Cytokine balance is restored as patient‐reported outcomes improve in patients recovering from chronic hepatitis C

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.

Patient‐reported outcomes in patients with non‐alcoholic fatty liver disease: A narrative review of Chronic Liver Disease Questionnaire‐non‐alcoholic fatty liver disease/non‐alcoholic steatohepatitis

“…24 FACIT‐F has been used in patients with cancer, chronic anemia, and in elderly persons 25 . In addition, the availability of FACIT‐F has been reported in patients with chronic liver disease 26 …”

“…Serum levels of cytokines including tumor necrosis factor‐alpha are known to be associated with CLDQ score in patients with chronic hepatitis C 26 . In patients with NASH, Younossi et al .…”

Patient‐reported outcomes in patients chronic viral hepatitis without cirrhosis: The impact of hepatitis B and C viral replication

“…From literature, other factors which are associated with active hepatitis (increased cytokine production, extrahepatic viral involvement) have also been suspected to drive PRO impairment . In fact, viral eradication in HCV and simultaneous changes in the cytokine profile of cured patients correlate well with improvement of HRQL and other PROs . It has been suggested that some of these PRO improvements may originate centrally (owing to changes in the brain after viral eradication) while others may be of peripheral origin (such as changes in proinflammatory cytokines that can affect fatigue and physical performance) .…”

Hepatitis C related cognitive impairment: Impact of viral and host factors and response to therapy

“…Fatigue has long been known to be associated with HCV infection, 22,34 and the association between PROs and cognitive function has been described in patients with liver disease 37 . Furthermore, PROs have been shown to improve following successful DAA treatment for HCV 38–40 …”