Anne Øvrehus

Historical epidemiology of hepatitis C virus (HCV) in selected countries

Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6 358 000 cases in 2008 and Brazil with 2 106 000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV‐infected populations are critical for addressing HCV‐related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.

Strategies to manage hepatitis C virus (HCV) disease burden

The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV‐related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3–5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.

Restrictions for reimbursement of interferon-free direct-acting antiviral drugs for HCV infection in Europe

All-oral direct-acting antiviral drugs (DAAs) for hepatitis C virus, which have response rates of 95% or more, represent a major clinical advance. However, the high list price of DAAs has led many governments to restrict their reimbursement. We reviewed the availability of, and national criteria for, interferon-free DAA reimbursement among countries in the European Union and European Economic Area, and Switzerland. Reimbursement documentation was reviewed between Nov 18, 2016, and Aug 1, 2017. Primary outcomes were fibrosis stage, drug or alcohol use, prescriber type, and HIV co-infection restrictions. Among the 35 European countries and jurisdictions included, the most commonly reimbursed DAA was ombitasvir, paritaprevir, and ritonavir, with dasabuvir, and with or without ribavirin (33 [94%] countries and jurisdictions). 16 (46%) countries and jurisdictions required patients to have fibrosis at stage F2 or higher, 29 (83%) had no listed restrictions based on drug or alcohol use, 33 (94%) required a specialist prescriber, and 34 (97%) had no additional restrictions for people co-infected with HIV and hepatitis C virus. These findings have implications for meeting WHO targets, with evidence of some countries not following the 2016 hepatitis C virus treatment guidelines by the European Association for the Study of Liver.

Model projections on the impact of HCV treatment in the prevention of HCV transmission among people who inject drugs in Europe

BACKGROUND & AIMS Prevention of hepatitis C virus (HCV) transmission among people who inject drugs (PWID) is critical for eliminating HCV in Europe. We estimated the impact of current and scaled-up HCV treatment with and without scaling up opioid substitution therapy (OST) and needle and syringe programmes (NSPs) across Europe over the next 10 years. METHODS We collected data on PWID HCV treatment rates, PWID prevalence, HCV prevalence, OST, and NSP coverage from 11 European settings. We parameterised an HCV transmission model to setting-specific data that project chronic HCV prevalence and incidence among PWID. RESULTS At baseline, chronic HCV prevalence varied from <25% (Slovenia/Czech Republic) to >55% (Finland/Sweden), and <2% (Amsterdam/Hamburg/Norway/Denmark/Sweden) to 5% (Slovenia/Czech Republic) of chronically infected PWID were treated annually. The current treatment rates using new direct-acting antivirals (DAAs) may achieve observable reductions in chronic prevalence (38-63%) in 10 years in Czech Republic, Slovenia, and Amsterdam. Doubling the HCV treatment rates will reduce prevalence in other sites (12-24%; Belgium/Denmark/Hamburg/Norway/Scotland), but is unlikely to reduce prevalence in Sweden and Finland. Scaling-up OST and NSP to 80% coverage with current treatment rates using DAAs could achieve observable reductions in HCV prevalence (18-79%) in all sites. Using DAAs, Slovenia and Amsterdam are projected to reduce incidence to 2 per 100 person years or less in 10 years. Moderate to substantial increases in the current treatment rates are required to achieve the same impact elsewhere, from 1.4 to 3 times (Czech Republic and France), 5-17 times (France, Scotland, Hamburg, Norway, Denmark, Belgium, and Sweden), to 200 times (Finland). Scaling-up OST and NSP coverage to 80% in all sites reduces treatment scale-up needed by 20-80%. CONCLUSIONS The scale-up of HCV treatment and other interventions is needed in most settings to minimise HCV transmission among PWID in Europe. LAY SUMMARY Measuring the amount of HCV in the population of PWID is uncertain. To reduce HCV infection to minimal levels in Europe will require scale-up of both HCV treatment and other interventions that reduce injecting risk (especially OST and provision of sterile injecting equipment).

Restrictions for reimbursement of interferon-free direct-acting antiviral therapies for HCV infection in Europe

[Marshall, A. D.; Cunningham, E. B.; Dore, G. J.; Grebely, J.] UNSW Sydney, Kirby Inst, Sydney, NSW, Australia. [Nielsen, S.] Freelance Epidemiologist, Madrid, Spain. [Aghemo, A.] Univ Milan, Fdn IRCCS CA Granda Osped Maggiore Policlin, Div Gastroenterol & Hepatol, Milan, Italy. [Alho, H.] Helsinki Univ Hosp, Abdominal Ctr, Helsinki, Finland. [Alho, H.] Univ Helsinki, Helsinki, Finland. [Backmund, M.] Univ Hosp Munich, Dept Med 2, Munich, Germany. [Bruggmann, P.] Arud Ctr Addict Med, Zurich, Switzerland. [Dalgard, O.] Univ Oslo, Akershus Univ Hosp, Dept Infect Dis, Oslo, Norway. [Dalgard, O.] Univ Oslo, Fac Med, Oslo, Norway. [Flisiak, R.] Med Univ Bialystok, Dept Infect Dis & Hepatol, Bialystok, Poland. [Foster, G.] Queen Mary Univ London, London, England. [Gheorghe, L.] Fundeni Clin Inst, Gastroenterol & Hepatol, Bucharest, Romania. [Goldberg, D.] Hlth Protect Scotland, Glasgow, Lanark, Scotland. [Goulis, I.] Dept Internal Med, Thessaloniki, Greece. [Hickman, M.] Univ Bristol, Social Med, Bristol, Avon, England. [Hoffmann, P.] Minist Hlth Luxembourg, Luxembourg, Luxembourg. [Jancoriene, L.] Vilnius Univ Hosp, Santariskiu Klin, Ctr Infect Dis, Vilnius, Lithuania. [Jarcuska, P.] Univ Hosp, Dept Internal Med 1, Kosice, Slovakia. [Jarcuska, P.] Univ Pavol Jozef Safarik, Kosice, Slovakia. [Kaberg, M.] Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden. [Makara, M.] St Istvan & St Laszlo Hosp, Hepatol Ctr, Budapest, Hungary. [Maimets, M.] Univ Tartu, Dept Internal Med, Tartu, Estonia. [Marinho, R.] Hosp Santa Maria, Med Sch Lisbon, Dept Gastroenterol & Hepatol, Lisbon, Portugal. [Maticic, M.] Univ Med Ctr, Clin Infect Dis & Febrile Illnesses, Ljubljana, Slovenia. [Norris, S.; Tait, M.] Dr Steevens Hosp, Natl Hepatitis Treatment Programme C, Hlth Serv Execut, Dublin, Ireland. [Olafsson, S.] Landspitali Univ Hosp, Dept Med, Div Gastroenterol, Reykjavik, Iceland. [Ovrehus, A.] Univ Southern Denmark, Odense Univ Hosp, Dept Infect Dis, Odense, Denmark. [Pawlotsky, J. -M.] Univ Paris Est, Hop Henri Mondor, Creteil, France. [Pocock, J.] Mater Hosp, Gastroenterol Dept, Msida, Malta. [Robaeys, G.] Ziekenhuis Oost Limburg, Dept Gastroenterol & Hepatol, Genk, Belgium. [Robaeys, G.] UHasselt, Dept Med & Life Sci, Hasselt, Belgium. [Robaeys, G.] UZLeuven, Dept Hepatol, Leuven, Belgium. [Roncero, C.] Univ Autonoma Barcelona, Hosp Univ Vall dHebron, Psychiat Serv, Addict & Dual Diag Unit, Barcelona, Spain. [Simonova, M.] Mil Med Acad, Dept Gastroenterol HPB Surg & Transplantol, Sofia, Bulgaria. [Sperl, J.] Inst Clin & Expt Med, Dept Hepatogastroenterol, Prague, Czech Republic. [Tolmane, I.] Infectol Ctr Latvia, Dept Hepatol, Riga, Latvia. [Tomaselli, S.] Off Publ Hlth, Vaduz, Liechtenstein. [van der Valk, M.] Acad Med Ctr, Dept Infect Dis, Amsterdam, Netherlands. [Vince, A.] Univ Zagreb, Sch Med, Univ Hosp Infect Dis, Zagreb, Croatia. [Lazarus, J. V.] Univ Copenhagen, Rigshosp, CHIP, Copenhagen, Denmark. [Lazarus, J. V.] Hosp Clin Barcelona, Barcelona Inst Global Hlth ISGlobal, Barcelona, Spain.

Comparison of the medical students’ perceived self-efficacy and the evaluation of the observers and patients

BackgroundThe accuracy of self-assessment has been questioned in studies comparing physicians’ self-assessments to observed assessments; however, none of these studies used self-efficacy as a method for self-assessment.The aim of the study was to investigate how medical students’ perceived self-efficacy of specific communication skills corresponds to the evaluation of simulated patients and observers.MethodsAll of the medical students who signed up for an Objective Structured Clinical Examination (OSCE) were included. As a part of the OSCE, the student performance in the “parent-physician interaction” was evaluated by a simulated patient and an observer at one of the stations. After the examination the students were asked to assess their self-efficacy according to the same specific communication skills.The Calgary Cambridge Observation Guide formed the basis for the outcome measures used in the questionnaires.A total of 12 items was rated on a Likert scale from 1–5 (strongly disagree to strongly agree).We used extended Rasch models for comparisons between the groups of responses of the questionnaires. Comparisons of groups were conducted on dichotomized responses.ResultsEighty-four students participated in the examination, 87% (73/84) of whom responded to the questionnaire. The response rate for the simulated patients and the observers was 100%.Significantly more items were scored in the highest categories (4 and 5) by the observers and simulated patients compared to the students (observers versus students: -0.23; SE:0.112; p=0.002 and patients versus students:0.177; SE:0.109; p=0.037). When analysing the items individually, a statistically significant difference only existed for two items.ConclusionThis study showed that students scored their communication skills lower compared to observers or simulated patients. The differences were driven by only 2 of 12 items.The results in this study indicate that self-efficacy based on the Calgary Cambridge Observation guide seems to be a reliable tool.

Sofosbuvir based treatment of chronic hepatitis C genotype 3 infections: A Scandinavian real-life study

Background and aims Chronic hepatitis C virus (HCV) genotype 3 infection with advanced liver disease has emerged as the most challenging to treat. We retrospectively assessed the treatment outcome of sofosbuvir (SOF) based regimes for treatment of HCV genotype 3 infections in a real life setting in Scandinavia. Methods Consecutive patients with chronic HCV genotype 3 infection were enrolled at 16 treatment centers in Denmark, Sweden, Norway and Finland. Patients who had received a SOF containing regimen were included. The fibrosis stage was evaluated by liver biopsy or transient liver elastography. The following treatments were given according availability and local guidelines: 1) SOF + ribavirin (RBV) for 24 weeks, 2) SOF + daclatasvir (DCV) +/-RBV for 12–24 weeks, 3) SOF + pegylated interferon alpha (peg-IFN-α) + RBV for 12 weeks or 4) SOF/ledipasvir (LDV) + RBV for 12–16 weeks. The primary endpoint was sustained virological response (SVR) assessed at week 12 (SVR12) after end of treatment. Results We included 316 patients with a mean age of 55 years (range 24–79), 70% men, 49% treatment experienced, 58% with compensated cirrhosis and 12% with decompensated cirrhosis.In the modified intention to treat (mITT) population SVR12 was achieved in 284/311 (91%) patients. Among 26 treatment failures, five had non-response, 3 breakthrough and 18 relapse. Five patients were not included in the mITT population. Three patients died from reasons unrelated to treatment and two were lost to follow-up. The SVR12 rate was similar for all treatment regimens, but lower in men (p = 0.042), and in patients with decompensated liver disease (p = 0.004). Conclusion We found that sofosbuvir based treatment in a real-life setting could offer SVR rates exceeding 90% in patients with HCV genotype 3 infection and advanced liver disease.

Four weeks of ledipasvir/sofosbuvir and ribavirin with or without pegylated interferon for chronic hepatitis C in non-cirrhotic people who inject drugs. A randomized trial

Citation for pulished version (APA): Øvrehus, A. L. H., Krarup, H., Birkemose, I., Holm, D. K., Mössner, B., Ernst, A., & Christensen, P. B. (2018). Four weeks of ledipasvir/sofosbuvir and ribavirin with or without pegylated interferon for chronic hepatitis C in non-cirrhotic people who inject drugs. A randomized trial. Journal of Hepatology, 68(4), 840-842. https://doi.org/10.1016/j.jhep.2017.11.031

Hepatitis C elimination among people who inject drugs: Challenges and recommendations for action within a health systems framework

The burden of hepatitis C infection is considerable among people who inject drugs (PWID), with an estimated prevalence of 39%, representing an estimated 6.1 million people who have recently injected drugs living with hepatitis C infection. As such, PWID are a priority population for enhancing prevention, testing, linkage to care, treatment and follow‐up care in order to meet World Health Organization (WHO) hepatitis C elimination goals by 2030. There are many barriers to enhancing hepatitis C prevention and care among PWID including poor global coverage of harm reduction services, restrictive drug policies and criminalization of drug use, poor access to health services, low hepatitis C testing, linkage to care and treatment, restrictions for accessing DAA therapy, and the lack of national strategies and government investment to support WHO elimination goals. On 5 September 2017, the International Network of Hepatitis in Substance Users (INHSU) held a roundtable panel of international experts to discuss remaining challenges and future priorities for action from a health systems perspective. The WHO health systems framework comprises six core components: service delivery, health workforce, health information systems, medical procurement, health systems financing, and leadership and governance. Communication has been proposed as a seventh key element which promotes the central role of affected community engagement. This review paper presents recommended strategies for eliminating hepatitis C as a major public health threat among PWID and outlines future priorities for action within a health systems framework.

Late Presentation for Care Among Patients With Chronic Hepatitis C: Prevalence and Risk Factors

Abstract Patients with chronic hepatitis C may have advanced fibrosis at first evaluation. Using the European Association for the Study of the Liver (EASL) definition (FibroScan® >9.5 kPa) for “late presenter for care” (LP), we found that 32% (169 of 527) of patients were LP. Being a LP was associated with increasing age and a history of alcohol overuse.