Evaluation of Cardiovascular Risk Factors after Hepatitis C Virus Eradication with Direct-Acting Antivirals in a Cohort of Treatment-Naïve Patients without History of Cardiovascular Disease

Abstract

Background: Hepatitis C virus (HCV) produces changes at multiple levels in host metabolism, especially in lipid profile and cardio-metabolic risk. It is unclear how HCV eradication by direct-acting antivirals (DAAs) modifies those changes. Objective: To evaluate the impact of DAA treatment on different risk factors associated with cardiovascular disease. Methods: Prospective study with two-year follow-up. All patients treated with DAAs in the Liver Clinic of a tertiary hospital were included. Patients co-infected with HBV or HIV, with other causes of liver disease, on lipid-lowering treatment, pregnant, or with previous HCV treatment were excluded. The results were analyzed using linear mixed models. Results: 167 patients (53% female, 9.6% cirrhosis) were included. Low plasma lipid levels were observed before initiating HCV eradication. During the first year after treatment with DAA, we observed a sustained increase in cholesterol, triglycerides, HDL cholesterol (only in men), and LDL-cholesterol levels. An ameliorated glycemic control was also observed with a decrease in fasting insulin and reduced HOMA. Iron metabolism and coagulation function also improved with lower levels of serum ferritin and prothrombin activity; these biochemical changes resulted in a new diagnosis of hypercholesterolaemia in 17.4% of patients, requiring initiation of statins in 15%. Two non-fatal cardiovascular events were observed during the first 2 years of follow-up. Conclusions: DAA treatments returned plasma lipids to the normal range without increasing either the occurrence of cardiovascular events or the consumption of lipid-lowering medication beyond what is normal in a sex- and age-matched population.

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

“…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 61 .…”

“…While the majority of studies did not evidence a significant change in TGs levels after SVR, in longer follow‐up studies TGs seem to be higher after 2 years from SVR compared to baseline, 37,58 especially in male patients 64 . Moreover, TGs seem to increase later compared to TC and LDL 104 …”

“…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 independent predictor of the amelioration of IR and glycemic parameters seems to be viral eradication itself 27,58,61–63 . The greater improvement in IR was observed in female patients, 64 and it was irrespective of the type of antiviral regimens 65 . The impact of previous treatment was contradictory.…”

Lipid Profile and Cardiovascular Risk Modification after Hepatitis C Virus Eradication

“…Our results describe how HCV-dependent lipid abnormalities are associated with insulin resistance and how DAA therapy can reverse this association. These findings suggest that monitoring the HDL-TG profile could predict changes in glucose tolerance and insulin resistance post-HCV clearance [ 78 ].…”