Peg-interferon lambda treatment induces robust innate and adaptive immunity in chronic hepatitis B patients

IFN-lambda (IFNλ) is a member of the type III IFN family and is reported to possess anti-pathogen, anti-cancer, and immunomodulatory properties; however, there are limited data regarding its impact on host immune responses in vivo. We performed longitudinal and comprehensive immunosurveillance to assess the ability of pegylated (peg)-IFNλ to augment antiviral host immunity as part of a clinical trial assessing the efficacy of peg-IFNλ in chronic hepatitis B (CHB) patients. These patients were pretreated with directly acting antiviral therapy (entecavir) for 12 weeks with subsequent addition of peg-IFNλ for up to 32 weeks. In a subgroup of patients, the addition of peg-IFNλ provoked high serum levels of antiviral cytokine IL-18. We also observed the enhancement of natural killer cell polyfunctionality and the recovery of a pan-genotypic HBV-specific CD4+ T cells producing IFN-γ with maintenance of HBV-specific CD8+ T cell antiviral and cytotoxic activities. It was only in these patients that we observed strong virological control with reductions in both viral replication and HBV antigen levels. Here, we show for the first time that in vivo peg-IFNλ displays significant immunostimulatory properties with improvements in the main effectors mediating anti-HBV immunity. Interestingly, the maintenance in HBV-specific CD8+ T cells in the presence of peg-IFNλ is in contrast to previous studies showing that peg-IFNa treatment for CHB results in a detrimental effect on the functionality of this important antiviral T cell compartment

The EASL-Lancet Liver Commission: protecting the next generation of Europeans against liver disease complications and premature mortality

Liver diseases have become a major health threat across Europe, and the face of European hepatology is changing due to the cure of viral hepatitis C and the control of chronic viral hepatitis B, the increasingly widespread unhealthy use of alcohol, the epidemic of obesity, and undiagnosed or untreated liver disease in migrant populations. Consequently, Europe is facing a looming syndemic, in which socioeconomic and health inequities combine to adversely affect liver disease prevalence, outcomes, and opportunities to receive care. In addition, the COVID-19 pandemic has magnified pre-existing challenges to uniform implementation of policies and equity of access to care in Europe, arising from national borders and the cultural and historical heterogeneity of European societies. In following up on work from the Lancet Commission on liver disease in the UK and epidemiological studies led by the European Association for the Study of the Liver (EASL), our multidisciplinary Commission, comprising a wide range of public health, medical, and nursing specialty groups, along with patient representatives, set out to provide a snapshot of the European landscape on liver diseases and to propose a framework for the principal actions required to improve liver health in Europe. We believe that a joint European process of thinking, and construction of uniform policies and action, implementation, and evaluation can serve as a powerful mechanism to improve liver care in Europe and set the way for similar changes globally. On the basis of these data, we present ten actionable recommendations, half of which are oriented towards health-care providers and half of which focus primarily on health policy. A fundamental shift must occur, in which health promotion, prevention, proactive casefinding, early identification of progressive liver fibrosis, and early treatment of liver diseases replace the current emphasis on the management of end-stage liver disease complications. A considerable focus should be put on underserved and marginalised communities, including early diagnosis and management in children, and we provide proposals on how to better target disadvantaged communities through health promotion, prevention, and care using multilevel interventions acting on current barriers. Underlying this transformative shift is the need to enhance awareness of the preventable and treatable nature of many liver diseases. Therapeutic nihilism, which is prevalent in current clinical practice across a range of medical specialities as well as in many patients themselves, has to end. We wish to challenge medical specialty protectionism and invite a broad range of stakeholders, including primary care physicians, nurses, patients, peers, and members of relevant communities, along with medical specialists trained in obesity, diabetes, liver disease, oncology, cardiovascular disease, public health, addictions, infectious diseases, and more, to engage in integrated person-centred liver patient care across classical medical specialty boundaries. This shift includes a revision in how we converse about liver disease and speak with our patients, and a reappraisal of disease-related medical nomenclature conducted to increase awareness and reduce the social stigmatisation associated with liver disease. Reimbursement mechanisms and insurance systems must be harmonised to account for patient-centric, multimorbidity models of care across a range of medical specialties, and the World Health Assembly resolution to improve the transparency and fairness of market prices for medicines throughout Europe should be reinforced. Finally, we outline how Europe can move forward with implementation of effective policy action on taxation, food reformulation, and product labelling, advertising, and availability, similar to that implemented for tobacco, to reduce consumption of alcohol, ultraprocessed foods, and foods with added sugar, especially among young people. We should utilise the window of opportunity created by the COVID-19 pandemic to overcome fragmentation and the variability of health prevention policies and research across Europe. We argue that the liver is a window to the 21st-century health of the European population. Through our proposed syndemic approach to liver disease and social and health inequities in Europe, the liver will serve as a sentinel for improving the overall health of European populations

The EASL-Lancet Liver Commission: protecting the next generation of Europeans against liver disease complications and premature mortality

Liver diseases have become a major health threat across Europe, and the face of European hepatology is changing due to the cure of viral hepatitis C and the control of chronic viral hepatitis B, the increasingly widespread unhealthy use of alcohol, the epidemic of obesity, and undiagnosed or untreated liver disease in migrant populations. Consequently, Europe is facing a looming syndemic, in which socioeconomic and health inequities combine to adversely affect liver disease prevalence, outcomes, and opportunities to receive care. In addition, the COVID-19 pandemic has magnified pre-existing challenges to uniform implementation of policies and equity of access to care in Europe, arising from national borders and the cultural and historical heterogeneity of European societies. In following up on work from the Lancet Commission on liver disease in the UK and epidemiological studies led by the European Association for the Study of the Liver (EASL), our multidisciplinary Commission, comprising a wide range of public health, medical, and nursing specialty groups, along with patient representatives, set out to provide a snapshot of the European landscape on liver diseases and to propose a framework for the principal actions required to improve liver health in Europe. We believe that a joint European process of thinking, and construction of uniform policies and action, implementation, and evaluation can serve as a powerful mechanism to improve liver care in Europe and set the way for similar changes globally. On the basis of these data, we present ten actionable recommendations, half of which are oriented towards health-care providers and half of which focus primarily on health policy. A fundamental shift must occur, in which health promotion, prevention, proactive case- finding, early identification of progressive liver fibrosis, and early treatment of liver diseases replace the current emphasis on the management of end-stage liver disease complications. A considerable focus should be put on underserved and marginalised communities, including early diagnosis and management in children, and we provide proposals on how to better target disadvantaged communities through health promotion, prevention, and care using multilevel interventions acting on current barriers. Underlying this transformative shift is the need to enhance awareness of the preventable and treatable nature of many liver diseases. Therapeutic nihilism, which is prevalent in current clinical practice across a range of medical specialities as well as in many patients themselves, has to end. We wish to challenge medical specialty protectionism and invite a broad range of stakeholders, including primary care physicians, nurses, patients, peers, and members of relevant communities, along with medical specialists trained in obesity, diabetes, liver disease, oncology, cardiovascular disease, public health, addictions, infectious diseases, and more, to engage in integrated person-centred liver patient care across classical medical specialty boundaries. This shift includes a revision in how we converse about liver disease and speak with our patients, and a reappraisal of disease-related medical nomenclature conducted to increase awareness and reduce the social stigmatisation associated with liver disease. Reimbursement mechanisms and insurance systems must be harmonised to account for patient-centric, multimorbidity models of care across a range of medical specialties, and the World Health Assembly resolution to improve the transparency and fairness of market prices for medicines throughout Europe should be reinforced. Finally, we outline how Europe can move forward with implementation of effective policy action on taxation, food reformulation, and product labelling, advertising, and availability, similar to that implemented for tobacco, to reduce consumption of alcohol, ultra- processed foods, and foods with added sugar, especially among young people. We should utilise the window of opportunity created by the COVID-19 pandemic to overcome fragmentation and the variability of health prevention policies and research across Europe. We argue that the liver is a window to the 21st-century health of the European population. Through our proposed syndemic approach to liver disease and social and health inequities in Europe, the liver will serve as a sentinel for improving the overall health of European populations

The EASL–Lancet Liver Commission: protecting the next generation of Europeans against liver disease complications and premature mortality

© 2021 Elsevier Ltd. All rights reserved.Liver diseases have become a major health threat across Europe, and the face of European hepatology is changing due to the cure of viral hepatitis C and the control of chronic viral hepatitis B, the increasingly widespread unhealthy use of alcohol, the epidemic of obesity, and undiagnosed or untreated liver disease in migrant populations. Consequently, Europe is facing a looming syndemic, in which socioeconomic and health inequities combine to adversely affect liver disease prevalence, outcomes, and opportunities to receive care. In addition, the COVID-19 pandemic has magnified pre-existing challenges to uniform implementation of policies and equity of access to care in Europe, arising from national borders and the cultural and historical heterogeneity of European societies. In following up on work from the Lancet Commission on liver disease in the UK and epidemiological studies led by the European Association for the Study of the Liver (EASL), our multidisciplinary Commission, comprising a wide range of public health, medical, and nursing specialty groups, along with patient representatives, set out to provide a snapshot of the European landscape on liver diseases and to propose a framework for the principal actions required to improve liver health in Europe. We believe that a joint European process of thinking, and construction of uniform policies and action, implementation, and evaluation can serve as a powerful mechanism to improve liver care in Europe and set the way for similar changes globally.The SHARE data collection has been funded by the European Commission through FP5 (QLK6-CT-2001-00360), FP6 (SHARE-I3: RII-CT-2006-062193; COMPARE: CIT5-CT-2005-028857; SHARELIFE: CIT4-CT-2006-028812), FP7 (SHARE-PREP: GA N°211909; SHARE-LEAP: GA N°227822; SHARE M4: GA N°261982; DASISH: GA N°283646), and Horizon 2020 (SHARE-DEV3: GA N°676536; SHARE-COHESION: GA N°870628; SERISS: GA N°654221; SSHOC: GA N°823782) and by DG Employment, Social Affairs & Inclusion. Additional funding from the German Ministry of Education and Research, the Max Planck Society for the Advancement of Science, the US National Institute on Aging (U01_AG09740-13S2; P01_AG005842; P01_AG08291; P30_AG12815; R21_AG025169; Y1-AG-4553-01; IAG_BSR06-11; OGHA_04-064; HHSN271201300071C), and from various national funding sources is gratefully acknowledged. PC acknowledges support by the French National Agency for HIV, hepatitis and emerging infectious diseases research (ANRS / EMERGING INFECTIOUS DISEASES).info:eu-repo/semantics/publishedVersio

Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study

Background Since the release of the first global hepatitis elimination targets in 2016, and until the COVID-19 pandemic started in early 2020, many countries and territories were making progress toward hepatitis C virus (HCV) elimination. This study aims to evaluate HCV burden in 2020, and forecast HCV burden by 2030 given current trends. Methods This analysis includes a literature review, Delphi process, and mathematical modelling to estimate HCV prevalence (viraemic infection, defined as HCV RNA-positive cases) and the cascade of care among people of all ages (age ≥0 years from birth) for the period between Jan 1, 2015, and Dec 31, 2030. Epidemiological data were collected from published sources and grey literature (including government reports and personal communications) and were validated among country and territory experts. A Markov model was used to forecast disease burden and cascade of care from 1950 to 2050 for countries and territories with data. Model outcomes were extracted from 2015 to 2030 to calculate population-weighted regional averages, which were used for countries or territories without data. Regional and global estimates of HCV prevalence, cascade of care, and disease burden were calculated based on 235 countries and territories. Findings Models were built for 110 countries or territories: 83 were approved by local experts and 27 were based on published data alone. Using data from these models, plus population-weighted regional averages for countries and territories without models (n=125), we estimated a global prevalence of viraemic HCV infection of 0·7% (95% UI 0·7–0·9), corresponding to 56·8 million (95% UI 55·2–67·8) infections, on Jan 1, 2020. This number represents a decrease of 6·8 million viraemic infections from a 2015 (beginning of year) prevalence estimate of 63·6 million (61·8–75·8) infections (0·9% [0·8–1·0] prevalence). By the end of 2020, an estimated 12·9 million (12·5–15·4) people were living with a diagnosed viraemic infection. In 2020, an estimated 641000 (623000–765000) patients initiated treatment. Interpretation At the beginning of 2020, there were an estimated 56·8 million viraemic HCV infections globally. Although this number represents a decrease from 2015, our forecasts suggest we are not currently on track to achieve global elimination targets by 2030. As countries recover from COVID-19, these findings can help refocus efforts aimed at HCV elimination