Including osteoprotegerin and collagen IV in a score-based blood test for liver fibrosis increases diagnostic accuracy

BACKGROUND: Noninvasive methods for liver fibrosis evaluation in chronic liver diseases have been recently developed, i.e. transient elastography (Fibroscan™) and blood tests (Fibrometer®, Fibrotest®, and Hepascore®). In this study, we aimed to design a new score in chronic hepatitis C (CHC) by selecting blood markers in a large panel and we compared its diagnostic performance with those of other noninvasive methods. METHODS: Sixteen blood tests were performed in 306 untreated CHC patients included in a multicenter prospective study (ANRS HC EP 23 Fibrostar) using METAVIR histological fibrosis stage as reference. The new score was constructed by non linear regression using the most accurate biomarkers. RESULTS: Five markers (alpha-2-macroglobulin, apolipoprotein-A1, AST, collagen IV and osteoprotegerin) were included in the new function called Coopscore©. Using the Obuchowski Index, Coopscore© shows higher diagnostic performances than for Fibrometer®, Fibrotest®, Hepascore® and Fibroscan™ in CHC. Association between Fibroscan™ and Coopscore© might avoid 68% of liver biopsies for the diagnosis of significant fibrosis. CONCLUSION: Coopscore© provides higher accuracy than other noninvasive methods for the diagnosis of liver fibrosis in CHC. The association of Coopscore© with Fibroscan™ increases its predictive value

Elevated creatine kinase activity in primary hepatocellular carcinoma

BACKGROUND: Inconsistent findings have been reported on the occurrence and relevance of creatine kinase (CK) isoenzymes in mammalian liver cells. Part of this confusion might be due to induction of CK expression during metabolic and energetic stress. METHODS: The specific activities and isoenzyme patterns of CK and adenylate kinase (AdK) were analysed in pathological liver tissue of patients undergoing orthotopic liver transplantation. RESULTS: The brain-type, cytosolic BB-CK isoenzyme was detected in all liver specimens analysed. Conversely, CK activity was strongly increased and a mitochondrial CK (Mi-CK) isoenzyme was detected only in tissue samples of two primary hepatocellular carcinomas (HCCs). CONCLUSION: The findings do not support significant expression of CK in normal liver and most liver pathologies. Instead, many of the previous misconceptions in this field can be explained by interference from AdK isoenzymes. Moreover, the data suggest a possible interplay between p53 mutations, HCC, CK expression, and the growth-inhibitory effects of cyclocreatine in HCC. These results, if confirmed, could provide important hints at improved therapies and cures for HCC

Collective opinion paper on findings of the 2011 convocation of experts on laboratory quality.

In April of 2011, Bio-Rad Laboratories Quality System Division (Irvine, CA, USA) hosted its third annual convocation of experts on laboratory quality in the city of Salzburg, Austria. As in the past 2 years, over 60 experts from across Europe, Israel, USA and South Africa convened to discuss contemporary issues and topics of importance to the clinical laboratory. This year's conference had EN/ISO 15189 and accreditation as the common thread for most discussions, with topics ranging from how to meet requirements like uncertainty to knowledge gained from those already accredited. The participants were divided into five discussion working groups (WG) with assigned topics. The outcome of these discussions is the subject of this summary

Bcl-2 protein level in blood of patients with acute myeloid leukaemia

We investigated the association between blood bcl-2 protein and the occurrence of acute myeloid leukaemia (AML), bcl-2 being an anti-apoptotic protein incriminated in cancer. Blood specimens were collected from 28 patients with AML, either de novo or following myelodysplastic syndrome, and from 25 healthy unrelated controls. In some specimens, the pro-apoptotic p53 protein and oligonucleosomes were also determined. In controls, bcl-2 was at 90.6 ± 27.8 U/ml, whereas p53 was detected in only 72 % of the specimens (0.15 ± 0.17 ng/ml); bcl-2 and p53 levels were inversely correlated. Oligonucleosomes were detected in all the controls but at low level and with no correlation to bcl-2 or p53. Bcl-2 level was higher in AML patients than in controls and some more increased in patients with de novo AML than in patients with secondary AML. In overall patients, bcl-2 correlated to lactico-dehydrogenase and to blood leukocytes, but weakly to blasts, and not to caryotype, cd-34 antigen and mdr-1 genotype. p53 was detected in only one patient with AML and oligonucleosomes were higher in patients than in controls. Studied on 12 patients without cytogenetic poor prognosis, bcl-2 level correlated to bad outcome. These data suggest that blasts that over express bcl-2 are resistant to apoptosis, defining this protein as a factor of bad prognosis in AML. Moreover, the determination of normal ranges for bcl-2 protein may be instrumental in the study of various diseases where apoptosis is enhanced, disrupted or delayed.Keywords: bcl-2; acute myeloid leukaemia; apoptosis; myelodysplastic syndrome; p53. Nous avons recherché la relation entre la protéine bcl-2 dans le sang et l’existence d’une leucémie myéloïde aiguë (LMA), bcl-2 étant une protéine anti-apoptotique incriminée dans le cancer. Des échantillons sanguins ont été prélevés chez 28 patients présentant une LMA, soit de novo soit à la suite d’un syndrome myélodysplasique, et chez 25 contrôles sains non reliés. Dans quelques échantillons, la protéine p53 proapoptotique et les oligonucléosomes ont aussi été mesurés. Chez les contrôles, bcl-2 était de 90,6 ± 27,8 U/ml, alors que p53 n’a été détectée que dans 72 % des échantillons (0,15 ± 0,17 ng/ml); bcl-2 et p53 étaient inversement corrélées. Les oligonucléosomes ont été détectés dans tous les échantillons contrôles mais à un niveau faible et sans corrélation à bcl-2 ni p53. Le niveau de bcl-2 était plus élevé chez les patients avec LAM que chez les contrôles, et même plus élevé chez les patients avec une LAM de novo que chez ceux avec une LMA secondaire. Chez l’ensemble des patients, bcl-2 était corrélée à la lactate-déshydrogénase et aux leucocytes sanguins, mais plus faiblement aux blastes, et pas du tout au caryotype, à l’antigène cd-40 et au génotype mdr-1. p53 n’a été détectée que chez un patient avec LAM et les oligonucléosomes étaient plus élevés chez les patients que chez les contrôles. Etudiée chez 12 patients sans mauvais pronostic cytogénétique, le niveau de bcl-2 était corrélé à un mauvais dénouement. Ces résultats suggèrent que les blastes qui sur-expriment bcl-2 sont devenus résistants à l’apoptose, qualifiant cette protéine de facteur de mauvais pronostic dans la LAM. De plus, la détermination des valeurs normales de la protéine bcl-2 pourrait être utile aux études portant sur diverses maladies où l’apoptose est soit augmentée, soit diminuée ou encore différée.Mots clés: proteine bcl-2; leucémie myéloïde aiguë; apoptose; syndrome de myelodysplastique;proteine p53.