The FIB-4 Index and its Role in Fatty Liver Screening

By Lindsay Hodgson, Dietetic Intern at Hailey Crean Nutrition LLC

What is Non-Alcoholic Fatty Liver Disease?

When there are imbalances in the body that interrupt the way the body metabolizes nutrients, the liver’s tissues can suffer. This is because most of the body’s nutrients are processed in the liver. Non-Alcoholic Fatty Liver Disease (NAFLD) is a common liver condition with known complications such as elevated blood lipid levels and type 2 diabetes (1).  An estimated 60-70% of people with type 2 diabetes may have NAFLD, versus a prevalence of about 24% in the general adult population (2,3).  In NAFLD, fat droplets deposit in liver cells (4).  Over time the fat deposits can cause inflammation in the liver tissue, and eventually progress the disease to scarred liver tissue (4,5).  Liver tissue has a remarkable ability to regenerate; however, once there has been scarring, the tissue cannot heal properly (4).  Early detection of fatty infiltration or inflammation in NAFLD is very important since interventions can occur while the tissue is healthy and responsive.

Progression: Inflammation → Fibrosis → Cirrhosis → End Stage Liver Disease

Since there are varying degrees of disease severity, medical professionals use a method of staging from inflammation in stage 1, to mild scar tissue called fibrosis in stage 2, to more severe accumulation of scar tissue called cirrhosis in stage 3, to end-stage liver disease in stage 4 (5).

How is NAFLD Diagnosed?

Interestingly, one of the main challenges medical providers face when working with patients who have liver conditions is accurately assessing the presence of inflammation, fat tissue, and scarring on the liver to be able to determine the NAFLD stage.

A liver biopsy is a procedure where doctors remove a small amount of liver tissue and examine it in the lab (6).  Biopsies are considered the “gold standard” to assign a stage to a NAFLD case, but they are invasive, expensive procedures that have associated risks (6).

Imaging methods like magnetic resonance imaging (MRI) and computerized tomography (CT) scans are also used to determine the degree of fibrosis in the liver (7).

Liver Function Tests (LFTs) are blood tests that give medical providers insight into a patient’s liver function. Some of the major ones are liver enzyme levels, blood proteins called albumin and a waste product called bilirubin.8 Inflammation may be suspected with results that demonstrated elevated liver enzymes and bilirubin, with low albumin because it suggests that the liver is having trouble building proteins and processing the end products in the body’s metabolism (8).

Liver enzymes- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)

These are enzymes in the liver that help the body utilize the protein and carbohydrate byproducts for cell functions and to produce energy. Alkaline phosphatase is an enzyme that helps the body utilize proteins. Inflammation or damage to the liver tissues can contribute to elevated blood levels of ALT, AST, and ALP.

Albumin

The liver makes a protein called albumin, which has important functions to transport nutrients throughout the body and keep normal balance of fluid between the blood and the organs. If albumin is low, the liver function may be compromised.
Bilirubin- Bilirubin is a waste product that accumulates when red blood cells die. The liver processes bilirubin in order to get rid of it. High levels of bilirubin therefore can mean that the liver is having problems processing waste products.

The Fibrosis-4, or FIB-4 Index

A non-invasive tool to assess inflammation in the liver.6 Medical professionals calculate FIB-4 index using the patient’s age, blood platelet count, and the levels of liver enzymes AST and ALT (6).  Platelet count is used because their interactions with liver cells helps the liver build new tissues (9).  So lower platelet count may be related to increased risk of fibrosis (9). FIB-4 index was observed to be the most effective tool when compared to the seven other noninvasive measures of fibrosis in NAFLD patients (6).  Higher degrees of liver scarring in NAFLD imaging results were correlated with higher FIB-4 indices among participants with diabetes (7).  However, researchers found that the FIB-4 index was 84.3% accurate as a diagnosing tool when they analyzed the data, and there were still false positives and negatives when identifying advanced scarring tissue (6,7).

It is important to know LFTs and FIB-4 cannot be used as a direct substitute for more direct screening methods like biopsies and imaging (6,7).  However, these methods can be helpful screening tools to assess a patient’s risk of liver scarring and can justify further diagnostic procedures.

Luckily, eating to support a healthy liver aligns well with nutrition to manage blood sugars. The recommendations have many similarities such as:

  • Increase intake of foods that are rich in fiber like whole grains, legumes, fruits, and vegetables
  • Emphasize balanced meals with carbohydrates, fats, and protein
  • Consume added sugars, sugar-sweetened beverages, and alcohol in moderation
  • Emphasize unsaturated fats like vegetable oils (olive oil, avocado oil, sunflower oil) nuts, seeds, avocados and fish
  • Practice physical activity, regular sleep schedule, and stress lowering techniques as needed

Each person has their own unique health challenges, but being aware of liver health and the relevant screenings can be an important part of preventative care in people with diabetes.

Reference List
  1. Dyson J, et al. Hepatocellular cancer: the impact of obesity, type 2 diabetes and a multidisciplinary team. J Hepatol. 2014;60:110–7. doi: 10.1016/j.jhep.2013.08.011.
    Hazlehurst JM, Woods C, Marjot T, Cobbold JF, Tomlinson JW. Non-alcoholic fatty liver disease and diabetes. Metabolism. 2016;65(8):1096-1108. doi:10.1016/j.metabol.2016.01.001
  2.  Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease—meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73–84. doi:10.1002/hep.28431
  3. Mahan LK, Raymond JL, Franz MJ, Evert AB. Krause’s Food & the Nutrition Care Process. 14th Edition. St. Louis, MO: Elsevier; 2017.
  4. Seladi-Schulman J. What Are the Stages of Liver Failure? Healthline. April 9, 2019. Accessed September 16, 2021. ​​https://www.healthline.com/health/liver-failure-stages
  5. Shah AG, Lydecker A, Murray K, Tetri BN, Contos MJ, Sanyal AJ; Nash Clinical Research Network. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2009 Oct;7(10):1104-12. doi: 10.1016/j.cgh.2009.05.033.
  6. Kawata N, Takahashi H, Iwane S, Inoue K, Kojima M, Kohno M, Tanaka K, Mori H, Isoda H, Oeda S, Matsuda Y, Egashira Y, Nojiri J, Irie H, Eguchi Y, Anzai K. FIB-4 index-based surveillance for advanced liver fibrosis in diabetes patients. Diabetol Int. 2020 Jul 9;12(1):118-125. doi: 10.1007/s13340-020-00453-7.
  7. Krans B. Liver Function Tests. Healthline. September 17, 2018. Accessed September 22, 2021. https://www.healthline.com/health/liver-function-tests#follow–up
  8. Zhong LK, Zhang G, Luo SY, Yin W, Song HY. The value of platelet count in evaluating the degree of liver fibrosis in patients with chronic hepatitis B. J Clin Lab Anal. 2020 Jul;34(7):e23270. doi: 10.1002/jcla.23270.

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