HIV-coinfected patients respond worse to direct-acting antiviral-based therapy against chronic hepatitis C in real life than HCV-monoinfected individuals: a prospective cohort study.

OBJECTIVE: HIV/HCV-coinfected patients and hepatitis C virus (HCV) monoinfected subjects are thought to respond equally to direct-acting antiviral (DAA)-based therapy despite the lack of data derived from clinical trials. This study is aimed to evaluate the impact of HIV coinfection on the response to DAA-based treatment against HCV infection in the clinical practice. PATIENTS AND METHODS: In a prospective multicohort study, patients who initiated DAA-based therapy at the Infectious Disease Units of 33 hospitals throughout Spain were included. The primary efficacy outcome variables were the achievement of sustained virologic response 12 weeks after the scheduled end of therapy date (SVR12). RESULTS: A total of 908 individuals had reached the SVR12 evaluation time-point, 426 (46.9%) were HIV/HCV-coinfected, and 472 (52%) received interferon (IFN)-free therapy. In an intention-to-treat analysis, SVR12 rates in subjects with and without HIV-coinfection were 55.3% (94/170 patients) versus 67.3% (179/266 subjects; p = 0.012) for IFN-based treatment and 86.3% (221/256 subjects) versus 94.9% (205/216 patients, p = 0.002) for IFN-free regimens. Relapse after end-of-treatment response to IFN-free therapy was observed in 3/208 (1.4%) HCV-monoinfected subjects and 10/231 (4.4%) HIV/HCV-coinfected individuals (p = 0.075). In a multivariate analysis adjusted for age, sex, transmission route, body-mass index, HCV genotype, and cirrhosis, the absence of HIV-coinfection (adjusted odds ratio: 3.367; 95% confidence interval: 1.15-9.854; p = 0.027) was independently associated with SVR12 to IFN-free therapy. CONCLUSIONS: HIV-coinfection is associated with worse response to DAA-based therapy against HCV infection. In patients receiving IFN-free therapy, this fact seems to be mainly driven by a higher rate of relapses among HIV-coinfected subjects.

Curación de un genotipo mixto, 1b y 4, de hepatitis C tras triple terapia basada en telaprevir / Hepatitis C genotype 1b and 4 cured after telaprevir-based therapy

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Prognostic value of inflammatory markers (notably cytokines and procalcitonin), nutritional assessment, and organ function in patients with sepsis.

OBJECTIVE: Procalcitonin is useful for the diagnosis of sepsis, but its prognostic value regarding mortality is unclear. Our objective was to determine the prognostic value of procalcitonin determined at the onset of sepsis, and to compare it with other markers of inflammatory response, malnutrition and organ dysfunction data. METHODS: We studied 253 hospitalized patients (146 men, 107 women) with a median age of 65 years. Sepsis was defined as infection, and at least two SIRS criteria. We assessed co-morbidities, nutritional status, bacteremia, procalcitonin and other inflammatory markers (PCR, TNF-alpha, IL6, TREM-1, IL-10, IL-1ra, CD14 and LBP), and organ function using the SOFA score. Mortality was assessed at 28 days after onset of sepsis. RESULTS: At day 28, 49 (19%) patients had died. Inflammatory markers showed only moderate predictive value for mortality, with IL-10 and IL-6 being the best predictors. Mortality was mainly related to organ dysfunction indicators (SOFA and Glasgow scores), serum lactate, ferritin and LDH levels, and to nutritional data such as subjective assessment, handgrip strength and serum transferrin levels. The most frequent location of sepsis was the lung, with 140 cases (55%), which showed more comorbidity, worse nutritional status, less frequent bacteremia and lower inflammatory response. When the analysis was limited to patients with non-pulmonary sepsis, organ dysfunction, nutritional status and inflammatory markers showed the best prognostic value. Of the inflammatory markers, procalcitonin showed only moderate predictive value; however it showed the highest correlation with bacteremia and the ability to discriminate non-complicated sepsis from severe forms. CONCLUSION: Procalcitonin only showed moderate predictive value for sepsis-related mortality, being surpassed by organ dysfunction, nutritional status, IL-10 and IL-6. However, it proved useful to discriminate between non-complicated and severe forms of sepsis.