1168-P: Serum MicroRNA-122 and -192 Are Increased in Adolescents with NAFLD: Potential Role as Biomarkers

Abstract

The best available blood biomarker for nonalcoholic fatty liver disease (NAFLD) is alanine aminotransferase (ALT), though it does not reliably distinguish NAFLD severity. Alternate biomarkers have been tested in adults, but fewer in children. We tested serum microRNA-122 (miR-122) as a biomarker for NAFLD in adolescents since it inhibts hepatic lipogenesis in animals and is exported from liver to blood with disease progression. The only prior study of miR-122 in children produced mixed results. We also measured miR-192, -130b, and -155 as they have roles in hepatic lipogenesis. Participants were boys and girls, 12-20 y, with biopsy-confirmed NAFLD (n=23), and peers without NAFLD who were either obese (Ob, n=22), or normal weight (NW, n=24). RNA was extracted from serum from all participants and from liver biopsies from the NAFLD group. Serum miR-122 and -192 were 12- and 10-fold higher (p< 0.01), respectively, in NAFLD patients compared to both Ob and NW controls. Within the NAFLD group, serum abundances of miR-122 and -192 were inversely correlated with their liver values (r = -0.51, p = 0.002 and r = -0.40, p = 0.067, respectively), and positively correlated with histological scores for steatosis (r = 0.39 and 0.28, respectively) and fibrosis (r = 0.56 and 0.54, respectively). mIR-122 and -192 content were also positively correlated with ALT (r = 0.78 for both) and with each other in both serum (r = 0.92) and liver (r = 0.74), suggesting similar regulation. Areas under the receiver operating curve for distinguishing NAFLD was 0.95 for miR-122 and -192. Serum miR-130b, which regulates PGC-1 alpha, was 2.6-fold higher in serum from NAFLD patients versus both control groups, while serum miR-155, which regulates lipogenesis and inflammation, did not differ in NAFLD. Serum miR-130b and miR-155 values were not correlated with their corresponding values in liver biopsies. These results support the potential use of miR-122 and -192 as biomarkers for the presence and severity of NAFLD in adolescents. Disclosure K. R. Short: None. S. Palle: None. D. S. Amaya hellman: None. S. Jiang: None. J. B. Tryggestad: None. E. Fematt garcia: None. Funding Oklahoma Shared Clinical & Translational Resource