Transient Elastography in Pediatric Liver Disease

AM Banc-Husu, LM Bass. JPGN 2021; 73: 141-144. Transient Elastography in Pediatric Liver Disease

This useful review explains the techniques/technologies/limitations of transient elastography and provides pediatric values which correlate with liver fibrosis. Confounding factors, however, may affect elastography measurements, such as obesity, severe inflammation, nonfasting state, and hepatic congestion.

From Table 2 for Elastography (FibroScan technology) Cut-Off Values and Correlation with Outcomes :

  • Biliary Atresia: >15.5 kPa distinguishes METAVIR F4 fibrosis and >12.7 kPa predicts development of varices
  • Any Chronic Liver disease: >10.6 kPa distinguishes METAVIR F2 fibrosis
  • Non-alcoholic fatty liver disease: >9 kPa distinguishes advanced fibrosis
  • Portal hypertension: >9.7 kPa distinguishes presence of portal hypertension
  • Liver transplant graft: >5.6 kPa distinguishes advanced fibrosis

My take: Elastography is most useful when values are at the very low and very high end. Low values provide a lot of reassurance against significant fibrosis and high values indicate a high likelihood of significant liver fibrosis.

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Elastography –Accuracy in Children

Background: Transient elastography may help identify patients at greater risk for advanced fibrosis but there is a significant overlap between fibrosis stages and values with transient elastography. In some conditions, like fatty liver, elastography may be less helpful than in others (eg. chronic viral hepatitis).

A recent study (J Pediatr 2018; 198: 84-9) examined the results of transient elastography in 267 children (97 for calibration, 170 for validation) between 2006-2016.  The median age was 13 years.  Liver diseases included autoimmune (21%), viral (19%), fatty liver (11%), cholestatic (9%), primary sclerosing cholangitis (9%) and post-transplantation (12%).

Key findings:

  • Cut points to discriminate F3-F4 and F4 were >8.6 kPa and >11.5 with 81% and 84% accuracy, respectively in calibration cohort
  • To discriminate F3-F4 and F4 in validation cohort, these cut points, >8.6 kPa and >11.5, had accuracy of 67% and 75% respectively

Figure 2 provides much greater detail in the typical values for each Metavir stage. For example, in the calibration cohort, the median values and range were the following:

  • F0   6.0 (3.2-12.4)
  • F1   6.2 (3.2-75)
  • F2   5.8 (2.5-52.7)
  • F3  10.3 (4.9-32.6)
  • F4  20.5 (5.9-68.1)

In the validation cohort, values were similar:

  • F0   6.2 (3.0-75.0)
  • F1   7.1 (3.3-31.6)
  • F2   7.1 (2.5-52.7)
  • F3  9.6 (4.4-75.0)
  • F4  20.8 (6.8-75.0)

My take: Elastography in measuring liver stiffness is a lot like checking a CRP for inflammatory bowel disease.  That is, it can be helpful but cannot be relied on the same way as many radiographic tests (eg. CT scans for appendicitis).

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Moving Away from Liver Biopsies

A recent review (EB Tapper, AS-F Lok. NEJM 2017; 377: 756-68) provides a good review of liver biopsy and liver imaging. My take of this review is that it highlights the emergence of noninvasive tools (imaging & fibrosis markers) which may supplant liver biopsy.  This article does not delve into how more widespread genetic testing may obviate a liver biopsy in many cases as well. The article notes that about 8% of persons in the U.S. have elevated liver enzymes.

Liver biopsy:

  • “A typical liver biopsy samples one fifty-thousandth of the liver.”
  • Limitations of liver biopsy: sampling error is common, biopsy interpretation is subjective, and biopsies can cause complications.  Pain is noted in 30-50% of patients, serious bleeding in 0.6%, injury to other organs (0.08%), and in rare cases, death (up  to 0.1%).
  • Cost: “the average direct cost of a percutaneous liver biopsy is $1448 (in 2016 U.S. dollars).” Transjugular biopsies are much more expensive.  In addition, there are unmeasured indirect costs, due to missing work.

Some prior blogs on liver biopsy

Blood tests:

  • The article details the formulas for biomarker measurements that predict the risk of fibrosis, inlcuding FIB-4, Lok Index, and NAFLD Fibrosis Score.
  • In most liver diseases, aspartate aminotransferase levels “exceed alanine aminotransferase levels when cirrhosis develops.”
  • Thrombocytopenia “is the earliest indicator of cirrhosis among routine blood tests…[due to] diminished liver function (throbopoietin underproduction) and portal hypertension (splenic sequestration).”
  • Proprietary algorithms to assess fibrosis have variable sensitivity, specificity –include FibroTest (aka FibroSure [LabCorp]), FibroMeter, HepaScore (Quest), FIBROSpect, and the Enhanced Liver Fibrosis Score.

Imaging:

  • Elastography with vibration-controlled transient elastography (VCTE) OR magnetic resonance elastography
  • “Elastography offers excellent negative likelihood ratios for advanced fibrosis but much poorer positive likelihood ratios.”
  • Patients with severe obesity are less likely to obtain adequate study with VCTE and could need magnetic resonance elastography to assess fibrosis.

My take: Noninvasive tests have already sharply reduced the need for liver biopsy.

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Defining the Role for Elastography

The ability to determine if a patient has cirrhosis/severe fibrosis with a noninvasive test can help determine appropriate monitoring and treatment for many liver conditions. As such the AGA has provided recommendations for the use of vibration-controlled transient elastography (VCTE).

  • JK Lim et al. Gastroenterol 2017; 152: 1536-43.
  • S Singh et al. Gastroenterol 2017; 152: 1544-77.

Many recommendations are based on the specific unit of measurement, kilopascals (kPa)

Specific recommendations (most with low  or very low quality evidence):

  • “In adults with chronic HCV, we can accurately diagnosis cirrhosis …with VCTE-defined liver stiffness of ≥12.5 (±1) kPa.”  The AGA suggests using VCTE rather than MRE for detection of cirrhosis.
  • “In adults with chronic HCV who have achieved SVR…we can accurately rule out advanced fibrosis (F3 and F4) with post-treatment VCTE-..of ≤9.5 (±1) kPa.” . Even in patients who have had HCV eradicated, if cirrhosis has been identified, careful followup is recommended.
  • “In adults with chronic HBV, we can accurately diagnosis cirrhosis…with VCTE…of ≥11.0 (±1) kPa.”
  • “The AGA makes no recommendation regarding the role of VCTE in the diagnosis of cirrhosis in adults with NAFLD.” For NAFLD, VCTE is not as helpful as with chronic HCV and HBV.  Currently, liver biopsy remains the “gold standard.” However, for noninvasive imaging, “the AGA suggest using MRE, rather than VCTE, for detection of cirrhosis.
  • For adults with suspected compensated cirrhosis, a VCTE of 19.5 or greater can be used “to assess the need for esophagogastroduodenoscopy to identify high risk esophageal varices.”

My take: These elastography recommendations are applicable for adults.  For pediatric patients, these reports suggest that elastography may be helpful in specific circumstances as well.

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