Chronic liver disease severity is determined by the liver’s landscape; the more liver cells that are damaged and scarred, the more advanced the liver disease is. Even after an initial diagnosis, the current state of your liver’s tissue is a major factor for predicting prognosis and making ongoing therapeutic decisions. Liver biopsy is the globally accepted reference test, but non-invasive techniques are becoming increasingly reliable methods for evaluating liver damage.
When liver damage outpaces the rate of liver cell regeneration, scarring of the liver can gradually lead to cirrhosis (permanent scarring and hardening of liver tissue). In liver tissue, scarring is an accumulation of extracellular matrix components. Liver biopsy and its alternative evaluation methods are designed to assess the degree of extracellular matrix components present. Although the liver biopsy is the best standard approach for determining how much scarring is present in the liver, it has several flaws.
In general, the histological staging systems for liver fibrosis currently used derive from the initial Knodell fibrosis score, and consist of either a five or seven tier rating. The higher the number, the more advanced the liver disease. The five tier rating system is most common, where the fibrosis score ranges from 0 to 4:
- 0 = no signs of fibrosis
- 1 = mild fibrosis
- 2 = moderate fibrosis
- 3 = severe fibrosis; fibrosis has spread and has connected to other areas on the liver
- 4 = cirrhosis
A liver biopsy is a medical procedure used to remove a small piece of liver tissue so doctors can examine the sample under a microscope. This enables them to:
- diagnose liver disease
- determine a score for fibrosis
- detect cancer and/or infections (although liver cancer is typically diagnosed via CT scan or MRI)
5 Drawbacks of Liver Biopsies
Although they are the accepted reference test, liver biopsies have drawbacks:
- There is a risk of pain and bleeding at the needle site.
- May be contraindicated for those with certain medical complications.
- There is a chance that the location being sampled does not represent the entire organ.
- They may not accurately sub-stage cirrhosis.
- Histological evaluation can be subjective; different clinicians may report different results.
6 Advantages of Non-Invasive Liver Fibrosis Tests
Liver biopsy is not the only way to evaluate liver tissue. Non-invasive methods are widely available, and their advantages include:
- The absence of contraindications and dangerous complications.
- Their reproducibility.
- The ability to evaluate fibrosis extent in the whole organ – not just the sampled section.
- Their potential ability to identify and differentiate between advanced fibrosis stages.
- Their high specificity and sensitivity to diagnose cirrhosis.
- Their easy application.
Categories for Non-Invasive Liver Fibrosis Tests
There are three basic categories for non-invasive liver fibrosis tests:
- Serologic Panels – The serologic fibrosis markers are broadly categorized into direct and indirect markers. Direct markers of fibrosis include indices reflecting collagen synthesis or collagen degradation. Indirect markers of fibrosis are simple routine blood tests reflecting alterations in liver function but not directly representing extracellular matrix metabolism. These panels are highly reproducible, well validated and easily available. However, they are unable to discriminate between intermediate stages of fibrosis.
- Combined Scores and Algorithms – The currently used clinical combined scores, also referred to as algorithms, utilize a combination of measurements to deliver information about the liver. The ones currently in use include Fibrotest,® Hepascore, Fibrospect, Fibrometer, Forns Index, Aspartate Aminotransferase-to-Platelet ratio index (APRI), European Liver Fibrosis panel (ELF), SAFE Biopsy (SAFE: Sequential Algorithm for Fibrosis Evaluation), BAAT score [body mass index (BMI), age, ALT, triglyceride (levels)], BARD score, NAFLD fibrosis score and FIB-4 score.
- Imaging Techniques – To improve non-invasive liver fibrosis detection and assessment, many imaging techniques have emerged. These techniques are based on classical tools such as ultrasonography, computed tomography and magnetic resonance imaging. These include transient elastography (TE), magnetic resonance elastography (MRE), acoustic radiation force impulses [ARFI, 2D-Shear wave elastography (2D-SWE)], and contrast-enhanced sonography. Imaging techniques are user-friendly and are good for identifying cirrhosis; however, they require a dedicated device.
Because each test has a different set of pros and cons, experts currently advise a combination of biopsy and non-invasive tests to get accurate fibrosis/cirrhosis information.
Listed below is a sampling of those pros and cons:
- APRI – This test is good for predicting severe fibrosis/cirrhosis or low risk of significant fibrosis, but does not accurately differentiate intermediate fibrosis from mild or severe fibrosis.
- FIB-4 – This test is easy-to-use, quick and inexpensive, and is good at excluding or confirming cirrhosis. However, mid-range values do not fully discriminate fibrosis and need an additional method to predict liver fibrosis.
- Forns Index – This algorithm has good predictive value in selecting those with low risk of significant fibrosis, but does not reliably predict more advanced fibrosis or cirrhosis.
- HepaScore – Also known as FibroScore, this method is good at excluding significant fibrosis but not as good at predicting cirrhosis.
- TE – Transient elastography helps with detection of advanced fibrosis and cirrhosis. However, liver inflammation, obesity, ascites and high central venous pressure can interfere with TE results. Most clinicians use TE in combination with other types of liver fibrosis tests.
- MRE – This imaging test has similar limitations to TE, although its high sensitivity and specificity results are proving to be clinically valuable. Unfortunately, this test is costly.
An increasing number of clinicians are knowledgeable about the pros and cons of liver fibrosis evaluation techniques, leading to the individualization of testing. As liver fibrosis identification becomes more specific, reproducible and sensitive, finding out what degree of damage your liver has incurred will get easier. Until then, find a competent practitioner who knows the pros and cons of these methods. They will likely order a combination of biopsy, serological, algorithm and imaging tests to get the most accurate image of your liver’s current landscape.
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