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TT virus infection in transfusion-dependent thalassemia
Poster Sessions
150
to: fulminant hepatic failure (n = 1); immune restoration syndrome (n = 1); HBeAg clearance in lamivudine treated subjects (n -- 2) or spontaneously (n = 1); HBeAg+ reactivation (n = 2); drug hepatotoxicity (n = 2); HBsAg seroconversion under lamivudine (n = 2); alcohol abuse (n = 3); lamivudine resistance (n = 1); and HBV acute severe reactivation in previous HBsAg negative (HBcAb+, HBV-DNA neg) (n = 2). Two of 3 patients were receiving lamivudine at the time of HBV reactivation. Latent HBV infection (HBsAg-, but HBV-DNA+) was ruled out in these three cases. Contusion: Hepatitis flares in HBV-HIV patients can be explained by multiple mechanisms. Development of lamivudine resistance, immune restoration syndrome and reactivation of HBV replication should be specially kept in mind. The role of silent HBV infection requires further clarification in coinfected individuals.
-0"~ TT VIRUS INFECTION IN TRANSFUSION-DEPENDENT THALASSEMIA U.S. Akarca, D. Canatan, N. Gul, O. Ozutemiz, H. Mete, Y. Batur.
Gastroenterology, Ege University Medical School, lzmir, Turkey TT virus (TTV) has been reported to be involved in the development of posttransfusion hepatitis. However its contribution to liver disease and transmission route are still obscure. To examine the role of blood transfusion as a transmission route of TTV and to check whether TFV contributes to liver disease we investigated the TTV prevalence in transfusion dependent thalassemia and its relation to the number of blood transfusion, presence of HCV infection, and transaminase elevation. Results: 102 patients (age: 11 + 8, 59 M, 43 F) with transfusion-dependent thalassemia were studied. TTV virus was detected by seminested PCR in 62% of the patients. Transfusion number in TTV positive patients was not different from that in TTV negatives (15.2 4- 7.7. vs. 12.9 :k 6.9). TTV was positive in 55.8% of patients with HCV infection and in 65.2% of HCV negative patients (NS). There was no relation between presence of T I N and age, ALT elevation, and HBV seropositivity of the patients. Conclusions: TTV is acquired at very early ages in thalassemic patients. It is probably transmitted through nonparenteral routes, and not an additive factor in liver enzyme elevation.
~-]
INCREASING MORTALITY AMONG HIV/ItCV COINFECTED PATIENTS TREATED WITH HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART)
J. Macias, J.A. Pineda, I. Melguizo, M. Leal, J. Delgado, R. Rosa, A. Sanchez-Quijano, J.M. Rivera, E. Lissen. Servicio de Medicina
Interna, Hospital de Valme, Seville, Spain In the pre-HAART era, HCV infection did not impact on the mortality nor survival of HIV infected patients, although HCV infection evolves rapidly to cirrhosis in these patients. Since 1997 the AIDS mortality has been reduced due to the use of HAART. Some antiretroviral drugs are hepatotoxic, and HAART has no effect on HCV infection. The mortality due to liver failure in HCV/HIV co-infected patients could be increasing. Because of this, we analyzed the mortality due to liver failure in HIV infected patients. A cohort of 529 HIV infected, antiretroviral-treated patients, followed up from 1989 to September 2000, was investigated. Patients were included when antiretroviral drugs were prescribed. HAART was introduced extensively in the cohort since 1997. Patients with more than one visit were selected (n = 492). The median follow-up period was 1392 days. The median baseline CD4+ cell counts were 300 cells/mcl. HCV, HBV and HDV infections were present in 333 (66%), 23 (4.5%) and 9 (1.8%) patients, respectively. Most deaths were due to AIDS before and after 1997. The frequency of deaths due to liver failure increased after 1997, from 4.5% to 18.2%. The mortality (deaths/100 patients-year) before 1997 was: AIDS 6.2, liver failure 0.4, other causes
2.4. After 1997, AIDS and other causes decreased to 2.8 and 0.46, respectively, but liver failure increased to 0.7. The cohort was divided into patients infected by HCV and without hepatitis virus infections. There was no difference in survival between the two groups (p = 0.95, log-rank). In the HAART era, morgality among HIV/HCV co-infected patients with moderate to severe immunosuppression is still mostly due to AIDS. However, liver failure is an emerging cause of death.
['-~
CD81 MODULATION BY IMMOBILIZED MONOCLONAL ANTIBODIES IS ABLE TO PROMOTE B-CELL PROLIFERATION AND C-MYC EXPRESSION
P. Caini, A. Mazzocca, C. Cordelia, C. Giannini, P. Pantaleo, R. Giulio Romanelli, M. Eugenia Marrocchi, G. Laffi, E Gentilini, A. Linda Zignego. Dipartimento di Medicina lnterna, University di
Firenze, Firenze, Italy
Background: HCV is closely associated with B-cell lymphoproliferative disorders (LPDs). It has been shown that HCV-E2 protein binds to CD81 tetraspanin molecule with high affinity. On B-ceils, CD81 is a part of a molecular complex including CD19, CD21, Leul3, betal-integrin and HLA-DR. Aim and Methods: In order to investigate CD81 binding to agonist molecules, we studied the effects of anti-CD81 mAbs on a well differentiated B-cell line (WIL2-NS) as well as a bepatoma cell line (Huh-7) by using 3H-thymidine incorporation, cell counting, immobilized antibody assay (JS81 and 1.3.3.22 Abs), Western blot and gel mobility shift methods. Results: Immobilized anti-CD81 mAbs induced a change in cell morfology (spreading), evident in both B-cell and hepatoma cell lines. In addition, in WIL2-NS an increase of DNA synthesis and cell counting at 72 hours together with increased expression of c-myc was observed. Conclusions: This study adds information about modalities and consequences of CD81 binding potentially helping current knowledge in HCV-related B-cell LPD pathogenesis.
~-7
DOES HCV CORE ANTIGEN DETECTION IN GRAFT DONORS IMPROVE ORGAN TRANSPLANTATIONVIRAL SAFETY?
D. Challine, P. Larderie, G. Dameron, D. Girard, J. Claquin, D. Dhumeanx, J.M. Pawlotsky. Virology, Hopital Henri Mondor,
Creteil, France Organ transplantation recipients are exposed to the transmission of various viruses. Viral safety is based on careful selection of the grafts, based on both clinical criteria and systematic screening for the following markers: anti-human immunodeficiency virus antibodies and p24 antigen, anti human T-cell leukemia virus antibodies, anti-cytomegalovirus antibodies, anti-Epstein-Barr virus antibodies, HBs antigen, anti-HBs antibodies and anti-HBc antibodies, and anti-hepatitis C virus (HCV) antibodies. A residual risk of HCV transmission is theoretically associated with the serological window that can occur in an acutely infected patient before seroconversion, and that can last for up to 70 days. The objective of this study was to determine the value of HCV core antigen detection to improve viral safety of organ grafts. We tested blood samples prospectively collected between 1993 and 1999 in 2000 consecutive organ donors from the Paris area for the presence of HCV core antigen with a new enzyme immunoassay (Core Antigen ELISA Test System, Ortho-Clinical Diagnostics, Radtan, New Jersey). Positive results were confirmed by neutralization. Of 2000 samples tested, 5 were found to be positive for the HCV core on first determination, among which 4 were confirmed to be specific (prevalence 0.20%; 95% confidence interval: 0.10%-0.30%). These four donors were also anti-HCV antibody-positive. The donor with a nonspecific reaction was antibody-negative and HCV RNA negative in PCR. In conclusion, the
150
to: fulminant hepatic failure (n = 1); immune restoration syndrome (n = 1); HBeAg clearance in lamivudine treated subjects (n -- 2) or spontaneously (n = 1); HBeAg+ reactivation (n = 2); drug hepatotoxicity (n = 2); HBsAg seroconversion under lamivudine (n = 2); alcohol abuse (n = 3); lamivudine resistance (n = 1); and HBV acute severe reactivation in previous HBsAg negative (HBcAb+, HBV-DNA neg) (n = 2). Two of 3 patients were receiving lamivudine at the time of HBV reactivation. Latent HBV infection (HBsAg-, but HBV-DNA+) was ruled out in these three cases. Contusion: Hepatitis flares in HBV-HIV patients can be explained by multiple mechanisms. Development of lamivudine resistance, immune restoration syndrome and reactivation of HBV replication should be specially kept in mind. The role of silent HBV infection requires further clarification in coinfected individuals.
-0"~ TT VIRUS INFECTION IN TRANSFUSION-DEPENDENT THALASSEMIA U.S. Akarca, D. Canatan, N. Gul, O. Ozutemiz, H. Mete, Y. Batur.
Gastroenterology, Ege University Medical School, lzmir, Turkey TT virus (TTV) has been reported to be involved in the development of posttransfusion hepatitis. However its contribution to liver disease and transmission route are still obscure. To examine the role of blood transfusion as a transmission route of TTV and to check whether TFV contributes to liver disease we investigated the TTV prevalence in transfusion dependent thalassemia and its relation to the number of blood transfusion, presence of HCV infection, and transaminase elevation. Results: 102 patients (age: 11 + 8, 59 M, 43 F) with transfusion-dependent thalassemia were studied. TTV virus was detected by seminested PCR in 62% of the patients. Transfusion number in TTV positive patients was not different from that in TTV negatives (15.2 4- 7.7. vs. 12.9 :k 6.9). TTV was positive in 55.8% of patients with HCV infection and in 65.2% of HCV negative patients (NS). There was no relation between presence of T I N and age, ALT elevation, and HBV seropositivity of the patients. Conclusions: TTV is acquired at very early ages in thalassemic patients. It is probably transmitted through nonparenteral routes, and not an additive factor in liver enzyme elevation.
~-]
INCREASING MORTALITY AMONG HIV/ItCV COINFECTED PATIENTS TREATED WITH HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART)
J. Macias, J.A. Pineda, I. Melguizo, M. Leal, J. Delgado, R. Rosa, A. Sanchez-Quijano, J.M. Rivera, E. Lissen. Servicio de Medicina
Interna, Hospital de Valme, Seville, Spain In the pre-HAART era, HCV infection did not impact on the mortality nor survival of HIV infected patients, although HCV infection evolves rapidly to cirrhosis in these patients. Since 1997 the AIDS mortality has been reduced due to the use of HAART. Some antiretroviral drugs are hepatotoxic, and HAART has no effect on HCV infection. The mortality due to liver failure in HCV/HIV co-infected patients could be increasing. Because of this, we analyzed the mortality due to liver failure in HIV infected patients. A cohort of 529 HIV infected, antiretroviral-treated patients, followed up from 1989 to September 2000, was investigated. Patients were included when antiretroviral drugs were prescribed. HAART was introduced extensively in the cohort since 1997. Patients with more than one visit were selected (n = 492). The median follow-up period was 1392 days. The median baseline CD4+ cell counts were 300 cells/mcl. HCV, HBV and HDV infections were present in 333 (66%), 23 (4.5%) and 9 (1.8%) patients, respectively. Most deaths were due to AIDS before and after 1997. The frequency of deaths due to liver failure increased after 1997, from 4.5% to 18.2%. The mortality (deaths/100 patients-year) before 1997 was: AIDS 6.2, liver failure 0.4, other causes
2.4. After 1997, AIDS and other causes decreased to 2.8 and 0.46, respectively, but liver failure increased to 0.7. The cohort was divided into patients infected by HCV and without hepatitis virus infections. There was no difference in survival between the two groups (p = 0.95, log-rank). In the HAART era, morgality among HIV/HCV co-infected patients with moderate to severe immunosuppression is still mostly due to AIDS. However, liver failure is an emerging cause of death.
['-~
CD81 MODULATION BY IMMOBILIZED MONOCLONAL ANTIBODIES IS ABLE TO PROMOTE B-CELL PROLIFERATION AND C-MYC EXPRESSION
P. Caini, A. Mazzocca, C. Cordelia, C. Giannini, P. Pantaleo, R. Giulio Romanelli, M. Eugenia Marrocchi, G. Laffi, E Gentilini, A. Linda Zignego. Dipartimento di Medicina lnterna, University di
Firenze, Firenze, Italy
Background: HCV is closely associated with B-cell lymphoproliferative disorders (LPDs). It has been shown that HCV-E2 protein binds to CD81 tetraspanin molecule with high affinity. On B-ceils, CD81 is a part of a molecular complex including CD19, CD21, Leul3, betal-integrin and HLA-DR. Aim and Methods: In order to investigate CD81 binding to agonist molecules, we studied the effects of anti-CD81 mAbs on a well differentiated B-cell line (WIL2-NS) as well as a bepatoma cell line (Huh-7) by using 3H-thymidine incorporation, cell counting, immobilized antibody assay (JS81 and 1.3.3.22 Abs), Western blot and gel mobility shift methods. Results: Immobilized anti-CD81 mAbs induced a change in cell morfology (spreading), evident in both B-cell and hepatoma cell lines. In addition, in WIL2-NS an increase of DNA synthesis and cell counting at 72 hours together with increased expression of c-myc was observed. Conclusions: This study adds information about modalities and consequences of CD81 binding potentially helping current knowledge in HCV-related B-cell LPD pathogenesis.
~-7
DOES HCV CORE ANTIGEN DETECTION IN GRAFT DONORS IMPROVE ORGAN TRANSPLANTATIONVIRAL SAFETY?
D. Challine, P. Larderie, G. Dameron, D. Girard, J. Claquin, D. Dhumeanx, J.M. Pawlotsky. Virology, Hopital Henri Mondor,
Creteil, France Organ transplantation recipients are exposed to the transmission of various viruses. Viral safety is based on careful selection of the grafts, based on both clinical criteria and systematic screening for the following markers: anti-human immunodeficiency virus antibodies and p24 antigen, anti human T-cell leukemia virus antibodies, anti-cytomegalovirus antibodies, anti-Epstein-Barr virus antibodies, HBs antigen, anti-HBs antibodies and anti-HBc antibodies, and anti-hepatitis C virus (HCV) antibodies. A residual risk of HCV transmission is theoretically associated with the serological window that can occur in an acutely infected patient before seroconversion, and that can last for up to 70 days. The objective of this study was to determine the value of HCV core antigen detection to improve viral safety of organ grafts. We tested blood samples prospectively collected between 1993 and 1999 in 2000 consecutive organ donors from the Paris area for the presence of HCV core antigen with a new enzyme immunoassay (Core Antigen ELISA Test System, Ortho-Clinical Diagnostics, Radtan, New Jersey). Positive results were confirmed by neutralization. Of 2000 samples tested, 5 were found to be positive for the HCV core on first determination, among which 4 were confirmed to be specific (prevalence 0.20%; 95% confidence interval: 0.10%-0.30%). These four donors were also anti-HCV antibody-positive. The donor with a nonspecific reaction was antibody-negative and HCV RNA negative in PCR. In conclusion, the