Proactive case finding of alcohol-related liver disease in high-risk populations: A systematic review.

BACKGROUND: Alcohol-related liver disease (ARLD) is often diagnosed at a late stage when mortality is unacceptably high. Earlier identification of ARLD may lead to reduced alcohol intake, participation in hepatocellular carcinoma surveillance and reduction in liver-related morbidity and mortality. People with alcohol use disorder (AUD) are at highest risk of ARLD. The aim of this systematic review was to understand the yield of proactive screening for ARLD amongst high-risk groups. METHODS: Embase, Medline, Scopus and grey literature were searched for studies describing proactive assessment for alcohol-related liver disease in people with a history of alcohol excess or diagnosed AUD. Outcomes of interest were fibrosis and cirrhosis detection rates, clinical outcomes, portal hypertension evaluation, attendance at follow-up and cost-effectiveness. RESULTS: Fifteen studies were identified for inclusion from 1115 returned by the search. Four key settings for patient engagement were identified as inpatient addiction services, outpatient addiction services, general acute hospital admissions and community outreach. Of these, acute hospital admissions were the highest yield for cirrhosis at 10.8%-29.6% and community outreach the lowest was 1.2%-2.3%. CONCLUSIONS: Targeted fibrosis assessment of high-risk populations for ARLD is feasible to conduct and identifies a proportion of patients at risk of advanced liver disease. The highest yield is amongst inpatients admitted with AUD. Prospective work is needed to establish which are the most effective and acceptable screening methods and the impact on long-term outcomes.

Transient Elastography and Video Recovery Narrative Access to Support Recovery From Alcohol Misuse: Development of a Novel Intervention for Use in Community Alcohol Treatment Services.

BACKGROUND: Mortality from alcohol-related liver disease has risen significantly for 3 decades. Transient elastography (TE) is a noninvasive test providing a numerical marker of liver disease. Preliminary evidence suggests that TE can reduce alcohol consumption. The KLIFAD (does knowledge of liver fibrosis affect high-risk drinking behavior?) study has developed a complex intervention wherein people receiving alcohol treatment are provided with access to TE, accompanied by scripted feedback tailored to their disease state, and access to video narratives describing alcohol misuse recovery after receiving TE. Recovery narratives are included due to preliminary evidence from mental health studies which suggest that access to digital narratives describing recovery from mental health problems can help people affected by mental health problems, including through mechanisms with the potential to be transferable to an alcohol treatment setting, for example, by increasing hope for the future, enabling learning from the experience of others, or promoting help-seeking behaviors. OBJECTIVE: We aimed to develop the KLIFAD intervention to the point that it could be delivered in a feasibility trial and to produce knowledge relevant to clinicians and researchers developing interventions making use of biomarkers of disease. METHODS: In research activity 1, standardized scripted feedback was developed by this study, and then iterated through focus groups with people who had experienced alcohol misuse and TE, and key alcohol workers with experience in delivering TE. We report critical design considerations identified through focus groups, in the form of sensitizing concepts. In research activity 2, a video production guide was coproduced to help produce impactful video-based recovery narratives, and a patient and public involvement (PPI) panel was consulted for recommendations on how best to integrate recovery narratives into an alcohol treatment setting. We report PPI recommendations and an overview of video form and content. RESULTS: Through research activity 1, we learnt that patient feedback has not been standardized in prior use of TE, that receiving a numeric marker can provide an objective target that motivates and rewards recovery, and that key alcohol workers regularly tailor information to their clients. Through research activity 2, we developed a video production guide asking narrators what recovery means to them, what helped their recovery, and what they have learned about recovery. We produced 10 recovery narratives and collected PPI recommendations on maximizing impact and safety. These led to the production of unplanned videos presenting caregiver and clinician perspectives, and a choice to limit narrative availability to alcohol treatment settings, where support is available around distressing content. These choices have been evaluated through a feasibility randomized controlled trial [ISRCTN16922410]. CONCLUSIONS: Providing an objective target that motivates and rewards recovery is a candidate change mechanism for complex interventions integrating biomarkers of disease. Recovery narratives can contain distressing content; intervention developers should attend to safe usage. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2021-054954.

Application and Extension of the Alcohol Recovery Narratives Conceptual Framework.

Recovery narratives are personal stories of health problems and recovery. A systematic review proposed a conceptual framework characterising alcohol misuse recovery narratives, consisting of eight principal dimensions, each with types and subtypes. The current study aims to apply and extend this preliminary conceptual framework. Semi-structured interviews were conducted to collect alcohol misuse recovery narratives from adult participants. A two-stage inductive and deductive thematic analysis approach was used to assess the relevance of the dimensions and types included in the preliminary conceptual framework and identify new components. The sample consisted of 11 participants from diverse socioeconomic backgrounds who had previously displayed varying degrees of alcohol misuse. All conceptual framework dimensions (genre, identity, recovery setting, drinking trajectories, drinking behaviours and traits, stages, spirituality and religion, and recovery experience) were present in the collected narratives. Three dimensions were extended by adding types and subtypes. Whilst the existing conceptual framework fitted the collected narratives, a new dimension describing the alcohol environment was required to fully characterise narratives. Types included in the alcohol environment dimension were policy and practice and social dynamics. The extended framework could guide the production of resources enabling clinicians to engage with narratives shared by their clients.

Does knowledge of liver fibrosis affect high-risk drinking behaviour (KLIFAD): an open-label pragmatic feasibility randomised controlled trial.

Background: Early identification followed by effective behaviour interventions is pivotal to changing the natural history of alcohol-related liver disease. We examined the feasibility of using transient elastography based advice and alcohol recovery video stories (ARVS) to change drinking behaviour in community alcohol services. Methods: A feasibility randomised control trial (RCT) was conducted in three community alcohol services. Adults 18+ years presenting with a primary alcohol problem were randomised (1:1) to receive either usual care (control group) or usual care and the KLIFAD Intervention, consisting of advice tailored to liver stiffness measure and access to ARVS (intervention group). Data were collected at baseline and six months. To establish definitive trial feasibility, recruitment and retention rates, study procedure safety and extent of effectiveness were measured (Start date: 02.10.2019, End date: 30.11.2022, ISRCTN.com: 16922410). Findings: 382 service users were screened, 184 were randomised (intervention: 93, control: 91), and baseline data were collected for 128 (intervention: 71, control: 59). Six months follow-up data were available in 87 (intervention: 53, control: 34). Intervention compared to the control group had a longer duration of engagement with services (mean difference 8.6 days SD = 18.4), was more likely to complete the allocated treatment program and reduced or stop drinking (54.9% vs 43.9%) and reduce AUDIT category (71.7% vs 61.8%). There were no reported serious adverse reactions, one intervention group participant reported an increase in AUDIT category. Interpretation: Integration of transient elastography in community alcohol services is feasible. It may improve engagement with services, retention in clinical trials and supplement the reduction in self-reported alcohol consumption. A definitive RCT is supported. Funding: National Institute for Health and Care Research (NIHR201146).

Diagnostic accuracy of serum ascites albumin gradient (SAAG) in a contemporary unselected medical cohort.

OBJECTIVES: To describe the different aetiologies of ascites and test the validity of serum ascites albumin gradient (SAAG) and cytology in a contemporary unselected medical cohort. METHODS: All adult patients admitted to Nottingham University Hospitals, UK, between 1 May 2013 and 30 April 2018 with new-onset radiologically-confirmed ascites were included. Data were analysed to determine the distribution of different aetiologies of ascites and the diagnostic accuracy of SAAG in portal hypertension and cytology in malignancy as underlying causes of ascites. RESULTS: Over 5 years, 286 patients presented with new-onset ascites; 122 surgical cases were excluded. Most patients were men (n = 84, 51.2%) over 50 years of age (n = 142, 86.6%). Cirrhosis accounted for 54.9% (n = 90) of the cases of ascites followed by malignancy (n = 48, 29.3%) and cardiac failure (n = 10, 6.1%). SAAG ≥11 g/L had a sensitivity of 85.5% and specificity of 60.6% for diagnosing portal hypertension as a cause of ascites (diagnostic accuracy = 78.5%, 95% confidence interval (CI): 69.8-85.5; area under the curve (AUC) = 0.756, 95% CI: 0.652-0.860). Ascitic fluid cytology was positive in 50% of malignant cases and 66% of primary peritoneal carcinomatosis cases. CONCLUSION: The underlying aetiology and the validity of available tests varied substantially compared with previous reports.

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.

Alcohol-related liver disease mortality and missed opportunities in secondary care: A United Kingdom retrospective observational study.

INTRODUCTION: Alcohol-related liver disease (ARLD) is a preventable cause of mortality. Historical epidemiological studies on ARLD often lack a detailed linked assessment of health-related contacts prior to death which limits understanding of opportunities for intervention. We aimed to analyse retrospective population-based data of all adult residents of Nottinghamshire dying from ARLD to determine the factors associated with delayed diagnosis of ARLD and the potential missed opportunities for interventions. METHODS: We linked the Office for National Statistics and Hospital Episode Statistics databases to identify adult (≥18 years) residents of Nottinghamshire, who died of ARLD over the 5-year period (1 January 2012 to 31 December 2017). Death was used as the primary outcome, and logistic regression analysis was conducted to test the association between key variables and mortality due to ARLD. RESULTS: Over 5 years, 799 ARLD deaths were identified. More than half had no diagnosis or a diagnosis of ARLD less than 6 months before death. Emergency presentation at first ARLD diagnosis and White ethnicity were significantly associated with a delay in diagnosis. Overall, the cohort had a median of five hospital admissions, four accident and emergency attendances and 16 outpatient appointments in the 5 years before death. Treatment was provided by a range of specialities, with general medicine the most common. Alcohol was associated with most admissions. DISCUSSION AND CONCLUSIONS: This study identified deficiencies in ARLD secondary care and provides us with a powerful methodology that can be used to evaluate and improve how alcohol issues are managed and where action can be best targeted.

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. PROTOCOL REGISTRATION: Prospero registration number: CRD42020164185.

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 the included 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.

The Effect of Covid-19 on Alcohol Use Disorder and the Role of Universal Alcohol Screening in an Inpatient Setting: A Retrospective Cohort Control Study.

AIM: To assess the impact of Covid-19 on alcohol use disorders (AUD) and the role of universal alcohol screening (UAS) in an inpatient setting. METHODS: Retrospective 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. RESULTS: A 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. CONCLUSIONS: The 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.

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.

How to interpret and manage abnormal liver blood test results in older people.

Ageing impairs liver function and reduces the liver's regenerative capacity. With the predicted increase in the older population, the burden of liver disease will proportionally rise in this age group. Elevated levels of liver enzymes in an otherwise asymptomatic older individual (≥65 years) are a common observation and positively associated with the metabolic syndrome, whereas a decline in albumin levels is linked with a rise in all-cause and liver-specific mortality. Deranged liver function tests do not always indicate liver disease, nor do normal liver function tests exclude liver disease. Therefore, clinicians need to consider individual patient risk factors during the assessment of abnormal liver function tests. This article discusses various liver function tests, their pathophysiology, and the approach to interpret and manage common abnormalities in liver function test results and liver disease in the older population.

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 AND AIMS: 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: Fourteen randomized controlled trials (RCTs) and two 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 g/week (95% confidence interval (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. The quality of the included studies was moderate for RCTs 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.

Trimethoprim-induced drug reaction with eosinophilia and systemic symptoms (DRESS) associated with reactivation of human herpes virus-6 (HHV-6) leading to acute liver failure.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome can have insidious symptoms which may lead to acute liver failure and death. Prompt recognition, stopping offending drug, and initiating corticosteroid are the mainstay of treatment. Early involvement of a specialist liver unit is vital.

Update on management of gastric varices.

Gastric varices (GV) have different physiology and clinical characteristics compared to oesophageal varices (OV). There is little information about the management of GV. Most part of the recommendations is extrapolated from studies where the majority of participants had OV. Thus, most recommendations lack of strong evidence. This is a comprehensive review on all aspects of management of GV, i.e., primary, secondary prophylaxis and management of acute bleeding. The papers on which international societies' recommendations are based are scrutinised in this review and areas of research are identified.