Hepatic Fibrosis and Pregnancy

Dr. Rifaat Safadi

Liver deterioration of cirrhotic women in pregnancy was reported mainly due to bleeding varices and renal impairment. It is still unclear either fibrosis deteriorates or attenuated following pregnancy. Recent data suggests that liver fibrosis is in part CD8-mediated disease as CD8 is increased in fibrotic mouse model, especially in the intrahepatic lymphocyte subpopulation. Moreover, the Natural killer (NK) cells were found to have anti-fibrotic effect in animal models and humans. Our preliminary results confirmed the increase of NK-T cells and CD8 subsets in pregnancy. In this proposal, we hypothesis that pregnancy is affecting progression of liver-fibrogenesis in patients with chronic liver injury and might increase the risk toward cirrhosis. Lymphocyte alterations mediate these effects. For this purpose, fibrosis model will be induced in pregnant and non-pregnant mice. Then, we will evaluate the lymphocyte and non-lymphocyte causes of increased fibrosis in pregnancy. Therefore, fibrosis model will also be induced in pregnant wild type, severe combined immune deficient and SCID-beige rodents. All fibrotic pregnant backgrounds will be compared to fibrotic non-pregnant, pregnant non-fibrotic and naïve states. Then, severity of fibrosis and lymphocyte alterations would be evaluated (CD4, CD8, NK, NK-T cells) in all groups. The study of fibrosis course in pregnancy can provide us an important tool for developing anti-viral treatments.