Hepatitis C viral load does not predict disease outcome: going beyond numbers

The analysis of 58 patients with chronic hepatitis C without cirrhosis and treated with interferon-alpha demonstrated that hepatitis C viral (HCV) load does not correlate with the histological evolution of the disease (p = 0.6559 for architectural alterations and p = 0.6271 for the histological activity index). Therefore, the use of viral RNA quantification as an evolutive predictor or determinant of the severity of hepatitis C is incorrect and of relative value. A review of the literature provided fundamental and interdependent HCV (genotype, heterogeneity and mutants, specific proteins), host (sex, age, weight, etc) and treatment variables (dosage, time of treatment, type of interferon) within the broader context of viral kinetics, interferon-mediated immunological response (in addition to natural immunity against HCV) and the role of interferon as a modulator of fibrogenesis. Therefore, viral load implies much more than numbers and the correct interpretation of these data should consider a broader context depending on multiple factors that are more complex than the simple value obtained upon quantification.     

Use of an immunoglobulin G avidity test to discriminate between primary and secondary dengue virus infections

An enzyme-linked immunosorbent assay-based immunoglobulin G (IgG) antibody avidity test was evaluated by using sera from 57 patients with acute dengue infection. Overall, 55 of 57 patients were correctly classified (27 of 27 with primary dengue and 28 of 30 with secondary dengue). We conclude that the IgG avidity test can be useful for differentiating between acute, primary, and secondary dengue infections.     

Pharmacodynamics of PEG-IFN-[alpha]-2a and HCV response as a function of IL28B polymorphism in HIV/HCV-coinfected patients

We examined the association between IL28B single-nucleotide polymorphism rs12979860, hepatitis C virus (HCV) kinetic, and pegylated interferon alpha-2a pharmacodynamic parameters in HIV/HCV-coinfected patients from South America. Twenty-six subjects received pegylated interferon alpha-2a + ribavirin. Serum HCV-RNA and interferon concentrations were measured frequently during the first 12 weeks of therapy and analyzed using mathematical models. African Americans and whites had a similar distribution of IL28B genotypes (P = 0.5). The IL28B CC genotype was overrepresented (P = 0.015) in patients infected with HCV genotype-3 compared with genotype-1. In both genotype-1 and genotype-3, the first-phase viral decline and the average pegylated interferon-alpha-2a effectiveness during the first week of therapy were larger (trend P <= 0.12) in genotype-CC compared with genotypes-TC/TT. In genotype-1 patients, the second slower phase of viral decline (days 2-29) and infected cells loss rate, [delta], were larger (P = 0.02 and 0.11, respectively) in genotype-CC than in genotypes-TC/TT. These associations were not observed in genotype-3 patients.     

Detection of HCV by PCR in serum and PBMC of patients with hepatitis C after treatment.

Although hepatitis C is mainly hepatotropic, some studies suggest that hepatitis C virus (HCV) infects peripheral blood mononuclear cells (PBMC), using them as a reservoir, which might contribute to the development of resistance to treatment. Fifty-four hepatitis-C patients, who had been submitted to treatment, were selected. Blood samples were collected on the same day for the detection of HCV RNA in serum and PBMC by PCR, using the Amplicor HCV 2.0 assay (Roche Diagnostics). HCV genotyping was performed using the INNO-LiPA HCV kit (Versant, Bayer Diagnostics). HCV RNA was detected in both serum and PBMC in 35 (64%) patients and no RNA in 16 (29.6%). Disagreement between the serum and PBMC results was observed for three patients (5.6%), with HCV RNA being detected in PBMC but not in serum. Four months later, new serum and PBMC samples were collected from one of these patients and HCV RNA was detected in both samples, showing that PBMC can reveal signs of a lack of response to treatment. We conclude that the absence of HCV in the serum of patients with chronic hepatitis C by the end of treatment does not mean that there is no circulating virus. HCV in mononuclear cells may be an indicator of the persisting infection.     

Amygdala subnuclei and healthy cognitive aging

Amygdala is a group of nuclei involved in the neural circuits of fear, reward learning, and stress. The main goal of this magnetic resonance imaging (MRI) study was to investigate the relationship between age and the amygdala subnuclei volumes in a large cohort of healthy individuals. Our second goal was to determine effects of the apolipoprotein E (APOE) and brain‐derived neurotrophic factor (BDNF) polymorphisms on the amygdala structure. One hundred and twenty‐six healthy participants (18–85 years old) were recruited for this study. MRI datasets were acquired on a 4.7 T system. Amygdala was manually segmented into five major subdivisions (lateral, basal, accessory basal nuclei, and cortical, and centromedial groups). The BDNF (methionine and homozygous valine) and APOE genotypes (ε2, homozygous ε3, and ε4) were obtained using single nucleotide polymorphisms. We found significant nonlinear negative associations between age and the total amygdala and its lateral, basal, and accessory basal nuclei volumes, while the cortical amygdala showed a trend. These age‐related associations were found only in males but not in females. Centromedial amygdala did not show any relationship with age. We did not observe any statistically significant effects of APOE and BDNF polymorphisms on the amygdala subnuclei volumes. In contrast to APOE ε2 allele carriers, both older APOE ε4 and ε3 allele carriers had smaller lateral, basal, accessory basal nuclei volumes compared to their younger counterparts. This study indicates that amygdala subnuclei might be nonuniformly affected by aging and that age‐related association might be gender specific.     

Study of Radiation-Induced Defects in p-Type Si1−xGex Diodes before and after Annealing

In this work, electrically active defects of pristine and 5.5 MeV electron irradiated p-type silicon–germanium (Si_1−xGe_x)-based diodes were examined by combining regular capacitance deep-level transient spectroscopy (C-DLTS) and Laplace DLTS (L-DLTS) techniques. The p-type SiGe alloys with slightly different Ge contents were examined. It was deduced from C-DLTS and L-DLTS spectra that the carbon/oxygen-associated complexes prevailed in the pristine Si_0.949Ge_0.051 alloys. Irradiation with 5.5 MeV electrons led to a considerable change in the DLT spectrum containing up to seven spectral peaks due to the introduction of radiation defects. These defects were identified using activation energy values reported in the literature. The double interstitial and oxygen complexes and the vacancy, di-vacancy and tri-vacancy ascribed traps were revealed in the irradiated samples. The interstitial carbon and the metastable as well as stable forms of carbon–oxygen (C_iO_i^* and C_iO_i) complexes were also identified for the electron-irradiated SiGe alloys. It was found that the unstable form of the carbon–oxygen complex became a stable complex in the irradiated and the subsequently annealed (at 125 °C) SiGe samples. The activation energy shifts in the radiation-induced deep traps to lower values were defined when increasing Ge content in the SiGe alloy.