The SCottish Alcoholic Liver disease Evaluation: a population-level matched cohort study of hospital-based costs, 1991-2011

Studies assessing the costs of alcoholic liver disease are lacking. We aimed to calculate the costs of hospitalisations before and after diagnosis compared to population controls matched by age, sex and socio-economic deprivation. We aimed to use population level data to identify a cohort of individuals hospitalised for the first time with alcoholic liver disease in Scotland between 1991 and 2011.Incident cases were classified by disease severity, sex, age group, socio-economic deprivation and year of index admission. 5 matched controls for every incident case were identified from the Scottish population level primary care database. Hospital costs were calculated for both cases and controls using length of stay from morbidity records and hospital-specific daily rates by specialty. Remaining lifetime costs were estimated using parametric survival models and predicted annual costs. 35,208 incident alcoholic liver disease hospitalisations were identified. Mean annual hospital costs for cases were 2.3 times that of controls pre diagnosis (£804 higher) and 10.2 times (£12,774 higher) post diagnosis. Mean incident admission cost was £6,663. Remaining lifetime cost for a male, 50-59 years old, living in the most deprived area diagnosed with acoholic liver disease was estimated to be £65,999 higher than the matched controls (£12,474 for 7.43 years remaining life compared to £1,224 for 21.8 years). In Scotland, alcoholic liver disease diagnosis is associated with significant increases in admissions to hospital both before and after diagnosis. Our results provide robust population level estimates of costs of alcoholic liver disease for the purposes of health-care delivery, planning and future cost-effectiveness analyses

Baclofen and the Alcohol Withdrawal Syndrome-A Short Review

The Alcohol Withdrawal Syndrome (AWS), which may occur with or without delirium, is a frequent consequence of sudden alcohol cessation in patients with moderate to severe Alcohol Dependence Syndrome (ADS). Withdrawal as a result of habituation to alcohol is part of the definition of the Alcohol Dependence Syndrome (ICD10). Since the recognition of Delirium Tremens, in the early nineteenth century, the management of the syndrome, an acute medical emergency, has proven controversial. The barbiturates, chlormethiazole, and recently the safer benzodiazepines transformed the management of these conditions. The benzodiazepines, particularly diazepam and chlordiazepoxide, are now the most used first line agents in the treatment of AWS. In addition, a number of other agents, including baclofen, a GABA-B receptor agonist, have the potential to suppress the alcohol withdrawal syndrome. In this review we review the potential use of baclofen in its role to treat AWS. We summarize initial case reports as well as more recent randomized trials of AWS treatment with baclofen. We conclude that currently there is not enough evidence to support the use of baclofen as a first line treatment for AWS. More research will be needed to determine where baclofen might have a role in second-line management of the Alcohol Withdrawal Syndrome on its own or in combination with benzodiazepines or other agents

Genome-wide association study of antisocial personality disorder diagnostic criteria provides evidence for shared risk factors across disorders

INTRODUCTION: While progress has been made in determining the genetic basis of antisocial behaviour, little progress has been made for antisocial personality disorder (ASPD), a condition that often co-occurs with other psychiatric conditions including substance use disorders, attention deficit hyperactivity disorder (ADHD), and anxiety disorders. This study aims to improve the understanding of the genetic risk for ASPD and its relationship with other disorders and traits. METHODS: We conducted a genome-wide association study (GWAS) of the number of ASPD diagnostic criteria data from 3217 alcohol-dependent participants recruited in the UK (UCL, N = 644) and the USA (Yale-Penn, N = 2573). RESULTS: We identified rs9806493, a chromosome 15 variant, that showed a genome-wide significant association (Z-score = -5.501, P = 3.77 × 10-8) with ASPD criteria. rs9806493 is an eQTL for SLCO3A1 (Solute Carrier Organic Anion Transporter Family Member 3A1), a ubiquitously expressed gene with strong expression in brain regions that include the anterior cingulate and frontal cortices. Polygenic risk score analysis identified positive correlations between ASPD and smoking, ADHD, depression traits, and posttraumatic stress disorder. Negative correlations were observed between ASPD PRS and alcohol intake frequency, reproductive traits, and level of educational attainment. CONCLUSION: This study provides evidence for an association between ASPD risk and SLCO3A1 and provides insight into the genetic architecture and pleiotropic associations of ASPD

Audit of medical (non-targeted) liver biopsy specimen quality, pathology reporting and effect on patient management

Aims: To evaluate our medical liver pathology practice and its influence on patient management, using audit templates published by the UK Royal College of Pathologists (RCPath). Methods: We audited medical liver biopsies reported in our centre in 2019 using RCPath proformas. Data were collected from pathology reports and corresponding electronic patient record. Results: 60 cases were selected for audit from 135 eligible biopsies reported in 2019. 58/60 cases were core biopsies and 2/60 were laparoscopic wedge biopsies. 53/57 (93%) core biopsies with available data met RCPath adequacy criteria (length >15 mm and/or ≥6 portal tracts). Most reports (57/60; 95%) were judged to have helped patient management. 25/60 (42%) biopsy reports helped to clarify the clinical diagnosis and 48/60 (80%) led to altered management. Conclusions: We demonstrate the utility of the RCPath audit templates, highlighting the clinical value of medical liver biopsies in the diagnostic work-up and management of patients with liver disease

The Addition of Vitamin D Supplementation to Interferon and Ribavirin in the Treatment of Hepatitis C Virus Infection:A Randomised Double-Blind PlaceboControlled Pilot Study

Background: Vitamin D is known to be involved in the immune response to hepatitis C virus infection and preliminary data suggests that supplementation may improve response to treatment with interferon and ribavirin.Methods: The ViaDUCT study was a pilot, multi-centre, randomised, double-blind, placebo-controlled, parallel group clinical trial. Participants with hepatitis C who were planned for treatment were recruited and were randomised to 100,000 units oral vitamin D3 supplementation or placebo each month whilst undergoing treatment with interferon and ribavirin-based regimens. The primary outcome was sustained virologic response at 12 weeks. Secondary outcomes were to identify the proportion of patients who dropped out and to assess for any increase in treatment-related toxicity. Study analyses were performed by modified intention to treat of the primary outcome which was compared between the two arms using logistic regression.Results: 72 participants were randomised; 35 to vitamin D and 37 to placebo. The mean age of participants was 42.5 and 41.7 years respectively. The majority of trial participants were male - 25 (71%) in the vitamin D arm and 24 (65%) in the placebo arm. Following treatment, 60 (83%) attended for assessment of sustained virologic response at 12 weeks. Sustained virologic response was achieved in 82.9% (95%CI 67.3-91.9%) in thevitamin D arm and 73.0% (95%CI 57.0-84.6%) in the placebo arm. The odds of sustained virologic response at 12 weeks in the intervention arm was not significantly greater than in the placebo arm (adjusted odds ratio 1.74; 95%CI 0.43-6.97, p= 0.44). Adverse events were in keeping with the expected side effect profile of interferon and ribavirin based regimens.Conclusion: Vitamin D supplementation did not significantly improve sustained virologic response when added to interferon and ribavirin-based treatment. The apparent effect size observed would require a largertrial to establish any true effect of this adjunctive therapy.Trial Registration: ClinicalTrials.gov Identifier: NCT02053519, URL: https://clinicaltrials.gov/ct2/show/NCT02053519, East of Scotland Research Ethics committee: 13/ES/0116<br/

The Use of Baclofen as a Treatment for Alcohol Use Disorder: A Clinical Practice Perspective

Alcohol use disorder (AUD) is a brain disorder associated with high rates of mortality and morbidity worldwide. Baclofen, a selective gamma-aminobutyric acid-B (GABA-B) receptor agonist, has emerged as a promising drug for AUD. The use of this drug remains controversial, in part due to uncertainty regarding dosing and efficacy, alongside concerns about safety. To date there have been 15 randomized controlled trials (RCTs) investigating the use of baclofen in AUD; three using doses over 100 mg/day. Two additional RCTs have been completed but have not yet been published. Most trials used fixed dosing of 30–80 mg/day. The other approach involved titration until the desired clinical effect was achieved, or unwanted effects emerged. The maintenance dose varies widely from 30 to more than 300 mg/day. Baclofen may be particularly advantageous in those with liver disease, due to its limited hepatic metabolism and safe profile in this population. Patients should be informed that the use of baclofen for AUD is as an “off-label” prescription, that no optimal fixed dose has been established, and that existing clinical evidence on efficacy is inconsistent. Baclofen therapy requires careful medical monitoring due to safety considerations, particularly at higher doses and in those with comorbid physical and/or psychiatric conditions. Baclofen is mostly used in some European countries and Australia, and in particular, for patients who have not benefitted from the currently used and approved medications for AUD