Serum bile acid profiles are associated with heart failure with preserved ejection fraction in patients with metabolic dysfunction-associated fatty liver disease: An exploratory study.

AIM: To analyse the association between serum bile acid (BA) profile and heart failure (HF) with preserved ejection fraction (HFpEF) in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). METHODS: We enrolled 163 individuals with biopsy-proven MAFLD undergoing transthoracic echocardiography for any indication. HFpEF was defined as left ventricular ejection fraction >50% with at least one echocardiographic feature of HF (left ventricular diastolic dysfunction, abnormal left atrial size) and at least one HF sign or symptom. Serum levels of 38 BAs were analysed using ultra-performance liquid chromatography coupled with tandem mass spectrometry. RESULTS: Among the 163 patients enrolled (mean age 47.0 ± 12.8 years, 39.3% female), 52 (31.9%) and 43 (26.4%) met the HFpEF and pre-HFpEF criteria, and 38 serum BAs were detected. Serum ursodeoxycholic acid (UDCA) and hyocholic acid (HCA) species were lower in patients with HFpEF and achieved statistical significance after correction for multiple comparisons. Furthermore, decreases in glycoursodeoxycholic acid and tauroursodeoxycholic acid were associated with HF status. CONCLUSIONS: In this exploratory study, specific UDCA and HCA species were associated with HFpEF status in adults with biopsy-confirmed MAFLD.

A global survey on the use of the international classification of diseases codes for metabolic dysfunction-associated fatty liver disease.

BACKGROUND: With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11. METHODS: Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members. RESULTS: A total of 890 international experts in various fields from 61 countries responded to the survey. We also achieved full coverage of provincial-level administrative regions in China. 77.1% of respondents agreed that MAFLD should be represented in ICD-11 by updating NAFLD, with no significant regional differences (77.3% in Asia and 76.6% in non-Asia, p = 0.819). Over 80% of respondents agreed or somewhat agreed with the need to assign specific codes for progressive stages of MAFLD (i.e. steatohepatitis) (92.2%), MAFLD combined with comorbidities (84.1%), or MAFLD subtypes (i.e., lean, overweight/obese, and diabetic) (86.1%). CONCLUSIONS: This global survey by a collaborative panel of clinical, coding, health management and policy experts, indicates agreement that MAFLD should be coded in ICD-11. The data serves as a foundation for corresponding adjustments in the ICD-11 revision.

'It was like coming back from the clouds': a qualitative analysis of the lived experience of overdose consequent to drug use among a cohort of people who use drugs in Scotland.

BACKGROUND: Globally, non-fatal overdose (NFOD) rates consequent to drug use, typically opioids, continue increasing at a startling rate. Existing quantitative research has revealed myriad factors and characteristics linked to experiencing NFOD, but it is critically important to explore the lived context underlying these associations. In this qualitative study, we sought to understand the experiences of NFOD among people who use drugs in a Scottish region in order to: enhance public policy responses; inform potential intervention development to mitigate risk; and contribute to the literature documenting the lived experience of NFOD. METHODS: From June to July 2021, two peer researchers conducted face-to-face semi-structured interviews with people who use drugs who had experienced recent NFOD attending harm reduction services in Tayside, Scotland. These were transcribed verbatim and evaluated using thematic analysis with an inductive approach which had an experiential and essentialist orientation. RESULTS: Twenty people were interviewed across two sites. Of those, 15 (75%) were male and mean age was 38.2 (7.7) years. All had experienced at least one NFOD in the prior six months, and all reported polydrug use. Five themes were identified, within which 12 subthemes were situated. The themes were: social context; personal risk-taking triggers; planned and impulsive consumption; risk perception; and overdose reversal. The results spoke to the environmental, behavioural, cognitive, economic, and marketplace, factors which influence the context of NFOD in the region. CONCLUSIONS: A complex interplay of behavioural, psychological, and situational factors were found to impact the likelihood of experiencing NFOD. Structural inequities which policy professionals and civic leaders should seek to remedy were identified, while service providers may seek to reconfigure healthcare provision for people who use drugs to account for the interpersonal, psychological, and social factors identified, which appear to precipitate NFOD. TRIAL REGISTRATION: Not applicable.

Liver fibrosis Assessed Via Non-invasive Tests is Associated With Incident Heart Failure in a General Population Cohort.

BACKGROUND & AIMS: The aim of this study was to determine whether liver fibrosis is associated with heart failure in a general population cohort, and if genetic polymorphisms (PNPLA3 rs738409; TM6SF2 rs58542926), linked to increased risk of liver fibrosis and decreased risk of coronary artery disease, modify this association. METHODS: Using UK Biobank data, we prospectively examined the relationship between noninvasive fibrosis markers (nonalcoholic fatty liver disease [NAFLD] fibrosis score [NFS], Fibrosis-4 [FIB-4] and aspartate transaminase [AST] to platelet ratio index [APRI]) and incident hospitalization/death from heart failure (n = 413,860). Cox-regression estimated hazard ratios (HRs) for incident heart failure. Effects of PNPLA3 and TM6SF2 on the association between liver fibrosis and heart failure were estimated by stratifying for genotype and testing for an interaction between genotype and liver fibrosis using a likelihood ratio test. RESULTS: A total of 12,527 incident cases of heart failure occurred over a median of 10.7 years. Liver fibrosis was associated with an increased risk of hospitalization or death from heart failure (multivariable adjusted high-risk NFS score HR, 1.59; 95% confidence interval [CI],1.47-1.76; P < .0001; FIB-4 HR, 1.69; 95% CI, 1.55-1.84; P < .0001; APRI HR, 1.85; 95% CI, 1.56-2.19; P < .0001; combined fibrosis scores HR, 1.90; 95% CI, 1.44-2.49; P < .0001). These associations persisted for people with metabolic dysfunction-associated steatotic liver disease (MASLD), MASLD with alcohol consumption (Met-ALD), and harmful alcohol consumption. PNPLA3 rs738409 GG and TM6SF2 rs58542926 TT did not attenuate the positive association between fibrosis markers and heart failure. For PNPLA3, a statistically significant interaction was found between PNPLA3 rs738409, FIB-4, APRI score, and heart failure. CONCLUSION: In the general population, serum markers of liver fibrosis are associated with increased hospitalization/death from heart failure. Genetic polymorphisms associated with liver fibrosis were not positively associated with elevated heart failure risk.

Association between primary hypothyroidism and metabolic dysfunction-associated steatotic liver disease: an updated meta-analysis.

OBJECTIVE: Epidemiological studies have reported an association between primary hypothyroidism and metabolic dysfunction-associated steatotic liver disease (MASLD). However, the magnitude of the risk and whether this risk changes with the severity of MASLD remains uncertain. We performed a meta-analysis of observational studies to quantify the magnitude of the association between primary hypothyroidism and the risk of MASLD. DESIGN: We systematically searched PubMed, Scopus and Web of Science from database inception to 31 January 2024, using predefined keywords to identify observational studies in which MASLD was diagnosed by liver biopsy, imaging or International Classification of Diseases codes. A meta-analysis was performed using random-effects modelling. RESULTS: We identified 24 cross-sectional and 4 longitudinal studies with aggregate data on ~76.5 million individuals. Primary hypothyroidism (defined as levothyroxine replacement treatment, subclinical hypothyroidism or overt hypothyroidism) was associated with an increased risk of prevalent MASLD (n=24 studies; random-effects OR 1.43, 95% CI 1.23 to 1.66; I2=89%). Hypothyroidism was also associated with a substantially higher risk of metabolic dysfunction-associated steatohepatitis or advanced fibrosis (n=5 studies; random-effects OR 2.84, 95% CI 2.07 to 3.90; I2=0%). Meta-analysis of data from four longitudinal studies showed that there was a marginally non-significant association between hypothyroidism and risk of developing MASLD over a median 4.5-year follow-up (random-effects HR 1.39, 95% CI 0.98 to 1.97; I2=85%). Sensitivity analyses did not modify these findings. The funnel plot did not reveal any significant publication bias. CONCLUSION: This large and updated meta-analysis provides evidence that primary hypothyroidism is significantly associated with both an increased presence of and histological severity of MASLD.

Cognitive Processing Speed and Loneliness in Stroke Survivors: Insights from a Large-Scale Cohort Study.

OBJECTIVE: Loneliness, when prolonged, is associated with many deleterious effects and has been shown to be highly prevalent in those with a history of stroke, yet the cognitive mechanisms underpinning this phenomenon remain unclear. Therefore, the current study aims to investigate the extent to which cognitive factors, with specific focus on processing speed, are associated with loneliness in those with a history of stroke. METHOD: Utilizing data from the British Cohort Study, a nationally representative dataset, we conducted secondary data analysis. A total of 7,752 participants completed relevant questions related to health, social interactions, demographics, loneliness, and cognitive assessments. Among them, 47 had experienced a stroke ("stroke," n = 47), 5,545 reported other health conditions ("ill," n = 5,545), and 2,857 were deemed healthy ("healthy," n = 2,857). RESULTS: Consistent with previous research, our findings confirmed a positive correlation between stroke history and heightened loneliness. However, inferential analysis revealed that processing speed, alongside other cognitive factors, had a minimal impact on loneliness, with correlations too small to draw definitive conclusions. CONCLUSION: This study suggests that cognitive processing speed alone is not a robust predictor of loneliness in stroke survivors. Consequently, when developing interventions to combat loneliness in this population, it is crucial to consider a broader spectrum of factors, such as social engagement, emotional wellbeing, and interpersonal relationships. This underscores the imperative need for comprehensive assessments to better comprehend the multifaceted nature of loneliness and inform more effective intervention strategies.

Relationship between Helicobacter pylori infection and risk of metabolic dysfunction-associated steatotic liver disease: An updated meta-analysis.

BACKGROUND: Recent observational studies examining the association between Helicobacter pylori infection and the risk of metabolic dysfunction-associated steatotic liver disease (MASLD) have reported conflicting results. We performed a meta-analysis to quantify the magnitude of the association between H. pylori infection and the risk of MASLD. METHODS: We systematically searched three large electronic databases to identify eligible observational studies (published up to 30 November 2023) in which liver biopsy, imaging methods or blood-based biomarkers/scores were used for diagnosing MASLD. Data from selected studies were extracted, and meta-analysis was performed using common and random-effects modelling. Statistical heterogeneity among published studies, subgroup analyses, meta-regression analyses and publication bias were assessed. RESULTS: A total of 28 observational studies (24 cross-sectional and 4 longitudinal studies) were identified, including 231 291 middle-aged individuals of predominantly Asian ethnicity (~95%). Meta-analysis of cross-sectional studies showed that H. pylori infection was significantly associated with a small increase in the risk of prevalent MASLD (n = 24 studies; random-effects odds ratio 1.11, 95% CI 1.05-1.18; I2 = 63%). Meta-analysis of data from longitudinal studies showed that H. pylori infection was significantly associated with an increased risk of developing incident MASLD over a mean 5-year follow-up (n = 4 studies; random-effects odds ratio 1.20, 95%CI 1.08-1.33; I2 = 44%). Sensitivity analyses did not modify these results. The funnel plot did not reveal any significant publication bias. CONCLUSIONS: H. pylori infection is associated with a mildly increased risk of prevalent and incident MASLD. Further well-designed prospective and mechanistic studies are required to better decipher the complex link between H. pylori infection and the risk of MASLD.

Psychosocial factors associated with overdose subsequent to Illicit Drug use: a systematic review and narrative synthesis.

BACKGROUND AND AIMS: Psychological and social status, and environmental context, may mediate the likelihood of experiencing overdose subsequent to illicit drug use. The aim of this systematic review was to identify and synthesise psychosocial factors associated with overdose among people who use drugs. METHODS: This review was registered on Prospero (CRD42021242495). Systematic record searches were undertaken in databases of peer-reviewed literature (Medline, Embase, PsycINFO, and Cinahl) and grey literature sources (Google Scholar) for work published up to and including 14 February 2023. Reference lists of selected full-text papers were searched for additional records. Studies were eligible if they included people who use drugs with a focus on relationships between psychosocial factors and overdose subsequent to illicit drug use. Results were tabulated and narratively synthesised. RESULTS: Twenty-six studies were included in the review, with 150,625 participants: of those 3,383-4072 (3%) experienced overdose. Twenty-one (81%) studies were conducted in North America and 23 (89%) reported polydrug use. Psychosocial factors associated with risk of overdose (n = 103) were identified and thematically organised into ten groups. These were: income; housing instability; incarceration; traumatic experiences; overdose risk perception and past experience; healthcare experiences; perception of own drug use and injecting skills; injecting setting; conditions with physical environment; and social network traits. CONCLUSIONS: Global rates of overdose continue to increase, and many guidelines recommend psychosocial interventions for dependent drug use. The factors identified here provide useful targets for practitioners to focus on at the individual level, but many identified will require wider policy changes to affect positive change. Future research should seek to develop and trial interventions targeting factors identified, whilst advocacy for key policy reforms to reduce harm must continue.

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.

An international multidisciplinary consensus on pediatric metabolic dysfunction-associated fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in children and adolescents, particularly those with obesity. NAFLD is considered a hepatic manifestation of the metabolic syndrome due to its close associations with abdominal obesity, insulin resistance, and atherogenic dyslipidemia. Experts have proposed an alternative terminology, metabolic dysfunction-associated fatty liver disease (MAFLD), to better reflect its pathophysiology. This study aimed to develop consensus statements and recommendations for pediatric MAFLD through collaboration among international experts. METHODS: A group of 65 experts from 35 countries and six continents, including pediatricians, hepatologists, and endocrinologists, participated in a consensus development process. The process encompassed various aspects of pediatric MAFLD, including epidemiology, mechanisms, screening, and management. FINDINGS: In round 1, we received 65 surveys from 35 countries and analyzed these results, which informed us that 73.3% of respondents agreed with 20 draft statements while 23.8% agreed somewhat. The mean percentage of agreement or somewhat agreement increased to 80.85% and 15.75%, respectively, in round 2. The final statements covered a wide range of topics related to epidemiology, pathophysiology, and strategies for screening and managing pediatric MAFLD. CONCLUSIONS: The consensus statements and recommendations developed by an international expert panel serve to optimize clinical outcomes and improve the quality of life for children and adolescents with MAFLD. These findings emphasize the need for standardized approaches in diagnosing and treating pediatric MAFLD. FUNDING: This work was funded by the National Natural Science Foundation of China (82070588, 82370577), the National Key R&D Program of China (2023YFA1800801), National High Level Hospital Clinical Research Funding (2022-PUMCH-C-014), the Wuxi Taihu Talent Plan (DJTD202106), and the Medical Key Discipline Program of Wuxi Health Commission (ZDXK2021007).

MAFLD as part of systemic metabolic dysregulation.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. In recent years, a new terminology and definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed. Compared to the NAFLD definition, MAFLD better emphasizes the pathogenic role of metabolic dysfunction in the development and progression of this highly prevalent condition. Metabolic disorders, including overweight/obesity, type 2 diabetes mellitus (T2DM), atherogenic dyslipidemia and hypertension, are often associated with systemic organ dysfunctions, thereby suggesting that multiple organ damage can occur in MAFLD. Substantial epidemiological evidence indicates that MAFLD is not only associated with an increased risk of liver-related complications, but also increases the risk of developing several extra-hepatic diseases, including new-onset T2DM, adverse cardiovascular and renal outcomes, and some common endocrine diseases. We have summarized the current literature on the adverse effect of MAFLD on the development of multiple extrahepatic (cardiometabolic and endocrine) complications and examined the role of different metabolic pathways and organ systems in the progression of MAFLD, thus providing new insights into the role of MAFLD as a multisystem metabolic disorder. Our narrative review aimed to provide insights into potential mechanisms underlying the known associations between MAFLD and extrahepatic diseases, as part of MAFLD as a multisystem disease, in order to help focus areas for future drug development targeting not only liver disease but also the risk of extrahepatic complications.

Serum PRO-C3 is useful for risk prediction and fibrosis assessment in MAFLD with chronic kidney disease in an Asian cohort.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is an emerging risk factor for chronic kidney disease (CKD). N-terminal propeptide of collagen type 3 (PRO-C3) is a biomarker of advanced fibrosis in MAFLD and PRO-C3 may be involved in renal fibrosis. We aimed to use PRO-C3 measurements to generate a new algorithmic score to test the prediction of MAFLD with chronic kidney disease (MAFLD-CKD). METHODS: A derivation and independent validation cohort of 750 and 129 Asian patients with biopsy-confirmed MAFLD were included. Serum PRO-C3 concentration was measured and regression analyses were performed to examine associations with MAFLD-CKD. A derivative algorithm for MAFLD-CKD risk prediction was evaluated with receiver operator characteristic (ROC) curve analysis. RESULTS: The study included two Asian cohorts (n = 180 with MAFLD-CKD; mean-eGFR: 94.93 mL/min/1.73 m2; median-urinary albumin-to-creatinine ratio: 6.58 mg/mmol). PRO-C3 was associated with the severity of MAFLD-CKD and independently associated with MAFLD-CKD (adjusted odds ratio = 1.16, 95% confidence interval [CI]: 1.08-1.23, p < .001). A new non-invasive score (termed PERIOD) including PRO-C3 efficiently predicted MAFLD-CKD (AUROC = .842, 95% CI: .805-.875). Accuracy, specificity and negative predictive values were 80.2%, 85.1% and 88.4%, respectively. In the validation cohort, the PERIOD score had good diagnostic performance (AUROC = .807, 95% CI: .691-.893) with similar results in all patient subgroups. In the MAFLD-CKD subgroup, the accuracy for identifying advanced fibrosis was further improved by combining the PRO-C3-based ADAPT with the Agile 3+ scores (AUROC = .90, 95% CI: .836-.964). CONCLUSIONS: The PERIOD score is helpful for accurately predicting the risk of MAFLD-CKD. PRO-C3 can also be used to assess liver fibrosis in people with MAFLD-CKD.

An Unusual and Protracted Course of a Haggitt 3 Malignant Polyp Recurrence.

Timely detection of colorectal cancer recurrence is paramount, as treatment of early-stage recurrence greatly improves survival and outcomes. Current guidelines outline post-resection surveillance through endoscopy, CT imaging, and tumor markers for five years; however, there is minimal data to guide follow-up beyond this. We present the case of a 60-year-old female with locoregional recurrence 15 years after endoscopic mucosal resection of a low-grade Haggit level 3 sigmoid colon polyp. Unusually the recurrence was noted as an incidental finding following investigation of an elevated alpha-fetoprotein level post liver transplant, and a retrospective review of imaging revealed a calcified sigmoid mesentery mass. While surgical pathology revealed locoregional recurrence, there was no evidence of this on surveillance and preoperative colonoscopy. Through this case, we discuss the risk factors for late recurrence of colorectal cancer whilst exploring the literature and guidelines around this subset of patients. As new guidelines are developed, it may be important to consider late recurrence and individualize follow-up regimes based on risk factors.

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.

Current status and future trends of the global burden of MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most common chronic liver disease globally, affecting more than a third of the world's adult population. This comprehensive narrative review summarizes the global incidence and prevalence rates of MASLD and its related adverse hepatic and extrahepatic outcomes. We also discuss the substantial economic burden of MASLD on healthcare systems, thus further highlighting the urgent need for global efforts to tackle this common and burdensome liver condition. We emphasize the clinical relevance of early interventions and a holistic approach that includes public health strategies to reduce the global impact of MASLD.

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.

Baseline and change in serum uric acid level over time and resolution of nonalcoholic fatty liver disease in young adults: The Kangbuk Samsung Health Study.

AIMS: To determine the association between: (i) baseline serum uric acid (SUA) level and (ii) SUA changes over time, and nonalcoholic fatty liver disease (NAFLD) resolution. MATERIALS AND METHODS: A retrospective cohort study, comprising 38 483 subjects aged <40 years with pre-existing NAFLD, was undertaken. The effects of SUA changes over time were studied in 25 266 subjects. Participants underwent a health examination between 2011 and 2019, and at least one follow-up liver ultrasonography scan up to December 2020. Exposures included baseline SUA level and SUA changes between baseline and subsequent visits, categorized into quintiles. The reference group was the third quintile (Q3) containing zero change. The primary endpoint was resolution of NAFLD. RESULTS: During a median follow-up of 4 years, low baseline SUA level and decreases in SUA levels over time were independently associated with NAFLD resolution (p for trend <0.001). Using SUA as a continuous variable, the likelihood of NAFLD resolution was increased by 10% and 13% in men and women, respectively, per 1-mg/dL decrease in SUA. In a time-dependent model with changes in SUA treated as a time-varying covariate, adjusted hazard ratios (95% confidence intervals) for NAFLD resolution comparing Q1 (highest decrease) and Q2 (slight decrease) to Q3 (reference) were 1.63 (1.49-1.78) and 1.23 (1.11-1.35) in men and 1.78 (1.49-2.12) and 1.18 (0.95-1.46) in women, respectively. CONCLUSIONS: Low baseline SUA levels and a decrease in SUA levels over time were both associated with NAFLD resolution in young adults.

Body composition and metabolism in adults with molecularly-confirmed Silver-Russell syndrome.

CONTEXT: Low birth weight, as seen in Silver-Russell syndrome (SRS), is associated with later cardiometabolic disease. Data on long term outcomes and adult body composition in SRS are limited. OBJECTIVE: To evaluate body composition and metabolic health in adults with SRS. DESIGN: This was an observational study. Body composition and metabolic health were assessed at a single appointment. Individuals with SRS were compared with unaffected men and women (from the Southampton Women's Survey (SWS)). SETTING: Clinical research facilities across the UK. PARTICIPANTS: 25 individuals with molecularly-confirmed SRS aged ≥18 years. MAIN OUTCOME MEASURES: Fat mass, lean mass, bone mineral density (BMD), blood pressure, lipids, and blood glucose were measured. RESULTS: 25 adults with SRS were included (52% female). The median age was 32.9 years (range 22.0-69.7). Fat percentage was greater in the SRS group than the SWS cohort (44.1% vs 30.3%, p<0.001). Fat mass index was similar (9.6 vs 7.8, p=0.3). Lean mass percentage (51.8% vs 66.2%, p<0.001) and lean mass index (13.5 kg/m2 vs 17.3 kg/m2, p<0.001) were lower in the SRS group than the SWS cohort. BMD was lower in the SRS group than the SWS cohort (1.08 vs 1.24, p<0.001) (all median values). Total cholesterol was ≥5mmol/L in 52.0%. Triglyceride levels were ≥1.7mmol/L in 20.8%. Fasting blood glucose levels were ≥6.1mmol/L in 25.0%. Hypertension was present in 33.3%. CONCLUSIONS: Adults with SRS have an unfavourable body composition and predisposition to cardiometabolic disease. These results support the need for a health surveillance strategy to mitigate adverse outcomes.

The future of International Classification of Diseases coding in steatotic liver disease: An expert panel Delphi consensus statement.

BACKGROUND: Following the adoption of new nomenclature for steatotic liver disease, we aimed to build consensus on the use of International Classification of Diseases codes and recommendations for future research and advocacy. METHODS: Through a two-stage Delphi process, a core group (n = 20) reviewed draft statements and recommendations (n = 6), indicating levels of agreement. Following revisions, this process was repeated with a large expert panel (n = 243) from 73 countries. RESULTS: Consensus ranged from 88.8% to 96.9% (mean = 92.3%). CONCLUSIONS: This global consensus statement provides guidance on harmonizing the International Classification of Diseases coding for steatotic liver disease and future directions to advance the field.