1 out of 3 people will develop this disease…

An estimated 100 million Americans suffer from a disease they’ve likely never heard of. Demonstrating the qualities of a true silent killer, this condition can progress for years in the absence of noticeable symptoms. How could the leading cause of liver cancer and the fastest growing driver of liver transplantation remain so obscure? (1,2,3)

The disease in question is non-alcoholic fatty liver disease (NAFLD), and it’s advanced form non-alcoholic steatohepatitis (NASH). Although NAFLD/NASH primarily affect metabolically unhealthy adults, doctors are finding patients as young as 10 years old with the condition. (4)

The pathogenesis of NAFLD/NASH begins with fat accumulation in the liver. This process, known as steatosis, is mediated by risk factors such as obesity, insulin resistance, and hypertension. As steatosis worsens, liver cells (hepatocytes) become chronically inflamed and thickened. This environment induces fibrosis, characterized by the scarification of liver tissue. If unidentified or left untreated, fibrosis can develop into its final form of cirrhosis, whereby liver function is significantly compromised. Crossing this threshold increases the risk of liver failure and cancer, namely hepatocellular carcinoma (HCC).

To simplify: fat buildup and inflammatory activity in the liver (steatosis), leads to tissue damage and impaired healing (fibrosis), which can result in organ damage (cirrhosis).

With such a large portion of the population affected by NAFLD, the need for early detection becomes obvious. While basic blood markers may point in the direction of NAFLD/NASH, an invasive biopsy is currently the primary method for diagnosis. Biopsy, surgical tissue extraction for testing, can be painful and cost prohibitive. Liver biopsies are rarely ordered without an existing suspicion of liver disease, meaning NASH may have years to develop under the radar. (5)

Clinicians and researchers have been working on the development of improved non-invasive diagnostics for fibrosis. Recently the Enhanced Liver Fibrosis (ELF) test has made headlines for its ability to detect and quantify fibrotic activity. The ELF Test is most effective at identifying patients with a high likelihood of developing cirrhosis. At Marek Health, ELF testing has become a staple for those at high risk of NAFLD/NASH, affording medical providers an early opportunity for disease detection. (6)

ELF testing offers several advantages over traditional liver screening. It is simple, fast, and inexpensive, and avoids the discomfort and risk associated with invasive biopsy. Furthermore, ELF testing is a highly reliable indicator of liver fibrosis, even in earlier stages. The test comprehensively evaluates three distinct biomarkers implicated in liver fibrosis:

Hyaluronic Acid (HA):

HA is a building block for connective tissue within the liver. Hepatic stellate cells respond to localized injuries from fat accumulation with collagen synthesis. Chronic stellate cell hyperactivity, consistent with fibrosis, results in the release of HA.

"Multiple studies have reported increased HA deposition in inflammatory diseases of the liver. Whereas the concentration of HA in the healthy liver is low, its concentration significantly increases in the inflamed liver, leading to increased levels of serum HA. As a result, the level of circulating HA has been proposed as a biomarker for cirrhotic liver disease, for monitoring liver function, for assessing liver fibrosis, and for diagnosing chronic viral hepatitis C" (7)

Fibrotic states and oxidative stress go hand in hand. Identified by reactive oxygen species (ROS), persistent oxidative stress leads to cellular dysfunction. ROS degrade hyaluronic acid polymers. Elevated HA upregulates pro-fibrotic transforming growth factor beta (TGF-B), indicating HA's active role in disease progression. (8)

Tissue inhibitor matrix metalloproteinase (TIMP1):

Matrix metalloproteinases (MMPs) are a family of enzymes responsible for breaking down the extracellular matrix. TIMP1 inhibits MMP activity to support the structural integrity of liver cells. Chronic overexpression of TIMP1 indicates liver cells are working overtime in response to sustained injury from steatosis/inflammation.

Aberrant TIMP1 signaling is noted in tumor-associated fibroblasts, mediated by the aforementioned TGF-B. TIMP1 as a biomarker can indicate fibrotic activity as well as potentially identify cancerous progression. (9)

Type 3 Procollagen Peptide (PIIINP):

Collagen supports wound repair at the site of injury. Deposition of collagen often becomes excessive when wound regeneration pathways are dysfunctional. PIIINP in serum indicates excessive collagen synthesis or degradation, which is associated with fibroproliferative disorders. PIIINP works synergistically with the other biomarkers to paint a comprehensive picture of fibrotic activity. (10,11)

The combination of these three novel biomarkers provide deep insight into liver fibrosis, specifically at the threshold of disease progression most associated with cancer risk. If we overlook opportunities for early detection, the so-called "silent killers" will remain inaudible. ELF Testing provides a unique opportunity to hear the footsteps of an otherwise silent killer.

Marek Health is committed to staying up to date on advancements in the world of disease prevention and total human optimization. If you want to learn more about how you can stay on top of your health, schedule an appointment with a Health Coach HERE.

Disclaimer: This blog post/article is for informational purposes only and does not constitute medical advice. This is not a substitute for professional medical advice and should not be relied upon. If you are considering a treatment, always consult your primary care physician to discuss the risks and benefits.

ELF Test- Marek Diagnostics

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