Introduction
Despite the severity of the infection caused by hepatitis C virus (HCV), HCV can be cured by direct-acting antiviral drugs (DAAs), which lead to a sustained virological response (SVR) in at least 95% patients with HCV [1], including those coinfected with HIV [2]. These new drugs have made the possibility of HCV elimination realistic, and in 2016, the WHO called for the elimination of viral hepatitis as a public health threat by 2030 in its Global Health Sector Strategy [3]. The specific targets for HCV elimination identified by WHO include diagnosing 90% of all HCV-infected individuals and treating 80% of those diagnosed [3]. Further, WHO prioritized anti-HCV treatment in HIV/HCV-coinfected individuals [3], who may experience a faster progression of liver fibrosis [4].
The progress towards achieving the HCV elimination targets differs by country and is attributed to factors such as DAA treatment availability and national policies [5,6]. In the WHO European region, some countries have developed and implemented effective national strategies to achieve the WHO targets [7], while other countries still have substantial gaps in their HCV policies [8]. Furthermore, treatment uptake varies significantly even in regions with available DAAs [9]. Measuring global progress towards the WHO targets requires the assessment of diagnostic and treatment coverage in HCV-infected individuals and comparison of the rates among regions and countries, which can be done using the cascade of care (CoC) method.
The CoC is an instrument that provides a simple summary of the medical care stages to identify gaps in the healthcare system hindering achieving good clinical outcomes, and allows for standardized cross-population comparisons. The most well known tool is the HIV CoC, widely used as a metric for HIV care quality assessment to monitor progress towards the 90–90–90 target [10]. The CoC framework can also be used for HCV infection to identify gaps between current data and WHO hepatitis elimination targets [11]. The objective of this study was to build an HCV CoC among HIV/HCV coinfected participants enrolled in the EuroSIDA cohort from 32 participating countries in the WHO European region [12,13]. Our previous study on the HCV CoC among individuals in EuroSIDA included data up until January 1, 2015, prior to the widespread access to DAA therapy [14]. In this study, we aim to update and extend our previous work by including all coinfected persons under follow-up in 2019 and to include country-specific data.
Materials and methods
Participants
Participants were enrolled from the large EuroSIDA cohort [12], which contains clinical and demographic data on 23 309 PWH from the WHO European Region [15] and Argentina. In this study, five European regions were defined as follows:
- (1) South: Greece, Israel, Italy, Portugal, and Spain;
- (2) Central-West: Austria, Belgium, France, Germany, Luxembourg, and Switzerland;
- (3) North: Denmark, Finland, Iceland, Ireland, the Netherlands, Norway, Sweden, and the UK;
- (4) Central-East: Bosnia-Herzegovina, Bulgaria, Croatia, Czech Republic, Hungary, Poland, Romania, Serbia, Slovakia, and Slovenia;
- (5) East: Belarus, Estonia, Georgia, Latvia, Lithuania, Russia, and Ukraine.Countries in italics did not provide data for this study.
EuroSIDA is a prospective noninterventional cohort study that has collected data on PWH since 1994 and started collecting anti-HCV antibodies and HCV-RNA data in 1997. Data are collected from participants’ routine clinical visits, retrieving information from medical records and/or local databases, which is then reported to a centralized EuroSIDA database. Data on anti-HCV IgG, HCV-RNA, HCV genotype and subtype, liver fibrosis stage, and HCV treatment are collected for participants at enrolment and annually thereafter. Detailed information on the EuroSIDA study has been published elsewhere [12,16].
All PWH coinfected with HCV under prospective follow-up on October 1, 2019 (index date) were included in this analysis. HCV coinfection was defined as a positive anti-HCV IgG result, a positive HCV-RNA result, data on HCV genotype or HCV treatment record before the index date. Prospective follow-up was defined as having at least one clinical visit, CD4+ cell count measurement or HIV RNA measurement from July 1, 2018, to the index date, allowing 12 months for persons visiting clinics once per calendar year and three additional months for a window of attendance around the 12-month period. Baseline variables were all defined as the last value prior to the index date unless otherwise specified.
Liver fibrosis was defined according to the previous EuroSIDA study [17] based on liver biopsy and Fibroscan test results, aspartate transaminase to platelet ratio (APRI), and hyaluronic acid. The most recent fibrosis marker measured prior to index date was used to define fibrosis stage and where more than one marker was measured priority was given to biopsy, Fibroscan, APRI followed by hyaluronic acid.
Hepatitis C virus cascade of care stages
HCV CoC stages have been defined and expanded based on the definitions used for the previous HCV CoC in EuroSIDA by Amele et al.[14]. The CoC constructed for the study population consists of diagnostic and treatment parts.
The diagnostic stages include
- (1) Stage 1 - Anti-HCV positive: defined as a positive anti-HCV IgG test result, or a positive HCV-RNA test result, or data on HCV genotype, or HCV treatment record before the index date;
- (2) Stage 2 - Ever HCV-RNA tested: at least one HCV-RNA test or HCV genotype test performed before the index date;
- (3) Stage 3 - Currently HCV-RNA positive: most recent HCV-RNA test before index date was positive; HCV genotyped but not treated before the index date.
- The treatment stages include
- (4) Stage 4a - Ever chronically infected with HCV: an estimated number of participants with chronic hepatitis C infection among all anti-HCV positive (based on multiple imputation);
- (5) Stage 4b - Ever diagnosed with chronic HCV: positive HCV-RNA result, or HCV genotype test, or HCV treatment record before the index date;
- (6) Stage 5 - Ever started treatment: initiation of HCV treatment on or before index date;
- (7) Stage 6 - Treatment completed: completion of HCV treatment on or before index date;
- (8) Stage 7 - Sufficient follow-up after treatment completion: over 12 weeks of follow-up after stopping DAA or over 24 weeks of follow-up after stopping interferons (IFN) available before the index date;
- (9) Stage 8 - Follow-up HCV RNA available: HCV RNA test more than 12 or 24 weeks after completing treatment (for IFN-free and IFN-based therapy, respectively) before the index date;
- (10) Stage 9 – Cured: the first HCV-RNA test at least 12 or 24 weeks after the end of last treatment (for IFN-free and IFN-based therapy, respectively) and before the index date was negative.The total number of HIV/HCV-coinfected participants (Stage 1) was used as the denominator for the diagnostic part of the cascade; while for the treatment part, the estimated number of ever chronically infected with HCV (Stage 4a) was used as the denominator. Using stage 4a as the denominator for the treatment part rather than stage 4b (ever diagnosed with chronic HCV) used in a previous EuroSIDA analysis [14] enables comparisons across countries and over time in terms of progress towards HCV elimination, because stage 4a is not influenced by differences in diagnostic activity.
In the subgroup analyses, HCV CoC were constructed on a country-level for 21 countries enrolling more than 50 anti-HCV positive participants in this study.
Statistics
Descriptive statistics were summarized as frequencies and proportions with χ2P values for categorical variables. For continuous variables, data were described using Kruskal--Wallis test and presented as medians and interquartile ranges (IQRs).
To calculate the estimated number of people with persistent chronic infection among those who have not been tested for HCV-RNA, multiple imputation by chained equations was used, with 100 imputations and including variables determined at the index date: sex, ethnic origin, HIV exposure group, HIV viral load, CD4+ cell count, prior AIDS diagnosis, hepatitis B status, region of Europe, smoking status, BMI, age, and last visit date. Results were combined using Rubin's rules [18].
All analyses were performed using SAS 9.4 software (version 9.4; SAS Institute, Cary, North Carolina, USA).
Results
Basic demographical data
Of 22 356 EuroSIDA participants from the WHO European region, 20 437 (91.4%) were ever tested for anti-HCV antibodies, and 9103 (40.7%) were anti-HCV positive. Among them, 4773 individuals (52.4%) were under prospective follow-up on October 1, 2019 (Table 1). Participants were enrolled in Southern Europe (23.4%), Central-Western Europe (24.7%), Northern Europe (15.2%), Central-Eastern Europe (13.2%), and Eastern Europe (23.5%). Overall, 70.6% were men, and the median age was 51 years (IQR 43–57) ranging from 42 years (IQR 38–46) in Eastern Europe to 56 years (IQR 50–60; P < 0.0001) in Central-Western Europe.
Table 1 -
Characteristics of the HIV/hepatitis C virus coinfected cohort in EuroSIDA at last visit.
| Variables, N (%) |
Overall |
South |
Central-West |
North |
Central-East |
East |
| Overall number |
|
4773 (100) |
1118 (23.4) |
1178 (24.7) |
724 (15.2) |
632 (13.2) |
1121 (23.5) |
| Sex |
Male |
3370 (70.6) |
799 (71.5) |
872 (74.0) |
555 (76.7) |
445 (70.4) |
699 (62.4) |
| Ethnicity |
White |
4211 (88.2) |
1026 (91.8) |
815 (69.2) |
632 (87.3) |
625 (98.9) |
1113 (99.3) |
| Mode of HIV transmission |
PWID |
2738 (57.4) |
751 (67.2) |
533 (45.2) |
315 (43.5) |
384 (60.8) |
755 (67.4) |
|
MSM |
953 (20.0) |
164 (14.7) |
379 (32.2) |
265 (36.6) |
131 (20.7) |
14 (1.2) |
|
Heterosexual |
781 (16.4) |
134 (12.0) |
159 (13.5) |
94 (13.0) |
67 (10.6) |
327 (29.2) |
| HIV RNA |
≥200 copies/ml |
307 (6.4) |
41 (3.7) |
21 (1.8) |
24 (3.3) |
37 (5.9) |
184 (16.4) |
| ART status |
Ever received ART |
4730 (99.1) |
1114 (99.6) |
1172 (99.5) |
717 (99.0) |
627 (99.2) |
1100 (98.1) |
|
Currently on ART |
4648 (97.4) |
1105 (98.8) |
1151 (97.7) |
711 (98.2) |
615 (97.3) |
1066 (95.1) |
| Prior AIDS |
|
1271 (26.6) |
340 (30.4) |
327 (27.8) |
141 (19.5) |
146 (23.1) |
317 (28.3) |
| HCV genotype |
1 |
1802 (37.8) |
488 (43.6) |
426 (36.2) |
356 (49.2) |
182 (28.8) |
350 (31.2) |
|
2 |
115 (2.4) |
16 (1.4) |
31 (2.6) |
32 (4.4) |
4 (0.6) |
32 (2.9) |
|
3 |
882 (18.5) |
201 (18.0) |
162 (13.8) |
115 (15.9) |
127 (20.1) |
277 (24.7) |
|
4 |
496 (10.4) |
176 (15.7) |
167 (14.2) |
62 (8.6) |
90 (14.2) |
1 (0.1) |
|
Unknown |
1478 (31.0) |
237 (21.2) |
392 (33.3) |
159 (22.0) |
229 (36.2) |
461 (41.1) |
| Fibrosis stage |
F0-F1 |
3378 (70.8) |
683 (61.1) |
883 (75.0) |
459 (63.4) |
453 (71.7) |
900 (80.3) |
|
F2 |
540 (11.3) |
175 (15.7) |
132 (11.2) |
62 (8.6) |
86 (13.6) |
85 (7.6) |
|
F3 |
344 (7.2) |
114 (10.2) |
69 (5.9) |
57 (7.9) |
48 (7.6) |
56 (5.0) |
|
F4 |
451 (9.4) |
145 (13.0) |
94 (8.0) |
89 (12.3) |
45 (7.1) |
78 (7.0) |
|
Unknown |
60 (1.3) |
1 (0.1) |
0 (0.0) |
57 (7.9) |
0 (0.0) |
2 (0.2) |
| HBV coinfection |
HBsAg + |
228 (4.8) |
35 (3.1) |
65 (5.5) |
32 (4.4) |
30 (4.7) |
66 (5.9) |
|
Unknown |
248 (5.2) |
48 (4.3) |
43 (3.7) |
80 (11.0) |
30 (4.7) |
47 (4.2) |
| Median (IQR) |
| Age, years |
|
51 (43–57) |
55 (50–58) |
56 (50–60) |
55 (48–59) |
46 (41–52) |
42 (38–46) |
| CD4+ cell count, cells/μl |
|
604 (423–820) |
638 (453–880) |
658 (490–867) |
606 (420–809) |
605 (429–806) |
510 (341–698) |
| CD4+ cell count (nadir), cells/μl |
|
168 (76–269) |
179 (83–284) |
154 (52–259) |
180 (98–280) |
164 (74–276) |
162 (83–254) |
Evidence of regional differences for all variables (P < 0.0001).ART, antiretroviral treatment; MSM, men who have sex with men; PWID, people who inject drugs.Last visit date for all participants on July 1, 2018, or later, allowing 12 months for persons visiting clinics once per calendar year and three additional months for a window of attendance from the index date defined as October 1, 2019.
The main mode of acquiring HIV was through injection drug use reported for 57.4% of all coinfected participants and ranging from 43.5% in Northern to 67.4% in Eastern Europe. HIV viral load was below 200 copies/ml in 93.6% of participants overall, with the highest prevalence of persons without viral suppression in Eastern Europe (16.4%). Of all participants, 26.6% have had a prior AIDS diagnosis, with the highest proportion of AIDS (30.4%) in Southern Europe.
Viral hepatitis
Of all 3295 participants with known HCV genotype (69%), the most frequent genotypes were genotype one (54.7%) and three (26.8%).
No or mild liver fibrosis (stage F0/F1) was reported for 70.8% of the participants, with the burden of stage four fibrosis (cirrhosis) ranging from 7.0% in Eastern Europe to 13.0% in Southern Europe. The median time between the last fibrosis assessment and index date was 3 months (IQR 1–10 months).
Hepatitis C virus cascade of care overall and by region
Of all 4773 anti-HCV positive individuals, 4446 (93.1%, 95% CI 92.4–93.9) had ever been tested for HCV-RNA, and 19.0% of individuals included in the analysis were HCV-RNA positive at October 1, 2019 (Fig. 1). Prevalence of current HCV-RNA positivity was highest in East and Central-East (33.7 and 29.6%, respectively).
;)
Fig. 1: HCV cascade of care, diagnostic and treatment stages (overall and by region).
An estimated 4300 (90.1%, 95% CI 89.2–91.0) anti-HCV positive individuals were ever chronically infected with HCV, of whom 4025 participants (93.6%, 95% CI 92.8–94.4) have ever been diagnosed (Fig. 1). In Eastern Europe, 78.1% of the estimated number of chronic infections have ever been diagnosed; in comparison to over 95% in the other regions.
Overall, 3116 persons ever started HCV treatment (72.5% of the estimated number of chronically infected, 95% CI 70.9–74.0); of whom 3061 (71.2% of ever chronically infected, 95% CI 69.6–72.8) completed treatment; and 2985 (69.4% of ever chronically infected, 95% CI 67.8–71.1) have had sufficient follow-up to assess treatment outcome. HCV cure was achieved in 55.9% (95% CI 53.9–57.9) of the estimated number of chronically infected overall.
On a regional level, the highest proportion of persons who ever started treatment was in Central-Western Europe (85.1%) with the lowest in Eastern Europe (46.7%). The cure proportion ranged from 72.2% of the estimated number of chronically infected in Central-West to 28.0% in East.
Hepatitis C virus cascade of care by country and intra-regional differences
HCV CoC were constructed for 21 countries that together contributed to 94.9% of all study participants.
No significant intra-regional difference was observed among the proportion of ever HCV-RNA tested in all regions except Eastern Europe, where the proportion of ever HCV-RNA tested ranged from 50.6% in Belarus to 100% in Georgia (Fig. 2 a). Intra-regional difference at ‘currently HCV-RNA positive’ stage was the most pronounced in Eastern Europe as well, with the lowest fraction of currently HCV-RNA positive in Georgia (13.3%) and the highest one in Estonia (55.9%, global P < 0.0001). The proportion of currently HCV-RNA positive individuals reached 30.2 and 29.7% of all anti-HCV positive participants in Hungary and Poland, respectively, and was below 25% in all countries of Southern, Central-Western and Northern Europe (global P < 0.0001).
Fig. 2: (a) HCV cascade of care, diagnostic stages, shown by country. (b) HCV cascade of care, treatment stages, shown by country.
Fig. 2 (Continued): (a) HCV cascade of care, diagnostic stages, shown by country. (b) HCV cascade of care, treatment stages, shown by country.
In the treatment part of the CoC, the most substantial intra-regional differences were observed in Central-Western and Eastern Europe (Fig. 2 b). In Central-West, significant difference between Belgium and other countries appeared at the ‘follow-up HCV-RNA measured’ and ‘cured’ HCV CoC stages (global P < 0.0001). While in Eastern Europe, the disparity between the number of ever chronically infected and ever diagnosed was large in Belarus and Ukraine, with 51.9 and 64.2% of the chronically infected being ever diagnosed with chronic HCV, respectively. In all countries in this region except Georgia, HCV cure proportion was below 40%, with the lowest one of 11.2% in Belarus (global P < 0.0001). In Southern Europe, the cure proportion ranged from 65.6% in Israel to 78.6% in Portugal (global P = 0.025). In Northern Europe, the UK demonstrated both the highest proportion of ever started treatment (85.6%) and cured (73.2%), with the lowest cure proportion in Denmark (57.3%; global P < 0.0001). In Central-Eastern Europe, the difference between the cure proportions in Hungary (41.2%) and Poland (42.5%) did not reach the level of statistical significance (global P = 0.83).
Over 70% of the estimated number of chronically infected were cured in seven out of 21 countries, exceeding 80% only in Austria (Fig. 3). Although in general Western European countries perform better than Eastern European, each region contains countries with different cure levels. The largest intra-regional difference in cure proportions was observed between the countries of the Eastern European region, though Central-Western region of Europe also demonstrated a broad intra-regional range in cure achievement.
Fig. 3: Proportion of hepatitis C virus cure, by country.
Discussion
In this study, the HCV CoC was constructed to provide more information on progress in Europe towards reaching the WHO 2030 hepatitis elimination targets of 90% of people with HCV diagnosed and 80% treated [3]. We assessed the HCV CoC in the DAA era in a large sample of HIV/HCV-coinfected individuals from 32 countries within the WHO European region, specifically examining the coinfected group due to treatment prioritization [3]. Two vulnerable groups – people who inject drugs (PWID) and MSM accounted for 77.4% of the studied HIV/HCV-coinfected group across Europe. PWID are known to be stigmatized by healthcare providers [19] and more likely to have suboptimal adherence to treatment in some settings [20], and MSM experience stigma and discrimination in Eastern [21,22] and Central Eastern Europe [23].
We used a 10-stage CoC structure that has been expanded with two stages since the previous study in EuroSIDA [14]. To our knowledge, this is the most detailed HCV CoC that includes essential stages (infected, diagnosed, treated, and cured) [11], although it does not capture some HCV care indicators reported by others, such as engagement in care [24], proportion of participants who underwent liver biopsy [25], or proportion of reinfections [26].
We found significant regional disparities with poor HCV-RNA testing coverage in Eastern Europe and less than 80% eligible persons covered by HCV treatment in Northern, Central-Eastern, and Eastern Europe.
The largest intra-regional differences in the HCV CoC diagnostic part were observed in Eastern region of Europe, while for treatment stages, differences were most prominent in Eastern and Central-Western Europe. In Eastern Europe, the low number of HCV-RNA tested in Belarus (50.6%), which enrolled the highest number of participants, affected the regional proportion (77.3%), while Estonia, Georgia, and Lithuania tested over 98% of participants.
The largest gaps between CoC treatment stages were observed: between the number of participants diagnosed with chronic HCV and the number of treated; and between the number of persons who completed treatment more than 12/24 weeks before the index date and the number of individuals with a follow-up HCV-RNA test available. Treatment uptake gap was more pronounced in Eastern and Central-Eastern Europe, but less than 80% of eligible individuals had started treatment also in some countries in Northern (Denmark and Sweden) and Central-Western Europe (Switzerland). Insufficient follow-up HCV-RNA testing coverage after treatment completion also affected the cure proportion. Improvement of follow-up testing will result in an increase in the proportion cured, especially for the countries with large follow-up HCV-RNA testing gap such as Belgium, Hungary, and Poland. The intra-regional differences described above could be attributed to the HCV policies and strategies implemented in each country [5,6,27], which we did not intend to analyze in this article.
We observed substantial changes in comparison to the HCV CoC in EuroSIDA before January 1, 2015 [14] when DAAs had only been available for a short time and at a very high cost per treated individual. Since then, the cost of DAA therapy has decreased and most countries in Europe have removed restrictions to its access [5]. In Eastern Europe, however, diagnostic and DAA treatment coverage remained unsatisfactory [28] with an exception of Georgia due to the successful national hepatitis C elimination program [29]. Positive changes were observed both in the diagnostic and treatment parts of HCV CoC, although it should be noted that the individuals included in the 2015 and 2019 analyses may differ. The proportion of ever HCV-RNA tested increased from 81.3 to 93.1% from 2015 to 2019, and the percentage of currently HCV-RNA positive persons decreased from 61.5 to 19.2% overall. The substantial increase in HCV-RNA testing was observed mainly in the Eastern (from 51.5 to 77.3%) and Central-Eastern (from 84.9 to 94.3%) regions of Europe, though other regions also demonstrated improved testing coverage. Before 2015, 43.7% of participants diagnosed with chronic HCV had started treatment. In our study update, 72.5% of the estimated number of chronically infected (or 77.4% of the exact number of diagnosed with chronic HCV) had started treatment. The overall cure rate increased from 16.2% of the ever HCV RNA-positive in EuroSIDA in 2015 to 55.9% of the estimated number of chronically infected (or 59.7% of persons ever diagnosed with chronic HCV) in the DAA era.
In the three European studies on HCV care indicators in PWH -- the Swiss [30], ATHENA [31], and AHIVCOS [32] cohort studies -- HCV-RNA testing has been performed in all study participants. Treatment uptake in Switzerland and Austria in our study was substantially higher compared with the data reported in the Swiss cohort in 2015 [30] and in AHIVCOS cohort in 2017 [32], due to the improved DAA access. We did not construct a separate CoC for the Netherlands in our study due to the limited number of participants. Cure proportion in ATHENA cohort was 76% of all retained in care [31], compared with 66.6% of ever chronically infected in Northern Europe in our study. This difference can possibly be attributed to the successful harm reduction policies in the Netherlands and lower proportion of PWID in the ATHENA cohort than in the Northern European subpopulation in our study.
The main strength of the current study is the comprehensive pan-European data on PWH from 32 countries, allowing to build a CoC at the regional and country levels. Participants are being prospectively followed, with new patients being enrolled in EuroSIDA every 2--3 years. This cohort structure allows to construct HCV CoC periodically to assess the healthcare changes across Europe.
A known limitation of the current study was that HIV/HCV-infected individuals included in EuroSIDA are not enrolled in direct proportion to the total infected population in each participating country. EuroSIDA enrolls participants attending HIV care primarily from clinics in large cities and does not include incarcerated or institutionalized persons. EuroSIDA also does not include data on HCV-monoinfected individuals; therefore, although WHO hepatitis elimination targets are developed for the overall population, our results can be generalizable only for the HIV/HCV-coinfected part.
We used the first HCV-RNA follow-up test after 12/24 weeks after treatment completion to define the cure, therefore we were unable to capture reinfections after the treatment success, which might be particularly important in the MSM group that has a high risk of reinfection [31,33]. These participants were therefore counted both in Stage 9 (cured) and Stage 3 (currently HCV-RNA positive) of the HCV CoC. Further, a lack of follow-up HCV-RNA testing data limited our ability to determine cure in some persons with chronic HCV. Possible reasons of the data lacking can include, aside from the possibility of the test not being performed, scheduling of the HCV-RNA test on the next visit in HIV clinics, which can be later than 12/24 weeks after HCV treatment completion; performing the test in another institution; and testing for HCV core antigen that was not collected in EuroSIDA before 2019, instead of HCV-RNA.
According to the study definitions, participants were considered cured (Stage 9) only after 12/24 weeks of follow-up after the treatment completion. Considering the treatment duration, participants should have started DAA treatment in the beginning of 2019 or earlier, in order to be included in Stage 9. For all participants who started treatment later, confirmatory HCV-RNA tests will be likely reported in the subsequent dataset that was unavailable at the time of this analysis.
Our cross-sectional HCV CoC for participants under prospective follow-up in 2019 demonstrated improvement both in HCV diagnostic and treatment coverage in HIV/HCV-coinfected population across Europe in DAA era. However, each region and each country had its own weak points in the HCV care system, and therefore, different approaches will be required to achieve the WHO hepatitis elimination targets. Countries of Western Europe are generally closer to these targets than is Eastern Europe, though significant differences exist across countries within one region, especially within Eastern and Central-Western Europe. Treatment coverage gap and insufficient follow-up HCV-RNA testing were the most prominent gaps between the CoC stages. In some settings in Eastern Europe, a high number of undiagnosed chronic infections was also identified as a major gap.
This detailed cascade structure allowed for identifying the gaps on a regional and national level to inform country's actions to overcome the obstacles on the way to reaching the WHO hepatitis C elimination targets.
Acknowledgements
EuroSIDA was supported by the European Union's Seventh Framework Programme for research, technological development, and demonstration under EuroCoord grant agreement no. 260694. Current support includes unrestricted grants by ViiV Healthcare LLC, GlaxoSmithKline R&D Limited, Janssen Scientific Affairs, Janssen R&D, Bristol-Myers Squibb Company, Merck Sharp & Dohme Corp, Gilead Sciences. The participation of centers from Switzerland was supported by The Swiss National Science Foundation (Grant 148522). The study is also supported by a grant [grant number DNRF126] from the Danish National Research Foundation and by the International Cohort Consortium of Infectious Disease (RESPOND).
The multicenter study group, EuroSIDA (national coordinators in parenthesis). Albania: (A Harxhi), University Hospital Center of Tirana, Tirana.
Argentina: (M. Losso), M Kundro, Hospital JM Ramos Mejia, Buenos Aires.
Austria: (B. Schmied), Klinik Penzing, Vienna; R. Zangerle, Medical University Innsbruck, Innsbruck.
Belarus: (I. Karpov), A. Vassilenko, Belarusian State Medical University, Minsk; V.M. Mitsura, Gomel State Medical University, Gomel; D. Paduto, Regional AIDS Centre, Svetlogorsk.
Belgium: (N. Clumeck), S. De Wit, M. Delforge, Saint-Pierre Hospital, Brussels; E. Florence, Institute of Tropical Medicine, Antwerp; L. Vandekerckhove, University Ziekenhuis Gent, Gent.
Bosnia-Herzegovina: (V. Hadziosmanovic), Klinicki Centar Univerziteta Sarajevo, Sarajevo.
Croatia: (J. Begovac), University Hospital of Infectious Diseases, Zagreb.
Czech Republic: (L. Machala), D. Jilich, Faculty Hospital Bulovka, Prague; D. Sedlacek, Charles University Hospital, Plzen.
Denmark: G. Kronborg, T. Benfield, Hvidovre Hospital, Copenhagen; J. Gerstoft, T. Katzenstein, Rigshospitalet, Copenhagen; C. Pedersen, I.S. Johansen, Odense University Hospital, Odense; L. Ostergaard, Skejby Hospital, Aarhus; L. Wiese, N.F. Moller, Sjællands Universitetshospital, Roskilde; L.N. Nielsen, Hillerod Hospital, Hillerod.
Estonia: (K. Zilmer), West-Tallinn Central Hospital, Tallinn; Jelena Smidt, Nakkusosakond Siseklinik, Kohtla-Järve.
Finland: (I. Aho), Helsinki University Hospital, Helsinki.
France: (J.-P. Viard), Hôtel-Dieu, Paris; K. Lacombe, Hospital Saint-Antoine, Paris; C. Pradier, E. Fontas, Hôpital de l’Archet, Nice; C. Duvivier, Hôpital Necker-Enfants Malades, Paris.
Germany: (J. Rockstroh), Universitäts Klinik Bonn; G Behrens, Medizinische Hochschule Hannover; O. Degen, University Medical Center Hamburg-Eppendorf, Infectious Diseases Unit, Hamburg; C. Hoffmann, H.J. Stellbrink, IPM Study Center, Hamburg; C. Stefan, J.W. Goethe University Hospital, Frankfurt; J Bogner, Medizinische Poliklinik, Munich; G. Fätkenheuer, Universität Köln, Cologne.
Georgia: (N. Chkhartishvili) Infectious Diseases, AIDS & Clinical Immunology Research Center, Tbilisi.
Greece: (H. Sambatakou), Ippokration General Hospital, Athens; G. Adamis, N. Paissios, Athens General Hospital ‘G Gennimatas’, Athens.
Hungary: (J. Szlávik), South-Pest Hospital Centre – National Institute for Infectology and Haematology, Budapest.
Iceland: (M. Gottfredsson), Landspitali University Hospital, Reykjavik.
Ireland: (E. Devitt), St. James's Hospital, Dublin.
Israel: (L. Tau), D Turner, M Burke, Ichilov Hospital, Tel Aviv; E Shahar, L.M. Wattad, Rambam Healthcare Campus, Haifa; H. Elinav, M. Haouzi, Hadassah University Hospital, Jerusalem; D. Elbirt, AIDS Center (Neve Or), Jerusalem.
Italy: (A. D’Arminio Monforte), Istituto Di Clinica Malattie Infettive e Tropicale, Milan; R. Esposito, I. Mazeu, C. Mussini, Università Modena, Modena; F Mazzotta, A Gabbuti, Ospedale S Maria Annunziata, Firenze; A. Lazzarin, A. Castagna, N. Gianotti, Ospedale San Raffaele, Milan; M. Galli, A. Ridolfo, Osp. L. Sacco, Milan.
Lithuania: (V. Uzdaviniene) Vilnius University Hospital Santaros Klinikos, Vilnius; R. Matulionyte, Vilnius University, Faculty of Medicine, Department of Infectious Diseases and Dermatovenerology, Vilnius.
Luxembourg: (T. Staub), R Hemmer, Centre Hospitalier, Luxembourg.
Montenegro: (S. Dragas), M Stevanovic, Clinical Center of Montenegro, Podgorica.
Netherlands: (Marc vd Valk), Academisch Medisch Centrum bij de Universiteit van Amsterdam, Amsterdam.
North Macedonia: (J. Trajanovska), University Clinic for Infectious Diseases & Febrile Conditions, Mother Teresa 17, Skopje.
Norway: (D.H. Reikvam), A Maeland, J Bruun, Oslo University Hospital, Ullevaal.
Poland: (B. Knysz), B. Szetela, M. Inglot, Medical University, Wroclaw; E. Bakowska, Centrum Diagnostyki i Terapii AIDS, Warsaw; R. Flisiak, A. Grzeszczuk, Medical University, Bialystok; M. Parczewski, K. Maciejewska, B. Aksak-Was, Medical University, Szczecin; M. Beniowski, E. Mularska, Osrodek Diagnostyki i Terapii AIDS, Chorzow; E. Jablonowska, J. Kamerys, K. Wojcik, Wojewodzki Szpital Specjalistyczny, Lodz; I Mozer-Lisewska, B. Rozplochowski, Poznan University of Medical Sciences, Poznan.
Portugal: (A. Zagalo), Hospital Santa Maria, Lisbon; K. Mansinho, Hospital de Egas Moniz, Lisbon; F. Maltez, Hospital Curry Cabral, Lisbon.
Romania: (R. Radoi), C. Oprea, Carol Davila University of Medicine and Pharmacy Bucharest, Victor Babes Clinical Hospital for Infectious and Tropical Diseases, Bucharest.
Russia: D. Gusev, Medical Academy Botkin Hospital, St Petersburg; T Trofimova, Novgorod Centre for AIDS, Novgorod; I Khromova, Centre for HIV/AIDS & and Infectious Diseases, Kaliningrad; E Kuzovatova, Academician I.N.Blokhina Nizhny Novgorod Scientific Research Institute of Epidemiology and Microbiology, Nizhny Novgorod; E Borodulina, E Vdoushkina, Samara State Medical University, Samara.
Serbia: (J Ranin), The Institute for Infectious and Tropical Diseases, Belgrade.
Slovenia: (J Tomazic), University Clinical Centre Ljubljana, Ljubljana.
Spain: (JM Miro), JM Miró, M. Laguno, E. Martinez, F. Garcia, JL Blanco, M. Martinez-Rebollar, J. Mallolas, P Callau, J Rojas, A Inciarta, Hospital Clinic – IDIBAPS University of Barcelona, Barcelona; S Moreno, S. del Campo, Hospital Ramon y Cajal, Madrid; B Clotet, A Jou, R Paredes, J Puig, JM Llibre, JR Santos, Infectious Diseases Unit & IrsiCaixa AIDS Research Institute, Hospital Germans Trias I Pujol, Badalona; P Domingo, M Gutierrez, G Mateo, MA Sambeat, Hospital Sant Pau, Barcelona; JM Laporte, Hospital Universitario de Alava, Vitoria-Gasteiz.
Sweden: (V Svedhem), A Thalme, A Sonnerborg, Karolinska University Hospital, Stockholm; J Brännström, Venhälsan-Sodersjukhuset, Stockholm; L Flamholc, Malmö University Hospital, Malmö.
Switzerland: (K Kusejko), D Braun, University Hospital Zurich; M Cavassini, University Hospital Lausanne; A Calmy, University Hospital Geneva; H Furrer, University Hospital Bern; M Battegay, University Hospital Basel; P Schmid, Cantonal Hospital St. Gallen.
Ukraine: A Kuznetsova, Kharkov State Medical University, Kharkov; J Mikhalik, Crimean Republican AIDS centre, Simferopol; M Sluzhynska, Lviv Regional HIV/AIDS Prevention and Control CTR, Lviv.
United Kingdom: A Milinkovic, St. Stephen's Clinic, Chelsea and Westminster Hospital, London; AM Johnson, E Simons, S Edwards, Mortimer Market Centre, London; A Phillips, MA Johnson, A Mocroft, Royal Free and University College Medical School, London (Royal Free Campus); C Orkin, Royal London Hospital, London; A Winston, Imperial College School of Medicine at St. Mary's, London; A Clarke, Royal Sussex County Hospital, Brighton; C Leen, Western General Hospital, Edinburgh.
The following centers have previously contributed data to EuroSIDA:
Medical University, Gdansk, Poland
Infectious Diseases Hospital, Sofia, Bulgaria
Hôpital de la Croix Rousse, Lyon, France
Hôpital de la Pitié-Salpétière, Paris, France
Unité INSERM, Bordeaux, France
Hôpital Edouard Herriot, Lyon, France
Bernhard Nocht Institut für Tropenmedizin, Hamburg, Germany
1st I.K.A Hospital of Athens, Athens, Greece
Ospedale Riuniti, Divisione Malattie Infettive, Bergamo, Italy
Ospedale di Bolzano, Divisione Malattie Infettive, Bolzano, Italy
Ospedale Cotugno,III Divisione Malattie Infettive, Napoli, Italy
Dérer Hospital, Bratislava, Slovakia
Hospital Carlos III, Departamento de Enfermedades Infecciosas, Madrid, Spain
Kiev Centre for AIDS, Kiev, Ukraine
Luhansk State Medical University, Luhansk, Ukraine
Odessa Region AIDS Center, Odessa, Ukraine
St Petersburg AIDS Centre, St Petersburg, Russia
Infectology Centre of Latvia, Riga, Latvia
University di Roma la Sapienza, Rome, Italy
Istituto Nazionale Malattie Infettive Lazzaro Spallanzani, Rome, Italy
EuroSIDA Steering Committee
Steering Committee: I Karpov, M Losso, J Lundgren, J Rockstroh, I Aho, LD Rasmussen, V Svedhem, G Wandeler, C Pradier, N Chkhartishvili, R Matulionyte, C Oprea, JD Kowalska, J Begovac, JM Miró, G Guaraldi, R Paredes
Chair: G Wandeler
Co-Chair: R Paredes
Study lead: L Peters
EuroSIDA staff
Coordinating Centre Staff: L Peters, JF Larsen, A Bojesen, B Neesgaard, N Jaschinski, O Fursa, M Sather, D Raben, EV Hansen, D Kristensen, AH Fischer, SK Jensen, TW Elsing
Statistical Staff: A Mocroft, A Phillips, J Reekie, A Cozzi-Lepri, S Amele, A Pelchen-Matthews, A Roen, ES Tusch, W Bannister
∗Study members are listed in the appendix.
Conflicts of interest
There are no conflicts of interest.
