Sa1036 Hepatic Fibrosis After Small-for-Size Liver Transplantation in Rats: Possible Role of TGFβ/SMAD Signaling

Abstract

this study, we explored whether concomitant medication altered the risk of hepatic fibrosis in NAFLD. Specifically, we sought to ascertain the association between RAS blocking agents (angiotensin converting enzyme blocker or angiotensin II receptor blocker) and severity of hepatic fibrosis in NAFLD patients with hypertension. Methods: This study cohort consisted of 259 hypertensive patients with biopsy proven NAFLD prospectively followed up in hepatology outpatient clinics in Cleveland, OH. Clinical data including demographics, anthropometry, medical history, medication history, biochemical and liver biopsy findings were evaluated. Patients with and without RAS blocker use were compared in relation to liver fibrosis stage. Utilizing electronic medical records, risk factors for advanced fibrosis were explored, in particular, the association between commonly used medications and advanced fibrosis. Independent risk factors for advanced fibrosis were ascertained using binary regression. Results: The mean age of the cohort was 52.2 years and mean BMI was 37.33 kg/m2. Females, diabetics and patients with advanced fibrosis comprised 64.9%, 60.2% and 35.9% of the cohort respectively. Patients treated with RAS blockers had significantly less ballooning (1.05 vs. 1.33, p=0.002) and lower fibrosis stage (1.64 vs. 2.24, p=0.001) on liver biopsy compared to patients not treated with RAS blockers. Compared to patients without advanced fibrosis, patients with advanced fibrosis were older (54.6 vs. 50.9 years, p=0.014), more often diabetic (76.3 vs. 50.9%, p=0.000), had more ballooning on histology (1.57 vs. 0.93, p=0.000), more likely to be on insulin (22.6 vs. 11.5%, p=0.018), and sulfonylureas (29.0 vs. 15.8%, p=0.011) while less likely to be on RAS blockers (49.5 vs. 70.3%, p=0.001). On multivariate analysis, grade of ballooning had an independent positive association with advanced fibrosis (OR 7.539; 95%CI 3.402-16.706, p=0.000) while usage of RAS blockers had a negative association with advanced fibrosis (OR 0.293; 95%CI 0.1090.787, p=0.015). Conclusion: Hypertensive patients with NAFLD treated with RAS blockers had less advanced hepatic fibrosis, suggesting a beneficial role for angiotensin blockers to protect against NASH fibrosis. Prospective clinical trials are warranted to explore this association in greater detail.