Effectiveness and safety of first-generation protease inhibitors in clinical practice: Hepatitis C virus patients with advanced fibrosis.

AIM: To evaluates the effectiveness and safety of the first generation, NS3/4A protease inhibitors (PIs) in clinical practice against chronic C virus, especially in patients with advanced fibrosis. METHODS: Prospective study and non-experimental analysis of a multicentre cohort of 38 Spanish hospitals that includes patients with chronic hepatitis C genotype 1, treatment-naïve (TN) or treatment-experienced (TE), who underwent triple therapy with the first generation NS3/4A protease inhibitors, boceprevir (BOC) and telaprevir (TVR), in combination with pegylated interferon and ribavirin. The patients were treatment in routine practice settings. Data on the study population and on adverse clinical and virologic effects were compiled during the treatment period and during follow up. RESULTS: One thousand and fifty seven patients were included, 405 (38%) were treated with BOC and 652 (62%) with TVR. Of this total, 30% (n = 319) were TN and the remaining were TE: 28% (n = 298) relapsers, 12% (n = 123) partial responders (PR), 25% (n = 260) null-responders (NR) and for 5% (n = 57) with prior response unknown. The rate of sustained virologic response (SVR) by intention-to-treatment (ITT) was greater in those treated with TVR (65%) than in those treated with BOC (52%) (P < 0.0001), whereas by modified intention-to-treatment (mITT) no were found significant differences. By degree of fibrosis, 56% of patients were F4 and the highest SVR rates were recorded in the non-F4 patients, both TN and TE. In the analysis by groups, the TN patients treated with TVR by ITT showed a higher SVR (P = 0.005). However, by mITT there were no significant differences between BOC and TVR. In the multivariate analysis by mITT, the significant SVR factors were relapsers, IL28B CC and non-F4; the type of treatment (BOC or TVR) was not significant. The lowest SVR values were presented by the F4-NR patients, treated with BOC (46%) or with TVR (45%). 28% of the patients interrupted the treatment, mainly by non-viral response (51%): this outcome was more frequent in the TE than in the TN patients (57% vs 40%, P = 0.01). With respect to severe haematological disorders, neutropaenia was more likely to affect the patients treated with BOC (33% vs 20%, P ≤ 0.0001), and thrombocytopaenia and anaemia, the F4 patients (P = 0.000, P = 0.025, respectively). CONCLUSION: In a real clinical practice setting with a high proportion of patients with advanced fibrosis, effectiveness of first-generation PIs was high except for NR patients, with similar SVR rates being achieved by BOC and TVR.

[Prognostic value of serum levels of tumor necrosis factor-alpha in patients with heart failure]. / Valor pronóstico de los niveles séricos del factor de necrosis tumoral alfa en pacientes con insuficiencia cardíaca.

INTRODUCTION AND OBJECTIVE: Tumor necrosis factor-alpha is an inflammatory cytokine which rises in heart failure and has prognostic value in severe cases. Its value is less established in moderate cases. Our aim was to determine its prognostic value in cases from a community hospital. PATIENTS: We studied 50 patients, average age 59.5 12.3 years, with dilated cardiomyopathy (72% non-ischemic) and moderate heart failure (59% functional class II). METHODS: Patients were evaluated with an echocardiogram and cardiopulmonary treadmill stress test (Naughton), muscular strength measurements (hand dynamometer), blood tumor necrosis factor levels, and an average follow-up of 17.5 9 months (range, 1-29 months). All causes of mortality, cardiac transplantation, and readmissions for heart failure were recorded. RESULTS: Twenty-three patients experienced events. These patients were older (63 +/- 12.7 vs 55.7 +/- 11.4 years; p = 0.042), had a lower peak VO2 (13.7 +/- 3.9 vs 16 +/- 3.3 ml/kg/min; p = 0.035), and higher peak VE/VCO2 and factor levels [41.9 +/- 10.6 vs 33.2 +/- 5.7; p = 0.001 and 4.3 (3.1-7.9) vs 3.3 (2.4-4.3) pg/ml; p = 0.021, respectively]. In the Cox model, the only variable with independent prognostic value was peak VE/VCO2 [HR 1.13 (1.07-1.19); p < 0.001]. The best cutoff point was 34.5 (sensitivity, 86.4%; specificity, 58.3%; p = 0.0007). The cytokine had no independent prognostic value. CONCLUSIONS: Our patients with events were older, had a lower peak VO2, and higher peak VE/VCO2 and serum tumor necrosis factor levels. However, only peak VE/VCO2 had independent prognostic value.

Valor pronóstico de los niveles séricos del factor de necrosis tumoral alfa en pacientes con insuficiencia cardíaca / Prognostic Value of Serum Levels of Tumor Necrosis Factor-Alpha in Patients with Heart Failure

Introducción y objetivos. El factor de necrosis tumoral alfa es una citocina inflamatoria que se eleva en la insuficiencia cardíaca, con valor pronóstico en casos graves, aunque menos establecido en casos moderados. Pretendemos conocer su valor pronóstico en los casos de un hospital secundario. Pacientes. Se estudian 50 pacientes de 59,5 ñ 12,3 años, con miocardiopatía dilatada (72 por ciento no isquémica), con insuficiencia cardíaca moderada (clase funcional II, 59 por ciento).Métodos. Se realizó un ecocardiograma y una ergoespirometría (Naughton), y se determinaron la fuerza muscular (dinamómetro de mano) y los valores plasmáticos del factor de necrosis tumoral; se efectuó un seguimiento de 17,5 ñ 9 meses (intervalo, 1-29), en el que se recogieron la mortalidad total, el trasplante cardíaco y el reingreso por insuficiencia cardíaca. Resultados. Tuvieron episodios 23 pacientes, que tenían mayor edad (63 ñ 12,7 frente a 55,7 ñ 11,4 años; p = 0,042), un VO2 pico (pVO2) más bajo (13,7 ñ 3,9 frente a 16 ñ 3,3 ml/kg/min; p = 0,035), y una relación pVE/VCO2 y valores del factor más elevados (41,9 ñ 10,6 frente a 33,2 ñ 5,7; p = 0,001 y 4,3 [3,1-7,9] frente a 3,3 [2,4-4,3] pg/ml; p = 0,021, respectivamente). En el análisis de Cox, la única variable con valor pronóstico independiente fue la relación pVE/VCO2 (RR = 1,13 [1,071,19]; p < 0,001), con un mejor punto de corte de 34,5 (sensibilidad, 86,4 por ciento; especificidad, 58,3 por ciento; p = 0,0007). La citocina no tuvo valor pronóstico independiente. Conclusiones. Nuestros pacientes con episodios tienen mayor edad, un pVO2 menor y la relación pVE/VCO2 y los valores séricos del factor de necrosis tumoral más elevados, aunque sólo el pVE/VCO2 tiene valor pronóstico independiente. (AU)