Biomedical subjects

J S Johansen

Publications and source records attributed to J S Johansen.

At least 19 recordsLinked to original sources

PubMed2006

YKL-40, a biomarker of inflammation, is elevated in patients with type 2 diabetes and is related to insulin resistance.

OBJECTIVE AND DESIGN: YKL-40 participates in inflammatory states and vascular processes, which implies that comparison can be made with other inflammatory markers associated with insulin resistance and type 2 diabetes (T2D). In the present study levels of plasma YKL-40 and serum hsCRP were evaluated in patients with T2D. MATERIALS AND METHODS: Patients with T2D and age-matched healthy controls participated in the study. Insulin resistance was estimated using HOMA-IR model. Biochemical parameters were measured in venous blood after a 10 h fast. RESULTS: Patients with T2D were insulin resistant (p<0.001) and had raised levels of plasma YKL-40 (p<0.001) and serum hsCRP (p<0.001). YKL-40 was correlated with HOMA-IR (r=0.23, p<0.01), NEFA (r=0.32, p<0.001) and triglycerides (r=0.24, p<0.05). YKL-40 and hsCRP were not correlated (r=0.17, p=NS). All participants with hsCRP<1 mg/l had higher insulin sensitivity (p<0.05 and p<0.01, respectively). HsCRP were predicted by HOMA-IR and BMI (r2=0.48, p<0.01). Plasma YKL-40 was predicted by HOMA-IR and triglycerides (r2=0.27, p<0.01). CONCLUSIONS: YKL-40 and hsCRP are elevated in patients with T2D and are related to insulin resistance. No correlation was found between YKL-40 and hsCRP indicating that increased levels of YKL-40 occur independently from elevated plasma hsCRP.

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PubMed2005

Magnetic resonance imaging for accelerated assessment of drug effect and prediction of subsequent radiographic progression in rheumatoid arthritis: a study of patients receiving combined anakinra and methotrexate treatment.

OBJECTIVES: By MRI to assess the efficacy of addition of anakinra for controlling synovitis and stopping erosive progression in patients with clinically active RA despite receiving methotrexate, and to determine the predictive value of MRI for subsequent radiographic erosive progression. METHODS: 100 mg anakinra subcutaneously/day was added to the treatment of 17 patients with clinically active RA despite methotrexate. MRI of the non-dominant wrist and 2nd-5th MCP joints (OMERACT evaluation) was performed at weeks 0, 12, and 36, and radiography of both hands and wrists (modified Sharp evaluation) at weeks 0 and 36. RESULTS: MRI synovitis scores were not significantly changed. Radiography of both hands and wrists after 36 weeks showed erosive progression in 11 patients, and MRI after 12 weeks in 10 patients. Nine of 10 patients with MRI progression at 12 weeks had radiographic progression at 36 weeks. Baseline MRI synovitis and erosion scores, but no clinical/biochemical parameters, correlated significantly with subsequent erosive progression. CONCLUSION: Addition of anakinra did not significantly reduce MRI signs of synovitis, and most patients had progressive joint destruction. Baseline MRI findings predicted subsequent radiographic erosive progression. Unilateral wrist and MCP joint MRI after 12 weeks had a similar sensitivity for detection of erosive progression as bilateral hand and wrist radiography after 36 weeks.

Adult↗

PubMed2005

Circulating YKL-40 levels during human endotoxaemia.

YKL-40 is secreted by macrophages and neutrophils and patients with bacterial infections have elevated circulating YKL-40. The aim was to evaluate changes in plasma YKL-40 (determined by enzyme-linked immunosorbent assay (ELISA) at 0, 2, 4, 8, 24 and 32 h) in eight healthy volunteers after injection with Esherichia coli endotoxin or saline. Plasma YKL-40 increased after endotoxin injection from 31 microg/l (range 19-39 microg/l) to a maximum of 159 microg/l (61-552 microg/l, P < 0.01) at 24 h. The finding that plasma YKL-40 increased after endotoxin injection compared with saline (P < 0.001) suggests that YKL-40 has a functional role in infections.

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PubMed2003

Serum YKL-40, a potential new marker of disease activity in patients with inflammatory bowel disease.

BACKGROUND: YKL-40 is secreted by macrophages and neutrophils and is a growth factor for vascular endothelial cells and fibroblasts. Elevated serum concentrations of YKL-40 are found in patients with diseases characterized by inflammation or ongoing fibrosis. The aim of this study was to seek association between serum YKL-40 in patients with ulcerative colitis (UC) and Crohn disease (CD) and clinical disease activity. METHODS: One-hundred-and-sixty-four patients with UC and 173 patients with CD were studied. The Simple Clinical Colitis Activity Index (SCCAI) and the Harvey-Bradshaw (H-B) score were used to assess disease activity. Serum YKL-40 (determined by ELISA) was related to C-reactive protein (CRP) and disease activity. RESULTS: In patients with UC, the median serum YKL-40 rose with increasing disease activity, and patients with severe active disease had higher serum YKL-40 (median 59 microg/L (95% CI: 26-258 microg/L), P < 0.001) than patients with inactive UC (33 microg/L (19-163)) and age-matched controls (43 microg/L (20-124)). Patients with severe active CD had higher serum YKL-40 (59 microg/L (21-654), P < 0.001) than age-matched controls, but not higher than inactive CD patients (43 microg/L (17-306)). Serum YKL-40 was elevated in 41% of the patients with severe UC, in 10% with inactive UC, in 46% with severe CD and in 30% with inactive CD. Serum YKL-40 correlated with SCCAI in UC patients but not with H-B score in CD patients. In both patient groups, low correlations were found between serum YKL-40 and CRP, albumin and leucocytes. CONCLUSIONS: Serum YKL-40 is elevated in patients with active IBD and may be complementary to inflammatory markers and clinical characteristics in the assessment of disease activity.

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PubMed2003

Effect of antiviral therapy on markers of fibrogenesis in patients with chronic hepatitis C.

BACKGROUND: The possible markers of liver fibrosis (plasma YKL-40, PIIINP, MMP-2 and TIMP-1) were measured at the start (t0) and end of treatment (t12) with alpha-interferon and ribavirin and repeated at 6-months follow-up (t18) in 51 patients with chronic hepatitis C. METHODS: We evaluated 1) whether treatment response is reflected by a decrease in these markers during antiviral therapy; 2) whether these markers reflect the activity of the disease; and 3) whether these markers could be used as predictors of the treatment response. RESULTS: Baseline plasma YKL-40, MMP-2, PIIINP and TIMP-1 were significantly increased in patients compared to normal controls. In responders (n = 30), plasma YKL-40 (P < 0.05), MMP-2 (P < 0.05) and TIMP-1 (P < 0.001) decreased significantly at t18, and no changes were observed at t12. Plasma PIIINP was unchanged in responders. In non-responders (n = 19), plasma MMP-2 (P < 0.01) and TIMP-1 (P < 0.01) decreased significantly at t18, whereas plasma YKL-40 and PIIINP were unchanged. The markers were significantly correlated at baseline (P < 0.001). Plasma PIIINP at baseline could predict treatment response (P = 0.01). CONCLUSIONS: Response to antiviral treatment is associated with a decrease in the fibrogenetic markers, but the markers do not reflect the biochemical disease activity during treatment. Baseline plasma PIIINP was the only marker predicting treatment response.

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PubMed2001

Regulation of YKL-40 production by human articular chondrocytes.

OBJECTIVE: YKL-40 (human cartilage glycoprotein 39) is one of the most abundant proteins secreted by cultured chondrocytes. The objectives of the present study were to identify regulators of YKL-40 production in cartilage and chondrocytes and to map the localization of YKL-40 in chondrocytes. METHODS: Human articular chondrocytes and cartilage explants (obtained from subjects at autopsy, from a tissue bank, and from osteoarthritis [OA] patients undergoing total joint replacement surgery) were stimulated with cytokines, growth factors, and other agents. YKL-40 expression was analyzed by Northern blot and polymerase chain reaction. YKL-40 secretion into the media was determined by enzyme-linked immunosorbent assay. RESULTS: YKL-40 production increased to very high levels during the early phase of chondrocyte monolayer culture and in normal cartilage explant cultures as a response to tissue injury. Spontaneous YKL-40 release was higher in OA than in normal cartilage explant cultures. In chondrocyte monolayer cultures, interleukin-1beta (IL-1beta) and transforming growth factor beta (TGFbeta) decreased the levels of secreted YKL-40, and this was associated with a reduction in YKL-40 messenger RNA levels. IL-1beta, but not TGFbeta, reduced YKL-40 production in cartilage explant cultures. Media from explants treated with cycloheximide had no detectable YKL-40, suggesting that the released protein was newly synthesized. Immunofluorescence microscopy showed YKL-40 staining in the Golgi system of the chondrocytes, but YKL-40 could not be detected in the extracellular matrix. CONCLUSION: The spontaneous increase in the production of YKL-40 in the early phase of culture appears to represent a cellular response to changes in the extracellular matrix environment. This, coupled with the profound suppressive effects of IL-1beta and TGFbeta on YKL-40 production, identifies a novel regulatory pattern for this major chondrocyte-derived protein.

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PubMed2001

Accumulation of the neutrophil-derived protein YKL-40 during storage of various blood components.

OBJECTIVE AND DESIGN: Post transfusion infectious complications associated with allogeneic blood components may depend on storage time and may be related to extracellular accumulation of bioactive substances during storage. YKL-40 is a glycoprotein located in the specific granules of the neutrophils. While exocytosed it may play a role in inflammation and remodelling of the extracellular matrix. We studied the potential accumulation of YKL-40 in blood components during storage. METHODS: Using a RIA method extracellular accumulation of YKL-40 was determined in supernatants from whole blood, plasma-reduced whole blood, buffy-coat-depleted SAGM (saline-adenine-glucose-mannitol) blood, whole blood leukocyte depleted by prestorage filtration, and whole blood leukocyte depleted by bedside filtration. The blood was donated by volunteer, healthy blood donors, and stored under standard blood bank conditions for 35 days. RESULTS: Extracellular accumulation of YKL-40 increased significantly in a time-dependent manner during storage for 35 days of non-filtered whole blood, plasma-reduced whole blood, and SAGM blood, respectively. Prestorage leukocyte depletion of whole blood prevented extracellular YKL-40 accumulation, while YKL-40 accumulation was not reduced by bedside leukocyte depletion. CONCLUSION: YKL-40 appears to accumulate extracellularly in a time-dependent manner in standard erythrocyte components. Prestorage leukocyte depletion by filtration of whole blood may be an effective procedure to prevent extracellular YKL-40 accumulation during storage of erythrocyte components.

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PubMed2001

Studies on YKL-40 in knee joints of patients with rheumatoid arthritis and osteoarthritis. Involvement of YKL-40 in the joint pathology.

OBJECTIVE: The presence of YKL-40 (human cartilage glycoprotein 39) in synovium, cartilage and synovial fluid (SF) from knee joints of patients with rheumatoid arthritis and osteoarthritis (OA) were related to histopathological changes in synovium and cartilage and to serum YKL-40 and other biochemical markers. METHODS: The localization of YKL-40 in synovium and cartilage was determined by immunohistochemistry. Synovial inflammation was estimated histologically and by magnetic resonance imaging (MRI). Biochemical markers of inflammation, neutrophil activation and cartilage metabolism were analysed. YKL-40 concentrations in serum and SF were determined by RIA and ELISA. RESULTS: In the synovium YKL-40 positive cells were found in lining and stromal cells (macrophages) and the number of YKL-40 positive cells was related to the degree of synovitis. In arthritic cartilage, YKL-40 was located to chondrocytes. YKL-40 levels in SF were higher in RA patients with moderate/severe or none/slight synovitis of the knee joint compared to OA patients with moderate/severe or none/slight synovitis. SF YKL-40 correlated with the synovial membrane and the joint effusion volumes determined by magnetic resonance imaging (MRI) and with other biochemical markers of intercellular matrix metabolism. SF YKL-40 was higher than serum YKL-40, and a relationship existed between the YKL-40 levels in SF and serum. Intraarticular glucocorticoid injection was followed by clinical remission and a decrease in serum YKL-40, which increased again at clinical relapse. CONCLUSIONS: YKL-40 in SF is derived from cells in the inflamed synovium, chondrocytes and SF neutrophils. Joint derived YKL-40 influences serum YKL-40. YKL-40 may be involved in the pathophysiology of the arthritic processes and reflect local disease activity.

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PubMed2001

Serum YKL-40 concentrations in patients with early rheumatoid arthritis: relation to joint destruction.

OBJECTIVE: YKL-40 is a secretory glycoprotein of chondrocytes, synovial cells, macrophages, and neutrophils. The aims were to determine serum YKL-40 in patients with early rheumatoid arthritis (RA) and seek associations with early joint erosions. METHODS: YKL-40 was measured by ELISA in serum samples collected every three month for 36 months from patients with early RA. The patients were treated with DMARDs and some were allocated to additional prednisolone. RESULTS: Serum YKL-40 was higher in RA patients compared with controls (98 vs. 42 microg/l, p<0.001). The mean serum YKL-40 during the study correlated with the progression in Larsen score (Pearson's test: p=0.004). Patients with a persistently high serum YKL-40 had larger progression in Larsen score compared with patients with normal serum YKL-40 (median progression: 7 vs. 0, p=0.003). CONCLUSION: These data suggest that elevated serum YKL-40 is related to progression in joint destruction in early RA patients.

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PubMed2000

Serum YKL-40 is increased in patients with hepatic fibrosis.

BACKGROUND/AIMS: YKL-40, a mammalian member of the chitinase family, is a lectin that binds heparin and chitin. The function of YKL-40 is unknown, but it may function in tissue remodelling. The aims of this study were to assess the level of circulating YKL-40 in patients with various kinds and degree of chronic liver disease and its possible relation to liver fibrosis. METHODS: Serum YKL-40 levels were determined by radioimmunoassay in 129 patients with suspected liver disease and related to histological findings and immunohistochemical staining of YKL-40 in a liver biopsy taken simultaneously with the blood sample. RESULTS: The median serum YKL-40 was highest in patients with alcoholic cirrhosis (532 microg/l), in particular in patients with additional alcoholic hepatitis (740 microg/l). Patients with alcoholic cirrhosis, post-hepatitic cirrhosis (425 microg/l) and non-cirrhotic fibrosis (330 microg/l) had significantly higher serum YKL-40 than normal subjects (102 microg/l), patients with fatty liver (195 microg/l) or patients with viral hepatitis without fibrosis (174 microg/l). Serum YKL-40 was significantly (p<0.001) related to the degree of liver fibrosis with the highest levels in patients with moderate (466 microg/l) to severe (676 microg/l) fibrosis. Serum YKL-40 was also increased (p=0.018) in patients with slight fibrosis (270 microg/l) compared to patients without fibrosis. Immunohistochemical analysis demonstrated positive staining for YKL-40 antigen in areas with fibrosis, particularly areas with active fibrogenesis. YKL-40 staining was never found in hepatocytes. CONCLUSIONS: Our study indicates that the increased serum YKL-40 in patients with liver disease of various degree and aetiology seems to reflect fibrosis and fibrogenesis.

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PubMed2000

Stability of YKL-40 concentration in blood samples.

The stability of YKL-40, a mammalian member of the family of 18 glycosylhydrolases, in blood samples handled under different temperatures and different time intervals before centrifugation was studied in paired serum and plasma samples from 25 healthy premenopausal Danish women. Significant elevations of YKL-40 were found in 8 paired serum samples left on the clot for more than 3 h at room temperature compared to paired serum samples left on the clot for 3 h or less. Significant elevations of YKL-40 were found in 8 paired plasma (EDTA) samples left on the blood cells for more than 8 h at room temperature compared to paired plasma (EDTA) samples left on the blood cells for 8 h or less. No elevations were found in YKL-40 levels in serum samples left on the clot at 4 degrees C for 24 h or in plasma (EDTA) samples left on the blood cells for 72 h before centrifugation. Significantly lower concentrations of YKL-40 were measured in plasma (EDTA) compared with paired serum samples with a serum/plasma ratio of 1.4 in samples left on the clot or on blood cells at 4 degrees C for up to 24 h. Repetitive freezing and thawing had no significant effect on the measured YKL-40 concentrations. In conclusion, we have shown that YKL-40 is very dependent on the handling procedures. All the blood samples must be processed into plasma (EDTA) within 8 h at room temperature or into serum in less than 3 h at room temperature. If this is not possible, the blood samples must be stored at 4 degrees C until processed.

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PubMed1999

YKL-40 in giant cells and macrophages from patients with giant cell arteritis.

OBJECTIVE: YKL-40, a mammalian member of the family 18 glycosyl hydrolases, is secreted by activated macrophages at a late stage of differentiation. Macrophages are present in inflammation of the arterial wall and are thought to participate in the pathogenesis of giant cell arteritis (GCA). The aim of this study was to evaluate whether macrophages and giant cells of patients with GCA produce YKL-40, and whether serum YKL-40 concentrations are elevated in these patients. METHODS: Serum YKL-40 was determined by radioimmunoassay in 19 patients with GCA and 8 patients with polymyalgia rheumatica (PMR) who were followed up prospectively during 1 year of treatment with prednisolone. Immunohistochemical staining for YKL-40 was performed in temporal artery biopsy samples that were obtained before treatment. RESULTS: In the arteritic vessels of patients with GCA, positive staining for the YKL-40 antigen was found in CD68+ giant cells and mononuclear cells located in the media. Macrophages located in the adventitia and intima were negative for YKL-40. At the time of diagnosis, patients with GCA had an increased median serum level of YKL-40 (256 microg/liter; P<0.01) compared with healthy age-matched controls (median 118 microg/liter), and the serum level of YKL-40 decreased to normal levels during prednisolone treatment (-38% after 1 month; P<0.001). Most patients with PMR had normal serum YKL-40 levels (median 158 microg/liter) and had no changes in the serum YKL-40 levels during prednisolone treatment. The observed changes in serum YKL-40 did not always parallel the changes in serum C-reactive protein levels and erythrocyte sedimentation rate during the 1-year study period. CONCLUSION: YKL-40 is found in CD68+ giant cells and mononuclear cells in the media of arteritic vessels of patients with GCA, and the concentration of serum YKL-40 may reflect the local activity of these cells in the inflamed artery.

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PubMed1999

Pulmonary damage after modest exposure to zinc chloride smoke.

Thirteen soldiers (11 men and two women) were exposed to zinc chloride smoke (ZCS) during a combat exercise. Even though their initial symptoms were modest, a prolonged follow up with lung function testing and blood samples was undertaken due to previous cases with fatal outcome after exposure to ZCS. Four weeks after exposure there were statistically significant declines from baseline values in lung diffusion capacity and total lung capacity of 16.2% and 4.3%, respectively. At the same time plasma levels of fibrinogen and zinc were significantly elevated, though mainly within the normal range. All variables showed a tendency towards normalization at follow up 8 weeks and 6 months after exposure. These findings indicate an unexpected quantifiable damage to lung parenchyma with a remarkable delay after modest exposure to zinc chloride smoke despite sparse initial symptoms. Exposure to high concentrations of ZCS may induce adult respiratory distress syndrome (ARDS) after a symptom free period of up to 12 days from exposure. Even though none of the soldiers in the present study developed ARDS the assessment of lung diffusion capacity and acute phase reactants is proposed as a supplement when monitoring patients after exposure to ZCS.

Adult↗

PubMed1999

Serum YKL-40 and colorectal cancer.

YKL-40 is a mammalian member of the chitinase protein family. Although the function of YKL-40 is unknown, the pattern of its expression suggests a function in remodelling or degradation of extracellular matrix. High serum YKL-40 has been found in patients with recurrent breast cancer and has been related to short survival. In the present study we analysed YKL-40 in preoperative sera from patients with colorectal cancer and evaluated its relation to survival. Serum YKL-40 was determined by RIA in 603 patients. Survival after operation was registered, and median follow-up time was 61 months. Three hundred and forty patients died. Sixteen per cent of the patients with Dukes' A, 26% with Dukes' B, 19% with Dukes' C and 39% with Dukes' D had high serum YKL-40 levels (adjusted for age). Analysis of serum YKL-40 as a continuous variable showed an association between increased serum YKL-40 and short survival (P < 0.0001). Patients with high preoperative serum YKL-40 concentration had significantly shorter survival than patients with normal YKL-40 (HR = 1.7; 95% CI: 1.3-2.1, P < 0.0001). Multivariate Cox analysis including serum YKL-40, serum CEA, Dukes' stage, age and gender showed that high YKL-40 was an independent prognostic variable for short survival (HR = 1.4; 95% CI: 1.1-1.8, P = 0.007). These results suggest that YKL-40 may play an important role in tumour invasion.

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PubMed1999

The distribution of YKL-40 in osteoarthritic and normal human articular cartilage.

YKL-40, also called human cartilage glycoprotein-39, is a major secretory protein of human chondrocytes in cell culture. YKL-40 mRNA is expressed by cartilage from patients with rheumatoid arthritis, but is not detectable in normal human cartilage. The aim was to investigate the distribution of YKL-40 in osteoarthritic (n=9) and macroscopically normal (n=5) human articular cartilage, collected from 12 pre-selected areas of the femoral head, to discover a potential role for YKL-40 in cartilage remodelling in osteoarthritis. Immunohistochemical analysis showed that YKL-40 staining was found in chondrocytes of osteoarthritic cartilage mainly in the superficial and middle zone of the cartilage rather than the deep zone. There was a tendency for high number of YKL-40 positive chondrocytes in areas of the femoral head with a considerable biomechanical load. The number of chondrocytes with a positive staining for YKL-40 was in general low in normal cartilage. The present findings, together with previous observations, suggests that YKL-40 may be of importance in cartilage remodelling/degradation of osteoarthritic joints.

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PubMed1999

YKL-40, a matrix protein of specific granules in neutrophils, is elevated in serum of patients with community-acquired pneumonia requiring hospitalization.

The serum concentration of YKL-40, a matrix protein of specific granules in neutrophils, was determined by RIA in 90 patients hospitalized with pneumonia of suspected bacterial origin. Of these, 64 were followed prospectively during antibiotic treatment with blood samples taken on day 0 (on admission and the start of treatment) and on days 1, 3, 5, 7, 10, and 21. Serum YKL-40 at admission was increased in patients with Streptococcus pneumoniae pneumonia (median, 893 microgram/L; 95% confidence interval [CI], 704-1560), compared with healthy subjects (median, 102 microgram/L; 95% CI, 64-247 microgram/L; P<.001) and in patients with pneumonia of unknown etiology (median, 448 microgram/L; 95% CI, 334-700; P<.05). Peak YKL-40 serum values were observed on day 1 and thereafter declined steeply to almost normal by day 3. During the first 10 days, there was a close relation between serum YKL-40 and markers of specific granules of neutrophils (serum lactoferrin and neutrophil gelatinase-associated lipocalin), which suggests that serum YKL-40 reflects exocytosis of specific granules of neutrophils in persons with acute bacterial pneumonia.

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PubMed1999

Serum YKL-40 concentrations in patients with rheumatoid arthritis: relation to disease activity.

OBJECTIVE: YKL-40, also called human cartilage glycoprotein-39, is secreted by chondrocytes, synovial cells, macrophages and neutrophils. Studies have shown that YKL-40 is an autoantigen in rheumatoid arthritis (RA). We evaluated whether serum YKL-40 was related to disease activity in patients with RA. METHODS: Serum YKL-40 was determined by radioimmunoassay in 156 patients with RA during a 1 yr longitudinal study. RESULTS: Serum YKL-40 was increased in 54% of the patients with clinically active disease. Patients with clinically active disease initially who became inactive after 12 months had a significant decrease in serum YKL-40 (-30%, P < 0.002) and patients who changed from inactive to active disease had an increase in serum YKL-40. Patients who remained active had unchanged serum YKL-40 during the study. Serum YKL-40 decreased rapidly (-24% after 7 days, P < 0.01) during prednisolone therapy, and more slowly in patients treated with methotrexate only (-15% after 60 days, P < 0.01). Patients with early RA (disease duration < 3 yr, n = 50) and a persistently elevated serum YKL-40 were at risk of radiological disease progression as determined by Larsen score. CONCLUSION: Serum YKL-40 varies according to disease activity in RA, but provides in some respect information different from conventional markers. Our previous studies are consistent with a local release of YKL-40 in the arthritic joint followed by a secondary increase in serum YKL-40. YKL-40 may prove to be a new tool for the study of disease activity and pathophysiology of RA.

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PubMed1997

Plasma YKL-40: a new potential marker of fibrosis in patients with alcoholic cirrhosis?

BACKGROUND: YKL-40 (human cartilage glycoprotein-39, or 38-kDa heparin-binding glycoprotein) is a mammalian member of a protein family that includes bacterial chitinases. YKL-40 mRNA is expressed by human liver and may play a role in tissue remodelling. The aims were to assess whether circulating YKL-40 is released or extracted in the hepatosplanchnic system and to localize YKL-40 in liver tissue. METHODS: Plasma YKL-40 was determined by radioimmunoassay in 25 patients with liver diseases (alcoholic cirrhosis (n = 20), chronic active hepatitis (n = 2), cirrhosis of unknown aetiology (n = 2), and fatty liver (n = 1) and in 18 subjects with normal liver function during a haemodynamic investigation with catheterization of liver vein and the femoral artery. Immunohistochemical studies of the localization of YKL-40 in cryostal liver biopsy specimens were obtained from eight other patients with alcoholic liver disease. RESULTS: Plasma YKL-40 was significantly increased in patients with alcoholic cirrhosis (median, 523 micrograms/l; P < 0.001) compared with controls (106 micrograms/l), and plasma YKL-40 in the hepatic vein was higher (P < 0.01) than that of the artery in both the patients and controls, showing release of YKL-40 from the hepatosplanchnic area. The release rate of YKL-40 from the hepatosplanchnic area was higher in patients with liver disease than in controls (11.0 versus 2.1 micrograms/min, P < 0.05). Furthermore, the highest plasma YKL-40 levels were found in patients with a moderate or severe degree of liver fibrosis, and immunohistochemical studies showed positive staining for YKL-40 antigen in areas of the liver biopsy with fibrosis. CONCLUSIONS: The increased plasma YKL-40 in patients with alcoholic cirrhosis may reflect the remodelling of liver fibrosis.

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