Original articleScreening for non-alcoholic fatty liver disease using liver stiffness measurement and its association with chronic kidney disease and cardiovascular complications in patients with type 2 diabetes
Introduction
Non-alcoholic fatty liver disease (NAFLD) is now recognized to be the most common chronic liver disease worldwide. The condition affects up to a third of adults in the general population of high-income countries, and its prevalence is even higher among patients with type 2 diabetes mellitus (T2DM), affecting up to 70–80% of such patients [1], [2]. Compared with people without diabetes, patients with T2DM are also more likely to have or to develop more severe histological forms of NAFLD, such as non-alcoholic steatohepatitis (NASH), advanced fibrosis and cirrhosis, even in those who have fairly “normal” serum liver enzyme levels [2], [3], [4]. In fact, a recent meta-analysis has confirmed that the global prevalence of biopsy-confirmed NASH among patients with T2DM was around 38%, and that the global prevalence of advanced fibrosis in those with both NAFLD and T2DM was about 17% [2].
It is also important to remember the clinical importance of the bidirectional relationship between NAFLD and T2DM [4], [5]. In particular, the coexistence of NAFLD and T2DM worsens the course of both conditions. Coexisting T2DM not only increases the risk of NAFLD progression to advanced fibrosis and cirrhosis, but also increases the risk of incident hepatocellular carcinoma, liver-related hospital admissions and liver-related deaths [4], [6], [7], [8], [9]. In addition, the presence of NAFLD makes achieving good glycaemic control more difficult, exacerbates hepatic/peripheral insulin resistance and promotes atherogenic dyslipidaemia, thereby further increasing the risk of developing extrahepatic diseases such as chronic kidney disease (CKD) and cardiovascular complications, particularly in T2DM patients with advanced NAFLD [3], [4], [10].
Collectively, these findings support the conclusion that, in patients with T2DM, the diagnosis and treatment of NAFLD should be considered a high clinical priority among diabetologists caring for patients at risk of progressive NAFLD. Therefore, this can also be argued to make a case for systematic screening for NAFLD among patients at high risk of advanced NAFLD, such as those with T2DM. This conclusion is in accordance with guidelines from the 2016 European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO) and Italian Association for the Study of the Liver (AISF) [11], [12], but not the 2016 England and Wales National Institute for Health and Care Excellence (NICE) NAFLD guidelines [13] or the 2018 American Association for the Study of Liver Diseases (AASLD) practice guidelines [14]. In fact, the latter has recommended against systematic screening for NAFLD in patients with T2DM because of the uncertainties surrounding diagnostic tests and treatment options, along with a lack of knowledge related to the long-term benefits and cost-effectiveness of screening [14]. Nevertheless, the AASLD guidelines have recommended that there be a high index of suspicion for NAFLD and NASH in patients with T2DM, and that clinical decision aids, such as vibration-controlled transient elastography (VCTE), may be used to identify those at low or high risk of advanced liver fibrosis, the strongest predictor of long-term adverse clinical outcomes with NAFLD [14]. Indeed, liver stiffness measurement (LSM) by VCTE (also known as FibroScan®) is proving to be a reliable diagnostic tool for non-invasively staging liver fibrosis in patients with various chronic liver diseases, including NAFLD [15].
Yet, despite the high prevalence and serious clinical implications of NAFLD in T2DM patients, this liver disease is frequently overlooked in routine diabetes care [2], [4]. This means that increasing awareness of the importance of NAFLD in patients with T2DM among primary-care physicians, specialists and health policy makers should be a priority.
Thus, the main aim of the present cross-sectional study was to non-invasively screen for the presence of NAFLD and liver fibrosis by using both ultrasonography and VCTE in a well-characterized sample of T2DM outpatients with no known liver disease(s), and to examine whether increased liver fibrosis is associated with the presence of CKD and cardiovascular complications in these patients.
Section snippets
Patients
This study enrolled 137 (48.2% male) patients with non-insulin-treated T2DM who had consecutively attended our diabetes outpatients’ service over a period of approximately 4 months, and agreed to undergo liver ultrasonography and VCTE for diagnosing and staging NAFLD. Excluded were all patients with:
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a history of significant alcohol consumption (defined as > 20 g/day of alcohol for men and women) or other known causes of chronic liver disease (viral infection, drug use, autoimmunity,
Results
A total of 137 patients (48.2% men) with non-insulin-treated T2DM were included in our study (mean ± SD: age 69.9 ± 7 years; BMI: 28.5 ± 4.7 kg/m2; waist circumference: 100 ± 12 cm; HbA1c: 6.9 ± 0.8%; median duration of diabetes: 11 years [IQR 6–18]). Of these patients, 28 (20.4%) had established cardiovascular disease [20 (14.6%) patients had previous IHD and eight (8.5%) had either ischaemic stroke or permanent atrial fibrillation]. In addition, 37 (27%) of these patients had CKD [14 (10.2%) had eGFR < 60
Discussion
A major finding of our study is that a substantial proportion of patients with T2DM routinely attending an outpatients’ service had NAFLD and significant or advanced liver fibrosis. Indeed, the majority of these patients (around 75%) revealed hepatic steatosis on ultrasonography, and a significant proportion also had increased liver fibrosis on VCTE: 17.5% had LSM ≥ 7 kPa and 10.2% had LSM ≥ 8.7 kPa (corresponding to Kleiner fibrosis stage ≥ F3 on histology) [14], [19]. It is also worth noting that
Funding
G.T. is supported in part by grants from the University School of Medicine of Verona, Verona, Italy. C.D.B. is supported in part by grants from the Southampton National Institute for Health Research Biomedical Research Centre, Southampton, UK.
Disclosure of interest
The authors declare that they have no competing interest.
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