Alcohol use disorder epidemiology and interventions to support behaviour change

Alcohol is a preventable leading cause of liver disease. In the United Kingdom (UK) 25% of the population drinks above the recommended level and 10% are harmful drinkers. Alcohol-related liver disease (ARLD) progresses silently, over 50% of patients are first diagnosed with liver disease after an emergency hospital admission at a stage when the scope of any medical and behavioural intervention is limited. Though the prevalence of alcohol use disorder is disproportionately higher among hospitalised patients as compared to the community, it is persistently underdiagnosed and undertreated in hospital settings. There is a large burden of undiscovered, asymptomatic, but clinically significant liver disease in patients attending community substance misuse services. Early detection of liver disease followed by targeted interventions is a logical and effective way to reduce the risk of late presentation of liver disease and other alcohol-related end organ damage. Although, providing tailored feedback based on non-invasive tests (NITs) for liver disease to people at risk of liver disease may affect their drinking behaviour, at present these markers are not widely incorporated into alcohol treatment settings. Hence, the potential of combining early diagnostic interventions and advice has not been extensively explored in alcohol services. First, I conducted a retrospective observational study to explore the epidemiology of alcohol use disorder among hospitalised patients. I demonstrated that one in six hospitalised were screened positive for alcohol use disorder (AUD) based on AUDIT-C alcohol assessment. Patients with AUD were more likely to be male, white, admitted as an emergency, and cared for by surgical specialities compared to those without AUD. Although there was an overall reduction in the number of hospital admissions, patients admitted during the pandemic compared to pre-pandemic were more likely to have possible alcohol dependence and mental disorders due to alcohol. Covid-19-positive patients with AUD died at a younger age compared to Covid-19-positive patients without AUD. I then, conducted a systematic review and meta-analysis to determine the effectiveness of non-invasive tests (NITs) based advice compared to routine care in changing high-risk drinking behaviour. Twenty papers comprising 14 RCTs, 2 observational studies, and n=3763 participants were included. The meta-analysis demonstrated a greater reduction in self-reported alcohol intake and liver biomarkers for the intervention compared to the control group: the mean difference for weekly alcohol intake was -74.4 grams per week (95%CI -126.1, -22.6, p=0.005); and mean difference for gamma-glutamyl transferase (GGT) -19.7 IU/L (95% CI -33.1, -6.4, p=0.004). There was a higher incidence of alcohol-attributed mortality, number of days spent in the hospital, physician visits and sickness absence in the non-intervention group. In addition to NITs based advice, I planned to include alcohol recovery video stories (ARVS) as part of the intervention in my future feasibility RCT. I conducted a systematic review and narrative synthesis and proposed a conceptual framework characterising alcohol recovery narratives. Based on the three-stage narrative synthesis approach I determined that alcohol recovery narratives are composed of eight principle narrative dimensions (genre, identity, recovery setting, drinking trajectory, drinking behaviours, stages, spirituality and religion, and recovery experience) each with types and subtypes. All dimensions were present in most subgroups. Shame was a prominent theme for female narrators, as a lack of sense of belonging for LGBTQ+ narrators, and alienation and inequality for indigenous Alaskan and Australian narrators. Moreover, spiritual awakening was more commonly sought rather than a religious affiliation in LGBTQ+ narratives. Finally, I conducted a feasibility randomised control trial (KLIFAD) at three community settings in Nottingham, including adult patients presenting to any of these services with a primary problem of alcohol use disorder. Participants were randomised (1:1) to either continue routine care (control group) or in addition to routine care have feedback based on transient elastography results and watch alcohol recovery video stories (intervention group). I demonstrated that the integration of transient elastography into community alcohol services is feasible. Over 76% of eligible participants agreed to be part of the trial and gave informed consent and were randomised, 65% stayed in services for three months, and a six-month follow-up was available in 59%. Implementing opportunistic screening in otherwise asymptomatic high-risk individuals showed one in five had raised liver stiffness measure (LSM), and of concern one in seven of them were in the cirrhotic range. The provision of feedback based on transient elastography results was associated with higher rates of completion of the allocated treatment program, reduction in self-reported alcohol intake, or complete cessation of alcohol consumption. A normal liver stiffness measure did not provide false reassurance to study participants

Alcohol use disorder epidemiology and interventions to support behaviour change

Alcohol is a preventable leading cause of liver disease. In the United Kingdom (UK) 25% of the population drinks above the recommended level and 10% are harmful drinkers. Alcohol-related liver disease (ARLD) progresses silently, over 50% of patients are first diagnosed with liver disease after an emergency hospital admission at a stage when the scope of any medical and behavioural intervention is limited. Though the prevalence of alcohol use disorder is disproportionately higher among hospitalised patients as compared to the community, it is persistently underdiagnosed and undertreated in hospital settings. There is a large burden of undiscovered, asymptomatic, but clinically significant liver disease in patients attending community substance misuse services. Early detection of liver disease followed by targeted interventions is a logical and effective way to reduce the risk of late presentation of liver disease and other alcohol-related end organ damage. Although, providing tailored feedback based on non-invasive tests (NITs) for liver disease to people at risk of liver disease may affect their drinking behaviour, at present these markers are not widely incorporated into alcohol treatment settings. Hence, the potential of combining early diagnostic interventions and advice has not been extensively explored in alcohol services. First, I conducted a retrospective observational study to explore the epidemiology of alcohol use disorder among hospitalised patients. I demonstrated that one in six hospitalised were screened positive for alcohol use disorder (AUD) based on AUDIT-C alcohol assessment. Patients with AUD were more likely to be male, white, admitted as an emergency, and cared for by surgical specialities compared to those without AUD. Although there was an overall reduction in the number of hospital admissions, patients admitted during the pandemic compared to pre-pandemic were more likely to have possible alcohol dependence and mental disorders due to alcohol. Covid-19-positive patients with AUD died at a younger age compared to Covid-19-positive patients without AUD. I then, conducted a systematic review and meta-analysis to determine the effectiveness of non-invasive tests (NITs) based advice compared to routine care in changing high-risk drinking behaviour. Twenty papers comprising 14 RCTs, 2 observational studies, and n=3763 participants were included. The meta-analysis demonstrated a greater reduction in self-reported alcohol intake and liver biomarkers for the intervention compared to the control group: the mean difference for weekly alcohol intake was -74.4 grams per week (95%CI -126.1, -22.6, p=0.005); and mean difference for gamma-glutamyl transferase (GGT) -19.7 IU/L (95% CI -33.1, -6.4, p=0.004). There was a higher incidence of alcohol-attributed mortality, number of days spent in the hospital, physician visits and sickness absence in the non-intervention group. In addition to NITs based advice, I planned to include alcohol recovery video stories (ARVS) as part of the intervention in my future feasibility RCT. I conducted a systematic review and narrative synthesis and proposed a conceptual framework characterising alcohol recovery narratives. Based on the three-stage narrative synthesis approach I determined that alcohol recovery narratives are composed of eight principle narrative dimensions (genre, identity, recovery setting, drinking trajectory, drinking behaviours, stages, spirituality and religion, and recovery experience) each with types and subtypes. All dimensions were present in most subgroups. Shame was a prominent theme for female narrators, as a lack of sense of belonging for LGBTQ+ narrators, and alienation and inequality for indigenous Alaskan and Australian narrators. Moreover, spiritual awakening was more commonly sought rather than a religious affiliation in LGBTQ+ narratives. Finally, I conducted a feasibility randomised control trial (KLIFAD) at three community settings in Nottingham, including adult patients presenting to any of these services with a primary problem of alcohol use disorder. Participants were randomised (1:1) to either continue routine care (control group) or in addition to routine care have feedback based on transient elastography results and watch alcohol recovery video stories (intervention group). I demonstrated that the integration of transient elastography into community alcohol services is feasible. Over 76% of eligible participants agreed to be part of the trial and gave informed consent and were randomised, 65% stayed in services for three months, and a six-month follow-up was available in 59%. Implementing opportunistic screening in otherwise asymptomatic high-risk individuals showed one in five had raised liver stiffness measure (LSM), and of concern one in seven of them were in the cirrhotic range. The provision of feedback based on transient elastography results was associated with higher rates of completion of the allocated treatment program, reduction in self-reported alcohol intake, or complete cessation of alcohol consumption. A normal liver stiffness measure did not provide false reassurance to study participants

Does advice based on biomarkers of liver injury or non-invasive tests of liver fibrosis impact high-risk drinking behaviour: A systematic review with meta-analysis

Background: Alcohol dependence affects over 240 million people worldwide and attributed to 3 million deaths annually. Early identification and intervention are key to prevent harm. We aim to systematically review literature on the effectiveness of adding advice based on biomarkers of liver injury or non-invasive tests of liver fibrosis (intervention-based advice ) to prevent alcohol misuse. Methods: Electronic search was conducted on Ovid Medline, PubMed, EMBASE, Psychinfo and CINAHL for articles published up to end of February 2020. Additionally, we searched study citations, Scopus, Ethos and Clinical trials. The primary outcome measure was changed in self-reported alcohol consumption analysed by random-effects meta-analysis. Secondary outcomes included change to liver blood markers and alcohol-related health outcomes.Results: 14 RCT and 2 observational studies comprising n=3763 participants were included. Meta-analyses showed a greater reduction in alcohol consumption and liver biomarkers for the intervention compared to control group: mean difference for weekly alcohol intake was -74.4 gram/week (95%CI -126.1, -22.6, p=0.005); and mean difference for GGT -19.7 IU/L (95% CI -33.1, -6.4, p=0.004). There was a higher incidence of alcohol attributed mortality, number of days spent in the hospital, physician visits and sickness absence in the non-intervention group. The quality of the included studies was moderate for RCT’s and high for observational studies. Conclusions: The review confirmed a significant association between the addition of intervention-based advice in routine care to the reduction of harmful alcohol consumption, GGT and alcohol-related mortality. The findings support the inclusion of this type of advice in routine alcohol care

The effect of Covid-19 on alcohol use disorder and role of universal alcohol screening in an inpatient setting: a retrospective cohort control study

AimTo assess the impact of Covid-19 on alcohol use disorders (AUD) and the role of universal alcohol screening (UAS) in an inpatient setting.MethodsRetrospective cohorts were defined as pre-pandemic and pandemic admitted to Nottingham University Hospitals (April to October; 2019 and 2020) and had alcohol assessment by AUDIT-C. AUDIT-C score was assessed against age, sex, ethnicity, admission type, speciality and primary diagnosis of mental disorders. Subgroup analysis for Covid-19 positive patients was performed.ResultsA total of 63,927 admissions (47,954 patients) were included. The pandemic period compared to pre-pandemic had fewer overall admissions (27,349 vs 36,578, P < 0.001), fewer with AUD (17.6% vs 18.4%, P = 0.008) but a higher proportion of alcohol dependents (3.7% vs 3.0%, P < 0.0001). In the pandemic those with AUD were more likely to be male (P = 0.003), white (P < 0.001), in relationship (P < 0.001), of higher socioeconomic background (P < 0.001), have alcohol-related mental disorders (P = 0.002), emergency admission (P < 0.001), medical speciality admission (P < 0.001) and shorter length of stay (P < 0.033) compared to pre-pandemic AUD. Covid-19 positive patients with concomitant AUD died at younger age (P < 0.05) than Covid-19 positive patients at low risk for AUD.ConclusionsThe pandemic changed the characteristics of inpatients with AUD. There was a higher proportion of alcohol-dependent admissions with evidence that a younger, less deprived group have been significantly impacted. UAS provides a useful tool to screen for AUD and to identify the change when facing sudden health crises

Prognostic non-invasive biomarkers for all-cause mortality in non-alcoholic fatty liver disease: A systematic review and meta-analysis

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) represents a growing public health concern, with patients having higher risk of morbidity and mortality. It has a considerably high prevalence in the general population, estimated 20%-40% in Europe, and is asymptomatic until late in the disease course. It is therefore important to identify and validate tools that predict hard outcomes such as mortality for use in clinical practice in risk-stratifying NAFLD patients. AIM To evaluate available evidence on the use of non-invasive test(s) as prognostic factors for mortality in NAFLD. METHODS We performed electronic searches of Medline and EMBASE (Ovid) until 7th January 2021 of studies in NAFLD populations. Prognostic markers included serum biomarkers, non-invasive scoring systems, and non-invasive imaging. The population included all spectrums of disease severity, including NAFLD and non-alcoholic steatohepatitis (NASH). Outcomes included all-cause, and cardiovascular mortality. All non-invasive tests were synthesised in a narrative systematic review. Finally, we conducted a meta-analysis of non-invasive scoring systems for predicting all-cause and cardiovascular mortality, calculating pooled hazard ratios and 95% confidence (STATA 16.1). RESULTS Database searches identified 2850 studies – 24 were included. 16 studies reported non-invasive scoring systems, 10 studies reported individual biomarkers, and 1 study reported imaging modalities. 4 studies on non-invasive scoring systems (6324 participants) had data available for inclusion in the meta-analysis. The non-invasive scoring system that performed best at predicting all-cause mortality was NAFLD fibrosis score (NFS) [pHR 3.07 (1.62-5.83)], followed by fibrosis-4 index [pHR 3.06 (1.54-6.07)], BARD [pHR 2.87 (1.27-6.46)], and AST to platelet ratio index [pHR 1.90 (1.32-2.73)]. NFS was also prognostic of cardiovascular-related mortality [pHR 3.09 (1.78-5.34)]. CONCLUSION This study reaffirms that non-invasive scoring systems, especially NFS, are reliable prognostic markers of all-cause mortality and cardiovascular mortality in NAFLD patients. These findings can inform clinical practice in risk stratifying NAFLD patients

Does knowledge of liver fibrosis affect high-risk drinking behaviour (KLIFAD)? protocol for a feasibility randomised controlled trial

Introduction: Heavy drinkers in contact with alcohol services do not routinely have access to testing to establish the severity of potential liver disease. Transient elastography by FibroScan can provide this information. A recent systematic review suggested providing feedback to patients based on markers of liver injury can be an effective way to reduce harmful alcohol intake. This randomised control trial (RCT) aims to establish the feasibility of conducting a larger national trial to test the effectiveness of FibroScan advice and Alcohol Recovery Video Stories (ARVS) in changing high-risk drinking behaviour in community alcohol services common to UK practice.Methods and analysis: This feasibility trial consists of three work packages (WP). WP1: To draft a standardised script for FibroScan operators to deliver liver disease-specific advice to eligible participants having FibroScan. WP2: To create a video library of ARVS for use in the feasibility RCT (WP3). WP3: To test the feasibility of the trial design, including the FibroScan script and video stories developed in WP1 and WP2 in a one-to-one individual randomised trial in community alcohol services. Semi-structured interviews will be conducted at 6 months follow-up for qualitative evaluation. Outcomes will be measures of the feasibility of conducting a larger RCT. These outcomes will relate to: participant recruitment and follow-up, intervention delivery, including the use of the Knowledge of LIver Fibrosis Affects Drinking trial FibroScan scripts and videos, clinical outcomes, and the acceptability and experience of the intervention and trial-related procedures. Data analysis will primarily be descriptive to address the feasibility aims of the trial. All proposed analyses will be documented in a Statistical Analysis Plan.Ethics and dissemination: This trial received favourable ethical approval from the West of Scotland Research Ethics Service (WoSRES) on 20 January 2021, REC reference: 20/WS/0179. Results will be submitted for publication to a peer-reviewed journal.Trial registration number ISRCTN16922410

Characteristics of alcohol recovery narratives: Systematic review and narrative synthesis

Background and aims Narratives of recovery from alcohol misuse have been analysed in a range of research studies. This paper aims to produce a conceptual framework describing the characteristics of alcohol misuse recovery narratives that are in the research literature, to inform the development of research, policy, and practice. Methods Systematic review was conducted following PRISMA guidelines. Electronic searches of databases (Ovid MEDLINE, EMBASE, CINHAL, PsychInfo, AMED and SCOPUS), grey literature, and citation searches for included studies were conducted. Alcohol recovery narratives were defined as “first-person lived experience accounts, which includes elements of adversity, struggle, strength, success, and survival related to alcohol misuse, and refer to events or actions over a period of time”. Frameworks were synthesised using a three-stage process. Sub-group analyses were conducted on studies presenting analyses of narratives with specific genders, ages, sexualities, ethnicities, and dual diagnosis. The review was prospectively registered (PROSPERO CRD42021235176). Results 32 studies were included (29 qualitative, 3 mixed-methods, 1055 participants, age range 17-82years, 52.6% male, 46.4% female). Most were conducted in the United States (n = 15) and Europe (n = 11). No included studies analysed recovery narratives from lower income countries. Treatment settings included Alcoholic Anonymous (n = 12 studies), other formal treatment, and ‘natural recovery’. Eight principle narrative dimensions were identified (genre, identity, recovery setting, drinking trajectory, drinking behaviours, stages, spirituality and religion, and recovery experience) each with types and subtypes. All dimensions were present in most subgroups. Shame was a prominent theme for female narrators, lack of sense of belonging and spirituality were prominent for LGBTQ+ narrators, and alienation and inequality were prominent for indigenous narrators. Conclusions Review provides characteristics of alcohol recovery narratives, with implications for both research and healthcare practice. It demonstrated knowledge gaps in relation to alcohol recovery narratives of people living in lower income countries, or those who recovered outside of mainstream services

Incidence and prevalence of venous thromboembolism in chronic liver disease: a systematic review and meta-analysis

Background and Aims: Historically, bleeding was thought to be a frequent and fatal complication of liver disease. However, thrombosis due to coagulation disorders in cirrhosis remains a real risk. We aim to systematically analyse published articles to evaluate epidemiology of venous thromboembolism (VTE) in chronic liver disease (CLD). Method: Electronic search was conducted on Ovid Medline, EMBASE and Scopus from inception to November 2021 to identify studies presenting epidemiology VTE (deep vein thrombosis and pulmonary embolism) in CLD in inpatients and/or community settings. Random-effects meta-analysis was performed to determine pooled per-year cumulative incidence, incidence rate and prevalence. Heterogeneity was measured by I² test, and, potential sources of heterogeneity by meta-regression and sensitivity analysis. PROSPERO registration-CRD42021239117. Results: Twenty-nine studies comprising 19,157,018 participants were included, of which 15,2049 (0.79%) had VTE. None of included the studies were done in the community. In hospitalised patients with CLD: pooled cumulative incidence of VTE was 1.07% (95%CI 0.80,1.38) per-year, incidence rate was 157.15 (95%CI 14.74,445.29) per 10,000 person-years, and period prevalence was 1.10% (95%CI 0.85,1.38) per year. There was significant heterogeneity and publication bias. Pooled relative risk (RR) of studies reporting incidence rate was 2.11 (95%CI 1.35,3.31). CLD patients (n=1644), who did not receive pharmacological prophylaxis were at 2.78 times (95% CI 1.11, 6.98) increased risk of VTE compared to those receiving prophylaxis. Conclusion: Hospitalised patients with CLD may be at an increased risk of VTE . For every 1000 hospitalised patients with CLD ten have new, and eleven have pre-existing diagnoses of VTE per-year

Transient Elastography in Community Alcohol Services: Can It Detect Significant Liver Disease and Impact Drinking Behaviour?

Introduction: Alcohol is the leading cause of cirrhosis in Western populations. The early identification of high-risk drinkers followed by intervention is an effective way to reduce harm. We aim to assess the feasibility of integrating transient elastography (TE) into community alcohol services, and to determine its impact on modifying drinking behaviours. Method: A prospective cohort study was conducted at a community alcohol clinic in Nottingham, UK (April 2012 to March 2014). Patients (>18 years) with a primary alcohol problem were recruited. Those known to liver services or those known to have chronic liver disease were excluded. Significant liver fibrosis was defined by a liver stiffness of >8 kilopascal (kPa). Follow-up was for a minimum of six months. Data were descriptively analysed for significant differences between patients with a normal liver stiffness versus raised liver stiffness. Results: 156 patients were invited; n = 87 attended and n = 86 underwent successful TE. The majority were male (n = 53, 70.0%), and the mean age was 46.3 years (SD ± 9.8). Median liver stiffness was 6.9 kPa (range 3.1–75.0kPa). Clinically significant liver fibrosis was identified in n = 33 (38.4%), of which n = 6 were in the cirrhotic range (≥15 kPa). The baseline median self-reported alcohol intake for normal stiffness was 126 units per week (range 24–378) and in raised stiffness was 149.0 units per week (range 39.0–420.0); this difference was nonsignificant (p = 0.338). The median reduction in self-reported alcohol intake in the whole cohort was 65.0 units per week (range 27.0–88.0, p < 0.001); in the normal liver stiffness group it was 25.0 units per week (range 18.0–75.0, p = 0.154), and in the raised liver stiffness group it was 78.5 units per week (range 36.0–126.0, p < 0.001). Conclusion: The study demonstrated that transient elastography is a feasible tool to stratify clinically significant liver disease in community alcohol services. It can stimulate a change in high-risk drinking behaviour and a normal liver stiffness result does not provide false reassurance to participants