Non-alcoholic fatty liver disease (NAFLD) is a major public health problem afflicting approximately one billion individuals worldwide. Liver biopsy is considered the gold standard for assessment of liver disease severity in patients with NAFLD. However, it is invasive, has high inter-observer variability, and is associated with adverse effects, including pain, infection and, albeit rarely, death. It is also impractical because of the large number of individuals who have NAFLD. Therefore, tools to non-invasively assess disease severity in NAFLD are urgently needed. Over the last two decades, tremendous advances have been made in the assessment of NAFLD by non-invasive imaging. In this review, we will discuss the different non-invasive imaging modalities available to quantify liver fat and liver fibrosis. We will also discuss the limitations of current modalities to detect the progressive form for NAFLD, termed non-alcoholic steatohepatitis. Finally, we will discuss the comparative efficacy of various imaging-based elastographic modalities for detection of advanced fibrosis or cirrhosis, as well as their diagnostic characteristics.

Non-alcoholic fatty liver disease (NAFLD) is a major public health problem afflicting approximately one billion individuals worldwide. Liver biopsy is considered the gold standard for assessment of liver disease severity in patients with NAFLD. However, it is invasive, has high inter-observer variability, and is associated with adverse effects, including pain, infection and, albeit rarely, death. It is also impractical because of the large number of individuals who have NAFLD. Therefore, tools to non-invasively assess disease severity in NAFLD are urgently needed. Over the last two decades, tremendous advances have been made in the assessment of NAFLD by non-invasive imaging. In this review, we will discuss the different non-invasive imaging modalities available to quantify liver fat and liver fibrosis. We will also discuss the limitations of current modalities to detect the progressive form for NAFLD, termed non-alcoholic steatohepatitis. Finally, we will discuss the comparative efficacy of various imaging-based elastographic modalities for detection of advanced fibrosis or cirrhosis, as well as their diagnostic characteristics.

Nonalcoholic fatty liver disease (NAFLD) is diagnosed across the age spectrum and contributes to significant morbidity and mortality. The pathophysiology of NAFLD is not entirely understood; however, recent evidence has implicated the intestinal microbiome. Through the effects on host appetite, energy expenditure, digestion, gene expression, intestinal permeability, as well as immune activation, a dysbiotic microbiome can contribute to the development and progression of the hepatocellular steatosis, inflammation and fibrosis seen in the context of NAFLD. As such, intestinal microbiota and products of their metabolism have been targeted as treatment approaches for NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming one of the most common causes of liver disease. The progressive subtype of NAFLD, nonalcoholic steatohepatitis (NASH), leads to cirrhosis, hepatocellular carcinoma, and mortality. Fibrosis is the strongest predictor for complications. Due to the invasive nature of liver biopsy, noninvasive testing methods have emerged to detect fibrosis and predict outcomes. Of these modalities, magnetic resonance elastography (MRE) has demonstrated the highest accuracy to detect fibrosis. In this review, we will focus on the emerging data regarding MRE and liver fibrosis, cirrhosis, and portal hypertension in NAFLD.

The microbiome was originally postulated to contribute to the pathogenesis of NAFLD when the first studies of dysbiosis in NAFLD were reported. Since then, a number of studies have investigated this finding further, in order to discern whether the dysbiosis is the result of the metabolic dysregulation seen with NAFLD or a contributor to the pathogenesis of this condition.

Liver fibrosis should be assessed in all individuals with chronic liver disease as it predicts the risk of future liver-related morbidity and thus need for treatment, monitoring and surveillance. Non-invasive fibrosis tests (NITs) overcome many limitations of liver biopsy and are now routinely incorporated into specialist clinical practice. Simple serum-based tests (eg, Fibrosis Score 4, non-alcoholic fatty liver disease Fibrosis Score) consist of readily available biochemical surrogates and clinical risk factors for liver fibrosis (eg, age and sex). These have been extensively validated across a spectrum of chronic liver diseases, however, tend to be less accurate than more 'complex' serum tests, which incorporate direct measures of fibrogenesis or fibrolysis (eg, hyaluronic acid, N-terminal propeptide of type three collagen). Elastography methods quantify liver stiffness as a marker of fibrosis and are more accurate than simple serum NITs, however, suffer increasing rates of unreliability with increasing obesity. MR elastography appears more accurate than sonographic elastography and is not significantly impacted by obesity but is costly with limited availability. NITs are valuable for excluding advanced fibrosis or cirrhosis, however, are not sufficiently predictive when used in isolation. Combining serum and elastography techniques increases diagnostic accuracy and can be used as screening and confirmatory tests, respectively. Unfortunately, NITs have not yet been demonstrated to accurately reflect fibrosis change in response to treatment, limiting their role in disease monitoring. However, recent studies have demonstrated lipidomic, proteomic and gut microbiome profiles as well as microRNA signatures to be promising techniques for fibrosis assessment in the future.

Assessing for the presence of non-alcoholic steatohepatitis (NASH) and the presence of advanced fibrosis is vital among patients with non-alcoholic fatty liver disease (NAFLD) as each is predictive of disease outcomes. A liver biopsy is the gold standard method for doing so but is impossible to perform among all patients with NAFLD. Reliable methods for noninvasively detecting for the presence of NASH and advanced fibrosis are thus a pressing need. The search for noninvasive tests has been more successful for advanced fibrosis than for NASH. Clinical prediction models and elastography have acceptable accuracy for ruling out advanced fibrosis; when used together, as in a fibrosis prediction algorithm presented in this review, it can avoid the need for liver biopsy among many patients with NAFLD. Several biomarkers for identifying the presence of NASH have been studied but none are sufficiently accurate or validated. Of those studied, the most promising include CK-18 fragments, lipodomic and metabolomics candidates, and magnetic resonance elastography with proton density fat fraction. However, none are ready for clinical use and ultimately large multicenter prospective cohort studies are needed to validate select novel biomarkers.