Summary of main literature
The majority of existing published economic evaluations of testing and treatment for HBV have been performed in HICs where the general population prevalence is low. Only one study was performed in a LIC setting [
22]. Two studies evaluated HBV testing in the general population [
23] and seven studies in ‘high-risk’ groups in HIC settings (all but one looked at testing in migrant or refugee populations) [
24‐
30]. The studies used different methods of testing the ‘high risk groups’ including, in the clinical setting, [
27,
26] community outreach methods [
26] and overseas screening [
30]. Eight out of 9 studies were cost-effectiveness analyses using various outcome measures including cost per QALY gained, cost per DALY averted and cost per case screened. Only one study was a cost-benefit analysis. All studies used static cohort models. Most models were simulated using hypothetical cohorts and only 2 used actual screening data to populate the model. The studies of ANC testing did not consider antiviral therapy to the mother and only looked at the benefit of testing in order to guide vaccination strategies to reduce mother-to-child transmission, and were therefore excluded in this review.
General population level testing
The studies looking at the cost-effectiveness of offering testing and treatment to the general population were from the USA [
23] and The Gambia [
5].
Eckman et al., [
23] examined the cost-effectiveness of HBsAg testing of asymptomatic outpatients in a primary care setting in USA to review the US guidelines on screening populations with a prevalence above 2%. They used a hypothetical cohort (35 year old male) living in a region with a prevalence of 2%. Screening was then followed by treatment with one of four regimens and compared to a no screening strategy. Screening and treatment with oral antiviral therapy was found to be cost-effective with an incremental cost effectiveness ratio (ICER) of $29,230/QALY (USD 2008). The ICER remained below their reported willingness-to-pay (WTP) threshold of $50,000/QALY gained, even down to a population prevalence of 0.3%. Limitations of this study include an unrealistic assumed 100% adherence to treatment. Furthermore, the screening costs only included the cost of a clinic visit and HBsAg testing and no sensitivity analysis was reported on the cost parameters.
The study by Nayagam et al. [
22] used primary cost and effectiveness data from the Prevention of Liver Fibrosis and cancer in Africa (PROLIFICA) study [
5] a large-scale intervention programme in The Gambia to determine the cost-effectiveness of adult community-based screening and treatment for HBV infection. The baseline HBsAg prevalence was 8.8%, uptake of screening 68.9%, linkage to care 81.3% and adherence to antiviral therapy 80.9%. Annual drug cost was $48, which is the generic price of tenofovir available to HIV programmes. Compared to status quo, the screen and treat strategy was found to have an ICER of $540 per DALY (USD 2013) averted ($645 per LY saved or $511 per QALY gained). The authors acknowledge that WTP thresholds levels, and their use, are highly debated in LMICs. However, it can be regarded as cost-effective if using the commonly used WHO WTP thresholds of one to three times the country’s GDP per capita to define a cost-effective intervention (GDP per capita = $487 in The Gambia [
31]). This was the only published study on the cost-effectiveness of HBV screening and treatment performed in a LMIC setting. A strength of this study includes the use of primary screening data to populate the model and comprehensive sensitivity analyses on prevalence, costs and epidemiological parameters.
Testing of ‘high-risk’ groups in HIC
There were six studies that evaluated the cost-effectiveness of screening and treatment in migrant or refugee populations in HICs [
24‐
28,
30], and one examined screening all groups classified as ‘high risk’, in accordance with Italian guidelines [
29].
The study by Wong and colleagues in 2011, looked at the cost-effectiveness of screening and treatment of immigrants for CHB, in Canada [
27]. They considered a screen and treat strategy and a screen, treat or vaccinate strategy, with status quo (no screening). Screening was offered by the primary care physician at a visit scheduled for another reason, described by the authors as a ‘case-finding’ strategy. They used a hypothetical cohort (35 year old male) with a baseline HBsAg prevalence among the immigrant population of 4.81%. Screening uptake was 100% and it was assumed that 90% of those eligible would receive treatment. The screen and treat strategy (with tenofovir) had an ICER of C$69,000/QALY gained (Canadian$ in 2008). The authors acknowledge the uncertainty around WTP thresholds and describe this is as likely to be a moderately cost-effective intervention. The study explores cost-effectiveness by country of origin, revealing higher cost-effectiveness of a screen and treat strategy for immigrants born in east Asia, central and West Africa, corresponding with higher prevalence rates. A strength of this model is that it is more clinically representative of HBV than many of the other models. However, it uses high, and probably unrealistic, assumptions for uptake of screening.
Another Canadian study by Rossi et al. (2013) [
25] looked at combinations of scenarios involving screening, treatment and vaccination, among newly arrived immigrants and refugees. A hypothetical cohort of 250,000 immigrants was modelled using a societal perspective. The baseline assumptions were 70% acceptance of screening, 60% linkage to care, 75% of those eligible will have treatment and annual cost of antiviral drugs $8089. The screen and treat scenario was found to be the most cost-effective with an ICER of C$40,880/QALY gained (Canadian $ in 2011) and remained robust over all one way sensitivity analyses. This strategy exceeds the Canadian WTP threshold adopted in this study of C$50,000/QALY, when HBsAg prevalence is less than 3%.
An earlier study by Hutton et al. [
24] looked at the cost-effectiveness of screening and vaccination of Asian Pacific Islander adults for HBV, comparing four strategies of combinations of screen, treatment and vaccination. They adopted a societal perspective and used a hypothetical cohort with an average age of 40 years and a HBsAg prevalence of 10%. The screen and treat strategy was the most cost-effective with an ICER of $36,000/QALY (USD in 2006) gained (compared to no screening), even down to an HBsAg prevalence of 1%.
Another, more recent, US study by Jezwa and colleagues [
30], compared the cost-benefits of two overseas programmes for reducing HBV infection among refugees. They compared two strategies i. vaccination only and ii. screening, vaccination and suggested onward treatment on arrival in USA if HBsAg positive. Their baseline assumptions included a HBsAg prevalence of 6.8%, 100% adherence with screening, 60% of those tested positive for HBsAg linked to specialist care and 90% adherence to treatment. This was the only economic evaluation which adopted a cost-benefit method, where mortality risk reduction benefits were estimated using a value of statistical life approach (VSL). They found that the screening strategy had a positive net benefit of $90 million after 5 years, when VSL was estimated at $5 million (USD 2012). A strength of this study was the use of original data sets of refugee populations in two US states for the epidemiological data.
The study by Veldhuijzen et al. [
28] was the only European study which looked at the cost-effectiveness of HBV screening & early treatment of migrants. An active screening method was used, where the target population is identified using the municipal population registry and they receive a postal invitation to attend screening. Their baseline HBsAg prevalence was 3.35%, with 35% participation rate in screening, 58% linkage to specialist care and 75% adherence. Compared to status quo, screening and treatment had an ICER of €8966/QALY gained and was therefore reported as cost-effective compared to the authors’ reported WTP threshold of €20,000/QALY gained. This study found that despite using low rates of participation throughout the cascade of care, that screening is still likely to be cost-effective. A strength of this study was the inclusion of comprehensive screening programme costs including personnel costs.
A study by Rein et al. [
26] looked at different methods of screening for HBV among the Asian migrant population in the USA, using actual screening data. This was a descriptive study with outcome measures given as cost per person screened and cost per positive case detected. The screening methods analysed included testing at a community clinic and other more active community outreach models where screening was performed at various events in the Asian community. The costs per person screened ranged from $40 to $280 depending on the method used. Integrating screening into clinical services was found to be the least costly method, but reached least people, whereas extending screening outside the clinical setting was more costly as it included costs of organising events and volunteer time, but reached more people. This study provides useful insights into the relative costs of various screening methods and, unlike some of the other studies, it includes full costs including those associated with recruiting patients. However, it does not provide long term outcomes following on from a positive screening test and is therefore limited in its generalizability.
Ruggeri et al. [
29] looked at screening of all groups defined as ‘high risk’ (according to local Italian guidelines), and compared the cost effectiveness of screening followed by antiviral treatment for CHB. This was compared to the status quo strategy of no screening, but treatment for cirrhosis and HCC stages only. A hypothetical cohort of 100,000 individuals was considered and screening and treatment was found to be cost-effective with an ICER €18,255/QALY. However, this study included treatment with suboptimal drug combinations and was based on unrealistic 100% adherence rates to testing and treatment.