Viral Hepatitis, Cholesterol Metabolism, and Cholesterol-Lowering Natural Compounds

Abstract

Hepatitis is defined as inflammation of the liver; it can be acute or chronic. In chronic cases, the prolonged inflammation gradually damages the liver, resulting in liver fibrosis, cirrhosis, and sometimes liver failure or cancer. Hepatitis is often caused by viral infections. The most common causes of viral hepatitis are the five hepatitis viruses—hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV). While HAV and HEV rarely (or do not) cause chronic hepatitis, a considerable proportion of acute hepatitis cases caused by HBV (sometimes co-infected with HDV) and HCV infections become chronic. Thus, many medical researchers have focused on the treatment of HBV and HCV. It has been documented that host lipid metabolism, particularly cholesterol metabolism, is required for the hepatitis viral infection and life cycle. Thus, manipulating host cholesterol metabolism-related genes and proteins is a strategy used in fighting the viral infections. Efforts have been made to evaluate the efficacy of cholesterol-lowering drugs, particularly 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, in the treatment of hepatitis viral infections; promising results have been obtained. This review provides information on the relationships between hepatitis viruses and host cholesterol metabolism/homeostasis, as well as the discovery/development of cholesterol-lowering natural phytochemicals that could potentially be applied in the treatment of viral hepatitis.

Studying T Cell Responses to Hepatotropic Viruses in the Liver Microenvironment

“…It is conceivable that other metabolic functions of the liver may also influence hepatic T cell immunity. For example, the liver is the main site of cholesterol metabolism and hepatitis viruses exploit host lipids and cholesterol for their life cycles [ 135 ]. Altered availability of cholesterol during infection may influence the antiviral immune response [ 136 ].…”

Mucosal-Associated Invariant T Cells in the Digestive System: Defender or Destroyer?

“…Infection with the hepatitis virus causes viral hepatitis, which can be acute or chronic in nature. 75 According to Du et al, 76 patients with acute HCV infection had a lower MAIT cell frequency in peripheral blood and reduced TNF-α and IFN-γ in response to E coli or IL-12 and IL-18 stimulation compared with healthy control subjects. Peripheral blood and intrahepatic MAIT cells were found to be reduced in patients with chronic hepatitis B, C, and D virus infection; however, residual peripheral blood MAIT cells were significantly activated.…”

Targeting lipid biosynthesis pathways for hepatitis B virus cure

“…Recently, a number of new host factors essential for HBsAg production were identified through a genome-wide CRISPR screen including a number of lipid related genes [ 13 ]. Interactions between hepatic lipid metabolism and HBV infection has previously been described in the literature [ 14 , 15 ] and it has been demonstrated in vitro that depletion of cellular cholesterol using lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, significantly reduced HBsAg secretion in Hep3B cells [ 16 ].…”