Preclinical and post-treatment changes in the HCC-associated serum proteome

SELDI-based proteomic profiling of body fluids is currently in widespread use for cancer biomarker discovery. We have successfully used this technology for the diagnosis of hepatocellular carcinoma (HCC) in hepatitis C patients and now report its application to serial serum samples from 37 hepatitis C patients before development of HCC, with HCC and following radiofrequency ablation of the tumour. As with alpha-fetoprotein, an accepted biomarker for HCC, we hypothesised that HCC-associated proteomic features would ‘return to normal' following successful treatment and the primary aim of our study was to test this hypothesis. Several SELDI peaks that changed significantly during HCC development were detected but they did not reverse following treatment. These data may be interpreted to suggest that the characteristic SELDI profile is not linearly related to tumour burden but may result from the progression of underlying liver disease or from the emergence of precancerous lesions. β2-Microglobulin, a protein previously reported to be markedly elevated in patients with HCV related HCC, was also the most significantly HCC associated proteomic feature (m/z 11720) in this study

Changes in the serum proteome associated with the development of hepatocellular carcinoma in hepatitis C-related cirrhosis

Early diagnosis of hepatocellular carcinoma (HCC) is the key to the delivery of effective therapies. The conventional serological diagnostic test, estimation of serum alpha-fetoprotein (AFP) lacks both sensitivity and specificity as a screening tool and improved tests are needed to complement ultrasound scanning, the major modality for surveillance of groups at high risk of HCC. We have analysed the serum proteome of 182 patients with hepatitis C-induced liver cirrhosis (77 with HCC) by surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI). The patients were split into a training set (84 non-HCC, 60 HCC) and a ‘blind' test set (21 non-HCC, 17 HCC). Neural networks developed on the training set were able to classify the blind test set with 94% sensitivity (95% CI 73–99%) and 86% specificity (95% CI 65–95%). Two of the SELDI peaks (23/23.5 kDa) were elevated by an average of 50% in the serum of HCC patients (P<0.001) and were identified as κ and λ immunoglobulin light chains. This approach may permit identification of several individual proteins, which, in combination, may offer a novel way to diagnose HCC

Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: An individual patient data meta-analysis

Objective Liver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Index (FIB-4) and NAFLD (non-alcoholic fatty liver disease) Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies. Design Individual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed individually and in sequential combinations. Results Data were included from 37 primary studies (n=5735; 45% women; median age: 54 years; median body mass index: 30 kg/m2; 33% had type 2 diabetes; 30% had advanced fibrosis). AUROCs of individual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs (&lt;1.3; ≥2.67) followed by LSM-VCTE cut-offs (&lt;8.0; ≥10.0 kPa) to rule-in or rule-out advanced fibrosis had sensitivity and specificity (95% CI) of 66% (63-68) and 86% (84-87) with 33% needing a biopsy to establish a final diagnosis. FIB-4 cut-offs (&lt;1.3; ≥3.48) followed by LSM cut-offs (&lt;8.0; ≥20.0 kPa) to rule out advanced fibrosis or rule in cirrhosis had a sensitivity of 38% (37-39) and specificity of 90% (89-91) with 19% needing biopsy. Conclusion Sequential combinations of markers with a lower cut-off to rule-out advanced fibrosis and a higher cut-off to rule-in cirrhosis can reduce the need for liver biopsies

Bone mineral density assessed by dual-energy X-ray absorptiometry in patients with viral or alcoholic compensated cirrhosis. A prospective study.

International audienceBackground/aim: Cirrhosis is considered as a risk factor for osteoporosis whose prevalence is poorly known. The aim was to assess prospectively bone mineral density (BMD) in patients with alcoholic or viral compensated cirrhosis. Methods: From 2006 to 2008, patients with viral or alcoholic compensated cirrhosis had BMD assessment by dual-energy X-ray absorptiometry. The prevalence of osteopenia (-2.5 SD < T-score < -1 SD) and osteoporosis (T-score <= -2.5 SD), and the influence of age, gender and aetiology of cirrhosis were assessed using univariate and multiple regression analysis. Results: One hundred and nine patients were studied (72 men, 55.3 +/- 11.4 years and 37 women, 65.2 +/- 11.0); with HBV (n = 35), HCV (n = 43), or alcoholic cirrhosis (n = 31). At the lumbar spine, 25 patients had osteopenia and 12 had osteoporosis. At the femoral site, 23 had osteopenia and 4 had osteoporosis. Female gender had an independent decreased effect on the total BMD. Conclusions: The prevalence of osteoporosis was up to 11% at the lumbar spine, greater in women independently of age, without significant difference according to the aetiology of cirrhosis. (C) 2011 Elsevier Masson SAS. All rights reserved

Selective growth of fully relaxed GeSn nano-islands by nanoheteroepitaxy on patterned Si(001)

In this letter, we explore in detail the potential of nanoheteroepitaxy to controllably fabricate high quality GeSn nano-structures and to further improve the crystallinity of GeSn alloys directly grown on Si(001). The GeSn was grown by molecular beam epitaxy at relatively high temperatures up to 750 degrees C on pre-patterned Si nano-pillars embedded in a SiO2 matrix. The best compromise between selective GeSn growth and homogenous Sn incorporation of 1.4% was achieved at a growth temperature of 600 degrees C. X-ray diffraction measurements confirmed that our growth approach results in both fully relaxed GeSn nano-islands and negligible Si interdiffusion into the core of the nanostructures. Detailed transmission electron microscopy characterizations show that only the small GeSn/Si interface area reveals defects, such as stacking faults. Importantly, the main part of the GeSn islands is defect-free and of high crystalline quality. The latter was further demonstrated by photoluminescence measurements where a clear redshift of the direct CC-CV transition was observed with increasing Sn content