M. Gigou - Academia.edu (original) (raw)
Papers by M. Gigou
Transplantation Proceedings
Gastroentérologie Clinique et Biologique
Gastroenterology, 1993
The role of hepatitis C virus (HCV) in the development of fulminant hepatitis is poorly understoo... more The role of hepatitis C virus (HCV) in the development of fulminant hepatitis is poorly understood. The polymerase chain reaction was used to detect HCV RNA and hepatitis B virus (HBV) DNA in serum and liver of 40 patients with fulminant or subfulminant hepatitis. HCV RNA was detected in none of the 23 subjects with hepatitis B surface antigen (HBsAg)-negative hepatitis of unknown etiology. HBV DNA was found in 1 of these 23 subjects. In contrast, 8 of the 17 patients with HBsAg-positive hepatitis were HCV RNA positive. Among the latter, 5 had immunoglobulin (Ig) M antibody to hepatitis B core antigen (anti-HBc) and thus were acutely coinfected by HBV and HCV, whereas 3 others without IgM anti-HBc had superinfection by HCV. The active replication of HCV in the liver was shown by detection of high titers of HCV RNA and of negative-stranded HCV RNA. This investigation therefore shows no evidence of a role for HCV infection in sporadic cases of fulminant hepatitis without defined etiol...
Liver, 1995
The objective of this study was to look for HBV precore mutations in three patients with chronic ... more The objective of this study was to look for HBV precore mutations in three patients with chronic active hepatitis B who developed HBV-DNA-positive/HBeAg-negative reactivation after HBe seroconversion induced by interferon therapy. Direct sequencing of polymerase chain reaction products was performed on serum collected before and after HBe seroconversion. In two patients precore sequence showed only wild-type HBV before and after interferon therapy. In one patient, precore sequence showed only wild-type HBV before interferon therapy and a mixed infection by wild-type HBV and precore mutant viruses (1858 and 1896 nucleotide mutations) after treatment. The presence of HBeAg/anti-HBe immune complexes was found after HBe seroconversion in all cases. Our results suggest that: 1) precore mutations are not always found in patients with chronic hepatitis B who develop HBV DNA-positive/HBeAg-negative reactivation; and 2) HBeAg negativity, despite the presence of wild-type HBV, might be due to...
Transplantation proceedings, 1981
Transplantation proceedings, 1991
Journal of Hepatology, 2009
Introduction: Subjects coinfected by HIV and HCV have a severe disease before and after liver tra... more Introduction: Subjects coinfected by HIV and HCV have a severe disease before and after liver transplantation.The aim of this study was to determine if the humoral response to HCV envelope protein, assessed through HCV pseudoparticles (HCVpp) could be modified by HIV coinfection and, in this case by antiretroviral therapies, or by liver transplantation (LT). Patients and Methods: Forty patients with plasmas before, 6 and 12 months after LT: 13 were coinfected by HIV and HCV, 12 were only infected by HCV and 12 were coinfected by HIV and HBV and not by HCV. All transplanted HIV patients were on HAART with low HIV viral loads and CD4 > 200. Thirteen non transplanted HIV-HCV patients with low CD4 without HAART were included and had available samples 12 months after. In 8 patients, HAART were initiated in the month following the first sample. Neutralisation of 146 tested plasmas was estimated by using 4 different HCVpp (genotypes 1a, 1b, 3 and 4) and control non-HCVpp in HuH7 and in triplicate. Results: Plasmas from mono-infected HCV-patients decreased the infection of HuH7 by the different tested HCVpp more efficiently (70%±24) than the plasmas from HIV-HCV coinfected patients treated by HAART (50%±15, p < 0.005) or not (35±25%; p < 0.01). After LT, neutralization by tested plasmas decreased more in HIV-HCV (15%±20) than in HCV monoinfected patients (50%±30). In non-LT coinfected HIV-HCV patients, neutralization increased together with CD4 counts in the eight treated patients and remained steady in the untreated group. In HIV-HBV as well as in HIV-HCV transplanted patients, the level of neutralization was null and facilitation was clearly observed in five subjects. These results were independent from the dosage of LDL/HDL in tested samples, of the HCV loads and of the severity of HCV recurrence in LT patients. Conclusion: In subjects chronically infected by HCV, the humoral response against HCV envelopes is clearly decreased in case of HIV coinfection or of LT. Conversely, the initiation of HAART lead to an increased HCV neutralization. The poor humoral control of HCV could explain the severity of Hepatitis C in HIV patients, before as well after LT.
Transplantation, 1988
Liver allografts have a privileged status with regard to hyperacute rejection. In this experiment... more Liver allografts have a privileged status with regard to hyperacute rejection. In this experimental study, we have used extracorporeal liver hemoperfusion in sensitized rats in order to analyze reactions between lymphocytotoxic antibodies and the liver. In sensitized BN rats, a donor-specific (Lewis) extracorporeal liver hemoperfusion can delay hyperacute rejection of heart allografts and reduce the level of lymphocytotoxic antibodies. The decrease in the level of antibodies could be due to massive absorption of antibodies by the liver or to release of major histocompatibility complex antigens in a soluble form. Immunofluorescent examination of the hemoperfused liver revealed important deposits of C3 on Kupffer cells and of IgG on sinusoidal cells. On the contrary, in control rats in which a third-party (DA) liver hemoperfusion was performed, heart allograft survival was less prolonged, the decrease in the level of lymphocytotoxic antibodies was not significant, and the deposits of IgG and C3 were much less evident. The level of circulating immune complexes was unchanged after a donor-specific or a third-party liver hemoperfusion. These results support the hypothesis that resistance of the liver to hyperacute rejection might be due to a massive and nontoxic absorption of lymphocytotoxic antibodies on nonparenchymal liver cells.
Transplantation, 1988
Liver allografts have a privileged status in regard to acute rejection. In this experimental stud... more Liver allografts have a privileged status in regard to acute rejection. In this experimental study, we have analyzed the immunosuppressive effects of an extracorporeal liver hemoperfusion. In the LEW-to-BN combination of inbred rats, donor-specific liver hemoperfusion can significantly delay acute rejection of heart allografts. Analysis of the immunological status of these animals revealed a significant decrease in donor-specific lymphocytotoxic antibodies and in cytotoxic T lympholysis. Reactivity in mixed lymphocyte culture was normal. After third-party (DA) liver hemoperfusion or after donor-specific (LEW) splenic hemoperfusion, prolongation of heart allograft survival was moderate. Previous blockade of Kupffer cells suppressed the effects of donor-specific liver hemoperfusion. These results suggest that the sequestration by Kupffer cells of a clone of cytotoxic T cells and/or lymphocytotoxic antibodies may explain the immunosuppressive effects of donor-specific liver hemoperfusion.
Transplantation, 1993
230 TRANSPLANTATION Vol. 55, No. 1 Table 1. Functional outcome of canine pancreas autografts Grou... more 230 TRANSPLANTATION Vol. 55, No. 1 Table 1. Functional outcome of canine pancreas autografts Group Preservation method Numbe] At 1 day г of functioning grafts At 7 days At 14 days 1 (n=8) UW 1 (12%) 1(12%) 1 (12%)&quot; 2 (n=7) UW/PFC + 02 6 (86%) 4 (57%) 4 (57%)b 3 ...
Liver Transplantation and Surgery, 1999
investigators, retransplantation appears contraindicated because of constant recurrence and a hig... more investigators, retransplantation appears contraindicated because of constant recurrence and a high mortality. We report our experience in this setting. Between January 1985 and December 1995, 10 patients who underwent retransplantation for HBV graft reinfection were studied. According to the antiviral treatment administered after HBV recurrence on the first liver graft and the protocol of antiviral prophylaxis after retransplantation, two groups were defined: group 1 underwent retransplantation before January 1992 (n ؍ 5), and group 2 underwent retransplantation after January 1992 (n ؍ 5). At the time of reinfection, serum HBV DNA was positive in all patients, hepatitis Be antigen (HBeAg) was positive in 6 patients. Antiviral therapy was administered to 7 patients (group 1, adenine arabinoside mono phosphate [ara-Amp; n ؍ 3]; group 2, ara-Amp [n ؍ 5], ganciclovir [n ؍ 4]). After retransplanta-tion, long-term antibody to HB surface antigen (anti-HBs) immunoglobulins were administered to achieve an anti-HBs titer greater than 100 IU/L in group 1 and to achieve an anti-HBs titer greater than 500 IU/L associated with prophylactic intravenous ganciclovir administration (5 mg/kg three times weekly) for 2 years in group 2. In group 1, all patients died, either perioperatively or secondary to HBV recurrence (1 year survival, 0%). In group 2, 1 patient died 50 months after retransplantation of HBV cirrhosis on the second graft, and 4 patients remained HBsAg negative at a mean of 41 months (range, 24 to 68 months) after retransplantation. The prognosis of retransplantation for HBV recurrence was dramatically improved by the administration of antiviral therapy before retransplantation and the maintenance of a high anti-HBs level combined with antiviral therapy after retransplantation.
Journal of Virology, 2001
The influence of viral factors on the severity of hepatitis C virus (HCV)-related liver disease i... more The influence of viral factors on the severity of hepatitis C virus (HCV)-related liver disease is controversial. We studied 68 liver transplant patients with recurrent hepatitis C, of whom 53 were infected by genotype 1 strains. Relationships between core sequences, serum HCV RNA levels, and fibrosis scores for each patient were analyzed in pairwise fashion 5 years after transplantation. We used Mantel's test, a matrix correlation method, to evaluate the correspondence between measured genetic distances and observed phenotypic differences. No clear relationship was found when all 68 patients were analyzed. In contrast, when the 53 patients infected by genotype 1 strains were analyzed, a strong positive relationship was found between genetic distance and differences in 5-year fibrosis scores (P ؍ 0.001) and differences in virus load (P ؍ 0.009). In other words, the smaller the genetic distance between two patients' viral core sequences, the smaller the difference between the two patients' fibrosis scores and viral replication levels. No relationship was found between genetic distance and differences in age, sex, or immunosuppression. In multivariate analysis, the degree of fibrosis was negatively related to the virus load (r ؍ ؊0.68; P ؍ 0.003). In the particular setting of liver transplantation, and among strains with closely related phylogenetic backgrounds (genotype 1), this study points to a correlation between the HCV genetic sequence and the variability of disease expression.
Journal of Virology, 2005
Differences in hepatitis C virus (HCV) variants of the highly conserved 5 untranslated region (UT... more Differences in hepatitis C virus (HCV) variants of the highly conserved 5 untranslated region (UTR) have been observed between plasma and peripheral blood mononuclear cells (PBMC). The prevalence and the mechanisms of this compartmentalization are unknown. Plasma and PBMC HCV variants were compared by single-strand conformation polymorphism (SSCP) and by cloning or by genotyping with a line probe assay (LiPA) in 116 chronically infected patients, including 44 liver transplant recipients. SSCP patterns differed between compartments in 43/109 analyzable patients (39%). Differences were significantly more frequent in patients with transplants (21/38 [55%] versus 22/71 [31%]; P < 0.01) and in those who acquired HCV through multiple transfusions before 1991 (15/20; 75%) or through drug injection (16/31; 52%) than in those infected through an unknown route (7/29; 24%) or through a single transfusion (5/29; 17%; P < 0.001). Cloning of the 5 UTR, LiPA analysis, and nonstructural region 5B sequencing revealed different genotypes in the two compartments from 10 patients (9%). In nine patients, the genotype detected in PBMC was not detected in plasma and was weak or undetectable in the liver in three cases. This genotypic compartmentalization persisted for years in three patients and after liver transplantation in two. The present study shows that a significant proportion of HCV-infected subjects harbor in their PBMC highly divergent variants which were likely acquired through superinfections.
Journal of Hepatology, 2010
Transplantation Proceedings
Gastroentérologie Clinique et Biologique
Gastroenterology, 1993
The role of hepatitis C virus (HCV) in the development of fulminant hepatitis is poorly understoo... more The role of hepatitis C virus (HCV) in the development of fulminant hepatitis is poorly understood. The polymerase chain reaction was used to detect HCV RNA and hepatitis B virus (HBV) DNA in serum and liver of 40 patients with fulminant or subfulminant hepatitis. HCV RNA was detected in none of the 23 subjects with hepatitis B surface antigen (HBsAg)-negative hepatitis of unknown etiology. HBV DNA was found in 1 of these 23 subjects. In contrast, 8 of the 17 patients with HBsAg-positive hepatitis were HCV RNA positive. Among the latter, 5 had immunoglobulin (Ig) M antibody to hepatitis B core antigen (anti-HBc) and thus were acutely coinfected by HBV and HCV, whereas 3 others without IgM anti-HBc had superinfection by HCV. The active replication of HCV in the liver was shown by detection of high titers of HCV RNA and of negative-stranded HCV RNA. This investigation therefore shows no evidence of a role for HCV infection in sporadic cases of fulminant hepatitis without defined etiol...
Liver, 1995
The objective of this study was to look for HBV precore mutations in three patients with chronic ... more The objective of this study was to look for HBV precore mutations in three patients with chronic active hepatitis B who developed HBV-DNA-positive/HBeAg-negative reactivation after HBe seroconversion induced by interferon therapy. Direct sequencing of polymerase chain reaction products was performed on serum collected before and after HBe seroconversion. In two patients precore sequence showed only wild-type HBV before and after interferon therapy. In one patient, precore sequence showed only wild-type HBV before interferon therapy and a mixed infection by wild-type HBV and precore mutant viruses (1858 and 1896 nucleotide mutations) after treatment. The presence of HBeAg/anti-HBe immune complexes was found after HBe seroconversion in all cases. Our results suggest that: 1) precore mutations are not always found in patients with chronic hepatitis B who develop HBV DNA-positive/HBeAg-negative reactivation; and 2) HBeAg negativity, despite the presence of wild-type HBV, might be due to...
Transplantation proceedings, 1981
Transplantation proceedings, 1991
Journal of Hepatology, 2009
Introduction: Subjects coinfected by HIV and HCV have a severe disease before and after liver tra... more Introduction: Subjects coinfected by HIV and HCV have a severe disease before and after liver transplantation.The aim of this study was to determine if the humoral response to HCV envelope protein, assessed through HCV pseudoparticles (HCVpp) could be modified by HIV coinfection and, in this case by antiretroviral therapies, or by liver transplantation (LT). Patients and Methods: Forty patients with plasmas before, 6 and 12 months after LT: 13 were coinfected by HIV and HCV, 12 were only infected by HCV and 12 were coinfected by HIV and HBV and not by HCV. All transplanted HIV patients were on HAART with low HIV viral loads and CD4 > 200. Thirteen non transplanted HIV-HCV patients with low CD4 without HAART were included and had available samples 12 months after. In 8 patients, HAART were initiated in the month following the first sample. Neutralisation of 146 tested plasmas was estimated by using 4 different HCVpp (genotypes 1a, 1b, 3 and 4) and control non-HCVpp in HuH7 and in triplicate. Results: Plasmas from mono-infected HCV-patients decreased the infection of HuH7 by the different tested HCVpp more efficiently (70%±24) than the plasmas from HIV-HCV coinfected patients treated by HAART (50%±15, p < 0.005) or not (35±25%; p < 0.01). After LT, neutralization by tested plasmas decreased more in HIV-HCV (15%±20) than in HCV monoinfected patients (50%±30). In non-LT coinfected HIV-HCV patients, neutralization increased together with CD4 counts in the eight treated patients and remained steady in the untreated group. In HIV-HBV as well as in HIV-HCV transplanted patients, the level of neutralization was null and facilitation was clearly observed in five subjects. These results were independent from the dosage of LDL/HDL in tested samples, of the HCV loads and of the severity of HCV recurrence in LT patients. Conclusion: In subjects chronically infected by HCV, the humoral response against HCV envelopes is clearly decreased in case of HIV coinfection or of LT. Conversely, the initiation of HAART lead to an increased HCV neutralization. The poor humoral control of HCV could explain the severity of Hepatitis C in HIV patients, before as well after LT.
Transplantation, 1988
Liver allografts have a privileged status with regard to hyperacute rejection. In this experiment... more Liver allografts have a privileged status with regard to hyperacute rejection. In this experimental study, we have used extracorporeal liver hemoperfusion in sensitized rats in order to analyze reactions between lymphocytotoxic antibodies and the liver. In sensitized BN rats, a donor-specific (Lewis) extracorporeal liver hemoperfusion can delay hyperacute rejection of heart allografts and reduce the level of lymphocytotoxic antibodies. The decrease in the level of antibodies could be due to massive absorption of antibodies by the liver or to release of major histocompatibility complex antigens in a soluble form. Immunofluorescent examination of the hemoperfused liver revealed important deposits of C3 on Kupffer cells and of IgG on sinusoidal cells. On the contrary, in control rats in which a third-party (DA) liver hemoperfusion was performed, heart allograft survival was less prolonged, the decrease in the level of lymphocytotoxic antibodies was not significant, and the deposits of IgG and C3 were much less evident. The level of circulating immune complexes was unchanged after a donor-specific or a third-party liver hemoperfusion. These results support the hypothesis that resistance of the liver to hyperacute rejection might be due to a massive and nontoxic absorption of lymphocytotoxic antibodies on nonparenchymal liver cells.
Transplantation, 1988
Liver allografts have a privileged status in regard to acute rejection. In this experimental stud... more Liver allografts have a privileged status in regard to acute rejection. In this experimental study, we have analyzed the immunosuppressive effects of an extracorporeal liver hemoperfusion. In the LEW-to-BN combination of inbred rats, donor-specific liver hemoperfusion can significantly delay acute rejection of heart allografts. Analysis of the immunological status of these animals revealed a significant decrease in donor-specific lymphocytotoxic antibodies and in cytotoxic T lympholysis. Reactivity in mixed lymphocyte culture was normal. After third-party (DA) liver hemoperfusion or after donor-specific (LEW) splenic hemoperfusion, prolongation of heart allograft survival was moderate. Previous blockade of Kupffer cells suppressed the effects of donor-specific liver hemoperfusion. These results suggest that the sequestration by Kupffer cells of a clone of cytotoxic T cells and/or lymphocytotoxic antibodies may explain the immunosuppressive effects of donor-specific liver hemoperfusion.
Transplantation, 1993
230 TRANSPLANTATION Vol. 55, No. 1 Table 1. Functional outcome of canine pancreas autografts Grou... more 230 TRANSPLANTATION Vol. 55, No. 1 Table 1. Functional outcome of canine pancreas autografts Group Preservation method Numbe] At 1 day г of functioning grafts At 7 days At 14 days 1 (n=8) UW 1 (12%) 1(12%) 1 (12%)&quot; 2 (n=7) UW/PFC + 02 6 (86%) 4 (57%) 4 (57%)b 3 ...
Liver Transplantation and Surgery, 1999
investigators, retransplantation appears contraindicated because of constant recurrence and a hig... more investigators, retransplantation appears contraindicated because of constant recurrence and a high mortality. We report our experience in this setting. Between January 1985 and December 1995, 10 patients who underwent retransplantation for HBV graft reinfection were studied. According to the antiviral treatment administered after HBV recurrence on the first liver graft and the protocol of antiviral prophylaxis after retransplantation, two groups were defined: group 1 underwent retransplantation before January 1992 (n ؍ 5), and group 2 underwent retransplantation after January 1992 (n ؍ 5). At the time of reinfection, serum HBV DNA was positive in all patients, hepatitis Be antigen (HBeAg) was positive in 6 patients. Antiviral therapy was administered to 7 patients (group 1, adenine arabinoside mono phosphate [ara-Amp; n ؍ 3]; group 2, ara-Amp [n ؍ 5], ganciclovir [n ؍ 4]). After retransplanta-tion, long-term antibody to HB surface antigen (anti-HBs) immunoglobulins were administered to achieve an anti-HBs titer greater than 100 IU/L in group 1 and to achieve an anti-HBs titer greater than 500 IU/L associated with prophylactic intravenous ganciclovir administration (5 mg/kg three times weekly) for 2 years in group 2. In group 1, all patients died, either perioperatively or secondary to HBV recurrence (1 year survival, 0%). In group 2, 1 patient died 50 months after retransplantation of HBV cirrhosis on the second graft, and 4 patients remained HBsAg negative at a mean of 41 months (range, 24 to 68 months) after retransplantation. The prognosis of retransplantation for HBV recurrence was dramatically improved by the administration of antiviral therapy before retransplantation and the maintenance of a high anti-HBs level combined with antiviral therapy after retransplantation.
Journal of Virology, 2001
The influence of viral factors on the severity of hepatitis C virus (HCV)-related liver disease i... more The influence of viral factors on the severity of hepatitis C virus (HCV)-related liver disease is controversial. We studied 68 liver transplant patients with recurrent hepatitis C, of whom 53 were infected by genotype 1 strains. Relationships between core sequences, serum HCV RNA levels, and fibrosis scores for each patient were analyzed in pairwise fashion 5 years after transplantation. We used Mantel's test, a matrix correlation method, to evaluate the correspondence between measured genetic distances and observed phenotypic differences. No clear relationship was found when all 68 patients were analyzed. In contrast, when the 53 patients infected by genotype 1 strains were analyzed, a strong positive relationship was found between genetic distance and differences in 5-year fibrosis scores (P ؍ 0.001) and differences in virus load (P ؍ 0.009). In other words, the smaller the genetic distance between two patients' viral core sequences, the smaller the difference between the two patients' fibrosis scores and viral replication levels. No relationship was found between genetic distance and differences in age, sex, or immunosuppression. In multivariate analysis, the degree of fibrosis was negatively related to the virus load (r ؍ ؊0.68; P ؍ 0.003). In the particular setting of liver transplantation, and among strains with closely related phylogenetic backgrounds (genotype 1), this study points to a correlation between the HCV genetic sequence and the variability of disease expression.
Journal of Virology, 2005
Differences in hepatitis C virus (HCV) variants of the highly conserved 5 untranslated region (UT... more Differences in hepatitis C virus (HCV) variants of the highly conserved 5 untranslated region (UTR) have been observed between plasma and peripheral blood mononuclear cells (PBMC). The prevalence and the mechanisms of this compartmentalization are unknown. Plasma and PBMC HCV variants were compared by single-strand conformation polymorphism (SSCP) and by cloning or by genotyping with a line probe assay (LiPA) in 116 chronically infected patients, including 44 liver transplant recipients. SSCP patterns differed between compartments in 43/109 analyzable patients (39%). Differences were significantly more frequent in patients with transplants (21/38 [55%] versus 22/71 [31%]; P < 0.01) and in those who acquired HCV through multiple transfusions before 1991 (15/20; 75%) or through drug injection (16/31; 52%) than in those infected through an unknown route (7/29; 24%) or through a single transfusion (5/29; 17%; P < 0.001). Cloning of the 5 UTR, LiPA analysis, and nonstructural region 5B sequencing revealed different genotypes in the two compartments from 10 patients (9%). In nine patients, the genotype detected in PBMC was not detected in plasma and was weak or undetectable in the liver in three cases. This genotypic compartmentalization persisted for years in three patients and after liver transplantation in two. The present study shows that a significant proportion of HCV-infected subjects harbor in their PBMC highly divergent variants which were likely acquired through superinfections.
Journal of Hepatology, 2010