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Non-alcoholic fatty liver disease (NAFLD) is common, affecting approximately 25% of the general population. The evidence base for the investigation and management of NAFLD is large and growing, but there is currently little practical guidance to support development of services and delivery of care. To address this, we produced a series of evidence-based quality standard recommendations for the management of NAFLD, with the aim of improving patient care. A multidisciplinary group of experts from the British Association for the Study of the Liver and British Society of Gastroenterology NAFLD Special Interest Group produced the recommendations, which cover: management of people with, or at risk of, NAFLD before the gastroenterology or liver clinic; assessment and investigations in secondary care; and management in secondary care. The quality of evidence for each recommendation was evaluated by the Grading of Recommendation Assessment, Development and Evaluation tool. An anonymous modified Delphi voting process was conducted individually by each member of the group to assess the level of agreement with each statement. Statements were included when agreement was 80% or greater. From the final list of statements, a smaller number of auditable key performance indicators were selected to allow services to benchmark their practice. It is hoped that services will review their practice against our recommendations and key performance indicators and institute service development where needed to improve the care of patients with NAFLD.

Alcoholic hepatitis (AH) is a severe condition with poor short-term prognosis. Specific treatment with corticosteroids slightly improves short-term survival but is associated with infection and is not used in many centers. A reliable method to identify patients who will recover spontaneously will minimise the numbers of patients who experience side effects of available treatments.We analysed the trajectory of serum bilirubin concentration over the course of hospital admissions in patients with AH to predict spontaneous survival and the need for treatment.data from 426 patients were analysed. Based on bilirubin trajectory, patients were categorized into three groups: 'fast fallers' (bilirubin0.8 x admission value at day 7), 'static' (bilirubin of0.9 -1.2 x admission value) and 'rapid risers' (bilirubin of ≥1.2 x admission bilirubin). Fast fallers had significantly better 90-day survival compared to other groups (log rank p.001), and showed no benefit of corticosteroid therapy (OR for survival at 28 days of treatment, 0.94, 95% CI 0.06 - 8.41). These findings remained even amongst patients with severe disease based on initial DF, GAHS or MELD scores.We present an intuitive method of classifying patients with AH based on the trajectory of bilirubin over the first week of admission. It is complimentary to existing scores that identify candidates for corticosteroid treatment or assess response to treatment. This method identifies a group of patients with AH who recover spontaneously and can avoid corticosteroid therapy.

ObjectiveHepatocellular carcinoma (HCC) incidence in the UK trebled between 1997 and 2017. With increasing numbers requiring treatment, understanding the likely impact on healthcare budgets can inform service planning and commissioning. The aim of this analysis was to use existing registry data to describe the direct healthcare costs of current treatments for HCC and estimate the impact on National Health Service (NHS) budgets.DesignA retrospective data analysis based on the National Cancer Registration and Analysis Service cancer registry informed a decision-analytic model for England comparing patients by cirrhosis compensation status and those on palliative or curative treatment pathways. Potential cost drivers were investigated by undertaking a series of one-way sensitivity analyses.ResultsBetween 1 January 2010 and 31 December 2016, 15 684 patients were diagnosed with HCC. The median cost per patient over 2 years was £9065 (IQR: £1965 to £20 491), 66% did not receive active therapy. The cost of HCC treatment for England over 5 years was estimated to be £245 million.ConclusionThe National Cancer Registration Dataset and linked data sets have enabled a comprehensive analysis of the resource use and costs of secondary and tertiary healthcare for HCC, providing an overview of the economic impact to the NHS England of treating HCC.

Background Hepatocellular carcinoma (HCC) incidence, management and survival across England were examined to determine if geographical inequalities exist. Method 15,468 HCC cases diagnosed 2010–2016 were included. Age-standardised incidence rates, net survival and proportions receiving potentially curative treatment and presenting through each route to diagnosis adjusted for age at diagnosis, sex and area-based deprivation quintile, were calculated overall and by Cancer Alliance. Results HCC incidence rates increased in men from 6.2 per 100,000 in 2010 to 8.8 in 2016, and in women from 1.5 to 2.2. The highest incidence rates, found in parts of the North of England and London, were nearly double the lowest. The adjusted proportion presenting as an emergency ranged 27–41% across Cancer Alliances. Odds increased with increasing deprivation quintile and age. Only one in five patients received potentially curative treatment (range 15–28%) and odds decreased with increasing deprivation and age. One-year survival in 2013–2016 ranged 38–53%. Conclusion This population-based, nationwide analysis demonstrates clear differences in HCC incidence, management and survival across England. It highlights socioeconomic-associated variation and the need for improvement in early diagnosis and curative treatment of HCC. This research should assist policymakers, service providers and clinicians to identify regions where additional training, services and resources would be best directed.

BACKGROUND: Impaired pretransplant performance status (PS) is associated with chronic liver disease (CLD). We studied its impact on hospital length of stay (LOS), complications, and readmissions in the first year after liver transplantation. METHODS: The Standard National Liver Transplant Registry was linked to a hospital administrative dataset, and all first-time liver transplant recipients with CLD aged ≥18 years in England were identified. A modified 3-level Eastern Cooperative Oncology Group score was used to assess PS. Linear- and logistic-fixed effect regression models were used to estimate the effect of specific posttransplant complications and readmissions in the first year after transplantation. RESULTS: Six thousand nine hundred sixty-eight recipients were included. Impaired PS was associated with an increased LOS in the initial posttransplant period (comparing ECOG 1-3, adjusted difference 7.2 d; 95% confidence [CI], 4.8-9.6; P < 0.001) and in time spent on the ITU (adjusted difference 1.2 d; 95% CI, 0.4-2.0; P < 0.001). There was no significant association between ECOG status and total LOS of later admissions (adjusted difference, 2.5 d; 95% CI, -0.4-5.5; P = 0.23). Those with a poorer ECOG status had an increased incidence of renal failure (odds ratio, 1.5; 95% CI, 1.1-2.0; P = 0.004) and infection (odds ratio, 1.2; 95% CI, 1.1-1.4; P = 0.02) but not an increased incidence of readmission (odds ratio, 1.2; 95% CI, 0.9-1.5; P = 0.13). CONCLUSIONS: In liver transplant recipients with CLD, impaired pretransplant PS is associated with prolonged LOS in the immediate posttransplant period but not with LOS of later admissions in the first year after transplantation. Impaired PS increased the risk of renal failure and infection.

Governments in the Global South have recently started to align their public procurement regulations considering Green Public Procurement (GPP) guidelines to achieve Sustainable Development Goal 12. In this context, it is important to establish environmental criteria to help decision making after analyzing the variety of options available in the market. Thus, using as examples two of the most acquired products in public procurement in Peru: Medium-density particleboard melamine furniture and paper offset, the aim of this paper is to determine the main environmental hotspots and therefore show the path to foster GPP in Peru. To achieve this goal, a Life Cycle Assessment was carried out considering it is a suitable environmental management tool to quantify environmental impacts. For this, a set of scenarios were modeled and compared for each of the two products selected, covering different geographical and technological options that are currently purchased by the Peruvian government. Results demonstrated that it is possible to attain considerable reductions in the environmental impact of the products analyzed if the main critical stages throughout their life cycle are identified and adequate solutions are applied to avoid burden shifting. Moreover, we argue that it is important for developing countries to carry out case-specific life-cycle inventories as they provide higher-quality information based on the particular characteristics of regional or local industries, allowing the determination of more realistic environmental impact mitigation benchmarks. Nevertheless, the inclusion of lifecycle-based criteria in GPP must be performed cautiously, avoiding command and control regulations, as numerous challenges remain in terms of capacity building, environmental awareness, and environmental information, and transparency in emerging and developing economies. Integr Environ Assess Manag 2022;18:1206-1220. © 2021 SETAC.

Background and aims Animal models of human disease are a key component of translational hepatology research, yet there is no consensus on which model is optimal for NAFLD. Approach and results We generated a database of 3,920 rodent models of NAFLD. Study designs were highly heterogeneous, and therefore, few models had been cited more than once. Analysis of genetic models supported the current evidence for the role of adipose dysfunction and suggested a role for innate immunity in the progression of NAFLD. We identified that high-fat, high-fructose diets most closely recapitulate the human phenotype of NAFLD. There was substantial variability in the nomenclature of animal models: a consensus on terminology of specialist diets is needed. More broadly, this analysis demonstrates the variability in preclinical study design, which has wider implications for the reproducibility of in vivo experiments both in the field of hepatology and beyond. Conclusions This systematic analysis provides a framework for phenotypic assessment of NAFLD models and highlights the need for increased standardization and replication.

Micro-mobility has increased in urban environments to reduce dependence on private vehicles. While electric micro-mobility alternatives are supposed to reduce environmental impacts, certain studies suggest that this can depend on the transport mode they substitute. In parallel, despite growing efforts, urban areas in developing and emerging economies struggle to implement sustainable mobility programs at a city-wide level. In March 2019 the first dockless e-scooter rental service appeared in the city of Lima, Peru. Although the social and environmental impacts of dockless e-scooters have been the center of multiple studies, these are mostly based in North America and Europe. Therefore, the main objective of the current study was to use Life Cycle Assessment (LCA) to address the environmental profile of e-scooter use in districts of central Lima. All stages of the life-cycle of e-scooters were modelled considering local conditions, from manufacture to end-of-life. A sensitivity analysis was conducted to account for the variability in environmental impact based on five parameters: lifespan, battery range, remaining battery charge, collection distance and collection vehicle. Results show that over two thirds of impacts are linked to manufacturing thanks to the low-carbon profile of electricity production in Peru, which lowers the burdens in the use phase, making e-scooter use competitive in the local market as compared to electric bikes or motorcycles. However, replacement trends show that net environmental gains are not always obtained. Poor maintenance and derived lifespan or battery range are important sources of variability for the impact categories assessed. Although e-scooters show potential for their implementation in developing cities with similar characteristics to Lima, we recommend that site-specific studies should be conducted to foster adaptive management strategies which take into account the means of transport being substituted by e-scooters.

Nonalcoholic steatohepatitis (NASH) has emerged as one of the important causes of cirrhosis and hepatocellular carcinoma, and over 50 therapeutic agents are in various Phases of clinical development. Recently, obeticholic acid has achieved the interim histological endpoint of fibrosis improvement with no worsening of NASH in the phase 3 REGENERATE study, and now patients are being followed for long-term clinical outcomes. Several drugs are in Phase 3 trials with a goal to achieve conditional registration under the subpart H pathway by the United States Food and Drug Administration (FDA). It is thus timely to consider the current situation and the way ahead in the management of NASH. In this article, we review the natural history of nonalcoholic fatty liver disease, upcoming treatments for NASH and various assessments. Based on the current knowledge, we discuss what should be the target treatment population and whether non-invasive tests are ready to guide NASH treatments, both for patient selection and evaluation of treatment response.

AIM To establish the diagnostic accuracy of the Liver Imaging Reporting and Data System (LI-RADS) for hepatocellular carcinoma (HCC) and compare its performance to that of international criteria from European Assofor the Study of the Liver (EASL), Japan Society of Hepatology (JSH), Asian Pacific Association for the Study of the Liver (APASL), and Organ Procurement and Transplantation Network (OPTN), and to the reporting radiologist's overall opinion regarding the probability of a nodule being a HCC by correlating with a histological diagnosis from whole liver explants. MATERIALS AND METHODS The present single-centre, retrospective review selected participants based on the following criteria: adults (≥18 years) listed for liver transplantation in 2014/2015, with liver cirrhosis at the time of magnetic resonance imaging (MRI) with hepatocyte specific contrast agent, and at least one liver lesion ≥10 mm on MRI with histology from subsequent liver explant for comparison. Each lesion was assessed against international criteria and given a “radiologist opinion” score of 1–5 (1 = definitely benign, 5 = definitely HCC). RESULTS Total 268 patient records were reviewed, with 105 eligible lesions identified from 47 patients. Median lesion size was 15.5 mm (range 10–68 mm). Sensitivity (%), specificity (%), and positive predictive value (PPV; %) for LI-RADS LR5 was 45, 89, and 89, for LI-RADS LR4+5 + TIV was 61, 80, and 86, for EASL was 44, 86 and 86, for JSH/APASL was 64, 81, and 87, for OPTN was 36, 90, and 88, and for “radiologist impression” of probably or definitely HCC was 79, 79, and 88 respectively. CONCLUSIONS MRI has moderate sensitivity and good specificity for the diagnosis of HCC with considerable variation depending on criteria used. OPTN criteria have the best specificity, but low sensitivity. “Radiologist opinion” gives highest overall accuracy with increases in sensitivity and reduction in specificity when compared to the imaging criteria.

Background & aims Liver fibrosis is the critical determinant of liver-related outcomes in persons with nonalcoholic fatty liver disease. The rate that fibrosis develops determines the time taken to reach cirrhosis and consequent clinical outcomes. Estimates of the fibrosis progression rate (FPR) are uncertain having been defined in small observational series that rely largely on nonstandardised repeat biopsy in selected patients. The aim of this study was to evaluate the FPR in placebo-treated participants with nonalcoholic steatohepatitis (NASH) in randomised controlled trials (RCTs). Methods Systematic review and meta-analysis of RCTs in NASH with data on fibrosis change extracted. Calculated fibrosis progression rates were pooled in meta-analysis. The pooled estimate was then used to model the proportion of hypothetical cohorts starting with no fibrosis at the age of 30 who develop cirrhosis. Results A total of 35 trials including 1419 placebo-treated participants who underwent repeat liver biopsy were evaluated. Considering all trials, the overall FPR was 0.00 stages per year, increasing to 0.03 stages per year in both trials at low risk of bias and trials including >50 placebo-treated participants. This estimate was markedly lower than the value derived from previously pooled analyses of observational data. Using a FPR of 0.03 resulted in a substantial reduction in the proportion of patients developing cirrhosis compared with the FPR derived from observational studies (13% vs 28%). Conclusions The FPR in placebo-treated participants in RCTs is lower than that described from observational data. Slower fibrosis progression predicts fewer persons with NASH will progress to cirrhosis than previously estimated.

Background Athletic underperformance is characterized by fatigue and an inability to sustain a consistent exercise workload. We describe five elite swimmers with prolonged fatigue and athletic underperformance. Based on our work in myalgic encephalomyelitis /chronic fatigue syndrome, we focused on orthostatic intolerance as a possible contributor to symptoms. Methods Participants were referred for evaluation of fatigue and underperformance to the Chronic Fatigue Clinic at the Johns Hopkins Children’s Center. All patients were evaluated for overtraining syndrome, as well as for features commonly seen in myalgic encephalomyelitis/chronic fatigue syndrome. The latter included joint hypermobility, orthostatic intolerance, and non-IgE mediated milk protein intolerance. Orthostatic intolerance was tested by performing a ten-minute passive standing test or a head-up tilt table test. Results Orthostatic testing provoked fatigue and other symptoms in all five swimmers, two of whom met heart rate criteria for postural tachycardia syndrome. Treatment was individualized, primarily consisting of an increased intake of sodium chloride and fluids to address orthostasis. All patients experienced a relatively prompt improvement in fatigue and other orthostatic symptoms and were able to either return to their expected level of performance or improve their practice consistency. Conclusions Orthostatic intolerance was an easily measured and treatable contributor to athletic underperformance in the five elite swimmers we describe. We suggest that passive standing tests or formal tilt table tests be incorporated into the clinical evaluation of athletes with fatigue and underperformance as well as into scientific studies of this topic. Recognition and treatment of orthostatic intolerance provides a new avenue for improving outcomes in underperforming athletes.

The aim of this review is to evaluate previous life cycle assessment (LCA) studies of first- and second-generation bioplastics, to understand the state of the art and the main problems addressed during the development of new bioplastics. Furthermore, it provides an overview on land use change (LUC) impacts accounted for, methodologies chosen, and the results obtained. Studies related to the impact assessment of bioplastics and published between 2007 and 2018 were gathered. Five keyword strings were used to perform a wide search and select relevant LCA studies. The study aimed to analyze critical methodological aspects in LCA, in order to determine the most common choices made during biobased material analyses, as well as major limitations. Three filters were applied to select comparable studies, ending with a final number of 17 papers. Recommendations were obtained by comparing common practices performed by different authors with suggested best available practices mentioned in handbooks and guidelines. Interestingly, LUC metrics and impacts were, most of the time, neglected. Thus, a specific assessment and discussion was performed regarding the methods used to quantify LUC impacts, considering its importance during the production of biobased materials. The study discussed the main environmental problems linked to the development of new biomaterials. LCA of agricultural products or systems, when compared with fossil-based counterparts, is expected to show higher environmental impacts in categories directly affected by fertilizer use, occupied and transformed land, among others. Thus, studies that included additional impact categories besides global warming (e.g., eutrophication or acidification) concluded that biobased materials present higher impacts, recommending improvements in farming practices to improve their overall environmental profile. Moreover, this review gathered methodologies used to account for LUC impacts and the results obtained. The main constraint of including LUC impacts was the lack of a standardized methodology, as well as large uncertainties in existing methodologies. Most studies concluded that improvements in farming practices might reduce the attributed environmental impacts with the reduction of the amount of land, fertilizer, pesticides, and water used. Studies computing LUC impacts agreed on the importance of including these impacts and concluded that greenhouse gas emissions of bioplastic production would increase, but in most cases would still be lower than the impact of their fossil-based counterparts. However, challenges remain when computing LUC impacts that need to be tackled when working with the available methodologies, including the collection of reliable inventory data (site-specific or regional data) and regionalized characterization factors.

Nonalcoholic steatohepatitis (NASH) with liver fibrosis is an increasingly important cause of liver-related morbidity and mortality. A diagnosis of NASH can only be made using liver biopsy. Liver histology also forms the endpoint for the expedited licensing strategies that have been approved by regulators to allow patients with NASH access to treatment before the impact of these on clinical outcomes is known. Validation of these histological surrogate endpoints is critical for the ongoing development of new therapies for NASH. The use of liver biopsy to define both trial entry and endpoints raises questions about the use of treatments for NASH in practice when the effectiveness of treatment will likely depend, at least in part, on the use of histology for patient selection in the real world.

Background and aims Identifying how the prognostic impact of performance status (PS) differs according to indication, era, and time period ("epoch") after liver transplantation (LT) could have implications for selection and treatment of patients on the waitlist. We used national data from the United Kingdom and Ireland to assess impact of PS on mortality separately for HCC and non-HCC recipients. Approach and results We assessed pre-LT PS using the 5-point modified Eastern Cooperative Oncology Group scale and used Cox regression methods to estimate hazard ratios (HRs) that compared posttransplantation mortality in different epochs of follow-up (0-90 days and 90 days to 1 year) and in different eras of transplantation (1995-2005 and 2006-2016). 2107 HCC and 10,693 non-HCC patients were included. One-year survival decreased with worsening PS in non-HCC recipients where 1-year survival was 91.9% (95% confidence interval [CI], 88.3-94.4) in those able to carry out normal activity (PS1) compared to 78.7% (95% CI, 76.7-80.5) in those completely reliant on care (PS5). For HCC patients, these estimates were 89.9% (95% CI, 85.4-93.2) and 83.1% (95% CI, 61.0-93.3), respectively. Reduction in survival in non-HCC patients with poorer PS was in the first 90 days after transplant, with no major effect observed between 90 days and 1 year. Adjustment for donor and recipient characteristics did not change the findings. Comparing era, post-LT mortality improved for HCC (adjusted HR, 0.55; 95% CI, 0.40-0.74) and non-HCC recipients (0.48; 95% CI, 0.42-0.55), but this did not differ according to PS score (P = 0.39 and 0.61, respectively). Conclusions Impact on mortality of the recipient's pretransplant PS is principally limited to the first 3 months after LT. Over time, mortality has improved for both HCC and non-HCC recipients and across the full range of PS.

Overexploitation or full exploitation of fishing stocks first became an important problem in the second half of the 20th century, with certain fisheries collapsing and others being exploited in an unsustainable manner. This situation led to dwindling fish landings worldwide, although final seafood demand has not suffered this decrease thanks to the growth of aquaculture. Currently, new threats to marine biota are emerging that could ultimately lead to further stress on fishing stocks. The current opinion article explores these growing threats, which include the spread of dead zones throughout coastal areas, marine litter, especially microplastics and nanoplastics that are ingested by marine organisms and ultimately by humans, or the effects of climate change on world oceans, including acidification due to carbon dioxide absorption from the atmosphere or alteration in ocean circulation due to melting glaciers. Consequently, it is critical for stakeholders in the fishing sector to gain awareness of what is at stake in the upcoming decades. In fact, not only will fisheries have to expand their approach from single-species stock assessment to ecosystem-based approaches but also other metrics will have to be brought forward to maintain competitiveness and minimize food security concerns.

Aquaculture is an increasingly important supplier of food worldwide. However, due to its high dependence on agricultural and fishing resources, its growth is constantly constrained by environmental impacts beyond aquaculture production systems. Within the European Union, Spain accounts for approximately 25 % of total aquaculture production, which implies that environmental impacts in rivers and marine ecosystems must be monitored to understand the role of aquaculture systems. While studies on the environmental performance of mussels or turbot production have been reported in the literature, Spanish rainbow trout (Oncorhynchus mykiss) has not received much attention despite its relative importance. In this sense, a Life Cycle Assessment (LCA) study of rainbow trout produced in a medium-sized plant in Galicia (NW Spain) was carried out in the present study. The study considered the production of round weight trout, as well as some commonly produced processed products, including filleting. The life cycle modelling included a high level of primary data in the foreground system. In addition to the widely considered environmental impact categories for this activity (e.g., global warming potential, terrestrial acidification and freshwater eutrophication), the recent proposed antibiotic resistance (ABR) enrichment impact category was included to explore the potential impact of antibiotic release in freshwater microbiota. The results highlighted the high contribution of aquafeed to most impact categories, due to upstream agricultural and fishing processes, whereas farm operation was responsible for the larger part of the impact in freshwater eutrophication, mainly due to direct emissions of nutrients from fish feeding. Amoxicillin release to recipient water bodies was the main driver to the ABR enrichment category. In contrast, the processing phase (i.e., gutting, freezing and packaging) showed low environmental burdens. In order to improve the environmental performance of the rainbow trout production system, decreasing the feed conversion ratio (FCR), shifting to renewable energy, using low environmental burden ingredients in aquafeed, and alternatives to control diseases without antibiotics could be considered.

In a context of increasing concern regarding food loss and waste (FLW) generation, different attempts have been made to standardize quantification methodologies. On the one hand, an important number of small-scale studies have been published that constitute direct measurement methodologies. On the other hand, the FAO Food Balance Sheets, which aggregate some of the prior studies, provides an indirect metric that has been applied using FLW coefficients in numerous food-related studies. However, to date, no standard methodology has been agreed upon to quantify FLW. This study performs an assessment of 237 studies in the field, aiming to identify existing FLW quantification methodologies, and if there is a need of developing alternative paths. Firstly, a descriptive review was performed. Secondly, an assessment of critical point of views was presented. For this, different critical voices in the scientific literature were retrieved, some of which highlight the high level of uncertainty and a certain degree of opacity in some of the most widespread FLW quantification and assessment reports. In this line, essential elements of quantification are being omitted. Moreover, the focus is being excessively placed on the role of the consumer, compared to the role played by agribusiness and large distribution chains. The authors are grateful for the funding of the Spanish Ministry of Science and Innovation through the KAIROS-BIOCIR project (PID2019-104925RB) (AEO/FEDER, UE). Dr. Ian Vázquez-Rowe and Dr. Ramzy Kahhat wish to thank the Department of Engineering, as well as the Dirección de Fomento de la Investigación (Project number PI0769) at PUCP, for funding their time dedicated to this study.

Background and aims Non-alcoholic fatty liver disease is common and there are a number of treatments in development. Patients with non-alcoholic steatohepatitis (NASH) and significant fibrosis are thought to be the population most in need of treatment. Identification of this group requires liver biopsy. The aim of this study was to identify the proportion of patients screened for phase 2 randomised controlled trials who subsequently entered these studies. Methods Large, multicentre, phase 2 randomised controlled trials of pharmacological therapies for NASH were identified by systematic review. The pooled proportion of potential participants who entered the trials was estimated by meta-analysis. The reasons for trial ineligibility were separately extracted and analysed. Results Thirteen reports of 14 trials were included. Overall, there were 4014 screened individuals included in the quantitative analyses and 53% were subsequently enrolled in a trial. Considering trials in which the entry criteria matched the current paradigm for treatment, that is, the presence of NASH and significant fibrosis, only 35% of screened individuals were eligible for trial entry. More than half of ineligible individuals were excluded on the basis of liver histology most often due to insufficient disease activity with or without insufficient fibrosis. Conclusion The majority of patients considered at risk of NASH and fibrosis sufficient for treatment in randomised controlled trials are ineligible for trial entry. Most often, this is due to ineligible liver histology. These findings have implications for the design of future trials in NASH and for the applicability of treatments after licensing.

Patients with chronic liver disease are often diagnosed during an index presentation to hospital with decompensated cirrhosis or liver-related events, and these presentations are associated with high mortality. However, there is often a long asymptomatic phase, in which there is an opportunity for earlier diagnosis and interventions to prevent progression to advanced disease. Therefore, strategies for early diagnosis and interventions (including behavioural changes and pharmacological treatments) that prevent patients progressing to cirrhosis and its associated complications probably have substantial benefits for patients and health-care services. Many community pathways have been generated. Some pathways focus on abnormal liver function tests as a starting point to diagnose liver disease. Other pathways target groups at greater risk of chronic liver disease-particularly people with harmful alcohol consumption, type 2 diabetes, and obesity. This systematic review summarises the existing strategies available for the early detection or risk stratification of liver disease, focusing primarily on alcohol-related liver disease and non-alcoholic fatty liver disease. Conducting randomised clinical trials that compare different strategies will be essential to elucidate which pathways are acceptable to patients, feasible, provide high diagnostic accuracy for the detection of liver disease, improve liver-related outcomes, and are most cost-effective at the population level.

Background Post hepatectomy liver failure (PHLF) remains a significant risk in patients undergoing curative liver resection for cancer, however currently available PHLF risk prediction investigations are not sufficiently accurate. The Hepatectomy risk assessment with functional magnetic resonance imaging trial (HEPARIM) aims to establish if quantitative MRI biomarkers of liver function & perfusion can be used to more accurately predict PHLF risk and FLR function, measured against indocyanine green (ICG) liver function test. Methods HEPARIM is an observational cohort study recruiting patients undergoing liver resection of 2 segments or more, prior to surgery patients will have both Dynamic Gadoxetate-enhanced (DGE) liver MRI and ICG testing. Day one post op ICG testing is repeated and R15 compared to the Gadoxetate Clearance (GC) of the future liver remnant (FLR-GC) as measure by preoperative DGE- MRI which is the primary outcome, and preoperative ICG R15 compared to GC of whole liver (WL-GC) as a secondary outcome. Data will be collected from medical records, biochemistry, pathology and radiology reports and used in a multi-variate analysis to the value of functional MRI and derive multivariant prediction models for future validation. Discussion If successful, this test will potentially provide an efficient means to quantitatively assess FLR function and PHLF risk enabling surgeons to push boundaries of liver surgery further while maintaining safe practice and thereby offering chance of cure to patients who would previously been deemed inoperable. MRI has the added benefit of already being part of the routine diagnostic pathway and as such would have limited additional burden on patients time or cost to health care systems. (Hepatectomy Risk Assessment With Functional Magnetic Resonance Imaging - Full Text View -ClinicalTrials.gov, n.d.) Trial registration ClinicalTrials.gov, ClinicalTrials.gov NCT04705194 - Registered 12th January 2021 – Retrospectively registered