Decoupled Glucose and Lipid Metabolic Recovery after Viral Clearance in Direct-Acting Antiviral-Treated HCV Patients: A 3-Year Prospective Cohort Study

Abstract

Background/Aim: The recovery pattern of hepatitis C virus (HCV)-associated metabolic alteration after sustained virological response (SVR) following direct-acting antivirals (DAAs) remains elusive. Methods: A prospective cohort study of chronic HCV-infected (CHC) patients (n = 415) receiving DAAs (n = 365) was conducted. Metabolic profiles were examined in SVR patients (n = 360) every 3–6 months after therapy and compared with those of sex- and age-matched controls (n = 470). Results: At baseline, of 415, 168 (40.5%) had insulin resistance (IR). The following were associated: levels of high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), HCV RNA, fibrosis-4 score, and interferon-λ3-rs12979860 genotype with total cholesterol (TC) levels; and TG levels and BMI with HOMA-IR. Over a 3-year follow-up, in SVR patients, BMI and TC levels and TG/HDL-C ratios increased from baseline, while HOMA-IR trended downward by 72 weeks after therapy and then increased. The increased HDL-C levels began to decrease after 72 weeks after therapy. TC and HOMA-IR were negatively associated with each other until 24 weeks after therapy. Earlier increases in BMI and decreases in HOMA-IR were noted in SVR patients with than in those without baseline IR. Compared with controls, in the subgroup without baseline IR, SVR patients had increased BMI and HOMA-IR levels. Metabolic profiles were similar between SVR patients and controls in the subgroup with baseline IR. Conclusions: In SVR patients treated with DAAs, the recovery of altered lipid and glucose metabolism was not coupled until 72-week post-therapy, when HOMA-IR reached its nadir. SVR patients with baseline IR recovered from HCV-associated metabolic alterations earlier than those without baseline IR.

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

“…On the other hand, a low fibrosis stage was associated with a reduction in HDL 61 . The study of Lee et al 91 . showed that patients with an increase in BMI and HOMA‐IR after SVR experienced a reduction in HDL 3 years after therapy.…”

“…All studies observed a worsening in TC and LDL after viral eradication by DAAs. Concerning HDL, 17 studies did not show a significant change after SVR, 20 studies observed an increase in HDL after SVR, especially in female patients with metabolic syndrome, 22,45,64,72,95 but not during the treatment when HDL declined, 13,91,96 and only 2 studies revealed a reduction in HDL 61,91 . Finally, 19 studies did not show significant changes in TGs after viral eradication, 13,22,26,40,45,46,53,60,73,74,97–103 in 16 TGs worsened, 12,16,28,36,37,39,52,58,61,64,68,72,91,92,104,105 and in 9 studies TGs decreased after SVR 38,43,54–56,69,79,106,107 …”

“…The increase in TC and LDL started during the therapy and reached a greater increase from the end of treatment 13 to 3 months after SVR 68,96 . After this point, the increase of TC and LDL was less marked, reached a plateau at 1 year after treatment, 91,104 and after 2 years from viral eradication, TC and LDL remained higher compared to baseline 95,104 . As a consequence of the increase in TC and LDL after SVR, approximately 20% of patients treated showed cholesterol levels over the optimal range 109 and the use of lipid‐lowering drugs increased 110 …”

Effects of late evening snacks on glucose homeostasis in cirrhotic patients: A meta-analysis

“…[35] Therefore, IR is an important therapeutic target in patients at any stage of chronic liver disease. [36]…”

“…[35] Therefore, IR is an important therapeutic target in patients at any stage of chronic liver disease. [36] As a result of impaired liver function, HD usually exhibits specific clinical characteristics and is closely linked to hypoglycemic episodes, but has a less association with risk factors such as age, body mass index and a family history of diabetes. This is due to the fact that chronic liver illness, rather than a genetic predisposition, caused the diabetic state.…”