Chronic hepatitis C and fibrosis: evidences for possible estrogen benefits

Abstract

The main injury caused by hepatitis C virus is the hepatic fibrosis, as a result of a chronic inflammatory process in the liver characterized by the deposit of components from the extracellular matrix. The fibrosis development leads to the modification of the hepatic architecture, of the hepatocellular function and to irregularities in the microcirculation. The tissue remodeling process observed in fibrosis has stellate cells, located at the space of Disse, as main acting agents. These cells, in response to a harmful stimulus, undergo phenotypic changes from nonproliferating cells to proliferating cells that express a-smooth-muscle actin (α α α α α-SMA), a process called as transdifferentiation. There are evidences that the oxidative stress is involved in the chronic liver disease and serves as bond between the injury and the hepatic fibrosis. A number of studies suggest that the estrogen, at physiological levels, presents an antifibrogenic action probably through an antioxidant effect, decreasing the levels of lipid peroxidation products in the liver and blood, thus inhibiting the myofibroblastic transformation of stellate cells and contributing for gender-associated differences in relation to the fibrosis development. The aim of this paper was to describe data from literature concerning the interaction between chronic hepatitis C and estrogens, pregnancy, use of oral contraceptives, menopause and hormone reposition therapy.

Cimicifuga racemosa impairs fatty acid β-oxidation and induces oxidative stress in livers of ovariectomized rats with renovascular hypertension

“…This result is not surprising considering that 70% of the liver blood flow is provided by portal vein. Therefore, this organ must be less susceptible to oxidative damage associated with hypertension, and the estrogen deficiency seems to be the major contributor to the enhanced oxidative stress in the liver [59][60][61][62].…”

A cis-acting regulatory variation of the estrogen receptor α (ESR1) gene is associated with hepatitis B virus-related liver cirrhosis

“…The majority of the biological effects of estrogen are mediated by ESR1 in the liver [Ahlbory-Dieker et al, 2009]. ESR1 has been well characterized in human liver [Rossini et al, 1989], and hepatic cytosolic ESR1 content was detected on the progression of chronic liver disease [Codes et al, 2007;Mizoguchi et al, 1989;Villa et al, 2002b]. The abnormal ESR1 expressions in the liver have been implicated in stimulating hepatocyte proliferation and may act as liver disease inducers or promoters [Giannitrapani et al, 2006].…”

Clinical research Value of α-smooth muscle actin and glial fibrillary acidic protein in predicting early hepatic fibrosis in chronic hepatitis C virus infection

“…The development of CHC is better estimated by the fibrosis stage rather than by the necroinflammatory activity level [3]. Currently, the cirrhosis resulting from chronic virus C infection is the main cause of hepatic transplantation worldwide [4]. …”