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Background: The Baveno VI consensus proposed a dual liver stiffness (LS) by transient elastography threshold of 15 kPa for excluding and diagnosing compensated advanced chronic liver disease (cACLD) in the absence of other clinical signs. Herein, we aimed to validate these criteria in a real-world multicentre study. Methods: We included 5,648 patients (mean age 51 ± 13 years, 53% males) from 10 European liver centres who had a liver biopsy and LS measurement within 6 months. We included patients with chronic hepatitis C (n = 2,913, 52%), non-alcoholic fatty liver disease (NAFLD, n = 1,073, 19%), alcohol-related liver disease (ALD, n = 946, 17%) or chronic hepatitis B (n = 716, 13%). cACLD was defined as fibrosis stage ≥F3. Results: Overall, 3,606 (66%) and 987 (18%) patients had LS 15 kPa, respectively, while cACLD was histologically confirmed in 1,772 (31%) patients. The cut-offs of 15 kPa showed 75% sensitivity and 96% specificity to exclude and diagnose cACLD, respectively. Examining the ROC curve, a more optimal dual cut-off at 12 kPa, with 91% sensitivity and 92% specificity for excluding and diagnosing cACLD (AUC 0.87; 95% CI 0.86–0.88; p 15 kPa dual cut-offs, we found that the 12 kPa dual cut-offs have better diagnostic accuracy in cACLD. Lay summary: The term compensated advanced chronic liver disease (cACLD) was introduced in 2015 to describe the spectrum of advanced fibrosis and cirrhosis in asymptomatic patients. It was also suggested that cACLD could be diagnosed or ruled out based on specific liver stiffness values, which can be non-invasively measured by transient elastography. Herein, we assessed the suggested cut-off values and identified alternative values that offered better overall accuracy for diagnosing or ruling out cACLD.

Background Paraoxonase-1 (PON-1) is a high-density lipoprotein (HDL)-associated hydrolase that appears to have a protective action against atherosclerosis. The aim of our study is to identify whether PON-1 levels may be associated with the manifestation of symptoms in patients with carotid artery stenosis. Methods We studied all patients who underwent carotid endarterectomy in the Vascular Surgery Department of Laikon Hospital, Athens, Greece, from July 2012 to July 2014. Medical history was recorded and PON-1 glucose, total cholesterol, HDL cholesterol, low-density lipoprotein cholesterol, and triglycerides levels were measured. Variables were compared between symptomatic and asymptomatic patients. A receiver operating characteristic (ROC) curve was constructed to evaluate the accuracy of PON-1 to predict symptoms. Results A total of 74 patients were included, 41 were asymptomatic and the mean age was 68.5 years. The 2 groups appear to differ significantly with regards to the PON-1 levels, with the symptomatic group showing lower levels (5.3 ± 1.19 vs. 4.6 ± 1.36 ng/mL; P = 0.025). ROC analysis demonstrated an area under the curve of 0.654 (P = 0.023). Conclusions Reduced PON-1 levels showed a significant association with symptomatic status, which was independent of other traditional cardiovascular factors. Further studies are required to prospectively assess the role of PON-1 in predicting cerebrovascular events in patients with carotid artery disease.

Background In primary breast cancer metastases frequently arise from a state of dormancy that may persist for extended periods of time. We investigated the efficacy of plasma micro-RNA (miR)-21, miR-23b, miR-190, miR-200b and miR-200c, related to dormancy and metastasis, to predict the outcome of patients with early breast cancer. Methods miRNAs were evaluated by RT-qPCR in plasma obtained before adjuvant chemotherapy. miRNA expression, classified as high or low according to median values, correlated with relapse and survival. Receiver operating characteristic (ROC) curves were constructed to determine miRNA sensitivity and specificity. Results miR-21 (p p = 0.028) and miR-200c (p p = 0.013) in relapsed (n = 49), compared to non-relapsed patients (n = 84). Interestingly, miR-190 was lower (p = 0.0032) in patients with early relapse (at n = 23) compared to those without early relapse (n = 110). On the other hand, miR-21 and miR-200c were higher (p = 0.015 and p n = 20) as compared to non-relapsed patients. High miR-200c was associated with shorter disease-free survival (DFS) (p = 0.005) and high miR-21 with both shorter DFS and overall survival (OS) (p p = 0.033, respectively) compared to low expression. ROC curve analysis revealed that miR-21, miR-23b, miR-190 and miR-200c discriminated relapsed from non-relapsed patients. A combination of of miR-21, miR-23b and miR-190 showed higher sensitivity and specificity in ROC analyses compared to each miRNA alone; accuracy was further improved by adding lymph node infiltration and tumor grade to the panel of three miRs (AUC 0.873). Furthermore, the combination of miR-200c, lymph node infiltration, tumor grade and estrogen receptor predicted late relapse (AUC 0.890). Conclusions Circulating miRNAs are differentially expressed among relapsed and non-relapsed patients with early breast cancer and predict recurrence many years before its clinical detection. Our results suggest that miRNAs represent potential circulating biomarkers in early breast cancer.

1086Background: Metastasis is the leading cause of breast cancer associated death. In the current study we evaluated the expression of (a) micro-RNA (miR)-23b and miR-190 which are involved in tumo...

e23030 Background: Disease relapse is usually a lethal development following treatment of early BC. Recurrence could arise from a state of tumour dormancy during which there is growth restriction of undetectable micrometastases. The expression of dormancy and metastasis related miRNAs was evaluated in the plasma of patients (pts) with early BC obtained before adjuvant therapy in order to discover novel biomarkers for the prediction of relapse. Methods: PlasmamiR-21, miR-23b, miR-190, miR-200b and miR-200c expression was assessed by qRT-PCR in 133 pts with early BC (non-relapsed, n = 84; relapsed, n = 49). Expression was classified as high or low according to the median values. Results: No correlation was observed between the expression of miRNAs and the clinicopathological characteristics of pts. After a median follow-up of 94 mo, median Disease Free Interval (DFI) was significantly lower in pts with high compared to low miR-21 [105.03 mo vs not reached (NR); p= 0.001], miR-200c (105.2 mo vs NR; p= 0.007), or both miR-21 and miR-200c expression (81.37 mo vs NR; p= 0.001). miR-21-high was also associated with decreased median Overall Survival (OS; p= 0.041). In multivariate analysis the number of infiltrated axillary lymph nodes (N3 vs N0-N2, HR: 2.86; p= 0.004) and miR-21 expression (high vs low, HR: 2.824; p= 0.001) were independent negative prognostic factors for DFI, whereas negative hormone receptor status (HR: 3.062; p= 0.024) and miR-21 high (HR: 3.545; p= 0.029) independently predicted for worse OS. Moreover, miR-21 expression was higher in pts with early relapse (defined as relapse at ≤ 3 yrs) compared to non-relapsed at 5 yrs ( p= 0.032). In addition, higher miR-21 ( p= 0.038), miR-23b ( p= 0.039), miR-200b ( p= 0.027) and miR-200c ( p< 0.001) levels were observed in pts with late relapse (at ≥ 5 yrs) compared to those without relapse. Conclusions: Differential expression levels of metastasis and/or dormancy related circulating miRNAs are detectable before adjuvant therapy in pts with early BC presenting subsequent relapse compared to non-relapsed pts. Circulating miRNAs can predict for early or late recurrence years before clinical detection of metastases. These results merit prospective validation in an independent patient cohort.