Meta-analysis of the standardized area under the ROC curves (AUROC) assessed in published studies of Fibrotest diagnostic value

<p><b>Copyright information:</b></p><p>Taken from "Meta-analyses of FibroTest diagnostic value in chronic liver disease"</p><p>http://www.biomedcentral.com/1471-230X/7/40</p><p>BMC Gastroenterology 2007;7():40-40.</p><p>Published online 15 Oct 2007</p><p>PMCID:PMC2175505.</p><p></p> There was no significant difference between the different liver diseases

Meta-analysis of the observed area under the ROC curves (AUROC) assessed in published studies of Fibrotest diagnostic value

<p><b>Copyright information:</b></p><p>Taken from "Meta-analyses of FibroTest diagnostic value in chronic liver disease"</p><p>http://www.biomedcentral.com/1471-230X/7/40</p><p>BMC Gastroenterology 2007;7():40-40.</p><p>Published online 15 Oct 2007</p><p>PMCID:PMC2175505.</p><p></p> AUROCs were all significantly higher for Fibrotest than the random 0.50 value (upper panel) (P < 0.001). There was no significant difference between the different liver diseases

High Prevalence of NASH and Advanced Fibrosis in Type 2 Diabetes: A Prospective Study of 330 Outpatients Undergoing Liver Biopsies for Elevated ALT, Using a Low Threshold

   OBJECTIVE Most people with type 2 diabetes (T2DM) and nonalcoholic steatohepatitis (NASH) or advanced fibrosis remain undiagnosed, resulting in missed opportunities for early intervention. This multicenter prospective study aimed at assessing the yield of using routinely available data for identifying these patients. RESEARCH DESIGN AND METHODS A total of 713 outpatients with T2DM, screened in four diabetology clinics for nonalcoholic fatty liver disease (NAFLD) according to American Diabetes Association criteria, were referred to hepatologists for further work-up (FIB-4 and vibration controlled transient elastography (VCTE)). A liver biopsy was proposed when ALT levels were persistently >20 IU/L in females or >30 IU/L in males, in the absence of other liver disease. RESULTS Liver biopsies were performed in 360 patients and considered adequate for reading after central review in 330 (median age 59 years, male 63%, BMI 32 kg/m2, HbA1C 7.5 %). Prevalence of NASH, advanced fibrosis, and cirrhosis were 58%, 38%, and 10%, respectively. Liver lesions were independently associated with the components of metabolic syndrome, but not with the micro- and macrovascular complications of T2DM. Models based on routinely available data with or without VCTE had good accuracy to predict advanced fibrosis (AUROC 0.84 and 0.77, correctly classified 59% and 45%, respectively) and NASH (AUROC 0.82 and 0.81, 44% and 42%, respectively).  CONCLUSIONS Despite the use of a low ALT threshold, prevalence of NASH (58%) or advanced fibrosis (38%) was high. Routinely available data had a high yield in identifying T2DM patients with advanced fibrosis and/or NASH requiring further liver assessment.</p

Gene expression interactions in breast cancer survival.

<p>(<b>A</b>) Kaplan–Meier survival curves based on categorization of <i>HMMR</i> (probe NM_012484) and <i>AURKA</i> (NM_003600) expression in tertiles (low, medium or high expression). For simplicity, only the tertiles for “high” <i>AURKA</i> are shown. The tumours with high expression levels for both genes were not those with the poorest prognosis. (<b>B</b>) Kaplan–Meier survival curves based on categorization of <i>HMMR</i> (NM_012484) and <i>TUBG1</i> (NM_016437) expression in tertiles (low, medium or high expression). For simplicity, only the tertiles for “high” <i>HMMR</i> are shown. The cases with high expression levels for both genes were those with the poorest prognosis.</p

The <i>HMMR</i> locus and breast cancer risk in <i>BRCA1</i> mutation carriers.

<p>(<b>A</b>) Forest plots showing rs299290 HRs and 95% CIs (retrospective likelihood trend estimation) for participating countries (relatively small sample sets are not shown) ordered by sample size. Left and right panels show results for <i>BRCA1</i> and <i>BRCA2</i> mutation carriers, respectively. The sizes of the rectangles are proportional to the corresponding country/study precision. (<b>B</b>) The rs299290-containing region, including the genes, variation and regulatory evidence mentioned in HMECs. Exons are marked by black-filled rectangles and the direction of transcription is marked by arrows in the genomic structure. The chromosome 5 positions (base pairs (bp)) and linkage disequilibrium structure from Caucasian HapMap individuals are also shown.</p

Potential GxG associated with breast cancer risk in <i>BRCA1/2</i> mutation carriers.

<p>*Each estimate is derived from the interaction term of a Cox regression model.</p><p>Potential GxG associated with breast cancer risk in <i>BRCA1/2</i> mutation carriers.</p

Predicted breast and ovarian cancer absolute risks for <i>BRCA1</i> mutation carriers at the 5^th, 10^th, 90^th, and 95^th percentiles of the combined SNP profile distributions.

<p>The minimum, maximum and average risks are also shown. Predicted cancer risks are based on the associations of known breast or ovarian cancer susceptibility loci (identified through GWAS) with cancer risk for <i>BRCA1</i> mutation carriers and loci identified through the present study. Breast cancer risks based on the associations with: 1q32, 10q25.3, 19p13, 6q25.1, 12p11, <i>TOX3</i>, 2q35, <i>LSP1</i>, <i>RAD51L1</i> (based on HR and minor allele frequency estimates from <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003212#pgen-1003212-t001" target="_blank">Table 1</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003212#pgen-1003212-t002" target="_blank">Table 2</a>, and <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003212#pgen.1003212.s016" target="_blank">Table S4</a>) and <i>TERT </i><a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003212#pgen.1003212-Bojesen1" target="_blank">[31]</a>. Ovarian cancer risks based on the associations with: 9p22, 8q24, 3q25, 17q21, 19p13 (<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003212#pgen-1003212-t001" target="_blank">Table 1</a>) and 17q21.31, 4q32.3 (<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003212#pgen-1003212-t002" target="_blank">Table 2</a>). Only the top SNP from each region was chosen. Average breast and ovarian cancer risks were obtained from published data <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003212#pgen.1003212-Antoniou10" target="_blank">[25]</a>. The methods for calculating the predicted risks have been described previously <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003212#pgen.1003212-Antoniou11" target="_blank">[28]</a>.</p

Study design for selection of the SNPs and genotyping of <i>BRCA1</i> samples.

<p>GWAS data from 2,727 <i>BRCA1</i> mutation carriers were analysed for associations with breast and ovarian cancer risk and 32,557 SNPs were selected for inclusion on the iCOGS array. A total of 11,705 <i>BRCA1</i> samples (after quality control (QC) checks) were genotyped on the 31,812 <i>BRCA1</i>-GWAS SNPs from the iCOGS array that passed QC. Of these samples, 2,387 had been genotyped at the SNP selection stage and are referred to as “stage 1” samples, whereas 9,318 samples were unique to the iCOGS study (“Stage 2” samples). Next, 17 SNPs that exhibited the most significant associations with breast and ovarian cancer were selected for genotyping in a third stage involving an additional 2,646 <i>BRCA1</i> samples (after QC).</p

Mapping of the 17q21 locus.

<p><i>Top 3 panels:</i> P-values of association (−log₁₀ scale) with ovarian cancer risk for genotyped and imputed SNPs (1000 Genomes Project CEU), by chromosome position (b.37) at the 17q21 region, for <i>BRCA1</i>, <i>BRCA2</i> mutation carriers and combined. Results based on the kinship-adjusted score test statistic (1 d.f.). <i>Fourth panel:</i> Genes in the region spanning (43.4–44.9 Mb, b.37) and the location of the most significant genotyped SNPs (in red font) and imputed SNPs (in black font). <i>Bottom panel:</i> Pairwise r² values for genotyped SNPs on iCOG array in the 17q21 region covering positions (43.4–44.9 Mb, b.37).</p

Associations with SNPs at the novel 17q21 region with ovarian cancer risk for <i>BRCA1</i> and <i>BRCA2</i> mutation carriers.

*<p>HRs estimated under the single disease risk model.</p