These guidelines on transjugular intrahepatic portosystemic stent-shunt (TIPSS) in the management of portal hypertension have been commissioned by the Clinical Services and Standards Committee (CSSC) ...of the British Society of Gastroenterology (BSG) under the auspices of the Liver Section of the BSG. The guidelines are new and have been produced in collaboration with the British Society of Interventional Radiology (BSIR) and British Association of the Study of the Liver (BASL). The guidelines development group comprises elected members of the BSG Liver Section, representation from BASL, a nursing representative and two patient representatives. The quality of evidence and grading of recommendations was appraised using the GRADE system. These guidelines are aimed at healthcare professionals considering referring a patient for a TIPSS. They comprise the following subheadings: indications; patient selection; procedural details; complications; and research agenda. They are not designed to address: the management of the underlying liver disease; the role of TIPSS in children; or complex technical and procedural aspects of TIPSS.
Liver disease in the UK stands out as the one glaring exception to the vast improvements made during the past 30 years in health and life expectancy for chronic disorders such as stroke, heart ...disease, and many cancers. Mortality rates have increased 400% since 1970, and in people younger than 65 years have risen by almost five-times.
Non-alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular risk irrespective of conventional risk factors. The role of gut-liver interaction is implicated in its ...development. We investigated the effects of VSL#3
probiotic supplementation on biomarkers of cardiovascular risk and liver injury in patients with NAFLD.
A randomised, double-blinded, placebo-controlled, proof-of-concept study was undertaken. Patients with NAFLD were randomly allocated to take 2 sachets VSL#3
probiotic or placebo twice daily for 10 weeks. Measurements of endothelial function (digital photoplethysmography, sVCAM-1 and cGMP), oxidative stress (glutathione ratio and LHP), inflammation (hsCRP), insulin resistance (HOMA-IR) and liver injury transaminases, fibrosis risk score and acoustic structure quantification (ASQ) were undertaken before and after intervention. Difference in baseline characteristics between the treatment groups was analysed using independent t-test or Mann Whitney U test for non-parametric data. Independent t-test was used to compare the outcomes at the end of the study between the two treatment groups. Wilcoxon Signed Rank test was used to determine the difference in fibrosis risk scores before and after treatment. Spearman's correlation was used to determine any association between cardiovascular and hepatic markers at baseline.
Thirty-five patients completed the study (28 males and 7 females) with a mean age of 57 ± 8 years, body mass index of 32.6 ± 5.0 kg/m
and a relatively short duration of NAFLD (median duration 0.3 IQR 2.0 years). No significant difference was observed in biomarkers of cardiovascular risk and liver injury following VSL#3
supplementation. Significant correlations were noted between sVCAM-1 and hsCRP (rho = 0.392, p = 0.01), and HOMA-IR and AST (rho = 0.489, p < 0.01) at baseline.
This is the first study to evaluate the effect of VSL#3
on ASQ in patients with NAFLD. VSL#3
did not significantly improve markers of cardiovascular risk and liver injury in patients with NAFLD. However, the study supports an association between endothelial dysfunction and inflammation in patients with NAFLD and suggests that NAFLD is linked with insulin resistance.
ISRCTN05474560 ( https://doi.org/10.1186/ISRCTN05474560 ) Registered 9 August 2012 (retrospectively registered).
The risk of significant liver fibrosis from prolonged methotrexate (MTX) exposure has been estimated at around 5%, prompting intensive monitoring strategies. However, the evidence is derived from ...retrospective studies that under-reported risk factors for liver disease. We evaluated the risk of long-term MTX therapy on liver fibrosis in a longitudinal cohort study using two non-invasive markers.
Between 2014-2021, adult patients diagnosed with rheumatoid arthritis (RA) or psoriasis for ≥2 years were recruited prospectively from six UK sites. The MTX group included patients who received MTX for ≥6 months, whereas the unexposed group included those who never received MTX. All patients underwent full liver profiling, with transient elastography (TE) and enhanced liver fibrosis (ELF) marker measurements.
A total of 999 patients (mean age 60.8 ± 12 years, 62.3% females) were included. Of 976 with valid TE values, 149 (15.3%) had liver stiffness ≥7.9 kPa. Of 892 with a valid ELF, 262 (29.4%) had ELF ≥9.8. Age and BMI were independently associated with elevated liver stiffness and ELF. Neither MTX cumulative dose nor duration was associated with elevated liver stiffness. Diabetes was the most significant risk factor associated with liver stiffness ≥7.9 kPa (adjusted odds ratio = 3.19; 95% CI 1.95–5.20; p <0.001). Regular use of non-steroidal anti-inflammatory drugs showed the strongest association with ELF ≥9.8 (odds ratio = 1.76; 95% CI 1.20–2.56; p = 0.003), suggesting the degree of joint inflammation in RA may confound ELF as a non-invasive marker of liver fibrosis.
The risk of liver fibrosis attributed to MTX itself might have been previously overestimated; there is a need to consider modifying current monitoring guidelines for MTX.
Current guidelines recommend intensive (2-3 monthly) monitoring strategies for patients on long-term methotrexate therapy due to the potential risk of liver fibrosis. Evaluation of the association using two validated non-invasive markers of liver fibrosis, liver stiffness and enhanced liver fibrosis score, in a large cohort of patients with rheumatoid arthritis or psoriasis shows that the reported risk has previously been overestimated. The clinical focus should be to improve patients’ metabolic risk factors, diabetes and BMI, that are independently associated with liver stiffness. There is a need to consider modifying current treatment monitoring guidelines for methotrexate.
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•Guidelines have recommended intensive monitoring based on the reported risk of liver fibrosis linked to methotrexate.•Using non-invasive markers, we show that the risk of liver fibrosis linked to long-term methotrexate may have been overestimated.•Our findings support the need to improve patients’ metabolic risk factors, which are significantly associated with liver fibrosis.•In patients with rheumatoid arthritis, transient elastography is more reliable to screen for liver fibrosis than ELF.
Abstract Purpose Vitamin D is increasingly thought to play a role in regulating immunity. This comprehensive review updates the current understanding regarding ways in which we believe that vitamin D ...regulates responsiveness of the immune system and how serum status modulates the host defense against pathogens. Methods The literature was searched by using PubMed and Scopus with the following key words: vitamin D , immunity , innate and adaptive immunity , infectious disease , and vaccine response. Findings Vitamin D deficiency remains a major public health concern worldwide. The overall body of evidence confirms that vitamin D plays an important role in modulating the immune response to infections. Epidemiologic studies suggest a clear association between vitamin D deficiency and susceptibility to various pathogens. However, translation of vitamin D use into the clinic as a means of controlling infections is fraught with methodologic and epidemiologic challenges. The recent discovery of alternative activation pathways, different active forms of vitamin D, and possible interaction with non–vitamin D receptors provide further complications to an already complex interaction between vitamin D and the immune system. Moreover, it has become apparent that the individual responsiveness to supplementation is more dynamic than presumed from the static assessment of 25-hydroxy vitamin D status. Furthermore, the epigenetic response at the level of the individual to environmental changes and lifestyle or health conditions provides greater variation than those resulting from vitamin D receptor polymorphisms. Implications To understand the future of vitamin D with respect to clinical applications in the prevention and better control of infectious diseases, it is necessary to determine all aspects of vitamin D metabolism, as well as the mechanisms by which active forms interact with the immune system globally. For the most part, we are unable to identify tissue-specific applications of supplementation except for those subjects at high risk of osteomalacia and osteoporosis.
Advanced age is one indicator of likely immune dysfunction. As worldwide, the global population contains progressively more and more older individuals there is likelihood of an increased prevalence ...and incidence of infectious diseases due to common and emergent pathogens. The resultant increase in mortality and morbidity would be matched by the risk of functional decline and disability. Maintaining immune function at a plateau throughout life may therefore be associated with considerable cost savings. The aim of improving immune function in older individuals may be achieved through considering a therapeutic approach to rejuvenate, stimulate or support the indigenous immune system to perform in a more optimal manner. In terms of cost effectiveness a therapeutic approach may prove difficult because of issues associated with; identifying those who would benefit the most from this treatment, identifying the type of treatment which would suit them and identifying whether the treatment was successful. The alternative of supporting or providing a stronger stimulus through vaccination, whilst more cost effective, may be a more valuable option in the short term. Both approaches will be addressed in this review.
Predictive vegetation modeling (PVM), is defined as predicting the distribution of vegetation across a landscape based on the relationship between the spatial distribution of vegetation and ...environmental variables. PVM requires digital maps of the environmental variables, as well as spatial information on the vegetation attribute of interest (e.g., species, type, abundance), usually from a sample of locations. Often these predictive models are developed using traditional statistical methods and are based on the implicit assumption that the distribution of vegetation is random and, therefore, each observation is independent. This approach violates one of the basic tenets of geography, the direct relationship between distance and likeness, as well as of ecological theory, that elements of an ecosystem close to one another are more likely to be influenced by the same generating process and will therefore be similar. Some of the spatial structure can be explained by the predictor variables used in the model. Environmental variables such as precipitation, temperature and elevation exhibit spatial dependence, some of which is responsible for spatial clustering in vegetation distribution, but remaining spatial dependence can result from either unmeasured environmental variables or biotic processes that cause spatial clustering. Spatial dependence in biogeographical data has been recently identified as an important area of future PVM research, and many studies have begun to explore ways to incorporate spatial dependence in predictive models. Here we review the different approaches to incorporating spatial dependence into predictive vegetation models focusing on four statistical methods: autoregressive models, geostatistics, geographically weighted regression, and parameter estimation models. Autoregressive models may be more capable of describing the fine-scaled spatial dependence that results from local biotic factors, such as disturbance, competition, or dispersal, while geostatistical methods may be more suitable for modeling broad-scale spatial dependence. The other methods focus on global and local parameter estimation in the presence of spatially structured or nonstationary data. While this review focuses on incorporating spatial dependence into statistical models for predictive purposes, explicitly including spatial dependence in models can also aid in clarifying the effect of different explanatory variables, thereby improving inferences.
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•There is an unmet need to identify patients with alcohol related liver disease at an earlier stage.•Our analysis of over 50,000 medical admissions shows that unselected screening for ...alcohol misuse is achievable.•Universal screening identifies:–Higher risk patients – mortality, younger age of death.–Recurrent attenders/readmissions.–Cohort of patients with very high unit consumption.–Higher frequency of alcohol related liver disease.•Lower risk patients can be given brief advice by any trained healthcare professional.•Alcohol screening can be delivered by general nurses working 24hours a day, 7days a week.•Populations at highest risk of ARLD can be selectively targeted for interventions.
Many people who die from alcohol related liver disease (ARLD) have a history of recurrent admissions to hospital, representing potential missed opportunities for intervention. Universal screening for alcohol misuse has been advocated but it is not known if this is achievable or effective at detecting individuals at high risk of ARLD.
We systematically screened all admissions to the Acute Medical Unit (AMU) of a large acute hospital using an electronic data capture system in real time. Patients at an increasing risk of alcohol harm were referred for either brief intervention (BI) or further assessment by an Alcohol Specialist Nursing Service (ASNS). Additional data were recorded on admission diagnoses, alcohol unit consumption, previous attendances, previous admissions, length of stay and mortality.
Between July 2011 and March 2014, there were 53,165 admissions and 48,211 (90.68%) completed screening. Of these, 1,122 (2.3%) were classified as “increasing”, and 1,921 (4.0%) as “high” risk of alcohol harm. High risk patients had more hospital admissions in the three previous years (average 4.74) than the low (3.00) and increasing (2.92) risk groups (p<0.001). The high risk patients also had more frequent emergency department (ED) attendances (7.68) than the lower (2.64) and increasing (3.81) groups (p<0.001 for both). A total of 1,396 (72.6%) of the high risk group were seen by the ASNS and 1,135 (81.2%) had an Alcohol Use Disorders Identification Test (AUDIT) score over 20 with 527 (37.8%) recording the maximum value of 40. Compared to the other groups, high risk patients had a distinct profile of admissions with the most common diagnoses being mental health disorders, gastro-intestinal bleeding, poisoning and liver disease.
Universal screening of admissions for alcohol misuse is feasible and identifies a cohort with frequent ED attendances, recurrent admissions and an elevated risk of ARLD. An additional group of patients at an increasing risk of alcohol harm can be identified in a range of common presentations. These patients can be targeted with interventions to reduce the burden of alcohol related harm.
Lay summary: Many people who die from alcohol related liver disease (ARLD) have a recent history of recurrent admissions to hospital. These admissions may represent missed opportunities to intervene earlier and offer effective therapies for alcohol misuse. Unfortunately, we know that patients are often missed because medical staff may not routinely ask about alcohol consumption.
In our study of over 50,000 admissions, we have demonstrated the feasibility of offering screening for alcohol misuse to all medical admissions to hospital and delivered this 24hours a day, 7days a week, with automatic referral to treatment services. We have shown that it is possible to identify those people who are at the highest risk of dependency, those who have attended the emergency department the most and those who are at an increased risk of ARLD. We hope this study will lead to improved detection and management of alcohol problems in acute hospitals.
Obesity-related liver disease and prevalence of primary hepatocellular carcinoma (HCC) are both increasing, with ever increasing costs to the National Health Service (NHS). The ten major ...recommendations in the Lancet Commission report were selected as needing urgent implementation on the basis of strong evidence and are considered below in terms of what has been achieved to date and where there is ongoing work.
In this analysis of the ASTRAL trials (non-opioid substitution therapy OST, n = 984; OST, n = 51) evaluating the once-daily, pan-genotypic regimen of sofosbuvir/velpatasvir for hepatitis C virus ...infection, OST did not impact completion, adherence, sustained virologic response (SVR12), or safety. SVR12 was 96% (95% confidence interval, 87%, >99%) in those receiving OST.
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