Acute hepatitis C infection lowers serum lipid levels

Replication of the hepatitis C virus (HCV) involves several important host lipid interactions. Hepatitis C virions complex with host lipoproteins to form lipoviroparticles in the host circulation [1]. Lipoviroparticles may then use low-density lipoprotein (LDL) receptors on hepatocytes as one mechanism of cell entry [2,3]. In addition, the HCV envelope glycoprotein E2 has been demonstrated in vitro to bind to lipoproteins and lead to enhanced LDL receptor and CD81 binding [4]. Once inside the hepatocyte, HCV replication requires geranylgeranylation of the host protein FBL2, a process dependent on the host cholesterol synthesis pathway [5]. Interruption of this pathway results in dissolution of the HCV replication complex [6]. Further, HCV secretion appears to be tied to host apolipoprotein B secretion [7,8]. Interaction between HCV and host lipids has been shown in clinical studies. Lower serum cholesterol and LDL levels are found in patients infected with hepatitis C when compared with patients with hepatitis B or without infection [9–11]. Recently, we demonstrated that chronic hepatitis C infection is associated with a decrease in cholesterol and LDL when compared with matched control subjects. We also found that this hypolipidaemia resolves with treatment-induced viral clearance, while patients without response to therapy remain hypolipidaemic [12]. Further, we demonstrated that in patients who achieve viral clearance, LDL and cholesterol often rebound to levels that may confer increased risk of cardiovascular disease and require treatment with lipid-lowering therapy. To strengthen the association between HCV infection and alterations in serum lipids, we sought to evaluate the impact of acute HCV infection on serum lipid levels. Acute HCV infection is a unique form of hepatitis C infection that presents symptomatically, thus bringing patients to clinical attention and allowing approximation of the date of infection. The ability to determine the time point of infection allows for the evaluation of lipid levels prior to infection and comparison of these levels to levels during and following infection. We hypothesized that, similar to chronic hepatitis C infection, acute infection would result in a lowering of LDL and cholesterol levels from baseline levels and rebound in those who cleared the infection but not in those who went on to develop a chronic infection. Further, we hypothesized that clearance of HCV would be associated with a rebound in LDL and cholesterol above pre-infection levels. In addition, we hypothesized that non-high-density lipoprotein (non-HDL) cholesterol levels, derived by subtracting HDL cholesterol from total cholesterol levels and increasingly recognized as an important risk factor for coronary heart disease (CHD) [13], would decrease with acute infection and rebound with resolution of infection.