Non-invasive Screening of Diabetics in Primary Care for NAFLD and Advanced Fibrosis by MRI and MRE

I. Doycheva; J. Cui; P. Nguyen; E. A. Costa; J. Hooker; H. Hofflich; R. Bettencourt; S. Brouha; C. B. Sirlin; R. Loomba


Aliment Pharmacol Ther. 2016;43(1):83-95. 

In This Article

Abstract and Introduction


Background Current guidelines do not recommend screening for non-alcoholic fatty liver disease (NAFLD) or advanced fibrosis. Patients with type 2 diabetes mellitus (T2DM) are known to be at increased risk for NAFLD and advanced fibrosis.

Aim To assess the feasibility in diabetics in a primary care setting of screening for NAFLD and advanced fibrosis, by using non-invasive magnetic resonance imaging (MRI) to estimate the hepatic proton density fat fraction (MRI-PDFF) and magnetic resonance elastography (MRE) to estimate hepatic stiffness.

Methods We performed a cross-sectional analysis of a prospective study that included 100 (53% men) consecutively enrolled diabetics who did not have any other aetiology of liver disease. All patients underwent a standardised research visit, laboratory tests, MRI-PDFF, and MRE.

Results Mean (±s.d.) age and body mass index (BMI) was 59.7 (±11.2) years and 30.8 (±6.5) kg/m2, respectively. The prevalence of NAFLD (defined as MRI-PDFF ≥5%) and advanced fibrosis (defined as MRE ≥3.6 kPa) was 65% and 7.1%, respectively. One patient with advanced fibrosis had definite hepatocellular carcinoma. When compared to those without NAFLD, patients with NAFLD were younger (P = 0.028) and had higher mean BMI (P = 0.0008), waist circumference (P < 0.0001) and prevalence of metabolic syndrome (84.6% vs. 40.0%, P < 0.0001). Only 26% of those with NAFLD had elevated alanine aminotransferase.

Conclusions This proof-of-concept study demonstrates that T2DM has significant rates of both NAFLD and advanced fibrosis. Concomitant screening for NAFLD and advanced fibrosis by using MRI-proton density fat fraction and magnetic resonance elastography in T2DM is feasible and may be considered after validation in a larger cohort.


Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world with an estimated prevalence in the United States ranging between 19% and 46% depending on the study population characteristics and diagnostic modality.[1,2] NAFLD is a frequent finding in patients with type 2 diabetes mellitus (T2DM) due to their common underlying pathogenic mechanism of insulin resistance.[3,4] Previous studies on the prevalence of NAFLD in T2DM were based on abdominal ultrasound evaluation,[5,6] magnetic resonance spectroscopy (MRS)[7,8] or small samples of patients with liver biopsies.[2,9] Due to the differences in the study methodologies and diagnostic techniques, the reported prevalence of NAFLD in T2DM patients ranges broadly between 43% and 94%.[2,5,6,7,8,9] It is also known that the presence of T2DM is an independent predictor of advanced fibrosis in NAFLD,[10] with a greater prevalence of cirrhosis in diabetic compared to nondiabetic patients.[11] However, the exact prevalence of NAFLD in T2DM as well as the utility of screening for NAFLD in T2DM remain uncertain.

With the steadily increasing prevalence of obesity and T2DM, the health burden of NAFLD in diabetes raises an important concern and imposes the need for early identification of patients who are at an increased risk of progressive liver disease and cirrhosis. Currently, routine screening of NAFLD in either diabetics (as a high-risk group for progression of liver disease) or in the general population is not recommended due to controversies regarding the lack of accurate non-invasive diagnosis of NAFLD and advanced fibrosis and limited therapeutic options.[12]

Serum aminotransferase elevation is an inaccurate marker of NAFLD as normal alanine aminotransferase (ALT) has been noted in up to 86% of patients with NAFLD.[5] Abdominal ultrasound lacks sensitivity for mild steatosis (<30%) and has high inter- and intra-observer variability.[13] Computed tomography has limited sensitivity for mild disease and is associated with radiation exposure. Therefore, liver biopsy remains the gold standard for the diagnosis and staging of NAFLD and assessment of fibrosis.[12] However, liver biopsy is an invasive procedure, which is limited due to its associated cost and risk of complications, including pain, infection, bleeding, and very rarely even death. Furthermore, liver biopsy has significant sampling variability and inter-observer variability, and it is impractical tool for screening of patients who are at increased risk for presence of NAFLD and advanced fibrosis.[14]

Therefore, we aimed to investigate the feasibility of screening for NAFLD in T2DM using magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF), a novel, recently validated imaging-based biomarker which allows for the quantification of liver fat content in the entire liver that correlates strongly with MR spectroscopy – measured liver fat[15,16,17] and liver histology-determined steatosis grade.[18,19,20] We also aimed to assess the usefulness of magnetic resonance elastography (MRE), a non-invasive imaging modality shown to differentiate advanced from non-advanced fibrosis,[21,22] to screen our cohort for advanced fibrosis. Our hypotheses were that the feasibility of using MRI-PDFF and MRE to screen for NAFLD and advanced fibrosis would be excellent with no or low failure rates, and that asymptomatic diabetics in primary care setting would have high prevalence of NAFLD and advanced fibrosis. We followed STROBE guidelines for the reporting of prospectively conducted cross-sectional studies.[23]