Publications
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Argemi J, Latasa MU, Atkinson SR, et al., 2023, Author Correction: Defective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis., Nat Commun, Vol: 14
Jambulingam N, Forlano R, Preston B, et al., 2023, Metabolic profile reflects stages of fibrosis in patients with non-alcoholic fatty liver disease, International Journal of Molecular Sciences, Vol: 24, Pages: 1-12, ISSN: 1422-0067
Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide, with fibrosis stage being the main predictor for clinical outcomes. Here, we present the metabolic profile of NAFLD patients with regards to fibrosis progression. We included all consecutive new referrals for NAFLD services between 2011 and 2019. Demographic, anthropometric and clinical features and noninvasive markers of fibrosis were recorded at baseline and at follow-up. Significant and advanced fibrosis were defined using liver stiffness measurement (LSM) as LSM ≥ 8.1 kPa and LSM ≥ 12.1 kPa, respectively. Cirrhosis was diagnosed either histologically or clinically. Fast progressors of fibrosis were defined as those with delta stiffness ≥ 1.03 kPa/year (25% upper quartile of delta stiffness distribution). Targeted and untargeted metabolic profiles were analysed on fasting serum samples using Proton nuclear magnetic resonance (1H NMR). A total of 189 patients were included in the study; 111 (58.7%) underwent liver biopsy. Overall, 11.1% patients were diagnosed with cirrhosis, while 23.8% were classified as fast progressors. A combination of metabolites and lipoproteins could identify the fast fibrosis progressors (AUROC 0.788, 95% CI: 0.703–0.874, p < 0.001) and performed better than noninvasive markers. Specific metabolic profiles predict fibrosis progression in patients with nonalcoholic fatty liver disease. Algorithms combining metabolites and lipids could be integrated in the risk-stratification of these patients.
Schmit N, Nayagam A, Lemoine M, et al., 2023, Cost-effectiveness of different monitoring strategies in a screening and treatment programme for hepatitis B in The Gambia, Journal of Global Health, Vol: 13, Pages: 1-11, ISSN: 2047-2978
Background:Clinical management of chronic hepatitis B virus (HBV) infection is complex and access to antiviral treatment remains limited in sub-Saharan Africa. International guidelines recommend monitoring at least annually for disease progression among HBV-infected people not meeting treatment criteria at initial diagnosis. This study aimed to assess the impact and cost-effectiveness of alternative strategies for monitoring.Methods:We used a mathematical model of HBV transmission and natural history, calibrated to all available West African data, to project the population-level health impact, costs and cost-effectiveness of different monitoring strategies for HBV-infected individuals not initially eligible for antiviral treatment. We assumed that these patients were found in the year 2020 in a hypothetical community-based screening programme in The Gambia. Monitoring frequencies were varied between every 5 and every 1 year and targeted different age groups.Results:The currently recommended annual monitoring frequency was likely to be not cost-effective in comparison with other strategies in this setting. 5-yearly monitoring in 15-45-year olds, at US$338 per disability-adjusted life year averted, had the highest probability of being the most effective cost-effective monitoring strategy.Conclusions:Monitoring less frequently than once a year is a cost-effective strategy in a community-based HBV screening and treatment programme in The Gambia, with the optimal strategy depending on the cost-effectiveness threshold. Efficiencies may be gained by prioritising the 15-45-year age group for more intensive monitoring.
Whitfield JB, Seth D, Morgan TR, 2022, All-cause and liver-related mortality risk factors in excessive drinkers: Analysis of data from the UK biobank, ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, Vol: 46, Pages: 2245-2257, ISSN: 0145-6008
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Forlano R, Stanic T, Jayawardana S, et al., 2022, Clinical and cost-effectiveness analysis of community-based screening strategies for non-alcoholic fatty liver disease in patients with type-2 diabetes mellitus
<jats:title>Abstract</jats:title> <jats:p>Background & Aims: We investigated the prevalence of non-alcoholic fatty liver disease(NAFLD) in patients with type 2 diabetes mellitus(T2DM) in primary care and developed a risk-stratification pathway. We also assessed the cost-utility of different screening strategies for NAFLD in the diabetic community.Methods Consecutive T2DM patients underwent screening for liver diseases, including liver stiffness measurement(LSM). Binary logistic was used to predict factors associated with significant fibrosis. We used independent predictors of significant and advanced fibrosis to generate a predictive score for this population (BIMAST),and validated it internally and externally. Five screening strategies were compared against standard of care (SOC): BIMAST score, ultrasound plus abnormal liver function tests, FIB-4, NAFLD fibrosis score, and fibroscan. A Markov model was built upon four health states based on fibrosis status. We generated the cost per quality-adjusted life year(QALY) gained and calculated the incremental cost-effectiveness ratio (ICER) in the base-case analysis conducted over a lifetime horizon.Results Among 300 patients enrolled (287 included), 64% (186) had NAFLD and 10% (28) other causes of liver disease. Patients with significant fibrosis, advanced fibrosis, and cirrhosis due to NAFLD accounted for 17% (50/287), 11% (31/287), and 3% (8/287), respectively. BIMAST score validation showed an excellent diagnostic performance in primary care improving false negatives from 38–10% compared to FIB-4. In the cost-utility analysis, ICER was £2,337.92/QALY for BIMAST and £2,480/QALY for fibroscan. When transition probabilities, utilities, screening effect, and cost inputs were modified, we found a > 99% probability of NAFLD screening tests being cost-effective compared to SOC in all evaluated scenarios.Conclusion Screening for NAFLD in diabetic patient
Ndow G, Cessay A, Cohen D, et al., 2022, Prevalence and clinical significance of occult hepatitis B infection in The Gambia, West Africa., Journal of Infectious Diseases, Vol: 226, Pages: 862-870, ISSN: 0022-1899
BACKGROUND: Prevalence of occult hepatitis B infection (OBI) and its clinical outcomes have been poorly studied in Africa. METHOD: Using the PROLIFICA cohort, we compared the prevalence of OBI between HBsAg-negative healthy adults screened from the general population (controls) and HBsAg-negative patients with advanced liver disease (cases) and estimated the population attributable fraction for the effect of OBI on advanced liver disease. RESULTS: OBI prevalence was significantly higher among the cases (15/82, 18.3%) than in the control group (31/330, 9.4%, p=0.03). Among participants with OBI, pre-S2 mutations were detected in 5/31 (16.1%) controls and 3/14 (21.4%) cases (p=0.7).After adjusting for age, sex, and anti-HCV serology, OBI was significantly associated with advanced liver disease [OR: 2.8 (95% CI: 1.3-6.0), p=0.006]. In HBsAg-negative people, the proportions of advanced liver disease cases attributable to OBI and HCV were estimated at 12.9% (7.5-18.1%) and 16.9% (15.2-18.6%), respectively. CONCLUSION: OBI is endemic and an independent risk factor of advanced liver disease in The Gambia, West Africa. This implies that HBsAg-negative people with liver disease should be systematically screened for OBI. Moreover, the impact of infant hepatitis B immunization to prevent end-stage liver disease might be higher than previous estimates based solely on HBsAg-positivity.
Sow A, Lemoine M, Toure PS, et al., 2022, HBV continuum of care using community- and hospital-based screening interventions in Senegal: Results from the PROLIFICA programme, JHEP REPORTS, Vol: 4
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U MRA, Shen EY-L, Cartlidge C, et al., 2022, Optimised systematic review tool: Application to candidate biomarkers for the diagnosis of hepatocellular carcinoma, Cancer Epidemiology, Biomarkers and Prevention, Vol: 31, Pages: 1261-1274, ISSN: 1055-9965
This review aims to develop an appropriate review tool for systematically collating metabolites that are dysregulated in disease and applies the method to identify novel diagnostic biomarkers for hepatocellular carcinoma (HCC). Studies that analysed metabolites in blood or urine samples where HCC was compared with comparison groups (healthy, pre-cirrhotic liver disease, cirrhosis) were eligible. Tumour tissue was included to help differentiate primary and secondary biomarkers. Searches were conducted on Medline and EMBASE. A bespoke 'risk-of-bias' tool for metabolomic studies was developed adjusting for analytical quality. Discriminant metabolites for each sample type were ranked using a weighted score accounting for the direction and extent of change and the risk of bias of the reporting publication. A total of 84 eligible studies were included in the review (54 blood, 9 urine and 15 tissue), with six studying multiple sample types. High-ranking metabolites, based on their weighted score, comprised energy metabolites, bile acids, acylcarnitines and lysophosphocholines. This new review tool addresses an unmet need for incorporating quality of study design and analysis to overcome the gaps in standardisation of reporting of metabolomic data. Validation studies, standardised study designs and publications meeting minimal reporting standards are crucial for advancing the field beyond exploratory studies.
Szabo G, Thursz M, Shah VH, 2022, Therapeutic advances in alcohol-associated hepatitis, JOURNAL OF HEPATOLOGY, Vol: 76, Pages: 1279-1290, ISSN: 0168-8278
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- Citations: 4
Morales-Arraez D, Ventura-Cots M, Altamirano J, et al., 2022, The MELD Score Is Superior to the Maddrey Discriminant Function Score to Predict Short-Term Mortality in Alcohol-Associated Hepatitis: A Global Study (vol 117, pg 301, 2022), AMERICAN JOURNAL OF GASTROENTEROLOGY, Vol: 117, Pages: 818-818, ISSN: 0002-9270
Lucey MR, Thursz MR, 2022, We need a new approach to clinical trials in alcohol-associated hepatitis: Is there a lesson in RECOVERY?, HEPATOLOGY, Vol: 76, Pages: 909-910, ISSN: 0270-9139
Whitfield JB, Schwantes-An T-H, Darlay R, et al., 2022, A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers (vol 76, pg 275, 2022), JOURNAL OF HEPATOLOGY, Vol: 76, Pages: 1244-1245, ISSN: 0168-8278
Atkinson SR, Aly M, Remih K, et al., 2022, Serum keratin 19 (CYFRA21-1) is a prognostic biomarker in severe alcoholic hepatitis, LIVER INTERNATIONAL, Vol: 42, Pages: 1049-1057, ISSN: 1478-3223
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Kaura A, Hartley A, Panoulas V, et al., 2022, Mortality risk prediction of high-sensitivity C-reactive protein in suspected acute coronary syndrome: a cohort study, PLoS Medicine, Vol: 19, ISSN: 1549-1277
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 (<2, 2 to 4.9, 5 to 9.9, and 10 to 15 mg/L). The main outcome measure was mortality within 3 years of index presentation. The association between hsCRP levels and all-cause mortality was assessed using multivariable Cox regression analysis adjusted for age, sex, haemoglobin, white cell count (WCC), platelet count, creatinine, and troponin. Following the exclusion criteria, there were 102,337 patients included in the analysis (hsCRP <2 mg/L (n = 38,390), 2 to 4.9 mg/L (n = 27,397), 5 to 9.9 mg/L (n = 26,957), and 10 to 15 mg/L (n = 9,593)). On multivariable Cox regression analysis, there was a positive and graded relationship between hsCRP level and mortality at baseline, which remained at 3 years (hazard ratio (HR) (95% CI) of 1.32 (1.18 to 1.48) for those with hsCRP 2.0 to 4.9 mg/L and 1.40 (1.26 to 1.57) and 2.00 (1.75 to 2.28) for those with hsCRP 5 to 9.9 mg/L and 10 to 15 mg/L, respectively. This relationship was independent of troponin in all suspected ACS patients and was further verified in those who were confirmed to have an ACS diagnosis by clinical coding. The main limitation of our study is that we did not
Morales-Arraez D, Ventura-Cots M, Altamirano J, et al., 2022, The MELD Score Is Superior to the Maddrey Discriminant Function Score to Predict Short-Term Mortality in Alcohol-Associated Hepatitis: A Global Study, AMERICAN JOURNAL OF GASTROENTEROLOGY, Vol: 117, Pages: 301-310, ISSN: 0002-9270
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- Citations: 6
Whitfield JB, Schwantes-An T-H, Darlay R, et al., 2022, A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers, JOURNAL OF HEPATOLOGY, Vol: 76, Pages: 275-282, ISSN: 0168-8278
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- Citations: 12
Forlano R, Mullish BH, Roberts LA, et al., 2022, The intestinal barrier and its dysfunction in patients with metabolic diseases and non-alcoholic fatty liver disease, International Journal of Molecular Sciences, Vol: 23, ISSN: 1422-0067
Non-alcoholic fatty liver disease (NAFLD) represents an increasing cause of liver disease worldwide, mirroring the epidemics of obesity and metabolic syndrome. As there are still no licensed medications for treating the disease, there is an ongoing effort to elucidate the pathophysiology and to discover new treatment pathways. An increasing body of evidence has demonstrated a crosstalk between the gut and the liver, which plays a crucial role in the development and progression of liver disease. Among other intestinal factors, gut permeability represents an interesting factor at the interface of the gut–liver axis. In this narrative review, we summarise the evidence from human studies showing the association between increased gut permeability and NAFLD, as well as with type-2 diabetes and obesity. We also discuss the manipulation of the gut permeability as a potential therapeutical target in patients with NAFLD.
Vincent JP, Ndow G, Ogawa S, et al., 2022, Mac-2 binding protein glycosylation isomer (M2BPGi) to evaluate liver fibrosis and cancer in HBV-infected in West Africa, JOURNAL OF GLOBAL HEALTH, Vol: 12, ISSN: 2047-2978
Mohamed Z, Scott N, Nayagam S, et 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
Forlano R, Mullish BH, Dhar A, et al., 2021, Liver function tests and metabolic-associated fatty liver disease: Changes in upper normal limits, does it really matter?, World Journal of Hepatology, Vol: 13, Pages: 2104-2112, ISSN: 1948-5182
BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) is the commonest cause of abnormal liver function tests (LFTs). Current upper normal of limit (UNL) of LFTs was derived from a “healthy” population, where undiagnosed MAFLD and viral hepatitis might be suspected.AIM :To evaluated potential implications of changes in UNL of alanine aminotrans-ferase (ALT) in MAFLD.METHODS:We retrospectively assessed consecutive first referrals with a diagnosis of MAFLD from 2010 to 2017. The conventional UNL of ALT was 45 IU/L for men and 34 IU/L for women, while a low UNL of ALT was 30 IU/L for men and 19 IU/L for women. The UNL of aspartate aminotransferase (AST) was 40 IU/L.RESULTS:Total 436 patients were enrolled; of these, 288 underwent liver biopsy. Setting a lower UNL reduced the percentage of those with significant disease despite normal ALT; specifically, patients with advanced fibrosis (F ≥ F3) or definite “metabolic-associated steato-hepatitis (MASH)” (NAS ≥ 5) within normal ALT decreased from 10% to 1% and from 28% to 4% respectively. However, the proportion of those with elevated ALT and no evidence of advanced fibrosis or “definite MASH” increased from 39% to 47% and from 3% to 19%. Overall, LFTs performed poorly in distinguishing “definite MASH” from simple steatosis (receiver operating characteristic areas under the curves 0.59 for ALT and 0.55 for AST).CONCLUSION:Liver function tests might both under- and overestimate MASH-related liver disease. Reducing the UNL might not be beneficial and imply an increase in healthcare burden. Risk stratification in MAFLD should rely on a combination of risk factors, not on LFTs alone.
Singal AK, Kwo P, Kwong A, et al., 2021, Research methodologies to address clinical unmet needs and challenges in alcohol-associated liver disease, HEPATOLOGY, Vol: 75, Pages: 1026-1037, ISSN: 0270-9139
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- Citations: 6
Vergis N, Patel V, Bogdanowicz K, et 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.
Innes AJ, Mullish BH, Ghani R, et 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.
Khamri W, Gudd C, Liu T, et al., 2021, Suppressor CD4+ T cells expressing HLA-G are expanded in the peripheral blood from patients with acute decompensation of cirrhosis, Gut, Vol: 71, Pages: 1192-1202, ISSN: 0017-5749
Objective Identifying components of immuneparesis, a hallmark of chronic liver failure, is crucial for our understanding of complications in cirrhosis. Various suppressor CD4+ T cells have been established as potent inhibitors of systemic immune activation. Here, we establish the presence, regulation and mechanism of action of a suppressive CD4+ T cell subset expressing human leucocyte antigen G (HLA-G) in patients with acute decompensation of cirrhosis (AD).Design Flow cytometry was used to determine the proportion and immunophenotype of CD4+HLA-G+ T cells from peripheral blood of 20 healthy controls (HCs) and 98 patients with cirrhosis (28 with stable cirrhosis (SC), 20 with chronic decompensated cirrhosis (CD) and 50 with AD). Transcriptional and functional signatures of cell-sorted CD4+HLA-G+ cells were delineated by NanoString technology and suppression assays, respectively. The role of immunosuppressive cytokine interleukin (IL)-35 in inducing this population was investigated through in vitro blockade experiments. Immunohistochemistry (IHC) and cultures of primary human Kupffer cells (KCs) were performed to assess cellular sources of IL-35. HLA-G-mediated T cell suppression was explored using neutralising antibodies targeting co-inhibitory pathways.Results Patients with AD were distinguished by an expansion of a CD4+HLA-G+CTLA-4+IL-35+ immunosuppressive population associated with disease severity, clinical course of AD, infectious complications and poor outcome. Transcriptomic analyses excluded the possibility that these were thymic-derived regulatory T cells. IHC analyses and in vitro cultures demonstrate that KCs represent a potent source of IL-35 which can induce the observed HLA-G+ phenotype. These exert cytotoxic T lymphocyte antigen-4-mediated impaired responses in T cells paralleled by an HLA-G-driven downregulation of T helper 17-related cytokines.Conclusion We have identified a cytokine-driven peripherally derived suppressive population that may contr
Forlano R, Harlow C, Mullish BH, et 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.
Lett A, Lim A, Skinner C, et al., 2021, Rapid, non-invasive measurement of gastric emptying rate using transcutaneous fluorescence spectroscopy, Biomedical Optics Express, Vol: 12, Pages: 4249-4264, ISSN: 2156-7085
Gastric emptying rate (GER) signifies the rate at which the stomach empties following ingestion of a meal and is relevant to a wide range of clinical conditions. GER also represents a rate limiting step in small intestinal absorption and so is widely assessed for research purposes. Despite the clinical and physiological importance of gastric emptying, methods used to measure GER possess a series of limitations (including being invasive, slow or unsuitable for certain patient populations). Here, we present a new technique based on transcutaneous (through-the-skin) fluorescence spectroscopy that is fast, non-invasive, and does not require the collection of samples or laboratory-based analysis. Thus, this approach has the potential to allow immediate reporting of clinical results. Using this new method, participants receive an oral dose of a fluorescent contrast agent and a wearable probe detects the uptake of the agent from the gut into the blood stream. Analysis of the resulting data then permits the calculation of GER. We compared our spectroscopic technique to the paracetamol absorption test (a clinically approved GER test) in a clinical study of 20 participants. Results demonstrated good agreement between the two approaches and, hence, the clear potential of transcutaneous fluorescence spectroscopy for clinical assessment of GER.
Lemoine M, Cooke GS, Thursz M, et al., 2021, Cuts to UK official development assistance budget jeopardise global viral hepatitis elimination goals., Lancet Gastroenterol Hepatol, Vol: 6, Pages: 527-528
Possamai L, Gudd C, Au L, et 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
Post G, Howell J, Sow A, et 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
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Gustot T, Stadlbauer V, Laleman W, et 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
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- Citations: 8
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