Sofosbuvir-based direct-acting antivirals and changes in cholesterol and low density lipoprotein-cholesterol

Area of Science:

• Hepatology and Viral Hepatitis
• Pharmacology and Drug Metabolism
• Cardiovascular Risk Assessment

Background:

• Direct-acting antivirals (DAAs) for chronic hepatitis C (CHC) can alter lipid profiles.
• Previous observations noted worsened lipid profiles with combination DAAs and tenofovir alafenamide (TAF).
• Structural similarity between sofosbuvir (SOF) and TAF suggests a potential impact on lipid metabolism.

Purpose of the Study:

• To investigate the effect of SOF-based DAAs on lipid profiles in CHC patients.
• To compare the impact of SOF-based versus non-SOF-based DAA regimens on total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C).

Main Methods:

• Retrospective analysis of 487 CHC patients achieving sustained virologic response 12 (SVR12).
• Comparison of TC and LDL-C levels at baseline, week 4, and SVR12 using Wilcoxon matched-pairs signed rank test.
• Logistic regression analysis to determine relative risks (RR) of TC and LDL-C elevation between SOF-based and non-SOF-based regimens.

Main Results:

• SOF-based regimens (Harvoni, Epclusa) showed a statistically significant elevation in TC and LDL-C at week 4.
• SOF-based DAAs had a 2.72-fold higher RR for 10% TC elevation and a 2.04-fold higher RR for 10% LDL-C elevation compared to non-SOF-based regimens.
• The significant increases in TC and LDL-C during the initial 4 weeks of SOF-based DAA treatment were not sustained until SVR12.

Conclusions:

• SOF-based DAAs are associated with a rapid, significant, but transient worsening of lipid profiles in CHC patients.
• Monitoring lipid levels during the initial weeks of SOF-based DAA therapy is warranted.
• The observed lipid changes do not appear to persist long-term following successful viral eradication.