The ADA recommends to screen for NASH and liver fibrosis individuals with type 2 diabetes (T2DM), obesity (OB) and/or elevated alanine aminotransferase (ALT). However, recent studies have questioned the clinical value of measuring ALT and AST for the detection of patients at risk of nonalcoholic fatty liver disease (NAFLD) or advanced liver fibrosis or cirrhosis. The aim of this study was to assess the clinical value of ALT and AST ≥40 IU/L, or their lower cut-offs ≥30 IU/L as recommended by recent AACE guidelines, to screen populations at risk. To this end, we recruited 714 participants (age: 56 ± 11 years, male: 42%; BMI: 30.8 ± 6.5 kg/m2; T2DM: 35%; A1c: 6.0 ± 1.2%) from primary care or endocrinology clinics, unaware of having NAFLD/fibrosis. Screening for NAFLD included laboratory tests and imaging with elastography (steatosis by controlled attenuation parameter [CAP]; fibrosis by liver stiffness measurement [LSM]). Elevated transaminases were more common in patients with vs. without T2DM, with ALT ≥40 IU/L occurring in 13% vs. 8% and AST in 9% vs. 3% of patients (both p<0.05). If using a cutoff of ≥30 IU/L: 25% vs. 18% and 20% vs. 13%; respectively (both p<0.05). Elevated ALT ≥30 IU/L was the highest in patients with T2DM and OB (n=164) vs. controls (without T2DM or OB; n=269; 27% vs 15%; p=0.02). The sensitivity for diagnosing steatosis by ALT or AST was very low, with ALT and AST ≥40 IU/L present in only 16% and 9%, respectively. However, steatosis by imaging (CAP) was often present if ALT or AST were high (81 and 90%, respectively). An ALT ≥40 IU/L was also not useful for diagnosing patients with fibrosis of any stage (LSM ≥7.0), missing the diagnosis in 63% of patients, and this did not improve when examining only those with more advanced fibrosis (≥F3) being elevated in only 40%. Conclusions: Plasma aminotransferases are of limited diagnostic value when screening patients with T2DM for NAFLD or fibrosis. This supports the ADA recent guidelines for using FIB-4 and additional noninvasive testing for screening.
A. Ortiz Rocha: None. E. Godinez Leiva: None. S. Kalavalapalli: None. R. Lomonaco: None. S.S. Shetty: None. S.A. Marangi: None. E. Valdez Saenz: None. S. Shrestha: None. M.A. Gonzalez: None. X. Chi: None. M.J. Gurka: None. D. Barb: None. K. Cusi: Research Support; Echosens, Inventiva. Consultant; Poxel SA. Research Support; LabCorp, Zydus. Consultant; Altimmune, Arrowhead Pharmaceuticals, Inc., AstraZeneca, 89bio, Inc., Bristol-Myers Squibb Company, Lilly, Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Medscape, Myovant, Novo Nordisk, ProSciento, Quest Diagnostics, Sagimet, Sonic Incytes, Terns.
National Institutes of Health (R01120331-01A1)