Alcoholic liver disease (ALD) is an umbrella term for liver damage caused by chronic alcohol abuse. Prolonged excessive alcohol consumption can reduce the livers’ ability to regenerate and can result in liver damage. ALD is normally divided into 3 stages; alcoholic fatty liver disease, alcoholic hepatitis and cirrhosis depending on the level of build-up fat, inflammation and fibrosis.

How many have alcoholic liver disease?
Alcoholic Liver Disease prevalence differs across the world as the level of alcohol consumption, in general, is dependent on cultural acceptance. In the United States, it is estimated that 3-5% 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 to halt alcohol consumption. Elimination of alcohol consumption reduces the risk of further damage of the liver to where there is a chance of the liver recovering. By implementing life-style changes, non-alcoholic steatohepatitis is reversible. However, alcoholic steatohepatitis pathology outlines in severe cases such as decompensated cirrhotics may require liver transplantation.

How is alcoholic liver disease or alcoholic steatohepatitis diagnosed?
The diagnosis of ALD and alcoholic steatohepatitis rely on blood tests to assess the liver function and questionnaires on alcohol consumption. If blood tests suggest decreased liver function and advanced liver damage, further tests including imaging and liver biopsies might be necessary to determine steatohepatitis pathology.

 

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

The medical need for serum biomarkers in alcoholic liver disease (ALD) and alcoholic steatohepatitis today is two-fold. Firstly, the diagnosis of ALD remains a challenge as the symptoms mimics those of other liver diseases as non-alcoholic fatty liver disease (NAFLD). Secondarily, prediction of progression to especially cirrhosis has proven difficult. Patients react differently to chronic alcohol abuse and which patients progress and when can currently not be predicted.

Diagnostic and prognostic biomarkers have the potential to greatly benefit patients, by aiding in early diagnosis of disease and directing the most appropriate treatment at the right time. Furthermore, use of predictive or prognostic biomarkers 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. Nordic Bioscience offers an accurate liver fibrosis biomarker panel that gives insight into disease progression.

Alcoholic liver disease (ALD) is characterized by both inflammation and scar formation in tissue (fibrosis).
The liver is rich in different collagens, proteoglycans and matricellular proteins. These proteins and remodeled as part of liver homeostasis and regeneration. During remodeling, proteins are broken down and rebuilt as part of normal repair and maintenance of the stroma in the liver. In ALD, the balance between degradation and formation of tissue is interrupted resulting in net formation (build-up and scar formation) of the stroma in the liver. Protein fingerprint biomarkers of liver damage can quantify this tissue turnover directly in serum plasma samples. Nordic Bioscience offers biomarkers for liver disease that in an accurate liver fibrosis biomarker panel that gives insight into disease progression.

While there are several diagnostic and disease activity measures in the liver field, some are invasive whereas other predictive capacity is limited. There is therefore still a medical and drug development need for biomarkers that can characterize and quantify structural tissue change and predict disease progression. The tissue-derived Protein Fingerprint serum biomarkers for liver fibrosis can be measured in serum and plasma. Their use allows to accurately quantify changes in tissue turnover in the different layers of liver tissues in the individual patient, without the need for invasive biopsies. For example, our liver fibrosis biomarker panel can accurately measure liver tissue remodeling (which includes the PRO-C3 assay, a biomarker that received a Letter of Support from the FDA).

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

Protein Fingerprint formation biomarkers measured in serum and plasma are generally increased in alcoholic liver disease (ALD) patients compared to healthy individuals.


Reference: Presented at EASL 2019 by the 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 further dysregulated in favor of degradation as seen by type IV collagen degradation (C4M) elevated in ALD patients

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


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

Reference: Leeming et al. 2013 Aliment Pharmacol. Ther.

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