Hepatitis C Cure Improved Patient-reported Outcomes in Patients With and Without Liver Fibrosis in a Prospective Study at a Large Urban Medical Center

Julie C. Sung; Ciara Bosh; Brooke Wyatt; Mark Miller; Alyson Harty; David Del Bello; Sterling Knight; Douglas T. Dieterich; Ponni V. Perumalswami; Andrea D. Branch

Disclosures

J Viral Hepat. 2020;27(4):350-359. 

In This Article

Abstract and Introduction

Abstract

Patient-reported outcomes (PROs) are important measures of quality of life. Direct-acting antiviral (DAA) drugs for hepatitis C virus (HCV) improved PROs in clinical trials. We prospectively evaluated the impact of DAA-based HCV cure on PROs and liver-related outcomes in real-world patients at a large urban medical center. The short form (SF)-36 and three additional validated instruments were used. F3–4 fibrosis was defined as > 9.6 kPa by transient elastography (TE); S2–3 steatosis was defined as > 270 dB/m by TE-controlled attenuation parameter (CAP). Data were analysed by paired and unpaired t tests. Patients (n = 16) who did not achieve a sustained virologic response at 12 weeks (SVR12) were excluded. The study achieved its primary endpoint and showed a significant 30% improvement in the SF-36 vitality score, measured baseline to SVR12: 63 versus 82, P < .001 (n = 111). Scores in 24 of 25 PRO domains improved at SVR12 (P < .05). Nearly all gains exceeded 5%, indicating their clinical significance. Transaminase values and liver stiffness improved (decreased) significantly, baseline to SVR12 (P < .005), but steatosis was unchanged (P = .58). Patients with baseline F0–2 fibrosis and those with F3-F4 fibrosis both improved in 22 domains. Patients with baseline S0-S1 steatosis improved in more domains (23) than patients with S2-S3 steatosis (19). At baseline, patients with F3-F4 fibrosis and patients with S2–3 steatosis had worse scores in certain PRO domains than patients with F0-2 fibrosis or S0-S1 steatosis, but this difference resolved by SVR12. HCV cure led to meaningful gains in PROs, and these findings may encourage patients to seek treatment.

Introduction

Despite the availability of highly effective direct-acting antiviral drugs (DAAs) to treat hepatitis C virus (HCV) infection, many patients remain untreated. Currently, over two million people are estimated to have chronic HCV infection in the United States, and the incidence of new infections is increasing as a consequence of the epidemic of opioid use.[1] If left untreated, HCV infection can lead to cirrhosis and liver cancer. Patients also suffer from symptoms of fatigue, irritability, depression, stigma, reduced mental acuity and abdominal pain.[2,3]

Standard instruments are valuable tools for collecting data on patient-reported outcomes (PROs) of disease and can be used to reliably measure health-related quality of life and the negative impact of disease on the ability to function effectively.[4] Previous studies established that HCV-infected patients experience a lower quality of life than controls.[5–7] Multiple investigations demonstrated that interferon-based therapy further decreased (worsened) PRO scores and work-related productivity during treatment.[8–10] The intense side effects of interferon-based therapy are widely known and are cited by both patients and providers as a source of fear that creates a barrier to accessing DAA-based therapy.[11,12]

DAAs, which are now the standard of care, improved PROs by sustained virologic response (SVR)12 when directly compared to interferon-based regimens.[8–10,13] These results are important; however, most studies examining the relationship between DAA treatment and PROs were carried out on patients enrolled in pharmaceutical registration trials, which may limit their generalizability. Clinical trials often enroll a selected population of highly engaged, adherent and relatively healthy patients. Members of racial and ethnic minorities, and patients with advanced liver disease and complex co-morbidities are often underrepresented, excluded or both. A recent study by Evon et al conducted in a real-world setting found only modest improvements in PROs (measured baseline to SVR).[14] However, this study analysed pooled data of patients who did and who did not achieve an SVR, which may obscure the impact of HCV cure on PROs. Additionally, it did not employ the short form (SF)-36, which is an instrument for measuring functioning and well-being that has been widely validated for both general and disease-specific populations.[14–17] There is a need for additional information about PROs in real-world patients and about the impact of liver disease on PROs. Very few investigations have probed the relationship between liver status (fibrosis and steatosis) and PROs. Two prior studies examined the relationship between the fibrosis stage and PROs,[18,19] but none, to our knowledge, has examined the effect of steatosis.

This prospective study was done to obtain additional PRO data in real-world patients cured of HCV with DAAs and to investigate the impact of liver fibrosis and steatosis on quality of life and the ability to perform in the workplace. The predetermined primary outcome measure was the change in the SF-36 Health Survey vitality score. In our investigation, patients cured of HCV reported improvements in 24 of 25 PRO domains, with most improvements greater than 5%. These findings may mitigate lingering fears caused by the intense and widely known side effects of interferon-based therapy and thereby reduce one of the barriers to DAA use.[15,16]

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