Hyaluronic Acid In Patients Research Articles

Serum hyaluronic acid with serum ferritin accurately predicts cirrhosis and reduces the need for liver biopsy in C282Y hemochromatosis #

Diagnosing the presence of cirrhosis is crucial for the management of patients with C282Y hereditary hemochromatosis (HH). HH patients with serum ferritin >1,000 microg/L are at risk of cirrhosis; however, the majority of these patients do not have cirrhosis. Noninvasive markers of hepatic fibrosis may assist in determining which patients with a serum ferritin >1,000 microg/L have cirrhosis and require liver biopsy. This study evaluated the utility of current diagnostic algorithms for detecting cirrhosis, including serum ferritin concentration, platelet counts, and aspartate aminotransferase (AST) levels, in combination with serum markers of fibrosis, hyaluronic acid and collagen type IV (CLIV), in predicting cirrhosis in HH patients. Stage of fibrosis, serum hyaluronic acid and CLIV levels, were measured in 56 patients with HH. No patient with a serum ferritin <1,000 microg/L had cirrhosis, but only 40% of patients with serum ferritin >1,000 microg/L were cirrhotic. A combination of platelet count (<200 x 10(9)/L), elevated AST, and serum ferritin >1,000 microg/L did not detect 30% of cirrhotic subjects. Serum hyaluronic acid was increased in HH compared with controls (42.0 +/- 9.8 ng/mL versus 19.3 +/- 1.8 ng/mL; P = 0.02). A hyaluronic acid concentration >46.5 ng/mL was 100% sensitive and 100% specific in identifying patients with cirrhosis. In patients with serum ferritin >1,000 microg/L, hyaluronic acid levels were significantly elevated in patients with cirrhosis versus those without cirrhosis (137 +/- 34.4 ng/mL versus 18.6 +/- 1.5 ng/mL, respectively; P = 0.006). CLIV >113 ng/mL was 100% sensitive but only 56% specific for cirrhosis (area under the curve = 0.78; P = 0.01). In HH, the measurement of hyaluronic acid in patients with serum ferritin >1,000 microg/L is a noninvasive, accurate, and cost-effective method for the diagnosis of cirrhosis. (HEPATOLOGY 2009;49:418-425.).

Diagnosis and Quantitation of Fibrosis

Hepatic fibrosis is the final common pathway for many different liver insults. Originally considered to be irreversible, hepatic fibrosis is now known to be a dynamic process with a significant potential for resolution. The diagnosis and quantitation of fibrosis have traditionally relied on liver biopsy. However, there are a number of drawbacks including the invasive nature of the procedure, sampling error, and interobserver variability. This article reviews the current role of liver biopsy in the assessment of hepatic fibrosis and discusses the role of the newer noninvasive methods including serum markers and radiologic tests.

Noninvasive assessment of liver fibrosis with combined serum aminotransferase/platelet ratio index and hyaluronic acid in patients with chronic hepatitis B

To construct a noninvasive assessment model consisting of routine laboratory data to predict significant fibrosis and cirrhosis in patients with chronic hepatitis B (CHB). A total of 137 consecutive patients with CHB who underwent percutaneous liver biopsy were retrospectively analyzed. These patients were divided into two groups according to their aminotransferase (ALT) level. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), the likelihood ratio (LR) of aminotransferase/platelet ratio index (APRI) > or = 1.5 or < 1.5 in combination with different hyaluronic acid (HA) cut-off points were calculated for the presence of moderate to severe fibrosis/cirrhosis (fibrosis stages 2 and 4) and no to mild fibrosis/cirrhosis (fibrosis stages 0 and 1). The APRI correlated with fibrosis stage in CHB patients. The APRI > or = 1.5 in combination with a cut-off HA cut-off point > 300 ng/mL could detect moderate to severe fibrosis (stages 2-4) in CHB patients. The PPV was 93.7%, the specificity was 98.9%. The APRI < 1.5 in combination with different HA cut-off points could not detect no to mild fibrosis in CHB patients. The APRI > or = 1.5 in combination with a HA cut-off point > 300 ng/mL can detect moderate to severe fibrosis (stages 2-4) in CHB patients.

Hylan versus hyaluronic acid for osteoarthritis of the knee: A systematic review and meta‐analysis

To compare the effectiveness and safety of intraarticular high-molecular hylan with standard preparations of hyaluronic acids in osteoarthritis of the knee. We performed a systematic review and meta-analysis of randomized controlled trials comparing hylan with a hyaluronic acid in patients with knee osteoarthritis. Trials were identified by systematic searches of Central, Medline, EMBase, Cinahl, the Food and Drug Administration, and Science Citation Index supplemented by hand searches of conference proceedings and reference lists (last update November 2006). Literature screening and data extraction were performed in duplicate. Effect sizes were calculated from differences in means of pain-related outcomes between treatment and control groups at the end of the trial, divided by the pooled standard deviation. Trials were combined using random-effects meta-analysis. Thirteen trials with a pooled total of 2,085 patients contributed to the meta-analysis. The pooled effect size was -0.27 (95% confidence interval [95% CI] -0.55, 0.01), favoring hylan, but between-trial heterogeneity was high (I(2) = 88%). Trials with blinded patients, adequate concealment of allocation, and an intent-to-treat analysis had pooled effect sizes near null. The meta-analyses on safety revealed an increased risk associated with hylan for any local adverse events (relative risk [RR] 1.91; 95% CI 1.04, 3.49; I(2) = 28%) and for flares (RR 2.04; 95% CI 1.18, 3.53; I(2) = 0%). Given the likely lack of a superior effectiveness of hylan over hyaluronic acids and the increased risk of local adverse events associated with hylan, we discourage the use of intraarticular hylan in patients with knee osteoarthritis in clinical research or practice.

Longitudinal evaluation of a fibrosis index combining MMP‐1 and PIIINP compared with MMP‐9, TIMP‐1 and hyaluronic acid in patients with chronic hepatitis C treated by interferon‐alpha and ribavirin

We have recently described a fibrosis index combining serum procollagen type III N-terminal peptide (PIIINP) and matrix metalloproteinase 1 (MMP-1) concentrations for evaluating the amount of liver fibrosis in chronic hepatitis C patients. The aims of the present study were to validate this score in another cohort of patients and to assess its variations along those of TIMP-1, hyaluronic acid (HA) and MMP-9 during antiviral treatment. Seventy-nine patients treated by interferon-alpha and ribavirin for 24 or 48 weeks were included. A liver biopsy was performed within the 6 months before the start of treatment. Serum markers were measured in serum collected the day of the liver biopsy, at start of treatment, and every 3 months during treatment and a 6-month follow-up period. The PIIINP/MMP-1 index was significantly correlated to the METAVIR fibrosis (r = 0.68, P < 0.001). Its overall diagnostic value defined by the area under the receiver operating characteristics curves was 0.77 for discriminating F1 vs F2F3F4, and 0.81 for discriminating F1F2 vs F3F4, and was better than that observed for HA and TIMP-1. At the end of follow-up, the PIIINP/MMP-1 index significantly decreased in responders and remained stable in nonresponder patients. This decrease occurred early and continued regularly during the treatment period. This variation was because of both a decrease of PIIINP and an increase of MMP-1 concentrations. HA and TIMP-1 serum concentrations were also significantly lower at the end of follow-up in responder patients, but early changes were minimal and not influenced by the response to treatment. Our study shows that a noninvasive index combining PIIINP and MMP-1 is a useful tool to follow-up fibrosis change during and after antiviral therapy chronic hepatitis C patients.

Efficacy of intra-articular hyaluronic acid in patients with osteoarthritis of the ankle: a prospective study

To investigate the efficacy, safety and the duration of treatment effectiveness of intra-articular hyaluronic acid (Artz, Japan) in patients with ankle osteoarthritis (OA). As a prospective clinical trial, 93 patients with unilateral ankle pain for at least 6 months and radiographically classified as Kellgren-Lawrence grade I or II ankle OA were included. After five weekly intra-articular Artz injections, the Ankle Osteoarthritis Scale (AOS), the American Orthopaedic Foot and Ankle Society (AOFAS) ankle/hindfoot score, ankle sagittal range of motion (ROM), patients' global satisfaction, local adverse events and consumption of rescue analgesics were analyzed. Seventy-five patients completed the study. Significant improvement in AOS and AOFAS ankle/hindfoot scores was noted at 1 week, 1 month, 3 months and 6 months post the fifth injection (P < 0.001 compared with baseline). The mean reduction of AOS score was 1.9, 2.6, 2.5 and 2.6 at each following visit (P < 0.001). The mean AOFAS ankle/hindfoot score improved from 64 points at baseline to 75, 78, 78, and 78 points at 1 week, 1 month, 3 months and 6 months, respectively, post the fifth injection (P < 0.001). Ankle sagittal ROM did not improve significantly (P > 0.05). The majority of patients reported satisfaction at 1 week (100%), 1 month (100%), 3 months (90.7%) and 6 months (86.7%) follow-up. Local adverse events occurred in 6.7% of patients. Acetaminophen consumption dropped significantly following treatment (P < 0.001). Five weekly intra-articular injections of Artz provide pain relief and functional improvements in patients with Kellgren-Lawrence grades I and II ankle OA. The clinical effect was rapid at 1 week and may last for 6 months or more.

Determination of serum levels of YKL-40 and hyaluronic acid in patients with hepatic fibrosis due to schistosomiasis japonica and appraisal of their clinical value

The objectives of this study were (i) to evaluate the serum levels of human cartilage glycoprotein 39 (YKL-40) and hyaluronic acid (HA) in people infected with Schistosoma japonicum, and (ii) to determine their clinical value. A total of 563 people were subjected to ultrasonography, and 60 patients were identified with either mild ( n = 30) or severe ( n = 30) hepatic fibrosis. In addition, 28 healthy subjects were included as controls. Blood sera of these 88 people were examined with regard to the levels of YKL-40 and HA. The former was measured by enzyme-linked immunosorbent assay, and serum HA was determined by a commercially available radioimmunoassay method. On the basis of the ultrasonographic investigations, HA levels in normal, mild, and severe cases of hepatic fibrosis were 83.0 ± 35.7, 216.1 ± 77.9 and 212.6 ± 80.9 μg/ml, respectively. When the same sera were tested for YKL-40, 49.0 ± 10.4, 92.3 ± 18.5 and 172.1 ± 35.9 μg/ml, respectively, were recorded in the three groups. Thus, the serum levels of YKL-40 are not only increased in patients infected with S. japonicum but they are also correlated with the stage of hepatic fibrosis. In conclusion, it appears that YKL-40 is more sensitive than HA in measuring the degree of hepatic fibrosis due to schistosomiasis, which warrants further investigation.

Intratympanic Dexamethasone and Hyaluronic Acid in Patients with Low-Frequency and Ménière's-Associated Sudden Sensorineural Hearing Loss

Steroids are widely used for the treatment of cochleovestibular disorders. Direct steroid application in the middle ear cavity, when combined with a round window membrane permeability-modulating substance, increases the level of the steroid reaching the target cells. We measured hearing in patients with idiopathic isolated low-frequency sensorineural hearing loss and in patients with sudden sensorineural hearing loss and a history of Ménière's disease. Contradictory reports about effectiveness of intratympanic steroid therapy on vertigo control and hearing improvement in patients with Ménière's disease exist in the literature. Eighteen patients with isolated low-frequency idiopathic sudden sensorineural hearing loss and 21 patients with sudden sensorineural hearing loss and a history of Ménière's disease were prospectively evaluated. The acute effect of the intratympanic application of dexamethasone with hyaluronic acid on hearing outcome after failure of an initial standard treatment with intravenous steroid and vasoactive substances was assessed. Evaluation was based on standard pure-tone audiometry findings. After intratympanic injection of dexamethasone and hyaluronic acid, 14 of the 18 patients with isolated low-frequency sensorineural hearing loss showed a significant improvement in hearing. After intratympanic therapy, 15 patients with a previous history of Ménière's disease and idiopathic isolated low-frequency sensorineural hearing loss showed an improvement in hearing on pure-tone audiometry, four remained unchanged, and two showed a tendency toward a slight deterioration. Intratympanic combined dexamethasone/hyaluronic acid application provides a reliable and safe therapeutic option for improvement of hearing in patients with isolated low-frequency idiopathic sudden sensorineural hearing loss or sensorineural hearing loss resulting from Ménière's disease who have failed intravenous steroid and vasoactive treatments.

P173 Predictive factors of the efficacy of viscosupplementation with non animal stabilized hyaluronic acid in patients with hip osteoarthritis

P173 Predictive factors of the efficacy of viscosupplementation with non animal stabilized hyaluronic acid in patients with hip osteoarthritis

Serum markers detect the presence of liver fibrosis: A cohort study

Histologic examination of a liver biopsy specimen is regarded as the reference standard for detecting liver fibrosis. Biopsy can be painful and hazardous, and assessment is subjective and prone to sampling error. We developed a panel of sensitive automated immunoassays to detect matrix constituents and mediators of matrix remodeling in serum to evaluate their performance in the detection of liver fibrosis. In an international multicenter cohort study, serum levels of 9 surrogate markers of liver fibrosis were compared with fibrosis stage in liver biopsy specimens obtained from 1021 subjects with chronic liver disease. Discriminant analysis of a test set of samples was used to identify an algorithm combining age, hyaluronic acid, amino-terminal propeptide of type III collagen, and tissue inhibitor of matrix metalloproteinase 1 that was subsequently evaluated using a validation set of biopsy specimens and serum samples. The algorithm detected fibrosis (sensitivity, 90%) and accurately detected the absence of fibrosis (negative predictive value for significant fibrosis, 92%; area under the curve of a receiver operating characteristic plot, .804; standard error, .02; P < .0001; 95% confidence interval, .758-.851). Performance was excellent for alcoholic liver disease and nonalcoholic fatty liver disease. The algorithm performed equally well in comparison with each of the pathologists. In contrast, pathologists' agreement over histologic scores ranged from very good to moderate (kappa = .97-.46). Assessment of liver fibrosis with multiple serum markers used in combination is sensitive, specific, and reproducible, suggesting they may be used in conjunction with liver biopsy to assess a range of chronic liver diseases.

939 Prevention of urinary tract infections by bladder installations of hyaluronic acid in patients with metastatic acute medullar compression

939 Prevention of urinary tract infections by bladder installations of hyaluronic acid in patients with metastatic acute medullar compression

Serum Levels of Hyaluronic Acid in Patients with Psoriatic Arthritis

The purpose of this study was to evaluate the serum levels of hyaluronic acid (HA) in a group of patients with psoriatic arthritis (PsA), with special emphasis on the relationships between HA levels and clinical parameters of joint and skin activity. Thirty-four patients with PsA, 34 patients with rheumatoid arthritis (RA) and 49 healthy volunteers participated in the study. Assessment of joint disease in patients with PsA included duration of morning stiffness, number of tender and swollen joints, right and left grip, the presence of inflammatory back pain and Schober's test. The current severity of skin involvement was graded according to the Psoriasis Area Severity Index (PASI). Serum levels of HA were measured by a radiometric assay. The mean HA serum levels of patients with PsA and RA were significantly increased in comparison with healthy controls (107 +/- 39.6 microg/dl in patients with PsA, whereas in patients with RA it was 168 +/- 32.4 microg/dl and 36.7 +/- 5.5 microg/dl in healthy controls). A highly significant correlation was found between levels of HA and index of skin involvement, but no association was found between HA levels and clinical parameters of joint severity. We conclude that in this cohort of patients with PsA, HA levels clearly reflected psoriatic skin involvement although it did not correlate with joint disease.

Measurement of serum hyaluronic acid in patients with chronic hepatitis C and its relationship to liver histology. Consensus Interferon Study Group.

Chronic hepatitis C is a slowly progressing inflammatory disease of the liver that can lead to cirrhosis and its complications. Assessment of liver damage in hepatitis C has been primarily via histological evaluation. Liver biopsy, while useful in determining the extent of liver damage, has associated costs and places patients at a small but finite risk of bleeding. Studies in small patient populations have identified serum markers shown to correlate with liver histology, including procollogen III peptide and hyaluronic acid (HA). To determine whether serum HA was a reliable predictor of cirrhosis and fibrosis, we examined serum HA concentrations from 486 chronic Hepatitis C virus (HCV) patients. Patients were anti-HCV and HCV RNA positive, with elevated alanine aminotransferase values and underwent a liver biopsy. Sera were obtained at the baseline for HA using radioimmunoassay methodology. Patients with cirrhosis had significantly higher serum HA concentrations compared with non-cirrhotic patients (382+/-31 vs 110+/-9 microg/L respectively, P< 0.001). Patients with fibrosis had significantly higher mean serum HA concentrations (179+/-11 microg/L) compared with patients without fibrosis (62+/-20 microg/L; P< 0.001). The correlation between HA concentration and the components of the Knodell histological activity index score revealed no strong associations with the exception of fibrosis, which showed moderate correlation (R=0.5421, P<0.001). The clinical value of HA measurement appears to be its ability to exclude cirrhosis. A HA value of < 60 microg/L excluded the presence of cirrhosis or significant fibrosis with a predictive value of 99 and 93%, respectively. Serum HA measurement may be clinically useful to non-invasively assess the degree of fibrosis and cirrhosis. Further prospective studies are warranted to determine the clinical utility of HA as a non-invasive marker of liver fibrosis.

INCREASED URINARY HYALURONIC ACID AND INTERSTITIAL CYSTITIS

Purpose We compared urinary levels of hyaluronic acid in patients who met the National Institute for Diabetes, and Digestive and Kidney Diseases criteria for interstitial cystitis and in age matched healthy female controls. Materials and Methods Urinary hyaluronic acid was measured by solid phase radiometric assay using hyaluronic acid binding protein. Hyaluronic acid and symptom scores were compared in interstitial cystitis patients who gave multiple urine samples during treatment. Since hyaluronic acid changed with treatment in some patients, 17 samples from untreated interstitial cystitis patients were selected and compared with 17 control samples. Results Mean plus or minus standard deviation urinary hyaluronic acid concentrations were similar in the 2 groups (interstitial cystitis group 574 ± 496, controls 512 ± 324 ng./ml., p = 0.77). When normalized to creatinine urinary hyaluronic acid was significantly higher in interstitial cystitis patients (interstitial cystitis group 674 ± 220, controls 446 ± 220 ng./mg. creatinine, p = 0.0019). Urinary creatinine concentrations did not differ significantly (interstitial cystitis group 842 ± 715, controls 1,162 ± 516 mg./l., p = 0.12). Conclusions Urinary hyaluronic acid was higher in interstitial cystitis patients than healthy controls. Since bladder hyaluronic acid is below the epithelium, this finding may indicate leakage across the epithelium into the urine in interstitial cystitis patients.

Intravesical Hyaluronic Acid in the Treatment of Refractory Interstitial Cystitis

Purpose Based on the assumption that interstitial cystitis results from a defective mucous lining of the bladder epithelium, we investigated the activity of hyaluronic acid in the treatment of this disease. Hyaluronic acid is an important glycosaminoglycan present in all connective tissues, including the glycosaminoglycan layer of the vesical mucosa. It exhibits a variety of pharmacological properties that enhance its appeal for the therapy of interstitial cystitis. Materials and Methods A total of 25 patients with characteristic findings of interstitial cystitis refractory to other medical treatments participated in a trial of intravesical hyaluronic acid at a dose of 40 mg. weekly for 4 weeks and then monthly. Response to therapy was evaluated by symptom score, voiding diaries and visual analog scales. Results An initial 56 percent positive (complete plus partial) response rate at week 4 increased to 71 percent by week 12 and response was maintained until week 20. Beyond week 24 there was a moderate decrease in the effectiveness of the medication. There was no significant toxicity attributable to hyaluronic acid in the bladder. Conclusions The response of patients with refractory interstitial cystitis to the intravesical administration of hyaluronic acid was gratifying. In the past many therapies for interstitial cystitis which were initially considered promising failed the test of a controlled study. Such a study to determine the activity of hyaluronic acid in patients with interstitial cystitis is currently under way.

慢性関節リウマチとヒアルロン酸 第１６回日本炎症学会ランチョンセミナーから

Rheumatoid arthritis (RA) is a deforming, destructive arthritis of unknown etiology. Although the true cause of RA is unknown, pathophysiology of joint destruction has been extensively studied for the past few years. The most pertinent pathological features of affected joint are neo-vascularization, cell infiltration, and thickening of synovial membrane, which all lead to joint destruction by eliciting abnormal immune reactions.The abnormal immune reactions include production of various cytokines from cells in synovial membrane, and upregulated expression of adhesions molecules. CD 44 is ubiquitously expressed on cells in synovial membrane and is considered to be adhesion molecule, since it binds to hyaluronic acid which is present abundantly in articular matrix. Thus adhesion molecules act not only for transmigration of lymphocytes into synovial membrane but also for perpetuation of rheumatoid inflammation by holding inflammatory cells in articular matrix.Hyaluronic acid has been used for treatment in patients with osteoarthritis. Recently, the double bind multi-center clinical trial clearly showed that the significant efficacy of hyaluronic acid in patients with RA. The basic and clinical profile of hyaluronic acid as an alternative therapeutic adjunct in patients with RA is briefly reviewed.

Serum hyaluronic acid and laminin in children with chronic hepatitis B

Objective: To evaluate whether hyaluronic acid and laminin PI serum concentrations reflect the presence of liver fibrosis and/or cirrhosis in children with chronic hepatitis B infection. Design and patients: Serum concentrations of hyaluronic acid and laminin PI were correlated with several clinical, biochemical and histological parameters in 54 children (mean age, 7.7 years) with chronic hepatitis B, in 13 healthy carriere, and in 18 age- and sex-matched controls. Results: Levels of hyaluronic acid in patients with cirrhosis were significantly higlher than in controls and patients without cirrhosis. Concentrations above 100μgfl were observed only in children with cirrhosis, but sensitivity was low. Serum concentrations of laminin PI in patients with cirrhosis were significantly higher than in controls, but overlapped with values in the other patient subgroups. The extent of fibrosis, assessed by computerized histomorphometry, correlated significantly with serum concentrations of both hyaluronic acid and laminin PI; no cut-off value discriminated between small and large lesions. The concentrations of hyaluronic acid and laminin P1 were highest in patients with marked capillarization of liver sinusoids at electron microscopy and/or thickened lesser omentum at sonography, two alleged features of portal hypertension. Conclusion: The correlation between serum concentrations of hyaluronic acid and laminin PI and the presence of liver fibrosis and/or cirrhosis in children with chronic hepatitis B virus infection was statistically significant but clinically limited.

Hyaluronic acid. A review of its pharmacology and use as a surgical aid in ophthalmology, and its therapeutic potential in joint disease and wound healing.

Hyaluronic acid is a naturally occurring polysaccharide with distinct physicochemical properties which underlie its application as a viscoelastic tool in ophthalmological surgery. In cataract surgery the role of hyaluronic acid in facilitating procedures and protecting the corneal endothelium is well established. Some benefit has also been gained with the use of hyaluronic acid in penetrating keratoplasty, trabeculectomy, retinal reattachment and trauma surgery, although its efficacy in these indications is less well-defined in the published literature. In addition to its lubricating and cushioning properties, demonstration of some in vitro anti-inflammatory activity and a possible disease-modifying effect for hyaluronic acid in animals has prompted its investigation as a treatment in osteoarthritis and, to a much lesser extent, in rheumatoid arthritis. Hyaluronic acid 20 mg, as weekly intra-articular injections for 3 to 7 weeks, improved knee pain and joint motion in patients with osteoarthritis. Although this occurred to a greater degree than with placebo in most comparisons, the effects of hyaluronic acid was similar to those of placebo in the largest trial. In the few available comparisons with other agents, hyaluronic acid appeared equivalent to methylprednisolone 40 mg (for 3 weeks) and to a single injection of triamcinolone 40 mg. Hyaluronic acid was distinguished from other therapies by providing a sustained effect after treatment discontinuation. Together with its very good tolerability profile, these properties justify further study of hyaluronic acid in patients with osteoarthritis. Some limited evidence of improvement in patients with rheumatoid arthritis, and a possible healing effect of hyaluronic acid on tympanic membrane perforations, represent additional areas of interest for future investigation. In summary, hyaluronic acid is a well-established adjunct to cataract surgery and may prove to be a promising option in the treatment of patients with osteoarthritis. Its very good tolerability provides further impetus for examination of its potential role in an extended scope of arthritic and ophthalmological indications, and in wound healing.

Serum hyaluronic acid in patients with disseminated neoplasm.

Hyaluronic acid concentrations were measured by a laser nephelometric assay in serum samples from 50 patients with advanced disseminated neoplasm and 50 healthy controls matched for age and sex. The identity of hyaluronic acid was confirmed by a combination of electrophoretic and enzymatic techniques. The mean serum hyaluronic acid concentration for the control group was 1.09 mg/l, with a range of 0-4 mg/l. The mean concentration for patients with neoplastic disease was 10.38 mg/l, with a range of 0-100 mg/l. Sixty two per cent of the patients with disseminated neoplasm had serum hyaluronic acid concentrations above the control range. There was no correlation between the increased concentration of hyaluronic acid and tumour type, serum bilirubin, serum alkaline phosphatase, or serum urea concentrations. There was a higher incidence of hypercalcaemia in patients with increased hyaluronic acid concentrations, but the correlation between hyaluronic acid and calcium concentrations was not significant. In view of the possible role of hyaluronic acid in cellular differentiation and morphogenesis the finding of increased hyaluronic acid concentrations in patients with advanced neoplastic disease may be of fundamental importance in cancer biology.