AsianScientist (Sep. 2, 2017) – Although it may not receive the same amount of attention as organs such as the heart or brain, the unassuming liver is nonetheless every bit as crucial to life. On top of the over 500 vital functions that it performs, the liver has the amazing ability to regenerate and return to its original size, even after the removal of up to 75 percent of the organ. Nonetheless, poor diets and unhealthy lifestyles have pushed the livers of millions of people to the limit, leading to what experts are calling a silent epidemic of liver disease.
A silent disease in progress
In a 2016 study published in the Journal of Hepatology, researchers found that a staggering 25 percent of the global population has non-alcoholic fatty liver disease (NAFLD), a condition where fat makes up more than five percent of the liver. Unfortunately, that figure is projected to increase in tandem with the rise of metabolic disorders such as obesity and diabetes, which are reaching epidemic proportions.
A prelude to chronic liver diseases, NAFLD also increases the risk of Type 2 diabetes. A recent study by the Institute for Diabetes Research and Metabolic Diseases (IDM) at the Helmholtz Zentrum München and the University of Tübingen found that a fatty liver can cause damage to other organs, including the pancreas. When affected, the pancreas is either unable to produce sufficient insulin, or produces insulin that does not work properly, eventually leading to high blood glucose levels.
Over time—years or decades in some cases—NAFLD progresses to a more serious condition called non-alcoholic steatohepatitis (NASH), where the liver becomes inflamed and scarred, and liver function goes awry. Without treatment, the disease worsens to liver cirrhosis, a late-stage disease where a liver transplant is the only life-saving option for the patient. In fact, NASH is projected to overtake Hepatitis C to become the biggest cause of liver transplants by 2020.
Despite the heavy—and rapidly growing—burden of NASH, there are currently no FDA-approved cures available. This in turn discourages patients from seeking a diagnosis, as the condition is usually discovered at a later stage when there are no effective treatments to alleviate their condition. Because of this, there is an urgent need to develop precise therapeutics, and the major markets for NASH drugs is currently estimated to reach US$49 billion by 2027.
Raising the standard of diagnosis
One of the reasons for the non-existence of treatments is that NASH is difficult to detect it in the first place. Symptoms are frustratingly subtle and not specific to the disease; majority of people show either no symptoms at all, or mild ones such as fatigue or pain in the upper abdomen.
Also, there is no accurate and reproducible tool to identify and stage the disease. Such a tool is essential for pharmaceutical companies to monitor the efficacy of drugs in development. At present, the liver biopsy is the gold standard procedure carried out to retrieve tissue samples. These are then stained and manually assessed by a pathologist for disease staging, based on his/her experience and a checklist of observable features. This process takes up much time and does not produce consistent and accurate results.
One company hoping to transform this process of diagnosing NASH is HistoIndex, a medical imaging company headquartered in Singapore. Over the years, HistoIndex has developed and refined Genesis®200, the world’s first fully-automated, stain-free imaging system capable of overcoming the limitations of the conventional histological assessment (which remains the current gold standard in characterising NASH). The Genesis®200 is able to accurately stratify fibrosis due to NASH, as recently reported in the Journal of Hepatology, and is expected to set a new standard for its diagnosis in the near future.
“The treatment for NASH is one of the most important healthcare needs facing our world today, and our desire is to address this need with the global adoption of our technology as a tool for the development of NASH drugs,” said Dr. Gideon Ho, CEO of HistoIndex.
In recognition of its efforts to aid in the diagnosis of NASH, HistoIndex has been presented with the 2017 Asia Pacific Nonalcoholic Steatohepatitis (NASH) Diagnostics New Product Innovation Award by Frost & Sullivan.
How it Works
Genesis®200 uses a biophotonic technology known as two-photon excitation (TPE) and second harmonic generation (SHG) to quantify endogenous biomarkers in stain-free tissues. With the ability to reveal collagen fibers as small as 0.1 µm, the system not only allows doctors to detect NASH at an early stage of fibrosis, but also helps them track how patients respond to treatment, as the disappearance of fine collagen fibers is one of the first signs that a treatment is working.
The system’s high-power femtosecond laser, coupled with an expanded range of optical functions, enables Genesis®200 to perform multi-organ and thick tissue 3D imaging at high throughput. Furthermore, its imaging system can be combined with software algorithms that can automatically detect fine collagen fibers, providing objective and quantifiable data to assist the pathologist in staging the degree of fibrosis. Instead of having to wait days or weeks, Genesis®200 can generate accurate diagnostic reports in less than a day, greatly speeding up the pathologists’ workflow.
Multi-center studies have shown the Genesis®200 to be a reliable method for the automated quantitative assessment of chronic liver disease; the system is able to provide precise data for clinical practice and drug trials and reduce misdiagnosis of NASH by at least 30 percent.
Conventional staining (left) stains collagen as well as the fibers, making it harder to detect specific areas of concern. The pathologist then uses a set of qualitative guidelines to reduce ambiguity and pinpoint the condition’s severity to form the diagnosis. Therefore, the accuracy of the diagnosis will be compromised if an error occurs in the diagnosis, thus affecting treatment.
The image on the right shows a refined area of collagen fibers on the same cross section of human liver tissue. Networks of fine collagen fibers are also detected within the islands of green. These are important indicators for the diagnosis and treatment of liver fibrosis: these fine fibers are the first to vanish during successful treatment, and hence are a reflection of how treatment is progressing. The Genesis system is consistently more accurate as a result of more specific and sensitive imaging. Credit: HistoIndex.
Partnering pharmaceutical companies and clinicians
The superior ability of Genesis®200 to detect even minute improvements in drug efficacy makes it an invaluable assessment tool. It is currently being used by pharmaceutical companies in US FDA Phase II/III clinical trials for NASH drug development.
“There is a global race to find a cure for NASH,” said Professor Stephen Harrison, Medical Director of Pinnacle Clinical Research and member of HistoIndex’s scientific advisory board. “The current gold standard has its limitations; therefore, we need to have an objective, stain-free and fully quantitative diagnostic tool such as HistoIndex’s Genesis®200, which can power both clinicians around the globe to efficiently diagnose NASH, and pharmaceutical companies to effectively develop treatments based on a more quantitative assessment of NASH and fibrosis.”
HistoIndex is actively involved in research and development efforts looking at all kinds of fibrosis and cancers, across 250 research groups in university hospitals, research institutes and pharmaceutical companies.
Although the twin threats of obesity and diabetes are likely to drive the rise of NASH, clinicians and researchers have a growing arsenal of innovative tools at hand to overcome the challenges in diagnosing and treating NASH efficiently.
“Our system has been used in various late-stage clinical trials to identify biomarkers for NASH, and we anticipate more pharmaceutical companies will benefit from partnering with HistoIndex in their drug development pursuits,” Ho added. “Ultimately, we want to see an effective cure developed for patients so that they will receive a better quality of life.”
Asian Scientist Magazine is a media partner of HistoIndex Pte Ltd. To find out more about Genesis®200, please visit this page.
Source: HistoIndex Pte. Ltd.; Photo: Shutterstock.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.