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

[50]
der Meer et al. were able to detect all-cause mortality benefit among patients with chronic HCV infection
and advanced hepatic fibrosis who achieved SVR to interferon-based treatment. However, the retrospec-
tive nature of the study could have led to selection of a relatively healthy cirrhotic HCV population, because
[50]
interferon therapy is contraindicated in patients with moderate to severe cirrhosis . This selection bias is
minimized by DAA therapies due to improved safety and efficacy profiles, even among patients with higher
Model for End-Stage Liver Disease (MELD) scores. There is much anticipation to observe data regarding
both all-cause and liver-related survival benefits, as the experience with DAA therapy accumulates. At the
[88]
latest European Association for the Study of the Liver conference, Calvaruso et al. reported results from
a large real-world setting cohort with patients using a variety of DAA regimens. According to the authors,
achieving SVR significantly reduced mortality from both liver disease-related and unrelated causes at all
stages of liver fibrosis. In another report from the same conference, the European Liver Transplant Registry
reported that, while the total number of liver transplants performed in Europe remained stable over the last
decade, the percentage of transplants related to HCV fell significantly from 23% in the interferon era to 11%
[89]
in the DAA era .

BARRIERS TO HCV ELIMINATION
The global burden of viral hepatitis is increasing since 1990, reaching 1.46 million deaths in 2013, exceeding
that of HIV (1.3 million), tuberculosis (1.2 million) and malaria (0.5 million deaths). HCV is responsible for
[90]
approximately 30% of the overall viral hepatitis mortality . The advent of DAA therapy and its extraordinary
clinical impact hold promise that HCV elimination as a public health threat is a reachable goal by 2030. Ac-
cording to the global health sector strategy on viral hepatitis 2016-2021, HCV elimination can be achieved by
diagnosing 90% of people infected and treating 80% of the people diagnosed. Such a strategy is predicted to re-
[9]
duce new infections by 90% and mortality by 65% . This report also established a baseline for tracking prog-
ress of this global strategy, where only 20% (14 million) of 71 million people living with chronic HCV knew
their diagnosis and a disappointing 7.4% of those diagnosed (1.1 million) started HCV treatment in 2015.

[91]
DAAs can only benefit patients who are screened, diagnosed, linked to care, engaged in care and treated .
The HCV care cascade concept, adapted from public health efforts in HIV, identifies multiple missed oppor-
tunities to address the HCV burden at local, national and global levels [92,93] . In order for each HCV infected
individual to move down the cascade from diagnosis to HCV treatment, a myriad of variables interact with
each other in multifaceted ways. Adapted health care utilization frameworks, such as the Gelberg-Andersen
model, are useful tools to examine and understand factors influencing the impact of specific care actions
(such HCV screening, linkage to care, engagement, treatment initiation) among vulnerable, high-risk popu-
[94]
lations . Health care utilization is in general influenced by traditional predisposing (ethnicity, age, educa-
tion, gender), enabling factors (source of care, health insurance, income) as well as need (perceived health,
medical conditions, awareness of HCV-positive status). For instance, progressive movement of HCV-positive
homeless individuals down the cascade would also be influenced by additional, more specific predisposing
(histories of child abuse, jail/prison, drug and alcohol use, mental illness, and risky sexual behavior), and
enabling factors (barriers to care, competing needs, lack of housing, food security, and case management).
It is known that the many of the highest HCV prevalent populations (i.e., PWID, homeless and socioeco-
[94]
nomically disadvantaged) often lack access to HCV testing and continuity of care . Case management and
regular sources of care attenuates social vulnerability, and robust support systems are needed in response to
these complex and challenging demands [95-97] .

Several determinants of health care utilization among vulnerable individuals, including illicit drug use, of-
ten introduce stigma to the care cascade equation, furthering the hardships of those in need of HCV care
[98]
and cure . Perceived stigma associated with HCV infection leads to anxiety, fear of transmission to oth-
ers, reduced intimacy in relationships, denial (reluctance to seek medical care for addiction and/or HCV