School of Health and Life Sciences
Department of Nursing and Community Health
Academic Session 2018-19
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HEPATITIS C SCOTLAND: A CRITICAL REVIEW OF EPIDEMIOLOGICAL RISK FACTORS AND
NATIONAL STRATEGIES TO INFORM FUTURE INTERVENTIONS:
The emergence of the hepatitis c virus (HCV) was first recognised in 1989 (Shiffman,
2012). Thereafter it has infected 71 million people and claims responsibility for
approximately 399,000 deaths despite being curable (WHO, 2017). Each year an
average of 1.75 million people is diagnosed with HCV with an estimated global
prevalence of 2-3% (WHO, 2017; Hafez, 2017). In Scotland, its estimated that 1% of
the population totalling 50,000 people have an HCV infection (HPS. 2018; SPHO,
2018). The wider implications of HCV include physical and social costs, risk of
mortality, reduced quality of life, and economic loss (Mohammadzadeh, Derafshi and
Ghari, 2018; Webster, Klenerman and Dusheiko, 2015). In America, the financial
burden of treating HCV infections was projected to exceed $10 billion dollars
(Stepanova, 2017). Thus, highlighting its growing significance to public health and
health systems.
In Scotland, the prevalence of HCV is higher than the UK average and is described as
a severe public health risk (McNaughton et al, 2015; PHE, 2017). Although
interventions and new therapies to reduce transmission and prevalence have been
successful challenges remain (Hutchinson et al, 2006; Martin et al, 2013; Palmateer
et al. 2014; Lin et al, 2017). Nationally, these challenges developed from transmission
trends and the uptake of screening and treatment associated with people who inject
drugs (Fraser et al, 2018). Therefore, the following will attempt to discuss the
epidemiological risk factors associated with HCV in Scotland, identify trends, and
critique current prevention and management strategies to inform future interventions.
Hepatitis C is a highly infectious agent which is transferred through contact with
infected blood (Schietroma et al, 2018). It is a positive stranded ribonucleic-acid (RNA)
based virus which affects the liver (Webster, Klenerman and Dusheiko, 2015). The
virion is made up of a lipid membrane envelope consisting up of two glycoproteins
which facilitate its attachment to other cells for replication (González-Aldaco et al,
2018). These glycoproteins help prevent the destruction of the virus from the immune
system by blocking antibodies from attaching to cellular receptors (Miyamura et al,
2016). The virion replicates in the peripheral blood mononuclear cells and in the
hepatocytes of the liver, they reach the hepatic cells through the endothelium of
bordering blood vessels where they continue to replicate (Dubuisson and Cosset,
2014). The non-structured proteins that facilitate viral replication have become areas
of interest in vaccine development (Ashfaq et al, 2011),
The HCV infection can be acute or chronic. In the acute stage, between 10% and 15%
of infected hosts can spontaneously destroy the virus naturally through immune
responses (Li and De Clercq, 2017). If the viral load remains in the bloodstream after
six months it develops into a chronic infection (Likis, 2017). The prolonged presence
of HCV commonly leads to hepatological complications such as inflammation, cirrhosis
and liver cancer which are the leading cause for HCV mortality (Heim and Thimme,
2014; Simmons et al, 2019). Naturally, the common asymptomatic nature of this virus
means individuals are unaware of the infection until complications arise (Fourati,
2018).
The virus is heterogenous and can be categorised into a minimum of seven pathogenic
genotypes and over 80 subtypes with their distribution varying between geographical
location because of historical evolution resulting in nucleotide dissimilarity (Ashfaq et
al, 2011; Smith et al, 2014; Kamal, 2018). According to a systematic review by
Petruzziello et al (2016) involving 138 countries, the most common genotypes
worldwide are genotype one at 49.1%, then genotype three at 17.9%, followed by
genotype four at 16.8%, and respectfully genotype two at 11%, however these
estimates are limited by the lack of data from less developed areas.
According to Iveren (2018) the distribution in Scotland differs with genotype one
accounting for 45.6% of cases, genotype two at 5.6%, and genotype three at 47.9%
which is endemic in people who inject drugs (PWID). Nevertheless, changes in global
migration, transmission trends and population demographics have increased the
spread and emergence of genotypes into other regions (Petruzziello et al, 2019).
Consequently, understanding differing genotype prevalence has a significant clinical
impact on HCV management strategies and the efficacy of certain antiviral therapies
which are linked to the genotype involved (Gower et al, 2014; Toyoda et al, 2018;
Petruzziello et al, 2019). However, Schietroma et al (2018) note that the development
of expensive direct acting antivirals has improved the effectiveness of treatment with
limitations varying between genotypes. As the viral genotypes retain differing
pathogenicity and infective capabilities, they may require tailored therapeutic
strategies that could lead to longer treatment periods (Ashfaq et al, 2011; Yasin, Riley,
and Schreibman, 2011). Therefore, epidemiological surveillance remains a critical
factor for clinical staff to effectively and efficiently identify, treat and manage infections.
According to Fierro (2017) the prevalence and transmission of HCV is heavily
influenced through the relationship between agent, host and environmental factors
resulting in a variation of regional endemics. Yet, it is widely recognised to be
transmitted primarily through parenteral means with a multitude of associated risk
factors and behaviours (Kamal, 2018).
The World health organisation (2017) categorise unsafe healthcare practices such as
nosocomial blood transfusions and therapeutic injections as leading worldwide risk
factors. However, in countries which implemented effective screening processes and
practice regulations these forms of transmissions less commonly occur (Engle, 2014;
Klevens et al, 2012; Alter, 2007). Historically, these proved to be problematic in
Scotland (Watson et al, 1996; Harris et al; 1999). As a response, Scotland requires
mandatory screening of blood products which has successfully safeguarded patients
against potential harm (SPHO, 2018). Nevertheless, unregulated blood transfusions
abroad may still pose a risk (Iveren, 2018).
Healthcare related transmissions are a universal occupational hazard. The results of
a systematic review by Westermann et al (2015) looking at the prevalence of HCV
infections in healthcare workers, involving 57 studies, identified occupational exposure
as an increased risk for HCV infection. This was attributed exclusively to needlestick
injury (Westermann et al, 2015), though any percutaneous or mucosal membrane
exposure to infected blood is considered a risk factor (Ward and Hartle, 2015). Overall,
the United Kingdom has seen a limited number of occupational transmissions
accounting for 17 cases between 2002 and 2014 (Tomkins et al, 2015). This low
transmission risk can be attributed to the implementation of harm reduction policies
such as The Control of Substances Hazardous to Health Regulations (2002).
Traditionally, sexual and vertical transmission of HCV were deemed low risk (PHE,
2017). However, an infected female host can transmit the virus vertically during birth
which is regarded as the most common source of childhood infection, the probability
of this happening is low at 5.8% and is dependent on higher viral loads (Benova et al,
2014; Koneru et al, 2016). However, Reid et al (2018) identified that the current and
historical use of injectable drugs by mothers increases the likelihood of HCV infection
through vertical transmission.
According to Creswell et al (2015) HCV transmission through at-risk sexual practices,
specifically between homosexual men has been increasing. The risk of permucosal
transmission heightened when the human immunodeficiency virus (HIV) is a present
factor (Hagan et al, 2015; Foster et al, 2017). Although the risk of HCV sexual
transmission remains relatively low, the unsafe use of injectable and recreational
drugs is also an associated behavioural risk (Yaphe et al, 2012). Consequently, men
account for 67% of Scottish HCV infections (HPS, 2018), likely due a larger proportion
of men who inject drugs (NESI, 2017).
The World health organisation (2018) identify that a leading source of HCV
transmission is needle sharing between people who inject drugs (PWID), the
contaminated needle acts as a reservoir for the virus instead of the host between
users. Health Protection Scotland (2018) estimate that PWID account for 91% of all
HCV transmissions, though this data is limited to 53% of the infected population
reporting risk factors. However, laboratory testing cites injecting drug use as the
associated risk in 90% of cases highlighting a clear trend in HCV transmission routes
(PHE, 2018). According to Martin et al (2013) the risk of reinfection after treatment is
thought to be equal to initial transmission among PWID. In England and Wales, half of
PWID are estimated to have a HCV infection, in comparison, Scotland is considerably
higher at 58% (PHE, 2017; NESI, 2017).
Worldwide, PWID are more likely to be imprisoned with one third of prisoners in
Scotland testing positive for drugs (Jürgens, Nowak and Day, 2011; SPHO, 2019).
However, Stone et al (2017) reports a lowered HCV prevalence and stable
transmission risk compared to the wider population. Subsequently, injection
transmission risk is drastically increased during the first six months of being released
from prison (Stone et al, 2017; Allen et al, 2012). Further highlighting the challenge
posed by injectable drug use and the importance of transmission reduction strategies
in controlling HCV in the population.
This prompted the development of a two phased action plan by the Scottish
government which aimed to provide effective preventative measures, surveillance,
diagnosis, and treatment of infected individuals in communities, hospitals, and prisons
(Scottish Government, 2006; Scottish Government, 2008). Furthermore, the World
Health Organisation (2016) assigned targets such as reducing HCV related mortality
by 65%, new incidences by 80%, and increasing surveillance and treatment to 90% of
those infected by 2030. These targets are widely accepted as bench markers for
national progress on transmission prevention, diagnosis and treatment (PHE, 2017;
Waheed et al, 2018). However, poor investments limited these strategies with the UK
being one of only twelve countries meeting preliminary targets (Polaris Observatory,
2017; Gore, Hicks and Deelder, 2017). Still, local challenges remain.
According to Hellard, Sacks-Davis and Doyle (2016), harm reduction programs are
essential in HCV prevention. The risk of transmission is vastly reduced amongst PWID
when the provision of safe needles and syringes or opioid substitution therapy is widely
available (Turner et al, 2011; Aitken et al, 2017; Azores-Gococo and Fridberg, 2017).
In Scotland, the availability of injection provision has drastically increased alongside
its uptake by PWID reducing the incidence and risk of needle sharing (ISD, 2018;
NESI, 2017). Furthermore, Fraser et al (2018) note that increased uptake in both
therapies is the single biggest influencer in transmission prevention among PWID.
Consequently resulting in reduced incidences of HCV in Scotland from 2022 cases to
1511 cases between 2014 and 2017 indicating moderate success in preventative
measures (HPS, 2018; PHE, 2017).
In modern public health strategies, disease prevention is of critical importance to
promote good health and reduce harm focussing on education, treatment as a
preventive measure, and adequality identifying infected individuals (Holland, 2015).
The Scottish Intercollegiate Guidelines Network (2013) advise that onsite dried blood
spot testing should be used as a targeted cost-effective measure to diagnose and help
prevent infection transmission amongst at risk groups. According to a review by Coats
and Dillon (2015) this method increased the uptake of testing and diagnosis rates from
PWID. Similarly, a longitudinal analysis by McAllister et al (2014) reported an
increased uptake of dried blood spot testing in at risk groups because of accessibility,
however, it found only 18% of PWID who tested positive commenced antiviral therapy
18 months after.
According to Lange et al (2017) the diagnostic ability of this targeted method is
relatively high, still, the quality of studies reviewed remained varied. In Scotland, this
method increased diagnosis rates within community third sector and nursing led clinics
identifying an estimated 13% of new cases (Mcleod et al, 2014; HPS, 2018).
Nevertheless, an estimated 15,500 people in Scotland remain undiagnosed (HPS,
2018), with PWID predicted to account for 83% of this figure (Prevost et al, 2015). This
highlights the scope of improvement required to meet WHO 2030 targets of 90%
population surveillance (WHO, 2016).
Although effective, targeted surveillance encounters barriers for testing uptake
amongst PWID such as fear of discrimination, judgement, inaccessibility, and lack of
awareness regarding HCV infection and its implications (Swan et al, 2010; Jones et
al, 2014). The system is designed to target at risk groups for testing, however, the fear
of judgement and reliance on self-reporting for risk factors further limits this measure
(Harris, Ward and Gore, 2016). According to feedback from PWID, overcoming these
challenges will require service providers to practice in a dignified non-judgmental
manner and improve access in community settings (Radley, Van Der Pol and Dillon,
2015). Moreover, clinicians providing pre-emptive counselling and education to PWID
improved the uptake of testing with the use of simplified care pathways improving
treatment commencement (Bajis et al, 2017). Thus, highlighting its wider implications
for diagnosis and treatment.
In accordance with the Public Health (Scotland) Act 2008, healthcare clinicians are
required to report the diagnosis of all hepatitis. After detection national policies
recommend treatment be commenced to reduce harm and prevent further
transmission (SIGN, 2013). The preferred mode of treatment recently transitioned from
less effective interferon-based therapies to direct acting antivirals as they reduced
treatment time, reduced resistance to treatment from varying genotypes, and improved
cure rates to over 90% with those co-infected with HIV reaching cure rates greater
75% (Schietroma et al, 2018; Boerekamps et al, 2018; De Clercq, 2014). Furthermore,
a systematic review surrounding the efficacy of non-interferon HCV therapies which
involved 29 studies concluded that direct antiviral therapies reduced some challenges
associated with treating HCV, specifically with genotype 3 which is the most prevalent
in Scotland because of its transmission among PWID (Gimeno-Ballester et al, 2017;
Iveren, 2018). Though direct acting antivirals are considered a cure, they are
expensive, with no prophylactic vaccines available because of genotype variation
prevention is seen as the most effective use of resources (Ashfaq and Idrees, 2014;
McNaughton et al, 2015).
Public Health England (2017) attribute direct acting antivirals to the first drop in HCV
related deaths in ten years by a total of 3%. Although promising the uptake of anti-viral
therapies is relatively low among PWID in Scotland because of a lack of awareness
regarding their success, negative perceptions of older therapies, and the limited
engagement associated with this group (Valerio et al, 2018; Treloar et al, 2012). The
introduction of clinical, professional and patient HCV education may limit barriers to
treatment (Bajis et al, 2017; Marinho et al, 2016; Bruggmann, 2012). According to Mah
et al (2017) increased uptake and engagement with treatment, care and testing among
PWID is reliant on an adequate understanding of HCV. Therefore, a cross-sectional
educational approach should be considered in HCV prevention and care uptake.
When implemented alongside harm reduction programs education has been shown to
improve overall HCV awareness amongst PWID (Norton et al, 2014; Mukherjee et al,
2017; Valerio et al, 2018). Subsequently, addressing wider inequities in health
determinants associated with PWID may improve educational interventions further
(Mukherjee et al, 2017). The increased knowledge may encourage the reduction of
risk-taking behavior associated with transmission and improve willingness to be
treated (Fatseas et al, 2012; Mah et al, 2017). However, research regarding behavioral
change in HCV interventions is limited.
In summary, the HCV virus is a growing public health concern. The large degree of
genotype variation has diminished the likelihood of a prophylactic vaccination. In
Scotland, the endemic distribution of HCV is driven by increasing transmission trends
among PWID, which is associated with other at risk behaviors. The national strategies
to prevent and combat the spread and incidence of HCV infections have been
somewhat successful; however, uptake of screening and treatments among PWID has
been sub-optimal. After evaluating perceptions from PWID regarding testing it was
found that fear of judgement and the implications of diagnosis were contributing factors
to lowered uptake. Thus, the need for non-judgmental service provision was
emphasized.
Similarly, the barriers for commencing treatment encompass negative perception and
lack of awareness from PWID. Subsequently, the research identified the importance
of providing pre-care education to at risk groups and healthcare professionals
including clinicians to facilitate increased engagement from PWID with testing, care
and eventual treatment uptake. Nevertheless, it has been suggested that educational
initiatives would be more successful if applied in conjunction with harm reduction
interventions such as needle provision services and opioid substitution therapy.
Therefore, it is recommended that a cross-sectional educational approach should be
considered which targets clinical professionals, third sector workers, and at-risk
stakeholders alongside harm-reductions measures to help identify and treat infections,
prevent HCV spread and reduce harm in the population. This approach will need to
emphasise dignity and empathy as its core values to limit the impact of damaging
perceptions. In future, research should be conducted regarding the sustainability of
behavioral change methods and specifically their impact on preventing HCV
transmission, spread and incidences.
