Intelligent Liver Function Testing (iLFT): An Intelligent Laboratory Approach to Identifying Chronic Liver Disease.

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.

Increased risk of chronic kidney disease and mortality in a cohort of people diagnosed with metabolic dysfunction associated steatotic liver disease with hepatic fibrosis.

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.

Long-term risk factors for developing Barrett's oesophagus in patients with gastro-oesophageal reflux disease: a longitudinal cohort study.

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/m2). 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.

Progress is impossible without change: understanding the evolving nomenclature of steatotic liver disease and its effect on hepatology practice.

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.

Viral hepatitis testing and treatment in community pharmacies: a systematic review and meta-analysis.

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 I2 = 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 I2 = 82.4%) compared with non-targeted or other recruitment methods 4.0% (95% CI 2.1%-6.5%; heterogeneity I2 = 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 I2 = 72.4%) compared with referral to non-pharmacy settings (53.5%, 95% CI 36.5%-70.1%; heterogeneity I2 = 92.3%). The pooled proportion initiating treatment was 85.6% (95% CI 74.8%-94.3%; heterogeneity I2 = 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.

Immunity to pathogenic mucosal C. albicans infections mediated by oral megakaryocytes activated by IL-17 and candidalysin.

The fungus Candida albicans can cause mucosal infections including oropharyngeal candidiasis (OPC) in immunocompromised patients. In humans, an increased risk of fungal infections correlates with thrombocytopenia. However, our understanding of platelets and megakaryocytes (Mks) in mucosal fungal infections is almost entirely unknown. When megakaryocyte- and platelet-depleted mice were infected with OPC, the tongue showed higher fungal burden, due to decreased neutrophil accumulation. Protection depended on a distinct population of oral-resident Mks. Interleukin-17, important in antifungal immunity, was required since mice lacking the IL-17 receptor had decreased circulating platelets and their oral Mks did not expand during OPC. The secretion of the peptide toxin candidalysin activated human Mks to release platelets with antifungal capacity. Infection with a candidalysin-deficient strain resulted in decreased expansion of tongue Mks during OPC. This is the first time that a distinct megakaryocyte population was identified in the oral mucosa which is critical for immunity against fungal infection.

Optimal ALT threshold for the automated diagnosis of MASLD: A population-based study using iLFT.

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.

A transient positive association between direct-acting antiviral therapy for hepatitis C infection and drug-related hospitalization among people who inject drugs: Self-controlled case-series analysis of national data.

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.

Implementation of a liver health check in people with type 2 diabetes.

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.

Rapid atrial pacing above the maximum sensor rate: a case report.

Background: While ventricular-based timing modes are known to cause elevated atrial pacing above the lower rate when intrinsic atrioventricular (AV) conduction is shorter than programmed AV delay, there is one case report in 2015 by Jafri et al. where rapid atrial pacing was induced in an Abbott device set DDI with a lower rate of 90 by an unsensed premature atrial complex and slow intrinsic AV conduction allowing pacemaker 'crossover.' Case summary: We present a very unusual case of rapid atrial pacing at >180 b.p.m. due to a perfect storm of events that we believe has not been previously reported. A patient with a St. Jude Abbott DCPPM set DDDR had an atrial tachyarrhythmia causing a mode switch to DDIR, which uses ventricular-based timing. This was followed by a period of rapid atrial pacing that terminated spontaneously. Discussion: This phenomenon depended on an initial atrial tachyarrhythmia causing a mode switch to DDIR. In addition, the set lower rate would not have led to a short enough calculated ventriculo-atrial interval (VAI), but because rate responsive pacing was enabled, the calculated VAI was short enough to promote the crossover in setting of slow AV conduction and allow the rapid atrial pacing. Understanding this unique mechanism requires careful attention to pacemaker timing cycles and appreciation of the limitations of device programming. While it appears that a similar phenomenon was reported once in the literature, we believe that this episode of rapid atrial pacing was even more serendipitous due to the unlikely series of events required for its inception.

Exploring changing attitudes to non-invasive liver fibrosis tests in secondary care pathways: comparison of two national surveys.

Introduction: The increasing availability of non-invasive tests (NITs) has created the opportunity to explore their use in improving risk stratification of advanced liver disease. The study aimed to determine the attitudes and practices among UK secondary care specialists, focusing primarily on attitudes to fibrosis assessment and the use of NITs. Methods: Two web-based surveys were circulated, first between 2014 and 2015 (survey 1), and again in 2021 (survey 2). The surveys were promoted via the British Society of Gastroenterology, the British Association for the Study of the Liver and using Twitter. Results: In survey 1, 215 healthcare professionals (HCPs) completed the online survey. 112 HCPs completed survey 2. 71 acute UK trusts were represented in survey 1 compared with 60 trusts in survey 2. Between the two surveys, the proportion of HCPs performing fibrosis assessment in all or nearly all cases rose from 45.1% to 74.1% (χ2=25.01; p<0.0001). 46.5% (n=33/71) respondents in acute services reported the use of NITs in clinical pathways in survey 1, rising to 70.0% (n=42/60) in survey 2 (χ2=7.35; p=0.007). Availability of tests has increased but is not universal. The proportion reporting availability as a barrier to uptake fell from 57.2% of responses in survey 1 to 38.4% in 2021 χ2=11.01; p=0.0009). Conclusion: Between 2014 and 2021, the role of NITs in fibrosis assessment has risen substantially, as has the proportion of clinicians using NITs in clinical pathways to assess risk of liver disease. Poor access to NITs remains the predominant barrier.

IκBζ is an essential mediator of immunity to oropharyngeal candidiasis.

Fungal infections are a global threat; yet, there are no licensed vaccines to any fungal pathogens. Th17 cells mediate immunity to Candida albicans, particularly oropharyngeal candidiasis (OPC), but essential downstream mechanisms remain unclear. In the murine model of OPC, IκBζ (Nfkbiz, a non-canonical NF-κB transcription factor) was upregulated in an interleukin (IL)-17-dependent manner and was essential to prevent candidiasis. Deletion of Nfkbiz rendered mice highly susceptible to OPC. IκBζ was dispensable in hematopoietic cells and acted partially in the suprabasal oral epithelium to control OPC. One prominent IκBζ-dependent gene target was ß-defensin 3 (BD3) (Defb3), an essential antimicrobial peptide. Human oral epithelial cells required IκBζ for IL-17-mediated induction of BD2 (DEFB4A, human ortholog of mouse Defb3) through binding to the DEFB4A promoter. Unexpectedly, IκBζ regulated the transcription factor Egr3, which was essential for C. albicans induction of BD2/DEFB4A. Accordingly, IκBζ and Egr3 comprise an antifungal signaling hub mediating mucosal defense against oral candidiasis.

A multicomponent holistic care pathway for people who use drugs in Tayside, Scotland.

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.

Mortality rates among patients successfully treated for hepatitis C in the era of interferon-free antivirals: population based cohort study.

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.

Mixed-methods evaluation of point-of-care hepatitis C virus RNA testing in a Scottish prison.

OBJECTIVES: Hepatitis C virus (HCV) poses a global public health threat. Prisons are a focus of prevention efforts due to high infection burdens. Expedition of treatment for incarcerated people is critical, as many are short-term sentenced. We evaluated point-of-care (PoC) HCV RNA testing in a maximum-security Scottish prison and assessed its impact on transition to treatment. We also evaluated costs and determinants of implementation. DESIGN: Mixed-methods evaluation of a single-centre care pathway pilot using National Health Service (NHS) data from 2018 to 2021. Descriptive statistics and survival analysis were undertaken. Cost analysis was assessed from a provider perspective. Healthcare staff participated in semistructured interviews and thematic analysis with a deductive approach was undertaken to identify implementation determinants. SETTING: A large maximum-security Scottish prison health centre administered by the NHS. PARTICIPANTS: 296 incarcerated NHS patients (all men) and six NHS staff members (two men and four women). INTERVENTIONS: HCV testing using the Cepheid GeneXpert platform with Xpert HCV VL Fingerstick assay. OUTCOME MEASURES: The main outcome was survival (in days) from HCV test to treatment initiation. Secondary outcomes were cost-per-cure obtained and implementation determinants. RESULTS: During the pilot, 167 Xpert tests were administered, with an 84% completion rate, and treatment transition was superior for those who received it (p=0.014). Where PoC tests were administered, shorter survival to treatment was observed (19 vs 33 days: adjusted HR (aHR) 1.91 (1.03-3.55), p=0.040; 19 vs 50 days; aHR 3.76 (1.67-8.46), p=0.001). PoC was costlier than conventional testing. In qualitative analysis, most facilitators were observed among characteristics of individual domain while most barriers were noted in the inner setting. CONCLUSIONS: Integrating PoC HCV RNA diagnosis into nurse-led HCV care in a maximum-security prison health centre shortens survival to HCV treatment. However, there are cost implications to this approach and multiple determinants that impact on implementation should be addressed.

Research Priorities for Precision Medicine in NAFLD.

NAFLD is a multisystem condition and the leading cause of chronic liver disease globally. There are no approved NAFLD-specific dugs. To advance in the prevention and treatment of NAFLD, there is a clear need to better understand the pathophysiology and genetic and environmental risk factors, identify subphenotypes, and develop personalized and precision medicine. In this review, we discuss the main NAFLD research priorities, with a particular focus on socioeconomic factors, interindividual variations, limitations of current NAFLD clinical trials, multidisciplinary models of care, and novel approaches in the management of patients with NAFLD.

Effects of SARS-CoV-2 vaccination on the severity of COVID-19 infection in patients on chronic dialysis.

BACKGROUND: COVID-19 is associated with increased morbidity and mortality in patients with end-stage kidney disease on dialysis. Efficacy of SARS-CoV-2 vaccination to prevent severe COVID-19 disease in end-stage kidney disease patients remains limited. We compared the incidence of COVID-19-related hospitalization and death in dialysis patients based on SARS-CoV-2 vaccine status. METHODS: Retrospective study of adults on chronic dialysis within Mayo Clinic Dialysis System in the Midwest (USA) between April 1st, 2020 and October 31st, 2022, who had a laboratory test positive for SARS-CoV-2 by PCR. Incidence of both COVID-19-related hospitalization and death were compared between vaccinated and unvaccinated patients. RESULTS: SARS-CoV-2 infection was identified in 309 patients, including 183 vaccinated and 126 unvaccinated. The incidence of death (11.1% vs 3.8%, p = 0.02) and hospitalization (55.6% vs 23.5%, p < 0.001) was significantly higher in unvaccinated compared to vaccinated patients. Age at infection, sex, Charlson comorbidity index, dialysis modality, and hospital stays did not differ between the two groups. The incidence of hospitalization was significantly higher in partially vaccinated (63.6% vs 20.9%, p = 0.004) and unboosted (32% vs 16.4%, p = 0.04) patients compared to fully vaccinated and boosted, respectively. Among the 21 patients who died in the whole cohort, 47.6% (n = 10) died during the pre-vaccine period. The composite risk of death or hospitalization was lower among vaccinated patients after adjusting for age, sex and Charlson comorbidity index (OR 0.24, 95% CI 0.15-0.40). CONCLUSIONS: This study supports the use of SARS-CoV-2 vaccination to improve COVID-19 outcomes in patients on chronic dialysis.

Improved health-related quality of life after hepatitis C viraemic clearance among people who inject drugs may not be durable.

BACKGROUND AND AIMS: Chronic infection with the hepatitis C virus (HCV) has a detrimental impact on health-related quality of life (QoL). Scale-up of HCV direct-acting antiviral (DAA) therapy among people who inject drugs (PWID) is underway in several countries since the introduction of interferon-free regimens. This study aimed to assess the impact of DAA treatment success on QoL for PWID. DESIGN: Cross-sectional study using two rounds of the Needle Exchange Surveillance Initiative, a national anonymous bio-behavioural survey and a longitudinal study involving PWID who underwent DAA therapy. SETTING: The setting for the cross-sectional study was Scotland (2017-2018, 2019-2020). The setting for the longitudinal study was the Tayside region of Scotland (2019-2021). PARTICIPANTS: In the cross-sectional study PWID were recruited from services providing injecting equipment (n = 4009). In the longitudinal study, participants were PWID on DAA therapy (n = 83). MEASUREMENTS: In the cross-sectional study, the association between QoL (measured using the EQ-5D-5L quality of life instrument) and HCV diagnosis and treatment was assessed using multilevel linear regression. In the longitudinal study, QoL was compared at four timepoints using multilevel regression, from treatment commencement until 12 months following commencement. FINDINGS: In the cross-sectional study, 41% (n = 1618) were ever chronically HCV infected, of whom 78% (n = 1262) were aware of their status and of whom 64% (n = 704) had undergone DAA therapy. There was no evidence for a marked QoL improvement associated with viral clearance among those treated for HCV (B = 0.03; 95% CI, -0.03 to 0.09). In the longitudinal study, improved QoL was observed at the sustained virologic response test timepoint (B = 0.18; 95% CI, 0.10-0.27), but this was not maintained at 12 months following start of treatment (B = 0.02; 95% CI, -0.05 to 0.10). CONCLUSIONS: Successful direct-acting antiviral therapy for hepatitis C infection may not lead to a durable improvement in quality of life among people who inject drugs, although there may be a transient improvement around the time of sustained virologic response. Economic models of the impact of scaling-up treatment may need to include more conservative quality of life benefits over and above reductions in mortality, disease progression and transmission of infection.