Alcoholic Liver Disease (ALD) 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. ALD 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 alcoholic liver disease?
The prevalence of Alcoholic 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 ALD.

How is alcoholic liver disease treated?
Currently, there is no specific treatment for ALD and the most successful intervention is 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 alcoholic liver disease or alcoholic steatohepatitis diagnosed?
Diagnosis of ALD and alcoholic steatohepatitis 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 alcoholic liver disease that you can browse.

 

The medical need for serum biomarkers in Alcoholic Liver Disease (ALD) and alcoholic steatohepatitis today is twofold. First, diagnosis of ALD remains challenging because symptoms are similar to those of other liver diseases such as non-alcoholic fatty liver disease (NAFLD). Second, predicting progression to cirrhosis has proven particularly difficult. Patients respond differently to chronic alcohol abuse, and which patients progress when cannot currently be predicted.

Diagnostic and prognostic biomarkers have the potential to greatly benefit patients by helping to diagnose the disease early and initiate the most appropriate treatment at the right time. In addition, the use of predictive or prognostic biomarkers to enrich or stratify patients likely to respond to a therapeutic in drug development trials can reduce the duration and size of studies required to determine therapeutic efficacy.

Nordic Bioscience offers an accurate liver fibrosis biomarker panel that provides information on disease progression.

Alcoholic Liver Disease (ALD) is characterized by both inflammation and tissue scarring (fibrosis). The liver is rich in various collagens, proteoglycans and matricellular proteins. These proteins are remodeled as part of liver homeostasis and regeneration.

During remodeling, proteins are degraded and rebuilt as part of the normal repair and maintenance of the stroma in the liver. At ALD, the balance between tissue degradation and rebuilding is disturbed, resulting in net formation (buildup and scarring) of stroma in the liver. Protein fingerprint biomarkers for liver injury can quantify this tissue turnover directly in serum plasma samples. Nordic Bioscience offers biomarkers for liver disease that provide insight into disease progression in an accurate liver fibrosis biomarker panel.

Although there are several diagnostic measures and measures of disease activity in the liver, some are invasive while others have limited predictive power. Therefore, there is still a need in medicine and drug development for biomarkers that can characterize and quantify structural tissue changes and predict disease progression.

Tissue-derived protein fingerprint serum biomarkers for liver fibrosis can be measured in serum and plasma. Their use allows for accurate quantification of changes in tissue turnover in different layers of an individual patient's liver tissue without the need for invasive biopsies. For example, our liver fibrosis biomarker panel can accurately measure liver tissue remodeling (this includes the PRO -C3 assay, a biomarker that has received a Letter of Support from the FDA).

Some examples of liver biomarkers include:

Some liver biomarker examples include:

Biomarkers and tissue characterization:
Pericellular fibrosis by type IV collagen fragments: C4M, PRO-C4.

Bridging fibrosis by type III collagen fragments: PRO-C3, PC3X, C3M.


Reference: Karsdal et al. , Hepatology 2020

Biomarkers of protein fingerprint formation measured in serum and plasma are generally elevated in patients with Alcoholic Liver Disease (ALD) compared with healthy individuals.


Reference: Presented at EASL 2019 by GALAXY consortium.

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

The basement membrane is also dysregulated in favor of degradation, as shown by the increased degradation of type IV collagen (C4M) in ALD patients.

Protein Fingerprint biomarkers measured in serum are associated with established disease parameters such as portal hypertension.


ALD patients suffering from portal hypertension, as measured by hepatic venous pressure gradient (HPVG), have elevated levels of both anabolic and degradative biomarkers. These include basement membrane proteins (type IV collagen; PRO -C4) and interstitial matrix proteins (type III collagens; PRO -C3, type V collagen; C5M, elastin; ELM).  Reference: Leeming et al. 2013 Aliment Pharmacol. Ther.

Please don't hesitate to contact us if you have any questions or other inquiries.

Please don't hesitate to contact us if you have any questions or other inquiries.

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