Advances in non-invasive assessment of hepatic fibrosis

Abstract

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.

Keywords: Nonalcoholic fatty liver disease; chronic liver disease; cirrhosis; elastography; serum biomarkers.

Figure 1

Comparative accuracy and accessibility of non-invasive fibrosis tests (NITs). 2D-SWE, two-dimensional sheer wave elastography; pSWE, pulse shear wave elastography; VCTE, vibration-controlled transient elastography.

Figure 2

Algorithm for assessment of advanced fibrosis in patients with chronic liver disease. A liver biopsy can be considered in the correct clinical context following an indeterminate or high serum test result in conjunction with a high elastography result as the positive predictive value for advanced fibrosis may be less than 80%. MRE, MR elastography; NPV, negative predictive value; VCTE, vibration-controlled transient elastography. ALT, alanine aminotransferase.