The development and increase in liver fibrosis is a key component of alcohol-related liver disease (ALD), formerly known as alcoholic liver disease (ALD). This progression can result in cirrhosis or further develop into hepatocellular carcinoma and increased mortality. Patient monitoring using fibrosis biomarkers in ALD patients represents a potential novel diagnostic and disease management tool.

Nordic Bioscience's non-invasive biomarkers based on extracellular matrix (ECM) remodeling can help to overcome the challenges in diagnosing ALD and finding patients at high risk of disease progression. Furthermore, the use of predictive or prognostic biomarkers of the ECM to enrich or stratify patients likely to respond to a therapeutic in drug development trials may reduce the trial length, and size required to determine therapeutic efficacy.

The hepatic extracellular matrix (ECM) is rich in different collagens, proteoglycans, and matricellular proteins. In alcohol-related liver disease, the disruption of the balance between degradation and formation of collagens results in ECM remodeling with net formation (build-up and scar formation) of the tissue. 

We have identified twenty types of collagens of relevance for liver health. These collagens have different structures and are distributed in different compartments of the ECM, therefore, have specific functions in the tissue. The dynamics of collagen turnover in alcohol-related liver fibrosis can be investigated using our biomarkers for the formation (nordicPRO-C3™, PRO-C4, PRO-C5, nordicPRO-C6™) and degradation (C3M, C4M, C5M, and C6M) of collagens[1].

Nordic Bioscience's biomarkers can be used to assess ALD severity by helping to identify patients with advanced fibrosis and to monitor the response to treatment and drug efficacy. We are happy to have our team of scientists discuss and understand your aims to select the most appropriate biomarkers that can help answer your research questions.

Explore our hepatic biomarker portfolio and choose a panel that suits your specific needs for your clinical research or drug development project!

Collagen formation of the interstitial matrix quantified by type III (nordicPRO-C3™) and VI (nordicPRO-C6™) collagens formation is elevated in ALD patients compared to healthy subjects (Ctrl).

The basement membrane is further dysregulated in favor of degradation as seen by type IV collagen degradation (C4M) elevated in ALD patients (Figure 1).

This heightened collagen formation in ALD patients suggests an ongoing tissue remodeling process within the interstitial matrix. This dysregulation of the basement membrane, characterized by elevated levels of type IV collagen degradation, underscores the complex interplay between collagen synthesis and degradation that contributes to the pathophysiology of ALD.

Figure 1. nordicPRO-C3™, nordicPRO-C6™, C4M diagnostic value, as presented at EASL 2019 by the GALAXY consortium

ALD patients suffering from portal hypertension, measured by Hepatic venous pressure gradient (HPVG), have elevated levels of both formation and degradations biomarkers. This includes basement membrane (type IV collagen; PRO-C4) and interstitial matrix (type III collagens; nordicPRO-C3™, type V collagen; C5M, Elastin; ELM) proteins (Figure 2.)

Figure 2. Formation and degradation biomarkers in alcoholic liver disease (ALD)[2]

NordicPRO-C3™ and nordicPRO-C6™ provide insights into the liver function of ALD patients and nordicPRO-C3™ has prognostic value for predicting outcomes and liver-related events (LRE) in patients with ALD.

NordicPRO-C3™ showed prediction value to identify which patients from a mixed-etiology cohort composed of patients with chronic hepatitis virus and compensated cirrhosis with or without a history of acute alcohol consumption (ALD) are at risk of liver-related outcomes[3].

As part of the GALAXY consortium, a prediction model was developed[4] based on nordicPRO-C3™ and independent predictors of LREs (platelets, AST/ALT) named ALPACA score which presented a superior prognostic performance for predicting LREs when compared to other liver scores currently used in the clinic such as ELF, TE, and FIB-4, see reference. With the ALPACA score, it was possible to differentiate between patients with a low and high risk of LREs.

Alcohol-related liver disease (ALD), formerly known as alcoholic liver disease, is a generic term for liver damage caused by chronic alcohol abuse. Prolonged excessive alcohol consumption can impair the liver's ability to regenerate and lead to liver damage. Alcoholic liver disease is usually divided into 3 stages: alcoholic fatty liver disease, alcoholic hepatitis and cirrhosis, depending on the degree of fat accumulation, inflammation, and fibrosis.

How many people have alcohol-related liver disease?
The prevalence of alcohol-related related liver disease varies around the world, as the amount of alcohol consumed generally depends on cultural acceptance. In the United States, an estimated 3-5% of people suffer from some degree of alcoholic liver disease.

How is alcohol-related liver disease treated?
Currently, there is no specific treatment for alcoholic liver disease and the most successful intervention is the cessation of alcohol consumption. Abstaining from alcohol reduces the risk of further damage to the liver to a level where there is a chance that the liver will recover. With lifestyle changes, nonalcoholic steatohepatitis is reversible. However, in alcoholic steatohepatitis, liver transplantation may be required in severe cases, such as decompensated cirrhotics.

How is alcohol-related liver disease diagnosed?
Diagnosis of alcohol-related related liver disease relies on blood tests to assess liver function and alcohol consumption questionnaires. If blood tests indicate decreased liver function and advanced liver damage, further testing including imaging and liver biopsies may be required to determine the pathology of steatohepatitis.

If you want to learn more, we have published a series of articles on alcohol-related liver disease that you can browse.

Biomarkers for other hepatic indications

The applications presented here are for research use only.

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