Serum markers detect the presence of liver fibrosis: a cohort study

BACKGROUND & AIMS: Histologic examination of a liver biopsy specimen is regarded as the reference standard for detecting liver fibrosis. Biopsy can be painful and hazardous, and assessment is subjective and prone to sampling error. We developed a panel of sensitive automated immunoassays to detect matrix constituents and mediators of matrix remodeling in serum to evaluate their performance in the detection of liver fibrosis. METHODS: In an international multicenter cohort study, serum levels of 9 surrogate markers of liver fibrosis were compared with fibrosis stage in liver biopsy specimens obtained from 1021 subjects with chronic liver disease. Discriminant analysis of a test set of samples was used to identify an algorithm combining age, hyaluronic acid, amino-terminal propeptide of type III collagen, and tissue inhibitor of matrix metalloproteinase 1 that was subsequently evaluated using a validation set of biopsy specimens and serum samples. RESULTS: The algorithm detected fibrosis (sensitivity, 90%) and accurately detected the absence of fibrosis (negative predictive value for significant fibrosis, 92%; area under the curve of a receiver operating characteristic plot, .804; standard error, .02; P < .0001; 95% confidence interval, .758-.851). Performance was excellent for alcoholic liver disease and nonalcoholic fatty liver disease. The algorithm performed equally well in comparison with each of the pathologists. In contrast, pathologists' agreement over histologic scores ranged from very good to moderate (kappa = .97-.46). CONCLUSIONS: Assessment of liver fibrosis with multiple serum markers used in combination is sensitive, specific, and reproducible, suggesting they may be used in conjunction with liver biopsy to assess a range of chronic liver diseases.     

Evaluation of a chromogenic commercial assay using VWF-73 peptide for ADAMTS13 activity measurement

Introduction

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA), related to a severe functional deficiency of ADAMTS13 activity (< 10% of normal). ADAMTS13 activity is thus crucial to confirm the clinical suspicion of TTP, to distinguish it from other TMAs, and to perform the follow-up of TTP patients.

Material and methods

We compared the performance of the commercial chromogenic assay Technozym® ADAMTS13 Activity ELISA (chromogenic VWF73 substrate, Chr-VWF73, Technoclone, Vienna, Austria), to that of our in-house FRETS-VWF73 used as reference method. A large group of 247 subjects (30 healthy volunteers and 217 patients with miscellaneaous TMAs) was studied.

Results

The lower limit of detection of the Chr-VWF73 was 3%, which is well adapted to the clinically relevant threshold for TTP diagnosis (10%). Our results showed a reasonable agreement between FRETS-VWF73 and Chr-VWF73 assays to distinguish samples with an ADAMTS13 activity < 10% from those with an ADAMTS13 activity > 10%. However, Chr-VWF73 assay provided false negative results in ~ 12% of acute TTP patients. Inversely, the Chr-VWF73 assay globally underestimated ADAMTS13 activity in detectable values ranging from 11 to 100% (with a great variability compared to FRETS-VWF73), which may be a concern for the follow-up of TTP patients in remission.

Conclusion

In-house assays developed and performed by expert laboratories remain the reference methods that should be used without limitation to control values provided by commercial assays when needed. Also, the development of an international reference preparation will be crucial to improve standardization.     

Hippocampus,caudate nucleus and entorhinal cortex volumetric MRI measurements in discrimination between Alzheimer’s disease,mild cognitive impairment,and normal aging

Background

Structural neuroimaging MR volumetric changes can predict progression of MCI to AD. Early effective treatment of MCI has been shown to delay institutionalization and improve cognition and behavioral symptoms.

Aim of the work

To evaluate the role of volumetric MRI to identify a pattern of regional atrophy characteristic in differentiation between Alzheimer’s disease, Mild Cognitive Impairment, and Normal elderly control.

Material and methods

The regional ethics committee approved the study and written informed consent was obtained from all participants. Between April 2012 and May 2013, prospective study was conducted on 25 patients (18 males and 7 females) and 15 healthy elderly controls (9 males and 6 females) referred to the Radiodiagnosis Department from the Neuropsychiatry Department that had clinical manifestations of suspected cognitive impairment, we used the Mini Mental State Examination (MMSE) as a measure of general cognitive function and the total learning from the Auditory Verbal Total Learning Test (AVTOT) as a measure of memory performance. One year follow up of patients was done to assess the disease progress.

Results

Twenty-five patients were included in this study {Alzheimer disease (10 cases), MCI (15 cases)} and 15 healthy elderly controls. Mean MMSE scores were significantly lower in patients with Alzheimer’s disease compared with MCI and control cases (P < 0.001). Positive correlation (except left caudate nucleus) between gray matter volume reduction in MCI and AD in relation to elderly control and MMSE score was observed. The Auditory Verbal Learning Test (AVTOT) was significantly lower in patients with Alzheimer’s disease compared with MCI and control cases (P < 0.001). No significant differences were found between groups as regards age, sex, education or dominant hand. Significant gray matter volume reductions were found in both AD and MCI compared to healthy elderly control however no significant differences were found among MCI patients or AD patients. Sensitivity, specificity, PPV and NPV of caudate nucleus and hippocampal volume reduction in AD and MCI in relation to elderly control were higher than entorhinal cortex.

Conclusion

Semi-automated MR volumetric measurements can be used to determine atrophy in hippocampus, caudate nucleus and entorhinal cortex which aided in discrimination of healthy elderly control subjects from subjects with AD and MCI and predict clinical decline of MCI leading to increase the efficiency of clinical treatments, delay institutionalization and improve cognition and behavioral symptoms.     

Multi-detector computed tomography imaging of blunt chest trauma

Background and purpose

Chest trauma is a significant cause of mortality and morbidity, especially in the younger population. The purpose of this study was to evaluate the role of multi-detector computed tomography (MDCT) in the assessment of patients with blunt chest trauma.

Patients and methods

A prospective study was conducted on thirty (30) patients with blunt chest trauma (21 males and 9 females, aged from 6 to 62 years) and 29 control patients presented with any trauma other than blunt chest trauma (23 males and 6 females, aged from 10 to 68 years) at the Emergency Department, Tanta University Hospital, from January 2013 to February 2014. Cases were subjected to clinical evaluation and radiological assessment of the chest using conventional chest X-ray (CXR) and multi-detector computed tomography.

Results

The most common mode of injury was motor vehicle accidents (56.7%). On MDCT scan, the frequency of chest injuries were; chest wall injuries (86.7%), pleural injuries (80%), parenchymal injuries (56.7%), mediastinal injuries (30%) and finally the dorsal spine injuries (16.7%). MDCT is more sensitive, specific, and accurate than CXR in the assessment of blunt chest trauma and management of patients.

Conclusion

MDCT is the modality of choice for rapid assessment of emergency chest trauma patients, when chest X-ray was inconclusive.