C型肝炎ウイルス持続感染患者の肝線維化における女性ホルモンの役割

The most common cause of hepatic fibrosis is chronic hepatitis C virus infection, the characteristic feature of which is hepatic steatosis. Hepatic steatosis leads to an increase in lipid peroxidation in hepatocytes, which in turn activates hepatic stellate cells (HSCs). HSCs are also thought to be the primary target cells for inflammatory stimuli, and produce extracellular matrix components. Clinical observations and death statistics support the view that chronic hepatitis C appears to progress more rapidly in men than in women, and cirrhosis is predominately a disease of men and postmenopausal women. It should be noted in this respect that estradiol (E2) is a potent endogenous antioxidant. Our studies showed that E2 suppressed hepatic fibrosis in hepatic fibrosis models, and attenuated HSC activation in primary culture. Recently, variant estrogen receptors (ERs) were found to be expressed to a greater extent in male patients with chronic liver disease than in female subjects. We also demonstrated decreased levels of ERs in postmenopausal women and cirrhotic patients of both genders. The present review summarizes our current knowledge of the biological functions of E2 and ER status as it relates to fibrogenesis in the liver.