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Staging Fibrosis in CHB
Pulling Back the Curtain: The Importance of Staging Fibrosis in Patients With Chronic Hepatitis B

Released: January 12, 2024

Expiration: January 11, 2025

Grace LH Wong
Grace LH Wong, MD
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Key Takeaways
  • Staging liver fibrosis in patients with chronic hepatitis B is integral to determine the need for antiviral therapy and hepatocellular carcinoma screening.
  • Owing to the invasive nature and inherent sampling variability of liver biopsies, noninvasive testing methods and radiographic techniques are recommended.

The current Asian Pacific Association for the Study of the Liver (APASL) clinical practice guidelines on the management of chronic hepatitis B emphasize the importance of accurate liver fibrosis staging and/or necroinflammatory grading for choosing therapeutic and management strategies including treatment response to antiviral therapy. But staging liver fibrosis may require techniques that may not be widely available (eg, specific serum biomarkers, specialized ultrasound techniques). In addition, guideline recommendations on which approach to use are not clearly defined.

Given the importance of staging liver fibrosis in determining hepatitis B virus (HBV) and hepatitis delta virus treatment candidacy, which approach should we use to measure it?

Noninvasive Testing
Liver biopsies have long been the gold standard for diagnosing and staging fibrosis. However, the APASL guidelines acknowledge the shortcomings of this method because of its invasive nature and inherent sampling variability. Hence, a handful of noninvasive tests based on serum fibrosis markers or imaging is recommended, including simple biomarkers (like alanine aminotransferase, aspartate aminotransferase, platelet counts that can be used individually or combined into scores), more specialized panels (like FibroTest), and radiographic techniques.

Each approach has its own strengths and weaknesses. Here is why—when it’s available—I prefer imaging over the others.

Biomarkers

Use of serum fibrosis markers can be a simple approach to stage fibrosis. Examples include the AST-to-ALT ratio, the fibrosis score-4 (FIB-4), and the AST-to-platelet ratio index. These methods to stage liver fibrosis are mostly used in primary care settings and have the advantage of high clinical utility with modest accuracy. However, further testing may be needed to confirm these results.

More specialized tests (eg, FibroTest, Fibrometer, Hepascore) include panels of serum biomarker tests that quantify multiple biochemical markers to enhance testing and increase accuracy, but they are not widely available.

Radiographic Techniques

Radiographic techniques include vibration-controlled transient elastography (VCTE), acoustic radiation force impulse imaging, and magnetic resonance elastography.

VCTE is one of the most popular tools used in practice; it is easy to perform with high clinical applicability and reproducibility.

In assessing the severity of liver fibrosis, vigorous validation studies have established the reliability and accuracy of using VCTE to obtain a liver stiffness measurement (LSM) as a surrogate for liver biopsy. This LSM provides robust prognostic value for clinical outcomes such as the development of hepatocellular carcinoma (HCC) and determining the need for treatment of varices. Furthermore, LSM has been incorporated into various HCC risk scores or prediction models, namely the LSM-HCC score. These scores guide us on when to begin antiviral therapy in a timely manner and offer appropriate intensity of HCC surveillance.

Despite this promising evidence, implementation of VCTE is limited in some parts of the world by its restricted availability. It can also be difficult to interpret LSM because there is variability in published cutoff values. Some clinical scenarios may also have a confounding effect on LSM, such as severe acute exacerbation of HBV manifested as grossly elevated ALT level, cholestasis, and obesity.

However, such gaps have been partially addressed in the recently published Baveno VII consensus, which proposed simplified cutoff values with the “rule of 5” to rule out (10 kPa) or rule in (15 kPa) compensated advanced chronic liver disease and to rule out (15 kPa) or rule in (25 kPa) clinically significant portal hypertension.

My Approach
Personally, when assessing people with chronic hepatitis B, I use VCTE as my first tool for fibrosis staging. I base my recommendations on the LSM result, using the following cutoffs:

  • Normal LSM (<10 kPa): repeat VCTE examination in 2-3 years
  • Borderline LSM (10-15 kPa): repeat VCTE examination in 6-12 months
  • Elevated LSM (>15 kPA): start antiviral therapy and perform HCC and variceal surveillance

If radiographic techniques like VCTE are not readily available, I would recommend a stepwise approach of using FIB-4 to rule out advanced fibrosis, followed by a radiographic technique for those with FIB-4 results above an established cutoff such as a score of 1.5.

Future Implications
Many of the key international HBV guidelines are being updated—including the APASL guidelines. I suspect that simpler and more inclusive fibrosis staging strategies will be recommended to facilitate the clinical application of noninvasive tests to benefit more patients with timely antiviral treatment and screening for liver-related complications.

Your Thoughts?
In your patients with chronic hepatitis B, what techniques do you use to stage liver fibrosis? Join the discussion by posting a comment.