A Lightbulb Moment: Non-Invasive Testing for Autoimmune Hepatitis Patients

I’ve been practicing internal medicine and hepatology for over 30 years, caring for patients with a variety of liver-related conditions. I’ve developed a special passion for helping those who suffer from autoimmune hepatitis (AIH) and its variants, having attended to more than 1,500 patients with this diagnosis over the course of my career. Although the percentage of the population affected by AIH is relatively small compared to some other types of liver disease, AIH is a disease worthy of further discussion because of its late diagnosis in the majority of patients.

I’ve spent many hours advising AIH patients on their prescribed immunosuppressive medications and steroids, planning their care pathways, and performing tests to assess if the treatments I’m recommending are effective or need to be tweaked. Until recently, the only truly reliable assessment tool at my disposal has been liver biopsy, which is an invasive and expensive procedure that is, at best, unappealing to patients. To be blunt, no one wants an invasive procedure if they can avoid it. Over the years, I’ve asked myself too many times to count, “Isn’t there is a better way to assess the level of liver disease activity during follow up?”

Today, I am thrilled to share that yes, indeed, a new option exists through Perspectum — a non-invasive magnetic resonance imaging (MRI) solution called LiverMultiScan.

I am more than ready to bring this new imaging diagnostic approach to all the patients and providers I support and spread the news across the global hepatology community through medical conferences, speaking engagements, and advocacy work with non-profits.

Autoimmune Hepatitis: What It Is, Who It Impacts, and How to Treat It

To understand why we need a better way to assess these patients, we first need to understand AIH — what it is, who it affects, and how it is treated today.

What it is

AIH is a liver disease where environmental and genetic factors intersect, resulting in the immune system mistakenly and directly attacking the liver. The result is inflammation and fibrosis in the liver. Interestingly, AIH can also be associated with many other diseases that affect other organ systems in the body, such as thyroid disease, lupus, and arthritis. None of AIH’s 16 subtypes has a signature diagnostic feature, so diagnosis is tricky, and currently, a baseline liver biopsy is required1. Physicians work painstakingly to connect the dots between a set of symptoms that vary in presentation between patients, which may also be the result of other types of liver diseases, thus further complicating AIH diagnosis.

Who it impacts

As a genetic and environmental disease, AIH prevalence differs widely between populations, as I’ve seen firsthand over my many years of practice. The majority of adult cases — approximately 71% to 95% — occur in women. Female children are also disproportionately affected1.

AIH also has a variable impact across ethnicities and, unfortunately, is seen more commonly in populations that have historically struggled to access healthcare resources. For example, there’s a particularly high incidence of AIH in Alaskan Native populations and Hispanic Americans who are more likely to progress to cirrhosis than other populations.?In addition, African Americans often experience accelerated complications and higher rates of AIH recurrence, even after a liver transplant.

Diagnosis, treatment, and complications

As mentioned earlier, diagnosing AIH is complicated, but it is essential that these patients are diagnosed at the earliest because this disease can cause cirrhosis, prompting the need for a liver transplant, and may even lead to death. In the U.S. alone, AIH accounts for 6% of liver transplants and typically progresses to the point of becoming deadly in just 10 to 20 years.

The good news? Modern treatment, made available in the form of immune suppressant drug therapy and corticosteroids (steroids), is highly effective in preventing the disease from progressing. Continuous monitoring and medication maintenance over the long term can scale liver enzymes back to normal quantities, and in this range, disease activity tapers down. However, the only way for hepatologists to determine the efficacy of a patient’s medication regimen is by performing biopsies every two to three years! That’s right, every two to three years, we need to perform an invasive procedure.

Nearly all patients are averse to being on medications their entire lives, especially due to the adverse long-term side effects, ranging from dermatological and weight gain issues to osteoporosis and unstable diabetes. Therefore, patients want to halt their immunosuppressive and steroid medications as soon as possible. Ironically, yet another biopsy is the only way to determine if this is a safe option.

The ongoing need for biopsies to assess treatment efficacy and inform changes to care plans makes for an unpleasant patient experience, not to mention astronomical medical bills.

Now you can start to see why I’ve been so fixated on finding an alternative to biopsy!

The Lightbulb Moment: Finding a Better Path with LiverMultiScan

Ten years ago, I was introduced to what was at the time an early-stage healthcare tech startup, Perspectum. Today, the company offers its flagship product, LiverMultiScan, clinically. This MRI-based, non-invasive imaging technology may provide an alternative to biopsy for quantifying liver tissue2. LiverMultiScan uses information from multiple biomarkers, including its proprietary biomarker corrected T1 (cT1) to measure fibro-inflammation, proton density fat fraction (PDFF) to quantify liver fat, and T2* that correlates with liver iron content. Not only does it provide rich data from these biomarkers, but it does so through an intuitive, clinician- and patient-friendly report3. The variation in cT1 values is depicted using an embedded green–red color scale, which corresponds with liver fibro-inflammatory activity. In a recent study, patients reported enhanced understanding of their liver disease after viewing their LiverMultiScan reports, increasing engagement as compared to other tools4. I immediately realized this technology’s potential to be the AIH monitoring tool that clinicians and patients have waited for decades.

A baseline scan creates a benchmark and starting point for subsequent future comparison and can be used to reveal comorbidities correlated with AIH. Not only can LiverMultiScan be used to obtain baseline information (alongside the liver biopsy), but it can also be used for ongoing assessment of AIH patients as an alternative to biopsy5.

A population of 17%-34% of patients with fatty liver disease have positive markers of AIH6,7. As patients with excess weight are more likely to have fatty liver disease, these patients are at risk of a positive AIH diagnosis. Since treatment for AIH includes both immunosuppressants and steroids, treating patients with both these diseases is challenging as steroids can worsen a patients fatty liver disease. Therefore, knowing the liver’s fat and fibro-inflammation levels at the outset offers clinicians comprehensive information about the potential treatment options available if the patient should develop AIH. LiverMultiScan is unique in showing both these aspects of liver health, which are usually distinguishable only through two different techniques like elastography and biopsy. With the early detection of comorbidities, it is possible to prevent future complications and judge the needed levels of immunosuppressants and steroids8,9. LiverMultiScan can also be used to support patient management by identifying if a patient has a stable disease and if it is safe to discontinue their medications10.

LiverMultiScan by the Numbers

In this piece, I’ve primarily focused on the value of LiverMultiScan for AIH assessment. However, this tool has benefits for a wide variety of liver conditions that impact significant portions of the adult population.

I always look to data to inform my clinical decisions, and the growing library of research supporting the effectiveness of this technology is what convinced me of its value. For example, a 2021 study in Frontiers in Endocrinology highlighted the power of using cT1 as a non-invasive biomarker, given its distinct ability to reveal changes in inflammation and fibrosis2. And a recent study in Abdominal Radiology that examined changes in liver fibrosis, fat, and iron content in patients with chronic hepatitis C virus demonstrated a decrease in liver cT1 in patients undergoing treatment, pointing to a likely reduction in inflammation rather than fibrosis regression11. This effective correlation of cT1 with inflammation signifies the biomarker’s potential to be used not only for diagnosing liver conditions but also for monitoring.

For all these reasons and more, I encourage my colleagues working in the field of hepatitis — as well as clinicians in general practice — to learn more about LiverMultiScan.

*Disclaimer: I am a medical consultant for Perspectum. See robertgish.com for other disclosures.

References:

1. Mack CL, Adams D, Assis DN, et al. Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of?Liver Diseases. Hepatol Baltim Md. 2020;72(2):671-722. doi:10.1002/hep.31065

2. Dennis A, Kelly MD, Fernandes C, et al. Correlations Between MRI Biomarkers PDFF and cT1 With Histopathological Features of Non-Alcoholic Steatohepatitis. Front Endocrinol. 2020;11:575843. doi:10.3389/fendo.2020.575843

3. Andersson A, Kelly M, Imajo K, et al. Clinical Utility of Magnetic Resonance Imaging Biomarkers for Identifying Nonalcoholic Steatohepatitis Patients at High Risk of Progression: A Multicenter?Pooled Data and Meta-Analysis. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. Published online October 7, 2021:S1542-3565(21)01056-9. doi:10.1016/j.cgh.2021.09.041

4. McKay A, Pantoja C, Hall R, Matthews S, Spalding P, Banerjee R. Patient understanding and experience of non-invasive imaging diagnostic techniques and the liver patient pathway. J Patient-Rep Outcomes. 2021;5(1):89. doi:10.1186/s41687-021-00363-5

5. Torres US, D’Ippolito G. Multiparametric magnetic resonance imaging of the liver: bridging the gap between theory and practice - a bridge too far? Radiol Bras. 2021;54(5):V-VI. doi:10.1590/0100-3984.2021.54.5e1

6. Vuppalanchi R, Gould RJ, Wilson LA, et al. Clinical significance of serum autoantibodies in patients with NAFLD: results from the nonalcoholic steatohepatitis clinical research network. Hepatol Int. 2012;6(1):379-385. doi:10.1007/s12072-011-9277-8

7. Cotler SJ, Kanji K, Keshavarzian A, Jensen DM, Jakate S. Prevalence and significance of autoantibodies in patients with non-alcoholic steatohepatitis. J Clin Gastroenterol. 2004;38(9):801-804. doi:10.1097/01.mcg.0000139072.38580.a0

8. Arndtz K, Shumbayawonda E, Hodson J, et al. Multiparametric Magnetic Resonance Imaging, Autoimmune Hepatitis, and Prediction of Disease Activity. Hepatol Commun. 2021;5(6):1009-1020. doi:10.1002/hep4.1687

9. Janowski K, Shumbayawonda E, Dennis A, et al. Multiparametric MRI as a Noninvasive Monitoring Tool for Children With Autoimmune Hepatitis. J Pediatr Gastroenterol Nutr. 2021;72(1):108-114. doi:10.1097/MPG.0000000000002930

10. Heneghan MA, Shumbayawonda E, Dennis A, Ahmed RZ, Rahim MN. Quantitative Magnetic Resonance Imaging to Aid Clinical Decision Making in Autoimmune Hepatitis. EClinicalMedicine. Accepted.

11. Jayaswal ANA, Levick C, Collier J, et al. Liver cT(1) decreases following direct-acting antiviral therapy in patients with chronic hepatitis C virus. Abdom Radiol N Y. 2021;46(5):1947-1957. doi:10.1007/s00261-020-02860-5