Chronic Liver Disease: The ‘Silent’ Disease Affecting 1 in 3 People with An Annual Mortality Rate of 2 Million

By: Amanda Chin, Senior Business Development Manager at Perspectum

Chronic liver disease is a major public health issue worldwide, affecting over 844 million people with an annual mortality rate of 2 million.

This is comparable to other chronic diseases with heavy socioeconomic burden, including diabetes (422 million affected, 1.6 million deaths), cardiovascular disease (540 million affected, 17.7 million deaths), and pulmonary disease (650 million, 6.17 million deaths).^1,2 There are several aetiologies for chronic liver disease, including viral hepatitis B and C, alcohol abuse, as well as non-alcoholic fatty liver disease (NAFLD).

What is NASH?

In particular, NAFLD and its more severe sub-type, non-alcoholic steatohepatitis (NASH), are burgeoning health issues affecting 83.1 million and 16.52 million people worldwide, respectively. Driven primarily by lifestyle modifications (less exercise, richer food), obesity, and Type 2 Diabetes, these figures are predicted to grow to 100.9 million (NAFLD) and 27 million (NASH) in 2030. Further, NASH is fastest-growing cause of both primary liver cancer and liver transplant in the USA.

The race to NASH

Effective treatment options are clearly urgently needed to address the pandemic. However, there is neither an approved treatment available nor a safe and accurate method for diagnosing the condition at present. Definitive diagnosis of NASH at present requires a liver biopsy – an invasive procedure with numerous limitations including associated pain (20% of patients), extending to bleeding (0.8 to 1.7%) and even death (up to. 0.14%).³ Given the high and growing prevalence of NASH, liver biopsy is not a scalable solution. Further, there are inconsistencies between reported histopathological findings, with diagnosis based on an unrepresentative sample size of 1/50,000^th of the liver for a steep cost (over $1,500 in the USA). There is clearly an unmet need in clinical care for a safer and more accurate diagnostic, not only to ensure patient welfare but also provide an objective, definitive assessment that can be verified with confidence.

Drug development

This need extends from the clinic to the pharmaceutical industry, where numerous companies have entered the first-to-market NASH therapeutic race. The opportunity is huge, with the global market for NASH drugs estimated at $35 billion.⁴ Clinical development needs to keep to a strict timeline for timely release of treatments to the market, and this requires both recruiting the right patients as well as being able to detect and monitor their response to an in-development treatment.  Utilising liver biopsies for these purposes not only creates risk for enrolled patients but also liabilities and high costs for biopharma companies.

Diagnosis

The lack of definitive and safe diagnostic tools for NASH, however, have led to the increasing utility of non-invasive liver tests, such as blood-based and imaging technologies. These ensure greater patient welfare and lower procedural cost, though validation of these tests against the ‘gold standard’ liver biopsy is necessary to demonstrate accuracy. In this regard, the ideal test has to be an accurate biomarker or provide accurate biomarkers for the hallmarks of NASH, including steatosis, fibrosis, inflammation and ballooning. It has to be sensitive to the state of and changes in patient liver health; not only detecting this in a relatively short timescale of a few weeks, but also provide a comprehensive view of its condition.

As an imaging modality, Magnetic Resonance Imaging (MRI) has been a longstanding reference for the high-resolution imaging of soft tissue. Multiparametric MRI, unlike conventional MRI, uses a series of images to calculate quantitative parametric maps; over the last decades, many of these parameters have been shown to correlate with physiological properties, offering the potential for non-invasive assessment.

LiverMultiScan – an accurate, non-invasive imaging solution

LiverMultiScan is a technology originating from the University of Oxford, developed and commercialised by Perspectum Ltd, that harnesses the power of multiparametric MRI to quantitatively characterise liver tissue, providing non-invasive biomarkers of liver fat and correlates of iron and fibro-inflammatory levels. LiverMultiScan has proven accuracy and correlation with biopsy^5,6 and also provides a more holistic view of liver health. Its sensitivity to changes in liver state, ability to detect early liver disease and predict clinical outcomes^7,8 have been shown in clinical studies, together with successful and reliable demonstration of compound efficacy in investigational studies.⁹ Importantly, it is very well received by patients for its safe, non-invasive MRI scan as well as comprehensive and communicable report on liver health.¹⁰

The future of NASH

There is a lot of promise in delivering treatments and better diagnostics for NAFLD/NASH patients. Though it is a race for market share in both cases, we cannot ignore the synergies of potential combination therapies or complementary technologies. Treating NASH is very much a work in progress in a field of many unknowns; however, it is encouraging to see the rapid progress being made to ultimately deliver benefit to our patients.

References:

1. Marcellin P, Kutala BK. Liver diseases: A major, neglected global public health problem requiring urgent actions and large-scale screening. Liver Int. 2018;38(Suppl. 1):2–6. https://doi.org/10.1111/liv.13682
2. Cotter TG, Rinella M. Nonalcoholic Fatty Liver Disease 2020: The State of the Disease. Gastroenterology. 2020; 158(7):1851-1864. https://doi.org/10.1053/j.gast.2020.01.052
3. Seeff LB, Everson GT, Morgan TR, et al. Complication rate of percutaneous liver biopsies among persons with advanced chronic liver disease in the HALT-C trial. Clin Gastroenterol Hepatol. 2010;8(10):877-883. doi:10.1016/j.cgh.2010.03.025
4. https://www.cnbc.com/2018/12/21/the-35-billion-race-for-a-cure-for-a-liver-disease-that-affects-millions.html
5. Banerjee R, Pavlides M, Tunnicliffe EM, et al. Multiparametric magnetic resonance for the non-invasive diagnosis of liver disease. J Hepatol. 2014;60(1):69-77. doi:10.1016/j.jhep.2013.09.002
6. Pavlides M, Banerjee R, Tunnicliffe EM, et al. Multiparametric magnetic resonance imaging for the assessment of non-alcoholic fatty liver disease severity. Liver Int. 2017;37(7):1065-1073. doi:10.1111/liv.13284
7. Pavlides M, Banerjee R, Sellwood J, et al. Multiparametric magnetic resonance imaging predicts clinical outcomes in patients with chronic liver disease. J Hepatol. 2016;64(2):308-315. doi:10.1016/j.jhep.2015.10.009
8. Jayaswal, A., et al. Prognostic value of multiparametric MRI, transient elastography and serum fibrosis markers in patients with chronic liver disease. Liver International. Avai2020. doi:10.1111/liv.14625