Impact and cost-effectiveness of scaling up HCV testing and treatment strategies for achieving HCV elimination among people who inject drugs in England: a mathematical modelling study.

Background: England aims to reach the World Health Organization (WHO) elimination target of decreasing HCV incidence among people who inject drugs (PWID) to <2 per 100 person-years (/100pyrs) by 2030. We assessed what testing and treatment strategies will achieve this target and whether they are cost-effective.

Methods: A dynamic deterministic HCV transmission model among PWID was developed for four England regions, utilising data on the scale-up of HCV treatment among PWID in prisons, drug treatment centres (DTC, where opioid agonist therapy is provided), and any other setting (e.

Qualitative service evaluation of a multimodal pilot service for early detection of liver disease in high-risk groups: 'Alright My Liver?'.

Objective: Liver disease is a growing cause of premature death in the UK. The National Health Service in England (NHS England) has funded regional early detection programmes through Community Liver Health Check pilots. 'Alright My Liver?' is Bristol and Severn's pilot service offering early detection of liver disease through screening events serving populations at risk, including people with a history of drug or alcohol use, type 2 diabetes and obesity.

Proactive case finding of alcohol-related liver disease in high-risk populations: A systematic review.

Background: Alcohol-related liver disease (ARLD) is often diagnosed at a late stage when mortality is unacceptably high. Earlier identification of ARLD may lead to reduced alcohol intake, participation in hepatocellular carcinoma surveillance and reduction in liver-related morbidity and mortality. People with alcohol use disorder (AUD) are at highest risk of ARLD.

EASL clinical practice guidelines: non-invasive liver tests for evaluation of liver disease severity and prognosis.

The European Association for the Study of the Liver has recently published updated guidelines on the use of non-invasive tests to identify and stratify chronic liver disease. Here, we provide a summary of the key recommendations from the guideline.

Evaluating future risk of NAFLD in adolescents: a prediction and decision curve analysis.

Background: Non-alcoholic fatty liver disease (NAFLD) is the commonest liver condition in the western world and is directly linked to obesity and the metabolic syndrome. Elevated body mass index is regarded as a major risk factor of NAFL (steatosis) and NAFLD fibrosis. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we sought to investigate whether other variables from adolescence could improve prediction of future NAFL and NAFLD fibrosis risk at 24 years, above BMI and sex.

Evaluating the interaction of human serum albumin (HSA) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes in different aqueous environments using anisotropy resolved multi-dimensional emission spectroscopy (ARMES).

Studying the interaction between plasma proteins and liposomes is critical, particularly for their use as drug delivery systems. Here, the efficacy of anisotropy resolved multidimensional emission spectroscopy (ARMES) for investigating the interaction of human serum albumin (HSA) with liposomes was explored and compared to conventional spectroscopic techniques. Dynamic Light Scattering (DLS) and absorbance spectroscopy (with Multivariate Curve Resolution (MCR) modeling) indicated that the highest degree of liposome rupturing, and aggregation occurred in water, with less in ammonium bicarbonate buffer (ABC) and phosphate buffered saline (PBS).

Association of maternal pre-pregnancy BMI and breastfeeding with NAFLD in young adults: a parental negative control study.

Background: The importance of the maternal-infant dyad in the genesis of nonalcoholic fatty liver disease (NAFLD) is of increasing interest. The Avon Longitudinal Study of Parents and Children (ALSPAC) showed that at age 24, 1 in 5 had NAFLD measured by transient elastography and controlled attenuation parameter (CAP). Our aim was to investigate the association between breastfeeding duration and maternal pre-pregnancy BMI on offspring NAFLD in young adulthood.

Advanced Spectroscopy and APBS Modeling for Determination of the Role of His190 and Trp103 in Mouse Thymidylate Synthase Interaction with Selected dUMP Analogues.

A homo-dimeric enzyme, thymidylate synthase (TS), has been a long-standing molecular target in chemotherapy. To further elucidate properties and interactions with ligands of wild-type mouse thymidylate synthase (mTS) and its two single mutants, H190A and W103G, spectroscopic and theoretical investigations have been employed. In these mutants, histidine at position 190 and tryptophan at position 103 are substituted with alanine and glycine, respectively.

Spontaneous portomesenteric thrombosis in a non-cirrhotic patient with SARS-CoV-2 infection.

Intra-abdominal thromboses are a poorly characterised thrombotic complication of COVID-19 and are illustrated in this case. A 42-year-old man with chronic hepatitis B (undetectable viral load, FibroScan 7.4 kPa) developed fever and cough in March 2020.

Modelling Förster resonance energy transfer (FRET) using anisotropy resolved multi-dimensional emission spectroscopy (ARMES).

Background: Förster Resonance Energy Transfer (FRET) is widely used to study the structure and dynamics of biomolecular systems and also causes the non-linear fluorescence response observed in multi-fluorophore proteins. Accurate FRET analysis, in terms of measuring changes in donor and acceptor spectra and energy transfer efficiency is therefore critical.

Methods: We demonstrate a novel quantitative FRET analysis using anisotropy resolved multidimensional emission spectroscopy (ARMES) in a Human Serum Albumin (HSA) and 1,8-anilinonaphathalene sulfonate (ANS) model.

Persistent Hepatitis E virus infection across England and Wales 2009-2017: Demography, virology and outcomes.

The first clinical case of persistent HEV infection in England was reported in 2009. We describe the demography, virology and outcomes of patients identified with persistent HEV infection in England and Wales between 2009 and 2017. A series of 94 patients with persistent HEV infection, defined by HEV viraemia of more than 12 weeks, was identified through routine reference laboratory testing.

Impact of direct-acting antiviral agents on liver function in patients with chronic hepatitis C virus infection.

Whilst the benefit of direct-acting antiviral agents (DAAs) in achieving sustained virological response (SVR) is now well-accepted, their impact on liver function, particularly in relation to achievement of SVR, has not been well documented. We studied 2394 patients with chronic HCV infection, 1276 receiving DAAs and 1118 interferon-based therapy. Liver function was assessed by the albumin-bilirubin (ALBI) score or grade.

Cost effectiveness of an intervention to increase uptake of hepatitis C virus testing and treatment (HepCATT): cluster randomised controlled trial in primary care.

Objective: To evaluate the effectiveness and cost effectiveness of a complex intervention in primary care that aims to increase uptake of hepatitis C virus (HCV) case finding and treatment.

Design: Pragmatic, two armed, practice level, cluster randomised controlled trial and economic evaluation.

Setting And Participants: 45 general practices in South West England (22 randomised to intervention and 23 to control arm).

Liver steatosis is a risk factor for hepatotoxicity in inflammatory bowel disease patients treated with azathioprine.

Background And Aims: The literature demonstrates that hepatic steatosis reduces the tolerance of immunosuppression in people with inflammatory bowel disease. It also shows that elevated methylmercaptopurine may be responsible for thiopurine-induced hepatitis. This exploratory study investigates the relationship between hepatic steatosis, methylmercaptopurine and alanine transaminase.

Implementing user-defined atlas-based auto-segmentation for a large multi-centre organisation: the Australian Experience.

Introduction: Contouring has become an increasingly important aspect of radiation therapy due to inverse planning, and yet is extremely time-consuming. To improve contouring efficiency and reduce potential inter-observer variation, the atlas-based auto-segmentation (ABAS) function in Velocity was introduced to ICON cancer centres (ICC) throughout Australia as a solution for automatic contouring.

Methods: This paper described the implementation process of the ABAS function and the construction of user-defined atlas sets and compared the contouring efficiency before and after the introduction of ABAS.

Cell block processing is optimal for assessing endoscopic ultrasound fine needle aspiration specimens of pancreatic mucinous cysts.

Aims: The cell block technique for assessing endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) specimens from pancreatic mucinous cystic lesions (MCLs) was systematically evaluated for the first time, including comparisons with three traditional methods of assessing such specimens.

Methods: The prospective arm comprised EUS-FNA specimens from EUS-suspected pancreatic MCLs. The retrospective arm comprised EUS-FNA specimens from pancreatic MCLs surgically resected before the study start.

Elbasvir/grazoprevir and sofosbuvir for hepatitis C virus genotype 3 infection with compensated cirrhosis: A randomized trial.

Unlabelled: Many direct-acting antiviral regimens have reduced activity in people with hepatitis C virus (HCV) genotype (GT) 3 infection and cirrhosis. The C-ISLE study assessed the efficacy and safety of elbasvir/grazoprevir (EBR/GZR) plus sofosbuvir (SOF) with and without ribavirin (RBV) in compensated cirrhotic participants with GT3 infection. This was a phase 2, randomized, open-label study.

Integration of palliative and supportive care in the management of advanced liver disease: development and evaluation of a prognostic screening tool and supportive care intervention.

Background And Objectives: Patients with decompensated cirrhosis rarely receive palliative and supportive care interventions, which are routine in other life-limiting diseases. We aimed to design and evaluate a prognostic screening tool to routinely identify inpatients with decompensated cirrhosis at high risk of dying over the coming year, alongside the development of a supportive care intervention.

Design: Clinical notes from consecutive patients admitted as an emergency to University Hospitals Bristol with a diagnosis of cirrhosis over two distinct 90-day periods were scrutinised retrospectively for the presence or absence of five evidence-based factors associated with poor prognosis.

Hepatitis C - Assessment to Treatment Trial (HepCATT) in primary care: study protocol for a cluster randomised controlled trial.

Background: Public Health England (PHE) estimates that there are upwards of 160,000 individuals in England and Wales with chronic hepatitis C virus (HCV) infection, but until now only around 100,000 laboratory diagnoses have been reported to PHE and of these 28,000 have been treated. Targeted case-finding in primary care is estimated to be cost-effective; however, there has been no robust randomised controlled trial evidence available of specific interventions. Therefore, this study aims to develop and conduct a complex intervention within primary care and to evaluate this approach using a cluster randomised controlled trial.

The impact on hospital resource utilisation of treatment of hepatic encephalopathy with rifaximin-α.

Background & Aims: Rifaximin-α reduces the risk of recurrence of overt hepatic encephalopathy. However, there remain concerns regarding the financial cost of the drug. We aimed to study the impact of treatment with rifaximin-α on healthcare resource utilisation using data from seven UK liver treatment centres.

Clinical skills in junior medical officers: a comparison of self-reported confidence and observed competence.

Background: The intern year is a key time for the acquisition of clinical skills, both procedural and cognitive. We have previously described self-reported confidence and experience for a number of clinical skills, finding high levels of confidence among Australian junior doctors. This has never been correlated with an objective measure of competence.