The Osteopontin Level in Liver, Adipose Tissue and Serum Is Correlated with Fibrosis in Patients with Alcoholic Liver Disease

<div><h3>Background</h3><p>Osteopontin (OPN) plays an important role in the progression of chronic liver diseases. We aimed to quantify the liver, adipose tissue and serum levels of OPN in heavy alcohol drinkers and to compare them with the histological severity of hepatic inflammation and fibrosis.</p> <h3>Methodology/Principal Findings</h3><p>OPN was evaluated in the serum of a retrospective and prospective group of 109 and 95 heavy alcohol drinkers, respectively, in the liver of 34 patients from the retrospective group, and in the liver and adipose tissue from an additional group of 38 heavy alcohol drinkers. Serum levels of OPN increased slightly with hepatic inflammation and progressively with the severity of hepatic fibrosis. Hepatic OPN expression correlated with hepatic inflammation, fibrosis, TGFβ expression, neutrophils accumulation and with the serum OPN level. Interestingly, adipose tissue OPN expression also correlated with hepatic fibrosis even after 7 days of alcohol abstinence. The elevated serum OPN level was an independent risk factor in estimating significant (F≥2) fibrosis in a model combining alkaline phosphatase, albumin, hemoglobin, OPN and FibroMeter® levels. OPN had an area under the receiving operator curve that estimated significant fibrosis of 0.89 and 0.88 in the retrospective and prospective groups, respectively. OPN, Hyaluronate (AUROC: 0.88), total Cytokeratin 18 (AUROC: 0.83) and FibroMeter® (AUROC: 0.90) estimated significance to the same extent in the retrospective group. Finally, the serum OPN levels also correlated with hepatic fibrosis and estimated significant (F≥2) fibrosis in 86 patients with chronic hepatitis C, which suggested that its elevated level could be a general response to chronic liver injury.</p> <h3>Conclusion/Significance</h3><p>OPN increased in the liver, adipose tissue and serum with liver fibrosis in alcoholic patients. Further, OPN is a new relevant biomarker for significant liver fibrosis. OPN could thus be an important actor in the pathogenesis of this chronic liver disease.</p> </div

: TCL1 and BPDCN diagnosis

International audienceDiagnosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN) or plasmacytoid dendritic cell leukemia (pDCL) is mainly based on immunophenotypical characterization of leukemic cells in blood or bone marrow samples. We tested by flow cytometry intracellular expression of the proto-oncogene T-cell leukemia 1 (TCL1), as well as membrane and intracellular expression of immunoglobulin-like transcript 7 (ILT7) in 21 pDCL samples and 61 non-pDC acute leukemia samples [i.e., 14 B-acute lymphoblastic leukemia (B-ALL), 9 T-ALL and 38 acute myeloid leukemia (AML)]. TCL1 is highly expressed in all pDCL samples while at a statistically lower level in all B-ALL and 34% of AML. Statistical analysis shows that intensity of TCL1 expression is a good marker for differential diagnosis of pDCL versus other acute leukemia (area under the receiver-operating characteristic curve, [AUC]: 0.96). By contrast, ILT7 positivity is limited to few pDCL samples and cannot be useful for diagnosis purpose. In conclusion, high intracellular intensity of TCL1 expression is currently the best marker for pDC lineage assignment by flow cytometry, which is particularly useful to distinguish pDCL from CD4(+) CD56(+/-) undifferentiated or monoblastic acute leukemia. Thus, intracellular TCL1 detection should be included in acute leukemia diagnosis panels used in hematology laboratories. © 2012 International Society for Advancement of Cytometry

Only Follow-up of Memory B Cells Helps Monitor Rituximab Administration to Patients with NeuroMyelitis Optica Spectrum Disorders

<p></p><p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>. </b><a href="https://link.springer.com/article/10.1007/s40120-018-0101-4">https://link.springer.com/article/10.1007/s40120-018-0101-4</a></p><p></p><p></p><p> </p><p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p><br><p></p

Comparison of nine blood tests and transient elastography for liver fibrosis in chronic hepatitis C: the ANRS HCEP-23 study.

International audienceBACKGROUND & AIMS: Blood tests and transient elastography (Fibroscan™) have been developed as alternatives to liver biopsy. This ANRS HCEP-23 study compared the diagnostic accuracy of nine blood tests and transient elastography (Fibroscan™) to assess liver fibrosis, vs. liver biopsy, in untreated patients with chronic hepatitis C (CHC). METHODS: This was a multicentre prospective independent study in 19 French University hospitals of consecutive adult patients having simultaneous liver biopsy, biochemical blood tests (performed in a centralized laboratory) and Fibroscan™. Two experienced pathologists independently reviewed the liver biopsies (mean length=25±8.4 mm). Performance was assessed using ROC curves corrected by Obuchowski's method. RESULTS: Fibroscan™ was not interpretable in 113 (22%) patients. In the 382 patients having both blood tests and interpretable Fibroscan™, Fibroscan™ performed similarly to the best blood tests for the diagnosis of significant fibrosis and cirrhosis. Obuchowski's measure showed Fibrometer® (0.86), Fibrotest® (0.84), Hepascore® (0.84), and interpretable Fibroscan™ (0.84) to be the most accurate tests. The combination of Fibrotest®, Fibrometer®, or Hepascore® with Fibroscan™ or Apri increases the percentage of well classified patients from 70-73% to 80-83% for significant fibrosis, but for cirrhosis a combination offers no improvement. For the 436 patients having all the blood tests, AUROC's ranged from 0.82 (Fibrometer®) to 0.75 (Hyaluronate) for significant fibrosis, and from 0.89 (Fibrometer® and Hepascore®) to 0.83 (FIB-4) for cirrhosis. CONCLUSIONS: Contrarily to blood tests, performance of Fibroscan™ was reduced due to uninterpretable results. Fibrotest®, interpretable Fibroscan™, Fibrometer®, and Hepascore® perform best and similarly for diagnosis of significant fibrosis and cirrhosis

Characteristics of the Estimation, Second Gene and Validation groups.

<p>Data are expressed as Means ± SEM or N (%). AST: aspartate amino-tranferase; ALT: alanine amino-transferase; γGT: Gamma Glutamyl Transpeptidase.</p

Hepatic OPN expression correlated with hepatic TGFβ expression, portal space neutrophils and the serum OPN level.

<p><b>A</b>) Hepatic OPN and TGFβ1 expression levels were analyzed by real-time quantitative PCR in 34 alcoholic patients from the estimation group without (<b>F0</b>) (N = 6) or with mild (<b>F1</b>) (N = 14), moderate (<b>F2</b>) (N = 6) or advanced (<b>F3/4</b>) (N = 8) fibrosis. The mRNA levels were normalized to the mRNA levels of RPLP0. Results are expressed relative to the expression levels in F0 patients and expressed as means ± SEM. The Kruskal-Wallis test compared the 4 groups F0, F1, F2 and F3/F4: OPN, <i>P</i> = 0.037; TGFβ1, <i>P</i> = 0.002. Mann Whitney test compared the two groups: &, <i>P</i>≤0.011, compared with F0; #, <i>P</i>≤0.029, compared with F1; $, <i>P</i> = 0.008, compared with F2. <b>B</b>) Correlation between hepatic OPN gene expression (ΔCt) and either the hepatic TGFβ1 expression level (ΔCt) or the serum OPN level were analyzed using the Spearman's rank correlation test. <b>C</b>) Correlation between the number of portal space neutophils (Cf. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035612#s2" target="_blank">Materials and methods</a>) and serum OPN level or hepatic OPN gene expression (ΔCt) in 11 alcoholic patients (2F0/3F1/1F2/5F4) were analyzed using the Spearman's rank correlation test.</p

The serum OPN level correlated with fibrosis and steatohepatitis in 109 alcoholic patients (estimation cohort).

<p>The circulating levels of OPN were measured in the serum of 109 alcoholic patients (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035612#pone-0035612-t001" target="_blank">Table 1</a>) and analyzed according to the grade of steatosis (S0, S1, S2, S3)(<b>A</b>), the presence of hepatic inflammation (I0, I1) (Hepatic inflammation was determined by the presence (I1) or absence (I0) of hepatocellular necrosis and ballooning degeneration, alcoholic Mallory's hyaline bodies, associated with an inflammatory reaction) (<b>B</b>) and the stage of fibrosis (F0, F1, F2, F3, F4)(<b>C</b>) (as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035612#s2" target="_blank">Materials and Methods</a>). Results were expressed as the median (25^th, 75^th percentile). The Kruskal-Wallis test was used to compare the 4 groups S0, S1, S2 and S3, <i>P</i> = 0.900 and the 5 groups F0, F1, F2, F3 and F4, <i>P</i><0.001. The Mann Whitney test compared A0 A1: <i>P</i> = 0.047. The Mann Whitney test compared the two groups (C): &, <i>P</i><0.015, compared with F0; #, <i>P</i><0.028, compared with F1; $, <i>P</i> = 0.007, compared with F2. Correlations between the serum OPN level with hepatic steatosis, hepatitis or fibrosis were analyzed using the Spearman's rank correlation test.</p

Levels of serum OPN in patients with chronic viral hepatitis C.

<p>(<b>A</b>) The circulating levels of OPN were measured in the serum of 86 patients with chronic hepatitis C (25 F1, 34 F2, 19 F3, 8 F4) and analyzed according to the stage of fibrosis. Results were expressed as the median (25^th, 75^th percentile). The Kruskal-Wallis test was used to compare the 4 groups F1, F2, F3 and F4: <i>P</i><0.001. The Mann-Whitney test compared the two groups: &, <i>P</i>≤0.048, compared with F1; #, <i>P</i>≤0.026, compared with F2. Correlation between the serum OPN level with hepatic fibrosis was analyzed using the Spearman's rank correlation test. (<b>B</b>) The areas under the ROC curves are shown for the performance of serum OPN levels in estimating significant fibrosis (F≥2) or advanced fibrosis (F≥3) in this cohort.</p