Litzroth et al. BMC Public Health (2019) 19:39 https://doi.org/10.1186/s12889-018-6347-z RESEARCH ARTICLE Open Access Low hepatitis C prevalence in Belgium: implications for treatment reimbursement and scale up Amber Litzroth1* , Vanessa Suin2, Chloé Wyndham-Thomas1, Sophie Quoilin1, Gaëtan Muyldermans1, Thomas Vanwolleghem3,4, Benoît Kabamba-Mukadi5, Vera Verburgh2, Marjorie Jacques2, Steven Van Gucht2 and Veronik Hutse2 Abstract Background: Prevalence data of chronic hepatitis C virus (HCV) infection are needed to estimate the budgetary impact of reimbursement of direct-acting antivirals (DAAs). In Belgium, the restricted reimbursement criteria are mainly guided by regional seroprevalence estimates of 0.87% from 1993 to 1994. In this first Belgian nationwide HCV prevalence study, we set out to update the seroprevalence and prevalence of chronic HCV infection estimates in the Belgian general population in order to guide decisions on DAA reimbursement. Methods: Residual sera were collected through clinical laboratories. We collected data on age, sex and district. HCV antibody status was determined with ELISA and confirmed with a line-immunoassay (LIA). In specimens with undetermined or positive LIA result, HCV viral load was measured. Specimens were classified seronegative, seropositive with resolved infection, indicative of chronic infection and with undetermined HCV status according to the test outcomes. Results were standardized for age, sex and population per district, and adjusted for clustered sampling. Results: In total 3209 specimens, collected by 28 laboratories, were tested. HCV seropositivity in the Belgian general population was estimated to be 0.22% (95% CI: 0.09–0.54%), and prevalence of chronic HCV infection 0.12% (95% CI: 0.03–0.41). In individuals of 20 years and older, these estimates were 0.26% (95% CI: 0.10–0.64%) and 0.13% (95% CI: 0.04–0.43), respectively. Of the total estimated number of HCV seropositive individuals in Belgium, 66% were between 50 and 69 years old. Conclusions: Prevalence of HCV seropositivity and chronic infection in the Belgian general population were low and comparable to many surrounding countries. These adjusted prevalences can help estimate the cost of reimbursement of DAAs and invite Belgian policy makers to accelerate the scaling up of reimbursement, giving all chronically infected HCV patients a more timely access to treatment. Keywords: Hepatitis C, Prevalence, Chronic hepatitis C virus infection, Seroprevalence, Direct-acting antivirals, Belgium * Correspondence: [email protected] 1Scientific directorate Epidemiology and public health, Sciensano, Juliette Wytsmanstreet 14, 1050 Brussels, Belgium Full list of author information is available at the end of the article © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Litzroth et al. BMC Public Health (2019) 19:39 Page 2 of 7 Background intensive care wards and with evidence of multiple The newly developed direct-acting antivirals (DAAs) pro- blood transfusions. Laboratories were not asked to sys- voked a revolution in the treatment of chronic hepatitis C tematically retrieve this information, but to only ex- virus (HCV) infection. With a 95% success rate, minimal clude these specimens if the information was known to side effects and shorter treatment duration, the burden of the person responsible for the collection. the disease can drastically be reduced. Elimination of We collected data on age, sex and district. Participat- hepatitis C could now be within reach [1, 2] and scaling ing laboratories were retrospectively asked if they per- up of treatment of chronic HCV infection is crucial in the formed analyses for correctional facilities and/or needle recently set hepatitis C elimination targets for 2030 of the exchange programs. The protocol was approved by the World Health Organization (WHO) [3, 4]. Several studies Ethics committee of the Antwerp University Hospital have indicated that treatment of all those with chronic and the University of Antwerp. HCV infection is cost-effective [5–7]. However, cost- effectiveness does not imply affordability and the high Laboratory testing strategy and specimen classification cost of DAAs has resulted in reimbursement restric- Laboratory tests were performed in 2017–2018 by the tions in many countries. Reimbursement criteria often National reference center for hepatitis C. HCV antibody target more severe liver fibrosis stages and sometimes status was determined using the HCV 4.0 Antibody include restrictions concerning drugs or alcohol use Enzygnost ELISA (Siemens healthcare diagnostics, Mun- [8, 9]. In Western Europe, Belgium remains one of the ich, Germany). ELISA anti-HCV antibody-positive speci- few countries restricting DAA reimbursement to fibrosis mens were confirmed with a line-immunoassay (LIA), stage F2 or higher [9]. the INNO-LIA HCV Score (Fujirebio, Gent, Belgium). In order to estimate the cost of different reimbursement In specimens with undetermined or positive LIA result, strategies, data on the prevalence of chronic HCV infec- HCV viral load was measured by reverse transcriptase tion are needed. In Belgium, no nationwide HCV preva- real-time PCR (RT-qPCR) with the Abbott RealTime lence data exist and the last regional study on serum HCV kit on the m2000 system (Abbott, Illinois, USA). samples was conducted in 1993–1994 without distinction Specimens were classified seropositive for HCV if they between resolved and current infection [10, 11]. The were either LIA-positive, or had an undetermined LIA Belgian restricted DAA reimbursement criteria are there- result with positive PCR. PCR-positive specimens were fore mainly guided by the 1993–1994 seroprevalence considered indicative of chronic HCV infection, while estimate of 0.87%, the lack of recent prevalence data and PCR-negative LIA-positive specimens were considered caution concerning the budgetary impact of different re- to indicate a resolved infection. PCR-negative specimens imbursement strategies. with an undetermined LIA result were considered to Here, we set out to update the HCV seroprevalence have an undetermined HCV status. All other specimens and prevalence of chronic HCV infection estimates in were classified HCV-seronegative. the Belgian general population in order to guide further decisions on DAA reimbursement criteria. Statistical analysis We calculated prevalence of HCV seropositivity and chronic Methods infection and the 95% confidence intervals (95% CI) in the Study design, specimen and data collection and ethics general Belgian population, per age group (younger than 20 In the context of a multiple disease seroprevalence study, as one group and further by decade), by region and by sex. residual sera were collected through clinical laboratories A weighting factor for age, population per district and between July 2013 and January 2015. The sample size per sex was applied to account for underrepresentation of age group aimed for was based on estimations of the certain groups. The weights applied were the inverse of European Sero-Epidemiology Network (ESEN), which in- the sampling fraction. To calculate the sampling frac- cluded an oversampling of individuals < 20 years old [12]. tion we used Belgian population data of 2013, made This strategy was chosen because the serum bank would available by the Belgian statistical office Statbel. We ad- also be tested for a number of other diseases, among justed for clustered sampling by defining laboratories as which some vaccine preventable diseases for which we the primary sampling units. For subgroups with zero wanted to obtain precise seroprevalence estimates in the positive observations, we calculated the 95% CI with younger age groups. the binomial approach. Based on the estimated preva- In order not to oversample an ill or susceptible popula- lences, we calculated the estimated number of HCV tion, laboratories were asked to preferably collect specimens seropositive and chronically infected individuals in the from surgery, orthopaedic, emergency and otorhinolaryngol- different demographic groups. We estimated the clear- ogy wards. We also asked the laboratories to exclude speci- ance rate by calculating the percentage of estimated mens from immunocompromised patients, patients from number of seropositive non-viraemic individuals among Litzroth et al. BMC Public Health (2019) 19:39 Page 3 of 7 the estimated number of seropositive individuals in the Belgian general population. The estimated clearance Belgian population. We used Stata version 14.0 (Stata rate was 45%. Of the total estimated number of HCV Corporation, Texas, US) for all statistical analyses. seropositive individuals in Belgium, 66% were between 50 and 69 years old (Table 2,Table3). Results In total 3209 specimens, collected by 28 laboratories, were Discussion tested. Specimens were representative of the Belgian popu- In this first Belgian nationwide HCV prevalence study, we lation in terms of sex and fairly representative for popula-