Sofosbuvir Is the Major Contributor to Elevation of Blood Cholesterol and Low-density Lipoprotein During HCV Treatment With DAAs

Abstract Background and aims: Worsened lipid profiles were observed in chronic hepatitis C (CHC) patients during direct-acting antivirals (DAAs) treatment, among which combination drugs confounded the effect of individual ingredient on lipid. Tenofovir alafenamide (TAF) also worsened lipid profiles in HIV patients. Structural similarity between sofosbuvir (SOF) and TAF prompted us to investigate rapid increase in total cholesterol (TC) and low-density lipoprotein (LDL) in CHC patients treated with SOF-based DAAs.Methods: A retrospective study was performed to analyze 487 CHC patients receiving DAAs with SVR12. Laboratory data were analyzed by logistic regression to determine relative risks of TC and LDL of SOF-based regimens over non-SOF-based regimens. Week 4 to baseline ratios of serum TC or LDL between regimens were compared by Mann-Whitney's test.Results: 487 patients were treated with Harvoni® (SOF-based, 206 patients), Epclusa® (SOF-based, 124 patients), Maviret® (non-SOF-based, 122 patients), or Zepatier® (non-SOF-based, 35 patients). At week 4 during drug treatment, Harvoni®, Epclusa®, and Maviret® induced statistically significant elevation of TC and LDL, but Zepatier® did not. SOF-based regimens had 2.72-fold higher relative risk (RR) causing 10% elevation of TC (95% CI: 1.84-4.02, p < 0.001) and 2.04-fold higher RR causing 10% elevation of LDL (95% CI:1.39-3.01, p < 0.001) than non-SOF-based DAAs. Conclusion: SOF-based DAAs were associated with significantly larger amplitude of increases in TC and LDL than non-SOFO-based regimens during the initial 4 weeks of treatment, but the amplitude was not sustained to SVR12.