Hepatitis C viremia and serum lipid levels: A clue from an epidemiology study
Authors: Chia-Yen Dai, Wan-Long Chuang, Chi-Kung Ho, Ming-Lung Yu
Journal: Journal of Hepatology (2008)

We would like to thank Dr. Giannini and Dr. Savarino for their interest in our article and we appreciate their comments. The clinical status of hepatitis C virus (HCV) infection in terms of the severity of histopathology is lacking in our study [[1]Dai C.Y. Chuang W.L. Ho C.K. Hsieh M.Y. Huang J.F. Lee L.P. et al.Associations between hepatitis C viremia and low serum triglyceride and cholesterol levels: a community-based study.J Hepatol. 2008; 49: 9-16Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar]. It is indeed neither appropriate nor possible to undergo liver biopsy for more than 11,000 residents in a large-scale study. Based on the cross-sectional survey in our community-based study, we found HCV-viremic patients had lower serum lipid levels than anti-HCV-negative or anti-HCV-positive (but non-viremic) individuals which provided strong evidence of the association between HCV viremia and lower serum lipid levels. Furthermore, with the advantage of a large scale study, our report demonstrated the impact of HCV viremia among anti-HCV positive individuals. We also observed hepatitis B virus surface antigen positivity was independently associated with low serum lipid levels by multivariate analysis. The residents enrolled were aged 40–65 years and around 10% of them, according to previous studies, may be positive for hepatitis B e antigen which has been recognized to be strongly associated with an increased risk of active cirrhosis [2Chu C.M. Liaw Y.F. Chronic hepatitis B virus infection acquired in childhood: special emphasis on prognostic and therapeutic implication of delayed HBeAg seroconversion.J Viral Hepat. 2007; 14: 147-152Crossref PubMed Scopus (128) Google Scholar, 3Chu C.M. Hung S.J. Lin J. Tai D.I. Liaw Y.F. Natural history of hepatitis B e antigen to antibody seroconversion in patients with normal serum levels of aminotransferases.Am J Med. 2004; 116: 829-834Abstract Full Text Full Text PDF PubMed Scopus (234) Google Scholar]. In addition, we have also observed a reciprocal viral interaction between hepatitis B virus (HBV) and HCV after interferon-alpha/ribavirin therapy [[4]Chuang W.L. Dai C.Y. Chang W.Y. Lee L.P. Lin Z.Y. Chen S.C. et al.Viral interaction and responses in chronic hepatitis C and B coinfected patients with interferon-alpha plus ribavirin combination therapy.Antivir Ther. 2005; 10: 125-133PubMed Google Scholar]. Hence, HBV infection might play a less important role among anti-HCV-positive subjects, particularly among the HCV viremic patients in our study. Nevertheless, the lack of HBV DNA is an important limitation in our study to validate the association between serum lipid levels and the severity as well as viral load of chronic HBV infection. Recently, the association between cholesterol metabolic pathway and the life cycle in terms of HCV production, secretion and entry by human hepatocytes has been reported [5Huang H. Sun F. Owen D.M. Li W. Chen Y. Gale Jr., M. et al.Hepatitis C virus production by human hepatocytes dependent on assembly and secretion of very low-density lipoproteins.Proc Natl Acad Sci USA. 2007; 104: 5848-5853Crossref PubMed Scopus (440) Google Scholar, 6Ye J. Reliance of host cholesterol metabolic pathways for the life cycle of hepatitis C virus.PLoS Pathog. 2007; 3: e108Crossref PubMed Scopus (116) Google Scholar]. HCV replicates on membrane vesicles involved in the assembly and secretion of very low-density lipoproteins and the low density lipoprotein receptor involved in HCV entry were observed [7Molina S. Castet V. Fournier-Wirth C. Pichard-Garcia L. Avner R. Harats D. et al.The low-density lipoprotein receptor plays a role in the infection of primary human hepatocytes by hepatitis C virus.J Hepatol. 2007; 46: 411-419Abstract Full Text Full Text PDF PubMed Scopus (232) Google Scholar, 8Agnello V. Abel G. Elfahal M. Knight G.B. Zhang Q.X. Hepatitis C virus and other Flaviviridae viruses enter cells via low density lipoprotein receptor.Proc Natl Acad Sci USA. 1999; 96: 12766-12771Crossref PubMed Scopus (810) Google Scholar]. Incidentally the development of drugs that target the cholesterol or lipoprotein metabolism and might be useful in treating HCV infection by inhibition of HCV RNA replication or production of HCV particles from infected cells is still ongoing, although their safety profiles and benefits require more sufficient evidence [5Huang H. Sun F. Owen D.M. Li W. Chen Y. Gale Jr., M. et al.Hepatitis C virus production by human hepatocytes dependent on assembly and secretion of very low-density lipoproteins.Proc Natl Acad Sci USA. 2007; 104: 5848-5853Crossref PubMed Scopus (440) Google Scholar, 9Chandler C.E. Wilder D.E. Pettini J.L. Savoy Y.E. Petras S.F. Chang G. et al.An MTP inhibitor that lowers plasma cholesterol and triglycerides in experimental animals and in humans.J Lipid Res. 2003; 44: 1887-1901Crossref PubMed Scopus (175) Google Scholar, 10Bader T. Fazili J. Madhoun M. Aston C. Hughes D. Rizvi S. et al.Fluvastatin inhibits hepatitis C replication in humans.Am J Gastroenterol. 2008; 103: 1383-1389Crossref PubMed Scopus (182) Google Scholar]. Accordingly, we believe our epidemiologic study, also taking the viral genotype into consideration, implicates an evident association between HCV RNA status and serum lipids. We deem it necessary at the same time to investigate the mechanisms of interaction between HCV and lipids.