Hepatitis C elimination in Sweden: Progress, challenges and opportunities for growth in the time of COVID‐19

Abstract Background & Aims In 2014, the burden of hepatitis C virus (HCV) in Sweden was evaluated, to establish a baseline and inform public health interventions. Considering the changing landscape of HCV treatment, prevention, and care, and in light of the COVID‐19 pandemic, this analysis seeks to evaluate Sweden's progress towards the World Health Organization (WHO) elimination targets and identify remaining barriers. Methods The data used for modelling HCV transmission and disease burden in Sweden were obtained through literature review, unpublished sources and expert input. A dynamic Markov model was employed to forecast population sizes and incidence of HCV through 2030. Two scenarios (‘2019 Base’ and ‘WHO Targets’) were developed to evaluate Sweden's progress towards HCV elimination. Results At the beginning of 2019, there were 29 700 (95% uncertainty interval: 19 300‐33 700) viremic infections in Sweden. Under the base scenario, Sweden would achieve and exceed the WHO targets for diagnosis, treatment and liver‐related death. However, new infections would decrease by less than 10%, relative to 2015. Achieving all WHO targets by 2030 would require (i) expanding harm reduction programmes to reach more than 90% of people who inject drugs (PWID) and (ii) treating 90% of HCV + PWID engaged in harm reduction programmes and ≥7% of PWID not involved in harm reduction programmes, annually by 2025. Conclusions It is of utmost importance that Sweden, and all countries, find sustainability in HCV programmes by broadening the setting and base of providers to provide stability and continuity of care during turbulent times.


| BACKG ROU N D
In 2014, the burden of hepatitis C virus (HCV) in Sweden was evaluated and published, to establish a baseline and inform public health interventions. 1 Just 2 years later, the 69th World Health Assembly unanimously voted to adopt a Global Health Sector Strategy for the elimination of hepatitis as a public health threat by 2030. 2 Those targets include increasing the proportion of diagnosed patients to 90%, increasing treatment coverage to 80%, reducing new infections by 90% and reducing mortality by 65%. 2 Since that initial analysis in 2014, Sweden has made large strides in HCV treatment and prevention. Access to HCV treatments has been established free of charge to patients through cost sharing agreements with the Swedish states and healthcare regions (70% of costs covered by the state and 30% covered by the healthcare region). National treatment guidelines have been expanded to include people who inject drugs (PWID) and those with acute infections.
Additionally, harm reduction programmes have been established across the country and strengthened to include HCV treatment and care. 3,4 In Stockholm, harm reduction programmes have been effective in lowering the viremic prevalence of HCV among participants from 55% to 40%. 5 The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), resulted in a unique challenge for healthcare systems globally and in Sweden. As of 18 November 2020, 196 446 people in Sweden tested positive for COVID-19 with 6321 total deaths reported. 6 Although Sweden never experienced a 'hard lockdown', COVID-19 impacted HCV care as well as harm reduction and addiction treatment services. Experiences vary by region and clinic and range from disrupted outreach activities (Stockholm) to a temporary pause in treatment starts (Örebro and Skåne) (personal communication with the authors). In Gothenburg, for example, the infectious disease clinic was used as the COVID-19 clinic, resulting in a temporary discontinuation, from April until May 2020, in treatment within that setting.
At a national level, the numbers of patients diagnosed with HCV (as reported to Folkhälsomyndigheten [The Public Health Agency of Sweden]) were reduced by 27% from January to October 2020, compared with the same time frame in 2019. 7 Similarly, HCV treatment starts were reduced by 55%, from January to October 2020, compared with the same time frame in 2019 (personal communication with Ola Weiland, InfCare Hepatitis Register). 8 Some reduction in treated patients could be attributed to a waning population of warehoused patients; however, a decrease in newly diagnosed patients and restricted availability to outreach programmes was also experienced (either due to not yet started activities or ongoing activities restricted due to . A further concern is that independently of COVID-19, Sweden has experienced large loss to follow up among diagnosed HCV infected patients in care at hospitals with available treatment, identifying an unmet need to expand care beyond this setting 9 Considering the changing landscape of HCV treatment, prevention and care in Sweden, and in light of the COVID-19 pandemic, this analysis seeks to evaluate Sweden's progress towards the World Health Organization (WHO) elimination targets and identify remaining barriers.

| ME THODS
The data used for modelling were obtained through literature review, unpublished sources and expert input. Next, a dynamic Markov model was used to forecast the disease burden and transmission of HCV. The methodology for calculating new infections due programmes to reach more than 90% of people who inject drugs (PWID) and (ii) treating 90% of HCV + PWID engaged in harm reduction programmes and ≥7% of PWID not involved in harm reduction programmes, annually by 2025.

Conclusions:
It is of utmost importance that Sweden, and all countries, find sustainability in HCV programmes by broadening the setting and base of providers to provide stability and continuity of care during turbulent times.

Lay Summary
Sweden is on-track to achieve three of the four World Health Organization targets for hepatitis C virus (HCV) elimination, but reducing new infections will require increased access to HCV treatment for people who inject drugs. COVID-19 exposed weaknesses in HCV outreach and care programmes that could be addressed by expanding the base of providers who can diagnose and treat HCV.
This would alleviate the burden on infectious disease clinics and hospitals dealing with COVID-19, while ensuring better continuity of care for HCV patients.
to transmission among PWID is described in the Appendix. Inputs are included in the Appendix and briefly described here.

| Hepatitis C virus disease burden model
Hepatitis C virus prevalence, prevalence by age and sex, and the number of persons previously diagnosed and treated were used to seed and calibrate the model. Many of these inputs have been described in detail previously, with newer inputs described briefly

| Subpopulations and the hepatitis C virus transmission module
To model transmission of HCV among PWID, data around population size, harm reduction and injecting behaviours were collected from Additionally, the size of the HCV-infected population in Swedish prisons was estimated using data on the number of prisoners, annual turnover of prisoners and the proportion testing positive for anti-HCV.

| Modelled scenarios for the elimination of hepatitis C virus in Sweden
Once the model was developed, a variety of 'what-if' scenarios were run to evaluate the impact of future decisions. These scenarios were first envisaged before the COVID-19 pandemic began, but a new scenario has been added to evaluate the impact of real-world delays in treatment that have been experienced in Sweden as a result of the pandemic and is discussed in more detail in the next section. The scenarios included are as follows.
A baseline scenario (Base 2019) was developed using empirical diagnosis and treatment data through 2019. After 2019, screening was assumed to remain constant, resulting in fewer newly diagnosed cases each year (Table 1). Assuming no major improvements in case finding or linkage to treatment or harm reduction, the number of patients starting treatment each year would decrease (Table). However, TA B L E 1 Annual number diagnosed and initiating treatment, as well as treatment eligibility and SVR under the 2019 base and WHO targets scenarios, 2018-2030

| Uncertainty analysis and the impact of COVID-19
Crystal Ball release 11.  Table 2). Of these, more than 80% had already been diagnosed; however, due to incomplete linkage to care and loss to follow-up, fewer than 20% of prevalent infections were initiated on treatment in the same year ( Figure 1) Under the 2019 base scenario, Sweden was projected to achieve and exceed the WHO targets for diagnosis, treatment and liverrelated deaths ( Figure 3, Table 2). Current efforts to treat HCV among PWID in OST and NSP would reduce total prevalent infections; however, new infections were projected to decrease by less than 10% relative to a 2015 comparison point (   A perhaps greater concern is that although more than 80% of HCV+ patients in Sweden currently are estimated to have been diagnosed, most infectious diseases clinics no longer have patients waiting for treatment. As a result, the number of patients treated annually is declining. The proportion of people previously diagnosed is based on cases notified to the PHA and previous publications 1 ;

| D ISCUSS I ON
however, this estimate has not been assessed by any recent general population studies. One study among pregnant women and their partners found that more than 83% of persons testing positive for HCV-RNA had been previously diagnosed, and more than 50% of the diagnosed persons were previously lost to follow up. 14 In order to eliminate HCV, all previously diagnosed patients need to be rescreened or reidentified and linked to care-either in a traditional setting or in a setting in which they are already linked to care (e.g.  screening with reliable linkage to treatment and care will be important for quickly identifying new infections and reinfections before patients are lost to follow up. Lastly, current regional reimbursement challenges may discourage smaller practices from treating for HCV, which should be addressed.

| CON CLUS ION
COVID-19 has impacted HCV treatment as well as NSP and OST in Sweden; but the full extent of the disruptions is yet to be seen. As a result, it is of utmost importance that Sweden, and all countries, find sustainability in treatment by broadening the setting and base of providers to provide stability and continuity of care during turbulent times. Through increased harm reduction efforts and treatment among PWID, Sweden can reduce the incidence of HCV by 90% by 2030 and achieve the WHO targets. This will require a concerted effort and prioritization of hepatitis at a time when patients may be reluctant or unable to seek traditional care.