Nonalcoholic Fatty Liver Disease (NAFLD), ranging from simple steatosis to its more severe form, steatohepatitis (NASH), is an increasingly common problem in patients with T2DM and is associated with progression to cirrhosis and extrahepatic complications (i.e., cardiovascular disease [CVD]). There is limited information on the clinical profile of T2DM patients with NASH in “real world” practice. Accordingly, we studied the clinical profile of participants (pts) with NASH, with or without T2DM (nonDM), enrolled in TARGET-NASH, a large longitudinal observational study of patients with NAFLD followed at 54 sites (39 academic/15 community) across the U.S. Data collected from medical records (including lab data, imaging, pathology, procedures, and outcomes) is sent to a central database utilizing novel data abstraction technology. Among 1743 pts studied to date in TARGET-NASH, 1261 had NASH diagnosed by biopsy or clinical criteria (699 T2DM and 562 nonDM). Pts with T2DM and NASH were older (median 61 vs. 56 years) and had a higher BMI than nonDM (34.0 vs. 32.0 kg/m2, both p<0.01). The prevalence rates of hypertension (68 vs. 41%), dyslipidemia (42 vs. 25%), CVD (26 vs. 17%) all p <0.001, and cancer (17 vs. 12% p=0.015), were higher in T2DM compared to nonDM. Median ALT in T2DM was lower than nonDM (33 vs. 38 U/L, p<0.001). Among pts with a liver biopsy, advanced fibrosis was seen in 55% of T2DM vs. 35% nonDM, including 38 vs. 19% with cirrhosis, respectively (both p<0.001). Among pts with a biopsy and NAFLD Activity Score total, more T2DM had severe steatohepatitis than nonDM (38 vs. 23% p<0.01). In this large cohort of NASH pts managed in standard clinical practice, pts with T2DM had substantially different clinical profiles compared to nonDM. ALT, only modestly elevated in most pts with NASH, is not a reliable marker for NASH. Diagnosis requires reliance on clinical features and additional testing. Further investigation of independent risk factors and long-term outcomes is ongoing.
K. Cusi: Consultant; Self; Janssen Global Services, LLC., Eli Lilly and Company. Research Support; Self; Cirius Therapeutics. Other Relationship; Self; Nordic Bioscience. Research Support; Self; Novartis Pharmaceuticals Corporation, Novo Nordisk Inc.. Other Relationship; Self; Quest Diagnostics. Research Support; Self; Zydus Pharmaceuticals (USA) Inc.. Other Relationship; Self; OWL metabolomics, Echosens. Research Support; Self; Janssen Global Services, LLC.. Consultant; Self; Tobira Therapeutics, Pfizer Inc. A.S. Barritt: Consultant; Self; Targetpharma solutions. Consultant; Spouse/Partner; Targetpharma solutions, Takeda Pharmaceuticals U.S.A., Inc., AbbVie Inc.. V. Clark: None. R.J. Firpi: None. S. Klein: Stock/Shareholder; Self; Aspire Bariatrics. Consultant; Self; Pfizer Inc.. Research Support; Self; Merck & Co., Inc., Johnson & Johnson Services, Inc., REMD Biotherapeutics. A. Lok: None. R. Loomba: Research Support; Self; Adheron, Arora, BMS, Daiichi-Sankyo Inc., Galectin, Galmed, GE, Genfit, Gilead, Immuron, Intercept, Kinemed, Madrigal, Merck, NGM, Promedior, Prometheus, Siemens, Sirius, Tobira. Advisory Panel; Self; Arrowhead Research, Conatus, Galmed, Gilead, Intercept, NGM, Nimbus, Octeta, Tobira. Consultant; Self; Alnylam, Bird Rock Bio, BMS, Boehringer Ingleheim, Celgene, Conatus, DeuteRx, Eli Lily, Enanta, Fibrogen, Genkyotex, Gilead, GRI Bio, ISIS, Janssen Inc.Kirin, Madrigal, Metacrine, NGM, Nitto Denko, Pf, Sanofi,Scholar Rock, Shire, Tasly, Viking, Yuhan Pharmaceuticals, Zafgen. L. Malahias: None. B. Neuschwander-Tetri: None. C. Schoen: None. K. Reddy: Advisory Panel; Self; Gilead Sciences, Inc., Merck & Co., Inc., AbbVie Inc.. Other Relationship; Self; Novartis AG, Gilead Sciences, Inc., Merck & Co., Inc., AbbVie Inc., Mallinckrodt Pharmaceuticals, Conatus Pharmaceuticals Inc., Intercept Pharmaceuticals, Inc.. J.L. Taunk: None. K. Wyne: Research Support; Self; Sanofi. Advisory Panel; Self; Novo Nordisk Inc.. Research Support; Self; Eli Lilly and Company. A.J. Sanyal: Stock/Shareholder; Self; Sanyal Bio, Genfit, Durect, Indalo, Exhalenz. Consultant; Self; Gilead, Boehringer Ingelheim, Intercept. Advisory Panel; Self; Galectin, NGM. Consultant; Self; Pfizer.