Ignite Creation Date:
2024-05-05 @ 6:31 PM
Last Modification Date:
2024-10-26 @ 9:34 AM
Study NCT ID:
NCT00499434
Status:
UNKNOWN
Last Update Posted:
2009-12-04
First Post:
2007-07-10
Brief Title:
Correlation Between Cytokines and Hepatic Histology in Patients Infected by HIV-1 and the Hepatitis-C Virus
Sponsor:
UPECLIN HC FM Botucatu Unesp
Organization:
UPECLIN HC FM Botucatu Unesp
Study Overview
Official Title:
Correlation Between Values of Serum Cytokines and of Those Dosed by mRNA Expression Through the Use of Real-time PCR and Hepatic Histology in Patients Infected by HIV-1 and the Hepatitis-C Virus
Status:
UNKNOWN
Status Verified Date:
2009-12
Last Known Status:
ACTIVE_NOT_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study aims at correlating TNF-α INF-γ IL-2 IL-4 IL-10 and TGF-β values as dosed by ELISA and mRNA expression by real-time PCR with histopathological hepatic biopsy findings in individuals with HIVHCV coinfection This population will be divided into three groups G1 with no HAART G2 with detected HIV viral load HIV VL G3 with undetected HIV VL which will be then compared to two control groups with monoinfection by HIV or by HCV in addition to a third control group comprising normal blood donors
Detailed Description:
Infection by the hepatitis-C virus HCV in people living with HIVAIDS PLHA has progressively gained distinction since the survival increase generated by the use of highly active antiretroviral therapy HAART has enabled the presentation of complications from HCV chronic infection There are approximately 10 million coinfected individuals that is 25 of the total PLHA as both viruses share transmission routes
HCV infection can be regarded as an opportunistic disease in this population once there is the acceleration of its natural history represented by the HCV high viral load early hepatic fibrosis and greater occurrence of steatosis cirrhosis and hepatocellular carcinoma leading to greater morbid-mortality by terminal hepatic disease The scenario is not also favorable as regards HCV treatment since the response rate in coinfected individuals is significantly lower than in mono-infected HCV patients
The complex relationship between immune response and HCV determines the velocity and the distinct outcomes found The major determinant for the development of cirrhosis and hepatic insufficiency is the accumulation of fibrosis and inflammatory activity closely related to collagen synthesis by fibroblasts and hepatocyte-apoptosis induction related to TGF-β production In individuals with more severe hepatic lesion there is the prevalence of expression of the Th-2 profile in the peripheral blood which is characterized by high levels of IL-4 and IL-10 whereas in the hepatic tissue a larger expression of cytokines of the Th-1 profile such as IL-2 and INF-γ is observed This phenomenon is known as compartmentalization of the immune response
If the immunopathogenic dynamics is already complex in HCV mono-infected individuals in the HIVHCV coinfection condition few studies specifically approach the topic without however evaluating the correlation between specific T-cell response and hepatic-lesion staging In HIV mono-infected patients without antiretroviral treatment and with disease progression the prevalence of the Th-0Th-2 profile is observed which is particularly influenced by IL-10 increase Even in individuals treated by HAART there is no recovery of the capacity to express the Th-1 profile and most of such patients show the mature Th-0 profile and low IL-2 levels
HCV viral load in PLHA is higher in both the plasma and the hepatic tissue and the replication of HCV in macrophages CD4 and CD8 T lymphocytes as well as in lymphnodes is also observed in such condition TGF-β is particularly high in this coinfection thus justifying the onset of faster fibrosis The reduction of CD8 T lymphocyte response to IFN-γ also occurs which favors the persistence of infection and prevents specific T-cell response As regards HIV treatment there is evidence that coinfected patients non-treated by HAART tend to present a Th-2 profile more often than treated individuals without however significant differences in TGF-β levels
Due to the lack of studies correlating the production tendencies of both pro-inflammatory and fibrogenesis-inducing cytokines with histopathological findings from hepatic biopsy in coinfected individuals investigations are necessary in order establish parameters that will allow the prediction of a better or worse prognosis and also more accurately indicate the performance of hepatic biopsy
This study aims at correlating TNF-α INF-γ IL-2 IL-4 IL-10 and TGF-β values as dosed by ELISA and mRNA expression by real-time PCR with histopathological hepatic biopsy findings in individuals with HIVHCV coinfection This population will be divided into three groups G1 with no HAART G2 with detected HIV viral load HIV VL G3 with undetected HIV VL which will be then compared to two control groups with monoinfection by HIV or by HCV in addition to a third control group comprising normal blood donors
HCV infection can be regarded as an opportunistic disease in this population once there is the acceleration of its natural history represented by the HCV high viral load early hepatic fibrosis and greater occurrence of steatosis cirrhosis and hepatocellular carcinoma leading to greater morbid-mortality by terminal hepatic disease The scenario is not also favorable as regards HCV treatment since the response rate in coinfected individuals is significantly lower than in mono-infected HCV patients
The complex relationship between immune response and HCV determines the velocity and the distinct outcomes found The major determinant for the development of cirrhosis and hepatic insufficiency is the accumulation of fibrosis and inflammatory activity closely related to collagen synthesis by fibroblasts and hepatocyte-apoptosis induction related to TGF-β production In individuals with more severe hepatic lesion there is the prevalence of expression of the Th-2 profile in the peripheral blood which is characterized by high levels of IL-4 and IL-10 whereas in the hepatic tissue a larger expression of cytokines of the Th-1 profile such as IL-2 and INF-γ is observed This phenomenon is known as compartmentalization of the immune response
If the immunopathogenic dynamics is already complex in HCV mono-infected individuals in the HIVHCV coinfection condition few studies specifically approach the topic without however evaluating the correlation between specific T-cell response and hepatic-lesion staging In HIV mono-infected patients without antiretroviral treatment and with disease progression the prevalence of the Th-0Th-2 profile is observed which is particularly influenced by IL-10 increase Even in individuals treated by HAART there is no recovery of the capacity to express the Th-1 profile and most of such patients show the mature Th-0 profile and low IL-2 levels
HCV viral load in PLHA is higher in both the plasma and the hepatic tissue and the replication of HCV in macrophages CD4 and CD8 T lymphocytes as well as in lymphnodes is also observed in such condition TGF-β is particularly high in this coinfection thus justifying the onset of faster fibrosis The reduction of CD8 T lymphocyte response to IFN-γ also occurs which favors the persistence of infection and prevents specific T-cell response As regards HIV treatment there is evidence that coinfected patients non-treated by HAART tend to present a Th-2 profile more often than treated individuals without however significant differences in TGF-β levels
Due to the lack of studies correlating the production tendencies of both pro-inflammatory and fibrogenesis-inducing cytokines with histopathological findings from hepatic biopsy in coinfected individuals investigations are necessary in order establish parameters that will allow the prediction of a better or worse prognosis and also more accurately indicate the performance of hepatic biopsy
This study aims at correlating TNF-α INF-γ IL-2 IL-4 IL-10 and TGF-β values as dosed by ELISA and mRNA expression by real-time PCR with histopathological hepatic biopsy findings in individuals with HIVHCV coinfection This population will be divided into three groups G1 with no HAART G2 with detected HIV viral load HIV VL G3 with undetected HIV VL which will be then compared to two control groups with monoinfection by HIV or by HCV in addition to a third control group comprising normal blood donors
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None