Background
Hepatitis C infection remains a significant public health concern, with an estimated 71 million people chronically infected worldwide [
1]. In Australia and other developed countries, the sharing of injecting equipment is the most common source of hepatitis C exposure, placing people who inject drugs (PWID) at greatest risk of infection [
2,
3]. Persistent infection may lead to fibrosis, liver disease, hepatocellular carcinoma, liver transplant and extrahepatic manifestations [
4,
5]. Fibrosis progression is variable, with approximately 10–20% of individuals with hepatitis C developing cirrhosis within 20–30 years of infection [
4,
6,
7]. In Australia, hepatitis C infection is the leading cause of liver transplant, with the burden of hepatitis C liver related disease predicted to triple by 2030 [
8].
Recently, the therapeutic landscape of hepatitis C has drastically changed. Non-invasive fibrosis assessment tools, such as transient elastography (TE) (an ultrasound like device which determines liver stiffness by measuring wave velocity [
9]) and highly effective interferon-free direct acting antiviral (DAA) medications are now considered standard of care [
10,
11]. These advances have made the elimination of hepatitis C as a public health threat a real possibility, particularly in Australia, where DAAs are widely accessible and heavily subsidised [
12,
13]. However, such advances may also alter the individual experience of living with hepatitis C.
The qualitative literature has long reported that diagnosis of a chronic illness such as hepatitis C fosters feelings of fear, shock, despair, condemnation, confusion and uncertainty [
14‐
19]. Mishel’s 1981 theory of
Uncertainty in Illness [
20] describes uncertainty as an ‘inability to determine the meaning of, or predict outcomes of illness-related events’ (p 225). This concept of
Uncertainty in Illness may be manifested through four forms; 1) ambiguity regarding illness state, 2) complexity regarding treatment and system of care, 3) lack of information received or understood, particularly around diagnosis and illness severity and/or 4) unpredictability of disease course and prognosis [
20,
21]. Experiences of illness-related uncertainty may jeopardise one’s sense of personal stability, culminating in stress [
19,
20]. The term uncertainty is used broadly in this paper to describe the concept of
Uncertainty in Illness.
Whilst the concept of uncertainty has been the focus of research in populations of people living with Parkinson’s disease [
22], Diabetes Mellitus [
23], Cancer [
24] and Human Immunodeficiency Virus [
25,
26], there are few studies exploring uncertainty in people living with hepatitis C [
27,
28]. Bailey et al. [
27] quantitatively measured uncertainty in people living with hepatitis C who were undergoing ‘watchful and waiting’ protocol, however, did not specify participants’ injecting status. Rhodes, Davis and Judd [
28] conducted in-depth interviews with PWID in London and found uncertainty, as a lack of knowledge of hepatitis C prominent, although only 32% of this sample was hepatitis C positive.
The advent of TE to measure the degree of fibrosis means that PWID living with hepatitis C can be more easily made aware of their liver disease progression. Hence, at first blush it seems reasonable to expect that the TE score introduces an aspect of certainty into the lives of those living with hepatitis C. DAA medication provides the prospect of effectively being cured [
12], however, for those with pre-existing advanced liver damage, considerable uncertainty about their future health outcomes will remain. Hence, testing and treatment advances may influence the experience of and degree of uncertainty felt by those living with hepatitis C.
This study explores how uncertainty in the context of TE scores and DAA treatment affects self-reported stress in PWID living with hepatitis C. In particular, we focus on how uncertainty in relation to degree of fibrosis and the prospect of receiving treatment is related to stress. Understanding sources of uncertainty in PWID living hepatitis C may aid in developing appropriate resources to reduce hepatitis C related stress.
Methods
Participants
Participants were recruited from the Treatment and Prevention (TAP) study, which examines the feasibility of treating hepatitis C mono-infected PWID in a community-based setting [
29]. All TAP participants were eligible for qualitative interview provided they had received a valid liver fibrosis assessment and positive (detected) hepatitis C RNA Polymerase Chain Reaction test, at TAP study screening between February 2015 and August 2016. All participants had received a liver stiffness score prior to interviews. Liver stiffness was measured by TE (FibroScan™; Echosense, France). Participants were recruited through a mix of stratified purposive and opportunistic sampling. Participants were grouped as either; ‘high-level fibrosis’ (liver stiffness ≥9.5 Kpa corresponding to METAVIR stage F3/F4) or ‘low-level fibrosis’ (liver stiffness < 9.5 Kpa or F0-F2). Initially a purposive sample of 22 potential participants was selected from TAP, stratified based on age, gender and level of fibrosis (as recorded at trial screening). All 22 participants were contacted via telephone but only two were available for interview (9% response rate). Of these 22 participants the majority had disconnected phone numbers.. Consequently, all eligible TAP participants accessing the trial field sites were sequentially invited to participate and, if they consented, were subsequently interviewed by the first author. Fifteen participants were invited to participate through this method, and 14 were interviewed (93% response rate) including seven participants from the original purposive sample. Through both recruitment methods a total of 16 participants were interviewed. Participants with high-level fibrosis were intentionally ‘over-sampled’ (the proportion of participants with high-level fibrosis in our sample does not reflect the general population) to provide sufficient data to compare experiences between those with high and low-level fibrosis.
Data collection
Qualitative methodology was employed to gain a more nuanced and in-depth understanding of liver health and wellbeing for PWID living with hepatitis C. Semi-structured interviewing occurred between June and August 2016 across five Melbourne metropolitan sites. Interviews were conducted at community health services, needle and syringe programs or a tertiary hospital.
The interview schedule was informed by the literature on qualitative methodology [
30,
31], the research question and discussion between co-authors. Interviews were informal and flexible, using broad prompts such as, ‘what are some things you find stressful at the moment?’ This allowed participants to discuss aspects of life they believed to be impacting on their wellbeing, without being directly asked or feeling obliged to talk about specific factors. Follow-up prompts were on topics such as the physical and emotional effects of hepatitis C and fibrosis and attitudes towards fibrosis and treatment.
Interviews lasted approximately 30 min (range: 17–46 min) and were digitally voice recorded. Participants were reimbursed $AUD40 for their time.
Data analysis
Participant characteristics collected at TAP screening were identified though pre-assigned unique participant numbers and were utilised to describe the sample. ‘Employed’ included: full-time, part-time or casual employment.
Interviews were transcribed verbatim using Microsoft Word and VLC Media Player (v 2.2.4, VideoLAN Organization, Paris, France). Interviewed participants were assigned unique interview codes and any identifying information was removed from transcripts to ensure anonymity.
Transcripts were read, re-read and then analysed thematically using both inductive and deductive analysis. Deductive codes were based on the four forms of
Uncertainty in Illness (ambiguity, complexity, lack of information and prognostic unpredictability). Three processes of coding were used; open, axial and thematic [
30]. During open coding each line of the transcript was assigned a summative word or phrase. Axial coding focussed on identifying themes from issues that emerged in the open coding stage. This included exploring the physical and emotional impacts of aspects of life that were frequently mentioned. Finally, thematic coding involved understanding what was driving major positive and negative impacts on stress levels and differences between fibrosis groups. The analysis process was conducted iteratively so themes that emerged later in analysis were applied to earlier transcripts. Axial and thematic codes were discussed among authors. Thematic codes were also developed with two independent fieldworkers who regularly interviewed PWID.
All participants provided informed consent and ethics approval was received by the Monash University Human Research Ethics Committee.
Discussion
Amidst a rapidly changing therapeutic environment, our study provides insight into the impact of liver health related uncertainty on self-reported stress levels in PWID living with hepatitis C. Our study also revealed motivations for seeking and impact of new DAA treatment in this population. There were three key findings. Firstly, whilst TE is intended to introduce an element of certainty into the lives of those living with hepatitis C, it may be a source of ambiguity, lack of information prognostic uncertainty and ultimately stress. Secondly, liver health uncertainty may be heightened among those with severe fibrosis, as the future appears more unstable, leading to a greater degree of self-reported stress and anxiety. Finally, treatment facilitates a sense of certainty and stability, which allows participants when treated to feel a sense of empowerment, confidence and agency over their life.
In our sample much of the TE related uncertainty was due to limited knowledge. This is consistent with the literature reporting low levels of health literacy and hepatitis C knowledge among PWID living with hepatitis C, which may cause confusion or act as a barrier to treatment [
16,
36,
37]. Treloar et al. [
38] conducted a self-administered survey with 132 hepatitis C positive clients from Australian opioid substitution therapy clinics. Consistent with our participants’ depictions of fibrosis; the authors noted that levels of knowledge surrounding hepatitis C disease progression were particularly low. Glacken, Kernohan and Coates [
16] conducted nine in-depth interviews with people living with hepatitis C. They reported diagnosis related uncertainty as arising from a lack of clinical and prognostic knowledge, which resulted in fear and anxiety. Nevertheless, we found such substantial gaps in knowledge somewhat surprising given participants’ involvement in a hepatitis C treatment trial. For example, numerous participants worried about receiving dialysis if their fibrosis were to progress to liver failure, despite dialysis not being a treatment option for decompensated cirrhosis. However, the broader literature regarding uncertainty in illness suggests that people often receive contradictory information regarding chronic illness [
18], do not passively accept expert information but rather reinterpret this knowledge through the scope of lay experiences [
39] or may encounter information overload which affects attention and recall [
19].
The finding that there was a greater degree of fibrosis related uncertainty and thus self-reported stress among those with more severe fibrosis has not previously been reported, but is not surprising. The combination of awareness of a serious degree of fibrosis, yet little clinical or prognostic knowledge fostered anxiety around life expectancy, disease progression and how fibrosis would impact everyday life. It has not been explored in hepatitis C specifically but others report a positive association between illness severity and uncertainty [
19]. Further, quantitative studies suggest that increased fibrosis may be associated with poorer health related quality of life [
40,
41]. Bailey et al. [
27] tested the Mishel Uncertainty in Illness Scale in 126 untreated people living with chronic hepatitis C. A moderate level of illness uncertainty was seen in this group. Further, the subscales (ambiguity, complexity, inconsistency and unpredictability) were correlated with outcomes such as; depressive symptoms, fatigue, pain and quality of life. However, participants were not distinguished based on disease stage.
There is currently little qualitative published work on the impact of DAA treatment on individuals. Our findings of the overwhelmingly positive psychosocial effects of treatment are also reflected in the treatment stories on numerous hepatitis C blogs and websites [
42‐
44].
Our study was not without limitations. All participants received a TE score prior to interview. However, the time lapse between TE and interview differed between participants, which may have influenced participants’ understanding of their fibrosis. Further, the response rate through the first wave of recruitment was far lower (9% compared to 93%). This is likely due to the first mode of recruitment relying on telephone contact from a telephone number unknown to participants. This is problematic as many PWID do not answer telephone calls from unfamiliar numbers, have limited credit to return calls, may be in contact with the justice system or rehabilitation services and frequently change contact information [
45].