“If I Get Cured, My Whole Quality of Life Will Change”: Patients’ Anticipated and Actualized Benefits Following Cure from Chronic Hepatitis C

Abstract

Background:

Patients’ motivations for undergoing direct-acting antiviral (DAA) therapy for chronic hepatitis C may include anticipation of treatment benefits not well-described in the literature.

Aims:

Evaluate patients’ anticipated and actualized improvements in several domains of functioning before and after viral cure.

Methods:

Pre-post study utilizing in-depth interviews with 28 patients prior to, and several months after, DAA therapy. Interviews were audio-recorded, transcribed, coded and analyzed by two qualitative experts.

Results:

Patients had a median age of 54 years, 43% were male, 57% white, 25% had cirrhosis, and 71% were treated with sofosbuvir/ledipasvir. Pre-treatment, patients hoped for improvements in several domains including psychological, emotional, physical, social and occupational functioning. After viral cure, increased energy and less fear of transmission were pathways to better quality of life. Psychological and emotional improvements positively affected physical, social and occupational functioning. Social improvements were due to better mood and motivation, fewer symptoms, and reduced fear of stigma and transmission. Occupational benefits were linked to increased stamina, self-confidence, and less pain, anxiety, and stigma. Reduced fear of stigma had a pervasive impact on all life improvements after cure. Patient characteristics such as presence of cirrhosis or psychiatric issues influence treatment motivations. Qualitative data correspond with change in pre-post survey scores.

Conclusions:

Tremendous hope is placed on the ability of DAA therapy to bring about substantial improvements in life functioning after viral cure. Highly interconnected effects on quality of life worked synergistically through improved physical and psychological well-being. Stakeholders should appreciate the multi-dimensional benefits that viral eradication bestows upon individuals and society.

Introduction

Many people infected with chronic hepatitis C virus (HCV) are eager to undergo curative treatment to eradicate the virus from the body and reduce risk of liver disease progression. Some patients infected with HCV experience symptoms that may be attributable to harboring chronic HCV. The most common symptoms reported by patients with HCV include: depression, anxiety, irritability, fatigue, cognitive dysfunction, sleep disturbance, and achiness/pain [1]. As a result, patients with HCV often have worse quality of life (QOL) compared to the general population [2]. Patients with HCV also perceive or experience social stigma or discrimination due to the infectious nature of the virus and the public’s misperception of causality related to addiction, sexual promiscuity, alcoholism, or HIV [3,4]. With direct-acting antiviral (DAA) regimens that now cure over 95% of those treated, patients may seek treatment in hopes of improvements to multiple domains of life functioning after viral eradication.

Although obtaining information about patients’ experiences after DAA therapy using patient-reported outcome measures is a step in the right direction towards conducting patient-centered outcomes research, some patient experiences are not easily captured by quantitative survey studies because surveys are inherently limited to the domains they are designed to measure. By contrast, qualitative studies using in-depth, open-ended interviews are extremely useful in uncovering and exploring patient perceptions and experiences that may not be elicited from surveys and can provide meaningful, rich narratives from the patients themselves about their experiences [5–9]. Interviews have revealed that patients experience gratitude and excitement for DAA treatment in hopes of achieving HCV cure and experiencing positive results [10]. What those positive results are have yet to be thoroughly explored.

The aim of this study was to conduct a qualitative evaluation to understand the comprehensive spectrum of benefits on life functioning that patients anticipate (“hope for”) experiencing after DAA therapy, as well as their perceptions of actualized benefits captured several months after being cured. Understanding anticipated and actualized benefits of viral cure from the patients’ perspective may be clinically meaningful to inform health policy, patient-provider communication about DAAs, treatment decision-making, and future DAA treatment outcome studies.

Methods

Study Design

This was a pre-post study utilizing in-depth qualitative interviews before and after DAA therapy. Pre-treatment interviews were conducted before therapy commenced among individuals who had decided to undergo DAA treatment to understand all anticipated or “hoped for” benefits of being cured of HCV. Post-treatment interviews occurred four to nine months after treatment ended to understand patients’ experiences of benefits to their lives following viral cure. The study was approved by the Institutional Review Board at the University of North Carolina at Chapel Hill. Informed consent was obtained from all individual participants included in the study.

Study Participants

Approximately 30 patients infected with HCV and ready to initiate DAA therapy with a sofosbuvir-containing regimen were invited to participate. Recruitment for the study ended once thematic saturation was achieved (i.e., no new information or themes emerged after five consecutive interviews). During recruitment, the study coordinator attempted to recruit patients with various characteristics to ensure heterogeneity of sampling related to age, cirrhosis status, and treatment experience. Inclusion criteria were age 21 years or older, English-speaking, and given a prescription for a sofosbuvir-containing DAA regimen by their provider. Patients were excluded if they were waitlisted or had received a liver transplant. Remuneration was $50 for completing the pre-treatment interview and $50 for completing the post-treatment interview.

Recruitment and Enrollment

Patients were recruited in clinic or via phone by trained research staff. Patients recruited in clinic were approached and consented prior to scheduling pre-treatment phone interviews. Patients recruited over the phone were mailed an informed consent packet, engaged in the consent process via phone, and returned the signed informed consent documentation to the research team prior to participating in phone interviews. Treatment end dates were tracked in electronic medical records and patients were contacted four to nine months after treatment to conduct post-treatment interviews.

Baseline Patient Characteristics

Patients completed a brief sociodemographic survey at baseline. The following clinical data were extracted from electronic medical records: HCV genotype, baseline cirrhosis status, prior treatment experience, sustained virological response (SVR) status, treatment regimen and duration. Additional data extracted from the electronic medical records included lifetime history and baseline alcohol use, substance use, and psychiatric issues. Excessive alcohol use was defined as: men drinking ≥5 standard alcoholic beverages in one sitting or ≥15 in one week, women drinking ≥4 standard alcoholic beverages in one sitting or ≥8 in one week. Substance use was defined as the use of illicit substances or abuse of prescription narcotics or benzodiazepines. An active psychiatric disorder was identified by the presence of ongoing pharmacotherapy, psychotherapy, or clinician documentation of uncontrolled psychiatric disease.

Pre- and Post-Treatment Qualitative Interview Guides

The semi-structured pre-treatment interview guide was developed by the research team to solicit information from patients regarding anticipated benefits of achieving viral cure (Appendix A). The interview guide included open-ended questions to encourage patients to speak openly and freely about their anticipation or “hoped for” treatment benefits or experiences (“If you are cured from Hep C after treatment, what do you hope or anticipate will change for you?”, “What kind of benefits do you hope to achieve if cured from Hep C?”). These questions were followed by specific probes for anticipated improvements/benefits in any of the following domains of functioning: (1) medical, physical, symptoms; (2) emotional, mental, psychological; (3) social; (4) other.

The semi-structured post-treatment interview guide sought to understand the patients’ perspectives about actualized benefits experienced after viral cure (Appendix B). Based on the themes identified during the pre-treatment interviews, patients were specifically probed about the following domains of functioning separately: (1) physical functioning and symptoms; (2) medical conditions; (3) cognitive/mental; (4) emotional; (5) psychological; (6) occupational; (7) social; and (8) other. In preparation for the post-treatment interviews, the interviewers reviewed each patient’s pre-treatment transcripts. After first asking open-ended questions about each of these eight domains (e.g., “How have you been feeling physically since being cured from Hep C?”, “What changes or differences have you experienced physically, since being cured of Hep C?”) the interviewer then used probing questions to follow-up on any specific anticipated benefits the participant had mentioned during the first interview (“During your first interview, you mentioned that you were experiencing low energy and feeling tired. How has this changed, if at all, since you were cured?”). Interviews took an average of 45 minutes to complete, were digitally-recorded and transcribed verbatim by Verbalink (https://www.verbalink.io/).

Qualitative Data Analysis

The pre- and post-treatment interview guides were used to create sets of a priori codes based on areas of functioning noted above. Transcripts were uploaded to Dedoose and the initial codebooks (one for pre- and one for post-treatment interviews) were pilot tested by independently coding two transcripts. Concept definitions and decision rules were revised and the final codebooks were applied to the remaining transcripts (Appendices C–D). Two team members coded interview transcripts individually, then reviewed each transcript together to ensure consistent use of codes; discrepancies in coding were reconciled by discussion and consensus. Once coding was complete, the code reports were used to generate themes related to the a priori domains in the interview guides. New domains and subthemes also emerged. In addition to analyzing data from the total cohort, we also explored thematic differences between participants with and without cirrhosis and between participants with and without psychiatric comorbidity at baseline.

To complement participants verbatim quotes about change in life domains and symptoms after viral cure, we provide the degree of improvement from baseline to post-treatment using some of the Patient-Reported Outcomes Measurement Information System^® (PROMIS^®) surveys. For several PROMIS measures, an improvement of 2 to 5 points has been used in studies as the minimal clinically important difference, with 2–3 point improvement connoting a small effect size, 5 point improvement connoting a moderate effect size difference, and >5 points connoting a large effect size difference [11–14].

Results

Patient Characteristics

A total of 28 pre-treatment interviews were conducted. Participants were, on average, 55 years old (range: 24–69), 46% male, 54% white, 39% black, and 25% had cirrhosis (Table 1). The majority had a history of excessive alcohol use or alcohol use disorder (64%), substance use (79%), and co-morbid psychiatric disorders (54%). Five participants had ongoing marijuana use. The most prevalent psychiatric disorders were depression (39%) and anxiety (25%). The majority of participants were naïve to HCV treatment (93%) and 71% underwent treatment with sofosbuvir/ledipasvir for 12 weeks. Patients completed pre-treatment interviews, on average, four days (range: 1–27) prior to starting DAA therapy.

Table 1.

Patient Characteristics (n=28)

Patient Characteristic	n (%)
Age, years (mean, range)	55 (24–69)
Sex
Male	13 (46)
Female	15 (54)
Race
Black	11 (39)
White	15 (54)
Other	2 (7)
Marital status
Married, with partner	8 (28)
Single	10 (36)
Divorced, Separated, Widowed	10 (36)
Education
Less than high school graduate	4 (14)
High school/GED graduate	13 (47)
Higher than high school education	11 (39)
Annual household income
< $40K	21 (75)
≥ $40K	7 (25)
Employment
Working full or part time	14 (50)
Receiving/applying for disability	7 (25)
Unemployed	3 (11)
Retired/homemaker/student	4 (14)
Health insurance
Private insurance	9 (32)
Public insurance (Medicaid, Medicare)	6 (22)
Uninsured	13 (46)
Alcohol use
History of excessive alcohol use or alcohol use disorder	18 (64)
Baseline alcohol use	3 (11)
Substance use
History of substance use	22 (79)
Baseline substance use	5 (18)
Baseline psychiatric disorder or treatment
Depression	11 (39)
Anxiety	7 (25)
Bipolar disorder	2 (7)
Posttraumatic stress disorder	1 (4)
Genotype
Genotype 1 or 4	22 (79)
Genotype 3	6 (21)
Cirrhosis status
Cirrhotic	7 (25)
Noncirrhotic	21 (75)
Treatment regimen
SOF/LED	20 (71)
SOF/VEL	8 (29)
Prescribed treatment duration
12 weeks	26 (93)
24 weeks	2 (7)
Treatment experience
Treatment naïve	26 (93)
Treatment experienced	2 (7)
SVR achieved
Yes	25 (89)
No/unknown^	3 (11)

NOTE: SOF/LED: sofosbuvir/ledipasvir, SOF/VEL: sofosbuvir/velpatasvir.

^{^}no SVR=1. Missing HCV RNA/SVR unknown=2

Pre-Treatment Anticipatory Benefits of Viral Cure

Twelve over-arching themes and additional subthemes emerged, some were anticipated due to direct interview probes (e.g., physical symptoms, medical, psychological) but other salient themes emerged (e.g., healthcare, stigma, occupational benefits). Patients hoped for abundant social benefits that were coded into four separate social-related main themes (personal and family, general social life, stigma reduction, romantic/sexual benefits) (Table 2).

Table 2.

Participants’ anticipated benefits of viral cure prior to receiving HCV treatment (n=28)

Main Themes and Sub-Themes	Illustrative Patient Quotes
Anticipated Benefits to Physical Health and Symptoms
Reduced fatigue and increased energy Most participants hoped that the fatigue or decreased energy that they attributed to HCV would remit after treatment, and also hoped that with increased energy, they would become more physically active and have an improved mood and outlook.	“I’m hoping that the sleep will get better. I’m hoping that the fatigue will go away or at least subside quite a bit.” (S73) “I want my energy back. I hope it gives me my energy back, I hope it gives me my smile back.” (S3) “…sometimes I think it might flare up to where I just feel like I just don’t have no energy… With me being cured, maybe that’ll help. I may not be as tired.” (S5) “I’m hoping to have more energy to get up and go… I wanna get up in the morning like I used to…I usually do it every morning, but I don’t now, I don’t do it anymore, and I wanna get back to doing that, and getting back in the gym and stuff.” (S4) “Well, I live across the street from the beach and so a lot of the things that I was doing at the beach like fishing and swimming and stuff like that, I’ve been putting off because I haven’t been feeling up to it…I’m hoping that I can get more energy and then I’ll feel more like going to do those things again.” (S34) “Hopefully I’ll be normal again, like energy-level-wise and be able to work out again and do my daily routine” (S94)
Reduced pain Many participants hoped that HCV-related aches and pains would improve if cured, and some described their pain as closely intertwined with their mental and emotional well-being.	“I won’t have this pain that I usually have sometimes, you know, in my liver.” (S4) “Well, I hope that it helps the aches and – I hope I don’t have all these aches and pains.” (S52) “I feel like once these things are cured, it’ll cure some of the other things in my life, which is even more – you know, being depressed all the time… Mental affects physical. If I – let’s say if I hurt, or if I can’t do something, it mentally upsets me… it’s kind of a circle thing. One makes the other one worse.” (S14) “But basically my anger is mainly with my anxiety and pain…So when I’m angry I just keep to myself and it’s not exactly healthy. I’d like to be able to change that, and a lot of times I’m angry because I don’t feel good.” (S9)
Anticipated Medical Benefits
Participants spoke in general terms about living longer and being in better health, and hoped for a stronger liver.	“I just want to live, have a better life for real, enjoy life. I just want to be able to enjoy life, without having to take medicine and getting sick and anything. I just want to enjoy life.” (S35) “Well… I hope to have a longer life than – you know, and be much more healthier.” (S15) “I’m hoping that my liver will get better because he said that I also have cirrhosis now because of the Hep C.” (S34) “I don’t know if it will, but it’ll just be a joy to me to know that I’m cured, that my liver is going to last at least 20 more years maybe…I’d like to see my grandchildren grow up more than they are. I have some that are grown and have children of their own, but I have small ones that I would like to see get older.” (S52)
Anticipated Healthcare Benefits
Participants hoped they would need to see their doctor less frequently and take fewer medications if cured.	“I’m hoping I’ll have to go to the doctor less, because I feel like I’m always going to the doctor these days.” (S8) “And it would be less medicine that I have to take. And I feel like, you know, when you get to start taking medicine, you have to continuously take different medicines to combat side effects from other medicines, and this would be one less thing to worry about.” (S93)
Anticipated Psychological Benefits
Psychological benefits tied to social benefits and stigma reduction Many anticipated psychological benefits were mentioned in relation to improving social functioning or removing internalized stigma due to having HCV.	“It’s kind of like your mind playing tricks on you. I don’t know. You know it, but you think everybody else does too. So when you go out I don’t wanna – I’m probably gonna be less – a lot less worried about being around people if I don’t – if I’m cured and don’t have it… It might help me to open up a little bit more to people like I used to. I used to be a social butterfly” (S67) “Knowing that you’re carrying something around that can kill you any day—well, that’s how I thought, anyway. That’s what put a toll on me. It’s you’re not equal with people when you’ve got something inside you that can hurt you down the line, so I didn’t feel equal. Like, most cool guys holler at pretty girls—I didn’t, because I knew I was carrying something that could hurt me and her. That could hurt her—I’m already hurt, so. I didn’t feel equal.” (S3)
Peace of mind Being cured would bring a great sense of relief and reduce the stress of worrying about having HCV.	“Just kind of relief that this is one of the last things over my head from the bad choices I made when I was a teenager. So I’ll definitely feel like I’m past everything, I’ve done, completely moved on to a new chapter, more matured.” (S4) “Well, the mental and psychological benefits will be immense because, like I said, I’ve been worrying about this for 14 years…” (S14) “I mean, it’ll be a relief though. I don’t know if that’s an emotion… Just to be done with it. I know how dangerous it is.” (S94)
Better outlook on self and life Many participants communicated the hope for new beginnings, a better outlook on life and improved self-esteem.	“If I am clear of it it’ll make me feel even better. I’m not using. I don’t plan on going back. I’m great in my life right now, in a place of mind that is great for me. But I’d just like to get this off under my belt. This is the last thing I have to complete to make sure I’m taken care of and be comfortable in my own skin again.” (S67) “Just my general state of mind and my optimism, hope. I just don’t want to have this hanging over me wondering if it’s going to become symptomatic. I’m hoping that I can leave all that behind me, and on top of that, I won’t have what they consider to be a sexually transmitted disease.” (S49) “I would feel better about myself. I would be more upbeat and more positive. I wouldn’t have this impending doubt or feeling of some impending doom or something that may happen… Well, I’m hoping it will be something I don’t have to think about anymore.” (S93)
Feeling less guilty about the past Some participants expressed feelings of guilt over past behaviors and hoped that being cured would resolve these feelings.	If I’m cured, my whole quality—I feel like, in my heart, if I get cured, my whole quality of life will change. I won’t have this sinking feeling in the back of my mind all the time… I won’t have this guilty feeling on me anymore. It’s gonna be the greatest thing in the world—I can’t wait.” (S4)
Anticipated Emotional and Mood Benefits
Worry reduction Participants hoped to have decreased worry and thought this decreased worry would have a beneficial impact on physical, social and work functioning.	“I think worrying—for me, it was mostly worrying, you know? Worrying what’s gonna happen, what’s gonna happen to me, what’s gonna happen when I take this, what’s gonna happen with this, or going to this doctor, going to that—it can wear you out, you know? So worrying, you know, that’s—ooh, man, that’s a benefit by itself. I won’t have to worry about none of this stuff no more. I can be free.” (S3) “Just not having to worry about it anymore would really ease the stress in my life.” (S5) “Well, it would be one less thing I have to worry about, but, you know, I’m hoping that when I have a good amount of energy and I’m keeping busy, I don’t really get depressed very often.” (S34)
Stronger grip on emotions and moods Some participants hoped they would be in better control of their emotions once cured of HCV	“Well, my emotions are, again, unpredictable. I may be sad for one moment, and then, I want to laugh about things the next. I’ll sit in one place, and I really don’t have to remember things, or I’ll be thinking about certain things that have bothered me in the past, and I’ll get emotional or even cry. These things, I want to stop these things. I’m hoping for them to stop. I’m hoping for all those things to get better, about my emotions to be more clear, more precise…” (S14)
Anticipated Cognitive/Mental Benefits
Participants who hoped to experience improvements in mental capacities looked forward to being more clear-headed, having better concentration, and experiencing decreased confusion.	“I hope to not have memory issues as bad as they’ve been getting or confusion…It’s tough when you say something to somebody and then can’t remember that you just said that, and it was just in a basic neutral conversation.” (S09) “…I’m looking forward to all these things changing, the pain, the fatigue, feeling much more clear-headed, not being completely occupied with trying to deal with this, or think about what the next day is going to be. I may be able to have all this time to feel good for a freaking change.” (S14)
Anticipated Personal and Family Benefits
Better physical and emotional well-being will lead to more quality time with the family About a third of participants described ways in which they hoped that improved physical and emotional functioning would allow them to spend more quality time with family and hoped that increased longevity would result in additional time spent with family.	“No, just being able to do – to feel better when I go places, and if I go with my daughter or whatever, and with the kids, and just being able to feel better physically, and mentally, to deal with – just to have fun with my family, instead of feeling in pain, and not feeling good.” (S52) “I’ve got my daughter here, and I’ve got my son in Florida. I’ve got two granddaughters, and I don’t want to die at the age of 60. It’s too soon, not over something like this, hm-hmm, no.” (S30) “Again, I hope to be able to feel comfortable around being – being around people, whether they’re strangers, or whether they’re my family, my immediate family, my children, my grandchildren. To be quite honest with you, I don’t go out. I haven’t been out in years.” (S14)
Anticipated Benefits to Social Life
Increased ability to engage in social activities with reduction of physical symptoms Participants looked forward to engaging in social activities once physical symptoms were ameliorated.	“The energy and the drive that I used to have, be able to – I’ll start doing things with people, start going places…I think I’d be a lot more motivated to do a lot more things, be around more people, be open.” (S35) “Well, there are times when my wife wants to go do something or when she wants to get together with some friends or something and I just – don’t feel up to it. I’m hoping that that will improve because I’m usually pretty outgoing” (S34)
Improvements in emotional and psychological health could lead to increased desire to socialize and increased comfort around others A number of participants reported that they hoped to feel less worried, have a better outlook, and feel more motivated, all of which could lead to increased desire to engage in social activities.	“I hope it’ll stop me from isolating, because I’ll feel equal again. I’ll feel equal with people. Right now, I don’t feel equal.” (S3) “Just a part of being a part of the human race again I think I’m – I just want to live life normally and not have to always worry about this…some days I just don’t want to leave the house. So I don’t wanna be around anyone socially at all. I just kind of wanna be alone.” (S67)
Anticipated Benefits to Romantic/Sexual Life
New romantic relationships will be possible once there is no longer fear of disclosure and sexual transmission Participants were hesitant about dating or starting a new relationship because they felt a need to disclose their HCV status and/or be concerned about transmitting the virus sexually.	“It’s one less thing I’ll have to disclose to any significant other. Just not having to worry about it anymore would really ease the stress in my life.” (S8) “I stopped the online dating because like I said, I don’t want to meet somebody and be around them and something happens as far as maybe passing it along to someone else. It may give me the courage to go back to try to date.” (S93) “So I guess hoping that if I find somebody I can be physical with them too and not have to worry about is there – am I gonna give that to him or someone and have a good – maybe a good relationship with someone.” (S67)
Participants hope that sexual relations with current partners will improve Participants described their hopes for improved sexual relations once worry was abated and if they had improved libido and sexual functioning.	“I’m hoping that my energy level gets better and I’m hoping that the erection problem gets better, and I’m just hoping that, you know, I can live a normal life after that.” (S34) “My motivation to do or want to do things with my mate I hope that gets better ‘cause it’s lacking now. I don’t have the energy for it, the drive for it.” (S35)
Anticipated Benefits to Stigma and Discrimination Reduction
Anticipated reduction or elimination in fear of disclosure and anticipated stigma A number of participants described feeling as though they had something to hide and were either worried about needing to disclose their disease status to others, or inadvertently disclosing their status. Fear of transmitting HCV to friends or family prevented some people from engaging in social activities; they hoped to return to social activities once the possibility of infecting others no longer existed.	“I won’t feel like I’m keeping a secret from people.” (S49) “I think I’ll feel more like myself and better about myself and have a little bit more confidence in knowing that I’m not hiding anything from anyone or trying to protect them without them even knowing what’s going on…” (S43) “Yeah, sometimes with certain things that I want to do, like certain social activities, certain sports activities, certain types of training where it involves contact, I will feel a little bit more optimistic about pursuing some of those options…” (S54) “Yeah. I think mainly being able to actually see that there’s a point in trying to make friends and being able to communicate with people better, and not having to worry about whether or not I’m gonna say I have Hep C.” (S9) “I’d be getting out more and socialize with people and be comfortable being around other people. I wouldn’t have to worry as far as whether or not I’m going to infect anybody…I could go back to having my barbecues and cooking meals if somebody calls me and asks me to make a certain dish or whatever, I won’t refuse it. I’ll just go ahead and do it for them…Because right now I don’t really feel comfortable [cooking for others].” (S93)
Anticipated reduction or elimination of actualized stigma and discrimination A few participants reported that they hoped being cured would lead people to feel more comfortable around them, think about them differently, and treat them better.	“I’ve had places and people that I work for, places that I work for that have found out about it that eventually, they found a reason to let me go or not use me anymore, and I’m hoping that that won’t happen anymore. Yeah, that’s definitely a thing that I want to keep from happening in my life ever again, being discriminated against in many ways, including that. Having an infectious disease is not a fun thing at all in a lot, a lot of reasons, in a lot of ways, and when one finds out about it, they find every way they possibly can to get away from you and get you away from them, and that’s the bottom line.” (S14) “And I think my – you know, people will look at me different then. As far as my wife anyway.” (S35)
Anticipated Benefits to Occupational Functioning
While most participants did not mention benefits of cure on their work or productivity, 25% were excited about the prospect of working with renewed energy and a stronger, healthier body. Several participants intertwined work benefits with psychological and emotional benefits such as less guilt and a broader, more positive outlook on life could lead to better work outcomes.	“I’d like to have more energy where I do like I used to in this business…Those 10–12 hour days, now they’re 6–8 hour days or more like 6, more times than not.” (S73) “I hope to be better at work by being stronger and being the person I once was.” (S3) “Yeah, I worked in a lot of kitchens, but I feel a little guilty about working in kitchens with hepatitis C…It’s just another reminder of a limitation that’s there professionally….and once cured, it’ll just allow me to be a little bit more optimistic about what advantages, what opportunities I can take advantage of. I won’t feel like my focus is so very narrow.” (S54) “I don’t like being out of work. I don’t like staying home all the time because work is what I like to do, to not only make my money, but fulfill my day. So I’m hoping to be able to just go back to work and just live a normal life.” (S34)
Other Anticipated Benefits
Some patients expressed hope for improvements in other areas not easily captured by the above themes. These included efforts to get healthier and stay healthy (e.g. exercising more, eliminating alcohol), general improvements in quality of life (e.g. more time), and a new ability and interest in helping to inform others about HCV prevention and cure.	“Well, like I said I will – my health, most definitely. My eating habits and all those things I know I need to get right. That is my hope.” (S25) “I hope my liver will straighten out and I will not – never go back to drinking and doing what I was doing…I mean if this is cured I know that, you know, there’s a chance for the cirrhosis to be cured so, you know, that’s my hope. I hope I can cure both of these and I will not go back to drinking or doing nothing crazy like that ever again.“ (064) “I’d have a whole lot more time on my hands [chuckles] not having to deal with it…so it’ll free up a lot of time not having to deal with it.” (S14) “So I’ve done as much as try and find out what I could do, either as an advocate or as a subcontractor in terms of spreading awareness and holding events. So yeah, I can see myself certainly advocating for some kind of hepatitis C initiative, yeah. I can see myself doing that…I could be, like, a living testimonial to, you know, my—and use my history.” (S54) “Like I said, I just want to go back to having a normal life, not worrying, and get a job, and not have all my back-to-back appointments 24/7, and get better, and be able to focus on life.” (S30)

Anticipated Benefits to Physical Health and Symptoms.

75% of participants expressed hope for improvements related to physical functioning, physical symptoms (e.g. aches, pains, skin issues, weakness, nausea), or quality of life related to physical health. While a few participants described hopes for improvements to general physical well-being, most described specific physical ailments they hoped would improve once cured. The most frequently cited symptoms were fatigue and pain. Most participants (61%) hoped that the fatigue or decreased energy that they attributed to HCV would remit after treatment, although some were uncertain if HCV was the cause of their fatigue. Participants also hoped that the worrying about the disease which led to low energy, would no longer exist. With less fatigue and increased energy, participants said they would generally become more physically active and hoped to return to activities that they used to enjoy. Participants also thought that increased energy would improve their mood and outlook on life. HCV-related aches and pains were the second most common physical ailment that participants hoped would improve. Participants described having abdominal pain, headaches, myalgias, and arthralgias that they hoped would improve. For some, the experience of aches/pains was closely intertwined with fatigue, mental and emotional well-being. A few participants hoped that digestive and skin issues would improve.

Anticipated Medical Benefits.

64% of participants expressed hope for improvements in liver disease, risk of liver cancer, or other medical conditions (e.g. skin disorder, diabetes, insomnia). Participants spoke in general terms about living longer and being in better health. Most participants hoped being cured would strengthen their liver, but they also hoped that other health issues would improve or that their bodies, in general, would be healthier and more capable of preventing future illnesses. Some wanted to turn their attention to other medical issues when cured.

Anticipated Healthcare Benefits.

39% of participants expressed hope for improvements with engagement in healthcare. Several participants hoped they would have fewer appointments, less frequent visits with their doctors, take fewer medications and have fewer blood draws if cured.

Anticipated Psychological Benefits.

61% of participants expressed hope for improvements related to psychological constructs such as positive coping, reframing, optimism, or self-perceptions such as low self-worth, self-esteem or shame. Participants did not discuss these issues in a vacuum or think of them as mutually exclusive. Most discussed psychological issues in relationship to other aspects of their lives (physical, social, work) and believed that feeling better psychologically would lead to improvements in other areas. Many anticipated psychological benefits were mentioned in relation to improving social functioning or removing self-inflicted internalized stigma due to having HCV, such as feeling less shame. Others stated that viral cure would bring a great sense of relief and reduce the stress of worrying about having HCV. Many participants felt great hope for new beginnings, a better outlook on life and improved self-esteem. Those who expressed guilt over past behaviors or how they contracted HCV, expressed powerful hopes that being cured would alleviate some of these negative thoughts.

Anticipated Emotional and Mood Benefits.

93% of participants expressed hope for improvements in their emotional well-being or mood including feeling depressed, anxious, irritable, fearful, scared, anxiety about their health. The primary anticipated emotional benefit was worry reduction, which was often discussed in relation to other anticipated benefits regarding physical, social and work functioning. Other anticipated emotional benefits included feeling happier, decreased irritation, reduced anxiety, and an overall sense of freedom. Most of the time, patients hoped that being cured of HCV would drastically reduce worry and negative mood states, which in turn, would lead to improvements in other aspects of functioning. Patients felt that being less worried about what HCV will do to them would lead to less stress, better sleep, more energy, feeling better physically, wanting to be around other people more often, and stronger desire to find or keep a job. A few participants hoped they would be in better control of their emotions once cured of HCV.

Anticipated Cognitive/Mental Benefits.

18% of participants expressed hope for improvements in cognitive impairment such as memory, forgetfulness, and processing speed. Very few participants believed that their cognitive issues were related to HCV, identifying other comorbidities or age as likelier causes. Thus, most did not anticipate cognitive improvements after viral cure. Those who did, hoped to feel more clear-headed, have better concentration, and experience less confusion.

Anticipated Personal and Family Benefits.

34% of participants expressed hope for improvements in their family life, relationships with significant others including spouses, parents, children, extended family and overall family functioning. Patients felt affected by HCV physically and emotionally, which limited their ability to spend time with others. Several participants described ways in which they hoped that improvements in physical and emotional functioning would, in turn, allow them to spend more quality time with family. Being cured of HCV would improve how they feel physically, mentally and emotionally, thereby allowing more quality time with partners and family. Given the serious nature of the virus, many participants expressed a hope that achieving cure will increase their lifespan, which would provide more quality time with family.

Anticipated Benefits to Social Life.

43% of participants expressed hope for improvements related their general social life (social activities) outside of the family if cured. For the most part, participants described improved social functioning as a consequence of improvements in other areas: physical, emotional, or psychological health; a reduction in the fear of transmission; a reduction in anticipated stigma; or a combination of these. Participants looked forward to engaging in social activities once physical symptoms like fatigue and pain were ameliorated. A number of patients suggested that improvements in emotional and psychological health could lead to increased desire to socialize and increased comfort around others.

Anticipated Benefits to Romantic/Sexual Life.

39% of participants expressed hope for improvements in their romantic/sex lives. Some participants were reluctant to date or start a new relationship due to feeling the need to disclose their HCV status and/or risk of transmitting HCV sexually. They looked forward to entering new relationships once cured and free from these worries. Participants also expressed hope for improvements in libido and erectile dysfunction. Some participants described hopes for improved sexual relations with spouses or current partners once worry was abated.

Anticipated Benefits to Stigma and Discrimination Reduction.

36% of participants expressed hope for improvements in anticipated and/or actualized stigma. Anticipated stigma included worry about the negative psychological or social consequences of disclosing HCV status, while actualized/experienced stigma include experiences of discrimination, being treated differently or unfairly due to HCV. A number of participants described feeling as though they had something to hide and were either worried about needing to disclose their disease status to others, or inadvertently disclosing their status. Fear of transmitting HCV to friends or family prevented some people from engaging in social activities; they hoped to return to social activities once the possibility of infecting others no longer existed. Anticipation of stigma decreased social engagement and was related to feeling unequal or ashamed. A few participants hoped that if they were cured, other people might feel more comfortable around them, think about them differently, and treat them better.

Anticipated Benefits to Occupational Functioning.

While most participants did not mention benefits of cure on their work or productivity, 25% were excited about the prospect of working with renewed energy and a stronger, healthier body. Several participants intertwined work benefits with psychological and emotional benefits such as less guilt and a broader, more positive outlook on life could lead to better work outcomes.

Other Anticipated Benefits.

Some patients expressed hope for improvements in other areas not easily captured by the above themes. These included efforts to get healthier and stay healthy (e.g. exercising more, eliminating alcohol), general improvements in quality of life (e.g. more time), and a new ability and interest in helping to inform others about HCV prevention and cure.

Subgroup Analysis for Anticipated Benefits.

Participants with cirrhosis tended to focus on hopes that achieving HCV viral cure would reduce disease progression, development of hepatocellular carcinoma, and premature death. They also hoped for psychological benefits such as reduced worry and stress after viral cure. By comparison, participants without cirrhosis more frequently expressed hope for improvements in fatigue and energy level, depression and anxiety, reductions in stigma, and improvements in their relationships with others.

Participants with active psychiatric comorbidity hoped for improvements in physical symptoms but more so focused on improvements in depression, anxiety, worry, guilt associated with past behaviors leading to contracting HCV, and internalized stigma associated with shame and experiences of discrimination. They also focused on improvements in social functioning and relationships with family, friends, and significant others. By comparison, participants without psychiatric comorbidity were focused on overall improvements in health and a reduction in liver-related illness and premature death. They also tended to focus on anticipated reductions in healthcare utilization compared to patients with active psychiatric comorbidities.

Post-Treatment Actualized Benefits from Viral Cure

Of the 28 pre-treatment interviewees, 25 participated in post-treatment interviews four to nine months after being cured. One patient did not achieve viral cure and two patients were lost to follow-up. The same over-arching themes emerged during the post-treatment interviews; however, the psychological and emotional/mood themes were combined because these themes were highly overlapping. Stigma and discrimination reduction overlapped with improvements in many areas of functioning, so these utterances were not pulled out separately into one theme but left as subthemes under other domains (Table 3).

Table 3.

Participants’ actualized experienced benefits after receiving HCV treatment and achieving viral cure (n=25)

Main Themes and Sub-Themes	Illustrative Patient Quotes
Actualized Benefits to Physical Health and Symptoms
Increased energy was the greatest physical improvement, although participants also experienced less pain, digestive issues, bruising, skin irritations and more rapid healing. Feeling better physically was associated with improvements in other areas of life.	“My pain level is not as intense… I have found that I have been able to do more physical things more because I’ve tried them and I said, “Well, this doesn’t hurt anymore.” So that has brought me out of – that has slowly brought me out of this depression that I was in… Being able to do more physical things and becoming stronger physically because of that has brought me out of a very, very deep hole.” (S14); [Belly pain score improved 2.9 points; Depression score improved 4.5 points] “Well, I think I feel healthier… I think that just minor scrapes and bruises tended to heal a little bit better. There’s not scarring. Before, was seen a lot of scarring which I contributed to the hep C… I’m seeing that that has definitely changed.” (S54) “I don’t have the itchiness… It’s not like it was. Because when I was, I mean I would scratch all the time. I mean I would scratch so bad sometimes that my skin would be broken and raw or bleeding.” (S67) “Well, I just feel more energetic and just my overall, general health, I feel is a lot better than it was…I certainly just feel a lot more confident just in terms of my general, overall health…I’m a lot more confident now. I’m not really worried about what’s going on with my blood and my liver.” (S54)
Reduced fatigue and increased energy The most frequently reported physical improvement was having more energy and less fatigue.	“I feel great. I feel outstanding, tons of energy, everything’s just wonderful…I feel like I’m 18 again…” (S94); [Fatigue score improved 32.7 points] “I have more energy… now I’m able to have more energy to do more things, and I feel like I have more stamina. My strength, it’s kind of hard to explain, but I feel my strength more. I’m not as fatigued.” (S14); [Physical function score improved 2.1 points] “Yeah, I feel different. I’m not tired like I used to be, exhausted. I used to go out and try to do stuff but would just end up laying around the house and stuff like that but I get out a bit more now but… I want to do a lot more physically.” (S35); [Physical function score improved 1.3 points]
Actualized Medical Benefits
Participants reported improvements in their liver disease and other medical conditions.	“There was scarring on my liver, but it rejuvenated that… When I took that scan, scan, scan, liver scan, whatever it was, they told me it was just some scarring. It hadn’t progressed to a long – a lot – a bad part.” (S41) “My diabetes…It [being cured] brought it down to a 6.1 for me and I’m still there…Yeah. It brought it down real good. I mean it really helped my sugar for some reason…” (S25)
Actualized Healthcare Benefits
Participants reported reductions in the frequency of healthcare visits, including fewer physician office visits and fewer blood draws, associated with less money spent on healthcare.	“Yes, yes, when she told me that she could cure me I was ready for it because I was ready to not have to be going to the hospital all the time and stuff like that, you know, taking blood and all that stuff – I was tired of that.” (S4) “Like I’m happy. I don’t have to worry about blood work every couple of months. And of course, after being an intravenous drug user and not using – three years clean now – I just couldn’t stand to have the needle every couple of months. It’s not fun.” (S9) “One thing that’s good is I did not have to stress out with a monthly health insurance bill…” (S9)
Actualized Psychological and Emotional/Mood Benefits
Worry reduction and sense of relief Many participants reported a general sense of relief about being cured of HCV, decreased worry about having HCV and the damage it could do to their health, and decreased internalized stigma. Decreased worry led to myriad other psychological improvements in well-being.	“The biggest change, I don’t have that worry – that cloud of darkness hanging over my head anymore…It feels good. It feels really good… Yes it does. A big sense of relief.” (S15) “My anxiety, my feeling helpless, feeling worthless, it’s not there. I’ve got a handle on that it seems…there’s kind of something new to me because I’ve been dealing with this for so long of a time.” (S14) “Oh, I mean it’s just a world of difference between before I took the medicine and now. Like I’m more like I used to be… Not all depressed and scared all the time.” (S34); [Anxiety score improved 2.5 points] “Like I said, the relief and peace of mind it’s brought me has been exponentially more than what I ever thought it would. I’m happier. I mean, I think it’s a mental thing. You know, mentally I know I’m healthier because I know I won’t have the risk of getting this disease and I continue to look to the future. It’s just, when you have that huge weight on your shoulders that “I’ve done something to myself that’s going to affect me for the rest of my life,” it just adds a lot of stress…” (S8); [Depression score improved 14 points; Anxiety score improved 9 points] “Yes, I see things more clearly now. I mean there are some less things I have to worry about as far as my health goes and that took a whole lot off me. I see things a lot more clearer now, just focus on 1 thing at a time now instead of having to worry about this and worry about that.” (S35) “I’m not really worried about what’s going on with my blood and my liver…as a result of that, I’m a lot more involved. I feel a lot more confident. I’m a lot more motivated to take better care of myself, that’s for sure. I’m a lot more active and I feel like I’m more motivated to be engaged in regular exercise now.” (S54)
Renewed self-esteem Achieving cure also helped participants feel better about themselves and lessen feelings of shame, guilt and worthlessness about having contracted the disease.	“I don’t have the shame, this cloud of shame hanging over me. I feel I have a higher level of self-esteem, certainly now… I no longer feel like I have something to hide.” (S54) “Improvements I would say – well I mean I just feel better about myself. I feel like I’ve got nothing wrong with me that I know of. That’s all I had was the Hep C and I had that for over 20 years…” (S68) “I guess just happier like overall. Like not as worried. But I’m just determined to continue to better myself. Like that was like the last thing holding me onto my past. That was the last thing holding me captive. And just the sense of a lot of relief after getting cured.” (S8); [Depression score improved 14 points]
Gratitude and hope One of the biggest unanticipated benefits of HCV treatment was a sense of gratitude for being cured of HCV, having hope for the future, and a renewed appreciation for life.	“I guess I’m mostly just feeling thankful that they have found a cure. Because I know for a while it was uncurable and they couldn’t do anything about it and if you had it, it was just bad…I’m just so grateful.” (S8) “Mentally I feel great and emotionally I feel great. You know, pretty much everything towards hepatitis I feel great about it… I feel a lot better about, you know, living longer… Oh, it’s a great amount of hope for the future and now I’m thinking that maybe they’ll even find a medicine that’ll cure my other problems.” (S49); [Anger score improved 10.4 points; Anxiety score improved 13.6 points] “I think the whole experience has just made me feel a whole lot more appreciative for life and health than I had before. That’s really a positive feeling, so that’s good…” (S19)
Psychological benefits tied to social benefits Participants also described how improved psychological and emotional well-being led to improvements in other aspects of life, such as social functioning and stigma reduction.	“Oh, I’ve been feeling real good, so secure, because I don’t have that to worry about… You know, it’s just knowing that I don’t have to hide it, and knowing that I can just go off and just do whatever I want and not worry about it. I mean that has been a big relief, you know.” (S34); [Anxiety score improved 2.5 points] “It’s more of peace of mind for me… I’m in a new relationship than I was in when I was infected and it’s not like I have to tell him. It’s not like there has to be a conversation, like, “By the way, I have this like disease,” and I can talk about I overcame it versus that I’m currently dealing with it.” (S8) “I’m not hiding that secret anymore… So that’s a weight off my shoulders and like I’m not thinking about what if someone finds out…” (S30) “I felt that when I had the Hep C… It definitely affected my interactions, dating, and just engaging people that I might be interested in because I was – felt really, really bad about that. I couldn’t see myself in any kind of a healthy relationship and sharing any kind of intimacy with anyone as long as I had the Hep C…I’m much more excited about pursuing relationships, that’s for sure.” (S54); [Ability to participate in social roles and activities score improved 0.8 points]
Actualized Cognitive/Mental Benefits
Some participants described improvements in their cognitive functioning after viral cure which were associated with improved work functioning.	“I would say I have a clearer head. I never thought about it that way before, but now that you mention it, I think I’m way more level-headed and like I’m able to keep a mental to-do list. I was honestly pretty forgetful. I didn’t realize that that was part of it. Yeah, I would forget things people told me.” (S8); [General cognitive concerns score improved 13.7 points] “I feel my memory is better, and brain fog is better…I’m not sure real sure that that has to do with the hepatitis or what… but I do feel a little bit sharper or clearer – I don’t know how to describe it – mentally…Yeah. Not as many word finding issues. Sometimes I had word finding problems, and I think that’s better.” (S19); [General cognitive concerns score improved 12.2 points] “Yeah the brain fog is lifted and just in general my brain feels a lot clearer. I don’t know if that makes any sense, but it does feel clearer than it was.” (S34); [General cognitive concerns score improved 0.3 points] “I would say it’s [focus and attention on job tasks] better. Yeah, it’s much better. I pay a lot more attention to what I’m doing and I’m a lot more focused than before.” (S54)
Actualized Personal and Family Benefits
Improved relationships with family members Some participants experienced improvements in relationships with family members after cure. Some had hoped for these changes, while others welcomed these unanticipated benefits.	“My relationships have changed somewhat with my children. They’ve gotten so used to seeing me as a dysfunctional person. That was one of the things that was killing me inside. I can see it, a very small amount in their eyes and in their face when they see me now, that they don’t see that person anymore.” (S14) “We actually have a better relationship. She [my sister] just recently went through a life-changing surgery for herself too… …we’ve never really been very close ever, but…We’re a lot better than we were.” (S67) “I guess we might be stronger, even more than we were before…. And overall the morale is better, knowing that her daughter is going to grow up with less of a chance to get liver cancer and other things.” (S8) “Oh, it feels great. It’s like I’m 10 years younger…in fact, there are times now when my wife will say we’ve got to go shopping and if she’s not feeling real well I just tell her to give me the list and I’ll go do it.” (S34); [Ability to participate in social roles and activities score improved 2.5 points]
Reduced fear of transmission to family members Not having to worry about transmission of HCV made some participants more comfortable around their family, especially children, a benefit that participants had hoped for prior to treatment.	“I am more social. I don’t feel like I can’t be around my loved ones, especially my children… I mean I’m still careful about that just in case but I don’t feel as afraid that I was.” (S67) “Yes. I don’t have this fear of what if I – ‘cause I like to cook… And that’s always in the back of my mind whether or not something happen, if I cut myself and somebody, you know… But having them get this and it be my fault… ‘Cause matter of fact, my great-nephew wanted to eat lasagna at Christmas and I fixed him one. Of course his father tried to eat half of it before he got to it.” (S93); [Anxiety score improved 1.9 points] “Oh, I don’t have any worries as far as interacting with them [nephews]. You know, we – I try to spend time with them as much as possible.” (S93); [Ability to participate in social roles and activities score improved 2.4 points]
Actualized Benefits to Social Life
Several participants reported a variety of benefits to their social lives following HCV cure, linked to less stigma, improved mood and optimism, increased energy, and having fewer physical symptoms.	“But really it’s just – getting cured, people aren’t scared to be around me, like what I felt before. Like they’re more willing to hang out because there’s no risk.” (S9); [Social isolation score improved 1.3 points; Ability to participate in social roles and activities score improved 15.7 points] “Well we talked about it but it’s still not really been much said about it… They just thought it was something real bad and, you know, it was kind of like the AIDS thing…So I think they – you know, they see now that I’m okay and it’s not like – you know, they’re not gonna catch anything or whatever.” (S46); [Stigma score improved 12.2 points] “Yes, I’m spending a lot more time out socializing with people than I was before…It feels good. I mean I can finally go and drive myself a little bit instead of lying around the house not wanting to do anything.” (S35); [Social isolation score improved 8.6 points] “I’m a lot more optimistic, a lot more engaging, a lot more willing to just share in dialogue. I’m not so guarded… For a long time, I was guarded in all of my conversations. I find that I’m much more spontaneous. Yeah, much more spontaneous with people now. (S54); [Ability to participate in social roles and activities score improved 0.8 points] “I go out a lot more than I used to. I’ve traveled actually a little bit since, too… I was afraid that I wouldn’t be able to do any of that but, you know, I was able to get out and travel and I’ve been traveling quite a bit… it was rarely ever that I left home [before]…” (S67) “Well I’m a little more social than I had been. I kind of got away socially from people because I wasn’t feeling well and stuff like that. So I’m socializing a lot more these days.” (S34); [Ability to participate in social roles and activities score improved 2.5 points]
Actualized Benefits to Romantic/Sexual Life
Reduced fears of being judged or stigmatized Some participants found it easier to enter into new romantic relationships, particularly as they no longer had the fear of being judged or stigmatized.	“…like I’m in a new relationship than I was in when I was infected and it’s not like I have to tell him. It’s not like there has to be a conversation, like, “By the way, I have this like disease,” and I can talk about I overcame it versus that I’m currently dealing with it.” (S8); [Stigma score improved 10.9 points] “Yeah, I’m much more excited about pursuing relationships, that’s for sure. I don’t see that as a hindrance anymore. When I meet someone that I’m intrigued with, I mean, that’s no longer a hindrance. So I can’t – I don’t find myself thinking, ‘Well, I can’t really interact with this person because I have this terrible disease and I don’t know if I’m really ready to share that with this person.’ That was something that I never did. I just abstained from all intimacy during the whole time that I was afflicted with the hepatitis C virus… So that’s no longer a problem for me.” (S54) “I mean, in terms of day-to-day existence, just transmitting the disease was a big concern, but when things became personal, it honestly became about what this other person perhaps thought of me.” (S54)
Reduced fears of transmission to sexual partners Being cured relieved concerns about sexually transmitting HCV to partners and this was most often an unanticipated benefit.	“And then my wife got monitored to make sure she didn’t get it…I don’t have to worry about that now, so that’s a big relief.” (S34) “…so that is a relief knowing that that’s been taken out of the picture as far as infecting her…” (S78) “The only thing that would change is if I had sex I wouldn’t have to worry if I ran out of condoms or something like that…because they told me it could be transmitted sexually.” (S49)
Actualized Benefits to Occupational Functioning
Some participants reported experiencing work-related benefits following treatment, including the ability to work due to increased confidence, reduced anxiety, improved physical condition and strength, and decreased fear of transmission and stigma.	“I’ve been able to work for a temporary service. They put me on a job, one they told me about. I said, ‘There’s no way in hell I can do this.’… Then I found out that I could do this…it took me by surprise, “I can actually do this.” It wasn’t easy to do it, but I could actually do it. The pain was there, but not as much. It was a pain that I could deal with and work through.” (S14); [Physical function score improved 2.1 points] “I would say it’s [focus and attention on job tasks] better. Yeah, it’s much better. I pay a lot more attention to what I’m doing and I’m a lot more focused than before. [Working relationships with colleagues] are better….I think my relationship with people in general, is a lot better now…there is less anxiety I feel. There is less anxiety just in terms of dealing with people.” (S54) “And I think a big thing for me; a lot of times, with different things that I was doing or different jobs I was pursuing, just knowing that I had hep C somehow – and sometimes made me question what type of jobs I would pursue, like restaurant jobs or part-time jobs working in the restaurant industry and stuff like that. Yeah, I was very, very uncomfortable exploring any of those opportunities …That’s no longer a big deal…” (S54)
Physically able to do more work tasks Several participants described ways in which improvements in physical health resulted in increased ability to perform work tasks. They often hoped for these improvements prior to treatment.	“Yeah, I think I have more energy than I had before. I was kind of dragging around before but now I feel like I got the energy and I can give it my all at work…Because at one point the doctor wanted to put me on disability and I told him I wasn’t going on disability unless I absolutely had to, you know. So things have been improving and work is one of them. I mean I got a lot more energy now to go to work.” (S34); [Fatigue score improved 8.2 points]; “Just having more energy. You know, I’ve been working out a lot and work just isn’t an issue anymore. It’s just almost easy now…Yeah, I’m doing that [manual labor] now as well and it’s just – yeah, it’s fine. Like they don’t have enough furniture for me to lift. [Laughs]” (S94); [Fatigue score improved 32.7 points] “The biggest thing about work again, that I notice, scrapes and bruises don’t seem to be as glaring when they heal as before. My energetic at work? Yeah, very energetic. I don’t know if I’m much more than I was before, but I do know that, in terms of just a regular fitness routine, I’m much more – I guess I feel better. I’m in better shape now. Yeah, I work much longer hours now.” (S54)
Other Actual Benefits
Health and wellness changes Participants talked about how they cut down or completely eliminated alcohol consumption, exercised more regularly, and were able to discontinue anti-depressant medications.	“I’m a wine-y girl so I liked my wine, and so I basically cut that back like 80 percent. I mean I know – and I understand and I’m telling the truth. If I go to a party or – I might have one glass, you know?… Before I would – I’d usually have wine at home and stuff like that.” (S30) “Because I had stopped drinking. I would not drink to the extreme, but I stopped drinking when I found out I was going to have to take this stuff, and I just stopped drinking… Yeah, I just don’t drink. I don’t smoke cigarettes anymore.” (S41) “I have more of a regular fitness routine now. For about the last year, I’ve been engaged to just regular fitness routines and yoga in the morning. Some push-ups, sit-ups, and some weight training. Not intense weight training, but a little weight training… I give a lot of credit that because it was a constant worry just in terms of my general health. It was extremely depressing. So now that that’s lifted, I think I’m a whole lot more optimistic. (54) “I stopped taking my antidepressant very slowly. I titrated off very slowly… So I started on some supplements to help with depression, and I’ve had to really get on an exercise routine to help with that. I’ve also been going to a therapist and doing meditation, and those things have really seemed to help me get over the hump and continue on without medication.” (S19); [Depression improved 14.4 points]
Educating others and advocating for treatment Participants felt that their story of being cured of HCV could help others and voiced their desire to spread the word about their experience to educate others.	“Just, like I said, it was a horrible experience that turned into a wonderful thing at the end. So I feel really lucky, so lucky. I would like to do whatever I can. The nurse in me of course makes me want to educate people and do whatever I can to help other people through or make sure people are getting tested and such.” (S19) “Just to let people know that taking the medication is not as bad as the rumors are that go around about it. That’s what stopped me in the beginning was, you know, rumors of bad reactions to the medication and all that. But, you know, I had no side effects and there was no big deal with it.” (S53) “And I’ve shared that with some people; that I went through treatment and it was good and I’m doing well… People generally are optimistic when they hear that and they appreciate knowing that. So yeah, it’s motivated people, I like to think, to follow-up with it and take advantage of the treatment options that are out there.” (S54)

Actualized Benefits to Physical Health and Symptoms.

Most patients (76%) reported experiencing physical improvements after viral cure, largely related to having more energy and feeling less fatigued. Of the 17 participants who specifically hoped for improvements in fatigue, 12 experienced improvements in energy and fatigue after achieving viral cure. Other improvements included less pain and digestive issues, bruises and cuts healing quicker, and less skin irritations. Participants mentioned that feeling better physically improved other areas of their lives, including psychological/emotional, social, and work-related activities, suggesting a strong link between improved physical health and other aspects of QOL. Some participants experienced minimal differences after cure, mainly because they did not have physical complaints before treatment. Some had difficulty knowing if their ailments were due to HCV, other health conditions or ageing.

Actualized Medical Benefits.

About 24% of participants felt they had achieved improvements in their liver disease, reduction in cancer risk, or to other conditions (e.g. skin disorder, diabetes, insomnia, etc.). Others reported knowing that they still had cirrhosis and needed to be monitored carefully. One participant was satisfied to know, at the very least, that the cause of some of her ailments was not HCV, thereby enabling her to pursue other remedies.

Actualized Healthcare Benefits.

Only a few participants (16%) reported benefits such as fewer visits to the doctor, fewer blood draws, better treatment by healthcare staff, and less money spent on healthcare.

Actualized Benefits to Psychological and Emotional/Mood.

These themes were combined for the post-treatment analysis because they were highly overlapping. Most participants (92%) who shared their hopes for psychological or emotional benefits before treatment, reported that these hopes had been realized, especially pertaining to an enormous “sense of relief” or “peace of mind” that accompanied viral cure. Decreased worry and anxiety about harboring an infection that could damage their health was closely related to myriad psychological and emotional benefits, including less sadness, more happiness, less anxiety, feeling more like themselves, more self-confident, less guilt, and the ability to focus on other aspects of their lives. Achieving cure increased participants’ self-esteem and reduced shame and internalized stigma about having contradicted HCV. Participants also described how improved psychological and emotional well-being led to improvements in other aspects of life, such as physical, social, occupational functioning, stigma reduction, and romantic relationships, highlighting the interconnectivity of all areas of functioning. The biggest unanticipated improvement was a strong sense of gratitude for being cured of HCV, having hope for the future, and a renewed appreciation for life. A few patients who felt they were not affected by HCV before treatment, did not experience psychological or emotional improvements after treatment.

Actualized Cognitive/Mental Benefits.

24% of participants described improvements in their cognitive functioning (memory, word retrieval, focus, attention, and reduced “brain fog”) after cure. Some were not certain whether to attribute these improvements to being cured, but noted that it was a possibility. A couple of participants mentioned a desire for improvements in cognitive abilities before treatment, but reported still experiencing issues post-treatment. For some participants, cognitive improvements were unanticipated but welcomed.

Actualized Family Benefits.

Some participants (24%) experienced improved relations with family members after being cured of HCV. For some participants, not having to worry about transmission made them feel more comfortable around their family, especially children. For one participant, getting rid of HCV led to his children having a more positive perception of him which, in turn, improved their relationships. Another reported an improved relationship with her sibling, in part, due to their shared experience of overcoming a health challenge. A couple of women described unanticipated improvements in their relationships with their mothers as a result of being cured.

Two participants described ongoing discomfort with HCV disclosure and would not be sharing their diagnosis or cure status with family or friends.

Actualized Benefits to Social Life.

Several participants (24%) commented on improvements in their social life, in general, due to increased mood, optimism, renewed motivation to socialize, and reduced fear of transmission and experiencing stigma. A couple of participants reported that they got the feeling that others were more comfortable around them now due elimination of transmission issues. Sometimes increased socialization was due to having fewer physical symptoms and more energy. Some patients had hoped for increased motivation to socialize before treatment and these hopes were often realized after treatment. One participant commented that now that treatment was over, she could resume drinking alcohol again which enabled more social interactions; albeit with better control of her alcohol consumption.

Actualized Benefits to Romantic/Sexual Life.

Participants (28%) described ways in which being cured improved romance, dating, and entering new romantic relationships. With no HCV status to disclose, participants had no need to fear being judged and stigmatized. Being cured also relieved concerns about transmitting HCV to spouses or current sexual partners, which was an unanticipated, but welcomed, benefit.

Actualized Occupational Benefits.

Some participants (20%) reported experiencing work-related benefits following treatment. These included the ability to work due to increased confidence, reduced anxiety, improved physical condition and strength, and decreased fear of transmission and stigma. One participant described a renewed ability to work due, in part, to reduced pain and increased self-confidence. Some participants described ways in which improvements in physical health (i.e., increased energy, stamina, and strength) enhanced their ability to perform work tasks. One participant described, as he had hoped before treatment, feeling more comfortable exploring job opportunities in his industry now that he no longer had to worry about transmission or disclosing his health status to potential employers.

Other Actualized Benefits.

Over half of participants (52%) commented on other benefits of viral cure that did not fall neatly into the themes above. Most of these benefits were improvements that were not verbalized or anticipated before treatment. Patients exclaimed that being cured of HCV had a rippling effect on all other areas of their life in specific and meaningful ways (e.g., financial, educational, spiritual). A few participants talked about wellness and health initiatives that began during HCV treatment (e.g., reducing or eliminating alcohol, exercising) that they continued after treatment. Participants also felt that their personal stories of overcoming HCV could help others and expressed a desire to share their experiences, serve as patient advocates, or educate friends about HCV and viral cure.

Subgroup Analysis for Actualized Benefits.

After achieving viral cure, participants with cirrhosis reported reduced worry about future liver damage and feeling a sense of relief from being cured, while those without cirrhosis tended to focus on improvements related to their energy level, mood, social interactions, and sex life, with many of these benefits being related to a reduction in internalized stigma.

After achieving viral cure, participants with psychiatric comorbidity most frequently reported improvements in fatigue and strength, reductions in general anxiety and worry about future health problems, and improvements in social relationships and interactions, partially due to reduced fear and worry about disease transmission. By contrast, participants without psychiatric comorbidity discussed having a better outlook on life, reduced worry about liver-related health, and able to focus on other health issues and a healthier life, such as eating better, being more physically active, and consuming less alcohol.

Discussion

Patients may have different personal motivations for wanting to undergo treatment for chronic HCV and may experience nuanced improvements in QOL outcomes after being cured. This qualitative study was designed to obtain a comprehensive picture of patients’ anticipated (hoped for) benefits of viral cure and their actualized experiences after being cured of HCV. Our findings highlight the substantial and widespread negative impact that patients perceive HCV having on many aspects of their lives, as well as the tremendous hope they have for DAA treatment to improve their lives. The majority of participants perceived broad reaching substantial improvements in many aspects of QOL for which they expressed continued hope and gratitude. Participants experienced improvements in many different aspects of their lives, consistent with broad domains captured by many QOL instruments. However, within these over-arching domains, nuanced and salient subthemes emerged that highlighted additional benefits to patients’ lives following viral cure that warrant more attention as patient-centered clinical outcomes in DAA trials. These findings also illuminated the complex ways in which different aspect of HCV patients’ well-being interact in a synergistic manner, such that improvements in some areas (physical, emotional) lead to improvements in other areas (social, occupational), ultimately improving overall quality of life in patients who are cured.

Before HCV treatment, patients hoped for improvements in many aspects of functioning. By far the greatest hopes for improvements were in the emotional and psychological realms, related to worry reduction that patients felt would have a positive rippling effect on other areas of life functioning. It is interesting that more patients hoped for improvements in their emotional and psychological health than simply improvements in their liver disease or medical conditions. Many patients believed there was a link between physical symptoms, such as fatigue and pain, and HCV and hoped that viral cure would bring symptom amelioration. Over half of patients hoped that being cured of HCV would improve aspects of social functioning. Potential improvements to family life, romantic /sexual relationships and social interactions due to decreased fear of transmission and anticipated stigma were explicitly described. Patients also hoped for improvements in employability, work performance, stamina and coworker relations if cured, usually related to improvements in energy, reductions in symptoms and less opportunity for discrimination.

After achieving viral cure, patients experienced improvements in multiple aspects of life functioning that were highly interconnected. Some benefits had been hoped for, while some were unanticipated yet welcomed. The vast majority expressed meaningful improvements in their psychological and emotional health, including renewed self-esteem, confidence, and peace of mind, as well as less anxiety, fear, irritability, depression, guilt and internalized stigma. Much of the reduction in anxiety and shame occurred as a result of the elimination of an infectious disease and the resultant fears of transmission, “being discovered,” and potential for stigma and discrimination. The vast majority also experienced improvements in their physical health, such as more vitality and energy, less pain, and improved healing of skin and abrasions. Due to having more energy, and less worry, self-inflicted stigma and fear of disclosure and transmission, patients’ social lives dramatically improved in broad and meaningful ways. ‘Brain fog’ and cognitive functioning improved in some. Occupational functioning improved and led to better work performance and seeking employment. Unanticipated benefits of viral cure were a sense of gratefulness, renewed vigor for life, healthier lifestyle habits, more controlled alcohol consumption, and a desire to share their experiences to encourage others to seek curative treatment. Improvements described by patients often corresponded with clinically important improvements in PROMIS scores, with large change scores seen for fatigue, depression, anxiety, cognitive concerns, and domains related to social functioning.

We found interesting differences in anticipated and experienced benefits of viral cure in our subgroup analyses. When seeking HCV treatment, patients with cirrhosis hoped most for improvements in liver-related outcomes and premature death, likely because they experience substantial morbidity and worry directly related to their liver disease. In contrast, patients without cirrhosis may not experience the same burden related to having liver disease, explaining their ability to focus on, and hope more for, improvements in physical and psychological symptoms they attribute to HCV, as well as improvements in their relationships and interactions with others. In a similar fashion, patients with baseline psychiatric comorbidity often suffer from significant depression and anxiety, and having HCV may heighten these symptoms, as well as make them more prone to feelings of guilt and internalized stigma, which affect their ability to socially function and develop relationships. Therefore, it makes sense that these patients would hope most for and experience improvements in these domains after achieving viral cure, whereas patients without psychiatric comorbidity hoped for and experienced benefits related to overall health, lifestyle, and healthcare utilization, and did not focus so much on psychological, emotional, or social improvements.

These findings have both clinical and research implications. The results highlight that people infected with HCV may be equally or even more motivated to undergo treatment for psychological and emotional benefits, relative to medical motivations related to worsening liver disease, per se. This may help explain the perspective of newly diagnosed patients who have minimal evidence of liver disease, yet still strongly desire treatment to reduce health-related worry, guilt, internalized stigma and feelings of low self-worth that may stymy other areas of life functioning. After being cured, patients experience a wearisome burden lifted (psychological benefit), which seems to pave the way for multiple substantial improvements in social functioning (engaging in society), mental health functioning (less depression, increased self-esteem), physical functioning (more vitality) and occupational functioning (getting and keeping a job, working longer hours). It is critical that providers and insurance payers involved in treatment decision-making and approvals of DAA medications are keenly aware of the multi-dimensional clinical benefits bestowed on individuals and our larger society that directly follows HCV viral eradication.

Regarding future research implications, many patient-reported outcome measures that are used commonly in DAA treatment outcome studies do not completely capture all of the challenges of living with HCV nor the nuanced benefits of treatment bestowed on patients’ lives [15]. Very few DAA studies have evaluated treatment benefits such as improvements in chronic pain, sexual functioning, feelings of stigma, personal identity, engagement in romantic relationships, or reductions in worry related to transmission and disclosure. However, newly-developed PRO instruments, such as the PROQOL-HCV, have been developed that capture a broader range of patient experiences, and other instruments, such as the Sexually transmitted and blood-borne infections (STBBI) Stigma Scale, appear promising for capturing specific constructs in more depth [16–17]. Consistent with the Food and Drug Administration’s guidelines on patient-focused drug development (PFDD) which mandates evaluating whether new medical therapies have clinically meaningful effects on how patients “feel, function, or survive” – it is likely that DAA outcome studies have been under-estimating the extent of clinical benefit, especially significant psychological and social benefits, bestowed on patients as a direct result of viral cure [18–19]. Our results also speak to the complexity of interconnected benefits from viral clearance. Based on our findings, Figure 1 shows a conceptual model of benefits of viral cure that begins with improvements in physical symptoms and reductions in worry and fear of disclosure and transmission which pave the way for subsequent improvements in work, psychological, emotional and social areas.

Figure 1:

Conceptual model of interconnected benefits of HCV viral cure

This study provides a comprehensive understanding of patients’ perceptions of anticipatory benefits from viral cure and actualized health benefits after cure. Although many of the overarching themes fall into traditional QOL domains, other salient and under-studied clinical benefits of viral cure were identified. While older PRO instruments capture some of these treatment benefits, investigators are encouraged to consider newly developed patient-reported clinical outcome instruments for future DAA treatment outcomes studies. Conceptually, it appears that symptom reduction and less worry and fear are the initial mechanisms by which improvements in subsequent psychological, social and occupational functioning are achieved. These QOL improvements are complex and interconnected, and may also be affected by other factors such as baseline severity of liver disease and psychiatric comorbidity as demonstrated in this study. The current study suggests that improvements in psychological, emotional, and social QOL outcomes may be more important to patients than providers’ emphasis on medical, physical and lifespan benefits.

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.