Is the hepatitis C virus epidemic over in Egypt? Incidence and risk factors of new hepatitis C virus infections.

OBJECTIVES: To estimate hepatitis C virus (HCV) incidence rates and identify risk factors for current HCV transmission with emphasis on the role of living with infected household family members in rural Egypt. METHODS: A 4-year population-based, cohort study of seronegative villagers was conducted to identify incident HCV seroconversion cases. A risk factor questionnaire and blood samples for anti-HCV EIA-3 and HCV RNA polymerase chain reaction testing were collected at two rounds of follow-up. Incidence rates, relative risks and 95% confidence interval (CI) were calculated based on a Poisson distribution. A matched case-control analysis to explore specific behavioural predictors of infection was conducted and odds ratios were obtained by conditional logistic regression. RESULTS: Twenty-five participants (11 females) seroconverted in 10,578 person years of follow-up (PY), (incidence rate of 2.4/1000 PY; 95% CI: 1.6-3.5). The median age at seroconversion was 26 years [interquartile range (IQR) 19-35] among males and 20 years (IQR 13-24) among females. The only significant risk factor identified for these cases was receiving injections [adjusted odds ratio (OR(adj))=3.3; 95% CI: 1.1-9.8]. Two of the 17 viraemic seroconvertors were infected with the same strain as at least one of their family members. CONCLUSION: This study identified the important role of injections in spreading HCV infection in this rural community. National healthcare awareness and infection control programmes should be strengthened to prevent further transmission. Screening of families of infected HCV subjects should be an essential part of case management for early detection and management.

Distinct hepatitis C virus core and F protein quasispecies in tumoral and nontumoral hepatocytes isolated via microdissection.

UNLABELLED: Hepatitis C virus (HCV) genetic variability may be involved in liver carcinogenesis. We investigated HCV core and corresponding putative F protein genetic variability in hepatocellular carcinoma (HCC) and cirrhotic nodules. Hepatocyte clusters from 7 patients with HCC and HCV1b-related cirrhosis were isolated via microdissection of HCC tissues and 2 nontumoral cirrhotic nodules. The HCV core complementary DNA was cloned and sequenced from each liver compartment and from the serum of 2 patients. Nucleotide diversity and synonymous and nonsynonymous substitutions were analyzed within and between compartments via phylogenetic analysis and Mantel's test. Liver HCV RNA accumulation was lower in HCC. Increased quasispecies diversity and complexity was observed with HCC in 6 of 7 patients. Mantel's test demonstrated marked compartmentalization of quasispecies between HCC and cirrhotic nodules in all 7 patients and also between the 2 nontumoral nodules in 5 of them. Synonymous-nonsynonymous substitution analysis indicated low selection against tumoral core quasispecies in all patients and a more selective pressure against F protein quasispecies in all compartments. In the 2 subjects analyzed, HCC and nontumoral hepatocyte quasispecies were only minor or undetected in serum. CONCLUSION: In tumoral hepatocytes, low-replicating hepatitis C quasispecies are compartmentalized and more diversified and are subjected to low selective pressure. Our study supports the importance of core genetic variability in hepatocellular carcinogenesis.

Hepatitis C virus transmission from a healthcare worker to a patient.

We investigated the source of infection in a patient who developed acute hepatitis C virus infection after cardiothoracic surgery. A healthcare worker was found to be infected with hepatitis C virus, and molecular analysis indicated the strain was similar to that found in the patient. The exact mode of transmission was not identified; however, atopic eczema on the healthcare worker's hands may have contributed to the transmission.

Change in hepatitis C virus genotype in hemodialysis patients after end-of-treatment response to interferon monotherapy--relapse or re-infection?

Hepatitis C virus (HCV) infection remains common among hemodialysis patients and its occurrence is related mainly to nosocomial spread. Although dialysis patients with HCV infection respond well to interferon-based therapy, relapse is frequent. This study aimed at a selected group of hemodialysis patients infected with HCV infection undergoing interferon therapy who achieved end-of-treatment virological response but became HCV-RNA positive again 6 months after end-of-treatment. It was evaluated whether de novo HCV-RNA positivity in these non-sustained responders occurred due to lack of clearance of HCV after the initial response to interferon-alpha (relapse) or due to re-infection with a new strain (re-infection). Genotyping by Inno-LiPA and by phylogenetic tree analysis using partial HCV-NS5B sequences at two evaluation points: pre-treatment (T0) and 6 months after end-of-treatment (T18). Non-sustained responders (n = 15) carried subtypes 1a (8 patients), 1b (4 patients), 3a (2 patients), and 4a (1 patient) before treatment. Identical subtypes were detected in 10 patients at T18. Five patients changed genotypes at T18, suggesting nosocomial re-infection. This study emphasizes the importance of epidemiologic measures to control the re-exposure of hemodialysis patients treated previously for HCV infection.

Impact of hepatitis B virus basic core promoter mutations on T cell response to an immunodominant HBx-derived epitope.

UNLABELLED: The hepatitis B X (HBx) protein is a crucial component in HBV infection in vivo and has been implicated in HCC. In this study, we aimed to detect and characterize peripheral HBx-specific T cells in chronically infected patients at the inactive carrier state of the disease. HBx-specific IFN-gamma-secreting T cells were found in 36 of 52 patients (69%), and 78% (28/36) of responding patients had T cells targeting epitopes in the carboxy-terminal part of HBx. IL-10 secretion after the stimulation of T cells with HBx-derived peptides was weak or undetectable. IFN-gamma-secreting T cells recognized a previously unknown immunodominant CD4+ T cell epitope, HBx 126-140 (EIRLKVFVLGGCRHK), in 86% (24 of 28) of patients. This peptide bound several HLA-DR molecules (HLA-DRB1*0101, HLA-DRB1*0401, HLA-DRB1*1301, and HLA-DRB5*0101). Its coding sequence overlaps a domain of the HBV genome encompassing the basic core promoter (BCP) region. Taking into account the selection of viral core promoter mutants during HBV infection, we found that HBV variants with BCP mutations were present in patient sera. We further demonstrated that these viral mutant sequences activated T cells specific for the immunodominant epitope only weakly, if at all. This is the first study linking BCP mutations and HBx-specific T cell responses. CONCLUSION: Wild-type and variant peptides may represent potential tools for monitoring the HBV-specific T cell responses involved in sequence evolution during disease progression. Finally, the degenerate HLA-DR binding of this promiscuous, immunodominant peptide would make it a valuable component of vaccines for protecting large and ethnically diverse patient populations.