Leyla de Avila1, Ali A Weinstein1,2, J Michael Estep1, Michael P Curry3, Pegah Golabi1, Carey Escheik1, Aybike Birerdinc1, Maria Stepanova4, Lynn Gerber1,5, Zobair M Younossi1,5. 1. Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia. 2. Center for the Study of Chronic Illness and Disability, George Mason University, Fairfax, Virginia. 3. Beth Israel Deaconess Medical Center, Boston, Massachusetts. 4. Center for Outcomes Research in Liver Diseases, Washington, District of Columbia. 5. Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia.
Abstract
BACKGROUND & AIMS: Chronic hepatitis C (CHC) has a negative impact on patient-reported outcomes (PROs). Although most CHC patients who achieve sustained virologic response (SVR) show an improvement in PRO scores, some continue to experience impairment in PROs. The aim was to investigate if serum biomarkers (selected neurotransmitters and cytokines) are associated with changes in PROs in CHC patients who achieve SVR. METHODS: Data were utilized from a prospective clinical trial of ledipasvir/sofosbuvir fixed-dose combination. Chronic genotype 1 HCV subjects without cirrhosis (N = 40, age: 45.3 ± 11.5, 48% male, 90% white) were treated for 12 weeks open label with 97% achieving SVR24. PRO questionnaires included Short Form-36 (SF-36), Fatigue Severity Scale (FSS), Beck Depression Inventory-II (BDI-II), Chronic Liver Disease Questionnaire-HCV (CLDQ-HCV) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Sera were used for measurement of selected neurotransmitters and cytokines. Data were collected at baseline and follow-up week 24. RESULTS: Changes in physical health correlated with changes in several biomarkers. BDNF negatively correlated with SF-36 physical health summary score (rho = -0.34, P < 0.05), SF-36 physical functioning (rho = -0.34, P < 0.05), SF-36 bodily pain (rho = -0.39, P < 0.05) and FACIT-F physical well-being (rho = -0.54, P < 0.001). Changes in emotional well-being (FACIT-F) were positively associated with changes in serotonin (rho = 0.34, P < 0.05), but negatively associated with changes in GABA and BDNF (rho = -0.4, P = 0.01, and rho = -0.35, P < 0.05 respectively). CONCLUSIONS: These data indicate relationships between PROs and serum biomarkers pre- and post-SVR in CHC. These concomitant changes may have important clinical relevance.
BACKGROUND & AIMS:Chronic hepatitis C (CHC) has a negative impact on patient-reported outcomes (PROs). Although most CHCpatients who achieve sustained virologic response (SVR) show an improvement in PRO scores, some continue to experience impairment in PROs. The aim was to investigate if serum biomarkers (selected neurotransmitters and cytokines) are associated with changes in PROs in CHCpatients who achieve SVR. METHODS: Data were utilized from a prospective clinical trial of ledipasvir/sofosbuvir fixed-dose combination. Chronic genotype 1 HCV subjects without cirrhosis (N = 40, age: 45.3 ± 11.5, 48% male, 90% white) were treated for 12 weeks open label with 97% achieving SVR24. PRO questionnaires included Short Form-36 (SF-36), Fatigue Severity Scale (FSS), Beck Depression Inventory-II (BDI-II), Chronic Liver Disease Questionnaire-HCV (CLDQ-HCV) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Sera were used for measurement of selected neurotransmitters and cytokines. Data were collected at baseline and follow-up week 24. RESULTS: Changes in physical health correlated with changes in several biomarkers. BDNF negatively correlated with SF-36 physical health summary score (rho = -0.34, P < 0.05), SF-36 physical functioning (rho = -0.34, P < 0.05), SF-36 bodily pain (rho = -0.39, P < 0.05) and FACIT-F physical well-being (rho = -0.54, P < 0.001). Changes in emotional well-being (FACIT-F) were positively associated with changes in serotonin (rho = 0.34, P < 0.05), but negatively associated with changes in GABA and BDNF (rho = -0.4, P = 0.01, and rho = -0.35, P < 0.05 respectively). CONCLUSIONS: These data indicate relationships between PROs and serum biomarkers pre- and post-SVR in CHC. These concomitant changes may have important clinical relevance.
Authors: Zobair M Younossi; Maria Stepanova; Mazen Noureddin; Kris V Kowdley; Simone I Strasser; Anita Kohli; Peter Ruane; Mitchell L Shiffman; Aasim Sheikh; Nadege Gunn; Stephen H Caldwell; Ryan S Huss; Robert P Myers; Vincent Wai-Sun Wong; Naim Alkhouri; Zachary Goodman; Rohit Loomba Journal: Hepatol Commun Date: 2021-05-12