Computed tomography for the diagnosis of varices in liver cirrhosis: a systematic review and meta-analysis of observational studies

<p><b>Objectives:</b> This systematic review and meta-analysis aimed to evaluate the diagnostic accuracy of contrast-enhanced computed tomography (CT) for varices in liver cirrhosis.</p> <p><b>Methods</b>: PubMed and EMBASE databases were searched for the literature identification. The area under the summary receiver operating characteristic curve (AUSROC), sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR), and diagnostic odds ratio (DOR) were calculated. We performed the subgroup analyses according to the location of varices, CT technique, and study design. The study quality was assessed according to the QUADAS-2 tool.</p> <p><b>Results:</b> Seventeen papers were eligible. The study quality was modest. The AUSROC was 0.8975 and 0.9494 for predicting any size and high-risk varices, respectively. Summary sensitivity, specificity, PLR, NLR, and DOR of CT for predicting any size and high-risk varices were 0.87/0.80/3.67/0.18/22.70 and 0.87/0.88/7.52/0.12/65.55, respectively. According to the location of varices, the AUSROC was 0.9127 for predicting any size gastric varices alone; and the AUSROC was 0.8958 and 0.9461 for predicting any size and high-risk esophageal varices alone, respectively. According to the CT technique, the AUSROC of multi-detector CT (MDCT) was 0.9047 and 0.9490 for predicting any size and high-risk varices, respectively; and the AUSROC of MDCT esophagograms for predicting any size and high-risk varices was 0.8735 and 0.9664, respectively. In the subgroup analysis of prospective studies, the AUSROC was 0.9122 and 0.9507 for predicting any size and high-risk varices, respectively.</p> <p><b>Conclusion:</b> CT had a high accuracy for the diagnosis of varices in liver cirrhosis.</p

Susceptibility of epithelial cells cultured from different regions of human cervix to HPV16-induced immortalization

<div><p>Persistent infection with high-risk human papillomavirus (HPV) is a major risk factor for cervical cancer. Greater than 90% of these cancers originate in the cervical transformation zone (TZ), a narrow region of metaplastic squamous epithelium that develops at the squamocolumnar junction between the ectocervix and endocervix. It is unclear why the TZ has high susceptibility to malignant transformation and few studies have specifically examined cells from this region. We hypothesized that cells cultured from TZ are more susceptible to cellular immortalization, an alteration that contributes to malignant development. We cultured primary epithelial cells from each region of human cervix (ectocervix, endocervix and TZ) and measured susceptibility to immortalization after transfection with the complete HPV-16 genome or infection of HPV16 E6/E7 retroviruses. Cells cultured from each cervical region expressed keratin markers (keratin 14 and 18) that confirmed their region of origin. In contrast to our prediction, cells from TZ were equally susceptible to immortalization as cells from ectocervix or endocervix. Thus, increased susceptibility of the TZ to cervical carcinogenesis is not due to increased frequency of immortalization by HPV-16. We developed a series of HPV16-immortalized cell lines from ectocervix, endocervix and TZ that will enable comparisons of how these cells respond to factors that promote cervical carcinogenesis.</p></div

Keratin expression in HPV-immortalized cell lines.

<p>A. Immunofluorescence staining for K14 and K18 in TZ, ectocervix and endocervix-derived immortalized CX16-RV2 cell lines. B. Quantitative analysis of K14 and K18 staining intensity in 12 HPV16 immortalized cervical cell lines. Bars represent the mean ± standard error of four experiments using samples from different donors. The asterisks show statistical differences [*** P < 0.001].</p

Structure and histology of the cervical TZ.

<p>A. Schematic representation of the cervix showing the TZ between ectocervix and endocervix. B. Histology of the cervical TZ showing the stratified squamous epithelium and underlying Nabothian cysts. C. Schematic showing the surface features of ectocervix, endocervix and TZ that aid in tissue dissection. The ectocervix is easily identified because the surface is smooth, white, and shiny with no mucous. The endocervix surface is rough, red in color, and covered with mucous. The TZ contains Nabothian cysts (swollen glands due to occlusion of ducts by squamous metaplasia). These large cysts are easily visible and diagnostic for the TZ. D. Photograph of a typical cervical specimen showing each region.</p

Cell morphology and keratin expression of monolayer cervical cell cultures.

<p>A. Phase contrast microscopy of primary human cervical cells from each region showing different cell morphology. B. K14 and K18 immunostaining showing different expression in cell culture <i>in vitro</i>. C. K17 and MMP7 immunostaining of cells cultured from each region of cervix. Irrelevant primary antibodies were used as the negative control for immunostaining.</p

Properties of HPV16-immortalized cell lines.

<p>Properties of HPV16-immortalized cell lines.</p

Infection and immortalization by retroviruses encoding HPV16 <i>E6</i>/<i>E7</i>.

<p>A. Infection efficiency of cells from ectocervix, TZ and endocervix. The bars represent the mean ± standard error of eight experiments using samples from different donors. B. Immortalization efficiency of cervical cells from each region that was normalized for differences in infection rate. Bars represent the mean ± standard error of eight experiments using samples from different donors. The asterisks show statistical differences [** P < 0.01; *** P < 0.001].</p

Liver-to-abdominal area ratio for predicting the in-hospital mortality in advanced liver cirrhosis

<p><b>Objectives</b>: To identify the value of liver-to-abdominal area ratio (LAAR) score for predicting the in-hospital mortality in advanced cirrhotic patients.</p> <p><b>Methods</b>: All cirrhotic patients with Child-Pugh class B or C who were admitted between July 2012 and June 2014 and underwent abdominopelvic CT scans were considered in this retrospective observational study. The association of LAAR with in-hospital death was calculated. Receiver operating characteristic curve analysis was performed. The area under curve (AUC) was calculated.</p> <p><b>Results</b>: In the overall analysis of 128 cirrhotic patients with Child-Pugh class B or C, LAAR score was significantly associated with the risk of in-hospital death (p = 0.012). The AUC of LAAR score for predicting the in-hospital mortality was 0.764 (p < 0.0001). The best cut-off value was 0.29 with a sensitivity of 75% and a specificity of 73.33%. In the subgroup analysis of 37 patients with Child-Pugh class C, LAAR score was significantly associated with the risk of in-hospital death (p = 0.008). The AUC of LAAR score was 0.821. The best cut-off value was 0.29 with a sensitivity of 85.71% and a specificity of 80%. In the subgroup analysis of 80 patients with moderate-severe ascites, LAAR score was not significantly associated with the risk of in-hospital death (p = 0.072). The AUC of LAAR score was 0.684 (p = 0.0158). The best cut-off value was 0.29 with a sensitivity of 75% and a specificity of 63.89%.</p> <p><b>Conclusion</b>: LAAR score might be effective for predicting the in-hospital death of advanced cirrhosis.</p

Supersonic shear imaging for the diagnosis of liver fibrosis and portal hypertension in liver diseases: a meta-analysis

<p><b>Background and aims</b>: The meta-analysis aimed to summarize the technical success rate of supersonic shear imaging (SSI) and to evaluate the diagnostic performance of liver and spleen stiffness measurement (LSM and SSM) with SSI for the detection of liver fibrosis, portal hypertension, and gastroesophageal varices in liver diseases.</p> <p><b>Methods</b>: PubMed, EMBASE, and Cochrane Library databases were searched. Technical success rate of SSI was pooled. Area under curve (AUC), sensitivity, and specificity with corresponding 95% confidence interval (CI) were calculated.</p> <p><b>Results</b>: Included studies regarding the diagnostic performance of SSI for liver fibrosis, portal hypertension, and esophageal varices numbered 28, 4, and 4 respectively. The pooled technical success rates of LSM and SSM were 95.3% and 75.5%, respectively. The AUC, sensitivity, and specificity of LSM/SSM for different stages of liver fibrosis were 0.85–0.94, 0.7–0.89, and 0.82–0.92, respectively. The AUC, sensitivity, and specificity of LSM were 0.84 (95%CI = 0.8–0.86), 0.79 (95%CI = 0.7–0.85), and 0.82 (95%CI = 0.72–0.88) for clinically significant portal hypertension, 0.85 (95%CI = 0.82–0.88), 0.8 (95%CI = 0.68–0.88), and 0.8 (95%CI = 0.6–0.92) for any varices, and 0.86 (95%CI = 0.83–0.89), 0.86 (95%CI = 0.76–0.92), and 0.61 (95%CI = 0.35–0.83) for high-risk varices, respectively.</p> <p><b>Conclusions</b>: LSM with SSI had a high diagnostic accuracy for liver fibrosis, but a moderate diagnostic accuracy for portal hypertension and esophageal varices.</p

Supplementary Tables -Supplemental material for Association of proton pump inhibitors with the risk of hepatic encephalopathy during hospitalization for liver cirrhosis

<p>Supplemental material, Supplementary Tables for Association of proton pump inhibitors with the risk of hepatic encephalopathy during hospitalization for liver cirrhosis by Jia Zhu, Xingshun Qi, Haonan Yu, Eric M Yoshida, Nahum Mendez-Sanchez, Xintong Zhang, Ran Wang, Han Deng, Jing Li, Dan Han and Xiaozhong Guo in United European Gastroenterology Journal</p