0245: Echocardiographic and clinical outcome in patients undergoing trans-catheter aortic valve replacement with concomitant mitral regurgitation

BackgroundSevere aortic stenosis (AS) is commonly associated with mitral regurgitation (MR) in patients undergoing transcatheter aortic valve replacement (TAVR). The natural history of MR is not well defined in this population.MethodsConsecutive high risk, inoperable patients undergoing TAVR between 2007 and 2011 for AS has echos at baseline and 1 year and were followed for clinical outcomes. MR severity was graded and patients were grouped as having minimal (none-mild) or significant (moderate- severe) MR.Results164 patients underwent TAVR, reducing gradients from 47 to 10mHg. LVEF increased from 48% to 52% while pulmonary aretry systolic pressure (PAPS), LVESD and LVEDD were unchanged. Signficant MR patents had a median 1 grade reduction (p<0,0001) in MR at 1 year. Median LVEF increased by 2% (p=0.0412). Median LVESD decreased by 2.3mm±7.5 (p=0.039). Univariate analysis showed no significant predictors of MR reduction in significant MR patients. Functional and organic significant MR decreased after TAVR but only functional MR patients had improved LVEF (6%, p=0.034), PAPS (5.9mmHg, p=0.022) and LVESD (3.8mm, p=0.013). Multivariate analysis showed functional MR to be a predictor of improved LVEF and PAPS. Clinical outcomes at a mean follow-up of 925 days were not different in patients with significant vs minimal MR; however organic MR patients tended to have more events than functional MR patients (p=0.06).Conclusion:Significant MR patients undergoing TAVR for severe AS improved in LVEF and LVESD, particularly patients with functional MR. Organic MR is marginally predictive of cardiac complications in AS patients

Detection of IL28B SNP DNA from Buccal Epithelial Cells, Small Amounts of Serum, and Dried Blood Spots

Background &amp; Aims: Point mutations in the coding region of the interleukin 28 gene (rs12979860) have recently been identified for predicting the outcome of treatment of hepatitis C virus infection. This polymorphism detection was based on whole blood DNA extraction. Alternatively, DNA for genetic diagnosis has been derived from buccal epithelial cells (BEC), dried blood spots (DBS), and genomic DNA from serum. The aim of the study was to investigate the reliability and accuracy of alternative routes of testing for single nucleotide polymorphism allele rs12979860CC. Methods: Blood, plasma, and sera samples from 200 patients were extracted (400 mL). Buccal smears were tested using an FTA card. To simulate postal delay, we tested the influence of storage at ambient temperature on the different sources of DNA at five time points (baseline, 48 h, 6 days, 9 days, and 12 days) Results: There was 100 % concordance between blood, plasma, sera, and BEC, validating the use of DNA extracted from BEC collected on cytology brushes for genetic testing. Genetic variations in HPTR1 gene were detected using smear technique in blood smear (3620 copies) as well as in buccal smears (5870 copies). These results are similar to those for whole blood diluted at 1/10. A minimum of 0.04 mL, 4 mL, and 40 mL was necessary to obtain exploitable results respectively for whole blood, sera, and plasma. No significant variation between each time point was observed for the different sources of DNA. IL28B SNPs analysis at these different time points showed the same results using the four sources of DNA

Hepatic resection and transplantation for hepatocellular carcinoma in patients with cirrhosis

OBJECTIVES: Liver resection and liver transplantation are the only curative treatments for hepatocellular carcinoma in patients with cirrhosis. The aim of this retrospective study was to compare survival and tumor recurrence in patients with cirrhosis after hepatic resection or liver transplantation for hepatocellular carcinoma in patients with cirrhosis. METHODS: Between March 1988 and March 1995, 34 patients underwent liver resection and 30 patients with cirrhosis had liver transplantation for hepatocellular carcinoma. The probability of survival and recurrence were studied according to clinical, biological and pathological factors, defined in liver specimens. Comparisons were performed by the actuarial method and log rank test. RESULTS: Five-year survival after resection and transplantation was 13% and 32.6%, respectively, and 5-year recurrence was 92.6% and 40.9%, respectively (P 5 cm and/or number of nodules > 3), and patients with small carcinoma (diameter < or = 5 cm and number of nodules < or = 3). The five-year survival rate of large hepatocellular carcinoma was 17.3% after resection and 0% after transplantation. The five-year survival rate of small hepatocellular carcinoma was 0% after resection and 69.3% after transplantation (P < 0.01). The five-year recurrence of large hepatocellular carcinoma was 72.3% after resection and 100% after transplantation. The five-year recurrence of small hepatocellular carcinoma was 82.6% after resection and 11.1% after transplantation (P < 0.01). CONCLUSIONS: Liver transplantation seems to be the best treatment for small hepatocellular carcinoma, mainly because of a lower recurrence rate. On the other hand, both treatments had a high recurrence rate in large hepatocellular carcinoma

HCVerso2: a phase III study of faldaprevir plus deleobuvir and ribavirin for chronic HCV genotype 1b infection in treatment naïve patients including those ineligible for pegylated interferon

peer reviewedIn treatment-naïve, non-cirrhotic patients with HCV GT1b infection, faldaprevir + deleobuvir + ribavirin for 16 or 24 w resulted in comparable SVR 12 rates (76% vs 82%) with similar tolerability profiles. Patients with cirrhosis achieved SVR 12 of 74% (24w). The adjusted SVR rates for 16 or 24w in patients with or without cirrhosis were significantly higher than historical control

Compliance With Hepatocellular Carcinoma Surveillance Guidelines Associated With Increased Lead-Time Adjusted Survival of Patients With Compensated Viral Cirrhosis: A Multi-Center Cohort Study

International audienceBackground & aims - Semi-annual surveillance for hepatocellular carcinoma (HCC) is recommended for patients with cirrhosis. We aimed to determine how compliance with HCC surveillance guidelines affects survival times of patients with hepatitis C virus- or hepatitis B virus-associated compensated cirrhosis who developed HCC. Methods - We collected data from the prospective ANRS CO12 CirVir study, from March 2006 through June 2012, on 1671 patients with biopsy-proven viral cirrhosis and no previous liver complications who were undergoing surveillance for HCC at 35 centers in France. Only 216 patients who developed HCC during the follow-up period were included in the analysis. Patients were considered to be compliant with surveillance guidelines if the time between their last surveillance image evaluation and diagnosis of HCC were fewer than 7 months and noncompliant if this time was 7 months or longer. Results - HCC was detected in 216 patients, at a median follow-up time of 59.7 months. Of these patients, 140 (80.5%) were Barcelona Clinic Liver Cancer stage 0/A, 135 (69.9%) received first-line curative treatment (15 underwent transplantation, 29 underwent resection, 89 received percutaneous ablation, and 2 received resection and percutaneous ablation), and 129 (60.0%) were compliant with surveillance guidelines. Seventy-nine of the patients with HCC died; 49 deaths were associated with tumor progression. After lead-time adjustment, overall survival (OS) time was longer in patients compliant with surveillance guidelines (median OS time, 53.2 months) than noncompliant patients (median OS time, 25.4 months) (P = .0107); this difference remained significant even when we changed lead time assumptions. In multivariate analysis adjusted for a propensity score, compliance with HCC surveillance guidelines was associated with low tumor burden, allocation of curative treatment, and increased OS time compared with noncompliance (hazard ratio for OS, 2.19; 95% confidence interval, 1.16-4.14; P = .0150). Conclusions - In an analysis of data from the ANRS CO12 CirVir cohort, we associated compliance with HCC surveillance guidelines (fewer than 7 months between image evaluations) with early diagnosis, allocation of curative treatment, and longer adjusted OS of patients with hepatitis C virus- or hepatitis B virus-associated compensated cirrhosis and a diagnosis of HCC

TASK channel deletion in mice causes primary hyperaldosteronism

When inappropriate for salt status, the mineralocorticoid aldosterone induces cardiac and renal injury. Autonomous overproduction of aldosterone from the adrenal zona glomerulosa (ZG) is also the most frequent cause of secondary hypertension. Yet, the etiology of nontumorigenic primary hyperaldosteronism caused by bilateral idiopathic hyperaldosteronism remains unknown. Here, we show that genetic deletion of TWIK-related acid-sensitive K (TASK)-1 and TASK-3 channels removes an important background K current that results in a marked depolarization of ZG cell membrane potential. Although TASK channel deletion mice (TASK−/−) adjust urinary Na excretion and aldosterone production to match Na intake, they produce more aldosterone than control mice across the range of Na intake. Overproduction of aldosterone is not the result of enhanced activity of the renin–angiotensin system because circulating renin concentrations remain either unchanged or lower than those of control mice at each level of Na intake. In addition, TASK−/− mice fail to suppress aldosterone production in response to dietary Na loading. Autonomous aldosterone production is also demonstrated by the failure of an angiotensin type 1 receptor blocker, candesartan, to normalize aldosterone production to control levels in TASK−/− mice. Thus, TASK−/− channel knockout mice exhibit the hallmarks of primary hyperaldosteronism. Our studies establish an animal model of nontumorigenic primary hyperaldosteronism and identify TASK channels as a possible therapeutic target for primary hyperaldosteronism

Incidence of Hepatocellular Carcinoma After Direct Antiviral Therapy for HCV in Patients With Cirrhosis Included in Surveillance Programs

International audienceBackground & aims - Retrospective studies have found an unexpectedly high incidence of hepatocellular carcinoma (HCC) among patients with hepatitis C virus (HCV)-associated cirrhosis who received direct-acting antiviral (DAA) agents. We analyzed data from the ANRS CO12 CirVir cohort to compare the incidence of HCC in patients with cirrhosis who received DAA therapy vs patients treated with interferon (IFN). Methods - Data were collected from 1270 patients with compensated biopsy-proven HCV-associated cirrhosis recruited from 2006 through 2012 at 35 centers in France. For descriptive purpose, patients were classified as follows: patients who received DAA treatment (DAA group, n = 336), patients who achieved a sustained virologic response (SVR) following an IFN-based regimen (SVR-IFN group, n = 495), or patients who never received DAA treatment and never had an SVR following IFN therapy (non-SVR group, n = 439). The patients were included in HCC surveillance programs based on ultrasound examination every 6 months, and clinical and biological data were recorded. To account for confounding by indication due to differences in patient characteristics at treatment initiation, we constructed a time-dependent Cox regression model weighted by the inverse probability of treatment and censoring (IPTCW) to assess the treatment effects of DAA on time until HCC. Results - Compared with patients in the SVR-IFN group, patients in the DAA group were older, higher proportions had diabetes or portal hypertension, and liver function was more severely impaired. The crude 3-year cumulative incidences of HCC were 5.9% in the DAA group, 3.1% in the SVR-IFN group, and 12.7% in the non-SVR group (overall P < .001; unadjusted hazard ratio [HR] for HCC 2.03; 95% confidence interval [CI] 1.07-3.84; P = .030 for the DAA group vs the SVR-IFN group). HCC characteristics were similar among groups. Among patients with HCC, the DAA group received less-frequent HCC screening than the other 2 groups (P = .002). After Cox analyses weighted by the IPTCW, we found no statistically significant increase in risk of HCC associated with DAA use (HR 0.89; 95% CI 0.46-1.73; P = .73). Conclusions - Analysis of data from the ANRS CO12 CirVir cohort reveals that the apparent increase in HCC incidence observed in patients with cirrhosis treated with DAAs compared with patients who achieved SVR following an IFN therapy can be explained by patient characteristics (age, diabetes, reduced liver function) and lower screening intensity