HCV New Drugs

In the United States, 2.7–3.9 million persons (1.2%–1.8% of the population) are chronically infected with hepatitis C virus (HCV) [1], and 49%–75% of them are unaware of their HCV status [2, 3]. In some European countries, the HCV prevalence is similar or even higher, and the proportion of persons unaware of their infection is identical. For example, in Spain, approximately 2% of the population is chronically infected with HCV [4], and 65% are unaware of their infection [5]. In Italy, where the prevalence rate is twice as high [6, 7], 55% of HCV-infected persons are unaware of their infection [8]. Because of the asymptomatic nature of chronic hepatitis C, most people infected with HCV are not aware that they have been infected until symptoms of cirrhosis or hepatocellular carcinoma appear, possibly years later. Prevention of these complications requires treatment before patients reach advanced stages of the disease, at which time treatment efficacy is significantly lower than at earlier stages of the disease. The recently marketed direct-acting antiviral drugs can significantly increase the rate of sustained virological response in treatment-naive patients with HCV genotype 1, the most prevalent circulating strain in North America and Western Europe: 70%–75% in patients with moderate fibrosis (fibrosis score ≤ F2) and 50%–60% in those with advanced fibrosis (F3–F4) [9–14]. HCV-infected patients should therefore be screened at earlier stages of the disease to benefit from a treatment of enhanced efficacy. Moreover, previous mathematical modeling work suggested that HCV antiviral treatment could prevent HCV transmission among injection drug users [15]. The recent availability of new, less aggressive approaches for determining liver fibrosis and suitability for treatment and, more important, of new and considerably more efficacious HCV combinations, underscores the importance of early screening of hepatitis C. 

Current US guidelines recommend screening for a history of risk of exposure to HCV virus and testing selected individuals having an identifiable risk factor [16, 17]. Most European countries apply similar screening policies [18–22]. However, the high proportion of HCV-infected patients unaware of their infection underscores the limits of this approach and the need to reconsider HCV testing strategies. 

Why does a risk-factor-based HCV screening strategy not work? Probably because, as with the human immunodeficiency virus (HIV) setting, patients report their risk status inaccurately, while providers lack the time and expertise necessary to conduct risk evaluation [23]; moreover, targeting can cause anxiety during the patient–provider discussion. When rethinking new HCV screening strategies, we might first consider training clinicians and developing tools, such as behavioral and clinical instruments, to better identify those at high risk of HCV infection. Recommendations and proposals for HCV screening could be expanded to one-time screening of regions or birth cohorts with a high prevalence of HCV. Finally, one-time HCV screening could be considered for the entire adult population. 

In this issue of Clinical Infectious Diseases, Coffin et al compare the effectiveness and cost-effectiveness of adding one-time chronic hepatitis C screening of the US population aged 20–69 years to the current risk factor–based approach and also considering one-time screening of only those born between 1945 and 1965 (who have the highest prevalence of hepatitis C) [24]. For this purpose, the authors use a decision-analytic model and available knowledge on the natural history of a disease and treatment efficacy to compare benefits and costs of various interventions and identify those that are most cost effective. When experimentation is not feasible, mathematical modeling, which would extend the time horizon of the usual epidemiological tools (ie, observational cohorts and randomized controlled trials) and evaluate more strategies than possible in a single trial, might be a valuable tool for evaluating alternative interventions and establishing priorities for health interventions. In their study, Coffin et al demonstrate that the addition of one-time screening of the general adult US population for chronic hepatitis C would be cost effective compared with the current practice of screening only high-risk individuals under various scenarios. They also emphasize the fact that screening only high-risk birth cohorts may be more cost effective than screening the general population. The study by Coffin et al is novel because it is one of the rare studies evaluating the cost-effectiveness of one-time HCV testing in adults. 

Two other analyses recently evaluated the cost-effectiveness of different HCV screening strategies in the United States, but they both considered only one-time screening of high-risk birth cohorts [25, 26]. Both studies indicated that this strategy was likely to provide substantial health benefits by reducing lifetime cases of advanced liver disease and HCV-related deaths. It would also be cost effective for conventional willingness-to-pay thresholds and should therefore be considered in place of a risk-based screening strategy alone [25]. 

In light of the results by Coffin et al, should we recommend one-time HCV testing in adults, or should we rather consider one-time screening of high-risk birth cohorts? The results the study by Coffin et al, which require confirmation in other developed-country settings, seem to assign priority to one-time HCV testing of adults from a cost-effectiveness point of view. One-time HCV testing in the general population would be of interest because it could be performed at the same time as HIV testing, which is now recommended in the United States and France [27, 28]. However, issues other than safety, efficacy, and “added value” should be evaluated when considering implementation of new strategies including affordability [29]. In addition to evaluating the cost-effectiveness of new interventions, it is important to assess the financial consequences of introducing a new technology in a specific setting over the short-to-medium term (ie, a budget-impact analysis). Such an analysis, which may favor one-time screening of high-risk birth cohorts because it targets a smaller number of patients, will provide additional information for decision making in a context in which financial resources are scarce. 

In the near future, we will probably move toward new HCV testing strategies that expand current recommendations. New strategies should be implemented promptly. Indeed, as stated by Coffin et al, given the peak of the HCV epidemic in the United States, the cost of the public health burden of hepatitis C will substantially increase in the near future, and the window of time available for intervening is limited [24]. By targeting either birth cohorts or the general population, these screening strategies can only be successful if efforts are implemented to increase acceptability of screening by patients and clinicians and improve linkage to care.