Publications
701 results found
Forrest EH, Atkinson SR, Richardson P, et al., 2018, The long-term prognosis of Alcoholic Hepatitis is poor and independent of disease severity for patients surviving an acute episode (Reply), Journal of Hepatology, Vol: 68, Pages: 1332-1332, ISSN: 0168-8278
Atkinson SR, McQuillin A, Morgan MY, et al., 2018, People who survive an episode of severe alcoholic hepatitis should be advised to maintain total abstinence from alcohol, Hepatology, Vol: 67, Pages: 2479-2480, ISSN: 0270-9139
Thursz M, Allison M, 2018, Liver transplantation for alcoholic hepatitis: Being consistent about where to set the bar, LIVER TRANSPLANTATION, Vol: 24, Pages: 733-734, ISSN: 1527-6465
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- Citations: 14
Heffernan A, Hallett T, Thursz M, et al., 2018, Global scale-up of hepatitis C interventions will reduce burden but not eliminate the disease, 16th International Symposium on Viral Hepatitis and Liver Diseases (ISVHLD), Publisher: WILEY, Pages: 26-26, ISSN: 1352-0504
McDonald JAK, Mullish BH, Pechlivanis A, et al., 2018, A novel route for controlling Clostridioides difficile growth via bile acid and short chain fatty acid modulation, ISME17
Dhar A, Sadiq F, Anstee QM, et al., 2018, Thrombin and factor Xa link the coagulation system with Liver fibrosis, BMC Gastroenterology, Vol: 18, ISSN: 1471-230X
Background:Thrombin activates hepatic stellate cells via protease-activated receptor-1. The role of Factor Xa (FXa) in hepatic fibrosis has not been elucidated. We aimed to evaluate the impact of FXa and thrombin in vitro on stellate cells and their respective inhibition in vivo using a rodent model of hepatic fibrosis.Methods:HSC-LX2 cells were incubated with FXa and/or thrombin in cell culture, stained for αSMA and relative gene expression and gel contraction calculated. C57BL/6 J mice were administered thioacetamide (TAA) for 8 weeks with Rivaroxaban (n = 15) or Dabigatran (n = 15). Control animals received TAA alone (n = 15). Fibrosis was scored and quantified using digital image analysis and hepatic tissue hydroxyproline estimated.ResultsStellate cells treated with FXa and thrombin demonstrated upregulation of procollagen, TGF-beta, αSMA and significant cell contraction (43.48%+/− 4.12) compared to culturing with FXa or thrombin alone (26.90%+/− 8.90, p = 0.02; 13.1%+/− 9.84, p < 0.001). Mean fibrosis score, percentage area of fibrosis and hepatic hydroxyproline content (2.46 vs 4.08, p = 0.008; 2.02% vs 3.76%, p = 0.012; 276.0 vs 651.3, p = 0.0001) were significantly reduced in mice treated with the FXa inhibitor compared to control mice. FXa inhibition was significantly more effective than thrombin inhibition in reducing percentage area of fibrosis and hepatic hydroxyproline content (2.02% vs 3.70%,p = 0.031; 276.0 vs 413.1,p = 0.001).Conclusions:FXa promotes stellate cell contractility and activation. Early inhibition of coagulation using a FXa inhibitor significantly reduces TAA induced murine liver fibrosis and may be a viable treatment for liver fibrosis in patients.
Bernsmeier C, Triantafyllou E, Brenig R, et al., 2018, CD14+CD15-HLA-DR- myeloid-derived suppressor cells impair antimicrobial responses in patients with acute-on-chronic liver failure, Gut, Vol: 67, Pages: 1155-1167, ISSN: 1468-3288
Objective Immune paresis in patients with acute-on-chronic liver failure (ACLF) accounts for infection susceptibility and increased mortality. Immunosuppressive mononuclear CD14+HLA-DR− myeloid-derived suppressor cells (M-MDSCs) have recently been identified to quell antimicrobial responses in immune-mediated diseases. We sought to delineate the function and derivation of M-MDSC in patients with ACLF, and explore potential targets to augment antimicrobial responses.Design Patients with ACLF (n=41) were compared with healthy subjects (n=25) and patients with cirrhosis (n=22) or acute liver failure (n=30). CD14+CD15−CD11b+HLA-DR− cells were identified as per definition of M-MDSC and detailed immunophenotypic analyses were performed. Suppression of T cell activation was assessed by mixed lymphocyte reaction. Assessment of innate immune function included cytokine expression in response to Toll-like receptor (TLR-2, TLR-4 and TLR-9) stimulation and phagocytosis assays using flow cytometry and live cell imaging-based techniques.Results Circulating CD14+CD15−CD11b+HLA-DR− M-MDSCs were markedly expanded in patients with ACLF (55% of CD14+ cells). M-MDSC displayed immunosuppressive properties, significantly decreasing T cell proliferation (p=0.01), producing less tumour necrosis factor-alpha/interleukin-6 in response to TLR stimulation (all p<0.01), and reduced bacterial uptake of Escherichia coli (p<0.001). Persistently low expression of HLA-DR during disease evolution was linked to secondary infection and 28-day mortality. Recurrent TLR-2 and TLR-4 stimulation expanded M-MDSC in vitro. By contrast, TLR-3 agonism reconstituted HLA-DR expression and innate immune function ex vivo.Conclusion Immunosuppressive CD14+HLA-DR− M-MDSCs are expanded in patients with ACLF. They were depicted by suppressing T cell function, attenuated antimicrobial innate immune responses, linked to secondary infection, disease severity and prognosis. TLR-3 ag
McDonald JAK, Mullish BH, Pechlivanis A, et al., 2018, 24 - A novel route to controlling Clostridioides Difficile growth via short chain fatty acid and bile acid modulation, Digestive Diseases Week, Publisher: Elsevier, Pages: S8-S8, ISSN: 0016-5085
Maurice J, Tsochatzis E, Nelson M, et al., 2018, Diagnostic accuracy of non-invasive markers of fibrosis in HIV mono-infected patients with histologically confirmed NAFLD, 4th Joint Conference of the British HIV Association (BHIVA) with the British Association for Sexual Health and HIV (BASHH), Publisher: WILEY, Pages: S75-S76, ISSN: 1464-2662
Forlano R, Mullish BH, Katertsidis N, et al., 2018, SAT-476 A mobile application for the management and follow-up of patients with Non-Alcoholic Fatty Liver Disease, International Liver Congress 2018, Paris, France
Forlano R, Mullish BH, Katertsidis N, et al., 2018, A mobile application for the management and follow-up of patients with Non-Alcoholic Fatty Liver Disease, International Liver Congress (ILC), Publisher: ELSEVIER SCIENCE BV, Pages: S819-S819, ISSN: 0168-8278
Maurice J, Kelleher P, Nelson M, et al., 2018, NAFLD in HIV mono-infection is a consequence of insulin resistance but not bacterial translocation, International Liver Congress (ILC), Publisher: ELSEVIER SCIENCE BV, Pages: S358-S358, ISSN: 0168-8278
Morrison R, Forlano R, Giannakeas N, et al., 2018, Lipofuscin is detected in early stages of the disease in liver biopsies of patients with Non-Alcoholic Fatty Liver Disease, International Liver Congress (ILC), Publisher: ELSEVIER SCIENCE BV, Pages: S819-S819, ISSN: 0168-8278
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- Citations: 1
Atkinson SR, Way MJ, McQuillin A, et al., 2018, Reply to: "The <i>PNPLA3</i> SNP rs738409:G allele is associated with increased liver disease-associated mortality but reduced overall mortality in a population-based cohort'', JOURNAL OF HEPATOLOGY, Vol: 68, Pages: 860-862, ISSN: 0168-8278
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- Citations: 3
Atkinson S, Allison M, Forrest E, et al., 2018, Bayesian sparse regression modelling more accurately predicts mortality risk than commonly used prognostic scoring systems in patients with severe alcoholic hepatitis, International Liver Congress (ILC), Publisher: ELSEVIER SCIENCE BV, Pages: S808-S809, ISSN: 0168-8278
Ndow G, Cohen D, Shimakawa Y, et al., 2018, Occult Hepatitis B infection is frequent and a risk factor of advanced liver disease in The Gambia, West Africa, International Liver Congress (ILC), Publisher: ELSEVIER SCIENCE BV, Pages: S485-S486, ISSN: 0168-8278
Kumar N, Khamri W, Sadiq F, et al., 2018, Circulating NK cells in cirrhosis are hypofunctional, with an expanded inhibitory liver-homing CD56dimCD16+/- NK cell population, International Liver Congress (ILC), Publisher: ELSEVIER SCIENCE BV, Pages: S611-S611, ISSN: 0168-8278
Forlano R, Mullish BH, Katertsidis N, et al., 2018, A mobile application for the management and follow-up of patients with Non-Alcoholic Fatty Liver Disease, Journal of Hepatology, Vol: 68, Pages: S819-S819, ISSN: 0168-8278
Atzori S, Hoogenboom T, Taylor-Robinson S, et al., 2018, Non invasive assessment of liver fibrosis by three different Shear Wave Techniques: Head-to-Head Performance, International Liver Congress (ILC), Publisher: ELSEVIER SCIENCE BV, Pages: S643-S644, ISSN: 0168-8278
Abellona U, Mark DP, Oleribe O, et al., 2018, Towards elucidating a universal panel of diagnostic biomarkers for early hepatocellular carcinoma, International Liver Congress (ILC), Publisher: ELSEVIER SCIENCE BV, Pages: S433-S433, ISSN: 0168-8278
Forlano R, Kockerling D, Nathwani R, et al., 2018, Prediction of decompensation events in NASH cirrhosis patients, International Liver Congress (ILC), Publisher: ELSEVIER SCIENCE BV, Pages: S818-S819, ISSN: 0168-8278
Louvet A, Labreuche J, Thursz M, et al., 2018, Combination of the Lille model with baseline scores is useful to predict mortality in severe alcoholic hepatitis: a confirmation study in a large database of patients, International Liver Congress (ILC), Publisher: ELSEVIER SCIENCE BV, Pages: S807-S807, ISSN: 0168-8278
Forrest EH, Atkinson SR, Richardson P, et al., 2018, Application of prognostic scores in the STOPAH trial: Discriminant function is no longer the optimal scoring system in alcoholic hepatitis, JOURNAL OF HEPATOLOGY, Vol: 68, Pages: 511-518, ISSN: 0168-8278
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- Citations: 54
Ortega-Prieto AM, Skelton JK, Wai SN, et al., 2018, 3D microfluidic liver cultures as physiological preclinical tool for hepatitis B virus infection, Nature Communications, Vol: 9, ISSN: 2041-1723
With more than 240 million people infected, hepatitis B virus (HBV) is a major health concern. The inability to mimic the complexity of the liver using cell line and regular primary human hepatocyte (PHH) cultures pose significant limitations for studying host/pathogen interactions. Here, we describe a 3D-microfluidic PHH system permissive to HBV infection, which can be maintained for at least 40 days. This system enables the recapitulation of all steps of the HBV life cycle, including the replication of patient-derived HBV and the maintenance of HBV cccDNA. We show that innate immune and cytokine responses following infection with HBV mimic those observed in HBV-infected patients, thus allowing the dissection of pathways important for immune evasion and validation of biomarkers. Additionally, we demonstrate that the co-culture of PHH with other non-parenchymal cells enables the identification of the cellular origin of immune effectors, thus providing a valuable preclinical platform for HBV research.
Cobbold JFL, Atkinson S, Marchesi JR, et al., 2018, Rifaximin in non-alcoholic steatohepatitis: An open-label pilot study, HEPATOLOGY RESEARCH, Vol: 48, Pages: 69-77, ISSN: 1386-6346
AimGut microbial dysbiosis is implicated in the pathogenesis of non‐alcoholic steatohepatitis (NASH). We investigated downstream effects of gut microbiota modulation on markers of hepatic inflammation, steatosis, and hepatic and peripheral insulin sensitivity in patients with NASH using rifaximin therapy.MethodsPatients with biopsy‐proven NASH and elevated aminotransferase values were included in this open‐label pilot study, all receiving 6 weeks rifaximin 400 mg twice daily, followed by a 6‐week observation period. The primary endpoint was change in alanine aminotransferase (ALT) after 6 weeks of rifaximin. Secondary endpoints were change in hepatic lipid content and insulin sensitivity measured with a hyperinsulinemic–euglycemic clamp.ResultsFifteen patients (13 men and 2 women) with a median (range) age of 46 (32–63) years were included. Seven had diabetes on oral hypoglycemic medications and 8 had no diabetes. After 6 weeks of therapy, no differences were seen in ALT (55 [33–191] vs. 63 [41–218] IU/L, P = 0.41), peripheral glucose uptake (28.9 [19.4–48.3] to 25.5 [17.7–47.9] μmol/kg/min, P = 0.30), hepatic insulin sensitivity (35.2 [15.3–51.7]% vs. 30.0 [10.8–50.5]%, P = 0.47), or hepatic lipid content (21.6 [2.2–46.2]% vs. 24.8 [1.7–59.3]%, P = 0.59) before and after rifaximin treatment. After 12 weeks from baseline, serum ALT increased to 83 (30–217) IU/L, P = 0.02. There was a significant increase in the homeostasis model assessment–estimated insulin resistance index (P = 0.05). The urinary metabolic profile indicated a significant reduction in urinary hippurate with treatment, which reverted to baseline after cessation of rifaximin, although there was no consistent difference in relative abundance of fecal microbiota with treatment.ConclusionThese data do not indicate a beneficial effect of rifaximin i
Nayagam S, Sicuri E, Lemoine M, et al., 2017, Economic evaluations of HBV testing and treatment strategies and applicability to low and middle-income countries, BMC Infectious Diseases, Vol: 17, Pages: 107-116, ISSN: 1471-2334
Background: Many people living with chronic HBV infection remain undiagnosed until later stages of disease.Increasing testing and treatment rates form part of the strategy to respond to the WHO goal of eliminating viralhepatitis as a public health threat by 2030. However, achieving these ambitious targets is dependent on findingeffective and cost-effective methods of scale up strategies. The aim of this study was to undertake a narrativereview of the literature on economic evaluations of testing and treatment for HBV infection, to help inform thedevelopment of the 2017 WHO Hepatitis Testing Guidelines.Methods: We undertook a focussed literature review for economic evaluations on testing for HBV accompanied byantiviral treatment. The search was carried out in Pubmed and included only articles published after 2000 and writtenin English. We narratively synthesise the results and discuss the key drivers of cost-effectiveness and their applicabilityto low and middle-income countries (LMICs).Results: Nine published studies were included in this review, only one of which was performed in a low or middleincomesetting in West Africa. Eight studies were performed in high-income settings, seven among high risk groupsand one among the general population. The studies were heterogeneous in many respects including the populationand testing strategy under consideration, model structure and baselines parameters, willingness to pay thresholds andoutcome measures used. However, most studies found HBV testing and treatment to be cost-effective, even at lowHBsAg prevalence levels.Conclusions: Currently economic evaluations of HBV testing and treatment strategies in LMICs is lacking, thereforelimiting the ability to provide formal recommendations on the basis of cost-effectiveness alone. Further implementationresearch is needed in order to help guide national policy planning.
Forlano R, Manousou P, Mullish BH, et al., 2017, Assessment of non invasive markers of fibrosis against collagen quantitation and NASH-CRN scoring in liver biopsies of NAFLD patients, The AASLD Liver Meeting 2017, Publisher: Wiley, Pages: 334A-334A, ISSN: 0270-9139
Mullish BH, Forlano R, Yee M, et al., 2017, Development of an algorithm for the prediction of cardiovascular events in patients with NAFLD: the role of mean platelet volume, The AASLD Liver Meeting 2017, Publisher: Wiley, Pages: 1175A-1176A, ISSN: 0270-9139
Kumar N, Khamri W, Sadiq F, et al., 2017, A Novel inhibitory NK cell subpopulation is expanded in Cirrhosis, 68th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) / Liver Meeting, Publisher: WILEY, Pages: 353A-353A, ISSN: 0270-9139
Atkinson SR, Forlano R, Manousou P, et al., 2017, CARRIAGE OF RS738409 IN PNPLA3 IS POSITIVELY ASSOCIATED WITH THE SEVERITY OF HISTOLOGICAL DAMAGE IN PATIENTS WITH ALCOHOLIC HEPATITIS, Publisher: OXFORD UNIV PRESS, ISSN: 0735-0414
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