HCV screening: Moving from theory to practice

To achieve hepatitis C virus (HCV) elimination by 2030, the WHO framework requires improved diagnostic yield, linkage to care and effective treatment.1 At present day, despite the great advances in response rates to HCV treatment, the WHO framework process is limited by the fact that only a minority of the HCV + population is identified and linked to care.2 For these reasons, it is important to identify optimal and realistic screening strategies. From a healthcare perspective, HCV represents an ideal condition to design population-based screening protocols. Indeed, a large number of patients are unaware of their condition, diagnosis is codified and can be established easily through blood tests, HCV negatively impacts on morbidity and mortality, and most importantly HCV is curable with safe and well-tolerated medications. Over the years different screening strategies for HCV have been proposed. The first to be implemented was based on risk factors, meaning that people at higher risk for HCV infection owing to history of intravenous drug use, blood transfusion before 1990 or HCV-positive family members were identified as ideal candidates for screening. However, this approach, currently in practice in many western countries, appears to be insufficient as demonstrated by the relatively stable share of undiagnosed population. Universal screening regardless of pretest risk or age, as endorsed by AASLD and ISDA guidelines, is intuitively the most comprehensive measure, although its applicability is hampered by several practical limitations, which include first and foremost costs.3 A universal screening requires the highest number of tests virtually equal to the whole population. Secondly, if actively implemented, universal screening could generate a bottleneck in the access to care and overload the health system, thus leading to a worse linkage to care. Finally, the challenge of reaching and testing the whole population might be impossible for any healthcare system. Of note, a successful example of universal HCV screening was conducted in Egypt between October 2018 and April 2019. In a paramount national effort, 79.4% of 62.5 million Egyptian adults were tested, of these 4.61% had positive HCV serology, although more than half (2.59%) had previously been treated with DAA. Overall, 1.5 million people were tested for HCV-RNA, 76.5% were positive and 91.8% of them started treatment. The overall cost of the campaign was $207.1 million corresponding to $85.41 per HCV viremic patient identified, and $130.62 per cured patient.4 For the abovementioned reasons, birth cohorts screening has been proposed as an alternative. These policies are based on the concept that if the epidemiology of HCV infection is well known and relatively stable over time, screening birth cohorts with the highest a priori risk for infection could prove cost-effective by combining both of the benefits of universal and risk-based testing. The epidemiological background shows that most HCV cases are clustered according to a common route of acquisition. For instance, in countries like Italy, France or Spain, most infections were acquired in the 1950s and 1960s through medical procedures including blood transfusion. On the other hand, in other countries, such as the US, HCV spread through intravenous drug use during the 1960s and 1970s. With these assumptions, it is possible to predict the prevalence (or pretest probability) of HCV infection in a given age cohort and concentrate screening efforts on it. Kondili et al demonstrate that in a high prevalence country, such as Italy, different screening programmes, including a universal screening, would be cost-effective.5 The authors conclude that the most cost-effective strategy in the Italian setting is a graduated cohort screening aiming at identifying younger patients at higher risk of transmitting HCV, although at lower prevalence of advanced disease, before expanding screening to the older population. Whether this approach is ethical and can be implemented in the framework of a universal public health system such as the Italian one cannot be proven by the current study. Targeting younger patients might prove beneficial in decreasing the incidence of new HCV infections and identifying asymptomatic patients with mild disease, but it could as well lead to a delay in diagnosis and treatment in patients with long-lasting HCV infection, significant comorbidities and more advanced liver disease. Most importantly, it remains unclear how cohort-based screening should be implemented. This last point is not trivial as all mass population screening campaigns, despite proven health benefits, are burdened by low adhesion rates, especially among individuals with lower socioeconomic status or with reduced access to primary care. Screenings for cervical, breast or colorectal cancer, which have been in practice for years, reach about 80%,6 70%,7 and 50%,8 respectively, of the desired population despite targeting conditions perceived as deadlier than hepatitis C. Interventions known to improve patient's engagement in screening protocols include contacting patients reminding them of their appointments, monetary incentives for primary care physicians who screen their patients and mailing testing kits for faecal occult blood