Hepatitis C virus infection, lipids, and coronary heart disease: A Pandora's box
Authors: Chia-Chi Wang, Jia-Horng Kao
Journal: Hepatology (2009)

We read with great interest the article by Corey et al.1 In this study, they found that hepatitis C virus (HCV) infection was associated with decreased cholesterol and low-density lipoprotein (LDL) levels and this hypolipidemic effect disappeared with successful hepatitis C treatment but persisted in nonresponders. Additionally, a significant portion of successfully treated patients had rebound of LDL and cholesterol to levels associated with increased risk of coronary heart disease (CHD). Although their results provide important data to improve our understanding about the interactions between HCV infection and lipid metabolism, several issues deserve further discussion. First, the most important finding was the LDL and cholesterol rebounded in patients with chronic hepatitis C who achieved sustained virologic response after discontinuation of therapy. However, this fact could be simply explained by the recovery of hepatic function after resolution of hepatic inflammation. Liver is known to mediate lipid metabolism including the uptake of circulating free fatty acid and the secretion of very low density lipoprotein into peripheral blood, which may influence serum concentration of cholesterol and LDL. Our previous case-control study consistently showed lower cholesterol and LDL levels in patients with chronic hepatitis C than in uninfected controls.2 However, HCV infection was associated with a higher cholesterol level in patients with normal alanine aminotransferase (ALT) levels,2 suggesting ALT level, a biomarker of hepatic inflammation, may play a role in modulating the relationship between HCV infection and lipid metabolism. Another study also reported a significant decrease of cholesterol level in patients with chronic active hepatitis compared to healthy controls.3 Therefore, the authors should perform analyses comparing patients with lipid rebound with those who were not stratified by pretreatment ALT levels or HCV viral load, in order to clarify the causal relationship between HCV clearance and cholesterol rebound. Second, cholesterol and LDL levels physiologically fluctuate with the changes of diet, exercise, or lifestyle. Although their cohort adopted complete paired lipid data before and after hepatitis C treatment to directly evaluate these changes in a given individual, it is still difficult to differentiate physiological fluctuation from significant lipid rebound by one spot measurement. To solve this issue, the authors should provide more lipid data during the follow-up period to exclude possible biases from the physiologic fluctuation of serum lipid concentrations. Finally, a previous cohort study found HCV infection was associated with a higher risk of CHD after adjustment for traditional risk factors.4 Furthermore, HCV infection may independently predict an increased severity of CHD based on Reardon severity score in a population of individuals with angiographically determined CHD.5 In this article, the authors demonstrated the association between HCV infection and relative hypolipidemia in several contexts. Paradoxically, this hypolipidemic effect could not provide appropriate explanation for the increased risk of CHD in patients with chronic hepatitis C. In addition, our previous data also indicated a positive association of HCV RNA level with insulin resistance in patients infected with chronic hepatitis C.6 Taking these lines of evidence together, chronic HCV infection may not only alter lipid metabolism, but also affect insulin resistance, leading to dysregulated glucose metabolism and metabolic abnormalities. Further longitudinal studies are thus needed to examine the net impact of HCV infection on the risk of CHD. Chia-Chi Wang M.D.*, Jia-Horng Kao Ph.D. , * Department of Hepatology, Buddhist Tzu Chi General Hospital, Taipei Branch and School of Medicine, Tzu Chi University, Hualien, Taiwan, Graduate Institute of Clinical Medicine and, Hepatitis Research Center, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan.