Restrictions for reimbursement of interferon-free direct-acting antiviral drugs for HCV infection in Europe.

All-oral direct-acting antiviral drugs (DAAs) for hepatitis C virus, which have response rates of 95% or more, represent a major clinical advance. However, the high list price of DAAs has led many governments to restrict their reimbursement. We reviewed the availability of, and national criteria for, interferon-free DAA reimbursement among countries in the European Union and European Economic Area, and Switzerland. Reimbursement documentation was reviewed between Nov 18, 2016, and Aug 1, 2017. Primary outcomes were fibrosis stage, drug or alcohol use, prescriber type, and HIV co-infection restrictions. Among the 35 European countries and jurisdictions included, the most commonly reimbursed DAA was ombitasvir, paritaprevir, and ritonavir, with dasabuvir, and with or without ribavirin (33 [94%] countries and jurisdictions). 16 (46%) countries and jurisdictions required patients to have fibrosis at stage F2 or higher, 29 (83%) had no listed restrictions based on drug or alcohol use, 33 (94%) required a specialist prescriber, and 34 (97%) had no additional restrictions for people co-infected with HIV and hepatitis C virus. These findings have implications for meeting WHO targets, with evidence of some countries not following the 2016 hepatitis C virus treatment guidelines by the European Association for the Study of Liver.

Glomerular filtration rate measured using the Patlak plot technique and contrast-enhanced dynamic MRI with different amounts of gadolinium-DTPA.

We determined the optimum gadolinium (Gd)-DTPA dose and time window for calculating the glomerular filtration rate (GFR) using contrast-enhanced (CE) dynamic MRI and the Patlak plot technique. Twelve adult volunteers with healthy kidneys were included in the study. As a reference method the GFR was measured by iopromide plasma clearance. A three-dimensional gradient-echo (GRE) sequence with a flip angle of 50 degrees was used for MRI. Signal was measured using a body surface coil with four elements. Each volunteer was examined on four days using 2 mL, 4 mL, 8 mL, or 16 mL of Gd-DTPA 0.5 mmol/mL dissolved with sodium chloride (NaCl) 0.9% to a total of 60 mL. The injection rate was 1 mL/second. A Patlak plot was calculated from the kidney and aorta signals. The mean reference GFR was 133 mL/min (min-max, 116-153 mL/min). The best correlation of GFR calculated from MRI data compared to the reference method was found in a time window 30-90 seconds after aortic signal rise using 16 mL Gd-DTPA. Pearson's correlation coefficient was r = 0.83, and the standard deviation (SD) from the line of regression was 10.5 mL/minute. We found a significantly lower average GFR(MR) using 16 mL Gd-DTPA compared to 4 mL and 2 mL in the late time window 60-120 seconds post aortic rise. A dose of 16 mL Gd-DTPA was optimal for measuring GFR using dynamic MRI and the Patlak plot technique. The slope should be measured in a time window of 30-90 seconds post aortic rise.