No hepatic iron overload 12 years after liver transplantation for hereditary hemochromatosis.
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Follow-Up Studies↗
Biomedical subjects
Catherine Guettier
Publications and source records attributed to Catherine Guettier.
Fatal disseminated Kaposi's sarcoma following human herpesvirus 8 primary infections in liver-transplant recipients.
Human herpesvirus 8 (HHV-8) is associated with the development of Kaposi's sarcoma (KS) and rare lymphoproliferative disorders in immunosuppressed patients. The risk of HHV-8 transmission by liver transplantation and the clinical manifestations of primary infection in this setting have yet to be determined. In order to evaluate this risk, we measured the seroprevalence of HHV-8 among 122 liver donors and their respective recipients before and after transplantation. Molecular methods and immunohistochemical analyses were performed to study the features of HHV-8 infection. Antibodies to HHV-8 were detected in sera of 4 donors before transplantation (3.3%) and of 3 recipients (2.4%). None of the 3 recipients, who were HHV-8 seropositive before transplantation, developed a KS during the follow-up. Four primary HHV-8 infections were detected among the 4 HHV-8 seronegative recipients who received a liver from an HHV-8 positive donor. Among these 4 recipients, 2 particularly immunosuppressed patients developed symptomatic diseases and died a few months after transplantation, harboring disseminated KS and HHV-8 positive lymphoproliferation. In these 2 patients, HHV-8 DNA genome sequences were detectable in peripheral blood mononuclear cells and other tissues with high viremia levels before and at the beginning of HHV-8-related diseases. In conclusion, in liver transplantation recipients, HHV-8 primary infection can be associated with fatal outcome. This study raises the question of screening liver donors for HHV-8--even in low HHV-8 infection prevalence countries--not systematically to exclude the graft but to monitor, clinically and biologically, patients who received a graft from an HHV-8-infected donor.
Adolescent↗
Intrasinusoidal cytotoxic CD8+ T cells in nodular regenerative hyperplasia of the liver.
Diffuse nodular regenerative hyperplasia (NRH) of the liver is an acquired architectural disturbance that can lead to portal hypertension. Although frequently associated with autoimmune or hematologic malignancies, its exact pathogenesis remains largely unknown. We observed CD8+ cytotoxic T cells in the liver sinusoids of 14 of 44 NRH patients and explored possible relationships between these lymphocytes and vascular damage. The immunophenotype of intrahepatic lymphocytes was determined using immunohistochemical analysis and endothelial injury using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method for apoptosis combined with endothelial cell labeling. Controls for the quantitative analysis of liver-infiltrating lymphocytes consisted of patients with chronic hepatitis C or normal liver (n = 13 and n = 6, respectively). Liver specimens from the 14 patients dislayed intrasinusoidal infiltrate composed of CD3+ and CD8+ lymphocytes, located near atrophic liver cell plates. Significantly more granzyme B+ and CD57+ lymphocytes were observed in NRH than chronic hepatitis C samples with quantitatively similar CD8+ infiltrates. Double-labeling revealed apoptotic endothelial sinusoidal cells in CD8+ T-cell-infiltrated areas in all NRH samples but never in chronic hepatitis C or normal livers. T-cell receptor rearrangement or immunoscope analysis suggested liver-specific polyclonal or oligoclonal T-cell expansions. Clinical and biological characteristics of the 14 patients were similar to those observed in the 30 patients with NRH devoid of lymphocytic infiltration. We report here that CD8+ cytotoxic T cells infiltrated the liver sinusoids of a high percentage (32%) of NRH patients and suggest that some NRH cases might result from chronic, cytotoxic CD8+ T-lymphocyte targeting of sinusoidal endothelial cells.
Adult↗
Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma.
We conducted a randomized trial to compare the intensive conventional chemotherapy regimen ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone) with standard CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) in previously untreated patients with poor-risk aggressive lymphoma. Patients aged 61 to 69 years who had aggressive non-Hodgkin lymphoma with at least one prognostic factor of the age-adjusted international prognostic index (IPI) were included. ACVBP consisted of an induction phase of intensified chemotherapy and central nervous system (CNS) prophylaxis followed by a sequential consolidation phase. Of the 708 patients registered for the study, 635 were eligible. The rate of complete response was 58% in the ACVBP group and 56% in the CHOP group (P =.5). Treatment-related death occurred in 13% of the ACVBP group and 7% of the CHOP group (P =.014). At 5 years, the event-free survival was 39% in the ACVBP group and 29% in the CHOP group (P =.005). The overall survival was significantly longer for patients treated with ACVBP, at 5 years it was 46% compared with 38% for patients treated with CHOP (P =.036). CNS progressions or relapses were more frequent in the CHOP group (P =.004). Despite higher toxicity, the ACVBP regimen, used as first-line treatment for patients with poor-risk aggressive lymphoma, is superior to standard CHOP with regard to both event-free survival and overall survival.
Aged↗
Human leukocyte antigen-G (HLA-G) expression in biliary epithelial cells is associated with allograft acceptance in liver-kidney transplantation.
BACKGROUND/AIMS: Liver allograft is known to protect simultaneously transplanted organs from acute rejection. We have reported that only 6% of combined liver-kidney recipients, versus 32.5% of kidney recipients, develop kidney graft acute rejection. Release of soluble human leukocyte antigen (HLA) molecules by the liver has been proposed as a possible tolerogenic mechanism involved in the better acceptance of double transplants. The HLA-G molecule is acknowledged to possess tolerogenic properties. METHODS: We investigated the involvement of HLA-G in allogeneic transplant acceptance by analyzing its expression in kidney and liver biopsies of 40 combined transplanted patients. RESULTS: We demonstrate the presence of HLA-G in 14 out of 40 liver and five out of nine kidney transplants biopsies. HLA-G is expressed de novo by cells that are otherwise frequently susceptible target cells of acute rejection, i.e. liver biliary and renal tubular epithelial cells. We show a significant association between HLA-G expression in liver biliary epithelial cells and the absence of liver graft rejection. No acute or chronic rejection of the kidney graft was observed in patients in whom HLA-G was expressed in the liver graft. CONCLUSIONS: HLA-G expression in the liver allograft is associated with a lower frequency of hepatic and renal acute rejection and may be involved in the acceptance of simultaneously transplanted organs.
Adult↗
HBV DNA persistence 10 years after liver transplantation despite successful anti-HBS passive immunoprophylaxis.
Long-term immunoprophylaxis with hepatitis B immune globulin (HBIG) is widely accepted for the prevention of recurrent hepatitis B virus (HBV) infection after liver transplantation in HBV-infected patients without viral replication. We report long-term results of HBIG administration in 284 hepatitis B surface antigen (HBsAg)-positive transplant patients. In protocol 1, 259 patients were given HBIG with the goal of maintaining the anti-HBs antibody (Ab) titer over 100 IU/L. After December 1993, 25 HBV DNA-positive patients received HBIG, with a target anti-HBs Ab titer over 500 IU/L, combined with posttransplantation antiviral therapy (protocol 2). At 10 years, 44 patients without recurrence were tested for the presence of HBV DNA in serum using real-time polymerase chain reaction (PCR); 28 were also tested in liver and peripheral blood mononuclear cells (PBMC). The overall 5- and 10-year posttransplantation actuarial rates of HBV recurrence were 24.2% and 25.4%, respectively. The 5-year recurrence rate in protocol 2 patients was 11.8%. On multivariate analysis, predictors of lower HBV recurrence risk were absence of serum HBV DNA before transplantation (P <.0001), acute liver disease (P =.0037), HDV superinfection (P =.012), and protocol 2 therapy (P <.0001). Low-level HBV DNA was detected by PCR in 45.4% of patients without HBV recurrence at 10 years. Overall actuarial 10-year survival was 74.4%. In conclusion, we confirm the efficacy of long-term HBIG immunoprophylaxis. Combination prophylaxis with HBIG and antiviral therapy is effective in patients with viral replication. Although there were only a few cases of HBV recurrence after 5 years, HBV DNA remained present in 45% of patients at 10 years.
Adult↗
Fulminant hepatitis after grand mal seizures: mechanisms and role of liver transplantation.
Fulminant liver failure is a rare complication of grand mal seizures with a high mortality, the prognosis being largely determined by the combination of the hepatic and neurologic insults. The mechanisms of acute liver failure secondary to grand mal epilepsy and the place of liver transplantation in this context are poorly defined and are the subject of this report. A series of 6 such patients is presented. All had a history of chronic primary or post-traumatic epilepsy and presented with acute liver failure shortly after a grand mal fit. Detailed accounts of background, presentation, and management are given and integrated with blood, radiologic, and histologic investigations. Two of the 6 patients survived, 1 making a full recovery and the other with neurologic sequelae. Two patients underwent liver transplantation but died with severe neurologic sequelae despite improving liver function. The remaining 2 patients were considered too ill to undergo liver transplantation and died in multiple organ failure. Liver histology from needle biopsy and/or native liver explants identified lesions compatible with a combination of steatosis and necrosis. Factor V and transaminase levels may allow early identification of patients in whom liver function is likely to improve spontaneously. In conclusion, the mechanisms of liver failure occurring after grand mal seizures appear multifactorial, including hypoxia, steatosis, and drug-induced components. The neurological prognosis and overall survival of these patients remains poor.
Adult↗