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Perez Guzman PN, Daunt A, Mukherjee S, et al., 2020, Report 17: Clinical characteristics and predictors of outcomes of hospitalised patients with COVID-19 in a London NHS Trust: a retrospective cohort study
Clinical characteristics and determinants of outcomes for hospitalised COVID-19 patients in the UK remain largely undescribed and emerging evidence suggests ethnic minorities might be disproportionately affected. We describe the characteristics and outcomes of patients hospitalised for COVID-19 in three large London hospitals with a multi-ethnic catchment population.We performed a retrospective cohort study on all patients hospitalised with laboratory-confirmed SARS-CoV-2 infection at Imperial College Healthcare NHS Trust between February 25 and April 5, 2020. Outcomes were recorded as of April 19, 2020. Logistic regression models, survival analyses and cumulative competing risk analyses were performed to evaluate factors associated with COVID-19 hospital mortality.Of 520 patients in this cohort (median age 67 years, (IQR 26) and 62% male), 302 (68%) had been discharged alive, 144 (32%) died and 74 (14%) were still hospitalised at the time of censoring. Increasing age (adjusted odds ratio [aOR] 2·16, 95%CI 1·50-3·12), severe hypoxia (aOR 3·75, 95%CI 1·80-7·80), low platelets (aOR 0·65, 95%CI 0.49·0·85), reduced estimated glomerular filtration rate (aOR 4·11, 95%CI 1·58-10·69), bilirubin >21mmol/L (aOR 2·32, 95%CI 1·05-5·14) and low albumin (aOR 0·77, 9%%CI 0·59-1·01) were associated with increased risk of in-hospital mortality. Individual comorbidities were not independently associated with risk of death. Regarding ethnicity, 209 (40%) were from a black and Asian minority, for 115 (22%) ethnicity was unknown and 196 (38%) patients were white. Compared to the latter, black patients were significantly younger and had less comorbidities. Whilst the crude OR of death of black compared to white patients was not significant (1·14, 95%CI 0·69-1·88, p=0.62), adjusting for age and comorbidity showed a trend towards significance
Kaura A, Arnold AD, Vasileios P, et al., 2020, Prognostic significance of troponin level in 3,121 patients presenting with atrial fibrillation (The NIHR Health Informatics Collaborative TROP-AF study), Journal of the American Heart Association, Vol: 9, ISSN: 2047-9980
Background-—Patients presenting with atrial fibrillation (AF) often undergo a blood test to measure troponin, but interpretation of theresult is impeded by uncertainty about its clinical importance. We investigated the relationship between troponin level, coronaryangiography, and all-cause mortality in real-world patients presenting with AF.Methods and Results-—We used National Institute of Health Research Health Informatics Collaborative data to identify patients admitted between 2010 and 2017 at 5 tertiary centers in the United Kingdom with a primary diagnosis of AF. Peak troponin results 7 were scaled as multiples of the upper limit of normal. A total of 3121 patients were included in the analysis. Over a median followup of 1462 (interquartile range, 929–1975) days, there were 586 deaths (18.8%). The adjusted hazard ratio for mortality associatedwith a positive troponin (value above upper limit of normal) was 1.20 (95% CI, 1.01–1.43; P<0.05). Higher troponin levels were associated with higher risk of mortality, reaching a maximum hazard ratio of 2.6 (95% CI, 1.9–3.4) at 250 multiples of the upper limit of normal. There was an exponential relationship between higher troponin levels and increased odds of coronary angiography.The mortality risk was 36% lower in patients undergoing coronary angiography than in those who did not (adjusted hazard ratio, 0.61; 95% CI, 0.42–0.89; P=0.01).Conclusions-—Increased troponin was associated with increased risk of mortality in patients presenting with AF. The lower hazard ratio in patients undergoing invasive management raises the possibility that the clinical importance of troponin release in AF may be mediated by coronary artery disease, which may be responsive to revascularization.
Shimakawa Y, Ndow G, Njie R, et al., 2020, Hepatitis B core-related antigen (HBcrAg): an alternative to HBV DNA to assess treatment eligibility in Africa, Clinical Infectious Diseases, Vol: 70, Pages: 1442-1452, ISSN: 1058-4838
BACKGROUND: To eliminate hepatitis B virus (HBV) infection, it is essential to scale up testing and treatment. However, conventional tools to assess treatment eligibility, particularly nucleic acid testing (NAT) to quantify HBV DNA, are hardly available and affordable in resource-limited countries. We therefore assessed the performance of novel immunoassay, hepatitis B core-related antigen (HBcrAg), as an inexpensive (US$ <10-15/assay) alternative to NAT to diagnose clinically important HBV DNA thresholds (≥2,000; ≥20,000; and ≥200,000 IU/ml), and select patients for antiviral therapy in Africa. METHODS: Using well-characterized cohort of treatment-naïve patients with chronic HBV infection in The Gambia, we evaluated the accuracy of serum HBcrAg to diagnose HBV DNA levels, and to indicate treatment eligibility determined by the American Association for the Study of Liver Diseases, based on the reference tests (HBV DNA, HBV e antigen (HBeAg), alanine transaminase (ALT), liver histopathology and/or FibroScan). RESULTS: A total of 284 treatment-naïve patients were included in the analysis. The area under the receiver operating characteristic curve (AUROC), sensitivity and specificity of serum HBcrAg were: 0.88 (95% CI: 0.82-0.93), 83.3% and 83.9% to diagnose HBV DNA ≥2,000 IU/ml; and 0.94 (0.88-0.99), 91.4% and 93.2% for ≥200,000 IU/ml. A simplified treatment algorithm using HBcrAg without HBV DNA showed high AUROC (0.91 (95% CI: 0.88-0.95)) with a sensitivity of 96.6% and specificity of 85.8%. CONCLUSIONS: HBcrAg might be an accurate alternative to HBV DNA quantification as a simple and inexpensive tool to identify HBV-infected patients in need of antiviral therapy in low- and middle-income countries.
Avila MA, Dufour J-F, Gerbes AL, et al., 2020, Recent advances in alcohol-related liver disease (ALD): summary of a Gut round table meeting, GUT, Vol: 69, Pages: 764-780, ISSN: 0017-5749
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Forlano R, Mullish BH, Nathwani R, et al., 2020, Non-alcoholic fatty liver disease and vascular disease, Current Vascular Pharmacology, Vol: 18, ISSN: 1570-1611
Non-Alcoholic Fatty Liver Disease (NAFLD) represents an increasing cause of liver disease worldwide. However, notably, the primary cause of morbidity and mortality in patients with NAFLD is cardiovascular disease (CVD), with fibrosis stage being the strongest disease-specific predictor. It is globally-projected that NAFLD will become increasingly prevalent, especially among children and younger adults. As such, even within the next few years, NAFLD will contribute considerably to the overall CVD burden. In this review, we discuss the role of NAFLD as an emerging risk factor for CVD. In particular, this article aims to provide an overview of pathological drivers of vascular damage in patients with NAFLD. Moreover, the impact of NAFLD on the development, severity and the progression of subclinical and clinical CVD will be discussed. Finally, the review illustrates current and potential future perspectives for screening for CVD in this high-risk population.
Pinato DJ, Guerra N, Fessas P, et al., 2020, Immune-based therapies for hepatocellular carcinoma, Oncogene, Vol: 39, Pages: 3620-3637, ISSN: 0950-9232
Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer-related death. The immune-rich contexture of the HCC microenvironment makes this tumour an appealing target for immune-based therapies. Here, we discuss how the functional characteristics of the liver microenvironment can potentially be harnessed for the treatment of HCC. We will review the evidence supporting a therapeutic role for vaccines, cell-based therapies and immune-checkpoint inhibitors and discuss the potential for patient stratification in an attempt to overcome the series of failures that has characterised drug development in this disease area.
Mohamed Z, Mbwambo J, Rwegasha J, et al., 2020, In-field evaluation of Xpert® HCV viral load fingerstick assay in people who inject drugs in Tanzania, Liver International, Vol: 40, Pages: 514-521, ISSN: 1478-3223
BackgroundAlthough novel hepatitis C (HCV) RNA point-of-care technology has the potential to enhance diagnosis in resource-limited settings, very little real-world validation of their utility exists. We evaluate the performance of HCV RNA quantification using the Xpert® HCV Viral Load Fingerstick assay (Xpert® HCV VL Fingerstick assay) as compared to the WHO pre-qualified plasma Xpert® HCV viral load assay among people who inject drugs (PWID) attending an opioid agonist therapy (OAT) clinic in Dar-es-Salaam, Tanzania. MethodsBetween December 2018 and February 2019 consecutive HCV seropositive PWID attending the OAT clinic provided paired venous and finger-stick samples for HCV RNA quantification. These were processed on-site using the GeneXpert® platform located at the Central tuberculosis reference laboratory. ResultsA total of 208 out of 220 anti-HCV positive participants recruited (94.5%) had a valid Xpert® HCV VL result available; 126 (61%; (95% CI 53.8-67.0) had detectable and quantifiable HCV RNA. 188 (85%) had paired plasma and finger-stick whole blood samples; the sensitivity and specificity for the quantification of HCV RNA levels were 99.1% and 98.7% respectively. There was an excellent correlation (R2=0.95) and concordance (mean difference 0.13 IU/mL, (95% CI -0.9 to 0.16 IU/mL) in HCV RNA levels between plasma samples and finger-stick samples.ConclusionThis study found excellent performance of the Xpert® HCV VL Fingerstick assay for HCV RNA detection and quantification in an African-field setting. Its clinical utility represents an important watershed in overcoming existing challenges to HCV diagnosis, which should play a crucial role in HCV elimination in Africa.
Atkinson SR, Hamesch K, Spivak I, et al., 2020, Serum transferrin is an independent predictor of mortality in severe alcoholic hepatitis., American Journal of Gastroenterology, Vol: 115, Pages: 398-405, ISSN: 0002-9270
OBJECTIVES: Severe alcoholic hepatitis (sAH) confers substantial mortality, but the disease course is difficult to predict. As iron parameters are attractive outcome predictors in other liver diseases, we tested their prognostic ability in sAH. METHODS: Serum ferritin, transferrin, iron, transferrin saturation, nontransferrin-bound iron, soluble transferrin receptor, and hepcidin were measured in 828 patients with sAH recruited prospectively through the STOPAH trial. The cohort was randomly divided into exploratory (n = 200) and validation sets (n = 628). RESULTS: Patients with sAH had diminished serum transferrin but increased transferrin saturation. Among iron parameters, baseline transferrin was the best predictor of 28-day (area under the receiver operated characteristic 0.72 [95% confidence interval 0.67-0.78]) and 90-day survival (area under the receiver operated characteristic 0.65 [0.61-0.70]). Transferrin's predictive ability was comparable with the composite scores, namely model of end-stage liver disease, Glasgow alcoholic hepatitis score, and discriminant function, and was independently associated with survival in multivariable analysis. These results were confirmed in a validation cohort. Transferrin did not correlate with markers of liver synthesis nor with non-transferrin-bound iron or soluble transferrin receptor (as markers of excess unbound iron and functional iron deficiency, respectively). DISCUSSION: In patients with sAH, serum transferrin predicts mortality with a performance comparable with commonly used composite scoring systems. Hence, this routinely available parameter might be a useful marker alone or as a component of prognostic models.
Ghani R, Mullish BH, McDonald J, et al., 2020, Disease prevention not decolonisation: a cohort study for faecal microbiota transplantation for patients colonised with multidrug-resistant organisms, ECCMID 2020
Kaura A, Panoulas V, Glampson B, et al., 2019, Association of troponin level and age with mortality in 250 000 patients: cohort study across five UK acute care centres, BMJ-British Medical Journal, Vol: 367, ISSN: 1756-1833
ObjectiveTo determine the relation between age and troponinlevel and its prognostic implication.DesignRetrospective cohort study.SettingFive cardiovascular centres in the UK National Institutefor Health Research Health Informatics Collaborative(UK-NIHR HIC).Participants257948 consecutive patients undergoing troponintesting for any clinical reason between 2010 and2017.Main outcome measureAll cause mortality.Results257948 patients had troponin measured during thestudy period. Analyses on troponin were performedusing the peak troponin level, which was the highesttroponin level measured during the patient’s hospitalstay. Troponin levels were standardised as a multipleof each laboratory’s 99th centile of the upper limitof normal (ULN). During a median follow-up of 1198days (interquartile range 514-1866 days), 55850(21.7%) deaths occurred. A positive troponin result(that is, higher than the upper limit of normal)signified an overall 3.2-fold higher mortality hazard(95% confidence interval 3.1-fold to 3.2-fold) overthree years. The mortality hazard varied markedly withage, from 10.6-fold (8.5-fold to 13.3-fold) in 18-29year olds to 1.5 (1.4 to 1.6) in those older than 90.A positive troponin result was associated with anapproximately 15 percentage points higher absolutethree year mortality across all age groups. The excessmortality with a positive troponin result was heavilyconcentrated in the first few weeks. Results wereanalysed using multivariable adjusted restrictedcubic spline Cox regression. A direct relation wasseen between troponin level and mortality in patientswithout acute coronary syndrome (ACS, n=120049),whereas an inverted U shaped relation was foundin patients with ACS (n=14468), with a paradoxicaldecline in mortality at peak troponin levels >70xULN.In the group with ACS, the inverted U shaped relationpersisted after multivariable adjustment in those whowere managed invasively; however, a direct positiverelation was found between troponin level
Mohamed Z, Al-Kurdi D, nelson M, et al., 2019, Time matters: Point of care screening and streamlined linkage to care dramatically improves hepatitis C treatment uptake in prisoners in England, International Journal of Drug Policy, ISSN: 0955-3959
Ryan J, Adams H, Atkinson S, et al., 2019, Type III interferon lambda derangements are associated with susceptibility to infection in alcohol-related liver disease, The International Liver Congress™ EASL - European Association for the Study of the Liver
Mullish BH, Forlano R, Abeles R, et al., 2019, Letter: role of mean platelet volume levels in prediction of major acute cardiovascular events in patients with non-alcoholic fatty liver disease – authors’ reply, Alimentary Pharmacology and Therapeutics, Vol: 50, Pages: 1140-1141, ISSN: 0269-2813
This article is linked to Abeles et al and Liu et al papers. To view these articles, visit https://doi.org/10.1111/apt.15192 and https://doi.org/10.1111/apt.15527.
Lebosse F, Gudd C, Tunc E, et al., 2019, CD8+ T cells from patients with cirrhosis display a phenotype that may contribute to cirrhosis-associated immune dysfunction, EBioMedicine, Vol: 49, Pages: 258-268, ISSN: 2352-3964
BackgroundCirrhosis-associated immune dysfunction (CAID) contributes to high sepsis risk in patients with chronic liver disease. Various innate and; to a lesser extent; adaptive immune dysfunctions have been described as contributors to CAID leading to immune-paresis and impaired anti-microbial response in cirrhosis. In this study, we examined the phenotype of CD8+ T cells in chronic liver disease with the aim to evaluate changes that might contribute to impaired immune responses.MethodsSixty patients with cirrhosis were prospectively recruited for this study. CD8+ T cells from peripheral blood, ascites and liver explants were characterized using flow cytometry and immunohistochemistry, respectively. The transcriptional signature of flow-sorted HLA-DR+CD8+ T cells was performed using Nanostring™ technology. HLA-DR+CD8+ T cells interactions with PBMCs and myeloid cells were tested in vitro.FindingsPeripheral CD8+ T cells from cirrhotic patients displayed an altered phenotype characterized by high HLA-DR and TIM-3 surface expression associated with concomitant infections and disease severity, respectively. Paired peritoneal CD8+ T cells expressed more pronounced levels of HLA-DR and PD-1 compared to peripheral CD8+ T cells. HLA-DR+CD8+ T cells were enriched in cirrhotic livers compared to controls. TIM-3, CTLA-4 and PD-1 levels were highly expressed on HLA-DR+CD8+ T cells and co-expression of HLA-DR and PD1 was higher in patients with poor disease outcomes. Genes involved in cytokines production and intracellular signalling pathways were strongly down-regulated in HLA-DR+CD8+ T cells. In comparison to their HLA-DR− counterparts, HLA-DR+CD8+ T cells promoted less proliferation of PBMCs and induced phenotypic and functional dysfunctions in monocytes and neutrophils in vitro.InterpretationIn patients with cirrhosis, CD8+ T cells display a phenotypic, functional and transcriptional profile which may contribute to CAID.FundThis work was supported by Medical Res
Forlano R, Mullish BH, Giannakeas N, et al., 2019, 2311 Impact of BMI and ethnicity on histology as assessed by automated quantitation in liver biopsies of patients with NAFLD, AASLD/ The Liver Meeting, Publisher: Wiley, Pages: 1359A-1359A, ISSN: 0270-9139
Schroeder SE, Pedrana A, Scott N, et al., 2019, Innovative strategies for the elimination of viral hepatitis at a national level: A country case series, LIVER INTERNATIONAL, Vol: 39, Pages: 1818-1836, ISSN: 1478-3223
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- Citations: 38
Rhodes F, Cococcia S, Vergis N, et al., 2019, AN ALGORITHM COMBINING HYALURONIC ACID, PROCOLLAGEN III AMINO-TERMINAL PEPTIDE AND THE GLASGOW ALCOHOLIC HEPATITIS SCORE IN A SINGLE NUMBER PREDICTS 90-DAY MORTALITY IN ALCOHOL-RELATED HEPATITIS., Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) / Liver Meeting, Publisher: WILEY, Pages: 817A-818A, ISSN: 0270-9139
Mullish BH, McDonald JAK, Pechlivanis A, et al., 2019, Microbial bile salt hydrolases mediate the efficacy of faecal microbiota transplant in the treatment of recurrent Clostridioides difficile infection, Gut, Vol: 68, Pages: 1791-1800, ISSN: 0017-5749
Objective Faecal microbiota transplant (FMT) effectively treats recurrent Clostridioides difficile infection (rCDI), but its mechanisms of action remain poorly defined. Certain bile acids affect C. difficile germination or vegetative growth. We hypothesised that loss of gut microbiota-derived bile salt hydrolases (BSHs) predisposes to CDI by perturbing gut bile metabolism, and that BSH restitution is a key mediator of FMT’s efficacy in treating the condition.Design Using stool collected from patients and donors pre-FMT/post-FMT for rCDI, we performed 16S rRNA gene sequencing, ultra performance liquid chromatography mass spectrometry (UPLC-MS) bile acid profiling, BSH activity measurement, and qPCR of bsh/baiCD genes involved in bile metabolism. Human data were validated in C. difficile batch cultures and a C57BL/6 mouse model of rCDI.Results From metataxonomics, pre-FMT stool demonstrated a reduced proportion of BSH-producing bacterial species compared with donors/post-FMT. Pre-FMT stool was enriched in taurocholic acid (TCA, a potent C. difficile germinant); TCA levels negatively correlated with key bacterial genera containing BSH-producing organisms. Post-FMT samples demonstrated recovered BSH activity and bsh/baiCD gene copy number compared with pretreatment (p<0.05). In batch cultures, supernatant from engineered bsh-expressing E. coli and naturally BSH-producing organisms (Bacteroides ovatus, Collinsella aerofaciens, Bacteroides vulgatus and Blautia obeum) reduced TCA-mediated C. difficile germination relative to culture supernatant of wild-type (BSH-negative) E. coli. C. difficile total viable counts were ~70% reduced in an rCDI mouse model after administration of E. coli expressing highly active BSH relative to mice administered BSH-negative E. coli (p<0.05).Conclusion Restoration of gut BSH functionality contributes to the efficacy of FMT in treating rCDI.
Mullish BH, 2019, The role of bile-metabolising enzymes in the pathogenesis of Clostridioides difficile infection, and the impact of faecal microbiota transplantation
Ong DJ, Hall A, Triantafyllou E, et al., 2019, Expression of Secretory Leukocyte Protease Inhibitor (SLPI) Detected by Immunohistochemistry in Hepatocellular and Cholangiocellular Tumours, 12th Joint Meeting of the British-Division-of-the-International-Academy-of-Pathology and the Pathological-Society-of-Great-Britain-and-Ireland (Leeds Pathology), Publisher: WILEY, Pages: S45-S45, ISSN: 0022-3417
Atkinson SR, Forrest E, Goh ET, et al., 2019, Previously Identified Candidate Gene Associations in Hepatic Encephalopathy Do Not Replicate in the STOPAH Cohort, 18th International-Society-for-Hepatic-Encephalopathy-and-Nitrogen-Metabolism Meeting, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: S39-S39, ISSN: 0002-9270
Chambers E, Byrne C, Rugyendo A, et al., 2019, The effects of dietary supplementation with inulin and inulin-propionate ester on hepatic steatosis in adults with non-alcoholic fatty liver disease, Diabetes, Obesity and Metabolism, Vol: 21, Pages: 372-376, ISSN: 1462-8902
The short chain fatty acid (SCFA) propionate, produced through fermentation of dietary fibre by the gut microbiota, has been shown to alter hepatic metabolic processes that reduce lipid storage. We aimed to investigate the impact of raising colonic propionate production on hepatic steatosis in adults with non‐alcoholic fatty liver disease (NAFLD). Eighteen adults were randomised to receive 20g/day of an inulin‐propionate ester (IPE), designed to deliver propionate to the colon, or an inulin‐control for 42‐days in a parallel design. The change in intrahepatocellular lipid (IHCL) following the supplementation period was not different between groups (P=0.082), however IHCL significantly increased within the inulin‐control group (20.9±2.9 to 26.8±3.9%; P=0.012; n=9), which was not observed within the IPE group (22.6±6.9 to 23.5±6.8%; P=0.635; n=9). The predominant SCFA from colonic fermentation of inulin is acetate, which in a background of NAFLD and a hepatic metabolic profile that promotes fat accretion, may provide surplus lipogenic substrate to the liver. The increased colonic delivery of propionate from IPE appears to attenuate this acetate‐mediated increase in IHCL.
Vergis N, Thursz M, Atkinson S, 2019, Assessment and management of infection in alcoholic hepatitis, Seminars in Liver Disease, Vol: 40, Pages: 11-19, ISSN: 0272-8087
Severe alcoholic hepatitis (SAH) is a condition characterized by jaundice and liver failure that develops after heavy and prolonged alcohol consumption. Infection frequently complicates the natural history of the disease and is independently associated with mortality. Objective recognition and recording of infection are therefore essential in the evaluation of therapeutic interventions and for antibiotic stewardship. This review will evaluate infections that complicate SAH at admission and beyond. Factors that associate with the development of infection will be identified and clinical and laboratory techniques available to identify infection will be discussed. Common pathogens and frequently used antibiotics will be reviewed and recommendations will be made for the management of infection for SAH patients. New techniques to assess infection earlier and more precisely may improve diagnosis and treatment of this important driver of mortality in SAH.
Forrest EH, Storey N, Sinha R, et al., 2019, Baseline neutrophil-to-lymphocyte ratio predicts response to corticosteroids and is associated with infection and renal dysfunction in alcoholic hepatitis., Alimentary Pharmacology and Therapeutics, Vol: 50, Pages: 442-453, ISSN: 0269-2813
BACKGROUND: Treating severe alcoholic hepatitis involves the exposure of patients to corticosteroids for 7 days to assess "response". AIM: To assess the prognostic and therapeutic implications of baseline Neutrophil-to-Lymphocyte ratio (NLR) in patients with severe alcoholic hepatitis. METHODS: Patients recruited to the STOPAH trial and an independent validation group were analysed retrospectively. Area under the Receiver Operating Curve (AUC) analysis was performed. Kaplan-Meier analysis was used to assess survival. Log-rank test and Odds ratio (OR) were used for comparative analysis. RESULTS: Baseline NLR was available for 789 STOPAH patients. The AUC for NLR was modest for 90-day outcome (0.660), but it was associated with infection, acute kidney injury (AKI) and severity of alcoholic hepatitis. Ninety-day survival was not affected by prednisolone treatment if NLR < 5 or > 8 < 5 but mortality was reduced with prednisolone treatment when the NLR was 5-8:21.0% cf. 34.5%; P = 0.012. Prednisolone treatment increased the chance of Lille response if the NLR was ≥ 5 (56.5% cf. 41.1%: P = 0.01; OR 1.86) but increased the risk of Day 7 infection (17.3% cf. 7.4%: P = 0.006; OR 2.60) and AKI (20.8% cf. 7.0%: P = 0.008; OR 3.46) if the NLR was > 8. Incorporation of NLR into a modified Glasgow Alcoholic Hepatitis Score (mGAHS) improved the AUC to 0.783 and 0.739 for 28-day and 90-day outcome, respectively. CONCLUSION: The NLR is associated with AKI and infection in severe alcoholic hepatitis. The NLR identifies those most likely to benefit from corticosteroids at baseline (NLR 5-8). The mGAHS has a good predictive value for 28- and 90-day outcomes.
Bennett K, Enki DG, Thursz M, et al., 2019, Systematic review with meta-analysis: high mortality in patients with non-severe alcoholic hepatitis, ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Vol: 50, Pages: 249-257, ISSN: 0269-2813
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Argemie J, Latasa MU, Atkinson SR, et al., 2019, Defective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis, Nature Communications, Vol: 10, Pages: 1-19, ISSN: 2041-1723
Alcoholic hepatitis (AH) is a life-threatening condition characterized by profound hepatocellular dysfunction for which targeted treatments are urgently needed. Identification of molecular drivers is hampered by the lack of suitable animal models. By performing RNA sequencing in livers from patients with different phenotypes of alcohol-related liver disease (ALD), we show that development of AH is characterized by defective activity of liver-enriched transcription factors (LETFs). TGFβ1 is a key upstream transcriptome regulator in AH and induces the use of HNF4α P2 promoter in hepatocytes, which results in defective metabolic and synthetic functions. Gene polymorphisms in LETFs including HNF4α are not associated with the development of AH. In contrast, epigenetic studies show that AH livers have profound changes in DNA methylation state and chromatin remodeling, affecting HNF4α-dependent gene expression. We conclude that targeting TGFβ1 and epigenetic drivers that modulate HNF4α-dependent gene expression could be beneficial to improve hepatocellular function in patients with AH.
Howell J, Atkinson SR, Pinato DJ, et al., 2019, Identification of mutations in circulating cell-free tumour DNA as a biomarker in hepatocellular carcinoma, European Journal of Cancer, Vol: 116, Pages: 56-66, ISSN: 0959-8049
BACKGROUND: Hepatocellular carcinoma (HCC) is increasing globally. Prognostic biomarkers are urgently needed to guide treatment and reduce mortality. Tumour-derived circulating cell-free DNA (ctDNA) is a novel, minimally invasive means of determining genetic alterations in cancer. We evaluate the accuracy of ctDNA as a biomarker in HCC. METHODS: Plasma cell-free DNA, matched germline DNA and HCC tissue DNA were isolated from patients with HCC (n = 51) and liver cirrhosis (n = 10). Targeted, multiplex polymerase chain reaction ultra-deep sequencing was performed using a liver cancer-specific primer panel for genes ARID1A, ARID2, AXIN1, ATM, CTNNB1, HNF1A and TP53. Concordance of mutations in plasma ctDNA and HCC tissue DNA was determined, and associations with clinical outcomes were analysed. RESULTS: Plasma cell-free DNA was detected in all samples. Lower plasma cell-free DNA levels were seen in Barcelona Clinic Liver Cancer (BCLC A compared with BCLC stage B/C/D (median concentration 122.89 ng/mL versus 168.21 ng/mL, p = 0.041). 29 mutations in the eight genes (21 unique mutations) were detected in 18/51 patients (35%), median 1.5 mutations per patient (interquartile range 1-2). Mutations were most frequently detected in ARID1A (11.7%), followed by CTNNB1 (7.8%) and TP53 (7.8%). In patients with matched tissue DNA, all mutations detected in plasma ctDNA detected were confirmed in HCC DNA; however, 71% of patients had mutations identified in HCC tissue DNA that were not detected in matched ctDNA. CONCLUSION: ctDNA is quantifiable across all HCC stages and allows detection of mutations in key driver genes of hepatic carcinogenesis. This study demonstrates high specificity but low sensitivity of plasma ctDNA for detecting mutations in matched HCC tissue.
Shen EY-L, Abellona U, Taylor-Robinson S, et al., 2019, Discovery and validation of plasma acylcarnitines for the early diagnosis of hepatocellular carcinoma, Annual Meeting of the American-Association-for-Cancer-Research (AACR), Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
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Ghani R, Gan C, Mullish BH, et al., 2019, P13-2 Prevalence of recurrent Extended Spectrum Beta-Lactamase (ESBL) urinary tract infections (UTIs) in patients within a Urology service and introducing the concept of Faecal Microbiota Transplantation (FMT) as a treatment modality, British Association of Urological Surgeons Annual Scientific Meeting, Publisher: SAGE Publications, Pages: 83-85, ISSN: 2051-4158
Mohamed Z, Kim JU, Magesa A, et al., 2019, High prevalence and poor linkage to care of transfusion transmitted infections among blood donors in Dar-es-Salaam, Tanzania, Journal of Viral Hepatitis, Vol: 26, Pages: 750-756, ISSN: 1352-0504
Blood transfusion is one of the most commonly relied upon therapies in sub‐Saharan Africa. Existing safeguards recommended include systematic screening for transfusion‐transmitted infections and restricted voluntary nonremunerated blood donor selection. We report the transfusion‐transmitted infection screening and notification practice at a large urban blood transfusion centre in Dar‐es‐Salaam, Tanzania. Between October 2016 and March 2017 anonymized records of all donors registered at the blood transfusion unit were accessed to retrospectively note demographic information, donor status, first‐time status, transfusion‐transmitted infection result and notification. 6402 consecutive donors were screened for transfusion‐transmitted infections; the majority were family/replacement blood donors (88.0%) and male (83.8%). Overall transfusion‐transmitted infections prevalence was 8.4% (95% CI 7.8‐9.1), with hepatitis B being the most prevalent infection (4.1% (95% CI 3.6‐4.6)). Transfusion‐transmitted infections were more common in family/replacement blood donors (9.0% (95% CI 8.3‐9.8)) as compared to voluntary nonremunerated blood donor (4.1% (95% CI 2.8‐5.7)). A minority of infected‐donors were notified of a positive result (8.5% (95% CI 6.3‐11.2)). Although transfusion‐transmitted infections are more prevalent among family/replacement blood donors, overall risk of transfusion‐transmitted infections across all groups is considerable. In addition, existing efforts to notify donors of a positive transfusion‐transmitted infection are poor. Future policies must focus on improving linkage to care for newly diagnosed patients with transfusion‐transmitted infections.
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