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Page 6 of 18 Franco et al. Hepatoma Res 2018;4:74 I http://dx.doi.org/10.20517/2394-5079.2018.94

egies [136] . The close relationship between injecting drug use, incarceration, and prevalence of blood-borne
viruses makes correctional centers a crucial setting for enhanced DAA therapy access and broad prevention
strategies [134] . The United Nations Basic Principles for the Treatment of Prisoners state that prisoners “shall
have access to the health services available in the country without discrimination on the grounds of their
[137]
legal situation” . Unfortunately, this principle has been infrequently applied in real life and in most coun-
tries prisoners have a lesser possibility of assistance and care than other citizens [138] . Once in prison, over-
crowding, violence, separation from family and emotional problems are additional reasons that may induce
inmates to start or continue unsafe habits, fueling high incidence rates that exceeds 30 per 100 persons per
year [139-141] . Proper treatment of chronic hepatitis C in prison is rare due to social and educational reasons
and, not least, because most inmates with HCV infection remain unaware of their status, and several other
barriers (drug abuse, stress, fear, lack of confidence, stigma, difficulty to relate to the health personnel) adds
up to the lack of liver disease specialists in prison [142-145] . Although many prisoners are incarcerated for long
periods, the average length of stay can be shorten to weeks or months in several cases, which makes it dif-
ficult to complete the clinical itinerary from screening to post-treatment follow-up [146,147] .

Compared to interferon, DAA therapies are easier to roll out in community and outreach settings, but in
reality there is a significant lack of experience and engagement in routine HCV screening and treatment
in primary care, and misconceptions about whom to screen, risk of progression of liver disease or therapy
itself in this setting [148-150] . Even specialists in liver disease may have limited experience treating HCV, or be
selective about which patients they consider as good candidates for therapy and fail to recommend treat-
ment because of concerns about nonadherence, drug use or risk of re-infection [151,152] . Furthermore, there are
insufficient numbers of providers who can and are willing to treat HCV, and insufficient resources for case
managers, navigators and social workers in suitable capacity to attend a growing demand of patients in need
of treatment [153] .

All-oral treatments are very expensive, with initial wholesale acquisition cost (WAC) of 90,000 US dollars
per 3 months treatment course (or $1000/pill). While the prices of DAAs have decreased rapidly in some
countries, they remain variably expensive and remain unaffordable in others [154] . In the US for example,
DAA pricing is influenced by a chain of multiple organizations, including pharmaceutical companies (who
determine the WAC), Pharmacy Benefit Managers (PBMs) (intermediaries between the former and health
insurance companies), insurance companies (who determine the preferred choice of regimens and out-of-
pocket expenses for patients), and specialty pharmacies (who receive dispensing fees and may contract with
insurance companies, PBMs, or pharmaceutical companies to provide adherence support, management of
adverse effects, and outcome measurements). In this system chain, negotiated drug prices are held as con-
fidential business contracts, with no transparency regarding the actual prices paid for hepatitis C drugs.
Nevertheless, the recently observed increases in WAC discounts or rebates have implied a reduction in drug
costs to payers [85,155,156] . In other countries, pharmaceutical companies negotiate pricing directly with the
payers (usually a nationalized system), where licensing agreements may allow for production of generic for-
mulations and transparency in negotiated cost of drugs to payers [155,157] . Increasing generic competition has
lowered DAA price, but those remain high (tens of thousands of dollars per treatment course) in developed
countries, in those middle-income countries that do not have access to generic formulations, and in those
countries who fall outside of license agreements. This creates a heavy financial burden on many health sys-
tems and leads to treatment rationing [154] . Comparatively, generic versions of new HCV medicines have been
available for under 500 US dollars per patient in some countries, and the production cost of two DAAs could
be as low as 200 US dollars per patient. Hence, further price reductions could be achieved and will be needed
to increase the number of patients treated [157] .

In addition to drug cost, the cost of diagnosis and disease evaluation also represent an important financial
burden, especially in low to middle income countries (LMICs), which has brought uncertainty as to the opti-