Validation of AGA clinical care pathway and AASLD practice guidance for nonalcoholic fatty liver disease in a prospective cohort of patients with type 2 diabetes

Abstract

Background and Aims: Recently, the American Gastroenterological Association (AGA) and American Association for the Study of Liver Diseases (AASLD) developed clinical pathways to evaluate populations at high-risk for nonalcoholic fatty liver disease (NAFLD). We assessed the diagnostic performance of the new guidance in a well-phenotyped cohort of patients with Type 2 diabetes mellitus (T2DM). Approach and Results: This prospective study enrolled adults age ≥50 years with T2DM. Participants underwent a standardized clinical research visit with magnetic resonance imaging (MRI) and ultrasound-based assessment of liver fat and stiffness and ELF testing. Of 417 participants (36% men) with T2DM with FIB-4 and MRE data, the prevalence of NAFLD was 64% and 12% had advanced fibrosis (MRE≥3.63 kPa). Applying the AGA pathway of FIB-4 and vibration controlled transient elastography (VCTE) the false negative rate was 3.3% and 18% would qualify for specialty referral. Applying FIB-4 + ELF AASLD pathway the false negative rate was 4.5% but 50% would qualify specialty referral. Applying higher ELF cut points improved the pathway yielding a similar false negative rate of 4.9% but decreased specialty referral to 27%. Conclusion: Validation of the AGA clinical pathway in a prospectively recruited cohort with T2DM revealed a low false negative rate and avoided specialty referral in a large percentage of patients. The AASLD pathway with FIB-4 + ELF resulted in a high rate of specialty referral, which improved with utilization of higher ELF cut-points and may serve as an alternative for primary care and endocrinology clinics without access to VCTE.

Associations of life’s essential 8 with MAFLD and liver fibrosis among US adults: a nationwide cross-section study

“…Impaired glycemic control and systemic insulin resistance may promote increased flux of free fatty acids from peripheral tissues to the liver, thereby predisposing to the development and progression of non-alcoholic fatty liver disease (NAFLD) even before the onset of diabetes mellitus ( 47 ). Ajmera et al ( 48 ) received that type 2 diabetic individuals have greater rates of liver fibrosis and steatosis ( 48 ). In a US study, HbA1c was significantly associated with liver steatosis and fibrosis.…”

The impact of genetic risk on the prevalence of advanced fibrosis and cirrhosis in prospectively assessed patients with type 2 diabetes

“…5,6 Although these NITs have good negative predictive values in excluding advanced fibrosis, their performance may be poorer among patients with T2DM and thus require further refinement based on real-world data. 3,[7][8][9] Genetic factors including multiple established common variants contribute to the risk of MASLD and disease severity 10,11 Family studies have revealed that first-degree relatives of probands with MASLD and advanced fibrosis have an elevated risk of advanced fibrosis. 12 Incorporating genetic risk determination may help improve current screening guidelines, particularly for the T2DM patient population.…”

Looking for the best algorithm in the diabetes population for advanced fibrosis detection: The best is the enemy of the good

“…[1] A perfect equilibrium between false negative rate and referral rate is the main goal to avoid the disappointing task of weed out patients without risk. In the current issue, Ajmera et al [2] reported interesting data from a well-defined cohort of patients with type 2 diabetes comparing 3 clinical pathways: the one proposed by AGA [using fibrosis-4 (FIB4) and vibrationcontrolled transient elastography (VCTE)], the one proposed by AASLD [using FIB4 and enhanced liver fibrosis (ELF)], and a third one AASLD but using higher cutoff points for ELF, which has been reported to increase ELF specificity. [3] The AGA pathway showed the lowest false negative rate and the best referral rate, assuming it is the most accurate pathway to detect advanced fibrosis.…”