Peer support for people living with hepatitis B virus-A foundation for treatment expansion.

Chronic hepatitis B infection (CHB) affects 300 million people worldwide and is being targeted by the United Nations 2030 Sustainable Development Goals (SDGs) and the World Health Organisation (WHO), working towards elimination of hepatitis B virus (HBV) as a public health threat. In this piece, we explore the evidence and potential impact of peer support to enhance and promote interventions for people living with CHB. Peer support workers (PSWs) are those with lived experience of an infection, condition or situation who work to provide support for others, aiming to improve education, prevention, treatment and other clinical interventions and to reduce the physical, psychological and social impacts of disease. Peer support has been shown to be a valuable tool for improving health outcomes for people living with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), but to date has not been widely available for communities affected by HBV. HBV disproportionately affects vulnerable and marginalised populations, who could benefit from PSWs to help them navigate complicated systems and provide advocacy, tackle stigma, improve education and representation, and optimise access to treatment and continuity of care. The scale up of peer support must provide structured and supportive career pathways for PSWs, account for social and cultural needs of different communities, adapt to differing healthcare systems and provide flexibility in approaches to care. Investment in peer support for people living with CHB could increase diagnosis, improve retention in care, and support design and roll out of interventions that can contribute to global elimination goals.

Multiple risk factors for persistent HBV viraemia in an adult receiving nucleos/tide analogue therapy.

Diagnosing and treating chronic hepatitis B virus (HBV) infection are key interventions to support progress towards elimination of viral hepatitis by 2030. Although nucleos/tide analogue (NA) therapy is typically highly effective, challenges remain for viral load (VL) suppression, including medication access, incomplete adherence and drug resistance. We present a case of a long-term HBV and HIV coinfected adult prescribed with sequential NA therapy regimens, with episodes of breakthrough viraemia. Multiple factors contribute to virological breakthrough, including exposure to old NA agents, initial high HBV VL, therapy interruptions, intercurrent illnesses and potential contribution from resistance mutations. The case underscores the importance of individualised treatment approaches and adherence support in achieving HBV suppression. Furthermore, it emphasises the need for improved clinical pathways addressing education, support and access to care, particularly for marginalised populations. Comprehensive data collection inclusive of under-represented individuals is crucial for maintaining retention in the care cascade and informing effective interventions.

Falling treatment uptake in the hepatitis C care cascade is a growing threat to achieving elimination.

Most high-income countries are not on track to achieve the World Health Organization hepatitis C elimination targets. As elimination programmes assess growing proportions of patients in community-based pathways, rates of treatment uptake may fall. We aimed to identify factors associated with DAA treatment uptake and measure changes in their prevalence over time. We performed a time-to-treatment analysis on 2728 patients approved for hepatitis C Direct-Acting Antiviral treatment in the North Central London region between January 2016 and October 2019. We investigated the association between treatment uptake and factors including assessment/treatment setting (hospital, drug service or prison), patient age, gender, injection drug use, harmful alcohol use, cirrhosis status and previous treatment. The likelihood of treatment uptake was reduced by three independent risk factors. These included assessment setting: prison-based or drug-service pathways (aHR 0.29 or 0.81 vs. hospital outpatient pathway, 95% CI 0.21-0.40 and 0.70-0.94 respectively, p < .001); being UK-born (aHR 0.89 vs. non-UK born, 0.82-0.98, p = .01); and history of harmful alcohol use (aHR 0.84 vs. no history, 0.72-0.99, p = .04). The average number of these risk factors for not starting treatment per patient increased over time (R2  = 0.66 p < .001). Independent of these, there was an additional 5% reduction in rate of treatment initiation in each successive year of the programme (aHR 0.95, 0.91-0.99, p = .02). In conclusion, disengagement from care before treatment uptake was found to be a growing threat to elimination. Despite provision of community-based test-to-cure pathways, there are persistent barriers to treatment uptake and these are increasing over time.

Delivery of biannual ultrasound surveillance for individuals with cirrhosis and cured hepatitis C in the UK.

BACKGROUND: Previous studies show the uptake of biannual ultrasound (US) surveillance in patients with cirrhosis is suboptimal. Here, our goal was to understand in broader terms how surveillance is being delivered to cirrhosis patients with cured hepatitis C in the UK. METHODS: Hepatitis C cirrhosis patients achieving a sustained viral response (SVR) to antiviral therapies were identified from the national Hepatitis-C-Research-UK resource. Data on (i) liver/abdominal US examinations, (ii) HCC diagnoses, and (iii) HCC curative treatment were obtained through record-linkage to national health registries. The rate of US uptake was calculated by dividing the number of US episodes by follow-up time. RESULTS: A total of 1908 cirrhosis patients from 31 liver centres were followed for 3.8 (IQR: 3.4-4.9) years. Overall, 10 396 liver/abdominal USs were identified. The proportion with biannual US was 19% in the first 3 years after SVR and 9% for all follow-up years. Higher uptake of biannual US was associated with attending a liver transplant centre; older age and cirrhosis decompensation. Funnel plot analysis indicated significant inter-centre variability in biannual US uptake, with 6/29 centres outside control limits. Incident HCC occurred in 133 patients, of which 49/133 (37%) were treated with curative intent. The number of US episodes in the two years prior to HCC diagnosis was significantly associated with higher odds of curative-intent treatment (aOR: 1.53; 95% CI: 1.12-2,09; p = .007). CONCLUSIONS: This study provides novel data on the cascade of care for HCC in the UK. Our findings suggest biannual US is poorly targeted, inefficient and is not being delivered equitably to all patients.

Kappa-on-Heavy (KoH) bodies are a distinct class of fully-human antibody-like therapeutic agents with antigen-binding properties.

We describe a Kappa-on-Heavy (KoH) mouse that produces a class of highly diverse, fully human, antibody-like agents. This mouse was made by replacing the germline variable sequences of both the Ig heavy-chain (IgH) and Ig kappa (IgK) loci with the human IgK germline variable sequences, producing antibody-like molecules with an antigen binding site made up of 2 kappa variable domains. These molecules, named KoH bodies, structurally mimic naturally existing Bence-Jones light-chain dimers in their variable domains and remain wild-type in their antibody constant domains. Unlike artificially diversified, nonimmunoglobulin alternative scaffolds (e.g., DARPins), KoH bodies consist of a configuration of normal Ig scaffolds that undergo natural diversification in B cells. Monoclonal KoH bodies have properties similar to those of conventional antibodies but exhibit an enhanced ability to bind small molecules such as the endogenous cardiotonic steroid marinobufagenin (MBG) and nicotine. A comparison of crystal structures of MBG bound to a KoH Fab versus a conventional Fab showed that the KoH body has a much deeper binding pocket, allowing MBG to be held 4 Å further down into the combining site between the 2 variable domains.

The fate of indeterminate liver lesions: What proportion are precursors of hepatocellular carcinoma?

BACKGROUND: The natural history and incidence of hepatocellular carcinoma (HCC) arising from indeterminate liver lesions are not well described. We aimed to define the incidence of HCC in a cohort of patients undergoing surveillance by magnetic resonance imaging (MRI) and estimate any associations with incident HCC. METHODS: We performed a retrospective follow-up study, identifying MRI scans in which indeterminate lesions had been reported between January 2006 and January 2017. Subsequent MRI scan reports were reviewed for incident HCC arising from indeterminate lesions, data were extracted from electronic patient records and survival analysis performed to estimate associations with baseline factors. RESULTS: One hundred and nine patients with indeterminate lesions on MRI were identified. HCC developed in 19 (17%) patients over mean follow up of 4.6 years. Univariate Cox proportional hazards analysis found incident HCC to be significantly associated with baseline low platelet count (hazard ratio (HR) = 7.3 (95% confidence intervals (CI) 2.1-24.9), high serum alpha-fetoprotein level (HR = 2.7 (95% CI 1.0-7.1)) and alcohol consumption above fourteen units weekly (HR = 3.1 (95% CI 1.1-8.7)). Multivariate analysis, however, found that only low platelet count was independently associated with HCC (HR = 5.5 (95% CI 0.6-5.1)). CONCLUSIONS: HCC arises in approximately one fifth of indeterminate liver lesions over 4.6 years and is associated with a low platelet count at the time of first diagnosis of an indeterminate lesion. Incidence of HCC was more common in people with viral hepatitis and in those consuming > 14 units of alcohol per week. Our data may be used to support a strategy of enhanced surveillance in patients with indeterminate lesions.

Identification of distinct conformations associated with monomers and fibril assemblies of mutant huntingtin.

The N-terminal fragments of mutant huntingtin (mHTT) misfold and assemble into oligomers, which ultimately bundle into insoluble fibrils. Conformations unique to various assemblies of mHTT remain unknown. Knowledge on the half-life of various multimeric structures of mHTT is also scarce. Using a panel of four new antibodies named PHP1-4, we have identified new conformations in monomers and assembled structures of mHTT. PHP1 and PHP2 bind to epitopes within the proline-rich domain (PRD), whereas PHP3 and PHP4 interact with motifs formed at the junction of polyglutamine (polyQ) and polyproline (polyP) repeats of HTT. The PHP1- and PHP2-reactive epitopes are exposed in fibrils of mHTT exon1 (mHTTx1) generated from recombinant proteins and mHTT assemblies, which progressively accumulate in the nuclei, cell bodies and neuropils in the brains of HD mouse models. Notably, electron microscopic examination of brain sections of HD mice revealed that PHP1- and PHP2-reactive mHTT assemblies are present in myelin sheath and in vesicle-like structures. Moreover, PHP1 and PHP2 antibodies block seeding and subsequent fibril assembly of mHTTx1 in vitro and in a cell culture model of HD. PHP3 and PHP4 bind to epitopes in full-length and N-terminal fragments of monomeric mHTT and binding diminishes as the mHTTx1 assembles into fibrils. Interestingly, PHP3 and PHP4 also prevent the aggregation of mHTTx1 in vitro highlighting a regulatory function for the polyQ-polyP motifs. These newly detected conformations may affect fibril assembly, stability and intercellular transport of mHTT.

Detection, stratification and treatment of hepatitis C-positive prisoners in the United Kingdom prison estate: Development of a pathway of care to facilitate the elimination of hepatitis C in a London prison.

The United Kingdom is committed to eliminating hepatitis C virus (HCV) infection by 2025. The prison estate provides an opportunity to identify and treat HCV-positive individuals in a high-prevalence environment. We designed and implemented a pathway of care within a London prison to diagnose, stratify and link HCV-positive prisoners into care. This study was a two-phase case study of a HCV care pathway. New arrivals to the prison were offered blood-borne virus screening with dried blood spot testing at their secondary health check. Those with active infection completed disease stratification tests and were reviewed at a weekly hospital-based multidisciplinary team meeting to determine management. In Phase-2, the pathway was redesigned to improve testing and the referral of HCV-positive prisoners into treatment. Over the 30-month evaluation period, 12,946 people were received in the prison. During Phase-1, 19.6% of new arrivals completed blood-borne virus testing, with 7.3% identified as HCV-positive. Just 8.3% of HCV-positive individuals were treated or referred for treatment in Phase-1. During Phase-2, 30% of new receptions completed BBV testing and 3.9% were identified as HCV-positive. Linkage into care was improved, with 38.9% treated or referred during the second phase. Poor access to testing and referral to treatment limit the effectiveness of care provision for prisoners with HCV. Elimination of HCV in prisons requires local service configuration to ensure high uptake of testing, with all HCV-positive cases then offered treatment during custody or referral on to treatment after release.

Liver transplant listing for hepatitis C-associated cirrhosis and hepatocellular carcinoma has fallen in the United Kingdom since the introduction of direct-acting antiviral therapy.

Following the introduction of direct-acting antivirals (DAA), there have been reports of declining incidence of hepatitis C (HCV)-related liver disease as a liver transplantation indication. In this study, we assessed the impact of DAA on liver transplant indications in the UK and waiting list outcomes for patients with HCV. We assessed UK adult elective liver transplant registrants between 2006 and 2017. The aetiology of liver disease at registration was reclassified using an accepted hierarchical system and changes were assessed over time and compared before and after the introduction of DAA. Registration UKELD scores and 1-year waiting list outcomes were also compared. The proportion of waiting list patients registered with HCV-related cirrhosis reduced after the introduction of DAA from 10.5% in 2013 to 4.7% in 2016 (P < 0.001). Alcohol-related liver disease (ARLD) was the leading indication for liver transplantation followed by liver cancer (26.1% and 18.4% in 2016, respectively). The proportion of registrations with Hepatocellular carcinoma (HCC) associated with HCV reduced from 46.4% in 2013 to 33.7% in 2016 (P = 0.002). For patients with HCV-related cirrhosis at one year the outcomes of death, transplantation, delisting due to improvement or deterioration and awaiting a graft at 1 year were similar. For patients with HCV-related HCC, the proportion dying at 1 year reduced significantly from 2.9% to 0.0% (P = 0.04). These data demonstrate an association between DAA and reduced listing rates for HCV-related cirrhosis and HCC, but no significant changes in waiting list outcomes other than reduced mortality in the HCC group.

Exploring health economics course competencies' value for nurse administrators.

BACKGROUND: A survey of nursing administrators in the United States was conducted to solicit opinions about health economics (HE) course competencies for baccalaureate nursing programs. PURPOSE: To provide rationale for intensifying educational efforts to increase nurses' awareness about the value of HE skills in their everyday work. METHODS: Participants were asked to rate six HE competencies using a Likert scale. Paired-samples t tests, bivariate correlations, and standard multiple linear regressions were used to analyze survey results. DISCUSSION: A strong direct relationship exists between the amount of prior knowledge nursing administrators have about HE and the perceived level of usefulness of HE skills. CONCLUSION: Nurses' contributions to creating value in healthcare must be encouraged. Increasing the share and accessibility of the HE content in continuing education offerings could be one way to expand HE knowledge among practicing nurses and promote cost-effective delivery of healthcare in the United States.