A comprehensive assessment of patient reported symptom burden, medical comorbidities, and functional well being in patients initiating direct acting antiviral therapy for chronic hepatitis C: Results from a large US multi-center observational study

Donna M Evon, Paul W Stewart, Jipcy Amador, Marina Serper, Anna S Lok, Richard K Sterling, Souvik Sarkar, Carol E Golin, Bryce B Reeve, David R Nelson, Nancy Reau, Joseph K Lim, K Rajender Reddy, Adrian M Di Bisceglie, Michael W Fried, Donna M Evon, Paul W Stewart, Jipcy Amador, Marina Serper, Anna S Lok, Richard K Sterling, Souvik Sarkar, Carol E Golin, Bryce B Reeve, David R Nelson, Nancy Reau, Joseph K Lim, K Rajender Reddy, Adrian M Di Bisceglie, Michael W Fried

Abstract

Background: Symptom burden, medical comorbidities, and functional well-being of patients with chronic hepatitis C virus (HCV) initiating direct acting antiviral (DAA) therapy in real-world clinical settings are not known. We characterized these patient-reported outcomes (PROs) among HCV-infected patients and explored associations with sociodemographic, liver disease, and psychiatric/substance abuse variables.

Methods and findings: PROP UP is a large US multicenter observational study that enrolled 1,600 patients with chronic HCV in 2016-2017. Data collected prior to initiating DAA therapy assessed the following PROs: number of medical comorbidities; neuropsychiatric, somatic, gastrointestinal symptoms (PROMIS surveys); overall symptom burden (Memorial Symptom Assessment Scale); and functional well-being (HCV-PRO). Candidate predictors included liver disease markers and patient-reported sociodemographic, psychiatric, and alcohol/drug use features. Predictive models were explored using a random selection of 700 participants; models were then validated with data from the remaining 900 participants. The cohort was 55% male, 39% non-white, 48% had cirrhosis (12% with advanced cirrhosis); 52% were disabled or unemployed; 63% were on public health insurance or uninsured; and over 40% had markers of psychiatric illness. The median number of medical comorbidities was 4 (range: 0-15), with sleep disorders, chronic pain, diabetes, joint pain and muscle aches being present in 20-50%. Fatigue, sleep disturbance, pain and neuropsychiatric symptoms were present in over 60% and gastrointestinal symptoms in 40-50%. In multivariable validation models, the strongest and most frequent predictors of worse PROs were disability, unemployment, and use of psychiatric medications, while liver markers generally were not.

Conclusions: This large multi-center cohort study provides a comprehensive and contemporary assessment of the symptom burden and comorbid medical conditions in patients with HCV treated in real world settings. Pain, fatigue, and sleep disturbance were common and often severe. Sociodemographic and psychiatric markers were the most robust predictors of PROs. Future research that includes a rapidly changing population of HCV-infected individuals needs to evaluate how DAA therapy affects PROs and elucidate which symptoms resolve with viral eradication.

Trial registration: (Clinicaltrial.gov: NCT02601820).

Conflict of interest statement

Donna M. Evon has received research funding from Gilead. Michael Fried has received research funding from and served as a consultant for AbbVie, BMS, Gilead, and Merck, and TARGET PharmaSolutions. Stock in TARGET PharmaSolutions is held in an independently managed trust. Anna S. Lok has received research support from AbbVie, BMS, Gilead, and Merck; and served as an advisor for Gilead. Richard K. Sterling has received research support from AbbVie, BMS, Gilead, Merck, and Roche and served as a consultant for Merck, Bayer, Salix, AbbVie, Gilead, Jansen, ViiV, Baxter, and Pfizer. Joseph K. Lim has received research support (paid to Yale University) and served as a consultant for Bristol-Myers Squibb and Gilead. Nancy Reau has received research funding (paid to Rush) from AbbVie and Intercept and has served as a consultant for AbbVie, Gilead, Merck, and BMS. Souvik Sarkar served on a Gilead and Abbvie Advisory Board. David R. Nelson has received research grant support from AbbVie, BMS, Gilead, Janssen, and Merck. K. Rajender Reddy is an Ad-Hoc Advisor to Gilead, BMS, Janssen, Merck, and Abbvie and has received research support from Gilead, BMS, Janssen, Merck, and AbbVie (paid to the University of Pennsylvania). Adrian M. Di Bisceglie has received research support from AbbVie, BMS and Gilead and has served on advisory boards for AbbVie, BMS and Merck. Paul Stewart has served as a consultant to TARGET PharmaSolutions. Jipcy Amador served as a biostatistics intern at TARGET PharmaSolutions in 2017. Carol E. Golin and Bryce Reeve declare that they have no conflict of interests to disclose. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Study flowchart.
Fig 1. Study flowchart.
Fig 2. Histograms of PROMIS symptom T-scores.
Fig 2. Histograms of PROMIS symptom T-scores.
*The vertical line in each histogram shows the proportion of patients reporting no symptoms or responses at the minimum score.

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