Association of the Low-density Lipoprotein Cholesterol/High-density Lipoprotein Cholesterol Ratio with Glecaprevir-pibrentasvir Treatment

Abstract

Objective The change in serum lipid levels by direct-acting antiviral (DAA) treatment for chronic hepatitis C varies depending on the type of DAA. How the lipid level changes induced by glecaprevir-pibrentasvir (G/ P) treatment contribute to the clinical outcome remains unclear. We conducted a prospective observational study to evaluate the effectiveness of G/P treatment and the lipid level changes. Methods The primary endpoint was a sustained virologic response at 12 weeks (SVR12). The total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels and LDL-C/HDL-C (L/H) ratio were measured every two weeks. Patients This study included 101 patients. Seventeen cases of liver cirrhosis and nine cases of DAA retreatment were registered. The G/P treatment period was 8 weeks in 74 cases and 12 weeks in 27 cases. Results SVR12 was evaluated in 96 patients. The rate of achievement of SVR12 in the evaluable cases was 100%. We found significantly elevated TC and LDL-C levels over the observation period compared to baseline. The serum levels of HDL-C did not change during treatment but were significantly increased after treatment compared to baseline. The L/H ratio was significantly increased two weeks after the start of treatment but returned to the baseline after treatment. Conclusion The primary endpoint of the SVR12 achievement rate was 100%. G/P treatment changed the serum lipid levels. Specifically, the TC and LDL-C levels increased during and after treatment, and the HDL-C levels increased after treatment. G/P treatment may be associated with a reduced thrombotic risk. Therefore, validation in large trials is recommended.

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

“…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 .…”

“…61,91 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.…”

“…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][98][99][100][101][102][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.…”

“…Among the studies that showed an increase in HDL, it appears to be consistent after the viral eradication, whereas during treatment HDL declined. 13,91,96 Higher baseline fibrosis, female sex, and the presence of metabolic syndrome seem to be the factors related to the increase in HDL after SVR. 22,45,46,64,72,95 On the other hand, a low fibrosis stage was associated with a reduction in HDL.…”

The Clinical Significance of Lipids/Lipoproteins Impairment in the Context of Cirrhosis: An Updated Review

“…Another prospective study evaluated the effectiveness of glecaprevir/pibrentasvir treatment and the resultant alterations pertinent to the lipid levels. 35 Relevant findings indicated a remarkable elevation of the TC and LDL-C levels during and after treatment, and the HDL-C levels increased after treatment. The LDL-C/HDL-C ratio increased during treatment but returned to baseline after treatment, and two possible explanations were clarified.…”