Non-invasive detection of hepatic amyloidosis: FibroScan, a new tool.

INTRODUCTION: FibroScan, a non-invasive tool for measuring liver stiffness (LS), is not specific to liver fibrosis. Other extra-hepatic conditions may modify the LS value. OBJECTIVES: Our aim was to examine whether amyloid deposition in the liver may modify LS. METHODS: LS was measured prospectively in 41 patients with systemic AL amyloidosis (AL) in the French AL Reference Center, comprising: 5 patients with liver involvement (LI) and no cardiac involvement (CI), 11 with CI and no LI, 12 with both LI and CI and 13 with neither (2005 consensus criteria); 26 negative controls, 50 patients infected with Hepatitis C virus (HCV)-infected and 18 AL-free patients with right-sided heart disease ('cardiac controls') were also examined. RESULTS: Median LS was significantly higher in patients with AL with liver involvement [27.4 (10.3-75) kPa] than in negative controls [4.8 (2.8-11.9) kPa] (p < 0.0001), and patients infected with HCV [(6.8 (2.9-69.1) kPa] (p = 0.001), and tended to be higher than in the 'cardiac controls' [11 (4.1-75) kPa] (p = 0.08). A cut-off value of 17.3 kPa, prioritising specificity, is proposed for routine diagnosis of significant AL liver infiltration. CONCLUSION: LS > 17.3 kPa is suggestive of AL hepatic disease in patients with non-fibrotic liver changes, and may have diagnostic value in patients with known AL.

A Model to Estimate the Amount of Primary Inoculum of Elsinoë ampelina.

In Eastern Canada, anthracnose, caused by the fungus Elsinoë ampelina, is a serious disease on susceptible grape cultivars. In the absence of management tools, anthracnose management relies almost exclusively on fungicide applications programmed at fixed intervals. Therefore, a better understanding of the factors affecting primary inoculum release and abundance would help in the timing of the first fungicide applications. The temporal dynamics of airborne primary inoculum released from cane cankers were investigated from 2007 to 2010. One to three times per week, starting in the first week of April, six 12-cmlong cane pieces were randomly selected from diseased canes that had overwintered on a vineyard floor. The concentration of E. ampelina conidia was expressed as the number of conidia per square millimeter of canker. In total, 27, 32, 33, and 118 samplings were conducted in 2007, 2008, 2009, and 2010, respectively, with the 118 samplings conducted on three sites at 49, 35, and 34 samplings for site 1, 2, and 3, respectively. Each year, the number of conidia per square millimeter of canker was expressed as the proportion of seasonal inoculum (PSI) at the same site and analyzed as a function of degree-days (DD; base temperature = 0°C) accumulated since 1 April (cumulative degreedays [CDD]). The nonlinear sigmoid model in the form PSI = 1.003/(1 + e-((CDD - 566.133)/139.204)) provided adequate fit to the observed data (P < 0.0001, R2 = 0.97). When the model was validated against independent data, the model adequately predicted PSI; however, reliability was improved by adding a "dry days" threshold of 6 days during which accumulation of DD is stopped. This study shows that primary inoculum of grape anthracnose is available early in the season before bud break; meaning that emerging leaves could be infected provided that weather conditions are favorable. The results also show that there is an overlap in the availability of primary and secondary inoculum, mainly during the period of rapid leaf growth, a situation that may explain the explosive nature of the disease. The results suggest that, on susceptible cultivars and when there is a history of anthracnose in the vineyard, a fungicide spray program should be initiated early in the season, as soon as leaves are present.

Ribavirin exposure after the first dose is predictive of sustained virological response in chronic hepatitis C.

UNLABELLED: The impact of ribavirin exposure on sustained virological response (SVR) in patients with chronic hepatitis C is unknown. Preliminary studies showed marked inter-individual variability of ribavirin concentrations despite dose adjustment for body weight (BW) and suggested there was a correlation between single time point concentrations and SVR. None of them evaluated the global exposure to ribavirin. This study was conducted to determine whether early ribavirin global exposure is related with SVR. An exploratory pharmacokinetic-pharmacodynamic (PK-PD) study was conducted in genotype 1 hepatitis C patients treated with peginterferon alfa-2a and ribavirin (dose-adjusted for BW) for 12 weeks, to which amantadine was added for the following 36 weeks. Full and abbreviated ribavirin area under the concentration time curves (AUC(0-12h), AUC(0-4h)) were derived from plasma concentration profiles at day 0 (D0), week 12 (W12), W12 + 1 day, and W24. Virological follow-up was performed at D0 (0, 12, and 24 hours), W2, W4, W6, and monthly until W72 (TaqMan polymerase chain reaction, cut-off 15 international units/mL). Twenty-eight patients were enrolled in the study and 24 completed it. Patients with a SVR had a significantly higher D0 AUC(0-12h) (3695 [1571-6916] versus 2937 [1266-4913] microg/hour/L, P = 0.03) and D0 AUC(0-4h) (2010 [615-3175] versus 1340 [622-2246] microg/hour/L, P = 0.03). Patients with D0 AUCs above the cut-off values defined by receiver operating characteristic curves (3014 microg/hour/L and 1755 microg/hour/L for AUC(0-12h) and AUC(0-4h), respectively) had a significantly better chance of achieving an SVR than patients with AUCs under the thresholds (odds ratio = 16.0, 95% confidence interval 1.54-166.6, P = 0.02 and odds ratio = 8.9, 95% confidence interval, 1.4-56.6; P = 0.02). CONCLUSION: Ribavirin exposure at D0 is significantly related to SVR. To our knowledge, this is the first study to give an early pharmacokinetic predictor of SVR. We propose a minimum AUC(0-4h) threshold of 1755 microg/hour/L at D0 as a target for ribavirin dose adjustment.