Stuart McPherson

Little is known about hepatitis B virus (HBV) and Hepatitis D virus (HDV) coinfection in the UK. HDV screening is recommended among all individuals with HBV, with coinfection associated with increased disease progression. Using data on HDV testing, shared by 11 laboratories in the UK who reported undertaking HDV testing, and national testing data for HBV we established a cohort of individuals tested for HDV, investigating testing pathways, describing characteristics and outcomes of those HDV‐RNA positive to inform targeted interventions for testing, diagnosis and linkage to care. Demographic information, clinical assessments, treatment and recent laboratory results from NHS trusts, and through linkage to national healthcare datasets was collected for HDV‐RNA positive individuals. Between 2011 and 2021, 42% of individuals newly diagnosed with HBV in England were linked to an HDV test. Anti‐HDV positivity was 5.0%, 55.8% were HDV‐RNA tested and 45.7% were ever HDV‐RNA positive. HDV‐RNA positivity in the absence of an anti‐HDV result was 6.4%. Among individuals who were HDV‐RNA positive, 94.3% were non‐UK born, with 24 different primary languages reported, 49% had evidence of treatment, and 48% had evidence of cirrhosis. 10% had died of which 58.4% died of liver disease. In conclusion, our findings indicate that HDV testing in HBV positive individuals in the UK is sub‐optimal against testing guidelines, including RNA testing among those who are anti‐HDV positive. Considerable work is needed to improve the patient care pathway, to ensure patients are appropriately diagnosed, linked and retained in care, with adequate access to treatment.

Background: Finite therapy resulting in sustained hepatitis B surface antigen (HBsAg) loss for patients with chronic HBV infection (CHB) is an important therapeutic goal. In patients with HBeAg-negative infection, nucleos(t)ide analog (NA) withdrawal may achieve HBsAg loss in 5%–20% of patients after 3 years. Pegylated interferon (PEG-IFNα) is a recognized treatment for CHB. Methods: NUC-B was a randomized, multicenter trial in NA-treated non-cirrhotic HBeAg-negative patients with CHB. Patients were allocated to either NA withdrawal alone (control) or NA withdrawal followed by a 16-week course of PEG-IFNα 180 μg weekly commencing 4 weeks after NA cessation (PEG-IFNα). The primary endpoint was HBsAg loss at 3 years. Results: The target recruitment of 240 patients was not achieved. In all, 156 patients, 82 to the control arm, 74 to the PEG-IFNα arm, were recruited between 2017 and 2021; median age 45 years, 24% female, HBV genotypes—A 16%, B 6%, C 4%, D 24%, E 22%, other 1%, ānd unknown 26%. At 3 years, 3% of patients in the control arm and 14% of patients in the PEG-IFNα arm lost HBsAg (OR 5.39; 95% CI (1.11, 26.19); p =0.037). In the control arm, 34.9% of patients returned to NA therapy compared with 28.4% in the PEG-IFNα arm. Exaggerated flares occurred in 27.9% of patients in the control arm compared with 13.4% in the PEG-IFNα arm. Conclusions: The use of adjuvant PEG-IFNα therapy after withdrawal of NA therapy increases the rate of HBsAg loss while simultaneously reducing the number of exaggerated flares.

Objective: Liver disease is a growing public health concern worldwide with increasing morbidity and mortality driven by alcohol-related liver disease (ALD), viral hepatitis and metabolic dysfunction-associated steatotic liver disease (MASLD). Early detection of compensated advanced chronic liver disease (cACLD) is critical to enable timely intervention and hepatocellular carcinoma surveillance. However, case finding in primary care remains limited. Our aim was to evaluate the outcomes of a primary care case-finding programme. Methods: Prospective evaluation of a pilot programme funded by National Health Service England across 12 primary care networks, implementing a non-invasive liver fibrosis assessment pathway using Fibrosis-4 (FIB-4), enhanced liver fibrosis (ELF) and vibration-controlled transient elastography. Adults with liver disease risk factors were identified via electronic health record searches and invited for testing. cACLD was defined as liver stiffness measurement (LSM) ≥11.5 kPa. Results: Of 47 243 individuals eligible for testing, 11 908 (25.2%) had testing with FIB-4. Among these, 3.2% had LSM ≥11.5 kPa, indicating probable cACLD. Prevalence was highest in individuals with known ALD (5.1%), hepatitis C (4.8%), MASLD (3.8%) and type 2 diabetes mellitus (3.7%). Age, body mass index and known history of ALD were independently associated with cACLD. Pathway adherence varied, with 71.9% following the protocol (significant overinvestigation and underinvestigation). Reflex ELF testing significantly improved adherence. Conclusions: This pilot demonstrates that liver fibrosis case finding in primary care can be conducted with reasonable uptake. However, suboptimal uptake and pathway adherence highlight the need for automated, integrated approaches. Work is ongoing to more clearly define the optimum case finding approach.

Background: People who inject drugs are disproportionately affected by hepatitis C virus. The emergence of direct-acting antiviral treatments for hepatitis C virus motivated England to achieve the World Health Organization’s elimination target of decreasing hepatitis C virus incidence among people who inject drugs to < 2 per 100 person-years (/100 person-years) by 2030. We determined whether existing testing and treatment strategies will reach this target in England, or whether improved strategies are needed and whether they are cost-effective. Methods: A dynamic hepatitis C virus transmission model among people who inject drugs was developed for four English regions. The model included the pathway from testing to treatment in prisons, drug treatment centres and other settings. Each pathway was parameterised using region-specific data, with yearly bio-behavioural surveys among people who inject drugs being used to parameterise and calibrate the model in a Bayesian framework. The model projected whether each region will reach the hepatitis C virus incidence target or what improvements (in testing and linkage to treatment) are needed from 2024 to achieve it. Hepatitis C virus care pathway costs were collated through interviews with practitioners and the published literature. The mean incremental cost-effectiveness ratio (per quality-adjusted life-year saved) was estimated for any ‘improved’ strategy that reached the incidence target compared to the baseline strategy. Incremental cost-effectiveness ratios were compared to a willingness-to-pay threshold of £20,000/quality-adjusted life-year saved over a 50-year time horizon (3.5% annual discount rate). Results: Across the four regions over 2016–22, an estimated 8831–9689 treatments occurred among 37,230 people who inject drugs, with the annual number treated increasing in prisons (7.8 times) and drug treatment centres (3.6 times). Model projections suggest that hepatitis C virus incidence among people who inject drugs has decreased across the regions by 56.1–85.4% (range of medians) over 2015–22, with incidence decreasing by 79.7–98.6% to 0.2–2.2/100 person-years by 2030. The World Health Organization incidence target (< 2/100 person-years) will be reached with > 80% probability in three regions and 40% probability in the other region. The probability of reaching the incidence target increases to > 65% in this region if screening is increased in drug treatment centres (80% screened annually) or prisons (75% of people get tested during their prison stay), with these screening strategies being cost-effective. Conclusion: Numerous England regions may be on target to decrease hepatitis C virus incidence among people who inject drugs to < 2/100 person-years. In regions that are not on target, further scale-up of testing in drug treatment centre or prison from 2024 could enable them to reach the World Health Organization elimination target and be cost-effective. Limitations: Projections were based on model estimations, which need to be confirmed with empirical data. Data uncertainties affected our model projections, including uncertainty in the number of people who inject drugs in each region and the number of treatments given to people who inject drugs in different settings. Sample sizes for the yearly bio-behavioural surveys among people who inject drugs were small, and so samples were pooled over multiple years. Testing rates among people who inject drugs could not be directly estimated because the sentinel surveillance had incomplete coverage and could not identify people who inject drugs; testing rates were estimated through model calibration. Future work: There is interest in understanding what scale-back in testing can occur after 2030 without resulting in a rebound in hepatitis C virus incidence, and in developing models for each devolved nation to determine their progress to World Health Organization hepatitis C virus elimination targets. Funding: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR128513.

The prevalence and burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is very high globally, especially in socially deprived areas. This trend parallels the increasing incidence of type 2 diabetes mellitus and obesity. While MASLD is influenced by multiple factors, including genetics, metabolism and the environment, key modifiable contributors include nutrition, sedentary behaviour, physical activity and sleep quality. The widespread shift towards consumption of ultra-processed food highlights growing concerns around food insecurity and nutritional quality. This review, produced by a multinational team, focuses primarily on the role of nutrition in the prevention and management of MASLD. While physical activity remains a vital component of lifestyle modification, the central emphasis of this review is placed on dietary factors. In this study, we summarise recommendations made by international clinical practice guidelines and highlight the important role that both macronutrients and micronutrients play in liver health. We also evaluate five major dietary patterns in the context of MASLD, outlining the benefits and limitations of each to best support evidence-based patient counselling. We emphasise the importance of personalised and culturally sensitive nutritional advice. Practical tools are provided, including a nutrient-focused summary of beneficial foods and culturally adaptable Mediterranean diet modifications suitable for South and Southeast Asian, African and socioeconomically disadvantaged populations. A sample menu is included to support implementation of the tools in diverse clinical settings.

Introduction: Liver disease disproportionately affects the most economically disadvantaged. Since 2019, Food insecurity (FI) prevalence has increased by 26% in Europe and 214% in the UK. FI compromises nutritional status and may also hamper the adoption of recommended dietary lifestyle advice. We aimed to assess the extent of FI and its associated factors among patients with liver disease. Methods: This cross‐sectional study recruited consecutive patients attending hepatology outpatient services at a tertiary centre between October 2023 and March 2024. Food security status was assessed using validated tools: the United States Department of Agriculture's Six‐item Household Food Security Survey and the Hunger Vital Signs Two‐Item Screener. Logistic regression was performed to assess associations between FI and clinico‐sociodemographic variables. Results: 103 (24%) of 426 patients screened were identified as food insecure. Predictive variables for FI included: high risk/dependent alcohol intake (OR 2.7, 95%CI 1.1–6.8, p = 0.03), alcohol related liver disease (ArLD) (OR 1.9, 1.1–3.1, p = 0.02), cirrhosis (OR 1.6, 1.1–2.6, p = 0.03) and depression (OR 1.7, 1.1–2.8, p = 0.023). After adjustment for co‐morbidities, clinical and socio‐demographic characteristics, ArLD (AOR = 3.2, 1.3–8.0, p = 0.013), metabolic dysfunction associated steatotic liver disease (MASLD) (AOR = 2.3, 1.1–5.0, p = 0.03) and cirrhosis (AOR = 1.9, 1.0–3.0, p = 0.034) were found to be associated with FI. Conclusion: FI was higher amongst patients with liver disease than the background population, and associated with ArLD, MASLD and cirrhosis. These results highlight an important paradox wherein FI contributes to obesity, so promoting consequent end‐organ damage in MASLD, and compromises nutritional status. It is also a barrier to implementation of recommended diet lifestyle advice. Healthcare professionals should consider FI within holistic patient assessment.

Objective: Clinical guidelines recommend structured education programmes for patients with metabolic dysfunction-associated steatotic liver disease (MASLD); however, these are uncommon in practice. We developed and implemented a structured group education programme and aimed to assess patient engagement, experiences of attending the groups and evaluate whether attendance led to weight loss. Methods: Patients with MASLD attending a tertiary liver unit were offered three 1-hour sessions, either face-to-face (F2F) or online. Content included: what MASLD is; how lifestyle change can improve outcomes; and signposting to appropriate resources. Patient-related experiences and weight data were collected prospectively. Results: 204 patients were invited to attend the groups between October 2023 and March 2025. 84% booked to attend and 54% attended (median age 62 years; 54% male; body mass index 38 kg/m²): 69% F2F; 31% online. Mean weight change at follow-up was −3.4 kg (−3.2%; p<0.001); 46% achieved ≥3% weight loss, 29%≥5% and 11%≥10%. There was no statistically significant difference in mean weight loss achieved between patients attending F2F versus online (−2.8 kg (−2.7%); vs −4.9 kg (−4.4%); p=0.154). Weight losses observed in those attending the groups were greater than those receiving standard care in our unit (p=0.005). Patients reported overall satisfaction with the programme (mean score: 9.4/10) and were likely to recommend the course to others (mean score: 9.8/10). Conclusions: The MASLD group education programme was feasible to deliver, well received by patients and achieved greater weight loss than standard care. Structured group education is a viable option to support patients with MASLD to make lifestyle changes and may help to expand clinical capacity.

Objective Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease worldwide. Weight loss, achieved by changes to lifestyle behaviours, is the recommended management approach. However, patients find this challenging. A MASLD-specific digital behavioural intervention (interVention to promote lIfesTyle change in metabolic dysfunction-Associated steatotic LIver diseaSE, VITALISE) to target changes in dietary and physical activity behaviours was developed to support weight loss. This study assessed the feasibility and acceptability of delivering VITALISE in routine secondary care. Methods A single-centre, one-arm feasibility study recruited participants from November 2022 to May 2023. VITALISE included MASLD-specific education, provision of self-regulation tools (ie, goal setting, food monitoring, step tracking, weight monitoring) and monthly health coaching appointments by telephone. Patients had access to VITALISE for 6 months. Primary outcomes were feasibility (recruitment, uptake, engagement, adherence, and follow-up rates) and acceptability (patient views). Secondary outcomes were body weight, liver enzymes, liver stiffness, blood pressure, lipid profile, glycated hemoglobin (HbA1c), physical activity and patient activation. Results 35 patients (mean age 54 years; 69% male) with MASLD were recruited to VITALISE (recruitment rate 59%). Of the 35 enrolled, 83% activated their VITALISE account. Patient interviews supported acceptability. At 6 months, mean weight loss was 4.0 kg (3.5%) and alanine transaminase reduced by 27%. A decrease in daily sedentary time and an increase in light physical activity were observed. Self-reported leisure-time physical activity and patient activation increased from baseline to 6-month follow-up. Conclusions VITALISE was feasible and acceptable to deliver in routine secondary care. Weight loss and improvements in lifestyle behaviours and liver enzymes were observed. Findings will inform intervention optimisation and future large-scale evaluation. Trial registration number ISRCTN12893503.