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Abstract
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 cholesterol (LDL-C) in CHC patients treated with SOF-based DAAs. A retrospective study was performed to analyze 487 CHC patients receiving DAAs with SVR12. Relative risks on elevating TC and LDL-C were analyzed by logistic regression to determine SOF-based over non-SOF-based regimens. TC or LDL-C levels at baseline, week-4 and SVR12 were compared by Wilcoxon matched-pairs signed rank test. Week 4 or SVR12 to baseline ratios of serum TC or LDL-C between regimens were compared by Mann–Whitney's test. 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-C, 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-C (95% CI 1.39–3.01, p < 0.001) than non-SOF-based DAAs. SOF-based DAAs were associated with significantly larger amplitude of increases in TC and LDL-C than non-SOF-based DAAs during the initial 4 weeks of treatment, but the increases were not sustained to SVR12.
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1 National Yang Ming Chiao Tung University, Institute of Pharmacology, College of Medicine, Taipei, Taiwan (GRID:grid.260539.b) (ISNI:0000 0001 2059 7017); National Yang Ming Chiao Tung University, Department of Pharmacy, College of Pharmaceutical Sciences, Taipei, Taiwan (GRID:grid.260539.b) (ISNI:0000 0001 2059 7017); National Yang Ming Chiao Tung University Hospital, Department of Pharmacy, Yilan, Taiwan (GRID:grid.260539.b)
2 Taipei Veterans General Hospital, Healthcare Center, Taipei, Taiwan (GRID:grid.278247.c) (ISNI:0000 0004 0604 5314)
3 Taipei Veterans General Hospital, Division of Gastroenterology and Hepatology, Department of Medicine, Taipei, Taiwan (GRID:grid.278247.c) (ISNI:0000 0004 0604 5314)
4 Taipei Veterans General Hospital, Division of Gastroenterology and Hepatology, Department of Medicine, Taipei, Taiwan (GRID:grid.278247.c) (ISNI:0000 0004 0604 5314); National Yang Ming Chiao Tung University, School of Medicine, Taipei, Taiwan (GRID:grid.260539.b) (ISNI:0000 0001 2059 7017); National Yang Ming Chiao Tung University, Institute of Clinical Medicine, College of Medicine, Taipei, Taiwan (GRID:grid.260539.b) (ISNI:0000 0001 2059 7017)
5 Taipei Veterans General Hospital, Division of Gastroenterology and Hepatology, Department of Medicine, Taipei, Taiwan (GRID:grid.278247.c) (ISNI:0000 0004 0604 5314); National Yang Ming Chiao Tung University, School of Medicine, Taipei, Taiwan (GRID:grid.260539.b) (ISNI:0000 0001 2059 7017)
6 National Yang Ming Chiao Tung University, Institute of Pharmacology, College of Medicine, Taipei, Taiwan (GRID:grid.260539.b) (ISNI:0000 0001 2059 7017); Taipei Veterans General Hospital, Department of Pharmacy, Taipei, Taiwan (GRID:grid.278247.c) (ISNI:0000 0004 0604 5314); National Yang Ming Chiao Tung University, Department of Pharmacy, College of Pharmaceutical Sciences, Taipei, Taiwan (GRID:grid.260539.b) (ISNI:0000 0001 2059 7017)
7 Taipei Veterans General Hospital, Department of Medical Research, Taipei, Taiwan (GRID:grid.278247.c) (ISNI:0000 0004 0604 5314); National Yang Ming Chiao Tung University, Institute of Biochemistry and Molecular Biology, College of Life Sciences, Taipei, Taiwan (GRID:grid.260539.b) (ISNI:0000 0001 2059 7017)
8 Taipei Veterans General Hospital, Division of Gastroenterology and Hepatology, Department of Medicine, Taipei, Taiwan (GRID:grid.278247.c) (ISNI:0000 0004 0604 5314); National Yang Ming Chiao Tung University, School of Medicine, Taipei, Taiwan (GRID:grid.260539.b) (ISNI:0000 0001 2059 7017); National Yang Ming Chiao Tung University, Institute of Pharmacology, College of Medicine, Taipei, Taiwan (GRID:grid.260539.b) (ISNI:0000 0001 2059 7017)