Furthermore, concerns have been raised on whether screening is cost-effective, especially since most available non-invasive tests have low positive predictive value and because treatment of liver fibrosis is lacking.
Nevertheless, to date, there is no clear consensus on how to implement these guidelines. Recently, the European Association for the Study of Diabetes (EASD), Obesity (EASO) and the Liver (EASL) proposed non-invasive screening for NAFLD and advanced fibrosis among patients with T2DM. These include magnetic resonance (MR)-based methods and serological marker testing. Consequently, non-invasive methods are being evaluated to replace liver biopsy. However, it has several limitations, including adverse events as well as sampling and observer variability. Liver biopsy is the current gold standard for diagnosing severity of NAFLD. And although NAFLD is strongly associated with the metabolic syndrome and T2DM, the association is bidirectional with a markedly higher prevalence of NAFLD in patients with T2DM (40–70%) than in individuals without T2DM, and an increased incidence of T2DM in patients with NAFLD. In the last four decades, there has been a steep increase in T2DM global prevalence, both in high/middle-, and low-income countries. Clinical and histological variables that predict overall mortality in NAFLD are age, type 2 diabetes mellitus (T2DM), and liver fibrosis. NAFLD increases the risk of liver-related and cardiovascular morbidity and mortality. In the near future, NAFLD is expected to become the leading cause for liver transplantation. Cirrhosis, in turn, is associated with a 2.5% annual risk of developing hepatocellular carcinoma (HCC). Histological features range from hepatic steatosis to non-alcoholic steatohepatitis (NASH), the latter being characterized by inflammation, with or without fibrosis, with the risk of progressing to cirrhosis. Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, with a worldwide prevalence of 20–30%.
Trial registration:, identifier NCT03864510. We expect that the study will uncover potential mechanisms of advanced hepatic fibrosis in NAFLD and T2DM and equip the clinician with better diagnostic tools for the care of T2DM patients with NAFLD.
Specifically, we will evaluate liver fat content using magnetic resonance imaging (MRI) hepatic fibrosis using MR elastography and vibration-controlled transient elastography muscle composition and body fat distribution using water-fat separated whole body MRI and cardiac function, structure, and tissue characteristics, using cardiovascular MRI. We will prospectively recruit 400 patients with T2DM using biomarkers to assess their status. Therefore, the purpose of the current study is to evaluate the prevalence and severity of NAFLD in patients with T2DM by recruiting participants from primary care, using the latest imaging modalities, to collect a cohort of well phenotyped patients. Consequently, the prevalence and characteristics of T2DM patients with advanced fibrosis are unknown. However, its utility is inherently limited. Liver biopsy is the gold standard for assessing hepatic fibrosis. NAFLD patients with type 2 diabetes mellitus (T2DM) are at an increased risk of advanced fibrosis, which puts them at risk of cardiovascular complications, hepatocellular carcinoma, or liver failure. Non-alcoholic fatty liver disease (NAFLD) affects 20–30% of the general adult population.