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1.
HPB (Oxford) ; 22(6): 900-910, 2020 06.
Article in English | MEDLINE | ID: mdl-31734238

ABSTRACT

BACKGROUND: To address the results of resection for hepatocellular carcinoma (HCC) in human immunodeficiency virus (HIV)-carriers, and to compare them against survival after liver transplantation (LT). METHODS: All patients with HIV and HCC listed for LT (candidates = LTc+) or resection (LR+) between 2000 and 2017 in our centre were analysed and compared for overall survival (OS) and disease-free survival (DFS). RESULTS: The LTc + group (n = 43) presented with higher MELD scores and more advanced portal hypertension and HCC stages than LR + group (n = 15). One-, 3- and 5-year intention-to-treat survival rates were: 81%, 60% and 44%, versus 86%, 58% and 58% in the LTc+ and LR + groups, respectively (p = 0.746). Eleven LTc + patients dropped out. After LT, OS was 81%, 68% and 59% (no difference with LR + group; p = 0.844). There tended to be better DFS after LT, reaching 78%, 68% and 56% versus 53%, 33% and 33% in the LR + group (p = 0.062). CONCLUSION: This was the largest series of resections for HCC in HIV + patients and the first intention-to-treat analysis. Although LT and resection do not always concern the same population, they enable equivalent survival. At the price of higher recurrence rate, resection could be integrated in the global armoury of liver surgeons.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Liver Transplantation , Carcinoma, Hepatocellular/surgery , Hepatectomy , Humans , Intention to Treat Analysis , Liver Neoplasms/surgery , Neoplasm Recurrence, Local/surgery , Retrospective Studies
2.
Aliment Pharmacol Ther ; 47(12): 1682-1689, 2018 06.
Article in English | MEDLINE | ID: mdl-29665081

ABSTRACT

BACKGROUND: In liver transplant recipients with hepatitis C virus recurrence, there is concern about renal safety of sofosbuvir-based regimens. Changes in serum creatinine or in the estimated glomerular filtration rate (eGFR) under treatment are used to look for possible renal toxicity. However, serum creatinine and eGFR are highly variable. AIM: To analyse renal function trajectory with numerous assays of serum creatinine over a long period of time. METHODS: In a multicentre cohort of 139 patients, the eGFR was obtained from serum creatinine using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. Slopes of eGFR were defined as a change in eGFR during a period divided by time. Pre-treatment, on-treatment and post-treatment periods were 9 months, 3-9 months and 4.5 months. Interactions between eGFR slopes and the pre-treatment eGFR, use of ribavirin or mycophenolate mofetil, and stage of fibrosis were addressed. On-treatment eGFR slopes were separated in tertiles. Pre- and post-treatment eGFR slopes were compared globally and according to tertiles. RESULTS: The post-treatment eGFR slope was significantly better than pre-treatment eGFR slope (+0.18 (IQR -0.76 to +1.32) vs -0.11 (IQR -1.01 to +0.73) mL/min/1.73 m2 /month, P = 0.03) independently of the pre-treatment eGFR (P = 0.99), ribavirin administration (P = 0.26), mycophenolate mofetil administration (P = 0.51) and stage of fibrosis (F3 and F4 vs lower stages, P = 0.18; F4 vs lower stages, P = 0.08; F4 Child-Pugh B and C vs lower stages, P = 0.38). Tertiles of on-treatment eGFR slopes were -1.71 (IQR -2.54 to -1.48), -0.78 (IQR -1.03 to -0.36) and +0.75 (IQR +0.28 to +1.47) mL/min/1.73 m2 /month. Pre- and post-treatment eGFR slopes were not significantly different according to tertiles (respectively, P = 0.34, 0.08, 0.73). CONCLUSION: The eGFR varies during treatment and gives a confusing picture of the renal safety of sofosbuvir-based regimens. In contrast, longitudinal assessment of the eGFR shows a rising trajectory over longer time, meaning that these therapies are safe for the kidneys in our cohort of liver transplant recipients.


Subject(s)
Hepatitis C/drug therapy , Kidney/pathology , Liver Transplantation/methods , Sofosbuvir/administration & dosage , Aged , Cohort Studies , Creatinine/blood , Female , Glomerular Filtration Rate , Hepacivirus/isolation & purification , Humans , Longitudinal Studies , Middle Aged , Prospective Studies , Recurrence , Renal Insufficiency, Chronic/epidemiology , Ribavirin/administration & dosage , Sofosbuvir/adverse effects
5.
Transpl Infect Dis ; 17(5): 662-70, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26192379

ABSTRACT

BACKGROUND: Few studies have investigated infections in human immunodeficiency virus (HIV)-infected liver transplant patients. The aim of this study was to describe the prevalence, time of onset, mortality of infectious complications, other than hepatitis C virus (HCV), and to identify risk factors for their development in a large single-center cohort of HIV-infected liver transplant patients. METHODS: We studied 109 consecutive HIV-infected patients who underwent liver transplantation (LT) between 1999 and 2010 and followed until December 2012. RESULTS: The median age was 44 years (interquartile range [IQR] 41-49), 82.6% were male, and the median follow-up was 45.7 months (IQR 14-65). The major indications for LT were HCV cirrhosis (61%) and hepatocellular carcinoma (19%). Forty patients (37%) developed at least 1 infection during the first year after LT. Twenty-eight (26%) patients had an episode of bacteremia. Five (4.6%) patients developed a cytomegalovirus infection. Fungal infections occurred in 5 (4.5%) patients. Four (3.6%) patients developed an HIV-related opportunistic infection. A total of 43 (39.4%) patients died during follow-up. Mortality related to infection occurred in 9 (7%) cases, and 20 (42.5%) patients died because of HCV recurrence. No patients died from opportunistic infections. Model for end-stage liver disease (MELD) score >17 was associated with a 2-fold higher risk (hazard ratio 1.96; 95% confidence interval 1.01-3.80) of developing infectious complications. CONCLUSIONS: Infections are not a major cause of mortality after LT in HIV patients and opportunistic infections of acquired immunodeficiency syndrome are infrequent. A MELD score >17 increased the risk of developing post-LT infectious complications. Recurrence of HCV infection remains a major cause of mortality.


Subject(s)
AIDS-Related Opportunistic Infections/etiology , Immunocompromised Host , Liver Transplantation , Postoperative Complications/etiology , AIDS-Related Opportunistic Infections/epidemiology , AIDS-Related Opportunistic Infections/immunology , Adult , Female , Follow-Up Studies , Humans , Male , Middle Aged , Postoperative Complications/epidemiology , Postoperative Complications/immunology , Prevalence , Risk Factors , Survival Analysis
6.
Transpl Infect Dis ; 17(2): 322-7, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25645691

ABSTRACT

Immunization against meningococcal disease is recommended for solid organ transplant (SOT) recipients at high risk for meningococcal disease or travelling to an endemic country. However, the immunogenicity of meningococcal vaccines has not been studied in this population. We analyzed the immune response of quadrivalent (against Neisseria meningitidis serogroups A, C, Y, and W) polysaccharidic non-conjugate and conjugate meningococcal vaccines in kidney- and liver-transplant patients using bactericidal assays against the targeted serogroups. Upon vaccination with a non-conjugate (n = 5) or a conjugate vaccine (n = 10), respectively, 40% and 50% of patients were able to mount an immune response, achieving at least the threshold correlated with protection defined as human serum bactericidal antibody titers of ≥4. Responders showed only partial and low responses (titers ≤64), thus predicting a rapid decline in bactericidal response. Only 1 patient developed a booster response to preexisting immunity. Our data argue for the need of additional measures for SOT recipients, when they are at risk of meningococcal disease.


Subject(s)
Antibodies, Bacterial/immunology , Immunocompromised Host/immunology , Kidney Transplantation , Liver Transplantation , Meningococcal Infections/prevention & control , Meningococcal Vaccines/therapeutic use , Neisseria meningitidis/immunology , Adult , Aged , Cohort Studies , Female , Graft Rejection/prevention & control , Humans , Immunosuppressive Agents/therapeutic use , Male , Meningococcal Vaccines/immunology , Middle Aged , Neisseria meningitidis, Serogroup A/immunology , Neisseria meningitidis, Serogroup C/immunology , Neisseria meningitidis, Serogroup W-135/immunology , Neisseria meningitidis, Serogroup Y/immunology , Prospective Studies , Transplant Recipients , Vaccines, Conjugate/immunology , Vaccines, Conjugate/therapeutic use
7.
Clin Microbiol Infect ; 20 Suppl 7: 119-30, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25040016

ABSTRACT

Solid organ transplantation (SOT) is an appropriate therapeutic option for HIV-infected patients with end-stage organ disease. Recent experience in North America and Europe indicates that 3- to 5-year survival in HIV/HCV-coinfected liver recipients is lower than that of HCV-monoinfected recipients. Conversely, 3- to 5-year survival of non-HCV-coinfected transplant patients (liver, kidney and heart) was similar to that of non-HIV-infected patients. Preliminary experience with lung transplantation and combined kidney and pancreas transplantation is also satisfactory. Infections in HIV-infected recipients during the post-transplant period are similar to those seen in non-HIV-infected patients, although the incidence rates of tuberculosis and fungal infections seem to be higher. HIV-infected patients who are being evaluated for SOT should follow the same recommendations as those used for non-HIV-infected patients in order to prevent infections during the pre-transplant period. After transplantation, HIV-infected SOT recipients must follow recommendations on post-SOT and anti-HIV immunization and on antimicrobial prophylaxis. The recommended antiretroviral regimen is one based on raltegravir or dolutegravir plus two nucleos(t)ide reverse transcriptase inhibitors (tenofovir + emtricitabine or abacavir + lamivudine), because it can prevent pharmacokinetic interactions between antiretroviral drugs, immunosuppressive drugs and some of the antimicrobial agents used to treat or prevent post-transplant infections. In this manuscript, we review current recommendations for preventing infections both before and after transplantation. We also analyse the incidence, aetiology and clinical characteristics of opportunistic and non-opportunistic bacterial, mycobacterial, fungal and viral infections in HIV-infected SOT recipients during the post-transplant period.


Subject(s)
Infection Control/methods , Opportunistic Infections/epidemiology , Opportunistic Infections/prevention & control , Organ Transplantation , Transplant Recipients , Europe , Humans , Immunocompromised Host , Immunosuppressive Agents/therapeutic use , Incidence , North America , Opportunistic Infections/diagnosis , Opportunistic Infections/therapy
8.
Osteoporos Int ; 25(11): 2573-80, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25027110

ABSTRACT

UNLABELLED: Wilson's disease is characterized by copper deposition, especially in the liver and central nervous system. We assessed the prevalent fractures and bone mineral density (BMD) and related risk factors in 85 patients. BMD was normal, but patients with severe neurological involvement, low BMI, and/or amenorrhea are at risk for fractures. INTRODUCTION: Wilson's disease (WD) is characterized by copper deposition, especially in the liver and central nervous system. Two studies showed a high prevalence of osteoporosis in WD patients. We wanted to assess the prevalent fractures and bone mineral density (BMD) and to identify risk factors for bone loss and fractures in a large group of WD patients. METHODS: In this prospective cross-sectional survey at National center of reference for WD, we included 85 patients, 47 women, and 38 men, with a mean age of 35 ± 10 years, and mean time from diagnosis to study of 21 ± 9 years; 57 (67%) patients had neurological signs. Peripheral fractures, prevalent radiological vertebral fractures (VFx), and dual-energy X-ray absorptiometry BMD measurements at the femoral neck (FN) and lumbar spine (LS) were studied. RESULTS: Mean LS and FN Z-score was normal (-0.37 ± 1.20 at LS and -0.06 ± 1.20 at FN). BMI <19 kg/m(2) and amenorrhea were associated with low BMD. Prevalent peripheral fractures were noted in 43 (51%) and VF in 7 (8%) patients. Severity of neurological involvement and male sex was associated with peripheral fractures, whereas older age, severe neurological involvement, and low BMD and Z-score values were associated with VF. CONCLUSION: Our data showing normal BMD overall do not support routine bone status evaluation in adults with WD. However, patients with severe neurological involvement, low BMI, and/or amenorrhea are at risk factors for fractures and may require specific monitoring.


Subject(s)
Hepatolenticular Degeneration/complications , Osteoporotic Fractures/etiology , Absorptiometry, Photon/methods , Adult , Aged , Biomarkers/blood , Bone Density/physiology , Cross-Sectional Studies , Female , Femur Neck/physiopathology , Hepatolenticular Degeneration/physiopathology , Humans , Lumbar Vertebrae/physiopathology , Male , Middle Aged , Osteoporotic Fractures/physiopathology , Spinal Fractures/etiology , Spinal Fractures/physiopathology , Young Adult
9.
Int J Antimicrob Agents ; 43(6): 566-9, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24787480

ABSTRACT

Amphotericin B is a powerful polyene antifungal drug used for treating systemic fungal infections and is usually administered for a short period. Side effects after prolonged use are unknown in humans. Here we report the case of a 28-year-old man suffering from chronic granulomatous disease (CGD), treated for invasive cerebral aspergillosis with liposomal amphotericin B (L-AmB) for a very long time (8 consecutive years). We describe the efficacy and safety of this treatment in the long term. Aspergillosis was kept under control as long as L-AmB therapy was maintained, but relapsed when the dose was reduced. No overt renal toxicity was noted. The patient gradually developed hepatosplenomegaly and pancytopenia. Abnormalities of bone marrow were similar to the sea-blue histiocyte syndrome. Liver biopsy showed images of nodular regenerative hyperplasia related to CGD as well as a histiocytic storage disease. We discuss the very prolonged use of L-AmB leading to the development of a lysosomal storage disease.


Subject(s)
Amphotericin B/adverse effects , Amphotericin B/therapeutic use , Antifungal Agents/adverse effects , Antifungal Agents/therapeutic use , Lysosomal Storage Diseases/chemically induced , Adult , Biopsy , Granulomatous Disease, Chronic/complications , Histocytochemistry , Humans , Liver/pathology , Male , Neuroaspergillosis/drug therapy
10.
Am J Transplant ; 13(9): 2458-61, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23834702

ABSTRACT

Immunization using live attenuated vaccines represents a contra-indication after solid organ transplantation (SOT): consequently, transplant candidates planning to travel in countries where yellow fever is endemic should be vaccinated prior to transplantation. The persistence of yellow fever vaccine-induced antibodies after transplantation has not been studied yet. We measured yellow-fever neutralizing antibodies in 53 SOT recipients vaccinated prior to transplantation (including 29 kidney recipients and 18 liver recipients). All but one (98%) had protective titers of antibodies after a median duration of 3 years (min.: 0.8, max.: 21) after transplantation. The median antibody level was 40 U/L (interquartile range: 40-80). For the 46 patients with a known or estimated date of vaccination, yellow-fever antibodies were still detectable after a median time of 13 years (range: 2-32 years) post-immunization. Our data suggest there is long-term persistence of antibodies to yellow fever in SOT recipients who have been vaccinated prior to transplantation.


Subject(s)
Antibodies, Viral/analysis , Kidney Transplantation , Liver Transplantation , Transplantation Immunology , Yellow Fever Vaccine/immunology , Humans , Prospective Studies
11.
Am J Transplant ; 11(8): 1686-95, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21749638

ABSTRACT

We characterized fibrosing cholestatic hepatitis (FCH) in a large cohort of HIV/HCV co-infected patients. Between 1999 and 2008, 59 HIV infected patients were transplanted for end-stage liver disease due to HCV. Eleven patients (19%) developed FCH within a mean period of 7 months [2-27] after liver transplantation (LT). At Week 1 post-LT, the mean HCV viral load was higher in the FCH group: 6.13 log(10) IU/mL ± 1.30 versus 4.9 log(10) IU/mL ± 1.78 in the non-FCH group, p = 0.05. At the onset of acute hepatitis after LT, activity was moderate to severe in 8/11 HIV+/HCV+ patients with FCH (73%) versus 13/28 (46%) HIV+/HCV+ non-FCH (p = 0.007) patients. A complete virological response to anti-HCV therapy was observed in 2/11 (18%) patients. Survival differed significantly between the two groups (at 3 years, 67% in non-FCH patients versus 15% in FCH patients, p = 0.004). An early diagnosis of FCH may be suggested by the presence of marked disease activity when acute hepatitis is diagnosed and when a high viral load is present. The initiation of anti-HCV therapy should be considered at this point.


Subject(s)
Biomarkers/blood , HIV Infections/blood , Hepatitis C/surgery , Liver Transplantation , Adult , Aged , Cholestasis, Intrahepatic , Cohort Studies , Female , HIV Infections/complications , Hepatitis C/blood , Hepatitis C/complications , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Viral Load
12.
Ann Biol Clin (Paris) ; 63(5): 457-66, 2005.
Article in French | MEDLINE | ID: mdl-16230279

ABSTRACT

Wilson disease is an autosomal recessive disorder of copper excess. This illness results from mutations of the ATP7B gene (chromosome 13, MIM# 277900). The discovery of the gene allowed a better understanding of cytosolic copper trafficking and its relationship with ceruloplasmin synthesis. Symptomatic patients may present with hepatic, neurologic or psychiatric forms. Clinical and phenotypic evidences provide only presumptive arguments for this disease which can be routinely assessed by molecular analysis. This genetic disease which can be efficiently treated was formerly biologically suspected after a careful but sometimes invasive study of copper metabolism. Genetic advances can now give a definite answer using linkage analysis and research for disease-causing mutations. However, this diagnosis strategy is limited since currently over 320 mutations and 80 polymorphisms have been currently identified.


Subject(s)
Adenosine Triphosphatases/genetics , Cation Transport Proteins/genetics , Hepatolenticular Degeneration/genetics , Mutation , Adenosine Triphosphatases/chemistry , Cation Transport Proteins/chemistry , Chelating Agents/therapeutic use , Chromosome Mapping , Chromosomes, Human, Pair 13 , Copper/metabolism , Copper-Transporting ATPases , Female , Hepatolenticular Degeneration/drug therapy , Hepatolenticular Degeneration/metabolism , Humans , Male , Pedigree , Polymorphism, Genetic
13.
Gut ; 52(6): 893-7, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12740348

ABSTRACT

BACKGROUND AND AIM: Autoimmune hepatitis (AIH) has been reported to recur after orthotopic liver transplantation (OLT) in 10-35% of patients in small series with a short follow up. The aim of the present study was to examine the clinical and histological outcome more than 10 years after OLT for AIH. PATIENTS AND METHODS: Seventeen women with a mean age of 30 (12) years at the time of OLT, selected from among 44 patients transplanted for AIH, were followed for more than 10 years. The criteria for definite AIH, as established by the International Autoimmune Hepatitis Group, were met in every case. Liver biopsies were performed 1, 2, 5, and 10 years after OLT, and when indicated by abnormal liver function tests. Specimens were examined for evidence of recurrent AIH, namely interface hepatitis, lobular activity, portal lymphoplasmocytic infiltration, and fibrosis. Other signs of recurrence included hypertransaminasaemia, serum autoantibodies, and the response to steroid reintroduction or significant steroid dose increments. RESULTS: AIH recurred in 7 (41%) of 17 patients. In four patients histological abnormalities were detected by means of protocol biopsies 1-5 years before the onset of biochemical abnormalities. Two patients developed severe recurrences after 10 and 15 years, respectively, and required treatment with steroids and tacrolimus. In the other three patients histological recurrence was detected 0.6-3 years post-OLT, concomitantly with biochemical abnormalities. CONCLUSIONS: AIH recurred in 41% of patients followed for more than 10 years after OLT. As histological signs preceded biochemical abnormalities in four patients (23.5%), regular liver biopsy is warranted after OLT. Detection of isolated histological signs may call for closer follow up and/or a change in immunosuppressive therapy.


Subject(s)
Hepatitis, Autoimmune/surgery , Liver Transplantation , Adolescent , Adult , Autoantibodies/blood , Autoantigens/immunology , Biomarkers/blood , Biopsy , Child , Drug Administration Schedule , Female , Follow-Up Studies , Glucocorticoids/administration & dosage , HLA-DR Antigens/analysis , Hepatitis, Autoimmune/immunology , Hepatitis, Autoimmune/pathology , Histocompatibility Testing , Humans , Immunosuppressive Agents/administration & dosage , Middle Aged , Prognosis , Recurrence
14.
Gastroenterol Clin Biol ; 25(8-9): 773-80, 2001.
Article in French | MEDLINE | ID: mdl-11598539

ABSTRACT

AIM: Liver-graft shortages justify the development of adult living-related liver transplantation. The preliminary experience with this technique at Paul-Brousse Hospital is reported. PATIENTS ET METHODES: From January to July 2000, 7 adult to adult living-related liver transplantations were performed. Donors were 5 females and 2 males aged 20 to 53 years old (median: 41). A right liver graft was harvested in all cases. Recipients were 5 males and 2 females aged from 17 to 58 years old (median: 50) transplanted for viral cirrhosis (4 cases including 2 with hepatocellular carcinoma), subfulminant hepatitis (1 case), hepatocellular carcinoma on a healthy liver (1 case), and epithelioid hemangioendothelioma (1 case). Follow-up ranged from 41 to 157 days (median: 117 days). RESULTS: One donor had a biliary fistula that healed spontaneously. One donor had asterixis for 24 hours. The 7 donors are alive at home without any late complications. One recipient was retransplanted for hepatic artery thrombosis and 2 recipients had a biliary fistula that healed spontaneously. The 7 recipients are alive at home with normal liver function. CONCLUSION: Our experience and other reports suggest that adult to adult living-related liver transplantation is feasible with rare mortality and low morbidity in donors. Results in recipients are comparable to those obtained with cadaveric grafts. For a given patient the possibility of living related donation might extend the indications for transplantation without penalizing patients waiting for a cadaveric graft.


Subject(s)
Liver Transplantation , Living Donors , Adolescent , Adult , Carcinoma, Hepatocellular/surgery , Female , Humans , Liver Cirrhosis/surgery , Liver Cirrhosis/virology , Liver Neoplasms/surgery , Male , Middle Aged , Postoperative Complications
15.
J Med Virol ; 65(3): 493-504, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11596084

ABSTRACT

Lamivudine, an antiviral agent, has a potential role in the treatment of recurrent or acquired de novo hepatitis B virus (HBV) infection after liver transplantation. During lamivudine therapy, residual HBV particles in serum, PBMC, and liver were quantified in 7 patients in whom hepatitis B occurred de novo (n = 4) or recurred (n = 3). HBV DNA and preS1 antigen were measured using a sensitive PCR technique and an in-house ELISA method, respectively. The genetic and antigenic properties of HBV variants that emerged during lamivudine treatment were also examined. One month after the outset of lamivudine treatment, all 7 patients remained positive for both HBV DNA and preS1 antigen in serum, reflecting residual HBV replication. At the end of therapy, four patients were considered to be lamivudine responders, including one who seroconverted to anti-HBs but remained HBV DNA positive in the liver (> 10(3) copies/microg of DNA). Among the three patients who did not respond to lamivudine, one had pol mutations (L450P and S550C) that had not been described previously, in addition to the common mutations within the YMDD locus and B domain. Defective core and preS viral proteins and atypical sedimentation profiles of HBV DNA-positive particles were observed in all three lamivudine-resistant patients. These findings confirm the persistence of HBV in liver transplant recipients despite strong inhibition of replication by lamivudine, and show abnormal viral transcription and/or morphogenesis in lamivudine-resistant patients.


Subject(s)
DNA, Viral/blood , Hepatitis B Surface Antigens/blood , Hepatitis B virus/physiology , Hepatitis B/drug therapy , Lamivudine/therapeutic use , Liver Transplantation/adverse effects , Protein Precursors/blood , Adult , Aged , Alanine Transaminase/blood , Antiviral Agents/therapeutic use , Enzyme-Linked Immunosorbent Assay , Female , Hepatitis B/virology , Hepatitis B e Antigens/blood , Humans , Male , Middle Aged , Polymerase Chain Reaction , Virion/physiology , Virus Replication
18.
Liver Transpl ; 7(6): 556-8, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11443588

ABSTRACT

A 34-year-old woman underwent orthotopic liver transplantation (OLT) for decompensated type 1 autoimmune hepatitis (AIH). She was administered standard triple-drug immunosuppressive therapy (cyclosporine, steroids, and azathioprine). Ten years after OLT, she developed a recurrence of AIH, with emergence of serological markers of autoimmunity (high anti--smooth muscle antibody [ASMA] titer, high serum gamma globulin level), abnormal liver function test results, and characteristic histological features on liver biopsy. Despite intensified steroid therapy, her clinical and liver function deteriorated. The onset of cutaneous alternariosis led to a steroid dose reduction and cyclosporine replacement by tacrolimus. Clear-cut amelioration was observed, with an improvement in liver function test results and reduction in ASMA titer. One year after the recurrence of AIH, the patient has normal liver function and physical findings. Tacrolimus therefore may be effective in patients with severe recurrent autoimmune liver disease. Further studies are needed to assess tacrolimus therapy in patients who fail to respond to standard immunosuppressive therapy.


Subject(s)
Hepatitis, Autoimmune/drug therapy , Immunosuppressive Agents/therapeutic use , Liver Transplantation/adverse effects , Tacrolimus/therapeutic use , Adult , Alanine Transaminase/blood , Autoantibodies/blood , Female , Hepatitis, Autoimmune/immunology , Hepatitis, Autoimmune/pathology , Hepatitis, Autoimmune/surgery , Humans , Liver Transplantation/immunology , Liver Transplantation/pathology , Recurrence , gamma-Globulins/metabolism
19.
Ann Med Interne (Paris) ; 152(6): 371-82, 2001 Oct.
Article in French | MEDLINE | ID: mdl-11907950

ABSTRACT

Autoimmune hepatitis is characterized by an inflammation of the portal tract with lymphocytes and plasma cells, an hypergammaglobulinemia and a variety of circulating autoantibodies. The presence of smooth muscle antibodies and/or antinuclear antibodies define type 1. Type 2 is characterized by the presence of liver-kidney--microsomal antibodies. Environmental, genetic and infectious factors may explain the autoreactivity of T cells. Different non specific clinical features may be present. Sometimes the presentation may be an acute hepatitis; in the remainder, the disease may not be recognized until liver damage is advanced. Hypergammaglobulinemia and presence of circulating autoantibodies are the key for diagnosis. The association of prednisolone in combination with azathioprine remains the established treatment. If relapse or non response occur, other immunosuppressive therapy such as cyclosporin may be useful. Liver transplantation is reserved for (sub)fulminant forms and end stage liver disease.


Subject(s)
Hepatitis, Autoimmune , Hepatitis, Autoimmune/classification , Hepatitis, Autoimmune/diagnosis , Hepatitis, Autoimmune/genetics , Hepatitis, Autoimmune/immunology , Hepatitis, Autoimmune/physiopathology , Hepatitis, Autoimmune/therapy , Humans
20.
Anticancer Res ; 21(6A): 4203-6, 2001.
Article in English | MEDLINE | ID: mdl-11911319

ABSTRACT

BACKGROUND: The treatment of malignancies in transplanted patients has become an emerging issue. The anticancer agent CPT-11 is hydrolysed to the active metabolite SN-38 and many drugs interact with its metabolism and toxicity. PATIENT AND METHODS: We studied the clinical and pharmacological interactions between CPT-11 and FK506 in a liver transplant patient. Serial plasma samples of FK506, CPT-11, SN-38 and SN-38 glucuronide were assayed by high-performance liquid chromatography. RESULTS: While no CPT-11 toxicity was observed pre-operatively, several post-operative cycles of CPT-11 were complicated with severe diarrhea. No change in FK506 plasma concentrations was noted in the presence of CPT-11 but the pharmacokinetics of CPT-11 was altered in the presence of FK506. SN-38 glucuronidation was reduced for up to 12 hours following CPT-11 infusion. This increase in plasmatic exposure to unbound SN-38 might account for diarrhea. CONCLUSION: The starting dose of CPT-11 should be reduced in FK506-treated liver transplant patients.


Subject(s)
Antineoplastic Agents, Phytogenic/adverse effects , Camptothecin/analogs & derivatives , Camptothecin/adverse effects , Diarrhea/chemically induced , Liver Transplantation , Tacrolimus/adverse effects , Adult , Antineoplastic Agents, Phytogenic/blood , Antineoplastic Agents, Phytogenic/pharmacokinetics , Camptothecin/blood , Camptothecin/pharmacokinetics , Drug Interactions , Glucuronides/blood , Glucuronides/pharmacokinetics , Humans , Irinotecan , Tacrolimus/blood , Tacrolimus/pharmacology
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