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  • 1.
    Blach, Sarah
    et al.
    Ctr Dis Anal Fdn, Lafayette CO, USA.
    Duberg, Ann-Sofi
    Örebro University, School of Medical Sciences.
    Razavi, Homie A.
    Ctr Dis Anal Fdn, Lafayette CO, USA.
    Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study2022In: The Lancet Gastroenterology & Hepatology, ISSN 2468-1253, Vol. 7, no 5, p. 396-415Article in journal (Refereed)
    Abstract [en]

    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 641 000 (623 000-765 000) 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.

  • 2.
    Burisch, Johan
    et al.
    Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark.
    Eriksson, Carl
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Odes, Selwyn
    Department of Internal Medicine, Ben-Gurion University of the Negev, Beer Sheva, Israel.
    Health-care costs of inflammatory bowel disease in a pan-European, community-based, inception cohort during 5 years of follow-up: a population-based study2020In: The Lancet Gastroenterology & Hepatology, ISSN 2468-1253, Vol. 5, no 5, p. 454-464Article in journal (Refereed)
    Abstract [en]

    Background: Inflammatory bowel disease (IBD) places a significant burden on health-care systems because of its chronicity and need for expensive therapies and surgery. With increasing use of biological therapies, contemporary data on IBD health-care costs are important for those responsible for allocating resources in Europe. To our knowledge, no prospective long-term analysis of the health-care costs of patients with IBD in the era of biologicals has been done in Europe. We aimed to investigate cost profiles of a pan-European, community-based inception cohort during 5 years of follow-up.

    Methods: The Epi-IBD cohort is a community-based, prospective inception cohort of unselected patients with IBD diagnosed in 2010 at centres in 20 European countries plus Israel. Incident patients who were diagnosed with IBD according to the Copenhagen Diagnostic Criteria between Jan 1, and Dec 31,2010, and were aged 15 years or older the time of diagnosis were prospectively included. Data on clinical characteristics and direct costs (investigations and outpatient visits, blood tests, treatments, hospitalisations, and surgeries) were collected prospectively using electronic case-report forms. Patient-level costs incorporated procedures leading to the initial diagnosis of IBD and costs of IBD management during the 5-year follow-up period. Costs incurred by comorbidities and unrelated to IBD were excluded. We grouped direct costs into the following five categories: investigations (including outpatient visits and blood tests), conventional medical treatment, biological therapy, hospitalisation, and surgery.

    Findings: The study population consisted of 1289 patients with IBD, with 1073 (83%) patients from western Europe and 216 (17%) from eastern Europe. 488 (38%) patients had Crohn's disease, 717 (56%) had ulcerative colitis, and 84 (6%) had IBD unclassified. The mean cost per patient-year during follow-up for patients with IBD was (sic)2609 (SD 7389; median (sic)446 [IQR 164-1849]). The mean cost per patient-year during follow-up was (sic)3542 (8058; median (sic)717 [214-3512]) for patients with Crohn's disease, (sic)2088 (7058; median (sic)408 [133-1161]) for patients with ulcerative colitis, and (sic)1609 (5010; median (sic)415 [92-1228]) for patients with IBD unclassified (p<0.0001). Costs were highest in the first year and then decreased significantly during follow-up. Hospitalisations and diagnostic procedures accounted for more than 50% of costs during the first year. However, in subsequent years there was a steady increase in expenditure on biologicals, which accounted for 73% of costs in Crohn's disease and 48% in ulcerative colitis, in year 5. The mean annual cost per patient-year for biologicals was (sic)866 (SD 3056). The mean yearly costs of biological therapy were higher in patients with Crohn's disease ((sic)1782 [SD 4370]) than in patients with ulcerative colitis ((sic)286 [1427]) or IBD unclassified ((sic)521 [2807]; p<0.0001).

    Interpretation: Overall direct expenditure on health care decreased over a 5-year follow-up period. This period was characterised by increasing expenditure on biologicals and decreasing expenditure on conventional medical treatments, hospitalisations, and surgeries. In light of the expenditures associated with biological therapy, cost-effective treatment strategies are needed to reduce the economic burden of inflammatory bowel disease.

  • 3.
    King, James A.
    et al.
    Department of Medicine and Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada.
    Underwood, Fox E.
    Department of Medicine and Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada.
    Panaccione, Nicola
    Department of Medicine and Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada.
    Quan, Josh
    Department of Medicine and Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada.
    Windsor, Joseph W.
    Department of Medicine and Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada.
    Kotze, Paulo G.
    Inflammatory Bowel Disease Outpatients Clinic, Colorectal Surgery Unit, Catholic University of Paraná, Curitiba, Brazil.
    Ng, Siew C.
    Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.
    Ghosh, Subrata
    National Institute for Health Research Biomedical Research Centre, University of Birmingham and University Hospitals National Health Service Foundation Trust, Birmingham, UK.
    Lakatos, Peter L.
    First Department of Medicine, Semmelweis University, Budapest, Hungary; Division of Gastroenterology, McGill University Health Centre, McGill University, Montreal QC, Canada.
    Jess, Tine
    Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
    Panaccione, Remo
    Department of Medicine and Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada.
    Seow, Cynthia H.
    Department of Medicine and Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada.
    Ben-Horin, Shomron
    Department of Gastroenterology, Sheba Medical Center, Tel Hashomer and Sackler Medical School, Tel Aviv University, Tel Aviv, Israel.
    Burisch, Johan
    Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
    Colombel, Jean-Frederic
    Icahn School of Medicine at Mount Sinai, New York NY, USA.
    Loftus, Edward V., Jr.
    Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester MN, USA.
    Gearry, Richard
    University of Otago, Christchurch, New Zealand.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Kaplan, Gilaad G.
    Department of Medicine and Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada.
    Trends in hospitalisation rates for inflammatory bowel disease in western versus newly industrialised countries: a population-based study of countries in the Organisation for Economic Co-operation and Development2019In: The Lancet Gastroenterology & Hepatology, ISSN 2468-1253, Vol. 4, no 4, p. 287-295Article in journal (Refereed)
    Abstract [en]

    Background: Hospitalisation rates for inflammatory bowel disease (IBD) vary across the world. We aimed to investigate temporal patterns of hospitalisation for IBD in member countries of the Organisation for Economic Co-operation and Development (OECD).

    Methods: From the OECD database, we assessed IBD-related hospitalisation rates (expressed as annual rates per 100 000 inhabitants) for 34 countries from 1990 to 2016. We calculated mean hospitalisation rates for the period 2010-15 and used joinpoint regression models to calculate average annual percentage changes with 95% CIs.

    Findings: Mean hospitalisation rates for IBD from 2010 to 2015 were highest in North America (eg, 33.9 per 100 000 in the USA), Europe (eg, 72.9 per 100 000 in Austria), and Oceania (eg, 31.5 per 100 000 in Australia). Hospitalisation rates for IBD were stabilising or decreasing over time in many countries in these regions but increasing in others. Countries in Asia and Latin America and the Caribbean had the lowest IBD-related hospitalisation rates but the greatest increases in rates over time. For example, Turkey had an annual hospitalisation rate of 10.8 per 100 000 inhabitants and an average annual percentage change of 10.4% (95% CI 5.2-15.9). Similarly, Chile had an annual hospitalisation rate of 9.0 per 100 000 inhabitants and an average annual percentage change of 5.9% (4.9-7.0).

    Interpretation: Hospitalisation rates for IBD are high in western countries but are typically stabilising or decreasing, whereas rates in many newly industrialised countries are rapidly increasing, which reflects the known increase in IBD prevalence in these countries. Potential explanations for these trends include changes in the epidemiology of IBD, health-care delivery, and infrastructure in these countries, as well as overall country-specific patterns in hospitalisations and differences between countries in data collection methods.

  • 4.
    Nguyen, Long H.
    et al.
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA: Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA.
    Örtqvist, Anne K.
    Division of Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden; Department of Obstetrics and Gynecology, Visby Lasarett, Gotland, Sweden.
    Cao, Yin
    Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA; Alvin J Siteman Cancer Centre, Washington University School of Medicine, St Louis MO, USA; Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St Louis MO, USA.
    Simon, Tracey G.
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA.
    Roelstraete, Bjorn
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Song, Mingyang
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA; Department of Epidemiology, Harvard T H Chan School of Public Health, Boston MA, USA; Department of Nutrition, Harvard T H Chan School of Public Health, Boston MA, USA.
    Joshi, Amit D.
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA.
    Staller, Kyle
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA.
    Chan, Andrew T.
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA; Department of Immunology and Infectious Disease, Harvard T H Chan School of Public Health, Boston MA, USA; Broad Institute of MIT and Harvard, Cambridge MA, USA.
    Khalili, Hamed
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA.
    Olén, Ola
    Division of Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden; Sachs' Children and Youth Hospital, Stockholm South General Hospital, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.;Orebro Univ Hosp, Dept Paediat, Orebro, Sweden.;Univ Nottingham, Sch Med, Div Epidemiol & Publ Hlth, Nottingham, England.;Columbia Univ Coll Phys & Surg, Dept Med, New York, NY USA; Department of Paediatrics, Örebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA.
    Antibiotic use and the development of inflammatory bowel disease: a national case-control study in Sweden2020In: The Lancet Gastroenterology & Hepatology, ISSN 2468-1253, Vol. 5, no 11, p. 986-995Article in journal (Refereed)
    Abstract [en]

    Background: Use of antibiotics in early life has been linked with childhood inflammatory bowel disease (IBD), but data for adults are mixed, and based on smaller investigations that did not compare risk among siblings with shared genetic or environmental risk factors. We aimed to investigate the association between antibiotic therapy and IBD in a large, population-based study.

    Methods: In this prospective case-control study, we identified people living in Sweden aged 16 years or older, with a diagnosis of IBD based on histology and at least one diagnosis code for IBD or its subtypes (ulcerative colitis and Crohn's disease). We identified consecutive patients with incident IBD from the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) study, cross-referenced with the Swedish Patient Register and the Prescribed Drug Register. We accrued data for cumulative antibiotic dispensations until 1 year before time of matching for patients and up to five general population controls per patient (matched on the basis of age, sex, county, and calendar year). We also included unaffected full siblings as a secondary control group. Conditional logistic regression was used to estimate multivariable-adjusted odds ratios (aORs) and 95% CIs for diagnosis of incident IBD.

    Findings: We identified 23 982 new patients with IBD (15 951 ulcerative colitis, 7898 Crohn's disease, 133 unclassified IBD) diagnosed between Jan 1, 2007, and Dec 31, 2016. 117 827 matched controls and 28 732 siblings were also identified. After adjusting for several risk factors, aOR in patients who had used antibiotics versus those who had never used antibiotics was 1.88 (95% CI 1.79-1.98) for diagnosis of incident IBD, 1.74 (1.64-1.85) for ulcerative colitis, and 2.27 (2.06-2.49) for Crohn's disease. aOR was higher in patients who had received one antibiotic dispensation (1.11, 1.07-1.15), two antibiotic dispensations (1.38, 1.32-1.44), and three or more antibiotic dispensations (1.55, 1.49-1.61) than patients who had none. Increased risk was noted for ulcerative colitis (aOR with three or more antibiotic dispensations 1.47, 95% CI 1.40-1.54) and Crohn's disease (1.64, 1.53-1.76) with higher estimates corresponding to broad-spectrum antibiotics. Similar but attenuated results were observed when siblings were used as the reference group, with an aOR of 1.35 (95% CI 1.28-1.43) for patients who had received three or more dispensations, compared with general population controls.

    Interpretation: Higher cumulative exposure to systemic antibiotic therapy, particularly treatments with greater spectrum of microbial coverage, may be associated with a greater risk of new-onset IBD and its subtypes. The association between antimicrobial treatment and IBD did not appear to differ when predisposed siblings were used as the reference controls. Our findings, if substantiated by longer-term prospective studies in humans or mechanistic preclinical investigations, suggest the need to further emphasise antibiotic stewardship to prevent the rise in dysbiosis-related chronic diseases, including IBD.

  • 5.
    Olén, Ola
    et al.
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Sachs' Children and Youth Hospital, Stockholm South General Hospital, Stockholm, Sweden.
    Erichsen, Rune
    Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; Department of Surgery, Randers Regional Hospital, Randers, Denmark.
    Sachs, Michael C.
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Pedersen, Lars
    Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Askling, Johan
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Ekbom, Anders
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Sørensen, Henrik Toft
    Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK; Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, USA.
    Colorectal cancer in Crohn's disease: a Scandinavian population-based cohort study2020In: The Lancet Gastroenterology & Hepatology, ISSN 2468-1253, Vol. 5, no 5, p. 475-484Article in journal (Refereed)
    Abstract [en]

    Background: Crohn's disease is a risk factor for colorectal cancer (CRC). However, available studies reflect older treatment and surveillance strategies, and most have assessed risks for incident CRC without taking surveillance and lead-time bias into account. Such biases can be accounted for by assessing CRC incidence by tumour stage and CRC mortality by tumour stage. We aimed to assess rates of incident CRC and CRC mortality among patients with Crohn's disease compared with the general population.

    Methods: For this nationwide register-based cohort study, we used International Classification of Disease codes in national patient registers and pathology reports to identify incident cases of Crohn's disease. In Denmark we searched for incident cases between January, 1977, and December, 2011, and in Sweden between January, 1969, and December, 2017. For each patient with Crohn's disease, we identified up to ten reference individuals in national population registers and matched them by sex, age, calendar year, and place of residence. Matched reference individuals had to be alive and free of inflammatory bowel disease at the start of follow-up of index patients with Crohn's disease, and stopped contributing to reference person-years if they were diagnosed with inflammatory bowel disease. Our main outcome was death from CRC (main or contributory cause of death) as captured in the cause-of-death registers. Our secondary outcome was incident CRC, as defined by the cancer registers. We used Cox regression to estimate hazard ratios (HRs) for incident CRC and CRC mortality, taking tumour stage into account. We used a series of Cox models to estimate cause-specific HRs of the different competing outcomes (CRC diagnosis, CRC death, and other causes of death) and adjusted for tumour stage at CRC diagnosis.

    Findings: During the 1969-2017 study period, we identified 47 035 patients with incident Crohn's disease (13 056 in Denmark and 33 979 in Sweden) and 463 187 matched reference individuals. During follow-up, 296 (0.47 per 1000 person-years) CRC deaths occurred among individuals with Crohn's disease compared with 1968 (0.31 per 1000 person-years) in reference individuals, corresponding to an overall adjusted HR of 1.74 (1.54-1.96). 499 (0.82 per 1000 person-years) cases of incident CRC were diagnosed in patients with Crohn's disease compared with 4084 (0.64 per 1000 person-years) cases in reference individuals, corresponding to an overall adjusted HR of 1.40 (95% CI 1. 27-1.53). Patients with Crohn's disease who were diagnosed with CRC were at increased risk of CRC mortality compared with reference individuals also diagnosed with CRC (HR 1.42 [1.16-1.75] when adjusted for tumour stage), and tumour stage at CRC diagnosis did not differ between groups (p=0.27). Patients with Crohn's disease who had follow-up of 8 years or longer or who were diagnosed with primary sclerosing cholangitis (PSC) and hence were potentially eligible for CRC surveillance had an increased overall risk of CRC death (HR 1.40 [1.16-1.68]) or CRC diagnosis (HR 1.12 [0. 98-1. 28]). However, in patients potentially eligible for CRC surveillance we only found significantly increased risks in patients diagnosed with Crohn's disease before the age of 40 years, patients with disease activity in the colon only, or patients with PSC.

    Interpretation: Patients with Crohn's disease are at increased risk of CRC diagnosis and CRC death. Patients with Crohn's disease who have CRC have a higher mortality than patients without Crohn's disease who are also diagnosed with CRC. CRC surveillance should likely be focused on patients diagnosed with Crohn's disease before the age of 40 years, on patients with colon inflammation, and on those who have PSC.

  • 6. Polaris Observatory, Collaborators
    Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study2018In: The Lancet Gastroenterology & Hepatology, ISSN 2468-1253, Vol. 3, no 6, p. 383-403Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate viral hepatitis by 2030. Although no virological cure exists for hepatitis B virus (HBV) infection, existing therapies to control viral replication and prophylaxis to minimise mother-to-child transmission make elimination of HBV feasible. We aimed to estimate the national, regional, and global prevalence of HBsAg in the general population and in the population aged 5 years in 2016, as well as coverage of prophylaxis, diagnosis, and treatment.

    METHODS: In this modelling study, we used a Delphi process that included a literature review in PubMed and Embase, followed by interviews with experts, to quantify the historical epidemiology of HBV infection. We then used a dynamic HBV transmission and progression model to estimate the country-level and regional-level prevalence of HBsAg in 2016 and the effect of prophylaxis and treatment on disease burden.

    FINDINGS: We developed models for 120 countries, 78 of which were populated with data approved by experts. Using these models, we estimated that the global prevalence of HBsAg in 2016 was 3·9% (95% uncertainty interval [UI] 3·4-4·6), corresponding to 291 992 000 (251 513 000-341 114 000) infections. Of these infections, around 29 million (10%) were diagnosed, and only 4·8 million (5%) of 94 million individuals eligible for treatment actually received antiviral therapy. Around 1·8 (1·6-2·2) million infections were in children aged 5 years, with a prevalence of 1·4% (1·2-1·6). We estimated that 87% of infants had received the three-dose HBV vaccination in the first year of life, 46% had received timely birth-dose vaccination, and 13% had received hepatitis B immunoglobulin along with the full vaccination regimen. Less than 1% of mothers with a high viral load had received antiviral therapy to reduce mother-to-child transmission.

    INTERPRETATION: Our estimate of HBV prevalence in 2016 differs from previous studies, potentially because we took into account the effect of infant prophylaxis and early childhood vaccination, as well as changing prevalence over time. Although some regions are well on their way to meeting prophylaxis and prevalence targets, all regions must substantially scale-up access to diagnosis and treatment to meet the global targets.

  • 7.
    Razavi, Homie A.
    et al.
    Center for Disease Analysis (CDA), Louisville CO, USA.
    Duberg, Ann-Sofi
    Örebro University, School of Medical Sciences.
    Hatzakis, Angelos
    Department of Hygiene, Epidemiology & Medical Statistics at Athens University Medical School, Athens, Greece.
    Hepatitis C virus prevalence and level of intervention required to achieve the WHO targets for elimination in the European Union by 2030: a modelling study2017In: The Lancet Gastroenterology & Hepatology, ISSN 2468-1253, Vol. 2, no 5, p. 325-336Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide. In the European Union (EU), treatment and cure of HCV with direct-acting antiviral therapies began in 2014. WHO targets are to achieve a 65% reduction in liver-related deaths, a 90% reduction of new viral hepatitis infections, and 90% of patients with viral hepatitis infections being diagnosed by 2030. This study assessed the prevalence of HCV in the EU and the level of intervention required to achieve WHO targets for HCV elimination.

    METHODS: We populated country Markov models for the 28 EU countries through a literature search of PubMed and Embase between Jan 1, 2000, and March 31, 2016, and a Delphi process to gain expert consensus and validate inputs. We aggregated country models to create a regional EU model. We used the EU model to forecast HCV disease progression (considering the effect of immigration) and developed a strategy to acehive WHO targets. We used weighted average sustained viral response rates and fibrosis restrictions to model the effect of current therapeutic guidelines. We used the EU model to forecast HCV disease progression (considering the effect of immigration) under current screening and therapeutic guidelines. Additionally, we back-calculated the total number of patients needing to be screened and treated to achieve WHO targets.

    FINDINGS: We estimated the number of viraemic HCV infections in 2015 to be 3 238 000 (95% uncertainty interval [UI] 2 106 000-3 795 000) of a total population of 509 868 000 in the EU, equating to a prevalence of viraemic HCV of 0·64% (95% UI 0·41-0·74). We estimated that 1 180 000 (95% UI 1 003 000-1 357 000) people were diagnosed with viraemia (36·4%), 150 000 (12 000-180 000) were treated (4·6% of the total infected population or 12·7% of the diagnosed population), 133 000 (106 000-160 000) were cured (4·1%), and 57 900 (43 900-67 300) were newly infected (1·8%) in 2015. Additionally, 30 400 (26 600-42 500) HCV-positive immigrants entered the EU. To achieve WHO targets, unrestricted treatment needs to increase from 150 000 patients in 2015 to 187 000 patients in 2025 and diagnosis needs to increase from 88 800 new cases annually in 2015 to 180 000 in 2025.

    INTERPRETATION: Given its advanced health-care infrastructure, the EU is uniquely poised to eliminate HCV; however, expansion of screening programmes is essential to increase treatment to achieve the WHO targets. A united effort, grounded in sound epidemiological evidence, will also be necessary.

     

  • 8.
    Razavi-Shearer, Devin
    et al.
    Center for Disease Analysis Foundation, Lafayette CO, USA.
    Duberg, Ann-Sofi
    Örebro University, School of Medical Sciences. Örebro University, School of Health Sciences.
    Razavi, Homie
    CDA Foundations, Lafayette CO, United States.
    Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: a modelling study2023In: The Lancet Gastroenterology & Hepatology, ISSN 2468-1253, Vol. 8, no 10, p. 879-907Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The 2016 World Health Assembly endorsed the elimination of hepatitis B virus (HBV) infection as a public health threat by 2030; existing therapies and prophylaxis measures make such elimination feasible, even in the absence of a virological cure. We aimed to estimate the national, regional, and global prevalence of HBV in the general population and among children aged 5 years and younger, as well as the rates of diagnosis, treatment, prophylaxis, and the future burden globally.

    METHODS: In this modelling study, we used a Delphi process with data from literature reviews and interviews with country experts to quantify the prevalence, diagnosis, treatment, and prevention measures for HBV infection. The PRoGReSs Model, a dynamic Markov model, was used to estimate the country, regional, and global prevalence of HBV infection in 2022, and the effects of treatment and prevention on disease burden. The future incidence of morbidity and mortality in the absence of additional interventions was also estimated at the global level.

    FINDINGS: We developed models for 170 countries which resulted in an estimated global prevalence of HBV infection in 2022 of 3·2% (95% uncertainty interval 2·7-4·0), corresponding to 257·5 million (216·6-316·4) individuals positive for HBsAg. Of these individuals, 36·0 million were diagnosed, and only 6·8 million of the estimated 83·3 million eligible for treatment were on treatment. The prevalence among children aged 5 years or younger was estimated to be 0·7% (0·6-1·0), corresponding to 5·6 million (4·5-7·8) children with HBV infection. Based on the most recent data, 85% of infants received three-dose HBV vaccination before 1 year of age, 46% had received a timely birth dose of vaccine, and 14% received hepatitis B immunoglobulin along with the full vaccination regimen. 3% of mothers with a high HBV viral load received antiviral treatment to reduce mother-to-child transmission.

    INTERPRETATION: As 2030 approaches, the elimination targets remain out of reach for many countries under the current frameworks. Although prevention measures have had the most success, there is a need to increase these efforts and to increase diagnosis and treatment to work towards the elimination goals.

  • 9.
    Song, Mingyang
    et al.
    Department of Epidemiology and Department of Nutrition, Harvard T H Chan School of Public Health, Boston MA, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA.
    Emilsson, Louise
    Institute of Health and Society, University of Oslo, Oslo, Norway; Vårdcentralen Årjäng and Centre for Clinical Research, County Council of Värmland, Värmland, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Bozorg, Soran R.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Nguyen, Long H.
    Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA.
    Joshi, Amit D.
    Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA.
    Staller, Kyle
    Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA.
    Nayor, Jennifer
    Division of Gastroenterology, Brigham and Women's Hospital, Boston MA, USA.
    Chan, Andrew T.
    Department of Epidemiology and Department of Nutrition, Harvard T H Chan School of Public Health, Boston MA, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston MA, USA; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge MA, USA.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Division of Digestive and Liver Disease, Department of Medicine, Columbia University Medical Center, New York NY, USA; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK.
    Risk of colorectal cancer incidence and mortality after polypectomy: a Swedish record-linkage study2020In: The Lancet Gastroenterology & Hepatology, ISSN 2468-1253, Vol. 5, no 6, p. 537-547Article in journal (Refereed)
    Abstract [en]

    Background: Long-term colorectal cancer incidence and mortality after colorectal polyp removal remains unclear. We aimed to assess colorectal cancer incidence and mortality in individuals with removal of different histological subtypes of polyps relative to the general population.

    Methods: We did a matched cohort study through prospective record linkage in Sweden in patients aged at least 18 years with a first diagnosis of colorectal polyps in the nationwide gastrointestinal ESPRESSO histopathology cohort (1993-2016). For each polyp case, we identified up to five matched reference individuals from the Total Population Register on the basis of birth year, age, sex, calendar year of biopsy, and county of residence. We excluded patients and reference individuals with a diagnosis of colorectal cancer either before or within the first 6 months after diagnosis of the index polyp. Polyps were classified by morphology codes into hyperplastic polyps, sessile serrated polyps, tubular adenomas, tubulovillous adenomas, and villous adenomas. Colorectal cancer cases were identified from the Swedish Cancer Registry, and cause-of-death data were retrieved from the Cause of Death Register. We collected information about the use of endoscopic examination before and after the index biopsy from the Swedish National Patient Registry, and counted the number of endoscopies done before and after the index biopsies. We calculated cumulative risk of colorectal cancer incidence and mortality at 3, 5, 10, and 15 years, and computed hazard ratios (HRs) and 95% CIs for colorectal cancer incidence and mortality using a stratified Cox proportional hazards model within each of the matched pairs.

    Findings: 178 377 patients with colorectal polyps and 864 831 matched reference individuals from the general population were included in our study. The mean age of patients at polyp diagnosis was 58.6 (SD 13.9) years for hyperplastic polyps, 59.7 (14.2) years for sessile serrated polyps, 63.9 (12.9) years for tubular adenomas, 67.1 (12.1) years for tubulovillous adenomas, and 68.9 (11.8) years for villous adenomas. During a median of 6.6 years (IQR 3.0-11.6) of follow-up, we documented 4278 incident colorectal cancers and 1269 colorectal cancer-related deaths in patients with a polyp, and 14 350 incident colorectal cancers and 5242 colorectal cancer deaths in general reference individuals. The 10-year cumulative incidence of colorectal cancer was 1.6% (95% CI 1.5-1.7) for hyperplastic polyps, 2.5% (1.9-3.3) for sessile serrated polyps, 2.7% (2.5-2.9) for tubular adenomas, 5.1% (4.8-5.4) for tubulovillous adenomas, and 8.6% (7.4-10.1) for villous adenomas compared with 2.1% (2.0-2.1) in reference individuals. Compared with reference individuals, patients with any polyps had an increased risk of colorectal cancer, with multivariable HR of 1.11 (95% CI 1.02-1.22) for hyperplastic polyps, 1.77 (1.34-2.34) for sessile serrated polyps, 1.41 (1.30-1.52) for tubular adenomas, 2.56 (2.36-2.78) for tubulovillous adenomas, and 3.82 (3.07-4.76) for villous adenomas (p<0.05 for all polyp subtypes). There was a higher proportion of incident proximal colon cancer in patients with serrated (hyperplastic and sessile) polyps (52-57%) than in those with conventional (tubular, tubulovillous, and villous) adenomas (30-46%). For colorectal cancer mortality, a positive association was found for sessile serrated polyps (HR 1.74, 95% CI 1.08-2.79), tubulovillous adenomas (1.95, 1.69-2.24), and villous adenomas (3.45, 2.40-4.95), but not for hyperplastic polyps (0.90, 0.76-1.06) or tubular adenomas (0.97, 0.84-1.12).

    Interpretation: In a largely screening-naive population, compared with individuals from the general population, patients with any polyps had a higher colorectal cancer incidence, and those with sessile serrated polyps, tubulovillous adenomas, and villous adenomas had a higher colorectal cancer mortality.

  • 10. The Polaris Observatory HCV, collaborators
    et al.
    Duberg, Ann-Sofi
    Örebro University, School of Medical Sciences. Department of Infectious Diseases.
    Global prevalence and genotype distribution of hepatitis C virus infection in 2015: a modelling study2017In: The Lancet Gastroenterology & Hepatology, ISSN 2468-1253, Vol. 2, no 3, p. 161-176Article, review/survey (Refereed)
    Abstract [en]

    Background: The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of—and expansion on—the 2014 analysis, which reported 80 million (95% CI 64–103) viraemic infections in 2013.

    Methods: We developed country-level disease burden models following a systematic review of HCV prevalence (number of studies, n=6754) and genotype (n=11 342) studies published after 2013. A Delphi process was used to gain country expert consensus and validate inputs. Published estimates alone were used for countries where expert panel meetings could not be scheduled. Global prevalence was estimated using regional averages for countries without data.

    Findings: Models were built for 100 countries, 59 of which were approved by country experts, with the remaining 41 estimated using published data alone. The remaining countries had insuffi cient data to create a model. The global prevalence of viraemic HCV is estimated to be 1·0% (95% uncertainty interval 0·8–1·1) in 2015, corresponding to 71·1 million (62·5–79·4) viraemic infections. Genotypes 1 and 3 were the most common cause of infections (44% and 25%, respectively).

    Interpretation: The global estimate of viraemic infections is lower than previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections.

  • 11.
    Wintzell, Viktor
    et al.
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Svanström, Henrik
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
    Melbye, Mads
    Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
    Jess, Tine
    Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
    Olén, Ola
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Department of Pediatric Gastroenterology and Nutrition, Sachs' Children and Youth Hospital, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Departments of Pediatrics, Örebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA.
    Pasternak, Björn
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
    Use of tumour necrosis factor-α inhibitors and the risk of serious infection in paediatric inflammatory bowel disease in Denmark: a nationwide cohort study2019In: The Lancet Gastroenterology & Hepatology, ISSN 2468-1253, Vol. 4, no 11, p. 845-853Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Studies have shown an association between use of tumour necrosis factor-α (TNFα) inhibitors and increased risk of serious infection in adult inflammatory bowel disease (IBD). However, data on this topic for paediatric patients are scarce and inconclusive. The aim of this study was to investigate whether there is an association between the use of TNFα inhibitors and the risk of serious infection in children with IBD.

    METHODS: In this nationwide Danish cohort study, we searched health registers (from Jan 1, 2007, to Dec 31, 2016) to identify episodes of children and adolescents (<18 years) with at least two recorded IBD diagnoses in specialist care. We categorised follow-up time in mutually exclusive episodes of incident TNFα inhibitor use or no TNFα inhibitor use from specialist care records. We used Cox proportional hazards models to estimate hazard ratios (HRs), adjusting using propensity score weighting for demographic characteristics, comorbidities, treatment history, health-care use, and indicators of disease severity. The primary outcome, incident serious infection, was defined as infection requiring a stay in hospital and was identified through hospital records.

    FINDINGS: Among 2817 paediatric patients with IBD, we identified 618 episodes of incident TNFα inhibitor use and 2925 episodes of no TNFα inhibitor use. In the cohort of exposed and not exposed episodes that was propensity-score weighted, 53·9% were of male sex, the mean age was 15·1 (SD 1·7) years, 69·9% had Crohn's disease, and 30·1% had ulcerative colitis or IBD-unclassified; median follow-up was 1·4 years (IQR 0·4-3·0). The weighted incidence of serious infection was 54·6 events per 1000 patient-years for the TNFα inhibitor episodes and 61·9 events per 1000 patient-years for the no-use episodes. The weighted HR of serious infection associated with TNFα inhibitor use was 0·81 (95% CI 0·54-1·21).

    INTERPRETATION: There was no significant association between use of TNFα inhibitors and the risk of serious infection in children with IBD, and, based on the upper bound of the confidence interval, a relatively small risk increase seems unlikely, contrary to previous findings in adults. Observational data such as these can support paediatric clinical practice.

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