1432-P: ALT Elevation Suggestive of NAFLD in Overweight and Obese Youth on Second-Generation Antipsychotics

Abstract

Second-generation antipsychotics (SGAs) increase risk for insulin resistance and metabolic syndrome. Less is known about the risk of nonalcoholic fatty liver disease (NAFLD) in youth treated with SGAs. MOBILITY is a large, multi-center, pragmatic study designed to assess the effect of metformin added to lifestyle instruction compared to lifestyle instruction alone on weight gain and metabolic parameters in youth with overweight and obesity (ages 8-19) and bipolar-spectrum disorders receiving SGAs. We examined baseline ALT as a marker for NAFLD in 840 youth in the study (78% with obesity; 46% female; 68% white; 17% black; 11% Hispanic) . Overall, 44% of subjects had mild ALT elevation (ALT>22 females; ALT>25 males) , and 10% had significantly elevated ALT≥ 45 (2× ULN) . Male sex (p<0.001) , obesity (p=0.007) , and white race (p=0.009) were significantly associated with ALT elevation. Hispanic ethnicity and age were not significantly associated with ALT elevation. There was no difference in duration of exposure to SGAs (< 1 year vs. > 1 year of exposure) . There was a trend towards an association between prediabetes and significant ALT elevation (2× ULN; p=0.06) ; however, glucose was not associated with ALT elevation overall. Although we had no imaging or biopsy data in these patients, our study demonstrates that a clinically relevant percentage of youth with overweight and obesity treated with SGAs have elevated ALT suggestive of NAFLD; in fact, the prevalence of elevated ALT is higher than expected with obesity alone. Given that NAFLD is the most common liver disease now in youth and can progress to cirrhosis and liver failure, our findings suggest that pediatric psychiatrists who treat these patients must screen for NAFLD with ALT and refer patients for further evaluation and management as needed. Disclosure N.A.Crimmins: None. M.Mouzaki: None. M.P.Delbello: Board Member; Sage Pharmaceuticals, Consultant; Alkermes, Sunovion Pharmaceuticals Inc., Research Support; Alkermes, Johnson & Johnson, Lundbeck, Shire plc., Speaker's Bureau; Sunovion Pharmaceuticals Inc. C.Correll: Consultant; Alkermes, Janssen Pharmaceuticals, Inc., Lundbeck, Medscape, Mylan N.V., Neurocrine Biosciences, Inc., Otsuka America Pharmaceutical, Inc., Sunovion Pharmaceuticals Inc., Takeda Pharmaceutical Company Limited, Teva Pharmaceutical Industries Ltd. J.Welge: None. Funding Mobility: Improving Patient-Centered Outcomes Among Overweight and Obese Youth with Bipolar Spectrum Disorders Treated with Second-Generation Antipsychotics. [PICORI (Delbello) ].