Hepatitis C viremia patterns in incident hepatitis C infection and one year later in 150 prospectively tested persons who inject drugs.

OBJECTIVES: To assess HCV viremia levels just before, during and one year after anti-HCV seroconversion in people who inject drugs (PWID). METHODS: PWID enrolling into a needle exchange program in Malmö, Sweden, 1997-2005 constituted the source population. Sera were obtained at enrolment and at approximately 3-4 monthly intervals afterwards, and were initially tested for anti-HIV, HBsAg/anti-HBc and anti-HCV and thereafter for markers previously negative. Seroconversion to anti-HCV had occurred during the study period in 186 out of 332 seronegative subjects. In these anti-HCV seroconverters, quantitative HCV RNA PCR was retrospectively performed on frozen sera to determine viremia levels in the last anti-HCV negative, the first anti-HCV positive and in one year follow-up samples. RESULTS: Among 150 subjects seroconverting to anti-HCV with samples available from all three defined time-points, eight different patterns of viremia were observed. Spontaneous clearance at one year was noted in 48 cases (32%) and was associated with female gender (p = 0.03, CI 0.17-1.00). In 13 cases HCV-RNA was not detected in any study sample. Among 61 subjects with pre-seroconversion viremia, viral load was significantly higher in the pre-seroconversion samples compared to subsequent samples. For the whole group, viral load declined to undetectable levels at seroconversion in 28% of cases (but with recurrent viremia in 15%). CONCLUSIONS: Different patterns of HCV RNA kinetics were observed among PWID with documented seroconversion to anti-HCV. The frequently observed absence of detectable HCV RNA in the first anti-HCV positive sample (irrespective of subsequent viremia) demonstrates the importance of repeated sampling and RNA testing for determination of the outcome of acute infection.

Prospective study of nosocomial transmission of hepatitis C in a Swedish gastroenterology unit .

A prospective study of incident hepatitis C in 515 gastroenterology patients was conducted by follow-up sampling at 3-6 months after admission to the gastroenterology unit to test for antibodies to hepatitis C virus and for hepatitis C virus RNA. Universal precautions were implemented, and the use of multidose vials had been banned in this unit. Despite 5,964 exposure-days for several risk factors associated with nosocomial hepatitis C virus transmission, no incident case of hepatitis C occurred.

Enhanced and resumed GB virus C replication in HIV-1-infected individuals receiving HAART.

In patients co-infected with HIV-1 and GB virus C (GBV-C), the disappearance of GBV-C RNA has been associated with accelerated disease progression. We studied longitudinal GBV-C viral titres in 28 HIV-1/GVB-C co-infected individuals receiving HAART. During HAART, median GBV-C RNA titres increased from 95 to 6000 copies/ml (P < 0.001). In patients interrupting HAART, GBV-C-RNA titres decreased as HIV replication resumed. These findings further support the theory that GBV-C replication could depend on the dynamics of HIV progression.

Genetic diversity in hepatitis C virus in Egypt and possible association with hepatocellular carcinoma.

Egypt has one of the world's highest prevalences of hepatitis C virus (HCV) infection, with a majority of genotype 4 infections. To explore the genetic diversity of HCV in Egypt, sera from 131 Egyptians [56 from community studies, 37 chronic hepatitis patients, 28 hepatocellular carcinoma (HCC) patients and 10 patients with non-Hodgkin's lymphoma] were genotyped by restriction fragment-length polymorphism and phylogenetic analyses of sequences from the mid-core and non-structural 5B regions. The different genotyping methods showed good agreement. The majority of the viruses (83 of 131; 63%) were of subtype 4a, but five other subtypes within genotype 4 were also observed, as well as three genotype 1b, five genotype 1g and one genotype 3a samples. Interestingly, subtype 4o, which was easily identifiable in all three genomic regions, showed an association with HCC (P=0.017), which merits further investigation.

GB virus C during the natural course of HIV-1 infection: viremia at diagnosis does not predict mortality.

OBJECTIVE: To investigate whether GBV-C viremia at diagnosis of HIV-1 infection predicts disease outcome in patients not receiving combination antiretroviral therapy (ART), and whether longitudinal changes in GBV-C viremia are associated with disease progression. DESIGN: Prospective cohort study. METHODS: 230 patients with a serum sample available for testing obtained within 2 years of HIV-1 diagnosis were followed until either initiation of ART, death, or their last visit to our clinic (median follow-up 4.3 years). Baseline and follow-up serum samples (available from 163 patients) were tested for GBV-C RNA and antibodies against GBV-C envelope E2 protein (anti-E2; signifying resolved GBV-C viremia). RESULTS: At inclusion, 62 patients (27%) had GBV-C viremia and 69 (30%) had anti-E2. Baseline GBV-C status was not associated with all-cause mortality (P = 0.12), HIV-related mortality (P = 0.18), or development of AIDS (P = 0.84). However, GBV-C RNA was less prevalent in patients with AIDS at inclusion (P = 0.008). Eleven of 44 patients with baseline GBV-C viremia lost GBV-C RNA during follow-up without showing anti-E2 seroconversion. In comparison with anti-E2-negative patients with either persistent absence, persistent presence, or acquisition of GBV-C viremia, these subjects had significantly increased all-cause mortality (P = 0.018), HIV-related mortality (P = 0.007), and AIDS incidence (P < 0.001). CONCLUSIONS: GBV-C status at diagnosis did not predict disease outcome in this HIV cohort. GBV-C viremia was rare in patients with AIDS, and tended to disappear without occurrence of anti-E2 in patients with progressive disease. This suggests that the GBV-C status of HIV-1-infected patients could be a phenomenon secondary to HIV progression, rather than an independent prognostic factor.

Evolution of hepatitis C virus variants following blood transfusion from one infected donor to several recipients: a long-term follow-up.

Variants of hepatitis C virus (HCV) from a single infected blood donor and 13 viraemic recipients who were traced were examined by sequencing and cloning to determine the extent of virus diversity in hypervariable region 1. Serum-derived viral isolates were studied from the donor when his HCV infection was discovered in 1993, in his recipients that year (0.3-5 years post-transfusion) and 5 years later in the donor and six viraemic recipients who were still alive. Viral variants of broad diversity were readily demonstrated in the baseline samples of the donor (nucleotide p-distance 0.130), but significantly less (P<0.00003) diversity was observed in the recipients' first samples (p-distances within recipients 0.003-0.062). In the first blood samples of the recipients, many of the viral variants identified were closely related to a strain variant from the donor. In follow-up samples drawn 5 years later from the donor and six recipients, the p-distance among donor clones had increased (0.172, P<0.0005) compared with the recipients, who displayed significantly narrower quasispecies (0.011-0.086). A common finding was that recipients of blood components processed from the same donation differed substantially in persisting HCV infectious sequence. Markedly few changes leading to changes of amino acids had occurred during follow-up in four of six recipients. These results question the significance of the development of viral variants as a necessary phenomenon in the evolution of HCV and pathogenesis of the disease.