Non-invasive diagnostic approach to non-alcoholic fatty liver disease: current evidence and future perspectives

Abstract

Non-alcoholic fatty liver disease is a new epidemic liver disease, thus, its early diagnosis and the identification of those patients with the worst prognosis is mandatory. Liver biopsy is still the diagnostic gold standard, even if it is associated to a significant rate of complications; moreover, the interpretation of histological samples is not always univocal. Several non-invasive alternative scores have been proposed for the diagnostic approach to non-alcoholic fatty liver disease. This article evaluates the performance of the currently available non-invasive diagnostic strategies. The authors also suggest a potential diagnostic algorithm, with two or more non-invasive techniques, to increase the overall accuracy for identifying patients with worst prognosis, and to minimize the recourse to liver biopsy.

Keywords:

• liver fibrosis
• NAFLD
• NASH
• Non-invasive diagnosis
• steatosis
• transient elastography

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issues

• Non-alcoholic fatty liver disease includes a wide spectrum of diseases (fatty liver, nonalcoholic steatohepatitis [NASH], cirrhosis) occurring in patients with a daily alcohol consumption ≤30 g/day for men and ≤20 g/day for women, and in the absence of other causes of secondary liver fat accumulation.

• Liver biopsy, the diagnostic gold standard, is associated to potential risks or complications (bleeding, perforation, or infection): mortality rate ranging from 1:10,000 to 1:12,000. The correct histopathological classification is affected by the quality and quantity of liver tissue collected, which could be scarcely representative of whole liver damage. Moreover, inter- and intra-observer agreement between pathologists could affect the estimation of liver damage.

• Detection of liver steatosis: ultrasonography is a valid first-line diagnostic tool, however its accuracy is operator dependent; serum scores help to identify patients at high risk of liver steatosis; CT scan is scarcely accurate for detection of mild steatosis; MR is more accurate, but expensive and not available in all centers.

• Detection of NASH: serum fragments of CK-18 are the most promising and accurate serum makers for the prediction of NASH; however, they are not widely available and it is still premature to recommend their use in clinical practice. Magnetic resonance elastography is a promising instrumental technique for discrimination between steatosis and NASH.

• Estimation of liver fibrosis: complex serum scores (FibroTest, ELF and non-alcoholic fatty liver disease fibrosis score) are mostly accurate to predict advanced fibrosis; TE is a promising method for the estimation of liver fibrosis, however severe obesity limits the achievement of a sufficient number of successful determinations and the correct estimation of liver fibrosis; the XL probe has a better diagnostic performance on obese patients; results about ARFI diagnostic performance are discordant; evidences about real-time tissue elastography are few. Magnetic resonance elastography is a promising technique but not widely available.

• The CAP is a specific application of transient elastography allowing an accurate simultaneous quantification of both liver steatosis and fibrosis; however, these encouraging results need further validation.

• The formulation of a diagnostic algorithm, with two or more sequential non-invasive techniques, increases the overall accuracy for identifying patients with worst prognosis, and leads to minimize the recourse to liver biopsy.

Notes