Impact of HAART on liver histology of HIV/HCV coinfected patients.

The impact of HAART on the progression of HCV related liver disease is controversial. This retrospective study compares the grading and staging of chronic viral hepatitis in HIV/HCV coinfected subjects treated or not with antiretroviral therapy (ART) including protease inibithors (PI). The liver histology of 44 HIV/HCV coinfected patients on ART for more than 12 months, 26 coinfected patients naïve for ART and 31 HCV monoinfected patients were analysed by the Ishak score. None of the multivariate models calculated to test if liver histopathology (Ishak grading or staging) between HIV/HCV coinfected patients versus HCV monoinfected or antiretroviral-treated versus untreated HIV+ subjects showed any statistical difference. No significant difference between grading and staging was evidenced either in PI treated subjects versus patients on ART without PI.

Acute self-limiting hepatitis C after possible sexual exposure: sequence analysis of the E-2 region of the infected patient and sexual partner.

We describe a case of symptomatic acute infection with HCV in a woman whose sexual partner had chronic hepatitis C. The patient cleared HCV RNA 8 weeks after the onset of acute hepatitis and was found to be persistently HCV-RNA negative during 90 weeks of follow-up. Part of the E-2 region of HCV was directly sequenced in the patient and her sexual partner. Four local controls with subtype-1a infection and 9 1a isolates obtained from GenBank were analyzed. The average nucleotide divergence between the sequences of the infected patient and her sexual partner was 5.1%, compared with an average nucleotide divergence of 19.4% (range 16.6-21.8%) between the sequences of the patient and those of controls. Comparison of the phylogenetic trees in the partial E-2 region showed that the sequence of the patient was closely related to that of her sexual partner. Our findings suggest that the infection was transmitted to the patient from her sexual partner. The resolution of acute hepatitis C in this case was probably related to the host rather than to intrinsic characteristics of the HCV genome.

Mother-to-child transmission of TT virus: sequence analysis of non-coding region of TT virus in infected mother-infant pairs.

To investigate vertical transmission of TT virus, TTV-DNA was looked for in serum samples taken from 22 mothers and their 22 infants at birth and during nine months of follow-up. Sixteen mothers at delivery and six infants within nine months of age had TTV-DNA detected by the amplification of the non coding (NC) region. Two of these newborns had positive viremia at birth. Sequence analysis of the NC region of five mother-infant pairs revealed that the TTV strains detected at three and six months of age in two of the infants were closely related to that of their mothers, whereas two that became TTV-DNA positive at three moths had a different nucleotide sequence from that of their mothers. One of the two infants with detectable viremia at birth also had a different nucleotide sequence from her mother. These findings suggest that both in utero and perinatal transmission of TT virus may occur, and that the strain detected in the infants was not invariably dominant in the mothers at delivery.

Evolution of the E2 region of hepatitis C virus in an infant infected by mother-to-infant transmission.

To demonstrate vertical transmission of hepatitis C virus from an HCV infected woman and to assess the evolution of HCV quasispecies in the infant, the variable E2 region was analyzed in one mother-infant pair at birth and in serial samples from the infected baby. Sequence analysis of the E2 region obtained by means of direct sequencing of PCR products of mother-infant pair at birth, showed that the sequence of the dominant strain in the infant was related closely but not identical to that of her mother. The HCV population in mother-infant pair at birth and in serial samples of the infant was analyzed by polymerase-chain reaction-mediated Single Strand Conformational Polymorphism analysis (SSCP), which can distinguish DNA fragments of the same size as different electrophoretic migration of single stranded DNA. Single Strand Polymorphism analysis revealed that the infant was infected with two mutant genomes whereas the mother had a unique variant. The prevalent strain detected in the baby was not dominant in the mother at delivery and the pattern of quasispecies in the infant at birth was not the same as her mother, suggesting that the infant acquired the infection in utero. Changes in the dominant strain and evolution of the pattern of quasispecies in the infant from the 10th month of age were possibly due to the immune selection of escape mutants.

Effect of increasing dose of interferon on the evolution of hepatitis C virus 1b quasispecies.

The effects of interferon therapy on hepatitis C virus (HCV) genome are still controversial in terms of biological and clinical significance. Changes in the quasispecies of the hypervariable (HVR) and non-structural 5A (NS5A) regions of HCV 1b were evaluated in nine patients treated with increasing doses of interferon and five untreated controls. HCV quasispecies were analyzed in HVR and NS5A by single-strand conformation polymorphism assay. The HVR quasispecies varied over time both in treated and untreated patients. However, at least one persistent strain was present in all patients. With low doses of interferon, variations in HVR complexity were found in seven of nine patients and in four patients new variants became detectable. A reduction in the heterogeneity of the HVR quasispecies was observed after increase of the interferon dose. In contrast, NS5A profiles remained unmodified in all but three cases in which direct sequencing showed no changes in amino acid sequences of the predominant strain. The results suggest that interferon sensitivity of some HCV strains may be dose dependent. The homogeneity of NS5A pattern populations during treatment suggests that interferon exerts much less pressure on this region.