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Franco et al. Hepatoma Res 2018;4:74 I http://dx.doi.org/10.20517/2394-5079.2018.94 Page 7of 18

mal testing approaches and who to prioritize for testing in this setting [158] . Diagnostic testing involves labora-
tory-based immunoassays required to meet minimum safety, quality and performance standards, and rapid
diagnostic tests (RDT) with important role in settings where there is limited access to laboratory infrastruc-
ture and/or in populations where access to rapid testing would facilitate linkage to care and treatment [158] .
Directly following a reactive HCV antibody serological test result, the use of quantitative or qualitative nu-
cleid acid testing (NAT) for detection of HCV RNA is recommended as the preferred strategy to diagnose
viraemic infection and monitor treatment response. An assay to detect HCV core (p22) antigen, which has
comparable clinical sensitivity to NAT, is an alternative to NAT to diagnose viraemic infection [159] . Accord-
ing to recent WHO guidelines, focused serologic testing with HCV antibody (anti-HCV) should be offered
with linkage to prevention, care and services to high-risk populations; general population testing should
be approached in settings of high prevalence in the general population (2%-5% infection prevalence); and
birth cohort testing should be applied to specific identified birth cohorts of older persons at higher risk of
infection and morbidity within populations that have an overall lower general prevalence [158,159] . Such testing
strategies, although incurring in significant cost if applied to massive testing scale-up, should still hold rea-
sonable cost-effectiveness tailored to broad variations in gross domestic product worldwide, although there
is lack of evidence among LMICs [158] . Interestingly, studies have shown that the cost-effectiveness of testing
for HCV seems most sensitive to variations in prevalence, treatment efficacy, progression rates from chronic
HCV to cirrhosis, and levels of linkage to care and treatment, and relatively insensitive to costs of screening
and treatment [158,160-162] . Another barrier to HCV testing and evaluation scale-up is the cost involved in HCV
genotype ascertainment. This is required for a number of DAA regimens available, and certainly makes the
use pan-genotypic regimens an attractive cost-effective option, especially in countries with high prevalence
of non-GT1 HCV, that could potentially bypass genotype confirmation [163] . Simplifying testing algorithms
and lowering the cost of monitoring can dramatically cut costs of treatment for HCV in the future. For
instance, the cost of the current step-wise evaluation algorithms (screening for exposure using serology or
RDT; quantitative NAT testing for viremia confirmation, monitoring, efficacy assessment; and genotyping)
can be as high as 220-1100 USD; whereas the cost of potential future scenarios (screening for exposure using
serology, RDT, oral fluids or dried blood spots; qualitative NAT for viremia confirmation without genotyp-
ing, minimal viral load monitoring and efficacy assessment) could be as low as 15-75 USD [164] .

PROGRESS IN PUBLIC HEALTH RESPONSE
Public health strategies addressing the remarkable challenges of HCV elimination has leveraged sound epi-
demiological data, detailed expert opinion input and mathematical modelling. In order to inform treatment
and prevention strategies, as well as public health policy, efforts have focused on gathering country-specific
data [165] . Collectively, evidence estimates suggest that the HCV infection burden is highly variable world-
wide. For instance, the population prevalence of HCV viremia seems to range widely, from 0.3% in Austria,
England, Germany and France to 7.3% in Egypt. The latter country is clearly unique, even when compared
to Portugal, Brazil and the US with viremia prevalence nearing 1.0%-1.2% [166,167] . Within the estimated vire-
mic population, there are also significant variations in the estimated rates of individuals newly diagnosed in
each country (3%-14% per year) and treated (1%-11% per year) [167,168] . Liver fibrosis burden is also estimated
to be greater in countries with more generalized, older epidemics such as Egypt and Brazil, in opposition to
younger epidemics with large contributions of PWIDs (Australia, Czech Republic and Australia) [166] . While
the overall number of new HCV infections is expected to decline worldwide, the number of cases with ad-
vanced liver disease is expected to increase [169] . This dichotomy and epidemiological contrasts between coun-
tries is fueled by high cumulative prevalence, reason why the global strategy calls for significant reductions
of both the number of new infections and HCV-related mortality.

Modeling-based evidence, calibrated by country-specific epidemiological data, shows that sizable reductions
in incidence, morbidity and mortality can only occur if high-efficacy therapies are combined with increased
diagnosis and treatment access. Yearly treatment rates in the order of 10% are likely to position most coun-