Test ID: NSFIB    
Nonalcoholic Steatohepatitis (NASH)-FibroTest, Serum and Plasma

Diagnosis and the follow-up of liver fibrosis, steatosis and inflammation

Estimating hepatic fibrosis

Assessing inflammation for metabolic diseases

Assessing severity of nonalcoholic steatohepatitis (NASH) in patients with nonalcoholic fatty liver disease with steatosis (NAFLD)

Assessing steatosis or fatty liver

Reassuring patients with steatosis only, without fibrosis

Managing patients with severe injuries such as advanced fibrosis and NASH

This test is a patented test algorithm developed by BioPredictive. It combines 10 standard biomarkers: gamma-glutamyltransferase (GGT), total bilirubin, alpha-2-macroglobulin, apolipoprotein A1, haptoglobin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol, triglycerides, and fasting glucose. These markers are weighted depending on the patient's age and gender.

Testing is compliant with BioPredictive's technical recommendations and approvals.

This test estimates the 3 elementary features of metabolic liver disease: steatosis, activity, and fibrosis. The estimation is made by measuring 10 standard serum biomarkers (gamma-glutamyl transferase, total bilirubin, alpha-2-macroglobulin, apolipoprotein A1, haptoglobin, alanine aminotransferase, aspartate aminotransferase, cholesterol, triglycerides and fasting plasma glucose). Results from these tests are combined with the patient's age and gender to estimate hepatic fibrosis (FibroTest), steatosis (SteatoTest 2) and activity (NashTest 2) scores.

NASHTEST 2 INTERPRETATION

*Boundary values can apply to 2 stages based on rounding. For example, a NashTest 2 score of 0.245 will round up to 0.25 and be staged N0. A NashTest 2 score of 0.254 will round down to 0.25 and be staged N2.

STEATOTEST 2 INTERPRETATION

*Boundary values can apply to 2 stages based on rounding. For example, a SteatoTest 2 score of 0.395 will round up to 0.40 and be staged S0. A SteatoTest 2 score of 0.404 will round down to 0.40 and be staged S1.

FIBROTEST INTERPRETATION

*Boundary values can apply to 2 stages based on rounding. For example, a FibroTest score of 0.305 will round up to 0.31 and be staged F1. A FibroTest score of 0.314 will round down to 0.31 and be staged F1-F2.

ALPHA-2-MACROGLOBULIN

< or =18 years: 178-495 mg/dL

>18 years: 100-280 mg/dL

ALANINE AMINOTRANSFERASE (ALT)

Males

<12 months: Not established

> or =1 year: 7-55 U/L

Females

<12 months: Not established

> or =1 year: 7-45 U/L

APOLIPOPROTEIN A1

Males

<24 months: Not established

2-17 years

Low: <115 mg/dL

Borderline low: 115-120 mg/dL

Acceptable: >120 mg/dL

> or =18 years: > or =120 mg/dL

Females

<24 months: Not established

2-17 years

Low: <115 mg/dL

Borderline low: 115-120 mg/dL

Acceptable: >120 mg/dL

> or =18 years: > or =140 mg/dL

GAMMA-GLUTAMYLTRANSFERASE (GGT)

Males

0-11 months: <178 U/L

12 months-6 years: <21 U/L

7-12 years: <24 U/L

13-17 years: <43 U/L

> or =18 years: 8-61 U/L

Females

0-11 months: <178 U/L

12 months-6 years: <21 U/L

7-12 years: <24 U/L

13-17 years: <26 U/L

> or =18 years: 5-36 U/L

HAPTOGLOBIN:

30-200 mg/dL

BILIRUBIN, TOTAL

0-6 days: Refer to www.bilitool.org for information on age-specific (postnatal hour of life) serum bilirubin values.

7-14 days: <15.0 mg/dL

15 days to 17 years: < or =1.0 mg/dL

> or =18 years: < or =1.2 mg/dL

ASPARTATE AMINOTRANSFERASE (AST)

Males

0-11 months: Not established

1-13 years: 8-60 U/L

> or =14 years: 8-48 U/L

Females

0-11 months: Not established

1-13 years: 8-50 U/L

> or =14 years: 8-43 U/L

CHOLESTEROL, TOTAL

The National Lipid Association and the National Cholesterol Education Program (NCEP) have set the following guidelines for lipids (total cholesterol, triglycerides, high-density lipoprotein [HDL] cholesterol, low-density lipoprotein [LDL] cholesterol, and non-HDL cholesterol) in adults 18 years old and older:

TOTAL CHOLESTEROL

Desirable: <200 mg/dL

Borderline high: 200-239 mg/dL

High: > or =240 mg/dL

The Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents has set the following guidelines for lipids (total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, and non-HDL cholesterol) in children 2 to 17 years of age:

TOTAL CHOLESTEROL

Acceptable: <170 mg/dL

Borderline high: 170-199 mg/dL

High: > or =200 mg/dL

TRIGLYCERIDES

The National Lipid Association and the National Cholesterol Education Program (NCEP) have set the following guidelines for lipids (total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, and non-HDL cholesterol) in adults 18 years old and older:

TRIGLYCERIDES

Normal: <150 mg/dL

Borderline high: 150-199 mg/dL

High: 200-499 mg/dL

Very high: > or =500 mg/dL

The Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents has set the following guidelines for lipids (total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, and non-HDL cholesterol) in children 2 to 17 years of age:

TRIGLYCERIDES

2-9 years

Acceptable: <75 mg/dL

Borderline high: 75-99 mg/dL

High: > or =100 mg/dL

10-17 years

Acceptable: <90 mg/dL

Borderline high: 90-129 mg/dL

High: > or =130 mg/dL

For SI unit Reference Values, see https://www.mayocliniclabs.com/order-tests/si-unit-conversion.html

GLUCOSE FASTING

0-11 months: not established

> or =1 year: 70-100 mg/dL

This test provides numeric scores that assess hepatic fibrosis (FibroTest), hepatic inflammation (NashTest 2), and steatosis (SteatoTest 2). Interpretation of the scores is provided in the report. Individual results from the 10 component tests are also provided with institution-specific reference intervals.

FibroTest is reported relative to a scale ranging from F0-F4 (F0=no fibrosis, F1=minimal fibrosis, F2=moderate fibrosis, F3=advanced fibrosis, F4=severe fibrosis [cirrhosis]). Fibrosis scores may overlap (eg, F0/F1, F1/F2).

NashTest 2 is reported relative to a scale ranging from N0-N3 (N0=no nonalcoholic steatohepatitis: NASH, N1=mild NASH, N2=moderate NASH, N3=severe NASH).

Steatosis is reported relative to a scale ranging from S0-S2S3 (S0=no steatosis [<5%], S1=mild steatosis [5-33%], S2/S3=moderate/severe steatosis [34-100%]). A stage of S1 or S2S3 is considered clinically significant.

The tests have to be deferred for: acute hemolysis, acute hepatitis, acute inflammation, extra hepatic cholestasis.

The advice of a specialist should be sought for interpretation in chronic hemolysis or Gilbert syndrome.

The test interpretation has not been validated for liver transplant patients.

Isolated extreme values of one of the components should lead to caution in interpreting the results.

In case of discordance between a biopsy result and a test, it is recommended to seek the advice of a specialist. The causes of these discordances could be due to a flaw of the test or to a flaw in the biopsy: ie, a liver biopsy has a 33% variability rate for one fibrosis stage.

NashTest 2 is set to N0 is the absence of steatosis based on the definition of nonalcoholic steatohepatitis (NASH). SteatoTest 2 scores of less than 0.40 (S0) will default NashTest 2 to N0.

1. BioPredictive: Technical Recommendations for FibroTest, FibroMax, and NASH-FibroTest assays, Bio Predictive. Version 3.0

2. Poynard T, Peta V, Munteanu M, et al: The diagnostic performance of a simplified blood test (SteatoTest-2) for the prediction of liver steatosis. Eur J Gastroenterol and Hepatol. 2019 Mar;31(3)393-402. doi: 10.1097/MEG.0000000000001304

3. Munteanu M, Pais R, Peta V, et al: Long term prognostic value of the FibroTest in patients with non-alcoholic fatty liver disease, compare to chronic hepatitis C, B, and alcoholic liver disease. Aliment Pharmacol Ther. 2018 Nov:48(10):1117-1127. doi: 10.1111/apt.14990

4. Poynard T, Munteanu M, Charlotte F, et al: Diagnostic performance of a new noninvasive test for nonalcoholic steatohepatitis using a simplified histological reference. Eur J Gastroenterol and Hepatol. 2018 May;30(5):569-577. doi: 10.1097/MEG.0000000000001064

5. Poynard T, Munteanu M, Charlotte F, et al: Impact of steatosis and inflammation definitions on the performance of NASH tests. Eur J Gastroenterol Hepatol. 2018 Apr;30(4):384-391. doi: 10.1097/MEG.0000000000001033

6. Munteanu M, Tiniakos D, Anstee Q, et al: Diagnostic performance of FibroTest, SteatoTest and ActiTest in patients with NAFLD using the SAF score as histological reference. Aliment Pharmacol Ther. 2016 Oct;44(8):877-889. doi: 10.1111/apt.13770

7. Vilar-Gomez E, Chalasani N: Non-invasive assessment of non-alcoholic fatty liver disease: Clinical prediction rules and blood-based biomarkers. J Hepatol. 2018 Feb;68(2):305-315. doi: 10.1016/j.jhep.2017.11.013

8. Ratziu V, Charlotte F, Heurtier A, et al: Sampling variability of liver biopsy in nonalcoholic liver disease. Gastroenterology. 2005 Jun;128(7):1898-1906. doi: 10.1053/j.gastro.2005.03.084