Hyaluronic acid as a non-invasive biomarker of liver fibrosis

Neuman, Manuela G.; Cohen, Lawrence B.; Nanau, Radu M.

doi:10.1016/j.clinbiochem.2015.07.019

Cited by 82 publications

(61 citation statements)

References 123 publications

(176 reference statements)

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“…Irrespective of whether HA is a cause or consequence of inflammation, HA is increased upon inflammation, and its abundance and/or size in the tissue, and possibly the serum, may provide a useful biomarker for the state of inflammation. This is an ongoing area of research, for example in arthritis49, breast cancer metastasis50, and liver fibrosis51.…”

Section: Discussionmentioning

confidence: 99%

Endotoxin free hyaluronan and hyaluronan fragments do not stimulate TNF-α, interleukin-12 or upregulate co-stimulatory molecules in dendritic cells or macrophages

Dong

Arif

Olsson

et al. 2016

Sci Rep

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The extracellular matrix glycosaminoglycan, hyaluronan, has been described as a regulator of tissue inflammation, with hyaluronan fragments reported to stimulate innate immune cells. High molecular mass hyaluronan is normally present in tissues, but upon inflammation lower molecular mass fragments are generated. It is unclear if these hyaluronan fragments induce an inflammatory response or are a consequence of inflammation. In this study, mouse bone marrow derived macrophages and dendritic cells (DCs) were stimulated with various sizes of hyaluronan from different sources, fragmented hyaluronan, hyaluronidases and heavy chain modified-hyaluronan (HA-HC). Key pro-inflammatory molecules, tumour necrosis factor alpha, interleukin-1 beta, interleukin-12, CCL3, and the co-stimulatory molecules, CD40 and CD86 were measured. Only human umbilical cord hyaluronan, bovine testes and Streptomyces hyaluronlyticus hyaluronidase stimulated macrophages and DCs, however, these reagents were found to be contaminated with endotoxin, which was not fully removed by polymyxin B treatment. In contrast, pharmaceutical grade hyaluronan and hyaluronan fragments failed to stimulate in vitro-derived or ex vivo macrophages and DCs, and did not induce leukocyte recruitment after intratracheal instillation into mouse lungs. Hence, endotoxin-free pharmaceutical grade hyaluronan does not stimulate macrophages and DCs in our inflammatory models. These results emphasize the importance of ensuring hyaluronan preparations are endotoxin free.

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Section: Discussionmentioning

confidence: 99%

Endotoxin free hyaluronan and hyaluronan fragments do not stimulate TNF-α, interleukin-12 or upregulate co-stimulatory molecules in dendritic cells or macrophages

Dong

Arif

Olsson

et al. 2016

Sci Rep

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“…A recent study performed a systematic review showing that serum HA can be used as a noninvasive biomarker to assess the presence of liver fibrosis, and to monitor disease progression [209]. Serum HA in combination with other measurements form a score system [210] or an algorithm model [211] may be used as a clinic tool to monitor liver fibrosis.…”

Section: Hyaluronan In Human Diseasesmentioning

confidence: 99%

Hyaluronan as a therapeutic target in human diseases

Liang

Jiang

Noble

2016

Advanced Drug Delivery Reviews

167

103

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Accumulation and turnover of extracellular matrix is a hallmark of tissue injury, repair and remodeling in human diseases. Hyaluronan is a major component of the extracellular matrix and plays an important role in regulating tissue injury and repair, and controlling disease outcomes. The function of hyaluronan depends on its size, location, and interactions with binding partners. While fragmented hyaluronan stimulates the expression of an array of genes by a variety of cell types regulating inflammatory responses and tissue repair, cell surface hyaluronan provides protection against tissue damage from the environment and promotes regeneration and repair. The interactions of hyaluronan and its binding proteins participate in the pathogenesis of many human diseases. Thus, targeting hyaluronan and its interactions with cells and proteins may provide new approaches to developing therapeutics for inflammatory and fibrosing diseases. This review focuses on the role of hyaluronan in biological and pathological processes, and as a potential therapeutic target in human diseases.

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“…6 Several noninvasive markers for liver fibrosis have been studied. Direct fibrosis markers like hyaluronic acid 7 and imaging studies to assess liver stiffness 8 are usually expensive and not readily available. On the other hand, simple fibrosis scores like aspartate aminotransferase/alanine aminotransferase ratio (AST/ALT ratio), aspartate aminotransferase/platelet ratio index (APRI), and fibrosis-4 index (FIB-4 index) have gained popularity because they are calculated using frequently available clinical variables such as liver enzymes and platelet count.…”

Section: Introductionmentioning

confidence: 99%

Untitled

Kabbany

Selvakumar²,

Guirguis³

et al. 2018

Exp Clin Transplant

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Objectives: Several scoring systems have been developed to noninvasively predict the presence of advanced fibrosis in patients with chronic liver disease. Hepatitis C virus and nonalcoholic fatty liver disease are the 2 most common indications for orthotopic liver transplant and are associated with disease recurrence that can lead to fibrosis progression. Here, we evaluated the performance of commonly used fibrosis scores in assessing the presence of advanced fibrosis in patients after orthotopic liver transplant. Materials and Methods: Our study consisted of consecutive patients with hepatitis C virus or nonalcoholic fatty liver disease who underwent a liver biopsy after transplant and had laboratory measurements within 1 week of biopsy. Graft fibrosis was determined by an experienced pathologist (stage F0-F4). Advanced fibrosis was defined as stage F3-F4. The following fibrosis scores were calculated for each patient: aspartate aminotransferase/alanine aminotransferase ratio, aspartate aminotransferase/platelet ratio index, and fibrosis-4 index. Results: We analyzed 93 patients with median age of 59 years (25th and 75th percentile of 53 and 64 y) and median body mass index of 31.8 kg/m 2 (25th and 75th percentile of 27 and 37.6 kg/m 2 ). Of total patients, 41 (44%) were diabetic. Median time to liver biopsy posttransplant was 27.7 months (25th and 75 percentile of 10.8 and 59.9 mo). We found that 54 patients (58%) had no fibrosis, 15 (16.1%) had F1, 8 (8.6%) had F2, 7 (7.5%) had F3, and 9 (9.7%) had F4. Overall, advanced fibrosis (F3-F4) was present in 16 patients. Aspartate aminotransferase/alanine aminotransferase ratio, aspartate aminotransferase/platelet ratio index, and fibrosis-4 index were not significantly different between patients with and without advanced fibrosis (all P > .05). The calculated fibrosis scores had poor diagnostic accuracy for presence of advanced fibrosis posttransplant. Conclusions: Commonly used liver fibrosis scores are not accurate in predicting the presence of advanced fibrosis in patients after liver transplant.

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Hyaluronic acid as a non-invasive biomarker of liver fibrosis

Cited by 82 publications

References 123 publications

Endotoxin free hyaluronan and hyaluronan fragments do not stimulate TNF-α, interleukin-12 or upregulate co-stimulatory molecules in dendritic cells or macrophages

Endotoxin free hyaluronan and hyaluronan fragments do not stimulate TNF-α, interleukin-12 or upregulate co-stimulatory molecules in dendritic cells or macrophages

Hyaluronan as a therapeutic target in human diseases

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