After successful hepatitis C virus antiviral therapy: It looks that normal alanine aminotransferase level is not the normal.

BACKGROUND: Normal serum alanine aminotransferase (ALT) levels differ with age, gender, and body mass index. Adjusting the upper limits of normal (ULN) for ALT needs further research in different populations. Aim of this work was to monitor the effect of successful chronic hepatitis C (CHC) treatment on the ALT levels in patients with normal pretreatment ALT. METHODS: Data of 1160 CHC patients with persistent pretreatment normal liver enzymes were retrospectively analyzed. Treatment response to direct acting antiviral agents (DAAs) therapy was recorded. Changes in ALT levels before and after treatment were analyzed by patients' demographic, laboratory, and radiologic characteristics. Areas under the receiver operating characteristic curve (AUROC) of ALT after treatment were used to generate a new ALT ULN. RESULTS: Males were 568 (49%) and females 592 (51%) with a mean age of 50.7 years. After treatment, mean (±SD) of ALT levels significantly decreased from (26.3±7.8) to (19.1±10.9). This reduction was more significant in interferon-free than interferon-based regimens. ROC curve analyses suggested a new ALT ULN cut off (26.4 IU/L) in the treated patients (sensitivity=78.6%, specificity=83.8%, AUROC=0.89. This cutoff dropped to 14.7 IU/L in cirrhotic patients (sensitivity=77.4%, specificity=44.7%, AUROC=0.612). The identified cutoffs were 16.3 IU/L (sensitivity=66.7%, specificity=47.5%, AUROC=0.499) and 15.5 IU/L (sensitivity=76.5%, specificity=51.3%, AUROC=0.576) in males and females, respectively. CONCLUSION: The current ALT ULN needs readjustment to identify new normal cutoffs in CHC patients. Posttreatment cutoffs differ according to gender, pretreatment liver affection, and treatment regimen.

Multimodal analysis of in vivo resorbable CaP bone substitutes by combining histology, SEM, and microcomputed tomography data.

This study introduced and demonstrated a new method to investigate the repair process of bone defects using micro- and macroporous beta-tricalcium phosphate (ß-TCP) substitutes. Specifically, the new method combined and aligned histology, SEM, and preimplantation microcomputed tomography (mCT) data to accurately characterize tissue phases found in biopsies, and thus better understand the bone repair process. The results included (a) the exact fraction of ceramic remnants (CR); (b) the fraction of ceramic resorbed and substituted by bone (CSB); and (c) the fraction of ceramic resorbed and not substituted by bone (CNSB). The new method allowed in particular the detection and quantification of mineralized tissues within the 1-10 µm micropores of the ceramic ("micro-bone"). The utility of the new method was demonstrated by applying it on biopsies of two ß-tricalcium phosphate bone substitute groups with two differing macropore sizes implanted in an ovine model for 6 weeks. The total bone deposition and ceramic resorption of the two substitute groups, having macropore sizes of 510 and 1220 µm, were 25.1 ± 8.1% and 67.5 ± 3.2%, and 24.4 ± 4.1% and 61.4 ± 6.5% for the group having the larger pore size. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1567-1577, 2018.

A novel method for segmenting and aligning the pre- and post-implantation scaffolds of resorbable calcium-phosphate bone substitutes.

Micro-computed tomography (microCT) is commonly used to characterize the three-dimensional structure of bone graft scaffolds before and after implantation in order to assess changes occurring during implantation. The accurate processing of the microCT datasets of explanted ß-tricalcium phosphate (ß-TCP) scaffolds poses significant challenges because of (a) the overlap in the grey values distribution of ceramic remnants, bone, and soft tissue, and of (b) the resorption of the bone substitute during the implantation. To address those challenges, this article introduces and rigorously validates a new processing technique to accurately distinguish these three phases found in the explanted ß-TCP scaffolds. Specifically, the microCT datasets obtained before and after implantation of ß-TCP scaffolds were aligned in 3D, and the characteristic grey value distributions of the three phases were extracted, thus allowing for (i) the accurate differentiation between these three phases (ceramic remnants, bone, soft tissue), and additionally for (ii) the localization of the defect site in the post-implantation microCT dataset. Using the similarity matrix, a 94±1% agreement was found between algorithmic results and the visual assessment of 556,800 pixels. Moreover, the comparison of the segmentation results of the same microCT and histology section further confirmed the validity of the present segmentation algorithm. This new technique could lead to a more common use of microCT in analyzing the complex 3D processes and to a better understanding of the biological processes occurring after the implantation of ceramic bone graft substitutes. STATEMENT OF SIGNIFICANCE: Calcium-phosphate scaffolds are being increasingly used to repair critical bone defects. Methods for the accurate characterization of the repair process are still lacking. The present study introduced and validated a novel image-processing technique, using micro-computed tomography (mCT) datasets, to investigate material phases present in biopsies. Specifically, the new method combined mCT datasets from the scaffold before and after implantation to access the characteristic data of the ceramic for more accurate analysis of bone biopsies, and as such to better understand the interactions of the scaffold design and the bone repair process.