My Take: Why and How We Should Assess Fibrosis in Patients With HBV
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Paul Y. Kwo, MD
Professor of Medicine
Director of Hepatology
Stanford University School of Medicine
Palo Alto, California
When evaluating a patient for HBV treatment candidacy, most healthcare practitioners are aware that you need HBV DNA and ALT levels. However, in many cases, you also need to determine the presence and degree of fibrosis and inflammation.
Why Perform Fibrosis Assessments?
Many patients with HBV infection will have elevated DNA levels with normal ALT levels or ALT levels above the upper limit of normal (ULN) but < 2 x ULN, below the treatment threshold per the AASLD guidance. However, recent studies from Asia and the United States suggest that > 20% of the individuals who do not meet these cutoffs for treatment may have at least moderate inflammation and/or moderate fibrosis (≥ A2/F2) on liver biopsy. Therefore, if we relied solely on DNA and ALT levels, some patients who would greatly benefit from treatment would be missed.
The AASLD guidance from 2018 also recognizes the importance of assessing disease severity and activity, and they now emphasize that individuals with high HBV DNA but ALT levels < 2 x ULN should be assessed for fibrosis and/or inflammation, especially individuals older than 40 years of age. Fibrosis and inflammation have classically been assessed by liver biopsy, but practically speaking, not everyone with HBV infection is willing or able to have a liver biopsy—hence, we rely on noninvasive markers.
Elastography
One common way to assess fibrosis noninvasively is via elastography. Transient elastography, such as a FibroScan, is a point-of-care test that determines the level of liver scarring and can rule in or rule out advanced fibrosis. Transient elastography also simultaneously provides an indication of the level of steatosis via controlled attenuation parameter.
There are also other types of elastography, including ultrasonographic exam with shear wave elastography. Because this type of elastography uses ultrasound, it also has the advantage of providing information on morphologic characteristics of the liver. For example, you may be able to identify the presence of nodular liver, splenomegaly, or a dilated portal vein—all of which would suggest advanced fibrosis. However, remember that if a patient has an intermediate level of scarring, the liver is likely going to look morphologically normal, and only the shear wave elastography score would indicate fibrosis.
Finally, magnetic resonance elastography is the most accurate of the liver imaging modalities. However, these tests require a radiology referral and are more expensive.
Biomarker Tests
Biomarker tests that can be derived from very simple blood measurements are also available. If you are in an area that has limited resources, the FIB-4 index, which incorporates age, AST, ALT, and platelet levels, and the AST to platelet ratio index (APRI) may be more available and affordable than imaging assessments. These tests can accurately predict advanced fibrosis and cirrhosis.
In addition, there are combinations of serum markers that can be assessed. One example is the commercially available FibroTest, which uses gamma glutamyl transpeptidase, haptoglobin, bilirubin, A1 apolipoprotein, and α-2 macroglobulin levels. I recommend using these with caution—some individuals will have abnormal levels of these markers for other reasons, which renders the test inaccurate in those cases. However, they also can be a useful tool to help guide you in the right direction.
I also recommend looking at the platelet count as a simple first step in the assessment of fibrosis: If the platelet count is < 150,000/mm3, this may be an indicator of more advanced fibrosis. Another useful indicator is the AST to ALT ratio because a higher AST level vs ALT level is also a very important marker that may indicate advanced fibrosis in the absence of alcohol use.
Interpreting Results
As you assess patients with HBV, ensure that all measurements point in the same direction. For example, if a patient has a FibroScan or a transient elastography score suggestive of elevated liver stiffness or cirrhosis, then you would expect the FIB-4 and APRI to indicate more advanced fibrosis. If a patient has a high FIB-4, you would expect higher liver stiffness on elastography.
In some cases, it is challenging to determine the level of fibrosis noninvasively and you need a liver biopsy. However, as we further refine and evolve noninvasive markers, I think that for most patients, you can determine a level of fibrosis accurate enough to decide if you should move forward with treatment or continue monitoring.
Patients With Cirrhosis
One of the important changes in the 2018 AASLD guidance regarded the recommendations for patients with cirrhosis. The guidelines now recommend that patients with compensated cirrhosis and detectable HBV DNA should be treated with nucleot(s)ide analogue therapy. Previous guidance documents did not recommend treatment in those with compensated cirrhosis and low-level viremia, and now it does not matter if the ALT is normal or if the HBV DNA is low—treatment is recommended. Note that the AASLD guidance and the US 2015 treatment algorithm both suggest that persons with undetectable HBV DNA and compensated cirrhosis are not recommended for treatment. However, in my opinion, these individuals, although rare, must either be followed closely or treatment should be initiated.
Similarly, all patients with decompensated cirrhosis, regardless of HBV DNA and ALT levels, should be treated. This is recommended to prevent reactivation, which can lead to a significant episode of worsening cirrhosis, and flares in patients with decompensated cirrhosis are tolerated very poorly, unfortunately. As we improve our screening efforts for hepatitis B, my hope is that we will see fewer and fewer patients presenting with decompensated cirrhosis. Nonetheless, we continue to encounter these patients, and once identified, they should be counseled that they will require lifelong therapy while they have decompensated cirrhosis.
Your Thoughts?
How do you incorporate noninvasive methods to assess fibrosis into your practice? Please share your thoughts in the comments section.作者: StephenW 时间: 2021-2-26 13:28
為什麼要進行纖維化評估？
許多HBV感染患者的DNA水平會升高，而正常ALT水平或ALT水平高於正常上限（ULN），但<2 x ULN，低於AASLD指南規定的治療閾值。但是，來自亞洲和美國的最新研究表明，超過20％的未達到上述臨界值進行治療的個體在肝活檢中可能至少具有中度炎症和/或中度纖維化（≥A2 / F2）。因此，如果僅依靠DNA和ALT水平，就會錯過一些將從治療中受益匪淺的患者。
2018年的AASLD指南也認識到評估疾病嚴重程度和活動的重要性，他們現在強調，應評估HBV DNA高但ALT水平<2 x ULN的個體的纖維化和/或炎症，尤其是40歲以上的個體年齡。肝組織活檢通常對纖維化和炎症進行了評估，但實際上，並不是每個感染HBV的人都願意或能夠進行肝活檢-因此，我們依靠非侵入性標記物。