Although the initial 4 weeks of treatment with a sofosbuvir (SOF)-based direct-acting antiviral (DAA) was associated with a significant increase in lower‑density lipoprotein (LDL) concentrations among patients with hepatitis C virus (HCV) infection, the increase in LDL disappeared after treatment was discontinued, according to results of a systematic review and meta-analysis published in BMC Infectious Diseases.

In this systematic review and meta-analysis, researchers identified 6 studies to investigate the effect of SOF-based medication regimens on changes in LDL in patients with HCV. Among a total of 1248 patients included in the analysis, 848 were treated with an SOF-based DAA and 400 were treated with a nonSOF-based DAA. The mean age of patients ranged from 62 to 76 years, and most achieved a sustained virologic response.

All 6 studies included data on changes in LDL from baseline to week 4, and analysis of the combined difference in mean changes showed significantly greater increases in LDL among patients treated with an SOF-based DAA vs those treated with a nonSOF-based DAA (12.61; 95% CI, 5.68-19.55; P =.001). Of note, the increases in LDL remained until the end of treatment in 4 studies (difference in means, 6.98; 95% CI, -0.30 to 14.26); however, the increases were not statistically significant (P =.060).

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The researchers performed a meta-analysis and found that the difference in mean changes in LDL from baseline to post-treatment week 12 and week 24 were similar between patients treated with an SOF-based DAA vs those treated with a nonSOF-based DAA (P =.263 vs P =.319).

Compared with patients treated with SOF/ledipasvir, the researchers observed a similar trend in changes in LDL among those treated with asunaprevir/daclatasvir. There also were significant increases in LDL from baseline to week 4 (P <.001) and at the end of treatment (P <.001), though similar changes were observed at post-treatment week 12 (P =.340) and week 24 (P =.582) between the 2 treatment groups.

Other study limitations were the small number of studies included in the analysis and potential publication bias. The most significant risk of bias was due to confounding factors. In addition, the researchers did not evaluate long-term changes in LDL, total cholesterol, triglycerides, high-density lipoproteins, or apolipoprotein.

“The potential mechanism underlying changes in lipid profiles with DAA treatment might be related with the cleaved products of phosphoramidate side chain of SOF and deserves [further] investigation,” the researchers concluded.


Wang YW, Lee WP, Huang YH, Hou MC, Lan KH. Effect of sofosbuvir-based DAAs on changes in lower-density lipoprotein in HCV patients: a systematic review and meta-analysis. BMC Infect Dis. 2021;21(1):984. doi:10.1186/s12879-021-06657-9