Limitations of non-invasive tests for assessment of liver fibrosis

Abstract

The diagnostic assessment of liver injury is an important step in the management of patients with chronic liver disease (CLD). Although liver biopsy is the reference standard for the assessment of necroinflammation and fibrosis, the inherent limitations of an invasive procedure, and need for repeat sampling, have led to the development of several non-invasive tests (NITs) as alternatives to liver biopsy. Such non-invasive approaches mostly include biological (serum biomarker algorithms) or physical (imaging assessment of tissue stiffness) assessments. However, currently available NITs have several limitations, such as variability, inadequate accuracy and risk factors for error, while the development of a newer generation of biomarkers for fibrosis may be limited by the sampling error inherent to the reference standard. Many of the current NITs were initially developed to diagnose significant fibrosis in chronic hepatitis C, subsequently refined for the diagnosis of advanced fibrosis in patients with non-alcoholic fatty liver disease, and further adapted for prognostication in CLD. An important consideration is that despite their increased use in clinical practice, these NITs were not designed to reflect the dynamic process of fibrogenesis, differentiate between adjacent disease stages, diagnose non-alcoholic steatohepatitis, or follow longitudinal changes in fibrosis or disease activity caused by natural history or therapeutic intervention. Understanding the strengths and limitations of these NITs will allow for more judicious interpretation in the clinical context, where NITs should be viewed as complementary to, rather than as a replacement for, liver biopsy.

Keywords: AGA, American Gastroenterology Association; ALT, alanine aminotransferase; APRI, AST-platelet ratio index; AST, aspartate aminotransferase; AUC, area under the curve; BMI, body mass index; Biomarkers; CAP, controlled attenuation parameter; CHB, chronic hepatitis B; CHC, chronic hepatitis C; CLD, chronic liver disease; CPA, collagen proportionate area; DAA, direct-acting antiviral; ELF, enhanced liver fibrosis; Elastography; FIB-4, fibrosis-4; FLIP, fatty liver inhibition of progression; HCC, hepatocellular carcinoma; IFN, interferon; LSM, liver stiffness measure; Liver biopsy; MR, magnetic resonance; MRE, magnetic resonance elastography; NAFLD, non-alcoholic fatty liver disease; NFS, NAFLD fibrosis score; NITs, non-invasive tests; Non-alcoholic fatty liver disease; SVR, sustained virologic response; US, ultrasound; VCTE, vibration-controlled transient elastography; Viral hepatitis.

Fig. 1

Guidance and consideration in using NIT for staging liver fibrosis. NIT, non-invasive test.