Diagnosing liver damage early could save your life, now researchers have developed a non-invasive method that does just that
A non-invasive method for detecting and diagnosing early-stage liver diseases, including liver fibrosis, has now been developed by scientists.
According to the Centers for Disease Control and Prevention or CDC, while the number of adults in the US with diagnosed liver disease is 4.5 million, the percentage of adults diagnosed with liver disease is just 1.8%.
From 2010 to 2015, deaths from chronic liver disease increased by 31% in the US among people ages 45 to 64, due to several factors, including alcohol abuse and obesity. Liver disease, says the research team led by Georgia State University, is a slow-moving process, but without an effective, non-invasive means of early diagnosis to prompt treatment, it can progress to more serious stages with severe consequences.
The new compound was also able to assess the severity or stage of liver damage without the need for biopsy. A biopsy is an invasive procedure, which involves the surgical removal of liver tissue, and is the current standard for diagnosing and staging chronic liver diseases.
According to Dr. Jenny Yang, a Regents’ professor in chemistry at Georgia State and the associate director of the university’s Center for Diagnostics and Therapeutics, the method will allow accurate detection of fibrosis at early stages, monitoring of liver fibrosis progression, and response to treatment.
“Our study opens a new way for non-invasive diagnosis of an early stage of liver fibrosis that can be revisable by lifestyle change. It will also help clinicians to monitor the fibrosis progression, and monitor the treatment efficacy. Currently, there is no sensitive way to quantify the changes of fibrosis upon treatment. Our imaging agent can help clinicians to stratify patients for precision therapy,” Dr. Yang, told MEA WorldWide (MEAWW).
The new compound, which binds to, and enables MRI imaging of liver cells in the early stage of the disease, has been developed by scientists supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the NIH.
Why is an early diagnosis of liver disease important?
There are different stages of liver disease: fibrosis (first stage of liver scarring), followed by cirrhosis, and even cancer.
Chronic liver failure, which is also called end-stage liver disease, progresses over years, or decades. Early diagnosis and non-invasive detection of liver fibrosis have remained a major unmet medical need for stopping further disease progression to a life-threatening condition.
“Biopsy is the gold standard for diagnosis and staging of chronic liver disease. However, it has many limitations such as sampling errors, and high variability with 33–50% error rates even for diagnosis of advanced stages of liver fibrosis such as cirrhosis,” says the study.
Most often, chronic liver failure is the result of cirrhosis, a condition in which scar tissue replaces healthy liver tissue until the liver cannot function adequately, according to UCSF experts.
According to Mayo Clinic, while the liver damage done by cirrhosis generally cannot be undone, if liver cirrhosis is diagnosed early and the cause is treated, further damage can be limited.
The leading causes of chronic liver disease are viral hepatitis B and C (HCV), harmful alcohol consumption and metabolic fatty liver disease associated with obesity and type 2 diabetes, say experts.
“From 2000 to 2015, death rates for chronic liver disease and cirrhosis in the US increased from 20.1 per 100,000 to 26.4 among persons aged 45-64 years. Rates in that age group increased by 21% for men (from 29.8 to 36.2) and 57% for women (from 10.8 to 17.0). Among persons aged 25-44 years, the death rate for men decreased 10% (from 6.1 to 5.5), and the rate for women increased 18% (from 2.8 to 3.3),” says CDC.
Further, show estimates, non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis (NASH), is the primary cause of chronic liver disease in the US, affecting an estimated 80-100 million Americans (30–40% of the population).
The study findings
In their findings, published in Nature Communications, the team reports that in imaging studies of animal models of liver disease, the new compound — which is a protein-based MRI contrast agent — can accurately detect early stages of chronic liver disease, including mild fibrosis.
The dyes used in MRI tests, referred to as contrast agents, are substances used to enhance the visibility of internal body structures during magnetic resonance imaging.
“Our developments of collagen-targeted protein-based MRI contrast agents and imaging methodology are expected to overcome the major clinical barriers in early diagnosis, non-invasive detection, and staging of chronic liver diseases, and have strong translational potential in facilitating effective treatment to halt further progression toward major clinical consequences including cirrhosis, impaired liver function, and hepatocellular carcinoma,” Yang told MEAWW.
The patented contrast agent — ProCA32.collagen1 — has been developed in collaboration with Yang’s start-up company, InLighta BioSciences, and biology and chemistry researchers from Georgia State and Emory University.
“Tests in animal models show the protein-based ProCA32.collagen1 can detect the early stage of alcohol-induced liver fibrosis and non-alcoholic steatohepatitis, which is the most severe form of non-alcohol fatty liver disease. The substance is twice as accurate as conventional contrast agents and can detect tumors as small as 0.1 to 0.2 millimeters — 100 times smaller than tumors detected by currently-approved contrast agents. Because it requires a significantly lower dosage than standard contrast agents, it reduces the risk of metal toxicity,” state the findings.
The researchers explain that ProCA32.collagen1’s black-and-white contrast imaging can differentiate “invisible” fibrotic regions from healthy background tissue, overcoming the limitations of invasive biopsies that cannot analyze the entire liver.
“Our contrast agent can do dual-color, so you have different contrast-colored features, and so the sensitivity shows up better, and accuracy is a lot better,” says Yang.
According to Dr. Yang, when identified in an early or moderate stage, alcoholic liver disease can be arrested by stopping alcohol consumption or lifestyle change. “The contrast agent can later be applied to many types of fibrotic diseases, including NASH. It will provide powerful and accurate non-invasive diagnostics for companies during drug development, which will accelerate their efforts to bring new therapeutics and improve treatment for NASH and hepatocellular carcinoma patients,” she says.
The next step, says Dr. Yang, is to get approval from the US Food and Drug Administration (FDA) to conduct clinical trials at Emory University Hospital.
“Our next step is to obtain IND (FDA’s Investigational New Drug program) for clinical trials and further demonstrate its applications in early detection of cancer and fibrosis in other organs,” Dr. Yang told MEAWW.