Diagnostic Accuracy of 2D-Shear Wave Elastography for Liver Fibrosis Severity: A Meta-Analysis

<div><p>Purpose</p><p>To evaluate the accuracy of shear wave elastography (SWE) in the quantitative diagnosis of liver fibrosis severity.</p><p>Methods</p><p>The published literatures were systematically retrieved from PubMed, Embase, Web of science and Scopus up to May 13^th, 2016. Included studies reported the pooled sensitivity, specificity, positive and negative predictive values, as well as the diagnostic odds ratio of SWE in populations with liver fibrosis. A bivariate mixed-effects regression model was used, which was estimated by the <i>I</i>^<i>2</i> statistics. The quality of articles was evaluated by quality assessment of diagnostic accuracy studies (QUADAS).</p><p>Results</p><p>Thirteen articles including 2303 patients were qualified for the study. The pooled sensitivity and specificity of SWE for the diagnosis of liver fibrosis are as follows: <b>≥</b>F1 0.76 (<i>p</i><0.001, 95% CI, 0.71–0.81, <i>I</i>^<i>2</i> = 75.33%), 0.92 (<i>p</i><0.001, 95% CI, 0.80–0.97, <i>I</i>^<i>2</i> = 79.36%); <b>≥</b>F2 0.84 (<i>p</i> = 0.35, 95% CI, 0.81–0.86, <i>I</i>^<i>2</i> = 9.55%), 0.83 (<i>p</i><0.001, 95% CI, 0.77–0.88, <i>I</i>^<i>2</i> = 86.56%); <b>≥</b>F3 0.89 (<i>p</i> = 0.56, 95% CI, 0.86–0.92, <i>I</i>^<i>2</i> = 0%), 0.86 (<i>p</i><0.001, 95% CI, 0.82–0.90, <i>I</i>^<i>2</i> = 75.73%); F4 0.89 (<i>p</i> = 0.24, 95% CI, 0.84–0.92, <i>I</i>^<i>2</i> = 20.56%), 0.88 (<i>p</i><0.001, 95% CI, 0.84–0.92, <i>I</i>^<i>2</i> = 82.75%), respectively. Sensitivity analysis showed no significant changes if any one of the studies was excluded. Publication bias was not detected in this meta-analysis.</p><p>Conclusions</p><p>Our study suggests that SWE is a helpful method to appraise liver fibrosis severity. Future studies that validate these findings would be appropriate.</p></div

Activation of Fas signaling promotes the migration of GC cells.

<p>(A) The Fas expression in AGS and MNK-45 cells were detected by real-time PCR (upper) and Western blot (down). (B) Susceptibility of AGS and MNK-45 cells to Fas-induced apoptosis was measured by staining with Annexin V and PI after both cells were stimulated with anti-Fas or ISO at the indicated concentrations for 24 h (left) and the apoptotic cells were statistically analyzed (right) (n = 3). (C) After stimulated with 5 μg/ml anti-Fas or ISO for 2 h, the AGS cells were collected and seeded into the top chamber. Forty-eight hours later, the number of cells on the bottom of the Transwell filter was imaged (left) and quantified (right) (n = 5). Magnification: 200×. (D) The proliferation of AGS cells was measured by CCK8 assay after stimulation with 5 μg/ml of anti-Fas or ISO in the indicated timepoint. Data are representative of three independent experiments. (*p <0.05, ***p <0.001)</p

Summaries of the studies included.

<p>Summaries of the studies included.</p

Activation of Fas signaling upregulated Fascin expression in AGS cells through activation of STAT3.

<p>The AGS cells were stimulated with 5 μg/ml of anti-Fas in the indicated times. (A) The phosphorylated STAT3 was detected by Western blot. (B) The expression of Fascin mRNA was assayed by real-time PCR. (C) After stimulation with 5 μg/ml anti-Fas for 24 h, the protein level of phosphorylated STAT3 and Fascin in AGS cells was detected by Western blot. (D) The AGS cells were pre-treated with 10 μM of Stattic for 2 h and followed by 5 μg/ml of anti-Fas stimulation for 24 h; the protein level of phosphorylated STAT3 and Fascin was detected by Western blot. After transfection with STAT3 siRNA or NC siRNA for 36 h, (E) the STAT3 expression in the AGS cells was detected by Western blot; (F) the AGS cells were then stimulated with 5 μg/ml of anti-Fas for 2 h, and the Fascin expression in the cells was detected by Western blot. Data are representative of three independent experiments.</p

Fas signaling promotes AGS cell metastasis <i>in vivo</i> through STAT3/Fascin pathway.

<p>2 × 10⁶ AGS tumor cells pre-stimulated with anti-Fas or ISO for 2 h were intravenously injected nude mice. (A) The number of lung tumor foci was counted (n = 5). (B) The expression of Fascin in tumor tissues from lung was detected by immunohistochemistry. 2 × 10⁶ AGS tumor cells were intravenously injected into nude mice and 24 h later, the mice received intravenous injection of S3I-201 at 5 mg/kg every 2 days for total 3 times. (C) The number of lung tumor foci was counted (n = 5). (D) The expression of Fascin in tumor tissues from lung was detected by immunohistochemistry (magnification: ×100). Data are representative of two independent experiments. (*p <0.05, ***p <0.001)</p

Flow diagram of the study selection process.

<p>Flow diagram of the study selection process.</p

SROC curve of SWE in ≥F1-4 stagings (A, B, C and D) for liver fibrosis.

<p>SROC curve of SWE in ≥F1-4 stagings (A, B, C and D) for liver fibrosis.</p

Correlation of the mRNA levels of Fas and Fascin in tumor tissues from GC patients.

<p>Fas and Fascin mRNA expression was measured by real-time PCR and normalized to β-actin mRNA (n = 23). Positive correlation was obtained by Spearman correlation analysis.</p

Quality assessment for included studies by QUADAS.

<p>Quality assessment for included studies by QUADAS.</p

Patient characteristics.

<p>NOTE: Data are mean ± standard deviation.</p><p>*According to American Joint Committee on Cancer.</p><p>Abbreviation: ECOG PS, Eastern Cooperative Oncology Group Performance Status.</p><p>Patient characteristics.</p