Persistence of Hepatitis C Virus during and after Otherwise Clinically Successful Treatment of Chronic Hepatitis C with Standard Pegylated Interferon α-2b and Ribavirin Therapy

Resolution of chronic hepatitis C is considered when serum HCV RNA becomes repeatedly undetectable and liver enzymes normalize. However, long-term persistence of HCV following therapy with pegylated interferon-α/ribavirin (PegIFN/R) was reported when more sensitive assays and testing of serial plasma, lymphoid cells (PBMC) and/or liver biopsies was applied. Our aim was to reassess plasma and PBMCs collected during and after standard PegIFN/R therapy from individuals who became HCV RNA nonreactive by clinical testing. Of particular interest was to determine if HCV genome and its replication remain detectable during ongoing treatment with PegIFN/R when evaluated by more sensitive detection approaches. Plasma acquired before (n = 11), during (n = 25) and up to 12–88 weeks post-treatment (n = 20) from 9 patients and PBMC (n = 23) from 3 of them were reanalyzed for HCV RNA with sensitivity <2 IU/mL. Clone sequencing of the HCV 5′-untranslated region from plasma and PBMCs was done in 2 patients. HCV RNA was detected in 17/25 (68%) plasma and 8/10 (80%) PBMC samples collected from 8 of 9 patients during therapy, although only 5.4% plasma samples were positive by clinical assays. Among post-treatment HCV RNA-negative plasma samples, 9 of 20 (45.3%) were HCV reactive for up to 59 weeks post-treatment. Molecularly evident replication was found in 6/12 (50%) among PBMC reactive for virus RNA positive strand collected during or after treatment. Pre-treatment point mutations persisted in plasma and/or PBMC throughout therapy and follow-up. Therefore, HCV is not completely cleared during ongoing administration of PegIFN/R otherwise capable of ceasing progression of CHC and virus commonly persists at levels not detectable by the current clinical testing. The findings suggest the need for continued evaluation even after patients achieve undetectable HCV RNA post-treatment

Effect of the optimize heart failure care program on clinical and patient outcomes – The pilot implementation in Vietnam

Background: The Ho-Chi-Minh-city Heart Institute in Vietnam took part in the Optimize Heart Failure (OHF) Care Program, designed to improve outcomes following heart failure (HF) hospitalization by increasing patient awareness and optimizing HF treatment. Methods: HF patients hospitalized with left ventricular ejection-fraction (LVEF) <50% were included. Patients received guideline-recommended HF treatment and education. Clinical signs, treatments and outcomes were assessed at admission, discharge, 2 and 6 months (M2, M6). Patients’ knowledge and practice were assessed at M6 by telephone survey. Results: 257 patients were included. Between admission and M2 and M6, heart rate decreased significantly, and clinical symptoms improved significantly. LVEF increased significantly from admission to M6. 85% to 99% of patients received education. At M6, 45% to 78% of patients acquired knowledge and adhered to practice regarding diet, exercise, weight control, and detection of worsening symptoms. High use of renin-angiotensin-aldosterone-system inhibitors (91%), mineralocorticoid-receptor-antagonists (77%) and diuretics (85%) was noted at discharge. Beta-blocker and ivabradine use was less frequent at discharge but increased significantly at M6 (from 33% to 51% and from 9% to 20%, respectively, p < 0.001). There were no in-hospital deaths. Readmission rates at 30 and 60 days after discharge were 8.3% and 12.5%, respectively. Mortality rates at 30 days, 60 days and 6 months were 1.2%, 2.5% and 6.4%, respectively. Conclusions: The OHF Care Program could be implemented in Vietnam without difficulty and was associated with high usage of guideline-recommended drug therapy. Although education was delivered, patient knowledge and practice could be further improved at M6 after discharge

Inhibition of the PKCγ-ε Pathway Relieves from Meningeal Nociception in an Animal Model: An Innovative Perspective for Migraine Therapy?

There is convincing evidence that nitric oxide (NO) may be a causative factor in the pathogenesis of migraine. We investigated the consequences of NO donors’ administration on meningeal processes related to the development of migraine pain in an animal model of meningeal nociception. The administration in mice of the NO donors nitroglycerin (GTN) and sodium nitroprusside (SNP) produced a delayed meningeal upregulation of interleukin-1ß and inducible NO synthase. A thermal allodynia and hyperalgesia devoid of side effects was produced 1 to 4 h after administration. To clarify the cellular pathways modulated by GTN and SNP, we examined the expression of cellular factors involved in pain modulation, such as protein kinase C (PKC) and its downstream effectors. Western blotting experiments showed an upregulation and increased phosphorylation of PKCγ and PKCε within dura mater after NO donors’ administration. A dramatic PKC-dependent increase of the phosphorylation of cyclic AMP response element binding protein (CREB) and signal transducer and activator of transcription (STAT)-1 was observed, along with an activation of the nuclear factor-κB (NF-κB) pathway, as reflected by a reduction of the inhibitory protein-κ-Bα (IκBα). Furthermore, the PKC blocker, Calphostin C, prevented the GTN and SNP-induced pain hypersensitivity. These results suggest the relevance of the PKC-mediated pathway in the induction of meningeal nociception and might help clarify the etiopathology of migraines. We can suggest PKC as a new target for migraine pain. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13311-012-0151-8) contains supplementary material, which is available to authorized users