, Charania A, Turner R, Kon OM, Cooke G, Thursz M, Cherlin S, Wason J, Milojkovic D, Innes AJ, Cooper Net al., 2021, Multi-arm Trial of Inflammatory Signal Inhibitors (MATIS) for hospitalised patients with mild or moderate COVID-19 pneumonia: a structured summary of a study protocol for a randomised controlled trial, Trials, Vol: 22, ISSN: 1745-6215

OBJECTIVES: The primary objective of MATIS is to determine the efficacy of ruxolitinib (RUX) or fostamatinib (FOS) compared to standard of care (SOC) with respect to reducing the proportion of hospitalised patients progressing from mild or moderate to severe COVID-19 pneumonia. Secondary objectives, at 14 and 28 days, are to: Determine the efficacy of RUX or FOS to reduce mortality Determine the efficacy of RUX or FOS to reduce the need for invasive ventilation or ECMO Determine the efficacy of RUX or FOS to reduce the need for non-invasive ventilation Determine the efficacy of RUX or FOS to reduce the proportion of participants suffering significant oxygen desaturation Determine the efficacy of RUX or FOS to reduce the need for renal replacement therapy Determine the efficacy of RUX and FOS to reduce the incidence of venous thromboembolism Determine the efficacy of RUX and FOS to reduce the severity of COVID-19 pneumonia [graded by a 9-point modified WHO Ordinal Scale* Determine the efficacy of RUX or FOS to reduce systemic inflammation Determine the efficacy of RUX or FOS to the incidence of renal impairment Determine the efficacy of RUX or FOS to reduce duration of hospital stay Evaluate the safety of RUX and FOS for treatment of COVID-19 pneumonia. TRIAL DESIGN: A multi-arm, multi-stage (3-arm parallel-group, 2-stage) randomised controlled trial that allocates participants 1:1:1 and tests for superiority in experimental arms versus standard of care. PARTICIPANTS: Patients will be recruited while inpatients during hospitalisation for COVID-19 in multiple centres throughout the UK including Imperial College Healthcare NHS Trust. INCLUSION: Patients age ≥ 18 years at screening Patients with mild or moderate COVID-19 pneumonia, defined as Grade 3 or 4 severity by the WHO COVID-19 Ordinal Scale Patients meeting criteria: Hospitalization AND SARS-CoV2 infection (clinically suspected or laboratory confirmed) AND Radiological change consistent with COVID-19 disease C

Journal article

Schmit N, Nayagam S, Thursz M, Hallett Tet al., 2021, The global burden of chronic hepatitis B virus infection: comparison of country-level prevalence estimates from four research groups, International Journal of Epidemiology, Vol: 50, Pages: 560-569, ISSN: 0300-5771

Background: Progress towards viral hepatitis elimination goals relies on accurate estimates of chronic hepatitis B virus (HBV) infection prevalence. We compared existing sources of the most recent country-level estimates from 2013-2017 to investigate the extent and underlying drivers of differences between them. Methods: The four commonly cited sources of global prevalence estimates, the Institute for Health Metrics and Evaluation, Schweitzer et al, World Health Organization (WHO) and CDA Foundation, were compared by calculating pairwise differences between sets of estimates and assessing their within-country variation. Differences in underlying empirical data and modelling methods were investigated as contributors to differences in sub-Saharan African estimates. Results: The four sets of estimates across all ages were comparable overall and agreed on the global distribution of HBV burden. WHO and CDA produced the most similar estimates, differing by a median of 0.8 percentage points. Larger discrepancies were seen in estimates of prevalence in children under 5 years of age and in sub-Saharan African countries, where the median pairwise differences were 2.7 and 2.4 percentage points for all age prevalence and in children, respectively. Recency and representativeness of included data, and different modelling assumptions of the age distribution of HBV burden, seemed to contribute to these differences. Conclusion: Current prevalence estimates, particularly those from WHO and CDA based on more recent empirical data, provide a useful resource to assess the population-level burden of chronic HBV infection. However, further seroprevalence data in young children is needed particularly in sub-Saharan Africa. This is a priority as monitoring progress towards elimination depends on improved knowledge of prevalence in this age group.

Journal article

Nathwani R, Koeckerling D, Mullish BH, Cole A, Lemoine M, Antoniades CG, Thursz M, Dhar Aet al., 2021, Non-selective beta-blocker use in cirrhosis: the additional benefit in preventing secondary infections, Frontline Gastroenterology, Vol: 13, ISSN: 2041-4137

Journal article

Nayagam AS, Chan P, Zhao K, Sicuri E, Wang X, Jia J, Wei L, Walsh N, Rodewald LE, Zhang G, Ailing W, Zhang L, Chang J, Hou C, Qiu Y, Sui B, Xiao Y, Zhuang H, Thursz M, Scano F, Low-Beer D, Schwartländer B, Wang Y, Hallett TBet al., 2021, Investment case for a comprehensive package of interventions against Hepatitis B in China; applied modelling to help national strategy planning, Clinical Infectious Diseases, Vol: 72, Pages: 743-752, ISSN: 1058-4838

Background:In2016,the first globalviralhepatitiselimination targetswere endorsed. Anestimated one-third of the world’schronic HBV infected population live in China and liver cancer is the sixth leading cause of mortality, but coverage of first line antiviral treatment was low. In 2015, China was one of the first countriesto initiate a consultative process for a renewed approach to viral hepatitis. We present the investment case for the scale-up of a comprehensive package of HBV interventions. Methods:Adynamic simulation modelof HBV was developedand used to simulate the Chinese HBV epidemic. We evaluated the impact, costs and return on investment of a comprehensive package of prevention and treatment interventions from a societal perspective, incorporating costs of management of end-stage liver disease and lost productivity costs. Results:Despitethe successes of historical vaccination scale-up since 1992, there will be a projected 60millionpeople still living with HBV in 2030 and 10 million HBV-related deaths, including 5.7millionHBV-related cancer deaths between 2015-2030. This could be reduced by 2.1million by highly active case-finding and optimal antiviral treatment regimens. The package of interventions is likely to have a positive return-on-investment to society, of 1.57US$ per US$ invested. Conclusions:Increases in HBV-related deaths for the next few decades pose a major public health threatin China. Active case-finding and access to optimal antiviral treatment is requiredto mitigate this risk. This investment case approachprovides a real-world example of howapplied modellingcansupportnational dialogue and inform policy planning.

Journal article

Howell J, Pedrana A, Schroeder SE, Scott N, Aufegger L, Atun R, Baptista-Leite R, Hirnschall G, 't Hoen E, Hutchinson SJ, Lazarus J, Olufunmilayo L, Peck R, Sharma M, Sohn AH, Thompson A, Thursz M, Wilson D, Hellard Met al., 2021, A global investment framework for the elimination of hepatitis B, JOURNAL OF HEPATOLOGY, Vol: 74, Pages: 535-549, ISSN: 0168-8278

Journal article

Guldiken N, Argemi J, Gurbuz B, Atkinson SR, Oliverius M, Fila P, Hamesch K, Bruns T, Cabezas J, Lozano JJ, Mann J, Cao S, Mathurin P, Shah VH, Trautwein C, Thursz MR, Bataller R, Strnad Pet al., 2021, Serum transferrin as a biomarker of hepatocyte nuclear factor 4 alpha activity and hepatocyte function in liver diseases, BMC MEDICINE, Vol: 19, ISSN: 1741-7015

Journal article

Forrest E, Petts G, Austin A, Lloyd K, Wright M, Vergis N, Atkinson S, Masson S, Patch D, Quaglia A, Thursz M, Goldin Ret al., 2021, The diagnostic and prognostic significance of liver histology in alcoholic hepatitis, Alimentary Pharmacology and Therapeutics, Vol: 53, Pages: 426-431, ISSN: 0269-2813

BackgroundLiver biopsy may be of diagnostic and prognostic value but its role in alcoholic hepatitis (AH) has been controversial.AimTo assess the utility of liver biopsy in the assessment of clinically severe AHMethodsThe histological features of alcoholic steatohepatitis (ASH) were recorded and scored in patients enrolled in the Steroids or Pentoxifylline for Alcoholic Hepatitis (STOPAH) trial who underwent liver biopsy. These features were then assessed relative to outcome and established clinical prognostic scores.ResultsThe STOPAH trial recruited 1068 patients; biopsies were obtained in 182 (17%). One hundred and sixty‐one biopsies were adequate for histological assessment and 140 (87%) were diagnostic for ASH. Only three biopsies (2%) did not have histological features of alcohol‐related liver injury. In biopsies performed prior to randomisation, ASH was identified in 92.5% of patients meeting clinical trial definitions of severe AH. In biopsies with ASH, taken before or within 48 hours of randomisation, survival differences between Alcoholic Hepatitis Histological Score (AHHS) groups were not significant: comparison of mild / moderate (91%: 21 of 23 patients) with severe (78%: 29 of 37 patients) groups: P = 0.18. The AHHS was not superior to clinical scores of prognosis: area under the curve for 28‐day mortality was 0.728, compared with 0.799 for the Glasgow alcoholic hepatitis score and 0.728 for the MELD score.ConclusionLiver histology taken before treatment rarely changes the diagnosis in patients meeting strict criteria for a clinical diagnosis of AH. The AHHS is similar to clinical scores in determining prognosis.Clinical trial registrationEudraCT reference number: 2009‐013897‐42.ISRCTN reference number: 88782125.MREC number: 09/MRE09/59.UKCRIN ID: 9143.

Journal article

Middleton P, Perez-Guzman PN, Cheng A, Kumar N, Kont M, Daunt A, Mukherjee S, Cooke G, Hallett TB, Hauck K, White PJ, Thursz MR, Nayagam Set al., 2021, Characteristics and outcomes of clinically diagnosed RT-PCR swab negative COVID-19: a retrospective cohort study, Scientific Reports, Vol: 11, Pages: 1-7, ISSN: 2045-2322

Patients with strong clinical features of COVID-19 with negative real time polymerase chain reaction (RT-PCR) SARS-CoV-2 testing are not currently included in official statistics. The scale, characteristics and clinical relevance of this group are not well described. We performed a retrospective cohort study in two large London hospitals to characterize the demographic, clinical, and hospitalization outcome characteristics of swab-negative clinical COVID-19 patients. We found 1 in 5 patients with a negative swab and clinical suspicion of COVID-19 received a clinical diagnosis of COVID-19 within clinical documentation, discharge summary or death certificate. We compared this group to a similar swab positive cohort and found similar demographic composition, symptomology and laboratory findings. Swab-negative clinical COVID-19 patients had better outcomes, with shorter length of hospital stay, reduced need for >60% supplementary oxygen and reduced mortality. Patients with strong clinical features of COVID-19 that are swab-negative are a common clinical challenge. Health systems must recognize and plan for the management of swab-negative patients in their COVID-19 clinical management, infection control policies and epidemiological assessments.

Journal article

Heffernan A, Ma Y, Nayagam S, Chan P, Chen Z, Cooke GS, Guo Y, Liu C, Thursz M, Zhang W, Zhang X, Zhang X, Jia M, Hallett TBet al., 2021, Economic and epidemiological evaluation of interventions to reduce the burden of hepatitis C in Yunnan province, China, PLoS One, Vol: 16, Pages: 1-17, ISSN: 1932-6203

BackgroundThe paradigm shift in hepatitis C virus (HCV) treatment options in the last five years has raised the prospect of eliminating the disease as a global health threat. This will require a step-change in the number being treated with the new direct-acting antivirals (DAAs). Given constrained budgets and competing priorities, policy makers need information on how to scale-up access to HCV treatment. To inform such decisions, we examined the cost effectiveness of screening and treatment interventions in Yunnan, China.Methods and findingsWe simulated the HCV epidemic using a previously published model of HCV transmission and disease progression, calibrated to Yunnan data, and implemented a range of treatment and screening interventions from 2019. We incorporated treatment, diagnosis, and medical costs (expressed in 2019 US Dollars, USD) to estimate the lifetime benefits and costs of interventions. Using this model, we asked: is introducing DAAs cost effective from a healthcare sector perspective; what is the optimal combination of screening interventions; and what is the societal return on investment of intervention? The incremental cost-effectiveness ratio (ICER) of switching to DAAs with a median cost of 7,400 USD (50,000 Chinese Yuan) per course is 500 USD/disability adjusted life year (DALY) averted; at a threshold of 50% of Yunnan gross domestic product (2,600 USD), switching to DAAs is cost effective 94% of the time. At this threshold, the optimal, cost-effective intervention comprises screening people who inject drugs, those in HIV care, men who have sex with men, and ensuring access to DAAs for all those newly diagnosed with HCV. For each USD invested in this intervention, there is an additional 0·80 USD (95% credible interval: 0·17–1·91) returned through reduced costs of disease or increased productivity. Returns on investment are lower (and potentially negative) if a sufficiently long-term horizon, encompassing the full stream

Journal article

Hui Z, Nayagam S, Chan P, Fuzhen W, Thursz M, Zundong Y, Ning M, Xiaojin S, Cui F, Guomin Z, Hallett TBet al., 2021, Progress towards elimination of mother-to-child transmission of hepatitis B virus infection in China: a modelling analysis., Bulletin of the World Health Organization, Vol: 99, Pages: 10-18, ISSN: 0042-9686

Objective: To determine the projected burden of hepatitis B virus (HBV) in China, the intervention strategies that can eliminate mother-to-child transmission (MTCT) by 2030 or earlier and the measurable parameters that can be used to monitor progress towards this target. Methods: We developed a dynamic, sex- and age-stratified model of the HBV epidemic in China, calibrated using hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) prevalence data from sequential national serosurveys (1979-2014) and the numbers of HBV-related cancer deaths (2012). We determined whether China can achieve elimination of MTCT of HBV by 2030 under current prevention interventions. We modelled various intervention scenarios to represent different coverage levels of birth-dose HBV vaccination, hepatitis B immunoglobulin to newborns of HBsAg-positive mothers and antiviral therapy (tenofovir) to HBeAg-positive pregnant women. Findings: We project that, if current levels of prevention interventions are maintained, China will achieve the elimination target by 2029. By modelling various intervention scenarios, we found that this can be brought forward to 2025 by increasing coverage of birth-dose vaccination, or to 2024 by the administration of tenofovir to HBeAg-positive pregnant women. We found that achievement of the target by 2025 would be predicted by a measurement of less than 2% MTCT in 2020. Conclusion: Our results highlight how high-quality national data can be combined with modelling in monitoring the elimination of MTCT of HBV. By demonstrating the impact of increased interventions on target achievement dates, we anticipate that other high-burden countries will be motivated to strengthen HBV prevention policies.

Journal article

Forlano R, Mullish BH, Maurice JB, Thursz MR, Goldin RD, Manousou Pet al., 2021, NAFLD: time to apply quantitation in liver biopsies as endpoints in clinical trials, Journal of Hepatology, Vol: 74, Pages: 241-242, ISSN: 0168-8278

Journal article

Triantafyllou E, Gudd C, Mawhin M-A, Husbyn H, Trovato F, Siggins M, O'Connor T, Kudo H, Mukherjee SK, Wendon JA, Bernsmeier C, Goldin R, Botto M, Khamri W, McPhail M, Possamai L, Woollard K, Charalambos AG, Thursz Met al., 2020, PD-1 blockade improves Kupffer cell bacterial clearance in acute liver injury, Journal of Clinical Investigation, Vol: 131, Pages: 1-16, ISSN: 0021-9738

Acute liver failure (ALF) patients display systemic innate immune suppression and increased susceptibility to infections. PD-1 expression by macrophages has been associated with immune suppression during sepsis and cancer. We therefore examined the role of PD-1/PD-L1 pathway in regulating Kupffer cell inflammatory and antimicrobial responses in acetaminophen (APAP) induced acute liver injury. Using intravital imaging and flow cytometry we found impaired Kupffer cell bacterial clearance and systemic bacterial dissemination in mice with liver injury. Increased PD-1 and PD-L1 expression was detected in Kupffer cells and lymphocyte subsets, respectively, during resolution of injury. Gene expression profiling of PD-1+ Kupffer cells revealed an immune-suppressive profile and reduced pathogen responses. Compared to wild-type, PD-1 deficient or anti-PD-1 treated mice with liver injury showed improved Kupffer cell bacterial clearance, reduced tissue bacterial load and protection from sepsis. Blood sample analyses of ALF patients revealed enhanced PD-1 and PD-L1 expression of monocytes and lymphocytes, respectively, and that plasma soluble PD-L1 levels predict patient outcome and sepsis. PD-1 in vitro blockade restored monocyte functionality. Our study describes a role for PD-1/PD-L1 axis in suppressing Kupffer cell and monocyte antimicrobial responses after liver injury and suggests anti-PD-1 immunotherapy as a strategy to reduce infection susceptibility in ALF.

Journal article

Innes AJ, Ghani R, Mullish BH, Szydlo R, Palanicawandar R, Olavarria E, Apperley JF, Thursz MR, Williams HR, Marchesi JR, Davies F, Pavlu Jet al., 2020, O105. Faecal microbiota transplant (FMT) can reduce the high NRM associated with multi-drug resistant organism (MDRO) colonisation prior to allogeneic HCT., The 46th Annual Meeting of the European Society for Blood and Marrow Transplantation, Publisher: Springer Nature [academic journals on nature.com], Pages: 122-122, ISSN: 0268-3369

Conference paper

Abeles R, Foxton M, Khan S, Goldin R, Smith B, Thursz M, Verma Set al., 2020, Androgenic Anabolic Steroid induced liver injury: 2 cases reports assessed for causality by the updated Roussel Uclaf Causality Assessment Method (RUCAM) score and a comprehensive review of the literature, BMJ Open Gastroenterology, Vol: 7, ISSN: 2054-4774

Background Anabolic androgenic steroids (AAS) usage is widespread and increasing. AAS drug-induced liver injury (DILI) is recognised but its clinical course and management is poorly described. We report 2 cases of AAS DILI with associated renal dysfunction, managed successfully with oral corticosteroids.Methods A comprehensive review identified 50 further cases to characterise the clinical and biochemical course. Causality grading was calculated using the updated Roussel Uclaf Causality Assessment Method (RUCAM) score. Data are presented as median values.Results The most common AAS taken was methyldrostanolone. Patients commonly present with jaundice and pruritus but may exhibit other constitutional symptoms. Patients presented 56 days after starting, and bilirubin peaked 28 days after stopping, AAS. Causality assessment was ‘unlikely’ in 1 (2%), ‘possible’ in 31 (60%) and ‘probable’ in 20 (38%). Peak values were: bilirubin 705 μmol/L, alanine transaminase 125 U/L, aspartate transaminase 71 U/L, alkaline phosphatase 262 U/L, gamma-glutamyl transferase 52 U/L, international normalised ratio 1.1. Liver biopsies showed ‘bland’ canalicular cholestasis. 43% of patients developed kidney injury (peak creatinine 225 μmol/L). Therapies included antipruritics, ursodeoxycholic acid and corticosteroids. No patients died or required liver transplantation.Conclusions Physicians are likely to encounter AAS DILI. Causality assessment using the updated RUCAM should be performed but defining indications and proving efficacy for therapies remains challenging.

Journal article

Arraez DM, Cots MV, Altamirano J, Abraldes JG, Clemente A, Alvarado-Tapia E, Argemi J, Pablo Arab J, Atkinson S, Brown RS, Araujo RC, Duarte-Rojo A, Fernandez-Carrillo C, Garcia-Tsao G, Alberto Gonzalez J, Higuera De La Tijera M, Kamath PS, Kim W, Louvet A, Lucey MR, Mathurin P, Rincon D, Carlos Restrepo J, Rautou P-E, Singal AK, Sarin SK, Shah V, Aldo T, Thursz MR, Verna EC, Vargas V, Zamarripa F, Bataller Ret al., 2020, A LARGE WORLDWIDE STUDY SHOWS THAT MELD IS THE BEST SCORING SYSTEM TO PREDICT MORTALITY IN ALCOHOL-ASSOCIATED HEPATITIS, Liver Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD), Publisher: WILEY, Pages: 148A-149A, ISSN: 0270-9139

Conference paper

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