Durability of virologic response, risk of de novo hepatocellular carcinoma, liver function and stiffness 2 years after treatment with ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin in the AMBER, real-world experience study.

We followed for 2 years patients treated with direct-acting agents (DAA) to assess long-term durability of virologic response, improvement of liver function, reduction in liver stiffness (LS) and risk of hepatocellular carcinoma (HCC). The study included patients from 16 hepatologic centres involved in the AMBER, investigator-initiated study on treatment of chronic hepatitis C patients within a programme preceding EU registration of ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin. A total of 204 patients among 209 from the primary study were enrolled, 200 with available testing at 2-year follow-up (2yFU) with undetectable HCV RNA (198 responders and 2 nonresponders retreated). During 2yFU, 4 patients died, 17 had hepatic decompensation and 3 needed liver transplantation. De novo hepatocellular carcinoma was diagnosed in 4 and its recurrence in 3 patients. Significant decreases in bilirubin, MELD, Child-Pugh scores and liver stiffness, and increases in albumin level were observed during 2yFU. Strengths of the study were a fixed period of post-treatment follow-up, prospective character of the study and high proportion of available patients from the primary study. The major weaknesses were lack of a comparative arm and relatively insufficient number of patients for subsets analysis. In conclusion, 2-year follow-up confirmed durability of virologic response after treatment of HCV infection with ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin. It was accompanied by significant improvement of major measures of hepatic function and reduction of hepatic stiffness. Successful therapy did not prevent hepatic decompensation, HCC or death in cirrhotics that support the need for longer than 2-year monitoring for possible disease progression.

Real-world effectiveness and safety of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin in hepatitis C: AMBER study.

BACKGROUND: Virologic and safety outcomes of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) therapy have shown high sustained virologic response (SVR) rates and good tolerability in most patient populations in pre-registration studies. AIM: To confirm these clinical trial findings in the treatment of genotype 1 and 4 hepatitis C under real-world conditions. METHODS: Patients enrolled for treatment with OBV/PTV/r ± DSV ± RBV based on therapeutic guidelines were included, and the regimen was administered according to product characteristics. Clinical and laboratory data, including virologic response, were collected at baseline, end of treatment (EOT) and 12 weeks after EOT. RESULTS: A total of 209 patients with chronic hepatitis C were enrolled, most were genotype 1b-infected (84.2%) and 119 (56.9%) had liver cirrhosis. Among these, 150 (71.7%) had failed previous anti-viral therapies and 84 (40.2%) were null-responders. At 12 weeks after EOT, SVR was achieved by 207 (99.0%) patients, ranging from 96.4% to 100.0% across subgroups. All Child-Pugh B and post-orthotopic liver transplantation patients achieved SVR. Adverse events occurred in 151 (72.2%) patients and were mostly mild and associated with the use of RBV. Serious adverse events, including hepatic decompensation, renal insufficiency, anaemia, hepatotoxicity and diarrhoea, were reported in eight (3.8%) patients. In five (2.4%) patients, adverse events led to treatment discontinuation. On-treatment decompensation was experienced by seven (3.3%) patients. CONCLUSIONS: The results of our study confirm previous findings. They demonstrate excellent effectiveness and a good safety profile of OBV/PTV/r± DSV±RBV in HCV genotype 1-infected patients treated in the real-world setting.

Different T-cell activation by streptozotocin and Freund's adjuvant in popliteal lymph node (PLN).

A popliteal lymph node (PLN) test was further validated for predictive screening of autoimmunity-inducing drugs. Autoimmune-like T-cell activation of streptozotocin (STZ) was compared with the effect of Freund's complete adjuvant (FCA), injected locally into the foot pad of BALB/c mice. Early cell activation in enlarged PLN was monitored by flow cytometry. Injection of both STZ and FCA markedly increased the absolute PLN cell number as well as specific T-helper (CD4+), T-suppressor/cytotoxic (CD8+), and B (Ig+) subsets. However, quantitative analysis of early T-cell activation revealed important differences between STZ-induced PLN reaction and FCA-related lymphoproliferation. At 72 h, the number of cells stained with anti-early activation marker (EAM+; CD69+) increased over 10 times in STZ-enlarged nodes and only 3 times in the FCA-inflamed nodes. Furthermore, different cytometric profiles were noted for STZ-activated and FCA-activated cells stained with anti-interleukin-2 receptor (IL-2R) (CD25+). The data suggest the applicability of early cytometric screening of enlarged PLN for predictive analysis detection of chemicals inducing an autoimmune-like reaction.

A new technology for the production of valuable vitamin extracts from wheat and rye germs.

A method for nearly complete extraction of the lipid fraction from wheat and rye germs was developed, and the technological parameters of the production process were specified. The resulting preparations are extracts rich in vitamin E and other biologically active components. Dermatological studies and application in the cosmetic industry have testified to the suitability of these preparations for use in cosmetic and pharmaceutical products. Owing to their high content of unsaturated fatty acids and to a natural combination of biologically active compounds, the preparations from wheat and rye germs obtained by our method on an industrial scale find increasingly wider application. The post-extraction residue free from the lipid fraction is high-value feed.

Production and application of flavour isolates of plant origin.

A method for preparation of natural flavour isolates from fruits, vegetables and herb spices, developed at the Institute of Fermentation Industry in Warsaw, was presented. It involves extraction of raw materials with CCl2F2 at 5 X 10(5) Pa. For the different groups of raw materials, three types of extracting apparatuses were developed. The quality of the preparations, technological parameters of their production, storage conditions and applications are the subject of several publications and non-published materials; therefore, the present paper is of an only general nature.

The role of sulphur compounds in evaluation of flavouring value of some plant raw materials.

The aim of the study was to determine the composition of flavour isolates from garlic and horse-radish, prepared by dichlorodifluoromethane extraction. Gas chromatography, with olfactory determination of the flavour of the resolved components, and gas chromatography combined with mass spectrometry were used. In the garlic extract 19 components comprising mono-, di-, and trisulphides and thiophene derivatives were detected. In the horse-radish extract 14 components including isothiocyanates, thiocyanates and cyanides were identified.