Factors Affecting Serum Concentrations of Hepatitis C Virus (HCV) RNA in HCV Genotype 1-Infected Patients with Chronic Hepatitis▿

The serum concentration of hepatitis C virus (HCV) RNA is usually stable (4 to 8 log10 IU/ml) in untreated patients with chronic hepatitis C. While this baseline HCV RNA concentration ([HCV RNA]BL) is predictive of a sustained virologic response to treatment, its determinants are only partially identified. We therefore analyzed the baseline characteristics of 2,472 HCV genotype 1-infected patients to identify correlations with gender, age, race, weight, body mass index (BMI), HCV acquisition mode, HCV subtype, alanine aminotransferase concentration, or histopathologic changes in the liver. After separation of the data according to four [HCV RNA]BL groups (≤5.0, >5.0 to 5.6, >5.6 to 5.9, and >5.9 log10 IU/ml), we determined that increasing [HCV RNA]BL correlated (P < 0.05) with increasing proportions of patients who were male, >40 years of age, or heavier (a weight of >85 kg or a BMI of >27 kg/m2). Histologic activity index (HAI) data were available for 1,304 of these patients: increasing [HCV RNA]BL correlated with higher fibrosis and necrosis-inflammation scores. As a continuous variable, [HCV RNA]BL correlated with age, gender, weight (continuous or ≤85 versus >85 kg), BMI (continuous or ≤27 versus >27 kg/m2), subtype, fibrosis score, and necrosis-inflammation score; however, multiple-regression analysis yielded P values of <0.1 only for age, gender, BMI (≤27 versus >27 kg/m2), and fibrosis score. While our findings are suggestive of a role for these factors in maintenance of the pretreatment state of HCV infection, the multiple-regression model accounted for only ≤4.6% of the [HCV RNA]BL differences between individuals (R2 = 0.046 for 1,304 patients with HAI scores; 0.043 for all 2,472 patients)

Accurate Representation of the Hepatitis C Virus Quasispecies in 5.2-Kilobase Amplicons

Hepatitis C virus (HCV) exists as a swarm of genetically distinct but related variants, or a quasispecies, whose complexity and sequence evolution are critical to studies of viral pathogenesis. Because most studies of the HCV quasispecies have focused on a relatively small genomic segment, the first hypervariable region of the E2 gene, it is possible that viral complexity is occasionally underestimated (due to primer mismatch) and that sequence evolution is misperceived due to unrecognized covariation. This report describes a sensitive and reproducible method to amplify most of the HCV genome as a single 5.2-kb amplicon by using primers directed at relatively conserved genomic segments. Using 52 specimens obtained during acute infection over a range of viral RNA concentrations, the overall rate of successful amplification was 94% and varied in a concentration-dependent manner, with successful amplification in 26 of 26 (100%) specimens at greater than 10(5) IU/ml, 15 of 16 (94%) at 10(4) to 10(5) IU/ml, 6 of 7 (86%) at 10(3) to 10(4) IU/ml, and 2 of 3 (67%) at less than 10(3) IU/ml. Quasispecies complexity, determined by using this novel long-amplicon method followed by heteroduplex mobility assay combined with single-stranded conformational polymorphism (HDA+SSCP) analysis, was very high, even during acute HCV infection, when 10 to 21 (median, 16) different HDA+SSCP patterns were detected among 33 cDNA clones examined. Replicate analyses indicate that this diversity is not dominated by random errors generated during amplification. Therefore, the HCV quasispecies is highly complex even during acute infection and is accurately represented in amplicons representing more than half of the viral genome

The Changes In Surface Energetics With Relative Humidity Of Carbamazepine And Paracetamol As Measured By Inverse Gas Chromatography.

NoThe surface energetic parameters of carbamazepine and paracetamol have been studied using inverse gas chromatography modified to produce dry and ambient conditions within the column. The values of the dispersive component of the surface free energy (¿DS) do not change significantly at the increased relative humidity. In contrast the specific component of the free energy of adsorption (-¿GSPA) as measured by polar probes, can either remain constant or decrease by up to 10%, depending on the material and the probe. This indicates that an increase in the relative humidity causes a decrease in the surface energetics of the powder surface. It is proposed that where the water molecules are adsorbing to the same sites as the polar probes, the interaction of these probes with the surface is decreased. To identify these sites, the preferential interaction of each probe, including water, with the drug molecule has been modelled

Epidemiology and Risk Factors of Incident Hepatitis E Virus Infections in Rural Bangladesh

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in the world. Most of South Asia is HEV endemic, with frequent seasonal epidemics of hepatitis E and continuous sporadic cases. This author group's epidemiologic work and clinical reports suggest that Bangladesh is HEV endemic, but there have been few population-based studies of this country's HEV burden. The authors calculated HEV infection rates, over an 18-month interval between 2003 and 2005, by following a randomly selected cohort of 1,134 subjects between the ages of 1 and 88 years, representative of rural communities in southern Bangladesh. Baseline prevalence of antibody to hepatitis E virus (anti-HEV) was 22.5%. Seroincidence was 60.3 per 1,000 person-years during the first 12 months and 72.4 per 1,000 person-years from >12 to 18 months (during the monsoon season), peaking by age 50 years and with low rates during childhood. Few of the seroconverting subjects reported hepatitis-like illness. Overall incidence was calculated to be 64 per 1,000 person-years, with 1,172 person-years followed. No significant associations were found between anti-HEV incidence and demographic or socioeconomic factors for which data were available. This is the first study to document annual HEV infection rates among “healthy” and very young to elderly subjects in a rural Bangladeshi population