Serum hyaluronan as a disease marker

Our plain-English summary of Serum hyaluronan as a disease marker, by T.C. Laurent, U.B. Laurent, J.R. Fraser (Annals of Medicine, 1996).

The study

• Authors: T.C. Laurent, U.B. Laurent, J.R. Fraser
• Journal: Annals of Medicine
• Published: 1996;28(3):241-53
• Type of article: Review
• Cited by: 153 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Hyaluronan is a connective tissue polysaccharide which has also been found in blood serum in concentrations < 100 micrograms/L (average 30-40 micrograms/L in middle-aged persons). The serum level is regulated by the influx of the polysaccharide from the tissues via lymph and its receptor-mediated clearance by liver endothelial cells. Markedly high serum levels are noted in certain liver diseases, especially in patients with cirrhosis, when the clearance is impaired. In these cases serum hyaluronan can be used to follow the development of the disease. Serum hyaluronan is also a sensitive marker for impending rejection of liver transplants. Patients with rheumatoid arthritis constitute another major group with increased serum hyaluronan, but in this case the level varies markedly during the day corresponding to physical activity. There are good indications that in these subjects the excess hyaluronan comes from the joints. Under stringent sampling conditions of serum it should be possible to extract interesting information on the inflammatory joint process. Increased hyaluronan levels are also seen in other inflammatory diseases and it is of special interest that high hyaluronan levels in patients with septic conditions is a sign of poor prognosis. Certain tumours, notably Wilms' tumour and mesothelioma, produce factors which activate synthesis of hyaluronan and increase its serum level. Rare hereditary diseases with disturbances of hyaluronan metabolism and elevated blood levels have also been discovered, e.g. Werner's syndrome and cutaneous hyaluronanosis. Information accumulated during the last decade regarding the metabolism of hyaluronan has made this polysaccharide an interesting clinical marker for a number of pathological conditions.

In plain English

This article was a review, not a new study. The authors summarised about a decade of published research on measuring hyaluronan, a connective tissue polysaccharide, in blood serum as a marker of disease. Studies they cited reported markedly high serum levels in liver cirrhosis, raised levels in rheumatoid arthritis that changed with physical activity during the day, and high levels in septic patients that signalled poor prognosis. For mesothelioma, the review reported that cited studies found serum hyaluronan on average significantly higher than in healthy people, in patients with pleural effusions from other causes, in patients with benign lung diseases, and in patients with several other cancers. Values varied greatly, from 25 to 38 880 micrograms per litre in one study. High levels seemed to indicate poor prognosis, and levels rose as the disease progressed. One conclusion drawn from these studies was that the test is probably not a good diagnostic tool for early mesothelioma but could help follow progression and prognosis. The article does not discuss asbestos. The authors concluded that serum hyaluronan seems of most distinctive value as a liver function test.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published studies (human and animal) on serum hyaluronan as a clinical marker
• Who was studied: No new population. The review covers published studies of serum hyaluronan in healthy people and in patients with liver disease, joint disease, systemic sclerosis, septicaemia, renal failure, burns and tumours, including mesothelioma. Patient numbers are those of the cited studies.
• Exposure: Not applicable. The review concerns serum hyaluronan levels in disease. It does not discuss asbestos or any fiber exposure.
• Main results:
  • In mesothelioma patients, cited studies found serum hyaluronan on average significantly elevated compared with healthy persons, with patients having pleural effusions for other reasons, with patients with benign pulmonary diseases, and with groups of patients with other cancers and benign tumours.
  • Serum hyaluronan varied greatly in mesothelioma patients. One cited study reported values between 25 and 38 880 micrograms per litre (printed as 'pg/L' in the scanned text). For comparison, the article gives a normal range in middle-aged people of 10 to 100 micrograms per litre.
  • In the mesothelioma studies cited, high serum hyaluronan seemed to indicate poor prognosis. Levels were lower at stage I than at stages II to IV, lower in patients responding to treatment than in those with progressive disease, and rose during progression.
  • Some mesothelioma patients with high pleural hyaluronan levels had low serum levels, and the reverse.
  • In a cited cell culture study, some mesothelioma cell lines hardly produced hyaluronan, unlike normal mesothelial cells. The suggested explanation was that they secrete factors that induce hyaluronan production in surrounding normal mesothelial cells and fibroblasts.
  • In liver allograft patients (a study by Adams and collaborators), serum hyaluronan was elevated in cases with rejection (median 22.3 times control), compared with stable cases (3.7 times control) and with patients who had post-transplant complications not related to rejection (6.8 times control).
• The authors' conclusion: The authors concluded that serum hyaluronan seems foremost to be of distinctive value as a test of liver function, especially as a pointer to cirrhosis developing in chronic hepatitis. They named the diagnosis of some tumours as another area of interest. For mesothelioma, one conclusion drawn from the cited studies was that the test is probably not a good diagnostic tool for early disease but could be used to follow progression and for prognosis.
• Limitations the authors state:
  • The authors stated that the large variation in levels over the day currently limits the practical value of the test in inflammatory joint disease.
  • The authors stated that they did not compare hyaluronan with other connective tissue markers.

Topics

Medical terms in this study, explained in our Lexicon: Prognosis, Mesothelioma.

Related studies

• CD44 and its ligand hyaluronan as potential biomarkers in malignant pleural mesothelioma: evidence and perspectives — L. Cortes-Dericks, R.A. Schmid (2017)
• Extracellular superoxide dismutase inhibits inflammation by preventing oxidative fragmentation of hyaluronan — F. Gao, J.R. Koenitzer, et al. (2008)
• Hyaluronan and N-ERC/mesothelin as key biomarkers in a specific two-step model to predict pleural malignant mesothelioma — F. Mundt, G. Nilsonne, et al. (2013)
• Telomerase activity analyzed with TRAP in situ provides additional information in effusions remaining equivocal after immunocytochemistry and hyaluronan analysis — E. Adell, A. Dejmek (2014)
• Clinical significance of the immunometric measurements of hyaluronic acid — E.H. Cooper, B.J. Rathbone (1990)
• Serum mesothelin has a higher diagnostic utility than hyaluronic acid in malignant mesothelioma — B. Grigoriu, B. Chahine, et al. (2009)

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