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Introduction Chronic Hepatitis C infection is considered a systemic disease with extrahepatic manifestations, mainly neuropsychiatric symptoms, which is associated with a chronic low-grade inflammatory state. Hepatitis C virus (HCV) eradication is currently achieved in >98% of cases with oral direct-acting antivirals (DAA). Objectives To study potential clinical neuropsychiatric changes (mood, cognition, sleep, gastrointestinal, sickness, and motion) in HCV-infected patients after HCV eradication with DAA. Methods Design: Cohort study. Subjects: 37 HCV-infected patients, aged Results NRS total score and dimensions where different between cases and controls (.000) at baseline. NRS total score (.000) and mood (.000), cognition (.000), sleep (.002), gastrointestinal (.017), and sickness (.003), except motor dimension score (.130) showed significant longitudinal improvement. Conclusions HCV-infected patients with mild liver disease presented significantly worse scores for neurotoxicity symptomatology in all dimensions compared to healthy individuals. After HCV eradication with DAA, both at short and long follow-up a significant improvement of the NRS total score and each of the dimensions (except motor) were observed. However, they did not reach the values of healthy individuals, suggesting a not complete neuropsychiatric restoration in the period studied. Grant: ICIII-FIS:PI17/02297.(One way to make Europe) (RMS) and Gilead Fellowship-GLD17/00273 (ZM); and the support of SGR17/1798 (RMS) Disclosure No significant relationships.

A four-node, four-lane SDM mesh network with CD-ROADM nodes performing dual spatial channel routing and lane changes is reported, under centralized SDN control for space/spectrum assignments. The architecture achieves high utilization and low implementation cost.

The aim of this study is to review clinical trial data on the newly approved protease inhibitors boceprevir and telaprevir to develop consensus recommendations on the optimal use of these agents for the treatment of patients with chronic hepatitis C virus (HCV) infection. An expert panel of seven leading authorities in viral hepatitis was convened to establish and disseminate a practical guide on best practices for incorporating boceprevir and telaprevir into therapy for HCV infection in both treatment-naive and treatment-experienced patients. The topics covered include selecting candidates for boceprevir- or telaprevir-based treatments, predictors of response and early viral kinetics, response-guided therapy approaches, on-treatment management strategies to optimize the likelihood of response and minimize the risk of drug resistance, management of adverse effects during therapy and key considerations for special populations. The expert panel incorporated the best available clinical evidence into recommendations on how boceprevir and telaprevir should be used in the clinical setting. They indicated how treatment regimens may differ according to the baseline factors, such as presence of cirrhosis and when therapy may need to be modified or stopped altogether because of adverse events or poor virologic response. This practical guide will serve as a valuable resource for clinicians embarking on the new treatment paradigm of boceprevir or telaprevir in combination with peginterferon/ribavirin for chronic genotype 1 HCV infection.

Liver biopsy is the reference standard to assess liver fibrosis in chronic hepatitis C.To validate and compare the diagnostic performance of non-invasive tests for prediction of liver fibrosis severity and assessed changes in extracellular matrix markers after antiviral treatment.The performances of Forns' score, AST to platelet ratio index (APRI), FIB-4 index and Enhanced Liver Fibrosis (ELF) score were validated in 340 patients who underwent antiviral therapy. These scores were determined 24 weeks after treatment in 161 patients.Forns' score, APRI, FIB-4 and ELF score showed comparable diagnostic accuracies for significant fibrosis [area under the receiver operating characteristic curve (AUROC) 0.83, 0.83, 0.85 and 0.81, respectively]. To identify cirrhosis, FIB-4 index showed a significantly better performance over APRI and ELF score (AUROC 0.89 vs. 0.83 and 0.82, respectively). ELF score decreased significantly in patients with sustained virological response (SVR) (P0.0001) but remained unchanged in nonresponders. Non-1 hepatitis C virus (HCV) genotype, baseline lower HCV RNA, glucose, hyaluronic acid and higher cholesterol levels were independently associated with SVR.Simple panel markers and ELF score are accurate at identifying significant fibrosis and cirrhosis in chronic hepatitis C. A decrease in ELF score after antiviral treatment reflects the impact of viral clearance in hepatic extracellular matrix and probably in the improvement of liver fibrosis.

In the last 2-3 years, adult living donor liver transplantation (ALDLT) has been developed on an international scale, multiplying the number of procedures performed. Despite this, analysis of the results is still incomplete. The aim of the present study was to perform a descriptive analysis of the results after the first 3 years of the initiation of the program.During this period, 30 ALDLT were performed. In all procedures, right lobe grafts were used. The mean age of donors and recipients was 31.8 and 52.7 years, respectively. The main indication for liver transplantation was liver cirrhosis due to hepatitis C virus (70%) and 38% of recipients were stage C in the Child-Pugh classification. A total of 46.7% of recipients had hepatocellular carcinoma.Donors: The mean volume of the remnant liver was 632 cc (40.5% of the previous hepatic mass). Ten donors (33%) presented complications. The most frequent complication was biliary fistula (20%) and three patients required reintervention. The mean length of hospital stay among donors was 11.7 days. Recipients: The mean weight of the graft was 775 g, with a mean difference between graft weight and that of the recipient of 1.11. Fifteen recipients (50%) presented biliary leaks and nine of these (30%) required reintervention. There were no graft losses for technical reasons. Four patients died. With a median follow-up of 14 months, actuarial survival at 18 months was 92.9%.ALDLT is an effective method for reducing the number of patients on the waiting list. The probability of survival is similar to that of cadaveric transplantation. Biliary complications in the recipient constitute a problem, the long-term repercussions of which remain to be resolved.

Two genomic regions of hepatitis C virus (HCV), the interferon sensitivity-determining region (ISDR) of the non-structural 5A gene (NS5A) and the protein kinase-RNA activated (PKR)-eukariotic transcription factor (eIF2-alpha) phosphorylation homology domain (PePHD) of the structural E2 gene, interact in vitro with the interferon-inducible cellular PKR protein kinase. Mutations within these regions might, therefore, influence the response to interferon therapy. Viral load at baseline and sequence heterogeneity of HCV in NS5A and E2 regions was studied in 74 HCV-1b and in 12 HCV-3a infected patients with chronic hepatitis C who were treated with interferon. As previously reported by us, in a smaller series of patients in which the ISDR region was analyzed [Saiz et al. (1998) Journal Infectious Diseases 177:839-847], in the present study a low viral load and a high number of amino acid mutations within the ISDR, but not within the PePHD region, were significantly associated with long-term response to interferon among HCV-1b infected patients. No relationship between these viral features and response to therapy was disclosed in patients infected with HCV-3a.

Hepatitis C virus (HCV) is an important cause of chronic liver disease worldwide. HCV is a positive-strand genotype RNA virus with extensive genetic heterogeneity; HCV isolates define 6 major genotypes, and HCV circulates within an infected individual as a number of closely related but distinct species, termed a quasispecies. This article reviews characteristic aspects of HCV molecular biology and their implications for treatment and vaccine development.

Recently, a novel DNA virus, TT virus (TTV), was identified in patients with post-transfusion non-A-G hepatitis. We analyzed the prevalence and clinical implications of TTV infection in a cohort of 96 Spanish patients on long-term hemodialysis. TTV DNA was detected by nested PCR in 51 (53%) of 96 patients, a prevalence significantly higher than that found in healthy blood donors. Persistent liver test abnormalities were found in only 2 (7.7%) of 26 patients infected with TTV alone, compared with 12 (75%) of 16 patients infected with hepatitis C or hepatitis B virus, or both (P0.01). Mixed infections with multiple strains of TTV, including different major genotypes, were common in patients on hemodialysis. These patients had received a significantly greater number of blood units (22.7 +/- 20) compared with patients apparently infected with a single strain of TTV (8.9 +/- 11) (P = 0.01). Phylogenetic analyses of TTV from infected patients identified strains of genotypes 1, 2, 3, and 4. In summary, TTV infection was common in patients on hemodialysis but was not associated with liver disease

A modified competitive RT-PCR (mcRT-PCR) to measure HCV RNA in serum and the Amplicor HCV Monitor assay were compared. For mcRT-PCR, the RNA extracted was retrotranscribed and coamplified in one step with a known amount of a DNA internal control (IC). Digoxigenin-labeled amplified products were hybridized to specific HCV DNA and IC-DNA probes and quantified by colorimetry. HCV RNA concentration was calculated by plotting the ratio of HCV/IC ODs against a calibration curve. Multiple samples were analyzed in the same round and tedious titration of each sample with a competitor was unnecessary. The mcRT-PCR assay was linear from 6 x 10(3) to 6 x 10(7) copies/ml, whereas Amplicor was linear up to 1-2 x 10(6) copies/ml. HCV RNA was measured in samples from 75 carriers. There was agreement between both methods in type 1 infections but not in type 2 or type 3 infections, in which the values measured by Amplicor were, on average, 15 times lower than those measured by the mcRT-PCR. HCV RNA measured by Amplicor was higher in type 1 infections than in type 2 or 3 infections, but no differences were found when viral load was assessed by mcRT-PCR. The binding efficiency of the Amplicor-probe was greater for type 1 than for types 2 or 3, suggesting Amplicor underestimates the viral load in the latter types. In contrast, the mcRT-PCR is not affected by genotype-related variation of HCV. This study suggests that mcRT-PCR assay is reliable for sensitive and accurate measurement of HCV RNA over a broad range of values independently of the HCV genotype.

Functional respiratory disorders in patients with systemic lupus erythematosus (SLE) have been previously reviewed. We report a patient with SLE who developed progressive dyspnea with a restrictive pattern in the functional respiratory tests, and diaphragmatic disfunction. Symptoms and functional tests improved after a treatment with steroids. We also review the pathophysiologic mechanisms of this disorder.

The case of a patient with a multisystemic process characterized by polyarthritis, hemoptysis, leucocytoclastic vasculitis, renal failure and ulcerated lesions in the palate and nasal bone is reported. The existence of antineutrophil anticytoplasmic antibodies (cytoplasmatic pattern) was proven by indirect immunofluorescence with an initial serum titration of 1:1.600. Detection of these antibodies permitted the establishment of immunosuppressive treatment when the clinical situation of the patient was considered serious (pulmonary hemorrhage with progressive diminution of the hematocrit). Four days after the initiation of treatment the histopathological results of the palate and nasal mucous biopsies were received and were compatible with Wegener's granulomatosis. Serial determination of the titers of these antibodies demonstrated a close correlation with the clinical biological activity of the process. Indeed, 3 days after initiation of the immunosuppressive treatment the concentration of the same had reduced to half, something which has not been previously reported. It is concluded that high specificity and sensitivity of antineutrophil anticytoplasmic antibodies with a cytoplasmatic pattern for Wegener's granulomatosis may contribute to the improvement, not only of the diagnosis but also to the prognosis, in permitting the immediate initiation of therapeutic measures when the clinical situation of the patient thus requires.