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.     

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 (H=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 cryostat 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 μg/l; P< 0.001) compared with controls (106μg/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 μg/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.     

Noninvasive estimation of liver fibrosis and response to interferon therapy by a serum fibrogenesis marker， YKL-40, in patients with HCV-associated liver disease

AIM: To evaluate the clinical utility of serum fibrosis markers, including YKL-40, in patients with HCV-associated liver disease. METHODS: A total of 109 patients with HCV-associated liver disease were enrolled. We measured serum type IV collagen, amino-terminal peptide of type III procollagen (PIIIP), hyaluronic acid (HA), YKL-40 levels and biochemical. Parameters by RIA or ELISA. Eighty-eight patients underwent liver biopsy, and 67 of 109 patients received interferon (IFN) therapy. We also investigated the relationship between the concentrations of serum fibrosis markers and histological fibrosis scores (METAVIR), and evaluated the changes of the levels of fibrosis markers before and after the IFN therapy. RESULTS: The increase in serum levels of all markers, particularly HA, was correlated with the progression of liver fibrosis (for type IV collagen, F= 9.076, P<0.0001; for PIIIP, F= 9.636, P<0.0001; for HA, F=13.128, P<0.0001; and for YKL-40, F= 8.016, P<0.0001). YKL-40 had strong correlation with HA (r= 0.536, P<0.0001). Based on the receiver operating curve (ROC), the ability of serum HA exceeded the abilities of other serum markers to determine fibrosis score 4 from fibrosis score 0-3 (AUC = 0.854). While YKL-40 was superior to other fibrosis markers for predicting severe fibrosis (F2-F4) from mild fibrosis (FO-F1) (YKL-40, AUC = 0.809; HA, AUC = 0.805). After IFN therapy, only YKL-40 values significantly decreased not only in the responder group, but also in the nonresponder group (P = 0.03). CONCLUSION: YKL-40 may be a useful non-invasive serum marker to estimate the degree of liver fibrosis and to evaluate the efficacy of IFN therapies in patients with HCV-associated liver disease.     

Serum levels of YKL-40 and PIIINP as prognostic markers in patients with alcoholic liver disease

BACKGROUND/AIMS: YKL-40 (growth factor) and PIIINP (N-terminal propeptide of Type III procollagen) are potential markers of liver fibrosis. The aim was to evaluate the prognostic value of serum YKL-40 and PIIINP levels in patients with alcoholic liver disease. METHODS: Three hundred and seventy patients with alcoholic liver disease were studied in a trial of malotilate with a median follow-up period of 470 days; 75 patients died; 336 patients had a liver biopsy on entry. Serum levels of YKL-40 and PIIINP were determined by radioimmunoassay (RIA). RESULTS: Serum YKL-40 and PIIINP were elevated in the patients compared to controls. Patients with steatosis or no fibrosis had the lowest serum levels of YKL-40 and PIIINP, whereas patients with alcoholic hepatitis and/or cirrhosis had the highest levels. Serum YKL-40 was associated with the presence of fibrosis, and serum PIIINP was also associated with the different grades of fibrosis. Patients with elevated serum YKL-40 or PIIINP had shorter survival than patients with normal serum levels of YKL-40 (P<0.0001) or PIIINP (P=0.044). High degree of fibrosis predicted shorter survival (P=0.004). CONCLUSIONS: Serum levels of YKL-40 and PIIINP are elevated in alcoholic patients, related to the presence of liver fibrosis and may provide prognostic information.     

Serum hyaluronate correlates with histological progression in alcoholic liver disease

OBJECTIVES: Chronic alcohol consumption may lead to the development of liver cirrhosis. Serum concentrations of hyaluronate were suggested as a predictor in chronic liver disease, but its power to distinguish between severity of fibrosis and inflammation had not been assessed. In order to evaluate hyaluronate as a marker to detect early stages of alcoholic liver disease and to establish a possible correlation with hepatic histology, serum concentrations were measured by radioimmunoassay in 87 patients with biopsy-proven fatty liver, fatty liver and mild fibrosis, fatty liver and inflammation, severe fibrosis and inflammation, and cirrhosis, and in 12 non-alcoholic control subjects. In addition, serum hyaluronate was determined in 40 non-cirrhotic alcoholic patients with either a normal serum aspartate aminotransferase (AST) or an AST elevated at least two-fold. RESULTS: Serum hyaluronate increased significantly with advanced stages of alcoholic liver disease, while levels in patients with fatty liver were elevated only slightly without reaching significance. Hyaluronate correlated well with histological stage and was highly sensitive for detecting fibrosis in general and perivenular fibrosis as an indicator of progression to cirrhosis. Hyaluronate levels were not influenced by AST levels. CONCLUSION: Serum hyaluronate is a good predictor of the presence of even moderate hepatic fibrosis in alcoholic liver disease, justifying its clinical use to assess morphological alterations of the liver in alcoholics.     

Increased serum YKL-40 in patients with pulmonary sarcoidosis--a potential marker of disease activity?

BACKGROUND: YKL-40, a growth factor for fibroblasts and vascular endothelial cells, is secreted by macrophages and neutrophils. Elevated serum YKL-40 is found in patients with diseases characterized by inflammation, tissue remodelling and ongoing fibrosis. The aim was to evaluate whether macrophages and giant cells in the granulomatous sarcoid lesions of patients with pulmonary sarcoidosis produce YKL-40 and to determine whether serum YKL-40 in these patients were associated with disease activity. METHODS: Serum YKL-40 was determined by radioimmunoassay in 27 patients with a histological diagnosis of pulmonal sarcoidosis. Immunohistochemical staining for YKL-40 antigen was performed in five biopsies with pulmonary sarcoid lesions. Serum YKL-40 was likewise measured in 173 healthy age-matched control subjects. RESULTS: Mononuclear cells/macrophages and giant cells in pulmonary sarcoid granulomas expressed YKL-40 protein. Serum YKL-40 was higher in patients with pulmonary sarcoidosis compared to controls (P<0.001) and 63% had elevated serum YKL-40. There was a positive correlation between serum YKL-40 and serum angiotensin converting enzyme (rho=0.55, P=0.0053). Patients with serum YKL-40>median value in the patient group had lower carbon monoxide diffusion capacity corrected for alveolar volume (DLCO/VA) than patients with serum YKL-40 the median value (P=0.015). Conclusions: Serum YKL-40 may be a novel biomarker of sarcoid disease activity and ongoing fibrosis in patients with pulmonary sarcoidosis.     

Serum levels of YKL-40 increases in patients with acute myocardial infarction

OBJECTIVES: YKL-40 is secreted by macrophages, including those in atherosclerotic plaques, neutrophils, and vascular smooth muscle cells. Circulating YKL-40 is elevated in patients with inflammation and increased tissue remodeling. The aim was to examine the sequential changes in serum YKL-40 in patients with acute myocardial infarction (AMI), with and without thrombolytic therapy, as compared with patients with stable coronary artery disease (CAD). METHODS: YKL-40 was measured by radioimmunoassay in serum from 63 patients. A total of 47 patients had their first AMI [30 with ST segment elevation myocardial infarction (STEMI) were thrombolyzed, 17 with non-STEMI were not thrombolyzed] and 16 patients had CAD. RESULTS: Serum YKL-40 at the time of admission was higher in patients with AMI (median: 156 microg/l, range: 40-3000 microg/l) than in patients with CAD (median: 106 microg/l, range: 54-300 microg/l, P=0.048) and healthy participants (median: 102 microg/l, range: 38-514 microg/l, P<0.001). No difference in serum YKL-40 between CAD patients and healthy participants (P=0.89) was observed. No difference in serum YKL-40 between the AMI patients with or without ST-elevations (P=0.12) was observed. The maximum serum YKL-40 during the first 24 h after admission was higher in thrombolyzed STEMI patients than in the nonthrombolyzed, non-STEMI patients (P=0.01) and the CAD patients (P<0.0001). Serum YKL-40 declined consistently from the maximum value just after the AMI and during follow-up. Serum YKL-40 at 90, 180, and 360 days after AMI were significantly higher in nonthrombolyzed than in thrombolyzed patients (P=0.004, P=0.008, P=0.017, respectively). CONCLUSION: These results demonstrated that serum concentrations of YKL-40 are greatly increased in AMI patients with and without thrombolytic therapy.     

High serum levels of YKL-40 in patients with systemic sclerosis are associated with pulmonary involvement

OBJECTIVES: YKL-40, a growth factor of connective tissue cells, is elevated in sera from patients with diseases characterized by inflammation, tissue remodelling, or fibrosis. The aim of the study was to determine serum YKL-40 levels in patients with systemic sclerosis (SSc) and to explore any possible clinical and prognostic associations. METHODS: YKL-40 was measured in sera from 88 patients with SSc (26 with diffuse and 62 with limited skin involvement) and in sera from 88 matched healthy controls. Immunohistochemical staining for YKL-40 antigen was performed in a biopsy from a patient with pulmonary SSc. RESULTS: Serum YKL-40 levels of the SSc patients were significantly higher than those of the controls (p<0.00001). Patients with pulmonary fibrosis by chest X-ray, obstructive ventilatory pattern, reduced diffusing capacity (DLco), and digital joint deformity due to skin retraction had significantly higher serum YKL-40 compared with patients without these findings. Patients with elevated serum YKL-40 had shorter survival times than patients with normal serum YKL-40 (p = 0.0005), although this was not independent of age and pulmonary function. YKL-40 protein expression was found in inflammatory cells in fibrosing pulmonary tissue from a patient with SSc. CONCLUSIONS: Serum YKL-40 is elevated in patients with SSc with pulmonary involvement.     

Evaluation of serum biomarkers of fibrosis and injury in Egyptian patients with chronic hepatitis C

BACKGROUND/AIMS: We evaluated whether surrogate serum biomarkers for liver injury are comparable to liver biopsy in Egyptian patients with hepatitis C virus (HCV) infection. SUBJECTS: Two hundred and twenty Egyptian patients, 91% infected with genotype-4 HCV, undergoing liver biopsy during evaluation for interferon/ribavirin therapy. METHODS: Liver biopsy scored by the Ishak method was compared to biochemical tests, platelet count and two fibrosis biomarkers: hyaluronic acid (HA) and YKL-40. Univariate and logistic regression analyses determined independent predictors of fibrotic, inflammatory, and fatty changes. Biomarkers were evaluated for ability to differentiate between severe fibrosis/cirrhosis and no/mild fibrosis. RESULTS: Although increasing age, HA, YKL-40, AST, reduced platelet count, and AST and HA/platelet count ratios were associated with fibrosis by univariate analysis, the other variables were not significant after controlling for HA (p=0.0001) and age (p=0.004). Although age and some biomarkers were associated with inflammation, none remained significant after controlling for fibrosis. YKL-40 (p=0.04) and aspartate aminotransferase (p=0.05) remained associated with steatosis after controlling for fibrosis. CONCLUSIONS: In Egyptians with chronic HCV, young patients with low levels of HA are at very low risk of fibrosis. This can limit the number of liver biopsies to those whose clinical findings conflict with the biomarker results.     

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.     

Serum level of YKL-40 is elevated in patients with Streptococcus pneumoniae bacteremia and is associated with the outcome of the disease

YKL40 is secreted by activated macrophages and neutrophils. Elevated serum concentrations of YKL40 are found in patients with diseases characterized by inflammation or ongoing fibrosis. The aim of this study was to evaluate serum YKL-40 levels in patients with Streptococcus pneumoniae bacteremia and to correlate these levels with clinical findings and outcomes. YKL40 was determined by ELISA and 89 patients were included in the study. Serum YKL-40 levels were significantly higher in patients with S. pneumoniae bacteremia (median 342 microg/l; range 20-20,400 microg/l) than in age-matched healthy subjects (44 microg/l; 20-184; p < 0.001). Serum YKL-40 levels were related to the severity of the infection, with significantly higher serum YKL-40 levels being observed in patients who needed hemodialysis (p < 0.001), pharmacological treatment of hypotension (p < 0.001) and mechanical ventilation (p = 0.003) compared to those in patients who did not need this supportive treatment. Nineteen patients died and these patients had significantly higher serum YKL-40 levels (980 microg/l; 88-20,400 microg/l) than those of survivors (256 microg/l; 20-9,100 microg/l; p < 0.001). Serum YKL40 level was an independent prognostic factor of survival in logistic multivariate regression analysis (p = 0.002). In conclusion, high serum levels of YKL40 indicated a poorer prognosis for patients with S. pneumoniae bacteremia.     

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.     

Serum YKL-40 predicts adverse clinical outcomes in patients with chronic heart failure

BackgroundHuman cartilage glycoprotein-39 (YKL-40), a novel inflammatory marker, is secreted into circulation by macrophages, neutrophils, chondrocytes, vascular smooth muscle cells and cancer cells. Circulating levels of YKL-40 are related to the degree of inflammation, tissue remodeling, fibrosis, and cancer progression.Methods and ResultsWe examined serum YKL-40 levels in 121 patients with chronic heart failure (CHF) and 39 control subjects. The patients were followed up to register cardiac events for a mean of 720 days. Serum YKL-40 levels were measured by sandwich enzyme-linked immunoassay. Serum YKL-40 was significantly higher in New York Heart Association (NYHA) Class III/IV patients than control subjects and NYHA Class I/II patients (P < .0001). Serum YKL-40 was also higher in patients with cardiac events than in event-free patients (P = .0023). Cutoff value of YKL-40 was determined by receiver operating characteristic curve analysis. Kaplan-Meier analysis demonstrated that high level of YKL-40 was associated with higher rates of cardiac events than low levels of YKL-40 (P = .003). The multivariate Cox hazard analysis demonstrated that serum YKL-40 level was an independent prognostic factor of cardiac events (hazard ratio 2.085, 95% confidence interval 1.233-3.499, P < .0048).ConclusionsSerum YKL-40, a new marker of inflammation, was increased in CHF, and YKL-40 detected high risk patients for adverse outcomes in CHF.     

SERUM YKL-40 LEVELS IN HEALTHY CHILDREN AND ADULTS. COMPARISON WITH SERUM AND SYNOVIAL FLUID LEVELS OF YKL-40 IN PATIENTS WITH OSTEOARTHRITIS OR TRAUMA OF THE KNEE JOINT

YKL-40 is a recently discovered human glycoprotein which isrelated in amino acid sequence to the chitinase protein family.YKL-40 is a major secretory protein of human chondrocytes andsynoviocytes, and could play a role in tissue remodelling. Theaim of the study was to establish the serum YKL-40 level innormal subjects and to evaluate serum YKL-40 as a marker forosteoarthritis. Serum YKL-40 was 80 µg/1 in healthy children(n = 476) and 102 µg/1 in healthy adults (n = 260). Noage or sex differences were found in serum YKL-40 in subjectsyounger than 70 yr, but thereafter serum YKL-40 increased significantly.Patients with late-stage osteoarthritis of the knee (n = 37)had significantly higher serum YKL-40 (1.5-fold; P < 0.01)compared to healthy age-matched subjects, whereas patients withearly-stage osteoarthritis of the knee or recent torn cruciateligaments or menisci did not have elevated serum YKL-40. Thelevel of YKL-40 in serum and synovial fluid correlated significantly,and 10-fold higher values were found in synovial fluid. YKL-40levels in serum and synovial fluid of patients with acute severesynovial inflammation were significantly higher (P < 0.05-P0.001) than those in patients with no, light or moderate synovitisof the knee joint. Furthermore, YKL-40 correlated significantly(P < 0.01) with the amino-terminal propeptide of type IIIprocollagen, but not with serum C-reactive protein. Our dataindicate that YKL-40 in synovial fluid and serum may reflecthuman articular cartilage degradation and the degree of synovialinflammation in the knee joint. KEY WORDS: Osteoarthritis, Biochemical markers     

Serum YKL-40 as a biomarker for liver fibrosis in chronic hepatitis B patients with normal and mildly elevated ALT

Purpose

YKL-40 is a chitinase-like protein expressed in multiple tissues including liver and is reported as a fibrosis marker. This study aimed to determine whether YKL-40 could serve as a diagnostic marker for the assessment of liver fibrosis in chronic hepatitis B patients with normal and mildly elevated ALT.

Methods

Six hundred and eighty-five patients with chronic hepatitis B infection were enrolled in this study from October 2013 to March 2016. All patients underwent liver biopsy and then staged based on Ishak histological system. Serum YKL-40 levels were measured by Human Magnetic Luminex Assays.

Results

Among chronic hepatitis B patients with normal and mildly elevated ALT, almost more than 30% of patients have significant liver fibrosis. Serum YKL-40 levels increased significantly in parallel with the progression of fibrosis in patients with ALT less than two times the upper limit of normal range (P?<?0.0001). Multivariate analysis revealed that serum YKL-40, hyaluronic acid, PLT, and AST were independently associated with significant fibrosis. We established a novel YKL-40-based fibrosis model for patients with ALT less than two times the upper limit of normal range (ULN). YKL-40 model was superior to APRI, FIB-4, Forns’ index, and Hui model for diagnosis of significant fibrosis in patients with ALT?<?2ULN, with AUROCs of 0.786 [95% confidence interval (CI) 0.726–0.846] in the training group, 0.831 (95%CI 0.752–0.910) in the validation group and 0.801 (95%CI 0.753–0.849) in the entire cohort.

Conclusion

Serum YKL-40 is a feasible biomarker of liver fibrosis in chronic hepatitis B patients. YKL-40 model was superior to APRI, FIB-4, Forns’ index and Hui model for diagnosis of significant fibrosis in patients with normal and mildly elevated ALT.

     

Non invasive prediction of severe fibrosis in patients with alcoholic liver disease

OBJECTIVES: The aim of this study was to assess the diagnostic accuracy of noninvasive markers of liver fibrosis in alcoholic liver disease. PATIENTS AND METHODS: Fifty-four clinical and biochemical parameters including serum fibrosis markers (hyaluronate and transforming growth factor beta1) were analyzed in 146 consecutive heavy drinkers (106 men, 40 women; mean age 49.2 years). Following liver biopsy, fibrosis was evaluated using a semi-quantitative scoring system (no fibrosis (0) to severe fibrosis (3 + )). Multivariate analysis was performed to determine the markers that were best correlated with the fibrosis score. RESULTS: Fifty-nine patients (40.4 %) had severe fibrosis (3 +) while 87 (59.6 %) had no fibrosis or moderate fibrosis (0 to 2 +). In multivariate analysis, serum hyaluronate and the prothrombin index were the best markers for the prediction of severe fibrosis. Hyaluronate and the prothrombin index had a diagnostic accuracy of 91.1 % and 89.7 %, respectively in the whole population. Finally, a significant negative correlation was found between hyaluronate and the prothrombin index (r =- 0.86, P <0.0001). CONCLUSIONS: Using only hyaluronate and the prothrombin index, 9 out of 10 alcoholic patients can be correctly classified according to the severity of liver fibrosis.     

Nonalcoholic steatohepatitis

This study reports a clinicopathological analysis of 105 patients whose liver histology showed a pattern of alcohol-like steatohepatitis. There were 32 nonalcoholic, 21 asymptomatic ambulatory, and 52 hospitalized alcoholic hepatitis patients. Female sex, obesity, and diabetes predominated in nonalcoholics. Clinical and laboratory presentation were similar in nonalcoholics and ambulatory alcoholics, but different from the hospitalized alcoholics. Histology showed an increasing degree of severity of hepatocellular damage. Mallory bodies, neutrophil and mononuclear infiltration, and pericellular and portal fibrosis from the nonalcoholics to the hospitalized alcoholics, with ambulatory alcoholics displaying an intermediate degree of severity. Steatosis and glycogenated nuclei were prevalent in the obese, diabetic nonalcoholics, of whom 47% had significant fibrosis and 8% cirrhosis, the latter present in 38% and 89% of ambulatory and hospitalized alcoholic hepatitis (P=0.0001), respectively. In asymptomatic subjects with suspected liver disease, a liver biopsy is the only way of establishing the type and severity of liver lesions.     

Progression of fibrosis in hepatitis C with and without schistosomiasis: correlation with serum markers of fibrosis

Serial liver biopsies are the gold standard by which the progression of fibrosis is evaluated. This longitudinal cohort study assessed the different rates in the progression of fibrosis using serial liver biopsies and serum fibrosis markers YKL-40 and PIIINP and the cytokines, transforming growth factor beta (TGF-beta) and tumor necrosis factor alpha (TNuF-alpha). A 10-year cohort study was performed in patients with hepatitis C virus (HCV) alone or HCV and schistosomiasis. Patients were enrolled at the time of acute HCV infection and prospectively evaluated with two liver biopsies (at entry and end of follow-up), and true rates in the progression of fibrosis were calculated per year. Serum YKL-40, N-terminal propeptide of collagen III (PIIINP), TGF-beta, and TNF-alpha were measured, as well as the expression of TGF-beta, TNF-alpha, and YKL-40 mRNA in liver tissue. A significant increase in the progression rates of fibrosis occurred in the coinfected group (0.61 +/- 0.13) compared with the HCV monoinfection group (0.1 +/- 0.06; P < .001)). The progression of fibrosis rate/year had a direct linear correlation for YKL-40 (r = 0.892, P < .001) and for PIIINP (r = 0.577, P < .01). YKL-40 showed a linear correlation with TGF-beta (r = 0.897, P < .001). Hepatic mRNA levels of YKL-40 and TGF-beta correlated with the serum levels, confirming a hepatic source for the elevated serum levels. In conclusion, serial cytokine and fibrosis markers can accurately determine the rate at which fibrosis is progressing, identifying both those with rapid fibrosis and those with stable disease.     

Nonalcoholic Steatohepatitis—A Long-Term Follow-Up Study: Comparison with Alcoholic Hepatitis in Ambulatory and Hospitalized Patients

A previous publication analyzed the clinicopathological characteristics of 105 patients with steatohepatitis: 32 nonalcoholic, 21 ambulatory alcoholics, and 52 hospitalized alcoholics; we now report an up to 12-year follow-up (mean 5.9 ± 4.7). Between 1988 and 1993, all patients with a histological diagnosis of steatohepatitis were included; necrosis, inflammation, Mallory bodies, and fibrosis were graded. Complete follow-up data were obtained in 78%. Survival curves were similar between nonalcoholic and ambulatory alcoholics; they were, however, better in nonalcoholic than hospitalized alcoholics (P < 0.0001), and in ambulatory relative to hospitalized (P = 0.0001) alcoholics. Nonalcoholics had a better prognosis than the combined alcoholic groups (P = 0.001). Patients with moderate to severe Mallory bodies and severe fibrosis had a significantly worse survival (P < 0.01), whereas severity of hepatocellular damage and neutrophil or mononuclear infiltration had no significant impact. In conclusion, alcoholic patients as a whole had a worse prognosis, yet the ambulatory subgroup had a prognosis similar to nonalcoholic patients.     

Clinical implication of plasma and urine YKL-40, as a proinflammatory biomarker, on early stage of nephropathy in type 2 diabetic patients

ObjectiveChronic inflammation has emerged as being a key pathophysiology in the early stages of diabetic nephropathy. YKL-40 has been established as an inflammatory marker in chronic inflammation. The aim of this study was to evaluate the association of plasma and urine YKL-40 with albuminuria in the early stage of type 2 diabetic nephropathy.Design and methodsA total of 75 type 2 diabetic patients and 22 nondiabetic controls with estimated glomerular filtration (eGFR) ≥ 60 ml/min/1.73 m² were enrolled. Plasma and urine concentrations of YKL-40 were analyzed by ELISA kit.ResultsThe plasma levels of YKL-40 were significantly higher in the normoalbuminuric group with diabetes than in the control group, and increased with increasing severity of albuminuria among diabetes. However, urine YKL-40 was only increased in macroalbuminuric state. Plasma YKL-40 was positively correlated with urine YKL-40 (r = 0.291, P = 0.011). Urinary albumin significantly correlated with both plasma and urine YKL-40 in a univariate analysis. After adjusting for several confounding factors, plasma YKL-40 was significantly correlated with albuminuria (r = 0.359; P = 0.001), whereas urine YKL-40 did not show significant correlation with albuminuria (r = 0.128, P = 0.241).ConclusionsAlthough urine YKL-40 has a limited role, plasma YKL-40, as an proinflammatory marker, was an independent factor associated with albuminuria in early stage of nephropathy in type 2 diabetes and might have an useful role as a noninvasive marker for the early diabetic nephropathy detection.