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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.
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Hepatitis B Crónica , Grupo Paritario , Apoyo Social , Humanos , Hepatitis B Crónica/terapia , Hepatitis B Crónica/psicologíaRESUMEN
BACKGROUND: As new therapeutic options become available, better understanding the potential impact of emerging therapies on clinical outcomes of hepatits D virus (HDV) is critical. OBJECTIVE: The aim of this study was to develop a natural history model for patients with hepatitis D virus. METHODS: We developed a model (decision tree followed by a Markov cohort model) in adults with chronic HDV infection to assess the natural history and impact of novel treatments on disease progression versus best supportive care (BSC). The model time horizon was over a lifetime (up to 100 years of age); state transitions and health states were defined by responder status. Patients in fibrosis stages 0 through 4 received treatment; decompensated patients were not treated. Response was defined as the combined response endpoint of achievement of HDV-RNA undetectability/≥2-log10 decline and alanine aminotransferase normalization; response rates of 50% and 75% were explored. Health events associated with advanced liver disease were modeled as the number of events per 10,000 patients. Scenario analyses of early treatment, alternate treatment response, and no fibrosis regression for treatment responders were also explored. RESULTS: The model was able to reflect disease progression similarly to published natural history studies for patients with HBV/HDV infection. In a hypothetical cohort of patients reflecting a population enrolled in a recent clinical trial, fewer advanced liver disease events were observed with a novel HDV treatment versus BSC. Fewer liver-related deaths were observed under 50% and 75% response (900 and 1,358 fewer deaths, respectively, per 10,000 patients). Scenario analyses showed consistently fewer advanced liver disease events with HDV treatment compared with BSC, with greater reductions observed with earlier treatment. CONCLUSION: This HDV disease progression model replicated findings from natural history studies. Furthermore, it found that a hypothetical HDV treatment results in better clinical outcomes for patients versus BSC, with greater benefit observed when starting treatment early. This validated natural history model for HBV/HDV infection can serve as a foundation for future clinical and economic analyses of novel HDV treatments that can support healthcare stakeholders in the management of patients with chronic HDV.
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Prevention of mother-to-child transmission of hepatitis B virus (HBV) infection is a cornerstone of efforts to support progress towards elimination of viral hepatitis. Current guidelines recommend maternal screening, antiviral therapy during the third trimester of high-risk pregnancies, universal and timely HBV birth dose vaccination, and post-exposure prophylaxis with hepatitis B immunoglobulin for selected neonates. However, serological and molecular diagnostic testing, treatment and HBV vaccination are not consistently deployed, particularly in many high endemicity settings, and models predict that global targets for reduction in paediatric incidence will not be met by 2030. In this article, we briefly summarise the evidence for current practice and use this as a basis to discuss areas in which prevention of mother-to-child transmission can potentially be enhanced. By reducing health inequities, enhancing pragmatic use of resources, filling data gaps, developing advocacy and education, and seeking consistent investment from multilateral agencies, significant advances can be made to further reduce vertical transmission events, with wide health, societal and economic benefits.
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Chronic hepatitis B virus disproportionately affects migrant communities in high-income countries, reflecting increased migration from sub-Saharan Africa. Chronic hepatitis B virus is endemic in sub-Saharan Africa, yet the natural history of chronic infection experienced by patients remains incompletely understood, with evidence of variability across genotypes and regions within sub-Saharan Africa. Clinical guidelines recommending treatment thresholds are not specific to sub-Saharan African patients and are based on natural history studies from Western Pacific Asian countries. Access to standard of care treatment is available for sub-Saharan African people with chronic hepatitis B virus infection in high-income countries; however, the evidence base for these treatments was not established in this cohort and areas of uncertainty remain, particularly regarding HCC surveillance and treatment discontinuation. Participation in phase III clinical trials for chronic hepatitis B therapies is almost non-existent amongst sub-Saharan African patients, even when residing in high-income countries that participate in multicentre trials. Engagement with sub-Saharan African patients with chronic hepatitis B in high-income countries is challenging because of the stigma associated with the diagnosis, absence of routine screening systems and the complexities involved in navigating the healthcare system. Nonetheless, improved engagement is critical if we are to achieve global hepatitis B virus elimination.
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INTRODUCTION: Given the hepatitis C virus (HCV) burden and despite curative treatments, more efforts focused on scaling-up testing and treatment in homeless populations are needed. This project aimed to implement education and flexible on-site HCV testing, treatment, and follow-up for a homeless population in south London and to evaluate engagement, therapy initiation, and cure rates. METHODS: A mobile unit (van) for on-site HCV education, screening, treatment, and follow-up was placed on the street in a well-known homeless population areas from January 2018 to September 2021. Homeless was defined as living in temporary housing (hostel/hotel-based) or living on the street (street-based). Sociodemographic status, risk factors, comorbidities, concomitant medication, and data related with HCV treatment were recorded. Univariable and multivariable modeling were performed for treatment initiation and sustained virological response (SVR). RESULTS: Nine hundred forty homeless people were identified and 99.3% participated. 56.2% were street-based, 243 (26%) tested positive for HCV antibody, and 162 (17.4%) were viremic. Those with detectable HCV RNA had significantly more frequent psychiatric disorders, active substance use disorders, were on opioid agonist treatment, had advanced fibrosis, and had lower rates of previous treatment in comparison with undetectable HCV RNA. Overall treatment initiation was 70.4% and SVR was 72.8%. In the multivariable analysis, being screened in temporary housing (odds ratio [OR] 3.166; P = 0.002) and having opioid agonist treatment (OR 3.137; P = 0.004) were positively associated with treatment initiation. HCV treatment adherence (OR 26.552; P < 0.001) was the only factor associated with achieving SVR. DISCUSSION: Promoting education and having flexible and reflex mobile on-site testing and treatment for HCV in the homeless population improve engagement with the health care system, meaning higher rates of treatment initiation and SVR. However, street-based homeless population not linked with harm reduction services are less likely to initiate HCV treatment, highlighting an urgent need for a broad health inclusion system.
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Hepatitis C Crónica , Hepatitis C , Humanos , Hepacivirus , Analgésicos Opioides/uso terapéutico , Hepatitis C/diagnóstico , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Atención a la Salud , ARN/uso terapéutico , Antivirales/uso terapéutico , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiologíaRESUMEN
INTRODUCTION: Lusutrombopag is an oral thrombopoietin receptor agonist (TPO-RA). Clinical trials have shown lusutrombopag's efficacy in reducing need for preoperative platelet transfusion in patients with chronic liver disease (CLD) and severe thrombocytopenia. This analysis assessed efficacy and safety of lusutrombopag in patients with severe thrombocytopenia and CLD undergoing planned invasive procedures. METHODS: An electronic database search (through 1 December 2020) identified three randomised, placebo-controlled, double-blind clinical trials comparing lusutrombopag with placebo in patients with CLD and platelet count below 50 × 109/L scheduled to undergo a procedure with a perioperative bleeding risk. A random-effects meta-analysis examined treatment effect, with Cochrane Collaboration's tool assessing risk of bias. RESULTS: The meta-analysis included 343 (lusutrombopag 3 mg, n = 173; placebo, n = 170) patients. More patients met the criteria for treatment response (platelet count at least 50 × 109/L and increase of at least 20 × 109/L from baseline anytime during the study) with lusutrombopag versus placebo (risk ratio [RR] 6.39; 95% confidence interval [CI] 3.69, 11.07; p < 0.0001). The primary efficacy outcome, proportion of patients requiring no platelet transfusion and no rescue therapy for bleeding for at least 7 days post procedure, was achieved by more patients treated with lusutrombopag versus placebo (RR 3.42; 95% CI 1.86, 6.26; p = 0.0001). The risk of any bleeding event was significantly lower with lusutrombopag compared to placebo (RR 0.55; 95% CI 0.32, 0.95; p = 0.03); conversely, thrombosis event rates were similar between lusutrombopag and placebo (RR 0.79; 95% CI 0.19, 3.24; p = 0.74). CONCLUSION: This meta-analysis showed that treatment of severe thrombocytopenia with lusutrombopag in patients with CLD prior to a planned invasive procedure was efficacious and safe in increasing platelet counts, avoiding the need for platelet transfusions, and reducing risk of bleeding, thereby enhancing the certainty of evidence supporting the efficacy and safety of lusutrombopag.
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Anemia , Hepatopatías , Trombocitopenia , Anemia/tratamiento farmacológico , Enfermedad Crónica , Cinamatos/efectos adversos , Hemorragia/tratamiento farmacológico , Humanos , Hepatopatías/complicaciones , Hepatopatías/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Tiazoles/efectos adversos , Trombocitopenia/complicaciones , Trombocitopenia/tratamiento farmacológicoRESUMEN
Hepatocellular carcinoma is a leading public health concern in sub-Saharan Africa, and it is most prevalent in young adults (median 45 years [IQR 35-57]). Overall, outcomes are poor, with a median survival of 2·5 months after presentation. Major risk factors for hepatocellular carcinoma are hepatitis B virus (HBV), hepatitis C virus, aflatoxin B1 exposure, and alcohol consumption, with metabolic dysfunction-associated fatty liver disease slowly emerging as a risk factor over the past few years. Crucially, these risk factors are preventable and manageable with effective implementation of the HBV birth-dose vaccination, treatment of chronic viral hepatitis, provision of harm reduction services, and by decreasing aflatoxin B1 exposure and harmful alcohol consumption. Primary prevention is central to the management of hepatocellular carcinoma, especially in poorly resourced environments. Effective screening and surveillance programmes with recall policies need to be implemented, because detection and curative management of hepatocellular carcinoma is possible if it is detected at an early stage, even in countries with minimal resources, with appropriate upskilling of medical personnel. The establishment of centres of excellence with advanced diagnostic and therapeutic capabilities within countries should improve hepatocellular carcinoma outcomes and assist in driving the implementation of much needed systematic data systems focused on hepatocellular carcinoma to establish the accurate burden in sub-Saharan Africa. Such data would support the public health importance of hepatocellular carcinoma and provide a strong basis for advocacy, programme development, resource allocation, and monitoring of progress in reducing mortality.
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Carcinoma Hepatocelular , Hepatitis C , Neoplasias Hepáticas , Aflatoxina B1 , África del Sur del Sahara/epidemiología , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Hepatitis C/complicaciones , Hepatitis C/diagnóstico , Hepatitis C/epidemiología , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/prevención & controlRESUMEN
Most patients who develop hepatocellular carcinoma reside in resource-poor countries, a category that includes most countries in sub-Saharan Africa. Age-standardised incidence rates of hepatocellular carcinoma in western, central, eastern, and southern Africa is 6·53 per 100 000 inhabitants to 11·1 per 100 000 inhabitants. In high-income countries, around 40% of patients are diagnosed at an early stage, in which interventions with curative intent or palliative interventions are possible. By contrast, 95% of patients with hepatocellular carcinoma in sub-Saharan Africa present with advanced or terminal disease. In high-income countries, targets of 30-40% that have been set for intervention with curative intent are regularly met, with expected 5-year overall survival rates in the region of 70%. These outcomes are in sharp contrast with the very small proportion of patients in sub-Saharan Africa who are treated with curative intent. Primary prevention through the eradication and reduction of risk factors is still suboptimal because of logistical challenges. The challenges facing primary prevention, in combination with difficult-to-manage historic and emerging risk factors, such as ethanol overconsumption and metabolic dysfunction-associated liver disease, mandates secondary prevention for populations at risk through screening and surveillance. Although the increased treatment needs yielded by screening and surveillance in high-income countries are manageable by the incremental expansion of existing interventional resources, the lack of resources in sub-Saharan Africa will undermine the possible benefits of secondary prevention. An estimate of the projected effect of the introduction and expansion of screening and surveillance, resulting in stage migration and possibilities for active interventions for hepatocellular carcinoma, would facilitate optimal planning and development of resources.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , África del Sur del Sahara/epidemiología , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/prevención & control , Etanol , Humanos , Incidencia , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/prevención & controlRESUMEN
BACKGROUND: Chronic hepatitis B remains a global health problem with an estimated 296 million people affected worldwide. Individuals are at risk of serious complications such as cirrhosis and hepatocellular carcinoma and accurately predicting these clinical endpoints has proven difficult. However, several viral biomarkers have recently been developed, including quantitative HBV surface antigen (qHBsAg), hepatitis B RNA (HBV RNA) and core-related antigen (HBcrAg), and shown promise in a range of clinical settings. AIMS: To critically appraise these novel biomarkers, exploring their potential uses, availability of assays and areas for future development. METHODS: We performed a literature search of PubMed, identifying articles published in the field of hepatitis B biomarkers between 2010 and 2022. RESULTS: Novel biomarkers such as HBcrAg, HBV RNA and qHBsAg may be useful in predicting treatment outcomes, stratifying the risk of future complications and estimating off-treatment viral reactivation. Furthermore, HBV RNA and HBcrAg titres may accurately reflect cccDNA transcriptional activity, and this is particularly informative in the context of nucleoside analogue therapy. On a cautionary note, most studies have been performed in Caucasian or Asian populations, and methods for detecting HBV RNA lack standardisation. CONCLUSION: Novel viral biomarkers have the potential to provide additional insights into the natural history of infection and allow a more bespoke, cost-effective framework of care. However, access remains limited, and further efforts are needed to validate their use in ethnically diverse populations, confirm predictive cut-off values, and establish their role in the era of novel antiviral therapies.
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Hepatitis B Crónica , Hepatitis B , Neoplasias Hepáticas , Biomarcadores , ADN Viral/genética , Hepatitis B/complicaciones , Hepatitis B/diagnóstico , Antígenos del Núcleo de la Hepatitis B , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B/genética , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/complicaciones , ARN/uso terapéuticoAsunto(s)
Hepatitis C , Hepacivirus , Hepatitis C/epidemiología , Hepatitis C/prevención & control , HumanosRESUMEN
BACKGROUND: First- and second- generation new treatments are being evaluated to provide a cure for hepatitis B. The life cycle of HBV includes several well- categorized steps that are targets for new treatments. A cure remains a major challenge even if it is measured by HBsAg seroclearance alone. The notion of a functional cure of hepatitis B has been accepted, while a partial functional cure has been more tentatively defined as a decline in HBsAg concentrations to lower levels after finite treatment. METHODS: More profound suppression of hepatitis B replication through the addition of capsid inhibitors with nucleoside analogues could improve patient prognosis and a sustained treatment response. Several strategies are being evaluated to achieve a cure: (a) deepening inhibition of HBV replication or (b) a reduction in HBsAg presentation for HBsAg seroclearance. RESULTS: Fortunately, there are signs of important progress in the treatment of hepatitis B including improved on- treatment reductions or seroclearance of HBsAg in phase 2 studies that was not achieved with chain terminators and inhibitors of initiation of DNA synthesis. Progress in immunomodulatory therapy has lagged behind that of antiviral therapy. CONCLUSIONS: Increasing the multilayered impaired and dysfunctional immune response in hepatitis B is perhaps more likely and feasible after a reduction in host antigen burden. Other potential experimental strategies include CRISPR- Cas9 genome- editing nucleases to specifically target and cleave cccDNA or novel monoclonal antibodies.
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Hepatitis B Crónica , Hepatitis B , Antivirales/uso terapéutico , ADN Viral , Hepatitis B/tratamiento farmacológico , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Nucleósidos/uso terapéuticoRESUMEN
Hepatitis B virus RNA is detectable in the serum of infected patients; however, the RNA species has been questioned. We tested 1827 specimens using a quantitative dual-target quantitative polymerase chain reaction assay and determined that full-length pregenomic RNA is the primary source. These results clarify the major identity of circulating HBV RNA species.