Making computed tomography safer for patients with Crohn's disease.

Computed tomography (CT), often more accessible than magnetic resonance imaging (MRI), remains widely used though radiation exposure is an obvious disadvantage. We previously showed that modern CT technology can achieve over 70% reduction in radiation-dose without loss of accuracy. Here, we compare low- versus conventional-dose CT in patients with known Crohn's disease to assess clinical confidence and accuracy of the low-dose procedure in the semi-acute setting.

Reverse epitope mapping of the E2 glycoprotein in antibody associated hepatitis C virus.

The humoral immune system responds to chronic hepatitis C virus (HCV) infection by producing neutralising antibodies (nAb). In this study we generated three HCV pseudoparticles in which E1E2 glycoprotein sequence was targeted by the host humoral immune system. We used patient derived virus free Fabs (VF-Fabs) obtained from HCV genotype 1a (n = 3), genotype 1b (n = 7) and genotype 3a (n = 1) for neutralisation of HCVpp produced in this study both individually and in combination.

Ultradeep Pyrosequencing of Hepatitis C Virus to Define Evolutionary Phenotypes.

Analysis of hypervariable regions (HVR) using pyrosequencing techniques is hampered by the ability of error correction algorithms to account for the heterogeneity of the variants present. Analysis of between-sample fluctuations to virome sub-populations, and detection of low frequency variants, are unreliable through the application of arbitrary frequency cut offs. Cumulatively this leads to an underestimation of genetic diversity.

Humoral immune system targets clonotypic antibody-associated hepatitis C virus.

Hypervariable region 1 (HVR1) is one of the potential neutralization domains in the E2 glycoprotein of hepatitis C virus (HCV). Point mutations of the HVR1 can lead to humoral immune escape in HCV-infected patients. In this study, we segregated the chronically infected viraemic sera from HCV-infected patients into populations of antibody-free virus and antibody-associated virus (AAV) and mapped potential epitopes within the E1E2 gene junction of AAV sequences (residues 364-430).

A single amino acid change in the hypervariable region 1 of hepatitis C virus genotype 4a aids humoral immune escape.

Longitudinal analysis of chronic hepatitis C virus (HCV) infection has shown that the virus has several adaptive strategies that maintain persistence and infectivity over time. We examined four serum samples from the same chronically infected HCV genotype 4a patient for the presence of IgG antibody-associated virus. RNA was isolated from antibody-associated and antibody-free virions.

Network Analysis of the Chronic Hepatitis C Virome Defines Hypervariable Region 1 Evolutionary Phenotypes in the Context of Humoral Immune Responses.

Unlabelled: Hypervariable region 1 (HVR1) of hepatitis C virus (HCV) comprises the first 27 N-terminal amino acid residues of E2. It is classically seen as the most heterogeneous region of the HCV genome. In this study, we assessed HVR1 evolution by using ultradeep pyrosequencing for a cohort of treatment-naive, chronically infected patients over a short, 16-week period.

Intensive temporal mapping of hepatitis C hypervariable region 1 quasispecies provides novel insights into hepatitis C virus evolution in chronic infection.

Hepatitis C virus (HCV) is an RNA virus which exists as swarms of closely related viruses known as quasispecies (QS). A number of studies have demonstrated associations between QS hypervariable region 1 (HVR1) characteristics (diversity and complexity) and treatment success. We investigated HCV QS change in chronic infection over intervals of 2-4 weeks in 23 chronically infected individuals to describe the natural history of virus evolution and establish whether HCV QS characteristics could be used to individualize treatment regimens at a molecular level.

Analysis of the evolution and structure of a complex intrahost viral population in chronic hepatitis C virus mapped by ultradeep pyrosequencing.

Unlabelled: Hepatitis C virus (HCV) causes chronic infection in up to 50% to 80% of infected individuals. Hypervariable region 1 (HVR1) variability is frequently studied to gain an insight into the mechanisms of HCV adaptation during chronic infection, but the changes to and persistence of HCV subpopulations during intrahost evolution are poorly understood. In this study, we used ultradeep pyrosequencing (UDPS) to map the viral heterogeneity of a single patient over 9.

The use of complementary and alternative medicine in an Irish cohort of people with an iatrogenic hepatitis C infection: results from a health and lifestyle survey.

Introduction: A cohort of people with iatrogenic HCV infection, current or resolved, in Ireland have access to primary and secondary health care services, including specified complementary and alternative medicine (CAM) services, free of charge.

Objectives: Information about their pattern of CAM usage and its association with various demographic and lifestyle factors, and current HCV status, was sought as part of a health and lifestyle survey, in order to provide information for health service planning.

Design And Methods: The survey was carried out by self-administered postal questionnaire.

Constraints on viral evolution during chronic hepatitis C virus infection arising from a common-source exposure.

Extraordinary viral sequence diversity and rapid viral genetic evolution are hallmarks of hepatitis C virus (HCV) infection. Viral sequence evolution has previously been shown to mediate escape from cytotoxic T-lymphocyte (CTL) and neutralizing antibody responses in acute HCV infection. HCV evolution continues during chronic infection, but the pressures driving these changes are poorly defined.

Insertion and recombination events at hypervariable region 1 over 9.6 years of hepatitis C virus chronic infection.

Hepatitis C virus (HCV) exists as a quasispecies within an infected individual. We have previously reported an in-frame 3 bp insertion event at the N-terminal region of the E2 glycoprotein from a genotype 4a HCV isolate giving rise to an atypical 28 aa hypervariable region (HVR) 1. To further explore quasispecies evolution at the HVR1, serum samples collected over 9.

The pan-genotype specificity of the hepatitis C virus anti-core monoclonal antibody C7-50 is contingent on the quasispecies profile of a population.

The inter/intra-genotype quasispecies makeup of hepatitis C virus (HCV) has retarded the development of antibodies capable of pan-genotype reactivity. Mutations, even in conserved domains, are tolerated to a degree. In this report, we characterise the pan-genotype specificity of the commercially available monoclonal anti-HCV core antibody C7-50.

Diagnostic accuracy of computed tomography using lower doses of radiation for patients with Crohn's disease.

Background & Aims: Magnetic resonance and ultrasonography have increasing roles in the initial diagnosis of Crohn's disease, but computed tomography (CT) with positive oral contrast agents is most frequently used to identify those with acute extramural complications. However, CT involves exposure of patients to radiation. We prospectively compared the diagnostic accuracy of low-dose CT (at a dose comparable to that used to obtain an abdominal radiograph) with conventional-dose CT in patients with active Crohn's disease.

Separation of Hepatitis C genotype 4a into IgG-depleted and IgG-enriched fractions reveals a unique quasispecies profile.

Background: Hepatitis C virus (HCV) circulates in an infected individual as a heterogeneous mixture of closely related viruses called quasispecies. The E1/E2 region of the HCV genome is hypervariable (HVR1) and is targeted by the humoral immune system. Hepatitis C virions are found in two forms: antibody associated or antibody free.

Correlation between pre-treatment quasispecies complexity and treatment outcome in chronic HCV genotype 3a.

Pre-treatment HCV quasispecies complexity and diversity may predict response to interferon based anti-viral therapy. The objective of this study was to retrospectively (1) examine temporal changes in quasispecies prior to the start of therapy and (2) investigate extensively quasispecies evolution in a group of 10 chronically infected patients with genotype 3a, treated with pegylated alpha2a-Interferon and ribavirin. The degree of sequence heterogeneity within the hypervariable region 1 was assessed by analyzing 20-30 individual clones in serial serum samples.

Serendipitous identification of natural intergenotypic recombinants of hepatitis C in Ireland.

Background: Recombination between hepatitis C single stranded RNA viruses is a rare event. Natural viable intragenotypic and intergenotypic recombinants between 1b-1a, 1a-1c and 2k-1b, 2i-6p, respectively, have been reported. Diagnostically recombinants represent an intriguing challenge.

Divergent and convergent evolution after a common-source outbreak of hepatitis C virus.

The genomic sequences of viruses that are highly mutable and cause chronic infection tend to diverge over time. We report that these changes represent both immune-driven selection and, in the absence of immune pressure, reversion toward an ancestral consensus. Sequence changes in hepatitis C virus (HCV) structural and nonstructural genes were studied in a cohort of women accidentally infected with HCV in a rare common-source outbreak.

Persistence of hepatitis C virus in a white population: associations with human leukocyte antigen class 1.

The aim of this study was to define novel associations between human leukocyte antigen (HLA) class 1 alleles and persistence or clearance of the hepatitis C virus (HCV) in a white population. All individuals in the study were seropositive for anti-HCV antibodies. Viral status was determined by the Roche HCV Amplicor test.