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Chan Keat Kang, Paul N Brennan, John F Dillon Division of Molecular and Clinical Medicine, School of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UKCorrespondence: John F Dillon, Email j.f.dillon@dundee.ac.ukAbstract: Hepatitis B virus (HBV) infection is a major global public health challenge associated with significant morbidity and mortality. Due to worldwide population aging, HBV infection in the elderly will become increasingly prevalent. Effective universal vaccination programs exist but these are largely targeted towards the younger population. Therefore, the elderly population remains at risk of higher disease burden. New diagnoses of HBV infection in the elderly are usually asymptomatic chronic infections which increases their risk of developing cirrhosis, hepatocellular carcinoma, and liver disease-related mortality, especially if left untreated. Physiological changes and the increasing prevalence of multimorbidity associated with aging also potentially worsen outcomes in elderly patients with chronic HBV infection. Therefore, this cohort of patients should be monitored closely and effectively. Current international clinical practice guidelines unfortunately do not provide hard treatment endpoints specific to elderly patients with chronic HBV infection. Management of these patients is complex and requires an individualized approach. Multiple factors such as physiological changes, comorbidities, compliance, treatment tolerability and efficacy, burden of treatment, and realistic treatment goals need to be considered. Shared decision-making between patient and clinician is essential to ensure that the final decision for or against treatment aligns with the patient’s values and preferences. This review article aims to summarize the monitoring and management of chronic HBV infection in the aging population.Keywords: chronic hepatitis B, aging, elderly, effective monitoring

V Bradford, JF Dillon, MH Miller Gut Group, Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland Abstract: The burden of non-alcoholic fatty liver disease (NAFLD) worldwide is a significant clinical and public health issue, affecting approximately one third of the Western population. This review assesses the effect and impact lifestyle interventions have on the treatment of this common condition. We review studies comparing the effect of calorie restriction and exercise programs, as well as comparison of lifestyle intervention with pharmaceutical intervention. Both calorie restriction and exercise programs are shown to be beneficial in improving features of metabolic syndrome and surrogate markers of NAFLD. The paucity of studies using histological improvement hinders the ability to conclude a benefit on improvement of histological NAFLD, although this is shown in a small number of studies. There is a need to extend the intervention period to show a sustained improvement with intervention as most studies have a follow up period of 12 months of less. Keywords: NAFLD, lifestyle intervention, exercise, diet

Hepatitis C virus (HCV) antiviral treatment for people who inject drugs (PWID) could prevent onwards transmission and reduce chronic prevalence. We assessed current PWID treatment rates in seven UK settings and projected the potential impact of current and scaled-up treatment on HCV chronic prevalence. Data on number of PWID treated and sustained viral response rates (SVR) were collected from seven UK settings: Bristol (37-48% HCV chronic prevalence among PWID), East London (37-48%), Manchester (48-56%), Nottingham (37-44%), Plymouth (30-37%), Dundee (20-27%) and North Wales (27-33%). A model of HCV transmission among PWID projected the 10-year impact of (i) current treatment rates and SVR (ii) scale-up with interferon-free direct acting antivirals (IFN-free DAAs) with 90% SVR. Treatment rates varied from

Objectives: Micro‐elimination of hepatitis C virus (HCV) in people living with HIV (PLHIV) and co‐infected with HCV has been proposed as a key contribution to the overall goal of HCV elimination. While other studies have examined micro‐elimination in HIV‐treated cohorts, few have considered HCV micro‐elimination among those not treated for HIV or at a national level. Methods: Through data linkage of national and sentinel surveillance data, we examined the extent of HCV testing, diagnosis and treatment among a cohort of PLHIV in Scotland identified through the national database of HIV‐diagnosed individuals, up to the end of 2017. Results: Of 5018 PLHIV, an estimated 797 (15%) had never been tested for HCV and 70 (9%) of these had undiagnosed chronic HCV. The odds of never having been tested for HCV were the highest in those not on HIV treatment [adjusted odds ratio (aOR) = 7.21, 95% confidence interval (CI): 5.15–10.10). Overall HCV antibody positivity was 11%, and it was at its highest among people who inject drugs (49%). Most of those with chronic HCV (91%) had attended an HCV treatment clinic but only half had been successfully treated (54% for those on HIV treatment, 12% for those not) by the end of 2017. The odds of never having been treated for HCV were the highest in those not on HIV treatment (aOR = 3.60, 95% CI: 1.59–8.15). Conclusions: Our data demonstrate that micro‐elimination of HCV in PLHIV is achievable but progress will require increased effort to engage and treat those co‐infected, including those not being treated for their HIV. [ABSTRACT FROM AUTHOR]

JA Todd [1] T Weston [2] D Steinke [2] DA Johnston [2] JF Dillon [2] (1.) Peterborough District Hospital, Peterborough, PE3 6DA; (2.) Ninewells Hospital & Medical School, Dundee, DD1 [...]

We estimated the excess risk of in-patient hospitalization in a large cohort of persons diagnosed with hepatitis C virus (HCV) infection, controlling for social deprivation. A total of 20 749 individuals diagnosed with HCV in Scotland by 31 December 2006 were linked to the Scottish hospital discharge database, and indirectly standardized hospitalization rates, adjusting for sex, age, year and deprivation were calculated. We observed significant excess morbidity considering episodes for: any diagnosis [standardized morbidity ratio (SMR) 3·4, 95% CI 3·3-3·5]; liver-related diagnoses (SMR 41·3, 95% CI 39·6-43·0); and only non-liver-related diagnoses (SMR 2·14, 95% CI 2·08-2·19). Cox regression analyses of the 2000-2006 data indicated increased relative risks of hospitalization for males [hazard ratio (HR) 1·1, 95% CI 1·0-1·2], older age (per 10 years) (HR 1·55, 95% CI 1·5-1·6), and those testing HIV-positive (HR 1·6, 95% CI 1·3-1·8). This study has revealed substantial excess all-cause and liver-related morbidity in the Scottish HCV-diagnosed population, even after allowing for deprivation. [ABSTRACT FROM AUTHOR]

Objective: Laryngopharyngeal reflux (LPR) is a syndrome associated with a constellation of symptoms usually treated by ENT surgeons. It is believed to be caused by the retrograde flow of stomach contents into the laryngopharynx, this being a supra-esophageal manifestation of gastroesophageal reflux disease (GERD). It has been cited that LPR and GERD can be considered separate entities. Our hypothesis was that LPR is a supra-esophageal manifestation of GERD and therefore that patients with GERD should have a degree of symptoms suggestive of LPR because of the reflux of the gastric contents. We examined a population of patients with both upper gastrointestinal endoscopy and symptom-proven GERD and, using a questionnaire, looked at their existing symptoms to help assess the prevalence of LPR. We also looked at whether, with more severe GERD (suggestive of increased gastric content reflux), the degree of symptoms suggestive of LPR would be increased, as would be expected. Methods: A population of patients with endoscopically proven GERD were recruited and divided into groups depending on the severity of their reflux disease. A questionnaire was then administered that examined both LPR and GERD scoring criteria. The relationship between GERD and LPR was then analyzed. Results: We recruited 1,383 subjects with GERD; those with severe GERD had significantly higher LPR scores compared with those with mild (P < .01), moderate (P < .05), or inactive disease (P < .001). Conclusions: The condition of LPR is likely to represent a supra-esophageal manifestation of GERD. This study examined a large number of patients with endoscopically proven GERD and has demonstrated a correlation between the severity of GERD and the prevalence of LPR. LPR and GERD are common and interlinked conditions. The subsequent prevalence of LPR in the population with GERD is therefore likely to be dramatically underestimated. [ABSTRACT FROM AUTHOR]

Background and Objectives: Esophageal cancer has one of the worst prognoses of all cancers, mainly due to its aggressive growth pattern and late presentation. Using radiotherapy, chemotherapy, or even surgery it is only possible to cure a small minority and so alternative strategies need to be evaluated. In this study we aim to investigate the feasibility of using liposomes to transfect genes into human esophageal biopsies at high enough levels to achieve a biological effect.Methods: Human esophageal biopsies were transfected with constructs encoding Green Fluorescent Protein or human wild type p53. Expression of Green Fluorescent Protein within these samples was determined by FACScan analysis and confocal microscopy, whereas p53 expression was assessed by Western blotting and Reverse Transcriptase Polymerase Chain Reaction, probing for p53 and a downstream effector WAF1/p21.Results: Confocal microscopy verified the expression of Green Fluorescent Protein in human esophageal biopsies in cells 7 to 10 layers deep. Green Fluorescent Protein expression has also been demonstrated by FACScan analysis. The successful introduction and expression of wild type p53 has been shown in normal esophageal biopsies by Western blotting and RT-PCR and in Barrett's esophageal biopsies by Western blotting alone. In addition, we have demonstrated an increase in the expression of WAF1/p21 in 50% of biopsies transfected with p53.Conclusion: Liposome-mediated transfer of genes into human esophageal cells is feasible and can be performed at a sufficient dose to achieve expression of downstream genes. [ABSTRACT FROM AUTHOR]

Background and Aims: Although the evidence is uncertain, existing estimates for hepatitis C virus (HCV) in sub-Saharan Africa (SSA) indicate a high burden. We estimated HCV seroprevalence and viraemic prevalence among the general population in SSA., Methods: We searched Medline, Embase, Web of Science, APA PsycINFO, and World Health Organization Africa Index Medicus for community-based studies. Study quality was assessed using the Joanna Briggs Institute critical appraisal tool, and heterogeneity using the index of heterogeneity (I 2 ). Two approaches were deployed. First, we used random-effects meta-analysis to pool prevalence. Second, to derive representative estimates, we weighted each country's HCV seroprevalence using 2021 United Nations country population sizes., Results: We synthesized 130 studies. Overall, SSA HCV seroprevalence from the random-effects model was 4.17% (95% confidence interval [CI]: 3.71-4.66, I 2  = 99.30%). There were no differences between males (4.31%) and females (4.03%). Seroprevalence was 2.25%, 3.31%, and 16.23% for ages ≤20, 21-64, and ≥65 years, respectively, and was higher in rural (6.63%) versus urban (2.93%). There was indication of decrement overtime from 5.74% to 4.35% to 3.03% in the years 1984-2000, 2001-2014, and 2015-2023, respectively. The weighted overall SSA HCV seroprevalence was estimated to be 2.30% (95% CI: 1.59-3.00) with regional variation: Africa-Southern (.79%), Africa-Central (1.47%), Africa-Eastern (2.71%), and Africa-Western (2.88%). HCV viremia among HCV seropositives was 54.77% (95% CI: 47.80-61.66)., Conclusions: HCV seroprevalence in SSA remains high. Populations aged ≥65 years, rural communities, Africa-Western, and some countries in Africa-Central and Africa-Eastern appear disproportionately affected. These results underline the need for governmental commitment to achieve the 2030 global HCV elimination targets., (© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Background Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) management guidelines have been published worldwide; we aimed to summarize, categorize and compare their lifestyle intervention recommendations., Approach Results: We searched MASLD/nonalcoholic fatty liver disease (NAFLD) management guidelines published between 1 January 2013 and 31 June 2024 via databases including PubMed/MEDLINE, Cochrane, and CINAHL. In total, 35 qualifying guidelines were included in the final analysis. Guideline recommendations were categorized into five domains (i.e., weight reduction goals, physical activity, nutrition, alcohol, and tobacco smoking) and were ranked based on how frequently they appeared. A recommendation was defined as widely adopted if recommended in ≥24 (≥66.6%) of the guidelines. These included increase physical activity; reduce body weight by 7-10% to improve steatohepatitis and/or fibrosis; restrict caloric intake; undertake 150-300 or 75-150 minutes/week of moderate or vigorous-intensity physical activity, respectively; and decrease consumption of commercially produced fructose. The least mentioned topics, in ≤9 of the guidelines, evaluated environmental determinants of health, mental health, referring patients for psychological or cognitive behavioral therapy, using digital health interventions (DHIs), and assessing patients' social determinants of health., Conclusions: Most guidelines recommend weight reduction through physical activity and improving nutrition, as these have proven positive effects on health outcomes when sustained. However, gaps regarding mental health and the social and environmental determinants of MASLD were found. To optimize behavioral modifications and treatment, we recommend carrying out studies that will provide further evidence on social support, environmental factors, and mental health, and further exploring DHIs., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: This aimed to develop a blueprint for an effective community pharmacy Hepatitis C virus (HCV) testing service by producing a consensus statement., Study Design: This was a modified Delphi process., Methods: We recruited a heterogenous panel of experts (who had been involved in the setup or delivery of a community pharmacy HCV testing service) by purposive and chain referral methods. We had three rounds of a modified Delphi process. The first was a series of questions with free text responses and was analysed using thematic analysis, and the second and third were statements for the respondents to rate using a 7-point Likert scale. Consensus was predefined in a published protocol, and the results were reviewed by a public and patient involvement panel before the statement was finalised., Results: We had 24 participants, including community and hospital-based pharmacists, local pharmaceutical committee members, charity representatives (Hepatitis C Trust), local clinical service lead, nurse specialists and doctors. The response rate of the first, second and third rounds were 100%, 96% and 88%, respectively. After the third round, we had 60 statements that reached consensus. We discussed the accepted statements with a patient and public involvement group. We used these statements to produce the I-COPTIC statement and a graphical summary., Conclusions: We developed a blueprint for the design of a gold standard community pharmacy HCV testing service. We believe this will support the successful implementation of community pharmacy testing for HCV. Community pharmacy testing is an important service to help achieve and maintain HCV elimination., (Copyright © 2024. Published by Elsevier Ltd.)

The American, European, and Latin American liver societies have proposed a change in the nomenclature we use to describe alcohol-related liver disease and non-alcoholic fatty liver disease. Additionally, a term encompassing both is now advocated: steatotic liver disease, which includes metabolic dysfunction associated steatotic liver disease (MASLD) and MASLD with greater alcohol consumption (MetALD). These classifications offer increased relevance for clinicians, researchers, and patients alike. In this Viewpoint, we discuss the basis for this nomenclature shift and how it was developed. We also explore the challenges that will be faced in the adoption of such change. The proposed change seeks to banish stigma associated with phrasing such as alcoholic and fatty. However stigma, particularly related to the term fatty, is culturally nuanced, and reflects different entities depending on location. If such a change is internationally accepted, there will be wide-reaching effects on practitioners in primary care and metabolic medicine, and on patients. We discuss those effects and the opportunities the nomenclature change could offer, particularly for patients with alcohol and metabolic risk factors who represent a group previously ignored by clinical trials., (Crown Copyright © 2024 Published by Elsevier Ltd. All rights reserved.)

The intelligent Liver Function Testing (iLFT) pathway is a novel, algorithm-based system which provides automated laboratory investigations and clinical feedback on abnormal liver function test (LFT) results from primary care. iLFT was introduced to NHS Tayside, Scotland, in August 2018 in response to vast numbers of abnormal LFTs, many of which were not appropriately investigated, coupled with rising mortality from chronic liver disease. Here, we outline the development and implementation of the iLFT pathway, considering the implications for the diagnostic laboratories, primary care services and specialist hepatology clinics. Additionally, we describe the utility, outcomes and evolution of iLFT, which was used over 11,000 times in its first three years alone. Finally, we will consider the future of iLFT and propose areas where similar 'intelligent' approaches could be used to add value to laboratory investigations.

Background and Aims: Metabolic dysfunction associated steatotic liver disease (MASLD) increases the risk of incident chronic kidney disease (CKD). However, the relative risk of CKD associated with increasing hepatic fibrosis, and consequent mortality risk, remains underexplored in real-world cohorts. In this study, we sought to establish whether hepatic fibrosis is associated with increased CKD risk and explore differences in mortality risk in a cohort of people living with MASLD, contingent on liver fibrosis and CKD status., Methods: This was an observational study of people who underwent routine liver function testing in Tayside, Scotland. MASLD was defined as: elevated ALT (>30 U/L) or GGT (>73 U/L); presence of diabetes, and/or hypertension, and/or obesity; weekly alcohol consumption <14 units (112g (+/-8g) alcohol); and negative screen for other aetiologies. Data was collected from digital health records. We used log-binomial models to quantify the risk of CKD among those with and without fibrosis, and Cox regression models to estimate differences in mortality risk dependent on fibrosis and CKD., Results: In our cohort (n = 2,046), 1,448 (70.8%) people had MASLD without fibrosis and 598 (29.2%) with fibrosis; 161 (11.1%) and 117 (19.6%) respectively also had CKD. After excluding individuals with structural, autoimmune, or malignant CKD (n = 22), liver fibrosis (n = 593; 18.9% with CKD) was associated with increased CKD risk (aRR = 1.31, 1.04-1.64, p = 0.021). Increased mortality risk was observed for those with liver fibrosis (aHR = 2.30, 1.49-3.56, p = <0.001) and was higher again among people with both fibrosis and CKD (aHR = 5.07, 3.07-8.39, p = <0.014)., Conclusions: Liver fibrosis was an independent risk factor for CKD in this cohort of people living with MASLD. Furthermore, those with MASLD with liver fibrosis had higher risk for mortality and this risk was further elevated among those with co-morbid CKD. Given the increased risk of CKD, and consequent mortality risk, among people living with MASLD fibrosis, renal function screening should be considered within liver health surveillance programmes and guidelines., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gurun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The risk of Hepatitis C Virus (HCV) acquisition among People Who Inject Drugs (PWID) remains high when injecting risk behavior within networks endures. Several psychosocial factors influence such behavior. Following a drive within Tayside, a geographic region in Scotland, to achieve World Health Organization HCV elimination targets, addressing HCV re-infection risk as a barrier to elimination is critically important. This cross-sectional study seeks to address this barrier to elimination by investigating associations between group identification (one's subjective sense of belonging and connectedness to a social group coupled with a sense of shared goals, beliefs and values with the other members of the group) and injecting risk behavior among PWID on HCV treatment at needle and syringe provision sites in Tayside. Participants completed psychosocial questionnaires between treatment weeks zero and three of treatment. Correlation analyses were undertaken, and significant factors included in multiple linear regression models for injecting risk behavior. Injecting frequency, drug network identification, and family identification, were correlated with injecting risk behavior, and drug network identification had a positive predictive on injecting risk behavior. Identification with a social group, conventionally associated with improved health, may pose health risks in specific contexts. Healthcare providers should consider stratifying individuals with higher group identification with PWID networks for enhanced harm reduction engagement to mitigate transmissible infection risk among PWID. Additionally, psychological interventions to strengthen group identification with networks which impact positively on health behavior should be explored.

Background and Aims: Several characteristics are known to affect the risk of Barrett's oesophagus (BO) in the general population, with symptomatic gastro-oesophageal reflux disease (GORD) being a critical risk factor. In this study, we examined factors that influence BO development in people living with GORD., Design: People living with GORD were recruited from an endoscopy unit with lifestyle, medical and prescribing history collected. Logistic regression analysis was undertaken to assess the effects of multiple parameters on the likelihood of developing BO., Results: 1197 participants were recruited. Most were Caucasian (n=1188, 99%), had no formal educational qualifications (n=714; 59.6%) and lived with overweight (mean body mass index >25 kg/m 2 ). Many lived in areas of least socioeconomic resource (n=568; 47.4%). 139 (11.6%) had BO at baseline. In adjusted baseline analysis (n=1197), male sex (adjusted OR, aOR 2.04 (95% CI 1.92 to 4.12), p≤0.001), increasing age (aOR 1.03 (95% CI 1.01 to 1.04), p≤0.0001) and proton pump inhibitor use (aOR 3.03 (95% CI 1.80 to 5.13), p≤0.0001) were associated with higher odds of BO. At follow-up (n=363), 22 (6.1%) participants developed BO; male sex (aOR 3.18 (95% CI 1.28 to 7.86), p=0.012), pack-years cigarettes smoked (aOR 1.04 (95% CI 1.00 to 1.08), p=0.046) and increased alcohol intake (aOR 1.02 (95% CI 1.00 to 1.04), p=0.013), were associated with increased odds of BO., Conclusion: Male sex, pack-years cigarettes smoked, and increasing alcohol intake, were independently associated with increased odds of developing BO over 20-year follow-up. These results align with research linking male sex and smoking with BO and extend this by implicating the potential role of alcohol in developing BO, which may require communication through public health messaging., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background & Aims: In community pathways for detection of liver disease the most common reason for referral is fibrosis assessment. We investigated the impact of adding the Enhanced Liver Fibrosis (ELF) score as a second-line test (subsequent to an indeterminate or high Fibrosis-4 index [FIB-4] and/or non-alcoholic fatty liver disease fibrosis score) to guide referral and prognostication in our multi-aetiology pathway., Methods: Patients with ELF results from the intelligent Liver Function Testing (iLFT) pathway were recruited. Case note review was undertaken to compare ELF with endpoints of cirrhosis, hepatic decompensation, and mortality (liver-related and all-cause death)., Results: In total, 1,327 individuals were included with a median follow-up of 859 days and median ELF score of 10.2. Overall sensitivity for cirrhosis at the 9.8 threshold was 94% (100% for metabolic-associated steatotic liver disease, 89% for alcohol-related liver disease). Determination of the ELF score as a second-line test reduced the referral rate by 34%. ELF scores predicted hepatic outcomes; each unit change was associated with increased decompensation (adjusted Hazard Ratio [aHR] 2.215, 95% CI: 1.934-2.537) and liver-related mortality (aHR 2.024, 95% CI: 1.674-2.446). ELF outperformed FIB-4 for risk of liver-related mortality, particularly in the short-term (area under the curve [AUC] 94.3% vs. 82.8% at six months). Where FIB-4 was indeterminate, ELF had higher AUC for all outcomes within at least 2 years. ELF ≥13 was associated with particularly high rates of decompensation (26% within 90 days) and all-cause mortality (38% at 1 year)., Conclusions: The addition of ELF reduced the number of individuals referred for fibrosis assessment following iLFT pathway testing and provided useful prognostic information. Individuals with ELF scores ≥13 were considered at high-risk of negative outcomes warranting urgent clinical assessment., Impact and Implications: Primary care pathways for suspected liver disease are increasingly common and often lead to increased specialist hepatology referrals for fibrosis assessment. This study, using clinical follow-up for liver-related outcomes, provides further evidence supporting ELF testing to safely reduce referrals in a two-step approach when combined with other simple fibrosis markers. Additionally, ELF scores predict liver-related morbidity and mortality, with ELF scores ≥13 indicating particularly high-risk patients. This study may help inform the implementation of diagnostic pathways for early detection of liver disease and highlights the need for urgent review of individuals with very high ELF scores., Competing Interests: ED: educational grants and honoraria from Abbott and Siemens. The other authors declare no conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2024 The Author(s).)

Competing Interests: Competing interests: PNB acknowledges consulting fees from Resolution Therapeutics and payment or honoraria from Takeda, outside of the submitted work. SZ-S has given presentations for and received support for attending meetings and/or travel from AbbVie, outside of the submitted work. AMA acknowledges grant support to her institution from the National Institutes of Health (NIH) (DK128127), Novo Nordisk, Pfizer and Target Pharma and advisory board participation for Novo Nordisk, outside of the submitted work. JFD has received research grants and lecture honoraria from MSD, AbbVie and Gilead, outside of the submitted work. JVL acknowledges grants and speaker fees from AbbVie, Gilead Sciences, MSD and Roche Diagnostics to his institution, speaker fees from Echosens, Janssen, Novo Nordisk and ViiV and consulting fees from Novavax, outside of the submitted work.

Introduction and Objectives: Early diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD), especially with advanced fibrosis, is crucial due to the increased risk of complications and mortality. Serum alanine aminotransferase (ALT) is commonly used; however, many patients have normal ranges (<55 U/L) who may remain undetected. We investigated the clinical implications of a lower ALT cut-off (>30 U/L) using intelligent liver function testing (iLFT) to identify MASLD patients with and without advanced fibrosis in primary care., Materials and Methods: All patients entering the iLFT diagnostic pathway had liver aetiological screening investigations if ALT >30 U/L. In those with MASLD the proportions with and without advanced fibrosis at different ALT thresholds: 31-41 U/L, 42-54 U/L and ≥55 U/L were compared., Results: 16,373 patients underwent iLFT between March 2016 to April 2022. 762 (5 %) patients had MASLD with abnormal fibrosis scores, while 908 (6 %) had MASLD with normal fibrosis scores. 428 (56 %) patients were assessed in liver clinics, where 169 (39 %) had evidence of fibrosis. Of these, 22 (13 %) had ALT 31-41 U/L, 31 (18 %) had ALT 42-54 U/L and 116 (69 %) had ALT ≥55 U/L. 145 (86 %) patients had advanced fibrosis or cirrhosis, where 20 (14 %) had ALT 31-41 U/L, 28 (19 %) had ALT 42-54 U/L and 97 (67 %) had ALT ≥55 U/L., Conclusions: 33 % of MASLD patients with advanced fibrosis or cirrhosis had ALT 31-54 U/L, who would have been missed using the conventional ALT range. This suggests that lowering the ALT cut-off improves diagnosis of MASLD with advanced fibrosis in primary care., Competing Interests: Conflicts of interest JL Declarations of interest: none; CJB Declarations of interest: none; PNB has consulted for Resolution Therapeutics and received educational honoraria from Takeda; IMcP Declarations of interest: none; ED declares educational grants from Siemens and Abbott unrelated to the submitted work; JFD reports grants and personal fees from AbbVie; grants and personal fees from Gilead; and grants and personal fees from MSD, outside the submitted work., (Copyright © 2024 Fundación Clínica Médica Sur, A.C. All rights reserved.)

Background: The World Health Organization seeks to eliminate viral hepatitis as a public health threat by 2030. This review and meta-analysis aims to evaluate the effectiveness of programs for hepatitis B and C testing and treatment in community pharmacies., Methods: Medline, Embase, Cochrane CENTRAL, and Global Health were searched from database inception until 12 November 2023. Comparative and single arm intervention studies were eligible for inclusion if they assessed delivery of any of the following interventions for hepatitis B or C in pharmacies: (1) pre-testing risk assessment, (2) testing, (3) pre-treatment assessment or (4) treatment. Primary outcomes were proportions testing positive and reaching each stage in the cascade. Random effects meta-analysis was used to estimate pooled proportions stratified by recruitment strategy and setting where possible; other results were synthesised narratively. This study was pre-registered (PROSPERO: CRD42022324218)., Findings: Twenty-seven studies (4 comparative, 23 single arm) were included, of which 26 reported hepatitis C outcomes and four reported hepatitis B outcomes. History of injecting drug use was the most identified risk factor from pre-testing risk assessments. The pooled proportion hepatitis C antibody positive from of 19 studies testing 5096 participants was 16.6% (95% CI 11.0%-23.0%; heterogeneity I 2  = 96.6%). The pooled proportion antibody positive was significantly higher when testing targeted people with specified risk factors (32.5%, 95% CI 24.8%-40.6%; heterogeneity I 2  = 82.4%) compared with non-targeted or other recruitment methods 4.0% (95% CI 2.1%-6.5%; heterogeneity I 2  = 83.5%). Meta-analysis of 14 studies with 813 participants eligible for pre-treatment assessment showed pooled attendance rates were significantly higher in pharmacies (92.7%, 95% CI 79.1%-99.9%; heterogeneity I 2  = 72.4%) compared with referral to non-pharmacy settings (53.5%, 95% CI 36.5%-70.1%; heterogeneity I 2  = 92.3%). The pooled proportion initiating treatment was 85.6% (95% CI 74.8%-94.3%; heterogeneity I 2  = 75.1%). This did not differ significantly between pharmacy and non-pharmacy settings., Interpretation: These findings add pharmacies to the growing evidence supporting community-based testing and treatment for hepatitis C. Few comparative studies and high degrees of statistical heterogeneity were important limitations. Hepatitis B care in pharmacies presents an opportunity for future research., Funding: None., Competing Interests: MJH and EB's institute received funding for their positions through Specialist Training Program funding initiative of the Australian Government Department of Health, which had no role in the design or conduct of this study. MT declared receipt of investigator-initiated research grants, speakers’ honoraria, and consultancy fees from Gilead Sciences, unrelated to the submitted work. JFD's institute has received grant funding from Gilead Sciences and JFD declared receipt of honoraria from Gilead Sciences, all unrelated to the submitted work. AR's institute has received research grants from Camurus, MSD, and Gilead Sciences, unrelated to the submitted work. SN declared receipt of untied research funding from Seqirus to study prescription opioid poisonings and was a named investigator (no funds received) on an implementation trial of buprenorphine depot funded by Indivior, both unrelated to the submitted work. CJB declared receipt of honoraria from the International Network on Health and Hepatitis in Substance Users (INHSU); bursary support in the form of payment and waiving of fees from the European Association for the Study of the Liver (EASL); and grant fees from the Scottish Society of Physicians, all unrelated to the submitted work. JR declared receipt of honoraria from Gilead Sciences and Abbvie and support from Abbvie for conference attendance, unrelated to the submitted work. PH's institutes received grant funding from the Australian Government Department of Health, the National Health and Medical Research Council and the Australian Research Council, unrelated to the submitted work. MEH and JSD's institute receives funding from Gilead Sciences and Abbvie for investigator-initiated research, unrelated to the submitted work., (© 2024 The Author(s).)

Background and Aims: Direct-acting antiviral (DAA) treatment has an established positive effect on liver outcomes in people with hepatitis C infection; however, there is insufficient evidence regarding its effects on the 'extra-hepatic' outcomes of drug-related hospitalization and mortality (DRM) among people who inject drugs (PWID). We investigated associations between these outcomes and DAA treatment by comparing post-treatment to baseline periods using a within-subjects design to minimize selection bias concerns with cohort or case-control designs., Design: This was a self-controlled case-series study., Setting: Scotland, 1 January 2015-30 November 2020., Participants: The study population of non-cirrhotic, DAA-treated PWID was identified using a data set linking Scotland's hepatitis C diagnosis, HCV clinical databases, national inpatient/day-case hospital records and the national deaths register. Three principal outcomes (drug overdose admission, non-viral injecting related admission and drug-related mortality) were defined using ICD codes., Measurements: Self-controlled case-series methodology was used to estimate the relative incidence (RI) of each outcome associated with time on treatment and up to six 90-day exposure risk periods thereafter., Findings: A total of 6050 PWID were treated with DAAs in the sampling time-frame. Compared with the baseline period, there was a significantly lowered risk of a drug overdose hospital admission in the second to fifth exposure risk periods only [relative incidence (RI) = 0.86, 95% confidence interval (CI) = 0.80-0.99; 0.89, 95% CI = 0.80-0.99; 0.86, 95% CI = 0.77-0.96; 0.88, 95% CI = 0.78-0.99, respectively]. For non-viral injecting-related admission, there was a reduced risk in the first, third and fourth exposure risk periods (RI = 0.76, 95% CI = 0.64-0.90; 0.75, 95% CI = 0.62-0.90; 0.79, 95% CI = 0.66-0.96, respectively). There was no evidence for reduced DRM risk in any period following treatment end., Conclusions: Among people who inject drugs in Scotland, direct-acting antiviral treatment appears to be associated with a small, non-durable reduction in the risk of drug-related hospital admission, but not drug-related mortality. Direct-acting antiviral therapy, despite high effectiveness against liver disease, does not appear to offer a panacea for reducing other drug-related health harms., (© 2023 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

As morbidity and mortality related to potentially preventable liver diseases are on the rise globally, early detection of liver fibrosis offers a window of opportunity to prevent disease progression. Early detection of non-alcoholic fatty liver disease allows for initiation and reinforcement of guidance on bodyweight management, risk stratification for advanced liver fibrosis, and treatment optimisation of diabetes and other metabolic complications. Identification of alcohol-related liver disease provides the opportunity to support patients with detoxification and abstinence programmes. In all patient groups, identification of cirrhosis ensures that patients are enrolled in surveillance programmes for hepatocellular carcinoma and portal hypertension. When considering early detection strategies, success can be achieved from applying ad-hoc screening for liver fibrosis in established frameworks of care. Patients with type 2 diabetes are an important group to consider case findings of advanced liver fibrosis and cirrhosis, as up to 19% have advanced fibrosis (which is ten times higher than the general population) and almost 70% have non-alcoholic fatty liver disease. Additionally, patients with type 2 diabetes with alcohol use disorders have the highest proportion of liver-related morbidity of people with type 2 diabetes generally. Patients with type 2 diabetes receive an annual diabetes review as part of their routine clinical care, in which the health of many organs are considered. Yet, liver health is seldom included in this review. This Viewpoint argues that augmenting the existing risk stratification strategy with an additional liver health check provides the opportunity to detect advanced liver fibrosis, thereby opening a window for early interventions to prevent end-stage liver disease and its complications, including hepatocellular carcinoma., Competing Interests: Conflict of interests LV reports consulting fees from Gilead, Pfizer, Astra Zeneca, Novo Nordisk, Intercept Pharmaceuticals, Diatech Pharmacogenetics, IONIS, and Boehringer Ingelheim; grant support from Gilead; and speaker fees from MSD, Gilead, AlfaSigma, AbbVie, and Viatris. JFD reports consulting fees from Intelligent Ultrasound and speaker fees for Gilead and GE systems. AMA reports consulting fees from NovoNordisk and grant support from Target, Novo Nordisk, and Pfizer. MN reports consulting fees from Altimmune, Cytodyn, 89bio, GlaxoSmithKline, Madrigal, Merck, Novo Nordisk, Northsea Therapeutics, Perspectum, Terns, and Takeda; grant support from Allergan, Akero, Bristol Myers Squibb, Gilead, Galectin, Genfit, GlaxoSmithKline, Conatus, Corcept, Enanta, Madrigal, Novartis, Novo Nordisk, Shire, Takeda, Terns, Viking, and Zydus; and stock options with Rivus Pharma, CIMA, Cytodyn, and ChronWell. MER reports consulting fees from Intercept Pharmaceuticals, Gilead Sciences, Genfit, NGM Biopharmaceuticals, Enanta, Immuron, Fractyl, Prociento, Gelesis, Merck, Bristol Myers Squibb, Metacrine, Viking Therapeutics, Allergan, Cymabay, Boehringer Ingelheim, Genentech, 89bio, Galecto, Terns, Sagimet, Thetis, Fractyl, Lipicine, GSK, Coherus, and Novartis. FT reports consulting fees for Allergan, AstraZeneca, Bayer, Gilead, Bristol Myers Squibb, Boehringer, Intercept, Ionis, Inventiva, Merz, Pfizer, Alnylam, NGM Biopharma, CSL Behring, Madrigal, Novo Nordisk, and Novartis; grant support from Allergan, Bristol Myers Squibb, Inventiva, and Gilead (funding to institution); speaker fees from Gilead, AbbVie, Falk, Merz, Intercept, Sanofi, and AstraZeneca; expert testimony for Alnylam; participation on a data safety monitoring board for Pfizer; and travel support from Gilead. SF reports consulting fees from AbbVie, Actelion, Aelin Therapeutics, Aligos Therapeutics, Allergan, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Meyers Squibb, CSL Behring, Coherus, Echosens, Eisai, Enyo, Galapagos, Galmed, Genentech, Genfit, Gilead Sciences, Intercept, Inventiva, Janssens Pharmaceutica, Julius Clinical, Madrigal, Medimmune, Merck Sharp & Dohme, NGM Bio, Novartis, Novo Nordisk, Promethera, and Roche; research grants from Astellas, Falk Pharma, Genfit, Gilead Sciences, GlympsBio, Janssens Pharmaceutica, Inventiva, Merck Sharp & Dohme, Pfizer, and Roche; and speaker fees from AbbVie, Allergan, Bayer, Eisai, Genfit, Gilead Sciences, Janssens Cilag, Intercept, Inventiva, Merck Sharp & Dohme, Novo Nordisk, and Promethera. MT reports speaker fees from Echosens and Siemens Healthcare. PNN reports consulting fees from Boehringer Ingelheim, Intercept, Madrigal, Bristol Myers Squibb, AstraZeneca, Gilead, Pfizer, GlaxoSmithKline, Novo Nordisk, Poxel Pharamceuticals, and Sun Pharma and grant support from Novo Nordisk. ING reports grant support from Gilead. JMS reports consulting fees from Apollo Endosurgery, Albireo Pharma, Bayer, Boehringer Ingelheim, Gilead Sciences, GlaxoSmithKline, Intercept Pharmaceuticals, Ipsen, Inventiva Pharma, Madrigal, MSD, Northsea Therapeutics, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi, and Siemens Healthineers; grant support from Gilead Sciences, Boehringer Ingelheim, and Siemens Healthcare; and speaker fees from Boehringer Ingelheim, Echosens, MedPublico, Novo Nordisk, and Madrigal Pharmaceuticals. AB reports consulting fees from Inventiva and grant support from Boehringer Ingelheim. AGH reports consulting fees from Inventiva, Echosens, Novo Nordisk, Gilead, and Julius Clinical. CC reports consulting fees from Novo Nordisk, Gilead, AstraZeneca, Bayer, E-Scopics, Intercept, and Lilly; research support from Echosens, E-scopics, and Gilead; and speaker fees from Madrigal, AstraZeneca, Gilead, Novo Nordisk, Lilly, and LVL. KC reports consulting fees from Altimmune, Arrowhead, AstraZeneca, Boehringer Ingelheim, Covance, 89bio, Bristol Myers Squibb, Lilly, Madrigal, Merck, Myovant, Novo Nordisk, Prosciento, Quest, Sagimet, Sonic Incytes, and Terns and grant support from Echosens, Inventiva, Novo Nordisk, Nordic Bioscience, Poxel, Labcorp, and Zydus. MR reports consulting fees from Boehringer, Pfizer, Novo Nordisk, and Eli Lilly and grant support from Boehringer, Novo Nordisk, Nutricia Danone, and Sanofi. HH reports consulting fees from AstraZeneca and grant support from AstraZeneca, EchoSens, Gilead, Intercept, MSD, and Pfizer. VW-SW reports consulting fees from AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Inventiva, Novo Nordisk, Pfizer, Sagimet Biosciences, TARGET PharmaSolutions, and Visirna; speaker fees from AbbVie, Gilead Sciences, Novo Nordisk, and Unilab; travel support from AbbVie and Gilead Sciences; grant support from Gilead Sciences; and stock options for Illuminatio Medical Technology. LC reports consulting fees from Echosens, Madrigal, MSD, Novo Nordisk, Pfizer, Sagimet, and Siemens Healthineers and speaker fees from Echosens, Inventiva, and Novo Nordisk. JVL reports grants and speaker fees from AbbVie, Gilead Sciences, MSD, and Roche Diagnostics and speaker fees from Intercept, Jannsen, Novo Nordisk, and ViiV, outside of the submitted work. EAT reports consulting fees from Alexion, Novo Nordisk, Pfizer, Boehringer, Orphalan, and Univar and speaker fees from Novo Nordisk, Orphalan, and Dr Falk. All other authors report no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: People Who Use Drugs (PWUD) are at high risk of non-fatal overdose and other drug-related harms. The United Kingdom drugs policy landscape makes it challenging to support those at risk. Tayside, in East Scotland, has a sizeable population at risk of drug-related harms. In 2021, the National Health Service implemented a care pathway for PWUD to provide multidimensional healthcare interventions. We aimed to quantify drug-related harms; assess wider health and well-being; and understand substance use trends and behaviours, among those engaged in the pathway., Methods: Existing community-embedded blood-borne virus pathways were adapted to provide multiple healthcare assessments over three visits. We undertook an observational cohort study to analyse uptake and outcomes for the initial cohort of PWUD engaged at appointment one., Results: From August 2021-September 2022, 150 PWUD engaged with the pathway. Median age was 39 (34-42) years, 108 (72%) were male, and 124 (83%) lived in deprived areas. Seventy (47%) had been disengaged from healthcare for over a year. Polysubstance use was reported by 124 (83%), 42 (28%) disclosed injecting daily, and 54 (36%) shared equipment. Fifty-four (36%) experienced recent non-fatal overdose, and there were six overdose fatalities (4.1 [1.5-9.0] per 100PY). The offer of take-home naloxone was accepted by 108 (72%). Fourteen (9%) were diagnosed with Hepatitis C and two (1%) with HIV. Renal, hepatological, and endocrine impairment were observed among 30 (20%), 23 (15%), and 11 (7%), people respectively. Ninety-six (65%) had high risk of clinical depression. Forty-eight (32%) declined Covid-19 vaccination., Conclusion: The pathway engaged PWUD with high exposure to recent non-fatal overdose and other drug-related harms, alongside co-morbid health issues. Our results suggest multi-dimensional health assessments coupled with harm reduction in community settings, with appropriate linkage to care, are warranted for PWUD. Service commissioners should seek to integrate these assessments where possible., Competing Interests: Declaration of Competing Interest C.J.B. has received honoraria from the International Network on Health and Hepatitis in Substance Users (INHSU), unrelated to the submitted work. A.R. declares receipt of research grants from Abbvie, BMS, Pfizer and Gilead. Lecture fees and honorariums from Abbvie and Gilead, unrelated to the submitted work. E.F. and D.T. declare no conflicts. B.P.S. has received honoraria for lectures from Janssen-Cilag, Merck Sharp & Dohme and Gilead Sciences, unrelated to the submitted work. J.F.D. declares receipt of research grants, lecture fees and honorariums from Abbvie, BMS, Gilead, MSD, and Roche, unrelated to the submitted work., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: To quantify mortality rates for patients successfully treated for hepatitis C in the era of interferon-free, direct acting antivirals and compare these rates with those of the general population., Design: Population based cohort study., Setting: British Columbia, Scotland, and England (England cohort consists of patients with cirrhosis only)., Participants: 21 790 people who were successfully treated for hepatitis C in the era of interferon-free antivirals (2014-19). Participants were divided into three liver disease severity groups: people without cirrhosis (pre-cirrhosis), those with compensated cirrhosis, and those with end stage liver disease. Follow-up started 12 weeks after antiviral treatment completion and ended on date of death or 31 December 2019., Main Outcome Measures: Crude and age-sex standardised mortality rates, and standardised mortality ratio comparing the number of deaths with that of the general population, adjusting for age, sex, and year. Poisson regression was used to identify factors associated with all cause mortality rates., Results: 1572 (7%) participants died during follow-up. The leading causes of death were drug related mortality (n=383, 24%), liver failure (n=286, 18%), and liver cancer (n=250, 16%). Crude all cause mortality rates (deaths per 1000 person years) were 31.4 (95% confidence interval 29.3 to 33.7), 22.7 (20.7 to 25.0), and 39.6 (35.4 to 44.3) for cohorts from British Columbia, Scotland, and England, respectively. All cause mortality was considerably higher than the rate for the general population across all disease severity groups and settings; for example, all cause mortality was three times higher among people without cirrhosis in British Columbia (standardised mortality ratio 2.96, 95% confidence interval 2.71 to 3.23; P<0.001) and more than 10 times higher for patients with end stage liver disease in British Columbia (13.61, 11.94 to 15.49; P<0.001). In regression analyses, older age, recent substance misuse, alcohol misuse, and comorbidities were associated with higher mortality rates., Conclusion: Mortality rates among people successfully treated for hepatitis C in the era of interferon-free, direct acting antivirals are high compared with the general population. Drug and liver related causes of death were the main drivers of excess mortality. These findings highlight the need for continued support and follow-up after successful treatment for hepatitis C to maximise the impact of direct acting antivirals., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the Medical Research Foundation for the submitted work; the following financial relationships, which might have an interest in the submitted work in the previous three years: STB has received consulting fees and/or honorariums from Falk, Gilead, Abbvie, and Intercept; AB has received honorariums from Gilead Sciences; HT has received honorariums from Abbvie, Gilead Sciences, Eisai, Terumo, and Fujifilm WAKO; NZJ has received honorariums from Gilead and Abbvie; PCH has received honorariums from Falk, Ferring, Gore, Lundbeck, and Norgine; he has participated on advisory boards for Abbvie BMS, Eisai, Ferring, Gilead, Janssen, MSD, Novartis, and ONO; WLI has received research funding from Gilead Sciences and Jansen-Cilag and consulting fees/honorariums from Gilead Sciences and Roche Diagnostics; SB has received grants/contracts from Gilead Sciences and consulting fees/honorariums from Abbvie, Gilead Sciences; JFD has received honorariums from Gilead Sciences, Abbvie, and MSD; KA has received honorariums and/or consulting fees from Aligos, Assembly, Arbutus, BMS, BI, Bluejay, Gilead, GSK, Janssen, Roche, Saigmet, and Sobil; he has participated on the advisory board for DrugFarm; MA has received honorariums from Gilead Sciences; EB has consulted for Roche, Astrazeneca, and Vaccitech; she has received honorariums for education events and manuscript writing with Roche, and has patents relating to vaccines against hepatitis B, hepatitis C, and liver imaging; she owns shares in Perspectum diagnostics in liver imaging. No other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)