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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.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery datasets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5×10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signaling and cytokine-cytokine pathways, for which relevant therapies exist.

Chr. Hansen had no input into any aspect of study design or conduct of the trial. Furthermore, Chr. Hansen will have no input into data analysis or subsequent reporting of the trial results. PCC has received consulting fees from Chr. Hansen, but not in relation to this trial.

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.Keywords. HCV; OST; PWID; sofosbuvir; velpatasvir.People who inject drugs (PWID) are disproportionately affected by hepatitis C virus (HCV) infection [1]. People with a history of injection drug use include those who have stopped injecting, those with recent injecting, and those receiving opioid substitution therapy (OST; eg, methadone or buprenorphine), some of whom may also have recently injected drugs. Data are lacking on HCV treatment outcomes with interferon-free direct-acting antiviral agents (DAAs) among people receiving OST, particularly people with genotypes (G) other than HCV G1. The phase 3 ASTRAL 1-3 trials evaluated the efficacy and safety of sofosbuvir/velpatasvir in patients with chronic HCV genotypes 1-6 [2, 3]. People receiving stable OST were eligible for inclusion, but people with clinically relevant illicit drug use within 12 months or a positive urine drug test at screening were excluded. No drug screens were performed during or following treatment. These clinical trial populations are highly selected, included people on stable OST, excluded people with recent drug use, and may not be representative of recent PWID populations. However, there are little data on interferon-free DAA therapy among people receiving OST.The aim of this post hoc analysis was to evaluate treatment completion, adherence, sustained virologic response (SVR), and safety of sofosbuvir/velpatasvir in people receiving OST without drug use at screening. METHODS Study Participants and DesignFrom 18 July 2014 to 19 December 2014 participants were enrolled in 3 international, multicenter, randomized open-label trials, including ASTRAL 1-3 (ClinicalTrials.gov: NCT02201940, NCT02220998, and NCT02201953) [2,3]. A fixed-dose combination tablet of sofosbuvir/velpatasvir 400 mg/100 mg was administered for 12 weeks in patients with chronic HCV genotypes 1-6. These studies have been described previously [2,3].Participants receiving OST were eligible for inclusion in the ASTRAL studies. Patients were excluded if they had clinically significant drug use within 12 months of screening (as assessed by the investigator) or a noncannabinoid detected by a positive urine drug test during the screening phase not explained by a prescription medication. No drug screens were performed during or following treatment. Study EndpointsIn this analysis, endpoints included treatment completion, adherence (≥90% of doses), SVR12, safety (adverse events [AEs] and serious AEs), and reinfection. The analysis population included all randomized patients who received at least 1 dose of sofosbuvir/velpatasvir. Adherence was calculated by dividing the number of total doses received during therapy...

Initiation of treatment with rifaximin-α was associated with a marked reduction in the number of hospital admissions and hospital length of stay. These data suggest that treatment of patients with rifaximin-α for hepatic encephalopathy was generally cost saving.

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This final report of the Lancet Commission into Liver Disease in the UK stresses the continuing increase in disease burden of liver disease from excess alcohol consumption and obesity, with high levels of hospital admissions and a worsening in deprived areas. It concludes that only with comprehensive food and alcohol strategies based on fiscal and regulatory measures including the Minimum Unit Price (MUP) for alcohol and the alcohol duty escalator, as well as an extension of the sugar levy on food content which has been proven by previous experience in this country, can the disease burden be curtailed. Further evidence of the value of MUP is shown by initial published results (1) of its introduction in Scotland showing an overall 3% reduction in consumption, with the major effect as predicted on heavy drinkers of low-cost alcohol products The major contribution of obesity and alcohol to the high rates of the ten most common cancers is also discussed. The measures outlined by the departing Chief Medical Officer, Dame Sally Davies, to combat rising levels of obesitythe highest of any country in the Westare described along with the estimated health costs. The latest audit analysis of unacceptable levels of mortality for severely ill patients with liver disease in District General Hospitals (DGHs)(2) indicates the need for developing a masterplan for improving hospital care and such a plan is proposed in this report based around specialist hospital centres linked to DGHs by Operational Delivery Networks (ODNs). It has received strong backing from the British Association for Study of the Liver (BASL) and British Society of Gastroenterology (BSG) but is held up at NHS England (NHSE). The value of day-case care bundles to reduce high hospital readmission rates with greater care in the community is described, along with examples of locally derived schemes for the early detection of disease and in particular schemes to allow general practitioners (GPs) to refer patients directly for elastography assessment. New funding arrangements for GPs will be required if these are to be taken up more widely around the country, as is recommended. A new ComRes poll, to be published in autumn 2019, shows an appalling lack of understanding of harm to health from lifestyle causes, with a poor knowledge of alcohol consumption and dietary guidelines. The Commission has serious doubts as to whether the initiatives described in the Prevention Green Paper(3), with the onus placed on the individual based on the use of information technology and the latest in behavioural science will be effective. The final section of the report raises questions of meaningful survival in paediatric liver disease where despite excellent overall survival results, there are high levels of cognitive impairment. In the Conclusion, a strong plea is made for greater coordination between the various official and non-official bodies that have expressed views on the unacceptable disease burden from liver disease in this country in presenting a single, strong voice to the ...