Liver Fibrosis, Fibrosis-4 (FIB-4) Index Panel
Liver Fibrosis, Fibrosis-4 (FIB-4) Index Panel
This test is used to assess the likelihood of advanced liver fibrosis.
Test Summary
Liver Fibrosis, Fibrosis-4 (FIB-4) Index Panel
Test code: 30555
Clinical use
- Assess likelihood of advanced liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), hepatitis B, or hepatitis C
Clinical background
NAFLD, hepatitis B, and hepatitis C are liver diseases that can result in abnormal development of scar tissue (ie, fibrosis). NAFLD (recently renamed metabolic dysfunction–associated steatotic liver disease [MASLD]1) is strongly associated with metabolic syndrome, type 2 diabetes, and dyslipidemia,2 whereas hepatitis B and C are caused by infection with the hepatitis B (HBV) and C (HCV) viruses, respectively.3,4 Chronic disease progression in patients with these liver diseases can lead to the development of fibrosis, cirrhosis, and associated complications such as hepatocellular carcinoma.2,3,5
Liver disease severity is characterized in part by the presence of advanced fibrosis, which is defined by fibrosis staging that indicates the degree of scarring.6 Fibrosis stage is associated with mortality in NAFLD and influences management of NAFLD, hepatitis B, and hepatitis C.3,4,7 A biopsy is the gold standard for assessing fibrosis stage/liver disease severity, but the procedure is highly invasive and involves safety risks.6 Thus, noninvasive tests that assess for advanced fibrosis have been developed.
One such noninvasive test, the FIB-4 index, uses a combination of routine blood tests to indicate whether a patient has a high or low probability of advanced fibrosis. The FIB-4 index formula yields a single score by combining patient age with measurements of 3 biomarkers: aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count.
The FIB-4 index is included in clinical practice guidance for management of NAFLD, hepatitis B, and hepatitis C:
- For NAFLD, the FIB-4 index is recommended for primary risk assessment of liver fibrosis in the care pathways indicated by the American Association for the Study of Liver Diseases (AASLD),6 American Gastroenterological Association,8 American Association of Clinical Endocrinology,9 and American Diabetes Association.10 For patients with an indeterminate or high FIB-4 index, a secondary risk assessment using elastography or the enhanced liver fibrosis (ELF) score is recommended, after which those with indeterminate or high risk are recommended referral to specialized gastroenterology or hepatology care.6,8-10
- For hepatitis B, the FIB-4 index is included in AASLD guidance as an alternative to biopsy for assessing disease severity; this assessment helps guide treatment decisions for patients with chronic HBV infection, such as eligibility for antiviral therapy and therapy duration.3
- For hepatitis C, the FIB-4 index is recommended during pretreatment assessment in a simplified HCV treatment algorithm indicated by the AASLD and Infectious Diseases Society of America; this guidance considers an elevated FIB-4 index to be evidence of cirrhosis, which, in turn, determines treatment strategy selection and indicates additional surveillance for associated complications.4
Individuals suitable for testing
- Individuals with NAFLD who are undergoing risk stratification for advanced fibrosis
- Individuals with chronic HBV infection who are being considered for or receiving antiviral therapy
- Individuals with HCV infection
Methods
- AST and ALT measured using spectrophotometry
- Platelet count measured using electronic cell sizing and counting/cytometry/microscopy
- FIB-4 index calculated with a formula using AST, ALT, platelet count, and patient age
Interpretive information
The Table contains information useful in interpreting FIB-4 index values for NAFLD, hepatitis B, and hepatitis C. For all testing indications, an elevated FIB-4 index is consistent with the presence of advanced fibrosis, whereas a low FIB-4 index is consistent with the absence of advanced fibrosis. Patient characteristics and clinical features should guide interpretation. Consider additional assessment for patients with an indeterminant result.
Table. Interpretation Information for the FIB-4 Index, by Testing Indication
Indication for testing |
Compatible with the absence of advanced fibrosis11,a |
Compatible with the presence of advanced fibrosis11,a |
Indeterminate result |
NAFLD |
<1.30 |
>2.67 |
1.30-2.67 |
Hepatitis B |
<1.00 |
>2.65 |
1.00-2.65 |
Hepatitis C |
<1.45 |
>3.25 |
1.45-3.25 |
| NAFLD, nonalcoholic fatty liver disease. | |
| a | Advanced fibrosis is defined as stage F3 (bridging fibrosis) or F4 (cirrhosis). |
References
- Rinella ME, Lazarus JV, Ratziu V, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2023;78(6):1966-1986. doi:10.1097/hep.0000000000000520
- Basu R, Noureddin M, Clark JM. Nonalcoholic fatty liver disease: review of management for primary care providers. Mayo Clin Proc. 2022;97(9):1700-1716. doi:10.1016/j.mayocp.2022.04.005
- Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67(4):1560-1599. doi:10.1002/hep.29800
- Bhattacharya D, Aronsohn A, Price J, et al. Hepatitis C guidance 2023 update: American Association for the Study of Liver Diseases–Infectious Diseases Society of America recommendations for testing, managing, and treating hepatitis C virus infection. Clin Infect Dis. Published 2023. doi:10.1093/cid/ciad319
- Martinello M, Solomon SS, Terrault NA, et al. Hepatitis C. Lancet. 2023;402(10407):1085-1096. doi:10.1016/s0140-6736(23)01320-x
- Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77(5):1797-1835. doi:10.1097/hep.0000000000000323
- Dulai PS, Singh S, Patel J, et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta-analysis. Hepatology. 2017;65(5):1557-1565. doi:10.1002/hep.29085
- Long MT, Noureddin M, Lim JK. AGA Clinical Practice update: diagnosis and management of nonalcoholic fatty liver disease in lean individuals: expert review. Gastroenterology. 2022;163(3):764-774.e1. doi:10.1053/j.gastro.2022.06.023
- Cusi K, Isaacs S, Barb D, et al. American Association of Clinical Endocrinology clinical practice guideline for the diagnosis and management of nonalcoholic fatty liver disease in primary care and endocrinology clinical settings: co-sponsored by the American Association for the Study of Liver Diseases (AASLD). Endocr Pract. 2022;28(5):528-562. doi:10.1016/j.eprac.2022.03.010
- American Diabetes Association Professional Practice Committee. 4. Comprehensive medical evaluation and assessment of comorbidities: standards of care in diabetes—2024. Diabetes Care. 2024;47(Suppl 1):S52-S76. doi:10.2337/dc24-s004
- Tapper EB, Lok ASF. Use of liver imaging and biopsy in clinical practice. N Engl J Med. 2017;377(8):756-768. doi:10.1056/nejmra1610570
Content reviewed 07/2024
This test is used to assess the likelihood of advanced liver fibrosis.
Test Summary
Liver Fibrosis, Fibrosis-4 (FIB-4) Index Panel
Test code: 30555
Clinical use
- Assess likelihood of advanced liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), hepatitis B, or hepatitis C
Clinical background
NAFLD, hepatitis B, and hepatitis C are liver diseases that can result in abnormal development of scar tissue (ie, fibrosis). NAFLD (recently renamed metabolic dysfunction–associated steatotic liver disease [MASLD]1) is strongly associated with metabolic syndrome, type 2 diabetes, and dyslipidemia,2 whereas hepatitis B and C are caused by infection with the hepatitis B (HBV) and C (HCV) viruses, respectively.3,4 Chronic disease progression in patients with these liver diseases can lead to the development of fibrosis, cirrhosis, and associated complications such as hepatocellular carcinoma.2,3,5
Liver disease severity is characterized in part by the presence of advanced fibrosis, which is defined by fibrosis staging that indicates the degree of scarring.6 Fibrosis stage is associated with mortality in NAFLD and influences management of NAFLD, hepatitis B, and hepatitis C.3,4,7 A biopsy is the gold standard for assessing fibrosis stage/liver disease severity, but the procedure is highly invasive and involves safety risks.6 Thus, noninvasive tests that assess for advanced fibrosis have been developed.
One such noninvasive test, the FIB-4 index, uses a combination of routine blood tests to indicate whether a patient has a high or low probability of advanced fibrosis. The FIB-4 index formula yields a single score by combining patient age with measurements of 3 biomarkers: aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count.
The FIB-4 index is included in clinical practice guidance for management of NAFLD, hepatitis B, and hepatitis C:
- For NAFLD, the FIB-4 index is recommended for primary risk assessment of liver fibrosis in the care pathways indicated by the American Association for the Study of Liver Diseases (AASLD),6 American Gastroenterological Association,8 American Association of Clinical Endocrinology,9 and American Diabetes Association.10 For patients with an indeterminate or high FIB-4 index, a secondary risk assessment using elastography or the enhanced liver fibrosis (ELF) score is recommended, after which those with indeterminate or high risk are recommended referral to specialized gastroenterology or hepatology care.6,8-10
- For hepatitis B, the FIB-4 index is included in AASLD guidance as an alternative to biopsy for assessing disease severity; this assessment helps guide treatment decisions for patients with chronic HBV infection, such as eligibility for antiviral therapy and therapy duration.3
- For hepatitis C, the FIB-4 index is recommended during pretreatment assessment in a simplified HCV treatment algorithm indicated by the AASLD and Infectious Diseases Society of America; this guidance considers an elevated FIB-4 index to be evidence of cirrhosis, which, in turn, determines treatment strategy selection and indicates additional surveillance for associated complications.4
Individuals suitable for testing
- Individuals with NAFLD who are undergoing risk stratification for advanced fibrosis
- Individuals with chronic HBV infection who are being considered for or receiving antiviral therapy
- Individuals with HCV infection
Methods
- AST and ALT measured using spectrophotometry
- Platelet count measured using electronic cell sizing and counting/cytometry/microscopy
- FIB-4 index calculated with a formula using AST, ALT, platelet count, and patient age
Interpretive information
The Table contains information useful in interpreting FIB-4 index values for NAFLD, hepatitis B, and hepatitis C. For all testing indications, an elevated FIB-4 index is consistent with the presence of advanced fibrosis, whereas a low FIB-4 index is consistent with the absence of advanced fibrosis. Patient characteristics and clinical features should guide interpretation. Consider additional assessment for patients with an indeterminant result.
Table. Interpretation Information for the FIB-4 Index, by Testing Indication
Indication for testing |
Compatible with the absence of advanced fibrosis11,a |
Compatible with the presence of advanced fibrosis11,a |
Indeterminate result |
NAFLD |
<1.30 |
>2.67 |
1.30-2.67 |
Hepatitis B |
<1.00 |
>2.65 |
1.00-2.65 |
Hepatitis C |
<1.45 |
>3.25 |
1.45-3.25 |
| NAFLD, nonalcoholic fatty liver disease. | |
| a | Advanced fibrosis is defined as stage F3 (bridging fibrosis) or F4 (cirrhosis). |
References
- Rinella ME, Lazarus JV, Ratziu V, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2023;78(6):1966-1986. doi:10.1097/hep.0000000000000520
- Basu R, Noureddin M, Clark JM. Nonalcoholic fatty liver disease: review of management for primary care providers. Mayo Clin Proc. 2022;97(9):1700-1716. doi:10.1016/j.mayocp.2022.04.005
- Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67(4):1560-1599. doi:10.1002/hep.29800
- Bhattacharya D, Aronsohn A, Price J, et al. Hepatitis C guidance 2023 update: American Association for the Study of Liver Diseases–Infectious Diseases Society of America recommendations for testing, managing, and treating hepatitis C virus infection. Clin Infect Dis. Published 2023. doi:10.1093/cid/ciad319
- Martinello M, Solomon SS, Terrault NA, et al. Hepatitis C. Lancet. 2023;402(10407):1085-1096. doi:10.1016/s0140-6736(23)01320-x
- Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77(5):1797-1835. doi:10.1097/hep.0000000000000323
- Dulai PS, Singh S, Patel J, et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta-analysis. Hepatology. 2017;65(5):1557-1565. doi:10.1002/hep.29085
- Long MT, Noureddin M, Lim JK. AGA Clinical Practice update: diagnosis and management of nonalcoholic fatty liver disease in lean individuals: expert review. Gastroenterology. 2022;163(3):764-774.e1. doi:10.1053/j.gastro.2022.06.023
- Cusi K, Isaacs S, Barb D, et al. American Association of Clinical Endocrinology clinical practice guideline for the diagnosis and management of nonalcoholic fatty liver disease in primary care and endocrinology clinical settings: co-sponsored by the American Association for the Study of Liver Diseases (AASLD). Endocr Pract. 2022;28(5):528-562. doi:10.1016/j.eprac.2022.03.010
- American Diabetes Association Professional Practice Committee. 4. Comprehensive medical evaluation and assessment of comorbidities: standards of care in diabetes—2024. Diabetes Care. 2024;47(Suppl 1):S52-S76. doi:10.2337/dc24-s004
- Tapper EB, Lok ASF. Use of liver imaging and biopsy in clinical practice. N Engl J Med. 2017;377(8):756-768. doi:10.1056/nejmra1610570
Content reviewed 07/2024