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1.
Clin Microbiol Infect ; 25(4): 513.e1-513.e6, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29981869

RESUMO

OBJECTIVES: The aim of the study was to characterize the differences in the frequencies of NS3 and NS5A resistance-associated variants (RAVs) among Polish therapy-naive genotype 1 (G1) hepatitis C virus (HCV)-monoinfected and human immunodeficiency virus (HIV)/HCV-coinfected patients including clustering patterns and association of RAV frequency with liver fibrosis. METHODS: NS3/NS5A RAVs were identified by population sequencing in 387 directly acting antiviral treatment-naive G1-infected individuals (54 with genotype 1a (G1a) and 333 with genotype 1b (G1b)). Liver fibrosis was assessed based on histopathology or ultrasound elastography. Phylogenetic clusters were identified using maximum likelihood models. For statistics, chi-squared or two-sided Fisher's exact tests and multivariate logistic regression models were used, as appropriate. RESULTS: NS3 RAVs were found in 33.33% (18/54) for G1a and 2.62% (8/297) for G1b whereas NS5A variants were present in 5.55% (3/54) G1a and 9.31% (31/333) G1b sequences. Variations in NS5A 31 and 93 codon positions were found only in G1b (4.2% (14/333) for L31I/F/M and 5.39% (17/333) for Y93H). NS5A RAVs were more frequent among patients with advanced liver fibrosis (17.17% (17/99) for F3-F4 versus 6.94% (17/245) for F0-F2; p 0.004) or liver cirrhosis (20.34% (12/59) for F4 versus 7.72% (22/285) for F0-F3; p 0.003). Liver cirrhosis (F4) was associated with higher odds ratio of the NS5A RAVs among HCV-infected patients (odds ratio 2.34, 95% CI 1.004-5.291; p 0.049). NS5A RAVs were less frequent among sequences forming clusters and pairs (5.16% (8/155) versus 11.21% (26/232); p 0.039). CONCLUSIONS: Presence of NS5A RAVs correlated with progression of liver fibrosis and represents de novo selection of variants rather than transmission of drug resistance. Hence, the presence of NS5A RAVs may be a predictor for a long-lasting HCV infection.


Assuntos
Farmacorresistência Viral/genética , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/virologia , Proteínas não Estruturais Virais/genética , Adulto , Antivirais/uso terapêutico , Feminino , Infecções por HIV/complicações , Hepacivirus/classificação , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/uso terapêutico , Polônia , Inibidores de Proteases/uso terapêutico , Simeprevir/uso terapêutico
2.
Aliment Pharmacol Ther ; 44(9): 946-956, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27611776

RESUMO

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.


Assuntos
Anilidas/administração & dosagem , Carbamatos/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Compostos Macrocíclicos/administração & dosagem , Ribavirina/administração & dosagem , Ritonavir/administração & dosagem , Sulfonamidas/administração & dosagem , Uracila/análogos & derivados , 2-Naftilamina , Adulto , Anilidas/efeitos adversos , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Carbamatos/efeitos adversos , Ciclopropanos , Diarreia/induzido quimicamente , Quimioterapia Combinada , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/diagnóstico , Humanos , Lactamas Macrocíclicas , Cirrose Hepática/diagnóstico , Cirrose Hepática/tratamento farmacológico , Compostos Macrocíclicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prolina/análogos & derivados , Ribavirina/efeitos adversos , Ritonavir/efeitos adversos , Sulfonamidas/efeitos adversos , Resultado do Tratamento , Uracila/administração & dosagem , Uracila/efeitos adversos , Valina
3.
Meat Sci ; 43S1: 125-34, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-22060646

RESUMO

Economical advantages favour hot processing of meat. Losses during chilling, cost of refrigeration, labour and transportation can be considerably reduced giving to meat processors extra value. However, several technical and technological problems delay implementation of this technology by industry. Beginning with cost of investment necessary to retrofit facilities into hot processing of meat, synchronizing organization of work at the factory according to this technology, and finally to insure the required, stable quality of meat and meat products. Therefore, before full industrial implementation several technological problems still should be solved in laboratory and pilot plant experiments and confirmed at full factory scale. This paper reviews the latest research publications on hot processing of meat.

4.
Meat Sci ; 6(3): 185-90, 1982 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22054862

RESUMO

The physico-chemical properties of meat model blends (basic composition: fresh lean pork, pork back fat, 2% NaCl, water with ice), with added mechanically recovered pork (MRM), were studied. Fresh MRM was added at levels of 10% and 20% substitution of meat protein with or without further substitution by 10% sodium caseinate or soya isolate. The addition of MRM to meat blends caused an increase in the pH, the water-holding capacity, the viscosity, the dominant wavelength and colour purity. No effects on emulsifying capacity were observed but thermal cooking losses and lightness of colour were reduced. The addition of blends of MRM and soya isolate or sodium caseinate caused lower values of the investigated features than those observed when only MRM was used.

5.
Meat Sci ; 2(2): 145-53, 1978 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22054974

RESUMO

Differences were found in a number of attributes (pH value, changes in volume and linear dimensions, cooking loss, tenderness and water-holding capacity) between porcine muscles subjected to vacuum massage and those in non-massaged controls. Histologically there were changes in the structure of massaged muscles. The content of connective tissue in massaged meat appears to influence water-holding capacity and cooking loss to some extent.

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