Sofosbuvir-based Direct-acting Antivirals and Changes in Cholesterol and Low Density Lipoprotein-cholesterol

Overview

Journal Sci Rep

Specialty Science

Date 2022 Jun 15

PMID 35705594

Authors

Yi-Kai Wang

Ying-Wen Wang

Chia-Ling Lu

Yi-Hsiang Huang

Ming-Chih Hou

Yuh-Lih Chang

Wei-Ping Lee

Keng-Hsin Lan

Affiliations

Soon will be listed here.

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.

References

Younossi Z, Stepanova M, Estep M, Negro F, Clark P, Hunt S . Dysregulation of distal cholesterol biosynthesis in association with relapse and advanced disease in CHC genotype 2 and 3 treated with sofosbuvir and ribavirin. J Hepatol. 2015; 64(1):29-36. DOI: 10.1016/j.jhep.2015.08.027. View

Sun H, Cheng P, Tseng C, Tsai W, Chiu Y, Young K . Favouring modulation of circulating lipoproteins and lipid loading capacity by direct antiviral agents grazoprevir/elbasvir or ledipasvir/sofosbuvir treatment against chronic HCV infection. Gut. 2017; 67(7):1342-1350. DOI: 10.1136/gutjnl-2017-313832. View

Hofer H, Bankl H, Wrba F, Steindl-Munda P, Peck-Radosavljevic M, Osterreicher C . Hepatocellular fat accumulation and low serum cholesterol in patients infected with HCV-3a. Am J Gastroenterol. 2002; 97(11):2880-5. DOI: 10.1111/j.1572-0241.2002.07056.x. View

Tellinghuisen T, Evans M, von Hahn T, You S, Rice C . Studying hepatitis C virus: making the best of a bad virus. J Virol. 2007; 81(17):8853-67. PMC: 1951464. DOI: 10.1128/JVI.00753-07. View

Milinkovic A, Berger F, Arenas-Pinto A, Mauss S . Reversible effect on lipids by switching from tenofovir disoproxil fumarate to tenofovir alafenamide and back. AIDS. 2019; 33(15):2387-2391. DOI: 10.1097/QAD.0000000000002350. View

Morihara D, Ko Y, Shibata K, Yamauchi R, Fukuda H, Tsuchiya N . IL28B gene polymorphism is correlated with changes in low-density lipoprotein cholesterol levels after clearance of hepatitis C virus using direct-acting antiviral treatment. J Gastroenterol Hepatol. 2019; 34(11):2019-2027. DOI: 10.1111/jgh.14741. View

. Hepatitis C Guidance 2018 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Clin Infect Dis. 2018; 67(10):1477-1492. PMC: 7190892. DOI: 10.1093/cid/ciy585. View

Emmanuel B, El-Kamary S, Magder L, Stafford K, Charurat M, Chairez C . Metabolic Changes in Chronic Hepatitis C Patients Who Carry IFNL4-ΔG and Achieve Sustained Virologic Response With Direct-Acting Antiviral Therapy. J Infect Dis. 2019; 221(1):102-109. PMC: 7325530. DOI: 10.1093/infdis/jiz435. View

Hashimoto S, Yatsuhashi H, Abiru S, Yamasaki K, Komori A, Nagaoka S . Rapid Increase in Serum Low-Density Lipoprotein Cholesterol Concentration during Hepatitis C Interferon-Free Treatment. PLoS One. 2016; 11(9):e0163644. PMC: 5040437. DOI: 10.1371/journal.pone.0163644. View

10.

Petruzziello A, Marigliano S, Loquercio G, Cozzolino A, Cacciapuoti C . Global epidemiology of hepatitis C virus infection: An up-date of the distribution and circulation of hepatitis C virus genotypes. World J Gastroenterol. 2016; 22(34):7824-40. PMC: 5016383. DOI: 10.3748/wjg.v22.i34.7824. View

11.

Sharma P, Balan V, Hernandez J, Rosati M, Williams J, Rodriguez-Luna H . Hepatic steatosis in hepatitis C virus genotype 3 infection: does it correlate with body mass index, fibrosis, and HCV risk factors?. Dig Dis Sci. 2004; 49(1):25-9. DOI: 10.1023/b:ddas.0000011597.92851.56. View

12.

Lacerda G, Medeiros T, Rosario N, Peralta R, Cabral-Castro M, Esberard E . Exploring lipid and apolipoprotein levels in chronic hepatitis C patients according to their response to antiviral treatment. Clin Biochem. 2018; 60:17-23. DOI: 10.1016/j.clinbiochem.2018.07.007. View

13.

Ichikawa T, Miyaaki H, Miuma S, Motoyoshi Y, Narita S, Toda S . Carotid Intima-media Thickness and Small Dense Low-density Lipoprotein Cholesterol Increase after One Year of Treatment with Direct-acting Antivirals in Patients with Hepatitis C Virus Infection. Intern Med. 2019; 58(9):1209-1215. PMC: 6543209. DOI: 10.2169/internalmedicine.1514-18. View

14.

Taramasso L, Di Biagio A, Riccardi N, Briano F, Di Filippo E, Comi L . Lipid profile changings after switching from rilpivirine/tenofovir disoproxil fumarate/emtricitabine to rilpivirine/tenofovir alafenamide/emtricitabine: Different effects in patients with or without baseline hypercholesterolemia. PLoS One. 2019; 14(10):e0223181. PMC: 6788691. DOI: 10.1371/journal.pone.0223181. View

15.

Mazzitelli M, Torti C, Sabatino J, DAscoli G, Costa C, Pisani V . Evaluation of cardiac function by global longitudinal strain before and after treatment with sofosbuvir-based regimens in HCV infected patients. BMC Infect Dis. 2018; 18(1):518. PMC: 6192073. DOI: 10.1186/s12879-018-3426-9. View

16.

Gastaminza P, Cheng G, Wieland S, Zhong J, Liao W, Chisari F . Cellular determinants of hepatitis C virus assembly, maturation, degradation, and secretion. J Virol. 2007; 82(5):2120-9. PMC: 2258938. DOI: 10.1128/JVI.02053-07. View

17.

Ghany M, Morgan T . Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases-Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Hepatology. 2019; 71(2):686-721. PMC: 9710295. DOI: 10.1002/hep.31060. View

18.

Ray A, Fordyce M, Hitchcock M . Tenofovir alafenamide: A novel prodrug of tenofovir for the treatment of Human Immunodeficiency Virus. Antiviral Res. 2015; 125:63-70. DOI: 10.1016/j.antiviral.2015.11.009. View

19.

Beig J, Orr D, Harrison B, Gane E . Hepatitis C Virus Eradication with New Interferon-Free Treatment Improves Metabolic Profile in Hepatitis C Virus-Related Liver Transplant Recipients. Liver Transpl. 2018; 24(8):1031-1039. DOI: 10.1002/lt.25060. View

20.

Dousson C . Current and future use of nucleo(s)tide prodrugs in the treatment of hepatitis C virus infection. Antivir Chem Chemother. 2018; 26:2040206618756430. PMC: 5890546. DOI: 10.1177/2040206618756430. View