Critical role of triglycerides for adiponectin levels in hepatitis C: a joint study of human and HCV core transgenic mice

Abstract

Background Both hepatitis C virus (HCV) infection and adiponectin are critically involved in metabolism. The reversal and associations of altering adiponectin levels after sustained virological responses (SVRs) following direct-acting antivirals (DAA) in HCV-infected patients remained elusive. Methods A joint study was conducted in a prospective cohort of 427 HCV-infected patients and a line of HCV core transgenic mice. Results Of 427, 358 had completed a course of DAA therapy and 353 had SVRs. At baseline, male sex (95% CI β: − 1.44 to − 0.417), estimated glomerular filtration rate (eGFR) (− 0.025 to − 0.008), triglycerides (− 0.015 to − 0.005), and fibrosis-4 levels (0.08–0.297) were associated with adiponectin levels; BMI (0.029–0.327) and triglycerides levels (0.01–0.03) were associated with homeostatic model assessment for insulin resistance (HOMA-IR) in HCV-infected patients. At 24-week post-therapy, in SVR patients, male sex (− 1.89 to − 0.5) and eGFR (− 0.02 to − 0.001) levels were associated with adiponectin levels, levels of BMI (0.094–0.335) and alanine transaminase (0.018–0.078) were associated with HOMA-IR; compared with baseline levels, adiponectin levels decreased (6.53 ± 2.77 vs. 5.45 ± 2.56 μg/mL, p < 0.001). In 12-month-old HCV core transgenic mice with hepatic steatosis, triglyceride levels (0.021–0.111) were associated with adiponectin levels, and hepatic adipopnectin expression was comparable with that of control mice. Conclusions Triglycerides and hepatic fibrosis are associated with HCV-specific alteration of adiponectin levels, and adiponectin may affect insulin sensitivity through triglycerides during HCV infection. In DAA-treated patients, after SVR, adiponectin levels decreased and the linking function of triglycerides between adiponectin and insulin sensitivity vanished. Moreover, HCV core with hepatic steatosis might affect extrahepatic adiponectin expression through triglycerides.

Adipokines as Diagnostic and Prognostic Markers for the Severity of COVID-19

“…Studies that determined serum adiponectin levels in patients with viral infections are still rare. In mouse models for HCV infection, the efficient elimination of the virus was related to a decline of adiponectin plasma levels [105]. Yet, the anti-viral therapy of HCV had no effect on circulating adiponectin amounts in patients, and this also applied to hepatitis B virus (HBV)-infected patients [106].…”

Effect of HCV eradication by DAAs on liver steatosis, carotid atherosclerosis, and associated metabolic comorbidities: A systematic review

“…Patients with baseline IR showed a significant decrease in HOMA‐IR after SVR until 72 weeks after therapy and then increased 26 . Conversely, patients without baseline IR had an increase in HOMA‐IR values after viral eradication 90,91 . Older age, higher baseline transaminases, higher TC and TGs, and higher fibrosis stage were the factors associated with baseline IR, 26,92 and the higher the BMI, the lower the reduction in IR 92 .…”

“…Changes in body weight and BMI did not seem to be related to modifications in physical activity or lifestyle, 61 and it was irrespective of previous antiviral treatment 61,90,114 …”

“…The majority of studies (21 out of 30) did not show a significant change in mean BMI or weight after SVR. Conversely, 7 studies revealed an increase in BMI after SVR, 27,40,90,114–117 while 3 studies showed a reduction in mean BMI 53,81,118 …”