Effective diagnostics for liver disease are urgently needed

The following article is an opinion piece written by Dr. Tram Tran. The views and opinions expressed in this article are those of the author and do not necessarily reflect the official position of Technology Networks.

Due to the increasing incidence of diabetes, obesity, and metabolic diseases in the United States, it is estimated that one in four patients has some form of fatty liver disease. The impact of this on the healthcare system has been realized and is likely to increase over time.

As primary care physicians continue to see increasing numbers of patients with fatty liver disease, it is important for them to be able to effectively triage these patients to ensure the best care possible. For many patients with non-alcoholic fatty liver disease (NAFLD), primary care would focus on diet and exercise to reduce the risk of liver disease progression.

However, many patients with NAFLD have a more severe inflammatory form of fatty liver disease called non-alcoholic steatohepatitis (NASH) which, if left untreated, could lead to significant complications including cirrhosis, liver cancer or dead.

It is therefore important for physicians to diagnose NASH, assess patients for stage or severity, monitor liver disease progression, and identify risk factors to initiate appropriate intervention.

Many primary care physicians may see patients in the early stages of liver disease when symptoms may be mild or non-existent, and therefore may not recognize the potentially progressive nature of NASH. Hepatologists and specialists who work with patients with advanced liver disease are aware, however, that the increase in NASH cases is expanding the list of patients who manifest serious disease and who may eventually need medical attention. liver transplant.

According to the results of a 2021 study,1 NASH was the second leading indication for liver transplantation in the United States and the largest increase since 2002. This overall burden on our healthcare system will only continue to grow.

The best way to prevent progression to advanced liver disease is to intervene early. However, the ability to effectively assess liver disease is limited by the primary diagnostic tool: liver biopsy.

A liver biopsy is a procedure in which a needle is inserted into the liver to remove a small piece of it for microscopic analysis and diagnosis. As one can imagine, many patients are reluctant to undergo this procedure. It’s invasive, carries the risk of bleeding and pain, and requires careful attention to the surrounding logistics that come with a procedure — getting time off work, being driven home, etc.

The nature of liver biopsy presents clinicians with a significant challenge. How can we effectively diagnose, stage and monitor fatty liver disease when patients are reluctant to routinely undergo the procedure?

From there, larger questions begin to emerge. How can you effectively triage patients to the appropriate treatment path? How can you monitor a patient’s response to treatment?

Fortunately, these types of questions are asked by many experts in the field.

Researchers have recently focused on measuring the properties of active liver disease biology, which is considered more beneficial than studying a single biopsy sample of the diseased liver. Indeed, liver injury can be heterogeneous and patchy in nature, and a small liver sample (approximately 1/50,000and) of the organ – as collected from a biopsy – might not accurately reflect the degree of damage. A dynamic biological measurement would provide a more systemic snapshot of disease state.

At the most recent American Association for the Study of Liver Diseases (AASLD) conference, Dr. Arun Sanyal (Virginia Commonwealth University), in collaboration with scientists from Glympse, presented data demonstrating the high precision (AUC 0 .97) of a biosensor blood test in predicting NASH compared to healthy patients.2 We achieved this by measuring the enzymatic activity of proteins a fundamental biopathology of NASH.

The activity of certain proteases, or enzymes involved in the cleavage of proteins, varies depending on the state of disease in the liver. By exposing these proteases to a selection of small protein fragments (peptides), we can measure this activity. Also, because liver proteases circulate in the bloodstream, we can measure this from a routine blood test sample.

We are at the forefront of understanding biomarkers in this field, driven by the promise of what this data could mean for patients in need.

In addition, the NIMBLE group made another important presentation at the AASLD conference. NIMBLE (Non-Invasive Biomarkers of Metabolic Liver Disease) is a joint effort between industry, academia and government. The group presented important data evaluating the performance of five different non-invasive tests with the aim of reducing the need for liver biopsy in this patient population, hopefully paving the way for the future use of clinical biomarkers.3

Any accurate, non-invasive diagnosis would have important implications for patients. Not only would a simple blood test improve both the patient experience and clinicians’ ability to monitor disease progression, but it would also improve access to experimental treatments for NASH and NAFLD in clinical trials, because researchers could better determine the right patients for studies.

Having a reliable tool for diagnosing liver disease would ensure that patients can access these experimental drugs in a timely manner, paving the way for better therapies and interventions before the most serious outcomes, such as liver transplants, are not necessary.

For everyone involved in liver disease biomarker research, our overarching goal is to optimize best practices for patient care. Of course, we recognize the urgent need for the healthcare system to triage patients with liver disease more efficiently, as the need for liver transplants continues to dramatically outstrip available donor organs.

At the heart of this research, however, is the individual patient and the need to effectively diagnose, monitor and prevent the progression of liver disease. Research at Glympse and elsewhere gives hope that this need will soon be met.

The references

1. Younossi, ZM et al. Non-alcoholic steatohepatitis is the fastest growing indication for liver transplantation in the United States. Clin. Gastroenterol. Hepatol. 2021; 19:580–589. do I: 10.1016/j.cgh.2020.05.064

2. Sanyal, Arun. Accurate diagnosis of NASH using a new protease-based liquid biopsy. Glympse at AASLD 2021. Nov. 2021. https://glympsebio.com/presentation-accurate-diagnosis-of-nash-using-novel-protease/. Accessed January 2022.

3. Sanyal A, et. al. Main results of the NIMBLE stage 1-NASH CRN study of circulating biomarkers of nonalcoholic steatohepatitis and its activity and stage of fibrosis. Summary of the AASLD meeting. Nov 2021. https://fnih.org/sites/default/files/2021-11/CWS_NIMBLE_Abstract.pdf. Accessed January 2022.

About the Author

Tram Tran, MD is the Chief Medical Officer of Glympse. She is a renowned liver and virus specialist with over 20 years of academic and industrial experience as a physician-scientist. Prior to Glympse, Dr. Tran worked at Gilead Sciences and before that at Cedars-Sinai Medical Center. She has authored and co-authored over 150 abstracts, published manuscripts, and book chapters, and has been extensively involved in clinical trials and research funded by the National Institutes of Health (NIH). Dr. Tran received his MD from New York Medical College.

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