HCV-infected Individuals (HCV-infect + individual)

Distribution by Scientific Domains

Selected Abstracts

Nonstructural 3/4A protease of hepatitis C virus activates epithelial growth factor,induced signal transduction by cleavage of the T-cell protein tyrosine phosphatase,

HEPATOLOGY, Issue 6 2009
Erwin Daniel Brenndörfer
The hepatitis C virus (HCV) is a worldwide major cause of chronic liver disease with a high tendency to establish a persistent infection. To permit persistent replication of viral genomes through the cellular translation machinery without affecting host cell viability, viruses must have developed mechanisms to control cellular cascades required for sufficient viral replication, on the one hand, and to adapt viral replication to the cellular requirements on the other hand. The present study aimed to further elucidate mechanisms by which HCV targets growth factor signaling of the host cell and their implications for viral replication. The study describes a novel mechanism by which HCV influences the activation of the epithelial growth factor receptor/Akt pathway through a nonstructural (NS)3/4A-dependent down-regulation of the ubiquitously expressed tyrosine phosphatase T cell protein tyrosine phosphatase (TC-PTP). NS3/4A is demonstrated to cleave TC-PTP protease-dependently in vitro at two cleavage sites. The in vivo relevance of this finding is supported by the fact that down-regulation of TC-PTP protein expression could also be demonstrated in HCV-infected individuals and in transgenic mice with intrahepatic expression of NS3/4A. Conclusion: This down-regulation of TC-PTP results in an enhancement of epithelial growth factor (EGF)-induced signal transduction and increases basal activity of Akt, which is demonstrated to be essential for the maintenance of sufficient viral replication. Hence, therapeutic targeting of NS3/4A may not only disturb viral replication by blocking the processing of the viral polyprotein but also exerts unforeseen indirect antiviral effects, further diminishing viral replication. (HEPATOLOGY 2009;49:1810,1820.) [source]

Sexual activity as a risk factor for hepatitis C

HEPATOLOGY, Issue S1 2002
M.P.H., Norah A. Terrault M.D.
The accumulated evidence indicates that hepatitis C virus (HCV) can be transmitted by sexual contact but much less efficiently than other sexually transmitted viruses, including hepatitis B virus and human immunodeficiency virus (HIV). However, because sex is such a common behavior and the reservoir of HCV-infected individuals is sizable, sexual transmission of HCV likely contributes to the total burden of infection in the United States. Risk of HCV transmission by sexual contact differs by the type of sexual relationship. Persons in long-term monogamous partnerships are at lower risk of HCV acquisition (0% to 0.6% per year) than persons with multiple partners or those at risk for sexually transmitted diseases (0.4% to 1.8% per year). This difference may reflect differences in sexual risk behaviors or differences in rates of exposure to nonsexual sources of HCV, such as injection drug use or shared razors and toothbrushes. In seroprevalence studies in monogamous, heterosexual partners of HCV-infected, HIV-negative persons, the frequency of antibody-positive and genotype-concordant couples is 2.8% to 11% in Southeast Asia, 0% to 6.3% in Northern Europe, and 2.7% in the United States. Among individuals at risk for sexually transmitted diseases (STDs), the median seroprevalence of antibody to HCV (anti-HCV) is 4% (range, 1.6% to 25.5%). HIV coinfection appears to increase the rate of HCV transmission by sexual contact. Current recommendations about sexual practices are different for persons with chronic HCV infection who are in steady monogamous partnerships versus those with multiple partners or who are in short-term sexual relationships. (HEPATOLOGY 2002;36:S99,S105). [source]

The impact of HIV-1 co-infection on long-term mortality in patients with hepatitis C: a population-based cohort study

HIV MEDICINE, Issue 2 2009
LH Omland
Objective To investigate the impact of HIV co-infection on mortality in patients infected with hepatitis C virus (HCV). Methods From a nationwide Danish database of HCV-infected patients, we identified individuals diagnosed with HCV subsequent to an HIV diagnosis. For each co-infected patient, four control HCV patients without HIV were matched on age, gender and year of HCV diagnosis. Data on comorbidity, drug abuse, alcoholism and date of death were extracted from two healthcare databases. We constructed Kaplan,Meier curves and used Cox regression analyses to estimate mortality rate ratios (MRRs), controlling for comorbidity. Results We identified 483 HCV,HIV co-infected and 1932 HCV mono-infected patients, yielding 2192 and 9894 person-years of observation with 129 and 271 deaths, respectively. The 5-year probability of survival was 0.74 [95% confidence interval (CI) 0.69,0.80] for HCV,HIV co-infected patients and 0.87 (95% CI 0.85,0.89) for HCV mono-infected patients. Co-infection was associated with substantially increased mortality (MRR 2.1, 95% CI 1.7,2.6). However, prior to the first observed decrease in CD4 counts to below 300 cells/,L, HIV infection did not increase mortality in HCV-infected patients (MRR 0.9, 95% CI 0.5,1.50). Conclusions HIV infection has a substantial impact on mortality among HCV-infected individuals, mainly because of HIV-induced immunodeficiency. [source]

Alcohol and Hepatitis C Virus,Interactions in Immune Dysfunctions and Liver Damage

ALCOHOLISM, Issue 10 2010
Gyongyi Szabo
Hepatitis C virus infection affects 170 million people worldwide, and the majority of individuals exposed to HCV develop chronic hepatitis leading to progressive liver damage, cirrhosis, and hepatocellular cancer. The natural history of HCV infection is influenced by genetic and environmental factors of which chronic alcohol use is an independent risk factor for cirrhosis in HCV-infected individuals. Both the hepatitis C virus and alcohol damage the liver and result in immune alterations contributing to both decreased viral clearance and liver injury. This review will capture the major components of the interactions between alcohol and HCV infection to provide better understanding for the molecular basis of the dangerous combination of alcohol use and HCV infection. Common targets of HCV and alcohol involve innate immune recognition and dendritic cells, the critical cell type in antigen presentation and antiviral immunity. In addition, both alcohol and HCV affect intracellular processes critical for hepatocyte and immune cell functions including mitochondrial and proteasomal activation. Finally, both chronic alcohol use and hepatitis C virus infection increase the risk of hepatocellular cancer. The common molecular mechanisms underlying the pathological interactions between alcohol and HCV include the modulation of cytokine production, lipopolysaccharide (LPS)-TLR4 signaling, and reactive oxygen species (ROS) production. LPS-induced chronic inflammation is not only a major cause of progressive liver injury and fibrosis, but it can also contribute to modification of the tissue environment and stem cells to promote hepatocellular cancer development. Alteration of these processes by alcohol and HCV produces an environment of impaired antiviral immune response, greater hepatocellular injury, and activation of cell proliferation and dedifferentiation. [source]

Is Hepatitis C Infection Associated with Increased Risk of Depression in Persons with Methamphetamine Dependence?

Ofilio Vigil MS
The abuse of methamphetamine (MA) has increased in the United States over the past 15 years and is associated with considerable negative social, psychological, and health effects, including symptoms of depression. Infection with the hepatitis C virus (HCV), which is independently associated with increased risk of depression, is common among MA users, possibly due to high rates of transmission risk behaviors in this cohort (eg, injection drug use). Given the prevalence of depression among HCV-infected individuals and MA users separately, the current study aimed to determine whether HCV infection and MA dependence are associated with additive effects on depression. Focused psychiatric evaluations were conducted on 39 individuals with both MA dependence and HCV infection (MA + HCV +), 57 persons with only MA dependence (MA + HCV ,), and a comparison sample of 46 participants with neither risk factor (MA , HCV ,). Consistent with prior research, greater self-reported symptoms of depression were observed in the MA + groups relative to MA , HCV , participants; however, there was no evidence to suggest an additive effect of HCV infection. Surprisingly, the prevalence of current and lifetime diagnoses of Major Depressive Disorder (MDD) did not differ across the study groups. Results from this study suggest that HCV infection does not confer an additive effect on the severity of depressive symptoms or the prevalence of major depression in persons with MA dependence. [source]