Noninvasive Liver Assessment: The US Plays Catch-up

Miriam E. Tucker

May 13, 2015

New European and Latin American guidelines on the use of noninvasive tests for liver evaluation are the first to specifically address an approach that has become the standard in much of the developed world, but has been slower to take hold in the United States.

The European Association for the Study of the Liver (EASL) and the Asociación Latinoamericana para el Estudio del Hígado (ALEH) jointly issued the evidence-based clinical practice guidelines on the use of noninvasive tests for evaluation of liver disease severity and prognosis during the EASL International Liver Congress 2015. The document is posted on the EASL website and was published online April 21 in the Journal of Hepatology.

The guidelines address the use of all currently available noninvasive alternatives to liver biopsy, including patented and nonpatented serum biomarkers and physical measures of liver stiffness, for both viral and nonviral chronic liver diseases. Although the document discusses several types of liver stiffness measures, a main focus is the use of the one-dimensional ultrasound transient elastography.

"We have guidelines for the first time. These methods are widely used, but we didn't have guidelines. Now, especially in the field of hepatitis C, where [transient elastography] is the most validated, this is the standard of care. This is the way we're prioritizing patients for treatment so far," guideline lead author and EASL vice-secretary Laurent Castera, MD, from Hôpital Beaujon, Clichy, France, told Medscape Medical News.

But that is not the case in the United States, where liver biopsy remains the gold standard, Don C. Rockey, MD, professor and chair of the Department of Medicine at the Medical University of South Carolina in Charleston, told Medscape Medical News.

"Europe is pushing for noninvasive assessment, especially transient elastography, whereas in the US, we still use liver biopsy. There are very few FibroScans in the US.... It's very expensive. The US hasn't grasped it the same way the Europeans have," Dr Rockey said.

Indeed, the FibroScan device, which assesses liver shear wave speed (expressed in meters per second) and equivalent stiffness (expressed in kilopascal) at 50 Hz, was only cleared by the US Food and Drug Administration in April 2013, a decade after it first arrived in Europe, and also years after becoming available in China (2008), Canada (2009), Brazil (2010), and Japan (2011). It is currently on the market in 70 countries, according to an Echosens statement.

"Vibration Controlled Transient Elastography" received a CPT code on January 1, 2015 (91200), and is reimbursed by Medicare at $134.80 per outpatient test, but not all private insurers are covering it as yet, and the machine itself costs $131,950. So far, in the United States, its use is mostly limited to major academic centers. At this time, there are about 200 FibroScan machines nationwide, according to Jerry Mabary, senior marketing director for FibroScan with the device's US distributor, Sandhill Scientific.

However, "expansion is occurring at a rapid pace," Mabary told Medscape Medical News.

Pros and Cons

Dr Rockey, who was the lead author of the 2009 liver biopsy recommendations of the American Association for the Study of Liver Diseases, acknowledged the down sides of liver biopsy outlined in the EASL/ALEH document: it is invasive, costly, and involves a small risk for bleeding and death. However, he pointed out that FibroScan also has negatives in addition to the machine's cost (also noted in the guidelines), including that although it performs well in identifying people with cirrhosis, it is unable to discriminate between intermediate stages of fibrosis, and it does not perform well in obese people.

"It's easy to do, I think it's pretty reproducible, and it's really good when you've got extensive fibrosis and cirrhosis," Dr Rockey said. "It's not so good when you have intermediate or lesser stages of fibrosis. That's one of the issues. In the US, we tend to be a little more precise."

However, Dr Castera sees advantage in being able to screen for the patients at greatest risk and in need of referral or treatment. "You can't do a biopsy on every patient with chronic liver disease. The next step after we cure hepatitis C will be [nonalcoholic fatty liver disease]. To perform a liver biopsy on every patient with suspected [nonalcoholic fatty liver disease] would be impossible. There are too many patients.... This is where the noninvasive methods could be very useful. You can stratify by patients who don't need a biopsy and don't need to be referred to a specialist."

For his part, Dr Rockey said that some treatment-naive patients with hepatitis C with intermediate stages of fibrosis who might benefit from antiviral treatment would be missed by the document's proposed algorithm, which calls for the combined use of transient elastography and serum biomarkers as follows: If the two noninvasive tests agree there is severe fibrosis or cirrhosis, then the patient is given antiviral treatment and screened for varices and hepatocellular carcinoma; if the two tests disagree, they should be repeated and explanations sought, and if there is still discordance, then the algorithm calls for liver biopsy if the results would influence management; and if the two tests agree that there is no severe fibrosis or cirrhosis, the EASL/ALEH guidelines recommend against both liver biopsy and antiviral treatment.

That last point is problematic, Dr Rockey said. "You can probably be sure they don't have cirrhosis, but you don't really know how much fibrosis they've got, because FibroScan and serum fibrosis tests are not really that accurate at lower levels of fibrosis.... If I had hepatitis C and F2 [moderate fibrosis on the Metavir liver histopathology scoring system], I'd want treatment."

In Europe, most patients with hepatitis C falling under the third point currently do not receive treatment, although that scenario could change if the price of the newer direct-acting hepatitis C treatments falls as expected, Dr Castera noted.

Similarly, in the United States, Mabary told Medscape Medical News, "The private insurers are adopting [FibroScan testing] as quickly as one could hope. Interestingly, the primary driver of rapid changes in private reimbursement for FibroScan testing is the urgent need for a test which can be used to qualify patients for the new antiviral therapies. No insurance company can afford to fund the treatment of all HCV patients. Treatment is being prioritized to patients with significant fibrosis or cirrhosis, or who are coinfected with HCV-HIV."

Moving Away From Biopsy

Despite his concern about the approaches' limitations, Dr Rockey anticipates that the United States will eventually adopt noninvasive liver assessment. "If FibroScan cost $25,000, I think everyone would have one already. If it was significantly less expensive, it would be easy to purchase and implement," he said, noting that his institution does not currently have one but probably will at some point.

"The idea to get away from liver biopsy to move more toward a noninvasive approach is not without merit. I think it's a good thing, because liver biopsy can be dangerous.... My hunch is that we're moving more toward a more noninvasive situation."

With regard to the EASL/ALEH document, Dr Rockey said, "I think there's at least enough data on hepatitis C to make a proposed guideline, and that's what they did."

The American Association for the Study of Liver Diseases currently has no plans to issue a similar guideline, a society spokesperson told Medscape Medical News.

Dr Castera said, "The US compared to the rest of the world is quite different. It's not just Europe, but in Asia, Russia, and the rest of the world, [noninvasive assessment] is the standard.... The US should catch up."

Dr Castera has received speaking and teaching fees from Echosens, as well as AbbVie, Biopredictive, Bristol-Myers-Squibb, Gilead, Merck, and Janssen. Five of the other seven guideline authors also have disclosures with Echosens, and all but one have disclosures with manufacturers of other liver stiffness measuring equipment and/or hepatitis C drugs. Mabary is an employee of Sandhill Scientific, the US distributor of FibroScan. Dr Rockey has no disclosures.

J Hepatol. Published online April 21, 2015. Full text


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