A multilevel approach for assessing the variability of hepatitis C prevalence in injection drug users by their gathering places.

OBJECTIVES: The aim of this study was to investigate the variation in hepatitis C virus (HCV) prevalence in injection drug users (IDUs) by their gathering places, using a multilevel approach. METHODS: IDUs recruited from their gathering places were invited to respond to a questionnaire on demographics, drug use history, injection behaviors, and methadone treatment. Dried blood spots were collected for HCV antibody testing by ELISA. Factors associated with the anti-HCV test result were explored by linear logistic regression, followed by the evaluation of heterogeneity between gathering places by multilevel analysis. RESULTS: A total of 622 respondents from 19 gathering places in Hong Kong, recruited between August and September 2011, were evaluated. Anti-HCV seroprevalence was 81.7% (95% confidence interval 78.6-84.7%), ranging from 67% to 100% by gathering place. HCV infection was associated with current practice of injection, needle-sharing, and midazolam injection. On multilevel analysis, there was a modest but significant variation in HCV antibody prevalence by gathering place, adjusted by midazolam injection (adjusted odds ratio (AOR) 3.91) and current injection (AOR 2.88) or injection over a long duration (AOR 3.17). CONCLUSIONS: There was heterogeneity in HCV antibody prevalence in IDUs by gathering place, while the influence of injection behaviors varied, suggesting interactivity between factors at the individual and group levels.

Molecular epidemiology of HCV monoinfection and HIV/HCV coinfection in injection drug users in Liuzhou, Southern China.

BACKGROUND: Hepatitis C virus (HCV) mono-infection and HCV/HIV (human immunodeficiency virus) co-infection are growing problems in injection drug users (IDU). Their prevalence and genotypic patterns vary with geographic locations. Access to harm reduction measures is opening up opportunities for improving the HIV/HCV profiling of IDU in China, where IDUs account for a significant proportion of the two infections especially in the southern part of the country. METHODOLOGY/PRINCIPAL FINDINGS: A cross sectional study was conducted. Through the Liuzhou Methadone Clinic, a total of 117 injection drug users (IDUs) were recruited from Guangxi, Southern China. A majority of the IDUs (96%) were HCV antibody positive, of which 21% were HIV infected. Unlike HCV monoinfection, there was spatial heterogeneity in the distribution of HIV/HCV coinfection, the latter also characterized by a higher prevalence of needle-sharing. Phylogenetic analysis revealed that genotype 6a was predominant in the study population. There were shorter genetic distances among the 6a sequences compared to the other HCV subtypes-1a, 3a, and 3b. CONCLUSION/SIGNIFICANCE: The results suggested that HIV and HCV were introduced at around the same time to the IDU populations in Southern China, followed by their differential spread as determined by the biologic characteristics of the virus and the intensity of behavioural risk. This pattern is different from that in other South East Asian countries where HCV infections have probably predated HIV.

Long-term expression of angiostatin suppresses metastatic liver cancer in mice.

Metastatic liver cancer has a very poor prognosis and lacks effective therapy. Anti-angiogenic therapies, which starve tumors of blood supply, have proven to be effective in preclinical models because tumor growth is angiogenesis dependent. However, long-term, high-level, and sustained expression of angiogenesis inhibitors, such as angiostatin, is necessary to prevent dormant tumors from becoming active again. To achieve this objective, we engineered a recombinant adeno-associated virus (AAV) vector encoding mouse angiostatin, an endogenous inhibitor of tumor vascularization. After intraportal delivery of this vector, high-level, stable transgene expression of angiostatin lasting for at least 6 months was observed locally in hepatocytes. Gene transfer of AAV-angiostatin via the portal vein led to significant suppression of the growth of both nodular and metastatic EL-4 lymphoma tumors established in the liver and prolonged the survival time of the mice. The growth of neovessels was inhibited significantly, and extensive apoptosis of tumor cells was observed. The anti-angiogenic activity of angiostatin was independent of vascular endothelial growth factor (VEGF). The AAV-angiostatin viruses did not appear to be toxic to mice, and there was no detectable apoptosis of hepatocytes. In conclusion, these encouraging results warrant future investigation of the use of AAV-mediated anti-angiogenic gene therapy for targeting unresectable liver metastases, especially after surgical removal of primary tumors.