Peripheral Blood Expression of Angiotensin II type 1- Receptor (AT1- R) as A Non Invasive Marker of Liver Disease Progression in Patients with Non Alcoholic Fatty Liver Disease

摘要

Angiotensin-II (AT-II) has been suggested to play an important role in liver fibrogenesis. It induces hepatic stellate cell (HSC) proliferation and up-regulates the transforming growth factor beta expression via AT-II type 1 receptor (AT1-R)in vitro. There is accumulating evidence that renin-angiotensin system (RAS) does not only play an important role in the regulation of systemic hemodynamics but is also involved in hepatic inflammation and fibrogenesis. Aim of the study: is to evaluate the efficacy ofAT1-R as a non-invasive marker of liver disease progression in patients with non alcoholic fatty liver disease (NAFLD). Patients and methods: This study was conducted on 62 NAFLD patients (33 with pure steatosis and 29 with non alcoholic steatohepatitis (NASH). All evidenced by the liver biopsy histopathological features of NAFLD. Twenty potential liver transplant donors were selected as a control group. All patients and control group were subjected to the following:- fasting insulin, HOMA index of insulin resistance, and serum Angiotensin II (AG II). Serum AT1R mRNA AT receptor was measured by Real-Time PCR. Results: a positive correlation was found between AT1R mRNA with fasting insulin, HOMA index of insulin resistance and serum AG-II levels in NAFLD patients. While a negative correlation was found between AT1R mRNA and ALT or AST in NAFLD patients. No significant differences between the two subgroups of steatosis and NASH for the all tested parameters except forAG-II and AT1 R mRNA that show a significant increase in NASH patients (p<0.01) for each. Conclusion: Increased expression of AT1R on circulating leukocyte subsets of NAFLD patients, suggesting its possible role in disease progression, and it could be used as a non invasive marker for disease diagnosis and prognosis. In the future, AT1R expression may be used as a follow up marker for monitoring of therapeutic efficacy of currently available agents.