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My Approach to Navigating the Clinical Workup for HBV
CME CE
Source: Addressing Key Challenges in Viral Hepatitis Management
Norah Terrault Headshot
Norah Terrault, MD, MPH
Released: March 4, 2022
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Before reading the activity, please provide a baseline answer to the following question. (We will ask the question again at the end of the activity to measure the educational impact of this program.)
Which of the following tests is not necessary for the clinical workup of a patient who has screened positive for hepatitis B surface antigen (HBsAg)?
29%A. Complete blood count (CBC)
8%B. Hepatitis B e antigen (HBeAg)
6%C. HBV DNA
47%D. Hepatitis B core antibody (anti-HBc)
10%E. Unsure
The clinical workup for patients with newly diagnosed HBV infection can be daunting, owing in part to the need for interpretation of multiple serologic assays. In this commentary, I will summarize my general approach and will explain the purpose of each test we include in the workup in our clinic.
Initial Testing for All or Most Patients With HBsAg Positive Test Result
When patients present with a new HBV diagnosis, they have been determined to be positive for HBsAg and anti-HBc. At this stage, we obtain the first set of tests:
Liver panel
HBV DNA quantitation
HBeAg
CBC for platelet count
Viral coinfection (HIV and hepatitis C virus [HCV])
HBeAg and HBV DNA
The main purpose of determining HBeAg status is to identify which viral load (HBV DNA) threshold should be used in combination with ALT levels for determining whether HBV treatment is indicated. According to the American Association for the Study of Liver Diseases (AASLD) guidelines, for patients who are HBeAg positive, treatment is recommended if the HBV DNA level is >20,000 IU/mL, whereas for patients who are HBeAg negative, treatment is recommended at a lower HBV DNA threshold of ≥2000 IU/mL. The presence of HBeAg is generally a marker of higher levels of viral replication, which is why the HBV DNA threshold levels differ according to HBeAg status.
Another key benefit of identifying HBeAg status is the role that it plays as an intermediate endpoint for consideration of HBV treatment discontinuation in patients who are HBeAg positive at the start of treatment. In patients who are HBeAg positive at the start of treatment, I repeat testing for HBeAg every 6 months once HBV DNA has become undetectable to identify when HBeAg loss occurs. In patients who are HBeAg negative at baseline or who become HBeAg negative during treatment, I recommend checking for antibody to HBeAg (anti-HBe) to confirm seroconversion. Once seroconversion is documented (ie, patient is HBeAg negative and anti-HBe positive), repeat monitoring of HBeAg and anti-HBe is not required.
Liver Panel and Serum Fibrosis Panels
The ALT level obtained from the liver panel and the HBV DNA level are the 2 key laboratory results that are used to determine whether HBV treatment is indicated. Per AASLD guidance, ALT ≥2x upper limit of normal in combination with an HBV DNA level above the thresholds described per HBeAg status indicates that the patient should receive treatment for their HBV infection. Note that normal ALT values are up to 25 U/L in women and 35 U/L in men. Sometimes ALT levels are elevated above normal but not twice the upper limit of normal – in a so called “grey zone.” In these patients, monitoring ALT levels for an additional 3-6 months helps to clarify whether treatment is indicated. Consideration of other liver conditions that may cause ALT elevation is worthwhile (eg, fatty liver). Sometimes HBV DNA levels may be close but not quite at the thresholds for treatment indication. It is important to keep in mind that these thresholds are “guides” and not absolutes, so if they are close to the threshold and ALT levels are elevated, I would recommend proceeding with treatment.
An additional critical factor that must be considered in the initial evaluation of patients with newly diagnosed HBV infection is the presence and extent of liver fibrosis/cirrhosis. This is because patients with cirrhosis should be treated regardless of ALT and HBV DNA levels. If available, hepatic elastography is an excellent way to estimate fibrosis state, with a score >11 kPa suggesting advanced fibrosis/cirrhosis. However, even simple blood tests (platelet count, AST, and ALT) are used to noninvasively estimate liver fibrosis using the APRI or the FIB-4. A FIB-4 value >3.25 or an APRI score >1.5 suggests the presence of advanced fibrosis/cirrhosis and warrants HBV treatment.
Viral Coinfection (HCV and HIV)
We test every patient for HCV using anti-HCV because US Preventive Services Task Force (USPSTF) guidelines recommend that every adult should undergo HCV testing at least once. We also test all patients for HIV infection, most importantly because HIV status influences HBV treatment considerations
Ultrasound
In most cases, I also obtain a baseline ultrasound to screen for radiologic signs of cirrhosis and, in patients with risk factors for hepatocellular carcinoma (HCC), to concurrently screen for HCC. In practice, most of our patients with HBV fall into an HCC risk group based on age, race, and/or presence of cirrhosis and thus warrant surveillance for HCC with ultrasound and alpha-fetoprotein level every 6 months.
Additional Tests
HDV. Additional tests that we consider and generally include for most patients in our clinic are testing for HDV coinfection (anti-HDV testing). Although the AASLD guidelines recommend a risk-based approach to screening for HDV infection among patients diagnosed with HBV infection, the European Association for the Study of the Liver guidelines are broader and recommend that every patient with HBV infection be tested for HDV coinfection. With considerable underdiagnosis of HDV coinfection, there has been discussion about expanding HDV screening in the United States, and we take a broader approach in our clinic.
Quantitative HBsAg. Guidance on the use of quantitative HBsAg testing is limited, but this quantitative test is available and there is growing interest in how it can be used in clinical practice. Given the emphasis on HBsAg loss as a goal of HBV therapy, I follow HBsAg levels over time in my HBeAg-negative patients who are receiving HBV treatment as an indicator of progress toward that endpoint. This information can be particularly helpful for cases where we may be considering stopping HBV treatment, for example, in patients who have been on long-term therapy and are interested in the potential for discontinuing treatment.
Anti-HBc. When screening for HBV infection in my practice, I always test for both total anti-HBc and HBsAg, because a positive anti-HBc result with a negative HBsAg result indicates that someone has been exposed to HBV infection. This information is useful if that person later requires immune-suppressive therapy where there may be a risk for reactivation of HBV infection. Any patient who is positive for HBsAg will also be positive for anti-HBc, and there is no value in repeat testing for anti-HBc beyond initial screening.
Another potential use for anti-HBc testing is to identify or rule out acute HBV infection in a patient who presents with an extremely high ALT level (>250 U/L) and with a history that suggests they may have recently acquired HBV. In such cases, I order an anti-HBc IgM test rather than total anti-HBc, because IgM positivity indicates acute rather than chronic infection.
Antibody to HBsAg (Anti-HBs). The current definition of “functional cure” of HBV infection requires only HBsAg loss and not seroconversion to anti-HBs positivity. Although anti-HBs presence is the true marker of fully resolved HBV infection, this endpoint is not considered to have much clinical relevance once HBsAg has been lost, and HBV treatment can be discontinued after HBsAg loss, regardless of anti-HBs status. People who lose HBsAg will typically acquire anti-HBs over time, but the interval between the 2 events may range from months to years. In my practice, I test for anti-HBs after HBsAg loss, and if it is not detected, I repeat testing again in 6 months to 1 year. In most cases, it has appeared by then. |
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发表于 2022-4-28 18:30
