Modulation of host lipid metabolism by hepatitis C virus: Role of new therapies

Abstract

It is well established that hepatitis C virus (HCV) infection and replication relies on host lipid metabolism. HCV proteins interact and associate with lipid droplets to facilitate virion assembly and production. Besides, circulating infective particles are associated with very low-density lipoprotein. On the other hand, higher serum lipid levels have been associated with sustained viral response to pegylated interferon and ribavirin therapy in chronic HCV infection, suggesting a relevant role in viral clearance for host proteins. Host and viral genetic factors play an essential role in chronic infection. Lipid metabolism is hijacked by viral infection and could determine the success of viral replication. Recently development of direct acting antiviral agents has shown a very high efficacy (> 90%) in sustained viral response rates even for cirrhotic patients and most of the viral genotypes. HCV RNA clearance induced by Sofosbuvir has been associated with an increased concentration and size of the low-density lipoprotein particles. In this review, host genetic factors, viral factors and the interaction between them will be depicted to clarify the major issues involved in viral infection and lipid metabolism.

Keywords: Direct acting antiviral agents; Genetic interaction; Hepatitis C virus; Lipid metabolism; Sofosbuvir.

Figure 1

Schematic representation of hepatitis C virus and host interplay during hepatitis C virus infection. Viral infection has a direct effect on lipid metabolism through two main mechanisms: first, by deregulating gene expression (FASN, DGAT, MTTP, SREBP). This effect can be modulated by certain SNPs in PNPLA3, among others. Secondly, VLDL synthesis is affected, since HCV replication takes place on lipid droplets. SNPs: Single nucleotide polymorphisms; VLDL: Very low-density lipoprotein; HCV: Hepatitis C virus; DGAT: Diacylglycerol acyltransferase; LD: Lipid droplet; PNPLA3: patatin-like phospholipase domain containing 3.