Hepatitis C virus replicates in the same immune cell subsets in chronic hepatitis C and occult infection.

BACKGROUND & AIMS: Infection of the lymphatic system by hepatitis C virus (HCV) appears to be an intrinsic characteristic of chronic hepatitis C (CHC) and low-level (occult) HCV infection, but the subsets of immune cells involved were not defined. The aim of this study was to characterize HCV replication status and to assess virus compartmentalization in CD4+ and CD8+ T lymphocytes, B cells, and monocytes in CHC, and silent infection persisting after resolution of hepatitis C. METHODS: Immune cell subtypes isolated from 7 patients with CHC and 7 individuals with occult infection were analyzed for HCV-RNA-positive and -negative strands and, in selected cases, nonstructural protein 5A display and HCV variants. RESULTS: All subtypes of immune cells investigated support HCV replication in both forms of infection, although significant differences were found between patients, and virus loads in the cells were greater in CHC than in occult infection. Although HCV RNA occurred at a comparable frequency in all cell subtypes in CHC, monocytes contained the greatest loads. In contrast, B cells tended to carry the highest virus quantities in occult infection, whereas monocytes appeared to be the least frequently infected. Detection of HCV nonstructural protein 5A and HCV variants that were not found in plasma confirmed virus replication in different immune cell types. CONCLUSIONS: This work documents that the immune system supports HCV replication regardless of clinical appearance of infection and identifies immune cells that are reservoirs of HCV in symptomatic and occult infections.

A nomogram to predict C282Y hemochromatosis.

Genetic testing of hemochromatosis has not been widely used as a diagnostic test because of unawareness of its existence and concerns about genetic discrimination. We developed a nomogram for the prediction of C282Y homozygotes for hemochromatosis from transferrin saturation and ferritin using Bayes theorem. The results of transferrin saturation and C282Y genotyping were available for 8,572 participants (5,042 men, and 3,530 women). The study group included patients in population-screening projects, referred cases, and family members. Likelihood ratios were calculated for transferrin saturation in predicting C282Y homozygotes. Pretest probabilities were estimated on the basis of serum ferritin concentration, and a predictive nomogram for men and women was created with the use of Bayes' theorem. In the highest-risk region of the nomogram in men, the probability of C282Y hemochromatosis was 89.7% (95% confidence interval = 85.1-94.3); in the lowest-risk zone it was 1.1% (0.4-1.9). The corresponding regions in women were 88.9% in the high zone (95% confidence interval = 77.0-100.0) and 6.5% in the lowest (95% confidence interval = 4.9-8.1). This approach allows the clinician to predict the probability of a patient's being a C282Y homozygote over a wide range of ferritin and transferrin saturation values instead of above a particular threshold.