Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disorder in Western countries, and its global prevalence is estimated at 25.2%. NAFLD may progress from liver steatosis to non-alcoholic steatohepatitis (NASH) and then to liver cirrhosis, which is associated with an increased risk of hepatocellular carcinoma and other cirrhosis-related complications.1 The main risk factors for NAFLD include components of the metabolic syndrome such as diabetes, obesity, dyslipidaemia and hypertension, and patients with these co-morbidities should be actively screened for NAFLD, even if their liver enzymes are within normal ranges.2–4 Currently, effective screening for NAFLD in clinical practice is hindered by a lack of clear guidelines concerning non-invasive diagnostic tools. Liver biopsy (LB) remains the gold standard for the diagnosis of NASH and assessment of fibrosis, but not for hepatosteatosis.1 Furthermore, biopsies have known disadvantages that include a risk of complications due to the invasive nature of the procedure, sampling variability because of the small size of tissue obtained, and the heterogeneous distribution of histological changes in liver parenchyma.5 Moreover, due to the extent of the condition (e.g., 80 million Americans are affected by NAFLD6) routine LBs to confirm NAFLD may be unwarranted and could even be considered unethical. Undoubtedly, LB remain the only tool available to confirm NASH, even though its prevalence among NAFLD patients is estimated at 1.5%-6.5%. Therefore LBs should only be considered in those patients at high risk for the progressive type of the disease.7
To find a new standard for liver steatosis screening, and to replace the use of LBs in most patients at low risk for NASH, non-invasive diagnostic methods (biomarkers and imaging-based techniques) are required. Controlled attenuation parameter (CAP) (FibroScan system; Echosens, Paris, France) integrated with Fibroscan — a modality estimating liver steatosis and fibrosis — remains one of the best quantitative tools that has been validated against LBs. CAP calculates the attenuation of an ultrasound beam traversing the liver tissue. It is observer independent and evaluates an area 100 times larger than an LB. CAP is considered to be an accurate tool for the diagnosis and staging of hepatic steatosis, with mean area under the receiver operating characteristic (AUROC) values for the diagnosis of mild, moderate and severe steatosis of 0.9, 0.8 and 0.7, respectively.4 However, the equipment needed to undertake this assessment is usually unavailable in non-hepatological centres, such as in clinics for general practitioners or peripheral hospitals.
During routine practice, liver steatosis is typically screened using abdominal ultrasound, despite its limitations, which include subjective evaluations, operator dependency and the ability to only recognize fatty liver infiltration that is greater than 15–20%. To enhance objectivity, Hamaguchi et al8 proposed an alternative, semi-quantitative, ultrasound-based, steatosis-assessment score that has 91.7% sensitivity and 100% specificity. Alternatively, the hepatorenal index (HRI) designed by Webb et al9 is another quantitative, ultrasound-based, hepatic-steatosis measure that correlates with LBs and has an AUROC of over 0.9 for all steatosis grades.10 To identify simpler and cost-effective approaches for the diagnosis of NAFLD, several scores based on easily measurable biochemical and clinical parameters such as the fatty liver index (FLI),11 hepatic steatosis index (HSI)12 and lipid accumulation product (LAP)13,14 have also been developed. All of these non-invasive tools are potentially useful screening methods for clinical practice; however, the choice of an optimal screening modality as part of a daily clinical routine is made difficult by a lack of comparative studies that assess their accuracy, as well as there being no clear guidelines for clinicians.
Therefore, the aim of this study was to undertake a comparative assessment of the diagnostic accuracy for the detection and quantification of hepatic steatosis using both ultrasound-based and biochemical techniques. Specifically, we investigated two validated ultrasound methods (Hamaguchi’s score and the HRI) and three biochemical panels (FLI, HSI and LAP) using CAP as the reference method.