Diagnosing autoimmune hepatitis (AIH) often requires an invasive biopsy procedure. But a new class of imaging allows for non-invasive diagnosis of new and recurring AIH.
By Chris Wolski
Autoimmune hepatitis (AIH) is a difficult disease to diagnosis as Matthew Kelly, PhD, recently explained during an interview with CLP and his colleague Elizabeth Shumbayawonda, PhD. None of its 16 subtypes have a signature diagnostic feature. The most common way to diagnose AIH is through a tissue biopsy or blood tests. Since AIH is a chronic genetic disease, requiring ongoing monitoring through additional biopsies and blood tests.
In their wide-ranging interview with CLP, Kelly, Perspectum’s chief innovation officer, and Shumbayawonda, a principal clinical scientist for Perspectum, discuss the importance of transitioning to an imaging test for diagnosing AIH, how the lines between clinical labs and imaging are blurring, and the results of a recent study using the company’s LiverMultiScan device.
Responses have been edited for length and clarity.
CLP: What are the limitations of traditional lab tests—liver biopsies and blood tests—for diagnosing and then monitoring AIH?
Matthew Kelly: Autoimmune hepatitis (AIH), a genetic disease in which the immune system mistakenly attacks the liver, is fundamentally challenging to diagnose. None of its 16 subtypes has a signature diagnostic feature, so diagnosis involves connecting disparate data points. And once a patient is diagnosed, this chronic disease requires perpetual monitoring.
Unfortunately, traditional tools for diagnosis and management of this complex disease possess inherent drawbacks. It’s not that practitioners are deploying these tools incorrectly; rather, the tools themselves can only go so far.
Take one blood test, for example. A serum ferritin blood test is used to estimate the amount of iron stored in the body by quantifying ferritin (a protein that stores iron) in cells. Unfortunately, multiple other conditions—such as rheumatoid arthritis, hyperthyroidism, leukemia, or simply a high number of blood transfusions—can also cause high ferritin levels. So abnormal results are quite common. To get accurate results, tests must be repeated, so valuable time and money are spent searching for a diagnosis at moments in the disease progression when actual care is needed. Blood biomarkers can also lack sensitivity, and therefore be unable to detect small but clinically relevant changes in disease activity. Because blood markers are controlled by medications, they may not give an accurate picture of disease severity. These discrepancies mean blood biomarkers alone are insufficient for diagnosis and monitoring.
Physicians often perform blood tests in the hope of avoiding liver biopsies; no patient wants to have a needle stuck into his or her liver, and doctors typically dislike doing the procedure as well. And beyond the unpleasant and painful experience, there are clinical limitations—a biopsy needle can only assess 1/50,000 of the liver and carries the risk of complications like bleeding, infection, and death. Furthermore, the heterogeneity of the liver means some parts can be healthy, and others unhealthy. Even the most eagle-eyed physician can misdiagnose when presented with the limited information provided by a biopsy.
For continual AIH monitoring, a biopsy is a time-intensive, painful procedure, especially when needed every two to three years. Modern medicine offers multiple effective pharmaceutical treatments; however, regular testing is essential to make recommendations and assess improvement over time. When the tests are invasive, the patient experience is enormously unpleasant, not to mention costly and time-consuming over the long haul.
CLP: How does LiverMultiScan eliminate these drawbacks? What’s its accuracy rate?
Elizabeth Shumbayawonda: LiverMultiScan, a product offered by Perspectum, offers a clear picture of liver health that current tools are inherently unable to deliver.
It relies on information from three key biomarkers: corrected T1 (cT1) to measure fibrosis and inflammation (fibro-inflammation), proton density fat fraction (PDFF) to quantify liver fat, and T2*, which correlates with the amount of iron in the liver. Since it measures these three components simultaneously, the entire procedure only lasts 15 minutes from start to finish.
For AIH, the cT1 score is most relevant. This biomarker measures the status of water in the tissue, which correlates with both fibrosis and inflammation; an inflamed, fibrotic liver contains high amounts of extracellular fluid, resulting in an elevated cT1 value. Typically, a cT1 score of greater than 800 milliseconds means the patient has a greater than 20% chance of relapse within 12 months, while a score of 1,000 milliseconds or higher indicates a 75% or greater chance.
A new study published in eClinical Medicine–The Lancet showed that LiverMultiScan outperforms blood biomarkers when identifying disease progression. Especially for patients with active sub-clinical disease (i.e., active disease that is not detected by blood tests), this tool identifies disease states often missed by other methods. It is clinically proven to provide high diagnostic accuracy for liver disease assessment and risk stratification.
CLP: What are the implications (costs, efficiency, etc.) for the healthcare enterprise and patient care overall with LiverMultiScan?
Kelly: More than any current diagnostic method, LiverMultiScan offers efficiency. Because it’s non-invasive and the procedure lasts 15 minutes, this tool makes a difference for patients dreading the pain of biopsy and physicians searching for a simpler and safer procedure. The seamless, cloud-based service delivers scan reports to clinicians in as little as two hours.
The reports bear no similarity to the complex data of a biopsy. Instead, this report shows cT1 values in a “stoplight” format—the green, amber, and red images correspond to normal and outside-of-normal ranges of fibro-inflammatory activity. By saving physicians time spent translating results, these intuitive images foster patient conversations about care pathways and productive next steps.
This straightforward information benefits physician decision-making. Clinicians reported the positive impact of LiverMultiScan’s information on intended management plans for patients with AIH. Providers expressed greater confidence when using LiverMultiScan for risk stratification, especially when caring for patients with sub-clinical symptoms—whose specific disease states might go undetected through traditional methods.
CLP: Do traditional laboratory testing and LiverMultiScan dovetail? If so, how?
Shumbayawonda: Patients with stable blood biomarkers (in the lower range) with inactive disease have lower cT1 scores, while those with clearly active disease and abnormal (raised) blood biomarkers have elevated cT1 scores. However, there is a significant proportion of patients with blood biomarkers in the normal range who do have sub-active clinical disease, indicated by elevated cT1 scores. Blood biomarkers can miss sub-active clinical disease due to the non-specificity mentioned above.
CLP: Broadly speaking—do you see further blurring of the lines between traditional laboratory testing and imaging? If so, what will testing look like in about a decade or so? If not, why not?
Shumbayawonda: As a means for long-term patient monitoring, liver biopsy simply isn’t feasible. The growing prevalence of liver disease means practitioners and patients urgently need non-invasive, cost-effective measures. Various other types of imaging are already being incorporated into patient clinical care pathways, and regulatory bodies such as the FDA are further examining the objective and repeatable biomarkers of disease provided by non-invasive imaging. As the lines between traditional laboratory testing and imaging continue to blur—with imaging disrupting the current clinical pathway—a combination of traditional laboratory testing and imaging will likely become the approved standard of liver disease care within a decade.
CLP: Is LiverMultiScan available in the U.S. for diagnosing AIH?
Kelly: LiverMultiScan is currently available in 39 US states; Washington, DC; and Puerto Rico. Health plans now reimbursing it include Anthem in 14 states, BlueCross BlueShield in five states, LifeWise Health Plans, Premera, and PacificSource. The Centers for Medicare and Medicaid Services has also established a base reimbursement rate of $950.50 for LiverMultiScan in hospital and outpatient settings. Perspectum is continuing to increase the availability and coverage of LiverMultiScan across the U.S.
In March 2022, AIM Specialty Health—a provider of evidence-based clinical guidelines for 50 million members—deemed Perspectum’s LiverMultiScan medically necessary for evaluating non-alcoholic fatty liver disease (NAFLD) and other chronic liver diseases. This new guideline includes a standalone CPT code 0648T to be used when billing for the LiverMultiScan procedure. This has broadened access and coverage for more than 77 million U.S. patients.
CLP: Can you give me an overview of your recent study—how did it work and what did you find?
Shumbayawonda: Our recent study was the first real world investigation of LiverMultiScan in a clinical setting—it evaluated the impact on decision-making and intended patient management. We explored the utility of LiverMultiScan’s multiparametric magnetic resonance (mpMR) biomarkers for patients and compared the efficacy of these mpMR biomarkers to other commonly used non-invasive markers, when identifying patients with previously undetected active sub-clinical disease.
Between June and November 2019, we recruited 82 patients with AIH as part of an observational cohort study. In addition to standard clinical investigations, these patients were scanned with LiverMultiScan. Then, the relationships between cT1 and other markers of disease were investigated, along with the impact of LiverMultiScan on clinical decision making and risk stratification of patients in biochemical remission.
The study found that cT1 outperformed other non-invasive markers when accurately staging and monitoring disease. It helped identify those with undetected active sub-clinical disease, despite having normal blood markers, in order to provide better clinical care
To measure the impact on clinical decision-making, the study surveyed clinicians before and after the scan. Prior to the scan, physicians were asked “How useful do you expect information from this report to be?” When asked afterward how useful it actually was, the number increased by 20%. This shift highlights the potential value of this technology in accurately informing care management.
The findings indicate the potential of mpMR biomarkers like LiverMultiScan cT1 as tools for improved patient management, and for early detection of at-risk patients most likely to relapse due to active sub-clinical disease.
CLP: What’s next for your technology and diagnosing AIH?
Kelly: We’re constantly innovating on our technology. A new version of LiverMultiScan, under review with the FDA, includes a more sophisticated iron metric called liver iron concentration (LIC). It will indicate the specific number of milligrams of iron per every gram (mg/g) of liver tissue.
Currently, LiverMultiScan reports T2*, a time constant measured in milliseconds, to assess the level of hepatic iron. Whereas T2* is an indirect measure of iron levels, LIC is a more direct and easy way to interpret measure of iron content in the liver.
While LiverMultiScan provides support for the management of chronic liver diseases such as AIH and fatty liver disease, Perspectum has extended this technology to support surgical decision-making in patients with liver cancer. The company’s FDA-cleared Hepatica product provides information on liver health and volume. We have also expanded beyond the liver to characterize other organs within the body, including the heart, kidneys, and pancreas through CoverScan, a product that is currently available in the U.K. and under review with the FDA in the U.S.
Chris Wolski is chief editor of CLP.
