Introduction
The estimated global prevalence of HCV is approximately 130–170 million with regional variations [
1]. Every year around 3–4 million people are infected with HCV and more than 350,000 people die from HCV [
2]. HCV is a major cause of morbidity and mortality due to liver disease including inflammation, cirrhosis and hepatocellular carcinoma. The majority of people with HCV are injecting drug users (IDUs) and a significant proportion of those have mental health problems [
3,
4]. Therefore, HCV involves widespread psychosocial morbidity that can pre-exist diagnosis, and be compounded by or result from the diagnosis of HCV due to it being a life threatening disease. As stated by Hirsch and Wright [
5] (2003: 536),
“Hepatitis C is an insidious, slowly progressive killer”. The standard treatment for HCV is combination therapy with peginterferon and ribavirin (hereafter interferon) with new direct acting antiviral drugs becoming available for patients with specific genotypes [
6]. Because interferon is associated with neuropsychiatric adverse effects [
7], in earlier clinical practice from around the 1990s, patients with mental health and substance use were often excluded from accessing interferon therapy [
8]. Current clinical guidelines demonstrate that such exclusion is no longer necessary except in certain circumstances [
9]. However, substantial increased access to interferon by populations with mental health and substance use problems has not been achieved to date. For example, in Australia, only approximately 3,500 people per year commence antiviral therapy, this figure is well below the required 6,000 to stabilize the population from progressing to advanced liver disease [
3], and potential adverse health effects post treatment is a deterrent [
10]. Therefore, access to HCV treatment and health care services by populations with mental health and substance use problems is complicated by a number of factors and barriers raising a key issue about equity.
As the WHO (2007) maintains, health care systems have a weak health equity orientation, are not pro-poor and do not effectively address the health needs of marginalized groups [
11]. In the case of HCV, treating patients with HCV and mental health co-morbidity is already complex, but is further compounded by inadequate health care systems and service delivery. Furthermore, HCV populations can experience stigma and discrimination in both health service use and in the community [
12,
13]. Common reasons for the exclusion of patients with HCV, mental health and substance use problems to access antiviral therapy include not only the possibility of psychiatric morbidity, but concerns about lack of adherence to the interferon regimen. In a recent study of physicians 48% refused to treat HCV infected patients because of alcohol and drug use, even though drug and alcohol use did not affect sustained virological response, and 46% refused naming mental health reasons as the barrier to treatment [
14]. At the primary care level only 39% of general practitioners were highly likely to discuss psychosocial issues with patients and 37% reported difficulty with having a central role in the psychological and medical care of their patients [
15].
Therefore, given the complexity of issues involved with HCV, mental health and access to antiviral therapy, we aimed to develop a review summary that would inform current directions for access to antiviral therapy and management of these vulnerable HCV populations. The main objective of this paper was to provide an overview of the main themes in the literature about HCV, mental health and antiviral therapy from which a critical discussion could be developed rather than an exhaustive systematic review. The main research question was: How do mental health and substance use co-morbidities affect access to interferon therapy?
Discussion
This review has identified emerging research evidence that overall populations with mental health and substance/alcohol use problems can and should have similar access to interferon as populations who do not have these comorbidities. In contrast to some clinical practices that have excluded populations with mental health and/or substance use problems from accessing interferon therapy, this review provides clear evidence based on original research, clinical observations and clinical reviews that these populations can be safely treated in a multidisciplinary care context [
18‐
20,
24,
27,
28,
30], that prior psychiatric or substance use history does not predict completion of IFN/ribavirin treatment [
23], and that clinical outcomes are comparable with those without these co-morbidities [
25]. Of particular note is the recent European Expert Consensus statement [
24] that maintains patients with pre-existing disorders can be treated with interferon based regimens and do not have an increased poor compliance, lower SVR, more severe depression during treatment or treatment failure. This finding is supported by some clinical guidelines for the management of HCV patients [
9].
This evidence has fundamental implications for equity in relation to patient access to health care, for health professionals, for the implementation of clinical guidelines for HCV management, and for health system change. Having clear evidence to support such widespread increased access to interferon, however, is not always translated into clinical practice. A number of reasons may account for the lack of evidence-based practice, including clinicians’ entrenched beliefs about populations with mental health/substance use problems being barriers to effective treatment, discrimination, economic considerations, lack of appropriate health service delivery and poor patient engagement.
Unlike the requirement that interferon commencement is conditional upon demonstrable improvement in patients’ mental health and/or abstinence from alcohol/substance use, in the above studies interferon was commenced within a period ranging from several weeks or months. This demonstrates a shortening of the length of time for treatment to commence from what was typically 6 months. During this period comprehensive pre-HCV therapy strategies were employed involving one or more of the following: (1) mental health and substance use screening and assessment, (2) HCV/IFN information, education and support, and (3) establishment of multidisciplinary care [
18‐
20,
22‐
25,
27,
28,
30]. Comprehensive regular monitoring was continued during and post interferon therapy. In cases where there was uncontrolled major depression adequate symptom remission was necessary prior to commencing interferon therapy [
23]. These studies demonstrate a different approach to patient access to interferon whereby on participation in or completion of a clearly defined pre-therapy preparatory program patients progress to commence therapy. Therefore, there is considerable variation across different global regions regarding the clinical requirement for some degree of remediation or rehabilitation from the patient in order to receive treatment. This suggests a need for changing some clinicians’ values and perceptions of these population groups to enable both an increase in the expansion of access to interferon treatment and earlier commencement of treatment.
The most common health care setting in which interferon was managed in the above studies was a specialist clinic in a major tertiary hospital. All studies refer to a multidisciplinary and/or integrated model of care for the management of interferon with patients with mental health and substance/alcohol use problems largely comprising, however, only a gastroenterologist or HCV/liver specialist and a psychiatrist [
18,
19,
23,
24,
27]. In the study by Dollarhide et al. [
23] the multidisciplinary team was expanded to include an addiction specialist. The study by Rifai et al. [
20] was the only one to report inclusion of a primary care physician.
Primary care generally provides low threshold, highly accessible and multidisciplinary comprehensive care with a focus on delivering high quality chronic disease management. It could therefore be an ideal environment to ensure management of chronic care services to vulnerable population groups such as HCV patients. However, the only other model of HCV interferon management identified was community based health care located in drug and alcohol clinics. In the study by Norman et al. [
22] they demonstrate that it is feasible to provide a quality HCV treatment service that had a high acceptability to substance using clients. The integrated multidisciplinary team included primary care medical practitioners, a visiting specialist liver physician, peer worker, nurse, pharmacist and allied health as required. Similarly, Sylvestre et al. [
28] maintain that interferon treatment can be successfully integrated into health care settings that provide care for populations with mental health and substance use problems such as methadone clinics, prisons and community-based ‘walk-in’ clinics. Arora et al. [
29] have combined integrated multidisciplinary care with videoconferencing to establish and increase access to HCV care in marginalized communities with significant improvements in providers’ experiences of care delivery. Finally, Sylvestre and Zweben [
30] report positive outcomes from a community-based program based on collaboration between medical providers and peer educators whereby the meaningful engagement of IDUs enabled screening and HCV treatment resulting in further positive effects on adherence. Currently, there appears to be some emerging randomized controlled trials of integrated care such as those by Evon et al. [
31] and Groessl et al. [
32] but these are restricted to major medical centres, and there is little focus on the potential of integrated multidisciplinary care of HCV management in primary health care settings. The emerging studies of community-based models of health care for interferon management were restricted to injecting drug user settings and no studies involving general practice were identified. Indeed, there is a paucity of research on the potential for interferon to be managed in general practice or other primary care settings. General practitioners, however, are reportedly not confident to initiate therapy, but do have an interest in education about HCV antiviral therapy [
33] demonstrating the need for more research investment into their education and service development needs.
The dominance of hospital managed HCV antiviral treatment clearly serves as a major barrier to the populations most affected by HCV; people with mental health and substance use co-morbidities. The research evidence suggests that for these populations it is imperative to establish their engagement through community-based clinics run by broad-based multidisciplinary teams. Therefore, we identified in this review an inverse relationship between the type of health service model best suited to HCV, mental health and substance use populations and what is actually available as the dominant model of care. The hospital specialist model was designed around the needs and convenience of medical specialists rather than those of the population groups and patient-centric care. We acknowledge that new medicines such as those on their way for HCV require specialist oversight when introduced, but for the majority of HCV populations this is not the case. The prior example of the transition of the management of insulin initiation away from hospitals and towards community-based clinics serves as an analogy for what we observe is unfolding in the area of HCV. In terms of models of service delivery, the Beacon practice model [
34], could be a framework for innovative HCV health service research to address increased access. As part of future models of HCV management it is also necessary to consider the introduction of interferon free HCV antiviral treatment regimens. However, given the current speculation about the timing of the availability of new HCV medications interferon may well continue to be the major treatment for some time yet, although the prescribing practice will be of significant interest in terms of access and equity.
This review drew on guiding principles of narrative review and in so doing involved searching the international literature. One of the limitations of the review was that the term ‘psychosocial’ was particularly problematic for a review using systematic principles because it has several different meanings in the HCV literature. Three particular types of use of the term ‘psychosocial’ were identified; first, it is used as an overarching term for one or more psychiatric/psychological diagnoses, and specifically, anxiety, depression, schizophrenia, psychosis, and co-morbidity of diagnoses. Second, in many articles mental health diagnoses were referred to as ‘psychiatric’ whereas ‘psychosocial’ referred to socio-economic status, unemployment, poor social support and even “chaotic living”. Third, in some articles mental health diagnoses were included within the term psychosocial together with socio-economic factors. Further to this, our search resulted in only 13 eligible articles and 2 of these were conference reports. Consequently, the extent to which the review identified the current evidence on HCV, mental health and access to interferon remains relatively opaque.
Recommendations
The promising early results emerging from community-based multidisciplinary care indicate that it would be timely to explore multidisciplinary, integrated interferon management in primary care. The potential benefits of this model of care are threefold; First, it would create a shift away from hospital-based health service delivery toward primary health care as the driver of service provision together with specialist input consistent with international health policy reforms [
35,
36]. Second, the reorientation of health service delivery is likely to result in considerable cost savings. Third, the expansion of community-based interferon management would facilitate increased equity and access to health services for marginalized populations.
So what is required to create such a change in health service delivery that could increase equity of access to interferon? First, general practitioners need to be motivated, educated and supported to lead comprehensive HCV treatment including interferon management in close collaboration with liver and mental health specialists. Second, there needs to be a systematic exploration of models of multidisciplinary, integrated care in the community-based setting to determine what constitutes quality, safety and the most cost effective model to manage the multiple psychosocial and medical needs of HCV patients. Third, patient engagement is crucial to any successful expansion of access to interferon through community-based services. This involves regular, extensive and well-informed interaction with HCV populations that builds trust between clinic staff and patients through which patients are prepared for interferon therapy, its potential side effects, adherence, and also the possibility of treatment failure.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
All authors participated in the conception and design of the study, analysis of the literature, contributed to drafts of the manuscript and read and approved the final manuscript.