Non-invasive assessment of liver fibrosis in patients with hepatitis C: shear wave elastography and colour Doppler velocity profile technique versus liver biopsy

Background and study aims: Determination of the presence and degree of liver fibrosis is essential for the prognosis and treatment of patients with chronic hepatitis C. Non-invasive methods of assessing fibrosis have been developed to reduce the need for biopsy. We determined the efficacy of shear wave elastography [SWE] and colour Doppler velocity as non-invasive methods for the assessment of liver fibrosis compared to liver biopsy among patients with chronic hepatitis C virus [HCV] infection

Patients and methods: In total, 117 patients with chronic HCV infection and 50 healthy age- and sexmatched control subjects were included. For each patient and control, abdominal ultrasonography, Doppler ultrasonography of the right portal vein [PV], and SWE were performed, whereas liver biopsy was performed for patients

Results: The mean value of the right PV maximum velocity was lower in patients with different stages of fibrosis than in controls [p < 0.001]. The mean value of liver stiffness determined by SWE was significantly higher in patients with different stages of fibrosis than in controls. Cutoff values for liver stiffness determined by SWE for assessing fibrosis stages were F2 >/= 4.815, F3 >/= 6.335, and F4 = 7.540 with a sensitivity of 84.6%, 96.2%, and 100.0%; specificity of 88.5%, 93.8%, and 100.0%; positive predictive value [PPV] of 93.6%, 98.0%, and 100.0%; negative predictive value [NPV] of 74.2%, 88.2%, and 100.0%; and overall accuracy of 85.9%, 95.6%, and 100.0% [area under the ROC curve [AUC]: 0.89, 0.96, and 1.0], respectively. Cutoff values for the right PV maximum velocity for assessing fibrosis stages were F2 < 23.4, F3 < 21, and F4 < 20 with a sensitivity of 65.0%, 57.4%, and 57.1%; specificity of 59.8%, 76.4%, and 75.5%; PPV of 33.8%, 58.3%, and 32.0%; NPV of 84.4%, 75.7%, and 89.7%; and overall accuracy of 61.1%, 69.5%, and 72.5% [AUC: 0.614, 0.696, and 0.625], respectively

Conclusion: SWE is effective for the non-invasive assessment of liver fibrosis in patients with HCV infection. SWE provides a more accurate correlation with liver fibrosis stage than colour Doppler velocity profile for the assessment of liver fibrosis, especially in advanced stages [F3 and F4]

Serum profiles of extracellualr matrix degradation inhibitors across the stages of liver fibrosis in chronic hepatitis C patients

Tissue inhibitor metalloproteinase-1 [TIMP-1] and alpha-2 macroglobulin [AMG] are extracellular matrix degeneration inhibitors that have been demonstrated to increase with liver fibrosis. However, date are lacking regarding their patterns of change. This study analyses their detailed serum profile across liver fibrosis stages in chronic hepatitis C [CHC]. Serum TIMP-1 and AMG measurements were evaluated for 78 adult male CHC patients versus liver fibrosis [F] stages [METAVIR F0-F4]. The performance characteristics for discrimination of sequential [close stages], significant [F >/= 2], and advanced [F >/= 3] fibrosis were assessed. Both TIMP-1 and AMG correlated significantly with fibrosis [r=0.31, p=0.005; r=0.37, p=0.001, respectively], but failed to discriminate sequential stages. For discrimination of significant fibrosis, the areas under receiver operating characteristics curves were small [0.59 and 0.57, respectively]. T a cut-off value of 743 ng/ml, TIMP-1 showed a 100% specificity [with 17.6% sensitivity], while at a cut-off of 3 gm/l, AMG showed 73.5% sensitivity [with 36.4% specificity]. A similarly modest discrimination was noted for advanced fibrosis. Interestingly, AMG showed an early rise with significantly higher values in F0 compared with healthy controls [3.6 +/- 1.1 vs. 1.8 +/- 0.6, respectively]. Neither TIMP-1 nor AMG could discriminate the sequential stages of fibrosis. Their modest performances for discrimination of significant and advanced fibrosis are related to the wide normal range f TIMP-1 and the early rise of AMG. A longitudinal monitoring would give a better understanding of their true changes, and examine whether patients having high AMG levels at F0 would be fast fibrosers or respond differently to therapy

Imprint cytology versus immunohistochemistry of sentinel lymph nodes in berast cancer with clinically negative axilla

The success of sentinel lymph node [SLN] biopsy in determining axillary lymph node status necessitates an accurate and rapid method for intraoperative examination of the nodes. The aim of this study was to evaluate the feasibility and accuracy of immunohistochemistry [IHC] of touch imprints in detecting axillary nodal metastasis. Sentinel lymph node biopsy was performed in 50 patients with clinical T1-2 No breast cancer. After harvesting, the SLN were bisected, imprinted and subjected to IHC. Results were compared with those of routine hematoxylin and eosin [H and E] and IHC examination of the same node. The SLN was the only site of metastasis in 15 patients [37.25%]. IHC staining of the imprinted SLNs is more accurate than H and E imprint or paraffin sections H and E and IHC stained. Immunohistochemistry was capable to detect micrometastasis in 4 paraffin sections of SLN. IHC of touch imprint is feasible and provide reliable results for intraoperative evaluation of SLN in patients with breast cancer. It is also more sensitive for detection of micrometastasis in paraffin sections

Alterations of the mononuclear inflammatory cells: cd4, cd8 T lymphocytes, IL-1beta, IL-17 and TNF-alpha in RA and OA blood and synovial fluid

Background: Rheumatoid [RA] and osteoarthritis [OA] are common joint diseases. The former is a multisystem disease with underlying immune mechanisms. The latter is a debilitating, progressive disease of diarthrodial joints associated with the aging process. We hypothesize that the development of RA and OA is associated with alterations in T cell subsets [CD4/CD8] as well as cytokine production in the blood and synovial fluid

Objectives: We carried out this investigation to test this hypothesis. Also, we took an aim at analyzing of RA and OA patients for: 1] the clinicopathologic characteristics of the lesions, 2] immunologic alterations in the synovial fluid [SF], peripheral blood [BP] and 3] the correlation between the clinicopathologic characteristics and immunologic alterations

Methodology: Samples [PB, SF] were obtained from 24 RA, 15 OA patients and six age and sex matched healthy controls [HCs]. The CD4/CD8 lymphocytes, levels of TNF-alpha, ILI -1beta and IL-17 cytokines were examined in SF and serum using Enzyme Linked Immunosorbent Assay, and immunoperoxidase staining methods

Results: The mean ages of RA and OA patients were 34.3 +/- 1.7 and 51.1 +/- 2.0 year. In RA, the mean values of the morning stiffness, pain scale, grip strength and Richie articular index were 87.5 +/- 11.5. 6.5 +/- 0.5, 51.0 +/- 8.8 and 29.5 +/- 2.4, respectively. As compared to HCs, in RA and OA, respectively, there were statistically significantly [p<0.05] higher: 1] ESR1 [8.5 +/- 51vs. 33.9 +/- 2.8 vs. 62.3 +/- 6.8]; 2] ESR2 [13.3 +/- 2.1vs. 50.6 +/- 4.3 vs. 88.9 +/- 6.4]; and 3] cytokine levels in the serum [7.5 +/- 2.1 vs. 25.8 +/- 2.3 vs. 26.2 +/- 1.5 for TNF-alpha; 9.2 +/- 6.2 vs. 18.5 +/- 1.6 vs. 17.8 +/- 1.3 for lL-1beta; and 0.01 +/- 0.0 vs. 0.07 +/- 0.02 vs. 0.2 +/- 0.1 for IL-17]. As compared to· OA, RA had significantly higher [p <0.05] cytokine levels in SF [105.6 +/- 39.5 vs. 245.2 +/- 22.2 for TNF-alpha; 14.3 +/- 1.3vs. 26.8 +/- 4.1 for lL-1beta and 0.5 +/- 0.2 vs. 6.4 +/- 2.3 for IL-17]. In the blood, as compared to HCs, there were a statistically significant higher CD4, CDS and CD4/CD8 ratio in both RA and OA [p<0.05]. There were significant direct correlations between the disease activity vs. TNF-alpha; CD4 vs. IL-17; CD8 vs. IL-1beta; and CD4 vs. TNF-alpha in SF

Conclusions: CD4/CD8 lymphocytes, cytokine are altered in RA and OA. In RA, some of these alterations correlated with the underling disease process and therefore may have pathogenetic, modulatory and potential prognostic roles in these lesions