Recent expert publications suggest a potential identification and referral algorithm that includes serum biomarker-based assessments to identify people with advanced fibrosis.1,2 Further information on these tests can be found in the Identifying people with NAFLD section.

If advanced fibrosis cannot be ruled out by serum biomarker-based assessments, patients should be referred to a liver specialist for additional diagnostic assessments.1 This section describes the further testing that may be performed by liver specialists to diagnose NASH and advanced fibrosis. 

Figure 1.0 Identifying and referring patients with suspected NASH.2

 

Diagnostic tests

Diagnostic imaging for steatosis

Diagnostic imaging can detect fatty infiltration of the liver. Ultrasound and proton magnetic resonance spectroscopy (1H-MRS) are two examples of methods for assessing this. Although ultrasound is recommended by EASL, this is not necessarily reflective of clinical practice.1  

Liver biopsy

Liver biopsy can be performed by a liver specialist to diagnose NASH and confirm advanced fibrosis due to NASH but while it may be valuable for some patients, the procedure is not routinely performed and is associated with a number of limitations:

  • Patient discomfort3
  • Potential complications4
  • Subjectivity of the interpretation5
  • Non-uniformity of liver/variability of sample6
  • Cost7

Liver specialists will consider the pros and cons of liver biopsy for their patients and determine how it may impact their future management.

Transient elastography

Transient elastography (fibroscan) is a commonly-used, noninvasive test in hepatology clinics for the assessment and grading of liver fibrosis.8,9 Fibroscan can be performed in 5–7 minutes and provides instant results.8 Fibrotic livers have reduced elasticity due to the deposition of fibrous tissue in the hepatic parenchyma.10 Fibroscan measures shear wave velocity to give a ‘liver stiffness measurement’ in kilopascals (kPa), allowing the stage of fibrosis to be determined.8,9 The accuracy of fibroscan in identifying liver fibrosis is high, and as the fibrosis stage increases, the diagnostic accuracy of fibroscan improves.11,12 Fibroscan may be less reliable in people who are obese or who have ascites.8,13

Larger kPa values correspond to a higher fibrosis stage, the values of which are summarised below.9

Table 1: Fibroscan reading results guide

Fibrosis stage

Fibroscan® reading (kPa)*

Description

Severity

F0 or F1

2–7

None/mild

F2

7.5–10

Moderate

F3

10–14

Bridging fibrosis

Advanced

F4

>14

Cirrhosis

Advanced

*Values are a guide and may vary between liver centres.

See Burden of NAFLD and NASH for more information on fibrosis stages.

 

Prognostic value of noninvasive tests

Noninvasive tests for fibrosis may provide sufficient accuracy to be used instead of liver biopsy for diagnosis of advanced fibrosis due to NASH.14 In addition to fibroscan, the enhanced liver fibrosis (ELF) and fibrosis-4 (FIB-4) calculators are both validated noninvasive tests, based on serum biomarker levels and other physiological measures (see Identifying people with NAFLD section for more information).15,16

An analysis of baseline data (N=3220) from an ongoing Phase III trial suggests that use of noninvasive tests can accurately diagnose advanced fibrosis and potentially reduce the need for biopsies. Fibroscan, in addition to FIB-4 and ELF, demonstrated good sensitivity and specificity for the identification of advanced fibrosis due to NASH, compared with liver biopsy.14 When used sequentially, FIB-4 followed by fibroscan and the ELF test accurately identified advanced fibrosis in 75% of patients, while accurately ruling it out in 82% of patients, when using test cutoffs defined by the study. In addition, the frequency of indeterminate results was as low as 9%.14

Diagnostic outcome

Using a variety of the tests outlined above, liver specialists can be supported in diagnosing and grading liver disease. Distinguishing between NAFL and NASH, and between stages of fibrosis will inform the management and follow-up approach.1 This may include a number of recommendations including lifestyle interventions, weight management and diet.1 More information on this can be found in the Management of NAFLD section.

NAFLD and NASH

The information on this page gives an overview of content in the NASH and NAFLD section of the site.

The burden of NAFLD and NASH

Content on this page focuses on definitions, fibrosis, natural history of NAFLD and NASH and more.

Identifying people with NAFLD

Exploring NAFLD risk factors and non-invasive testing in primary care.

Management of NAFLD and NASH

An overview of management approaches for people with NAFLD and NASH.

Obesity and NASH

An overview of advanced fibrosis due to NASH in people with obesity.

Diabetes and NASH

Information of the prevalence of NAFLD in the context of type 2 diabetes mellitus, the burden of NAFLD and NASH in diabetes, assessment and diagnosis and referral and management.

References

  1. European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO). EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol 2016;64:1388–402.
  2. Castera L, et al. Non-invasive assessment of liver disease in patients with NAFLD. Gastroenterol 2019 Jan 18 [Epub ahead of print].
  3. Cadranel JF, et al. Practices of liver biopsy in France: results of a prospective nationwide survey. For the Group of Epidemiology of the French Association for the Study of the Liver (AFEF). Hepatology 2000;32:477–81.
  4. Andronescu I, et al. The role of noninvasive tests and liver biopsy in the diagnosis of nonalcoholic fatty liver disease. J Med Life 2018;11:243–6.
  5. Soloway RD, et al. Observer error and sampling variability tested in evaluation of hepatitis and cirrhosis by liver biopsy. Am J Dig Dis 1971;16:1082–6.
  6. Ratziu V, et al. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology 2005;128:1898–906.
  7. Tapper EB, et al. Cost-Effectiveness Analysis: Risk Stratification of Nonalcoholic Fatty Liver Disease (NAFLD) by the Primary Care Physician Using the NAFLD Fibrosis Score. PLoS One 2016;11:e0147237
  8. Afdhal NH. Fibroscan (transient elastography) for the measurement of liver fibrosis. Gastroenterol Hepatol 2012;8:605–7.
  9. Memorial Sloan Kettering Cancer Center. Understanding your FibroScan® Results 2018. Available at: https://www.mskcc.org/cancer-care/patient-education/understanding-your-fibroscan-results (last accessed January 2019).
  10. Lurie Y, et al. Non-invasive diagnosis of liver fibrosis and cirrhosis. World J Gastroenterol 2015;21:11567–83.
  11. Hashemi SA, et al. Assessment of transient elastography (FibroScan) for diagnosis of fibrosis in non-alcoholic fatty liver disease: A systematic review and meta-analysis. Casp J Intern Med 2016;7:242–52.
  12. Cassinotto C, et al. Liver stiffness in nonalcoholic fatty liver disease: A comparison of supersonic shear imaging, FibroScan, and ARFI with liver biopsy. Hepatology 2016;63:1817–27.
  13. Castéra L, et al. Pitfalls of liver stiffness measurement: a 5-year prospective study of 13,369 examinations. Hepatology 2010;51:828–35.
  14. Younossi ZM, et al. Algorithms using noninvasive tests can accurately identify patients with advanced fibrosis due to NASH: data from the STELLAR clinical trials. Presented at AASLD 2018, San Francisco, USA, November 9–13, 2018. Abstract #LB 10.
  15. Sterling RK, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology 2006;43:1317–25.
  16. Xie Q, et al. The performance of enhanced liver fibrosis (ELF) test for the staging of liver fibrosis: a meta-analysis. PLoS One 2014;9:e92772.

LID/IHQ/18-12//1048d(1) Date of preparation August 2019