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1.
Mov Disord ; 38(2): 321-332, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36573661

RESUMO

BACKGROUND: Wilson's disease (WD) is usually diagnosed in children and young adults; limited data exist on late-onset forms. OBJECTIVE: The aim was to characterize the clinical and paraclinical presentations, therapeutic management, and outcomes in patients with late-onset WD. METHODS: Patients diagnosed with WD after age 40 years were identified from the French Wilson's Disease Registry (FWDR). Clinical, laboratory, and imaging findings and treatment were reported at diagnosis and last follow-up. RESULTS: Forty-five patients were identified (median age: 49, range: 40-64) and placed in three groups according to their clinical presentation: neurological (n = 20, median diagnostic delay: 20 months), hepatic (n = 13, diagnostic delay: 12 months), and family screening (n = 12), all confirmed genetically. Six neurological patients had an atypical presentation (1 torticollis, 2 writer's cramps, 2 functional movement disorders, and 1 isolated dysarthria), without T2/fluid-attenuated inversion recovery brain magnetic resonance imaging (MRI) hyperintensities; 5 of 6 had no Kayser-Fleischer ring (KFR); 5 of 6 had liver involvement. In the neurological group, 84% of patients improved clinically, and 1 developed copper deficiency. In the hepatic group, 77% had cirrhosis; 6 patients required liver transplantation. In the screened group, 43% had mild liver involvement; 3 were not treated and remained stable; 24-h urinary copper excretion was normal in 33% of patients at diagnosis. CONCLUSIONS: In the FWDR, late-onset forms of WD affect 8% of patients, mostly with neurological presentations. Thirty percent of the neurological forms were atypical (isolated long-lasting symptoms, inconspicuous brain MRI, no KFR). With personalized treatment, prognosis was good. This study emphasized that WD should be suspected at any age and even in cases of atypical presentation. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Assuntos
Degeneração Hepatolenticular , Adulto , Criança , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Ceruloplasmina/metabolismo , Ceruloplasmina/uso terapêutico , Cobre/metabolismo , Cobre/uso terapêutico , Diagnóstico Tardio , Degeneração Hepatolenticular/diagnóstico
2.
Transpl Int ; 34(7): 1293-1305, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33932239

RESUMO

Recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) occurs in 10%-20% of patients transplanted for HCC. The treatment of HCC recurrence after LT remains a challenge. Consecutive patients who underwent LT for HCC between 2005 and 2015 at our center were recruited. Characteristics of patients with recurrence, modalities of treatment and outcome were collected retrospectively. Patient survival was analyzed according to HCC recurrence therapeutic strategy. Among 306 transplanted patients, 43 patients (14.1%) developed recurrence with a median survival time after recurrence of 10.9 months (95%CI: 6.6-18.6). Survival of patients treated with Sorafenib (SOR) and everolimus (EVL) (n = 19) was significantly better than that of the group treated with other strategies (n = 24) (P = 0.001). Multivariable analysis demonstrated that SOR plus EVL therapy and absence of dissemination at diagnosis of recurrence were independent predictive factors of prolonged survival after recurrence. Among the patients who treated with EVL, survival of patients with controlled EVL blood trough levels ≥5 ng/ml was significantly better compared to those with EVL trough levels <5 ng/ml (P = 0.021). Combination therapy of sorafenib and everolimus was an independent predictor for better survival after HCC recurrence. Patients with controlled everolimus trough level ≥5 ng/ml might get the best survival benefit.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Everolimo/uso terapêutico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Retrospectivos , Sorafenibe/uso terapêutico
3.
J Pediatr Gastroenterol Nutr ; 73(4): e80-e86, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34091542

RESUMO

OBJECTIVES: To describe a cohort of Wilson disease (WD) pediatric cases, and to point out the diagnostic particularities of this age group and the long-term outcome. METHODS: Clinical data of 182 pediatric patients included in the French WD national registry from 01/03/1995 to 01/06/2019 were gathered. RESULTS: Diagnosis of WD was made at a mean age of 10.7 ±â€Š4.2 years (range 1-18 years). At diagnosis, 154 patients (84.6%) had hepatic manifestations, 19 (10.4%) had neurological manifestations, and 9 patients (4.9%) were asymptomatic. The p.His1069Gln mutation was the most frequently encountered (14% of patients).Neurological patients were diagnosed at least 1 year after they presented their first symptoms. At diagnosis, the median urinary copper excretion (UCE) was 4.2 µmol/24 hours (0.2-253). The first-line treatment was d-penicillamine (DP) for 131 (72%) patients, zinc salts for 24 (13%) patients, and Trientine for 17 (9%) patients. Liver transplantation was performed in 39 (21.4%) patients, for hepatic indications in 33 of 39 patients or for neurological deterioration in 6 of 39 patients, mean Unified Wilson's Disease Rating Scale of the latter went from 90 ±â€Š23.1 before liver transplantation (LT) to 26.8 ±â€Š14.1 (P < 0.01) after a mean follow-up of 4.3 ±â€Š2.5 years. Overall survival rate at 20 years of follow-up was 98%, patient and transplant-free combined survival was 84% at 20 years. CONCLUSION: Diagnosis of WD can be challenging in children, particularly at the early stages of liver disease and in case of neurological presentation; hence the support of clinical scores and genetic testing is essential. Diagnosis at early stages and proper treatment ensure excellent outcomes, subject to good long-term treatment compliance. LT is a valid option for end-stage liver disease not responding to treatment and can be discussed for selected cases of neurological deterioration.


Assuntos
Degeneração Hepatolenticular , Adolescente , Criança , Pré-Escolar , Cobre , França/epidemiologia , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/genética , Degeneração Hepatolenticular/terapia , Humanos , Lactente , Penicilamina/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
4.
Liver Transpl ; 26(11): 1465-1476, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32869469

RESUMO

Longterm use of a calcineurin inhibitor (CNI)-based regimen is one of the major reasons for chronic renal failure in liver transplantation recipients (LTRs). The Everolimus Liver registry (EVEROLIVER) evaluated renal function in LTRs who were converted to everolimus (EVR). This observational registry included all LTRs receiving EVR across 9 centers from France. Data are being collected in an electronic database over 10 years (12 visits/patient) to evaluate efficacy, renal function (estimated glomerular filtration rate [eGFR]), and safety of EVR use in clinical practice, and the current analysis is reporting up to 60 months of findings. Until September 2017, 1045 patients received EVR after a mean time of 3.6 ± 5.1 years. CNI withdrawal was feasible in 57.7% of patients as of month 60. Mean eGFR improved in patients with baseline eGFR <60 mL/minute/1.73 m2 and was maintained in those with baseline eGFR ≥60 mL/minute/1.73 m2 . Among patients with chronic kidney disease (CKD; baseline eGFR <60 mL/minute/1.73 m2 ), 55% converted to EVR within 3 months (early conversion) and 39.4% converted between 4 and 12 months after transplantation (mid-conversion) experienced improvement in eGFR (≥60 mL/minute/1.73 m2 ) at month 36. Only 20.9% and 17.4% among those converted beyond 12 months (late conversion) experienced improvement respectively at month 36 and 60. A logistic regression analysis in patients with CKD stage ≥3 demonstrated that late conversion, age, and female sex were associated with nonimprovement of eGFR (≥60 mL/minute/1.73 m2 ). Data from this real-life use of EVR indicate that renal function was maintained from the preconversion period until month 36 even in patients with advanced CKD. However, early rather than late conversion appears to be a safe approach to preserve longterm renal function in LTRs.


Assuntos
Everolimo , Transplante de Fígado , Inibidores de Calcineurina/efeitos adversos , Everolimo/efeitos adversos , Feminino , França , Taxa de Filtração Glomerular , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Imunossupressores/efeitos adversos , Fígado , Transplante de Fígado/efeitos adversos , Sistema de Registros , Transplantados
5.
Liver Int ; 39(1): 136-146, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29947467

RESUMO

BACKGROUND & AIMS: HIV/HCV co-infected patients with hepatocellular carcinoma (HCC) have poorer survival than HCV mono-infected patients. We aimed to evaluate the prognostic factors for survival. METHODS: From 2006 to 2013, 55 incident HCCs among HIV+/HCV+ patients, from three ANRS cohorts, were compared with 181 HCCs in HIV-/HCV+ patients from the ANRS Cirvir cohort. RESULTS: HIV+/HCV+ patients were younger (50 years [IQR: 47-53] vs 62 [54-70], P < 0.001), male (89% vs 63%, P < 0.001) than HIV-/HCV+ patients. At HCC diagnosis, both groups had a majority of non-responders to anti-HCV-therapy, and HIV+/HCV+ patients had more frequently known a previous cirrhosis decompensation (31% vs 14%, P = 0.005). At diagnostic imaging, there were more infiltrative forms of HCC in HIV+/HCV+ group (24% vs 14%, P < 0.001), associated with tumour portal thrombosis in 29%. During a median follow-up period of 11.96 [5.51-27] months since HCC diagnosis, a majority of palliative treatments were decided in HIV+/HCV+ patients (51% vs 19%, P < 0.001). The 1 and 2-year crude survival rates were 61% versus 78% and 47% versus 63%, P = 0.003 respectively. In a Cox model multivariate analysis adjusted for the cohort, age and sex, the most important prognostic factor for survival was the infiltrative form of the tumour (aRR: 8.10 [4.17-15.75], P < 0.001). CONCLUSIONS: The radiological aggressiveness of the tumour is the best prognostic factor associated with poorer survival of HCC in HIV+/HCV+ patients. High α-foetoprotein level and decompensated cirrhosis are other ones. This justifies a particular attention to the detection and the management of small nodules in this high-risk population.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Infecções por HIV/tratamento farmacológico , Hepatite C/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Idoso , Carcinoma Hepatocelular/terapia , Coinfecção/tratamento farmacológico , Coinfecção/virologia , Feminino , França , Infecções por HIV/complicações , Hepatite C/complicações , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida
8.
Radiology ; 277(2): 443-53, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25961631

RESUMO

PURPOSE: To evaluate the effect of human immunodeficiency virus (HIV) coinfection on hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-infected patients with cirrhosis in terms of HCC morphologic subtypes and survival prognosis at the time of radiologic diagnosis. MATERIALS AND METHODS: The study was approved by the institutional review board and patients gave their written informed consent. Two databases, one for HIV-HCV patients and the other for HCV-infected patients without HIV infection, were obtained from prospective multicenter cohorts. Inclusion criteria were a confirmed diagnosis of cirrhosis and the discovery of HCC at imaging between January 2008 and December 2012. This study included 35 HIV-HCV patients with cirrhosis (32 men and three women; median age, 50 years [age range, 40-65 years]; Child-Pugh classification A, 21 patients; classification B, 10 patients; classification C, four patients) and 35 infected HCV patients with cirrhosis (29 men and six women; median age, 56 years [age range, 41-83 years]; Child-Pugh classification A, 26 patients; classification B, six patients; classification C, three patients) who were the control group. Computed tomographic or magnetic resonance images were analyzed for HCC subtypes, the number and size of nodules, and evidence of portal obstructing tumors. Fisher exact and Wilcoxon tests were used for comparisons and Kaplan-Meier plots were used for survival analysis. RESULTS: Infiltrative HCC was found in eight HIV-HCV patients with cirrhosis (23%) and in no HCV patients with cirrhosis (P = .002). All other HCCs were of a nodular type, with similar nodule sizes in the two groups. Portal-obstructing tumors were found in 10 HIV-HCV patients (eight of eight tumors were infiltrative and two of 27 tumors were nodular) but none were found in HCV patients (P = .001). Survival was dramatically shorter for HIV-HCV patients than for those with HCV, with a median of 17.2 months versus 54.7 months (P = .004). Survival time was dependent on the type of HCC, with probabilities of death at 12 months of 87% in infiltrative-type HCC, 32% in multiple-nodule type, and 5% in single-nodule type, which was found in both groups (log-rank test, P < .001). CONCLUSION: Unlike HCV-infected patients with cirrhosis, patients with cirrhosis coinfected with HIV and HCV frequently present at radiologic diagnosis with infiltrative-type HCC and portal-obstructing tumors, which results in dramatically shorter survival.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Coinfecção/diagnóstico , Diagnóstico por Imagem , Infecções por HIV/diagnóstico , Hepatite C/diagnóstico , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/diagnóstico , Adulto , Idoso , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/virologia , Coinfecção/terapia , Coinfecção/virologia , Meios de Contraste , Feminino , França , Infecções por HIV/tratamento farmacológico , Hepatite C/terapia , Humanos , Interpretação de Imagem Assistida por Computador , Iohexol/análogos & derivados , Iopamidol/análogos & derivados , Cirrose Hepática/terapia , Cirrose Hepática/virologia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos , Prognóstico , Estudos Retrospectivos
9.
J Hepatol ; 60(3): 579-89, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24211743

RESUMO

BACKGROUND & AIMS: Liver transplantation (LT) is the therapeutic option for severe complications of Wilson's disease (WD). We aimed to report on the long-term outcome of WD patients following LT. METHODS: The medical records of 121 French patients transplanted for WD between 1985 and 2009 were reviewed retrospectively. Seventy-five patients were adults (median age: 29 years, (18-66)) and 46 were children (median age: 14 years, (7-17)). The indication for LT was (1) fulminant/subfulminant hepatitis (n = 64, 53%), median age = 16 years (7-53), (2) decompensated cirrhosis (n = 50, 41%), median age = 31.5 years (12-66) or (3) severe neurological disease (n = 7, 6%), median age = 21.5 years (14.5-42). Median post-transplant follow-up was 72 months (0-23.5). RESULTS: Actuarial patient survival rates were 87% at 5, 10, and 15 years. Male gender, pre-transplant renal insufficiency, non elective procedure, and neurological indication were significantly associated with poorer survival rate. None of these factors remained statistically significant under multivariate analysis. In patients transplanted for hepatic indications, the prognosis was poorer in case of fulminant or subfulminant course, non elective procedure, pretransplant renal insufficiency and in patients transplanted before 2000. Multivariate analysis disclosed that only recent period of LT was associated with better prognosis. At last visit, the median calculated glomerular filtration rate was 93 ml/min (33-180); 11/93 patients (12%) had stage II renal insufficiency and none had stage III. CONCLUSIONS: Liver failure associated with WD is a rare indication for LT (<1%), which achieves an excellent long-term outcome, including renal function.


Assuntos
Degeneração Hepatolenticular/cirurgia , Transplante de Fígado , Adolescente , Adulto , Idoso , Criança , Feminino , França , Sobrevivência de Enxerto , Degeneração Hepatolenticular/mortalidade , Humanos , Terapia de Imunossupressão , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Resultado do Tratamento
10.
Hepatology ; 57(2): 689-99, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22911395

RESUMO

UNLABELLED: The development of potentially severe non-graft-versus-host disease (GVHD) hepatitis resembling autoimmune hepatitis (AIH) has been reported after bone marrow transplantation (BMT). The aim of this study was to better characterize this form of hepatitis, particularly through the identification of autoantigens recognized by patient sera. Five patients who received an allogeneic BMT for the treatment of hematological diseases developed liver dysfunction with histological features suggestive of AIH. Before and during the onset of hepatic dysfunction, sera were tested on immunoblottings performed with cytosolic, microsomal, mitochondrial, and nuclear proteins from rat liver homogenate and resolved by two-dimensional electrophoresis. Antigenic targets were identified by mass spectrometry. During the year that followed BMT, all patients presented with GVHD. Acute hepatitis then occurred after the withdrawal, or during the tapering, of immunosuppressive therapy. At that time, no patients had a history of liver toxic drug absorption, patent viral infection, or any histopathological findings consistent with GVHD. Immunoreactive spots stained by sera collected at the time of hepatic dysfunction were more numerous and more intensely expressed than those stained by sera collected before. Considerable patient-dependent pattern heterogeneity was observed. Among the 259 spots stained exclusively by sera collected at the time of hepatitis, a total of 240 spots were identified, corresponding to 103 different proteins. Twelve of them were recognized by sera from 3 patients. CONCLUSIONS: This is the first immunological description of potentially severe non-GVHD hepatitis occurring after BMT, determined using a proteomic approach and enabling a discussion of the mechanisms that transform an alloimmune reaction into an autoimmune response. Any decision to withdraw immunosuppression after allogeneic BMT should be made with caution.


Assuntos
Transplante de Medula Óssea/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Hepatite Autoimune/etiologia , Transplante Homólogo/imunologia , Adulto , Animais , Feminino , Doença Enxerto-Hospedeiro/imunologia , Hepatite Autoimune/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteômica , Ratos
11.
JHEP Rep ; 6(1): 100929, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38074503

RESUMO

Background & Aims: Retrospective studies have reported good results with liver transplantation (LTx) for acute-on-chronic liver failure (ACLF) in selected patients. The aim of this study was to evaluate the selection process for LTx in patients with ACLF admitted to the intensive care unit (ICU) and to assess outcomes. Methods: This prospective, non-interventional, single high-volume center study collected data on patients with ACLF admitted to the ICU between 2017-2020. Results: Among 200 patients (mean age: 55.0 ± 11.2 years and 74% male), 96 patients (48%) were considered potential candidates for LTx. Unfavourable addictology criteria (n = 76) was the main reason for LTx ineligibility. Overall, 69 patients were listed for LTx (34.5%) and 50 were transplanted (25% of the whole population). The 1-year survival in the LTx group was significantly higher than in the non-transplanted group (94% vs. 15%, p <0.0001). Among patients eligible for LTx, mechanical ventilation during the first 7 days of ICU stay and an increase in the number of organ failures at day 3 were associated with the absence of LTx or death (odds ratio 9.58; 95% CI 3.29-27.89; p <0.0001 for mechanical ventilation and odds ratio 1.87; 95% CI 1.08-3.24; p <0.027 for increasing organ failures). The probability of not being transplanted in patients with ACLF under mechanical ventilation is >85.4% in those experiencing an increase of 2 organ failures since admission or >91% if experiencing an increase >2 organ failures, at which point futility could be considered. Conclusion: This prospective analysis of outcomes of patients with ACLF admitted to the ICU highlights the drastic nature of selection in this setting. Unfavourable addictology criteria, mechanical ventilation and increasing number of organ failures since admission were predictive of absence of LTx, futility and death. Impact and implications: Liver transplantation (LT) is the best therapeutic option in selected cirrhotic patients admitted to the ICU with acute on chronic liver failure. However, the selection criteria are poorly described and based on retrospective studies. This is the first prospective study that aimed to describe the selection process for LT in a transplant center. Patients with ACLF should be admitted to the ICU and evaluated within a short period of time for LT. In the context of organ shortage, eligibility for LT and either absence of LT, futility of care or death are better clarified in our study. These are mainly determined by prolonged respiratory failure and worsening of organ failures since ICU admission. Considering worldwide variations in the etiology and definition of ACLF, transplant availability and a narrow therapeutic window for transplant further prospective studies are awaited.

12.
JAMA ; 310(10): 1033-41, 2013 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-24026598

RESUMO

IMPORTANCE: Prednisolone or pentoxifylline is recommended for severe alcoholic hepatitis, a life-threatening disease. The benefit of their combination is unknown. OBJECTIVE: To determine whether the addition of pentoxifylline to prednisolone is more effective than prednisolone alone. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized, double-blind clinical trial conducted between December 2007 and March 2010 in 1 Belgian and 23 French hospitals of 270 patients aged 18 to 70 years who were heavy drinkers with severe biopsy-proven alcoholic hepatitis, as indicated by recent onset of jaundice in the prior 3 months and a Maddrey score of at least 32. Duration of follow-up was 6 months. The last included patient completed the study in October 2010. None of the patients were lost to follow-up for the main outcome. INTERVENTION: Patients were randomly assigned to receive either a combination of 40 mg of prednisolone once a day and 400 mg of pentoxifylline 3 times a day (n=133) for 28 days, or 40 mg of prednisolone and matching placebo (n=137) for 28 days. MAIN OUTCOMES AND MEASURES: Six-month survival, with secondary end points of development of hepatorenal syndrome and response to therapy based on the Lille model, which defines treatment nonresponders after 7 days of initiation of treatment. RESULTS: In intention-to-treat analysis, 6-month survival was not different in the pentoxifylline-prednisolone and placebo-prednisolone groups (69.9% [95% CI, 62.1%-77.7%] vs 69.2% [95% CI; 61.4%-76.9%], P = .91), corresponding to 40 vs 42 deaths, respectively. In multivariable analysis, only the Lille model and the Model for End-Stage Liver Disease score were independently associated with 6-month survival. At 7 days, response to therapy assessed by the Lille model was not significantly different between the 2 groups (Lille model score, 0.41 [95% CI, 0.36-0.46] vs 0.40 [95% CI, 0.35-0.45], P = .80). The probability of being a responder was not different in both groups (62.6% [95% CI, 53.9%-71.3%] vs 61.9% [95% CI, 53.7%-70.3%], P = .91). The cumulative incidence of hepatorenal syndrome at 6 months was not significantly different in the pentoxifylline-prednisolone and the placebo-prednisolone groups (8.4% [95% CI, 4.8%-14.8%] vs 15.3% [95% CI, 10.3%-22.7%], P = .07). CONCLUSION AND RELEVANCE: In patients with alcoholic hepatitis, 4-week treatment with pentoxifylline and prednisolone, compared with prednisolone alone, did not result in improved 6-month survival. The study may have been underpowered to detect a significant difference in incidence of hepatorenal syndrome, which was less frequent in the group receiving pentoxifylline. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01214226.


Assuntos
Sequestradores de Radicais Livres/administração & dosagem , Glucocorticoides/administração & dosagem , Hepatite Alcoólica/tratamento farmacológico , Pentoxifilina/administração & dosagem , Prednisolona/administração & dosagem , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Síndrome Hepatorrenal , Humanos , Fígado/efeitos dos fármacos , Fígado/fisiopatologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Análise de Sobrevida
13.
Transplantation ; 107(2): 410-419, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36117256

RESUMO

BACKGROUND: The objectives of this study were to evaluate incidence and to identify the risk factors of occurrence and the predictive factors of symptomatic forms of nodular regenerative hyperplasia (NRH) after liver transplantation (LT). METHODS: To identify risk factors of NRH following LT, we included 1648 patients transplanted from 2004 to 2018 and compared the patients developing NRH after LT to those who did not. To identify predictive factors of symptomatic NRH, we selected 115 biopsies displaying NRH and compared symptomatic to asymptomatic forms. Symptomatic NRH was defined as the presence of ascites, esophageal varices, hepatic encephalopathy, portal thrombosis, retransplantation, or death related to NRH. RESULTS: The incidence of NRH following LT was 5.1%. In multivariate analysis, the independent factor of developing NRH after LT was the donor's age (odds ratio [OR] = 1.02; confidence interval, 1.01-1.03; P = 0.02). Symptomatic forms occurred in 29 (25.2%) patients: 19 (16.5%) patients presented with ascites, 13 (11.3%) with esophageal varices, 4 (3.5%) with hepatic encephalopathy, and 8 (7%) with portal thrombosis. The median period before the onset of symptoms was 8.4 (1.5-11.3) y after LT. The spleen size at diagnosis/before LT ratio (OR = 12.5; 114.17-1.37; P = 0.0252) and thrombectomy during transplantation (OR = 11.17; 1.48-84.11; P = 0.0192) were associated with symptomatic NRH in multivariate analysis. CONCLUSIONS: NRH following LT is frequent (5.1%) and leads to symptomatic portal hypertension in 25.2% of patients. Using older grafts increases the risk of developing NRH after LT. Clinicians should screen for signs of portal hypertension, particularly in measuring spleen size.


Assuntos
Varizes Esofágicas e Gástricas , Encefalopatia Hepática , Hipertensão Portal , Transplante de Fígado , Trombose , Humanos , Transplante de Fígado/efeitos adversos , Fígado/patologia , Hiperplasia/complicações , Hiperplasia/patologia , Varizes Esofágicas e Gástricas/complicações , Varizes Esofágicas e Gástricas/patologia , Ascite/epidemiologia , Ascite/etiologia , Encefalopatia Hepática/complicações , Encefalopatia Hepática/patologia , Incidência , Hipertensão Portal/diagnóstico , Hipertensão Portal/epidemiologia , Hipertensão Portal/etiologia , Trombose/patologia
14.
Clin Res Hepatol Gastroenterol ; 47(8): 102206, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37714512

RESUMO

BACKGROUND AND AIMS: Treatment of patients with acute on chronic liver failure (ACLF) admitted to the ICU is very limited. The aim of this pilot study was to evaluate the efficiency on liver function and safety of therapeutic plasma exchange (TPE) in critically ill cirrhotic patients admitted with ACLF in a liver ICU. METHODS: This is a prospective cohort of patients with ACLF grade > 2 treated by TPE admitted to the ICU that was matched to a control group. TPE was performed using a plasma filter (TPE2000, BAXTER®) on a CRRT machine (Prismaflex®, Baxter®). Ratio and type of fluid replacement were 50 % with 5 % albumin solution followed by 50 % with fresh frozen plasma. RESULTS: Seven patients with a mean age of 50.6 ± 7.8 years (all males) and 14 controls matched to age, sex, etiology and cause of decompensation were recruited. At ICU admission, mean MELD score was 39.1 ± 2.7, mean SOFA score was 11.6 ± 5.2 and mean CLIF SOFA score was 12.9 ± 2.6. The grade of ACLF was 3 for 3 patients (42.9 %) and 2 for 4 patients (57.1 %). The TPE group had significantly higher levels of bilirubin (392.3 ± 117.1µmol/l vs. 219 ± 185µmol/l , p = 0.04), and INR values (5.7 ± 3.4 vs. 3.5 ± 0.9, p < 0.005) compared to the control group. Patient survival was respectively 28.6 % and 14.3 % at 30 and 90 days in the TPE group and 35.7 % and 7.14 % in the control group respectively (HR: 1 (95 % CI 0.19- 5.2; p = 1). One patient in the TPE group had a liver transplantation 13 days after admission to ICU and is still alive and none in the control group. Two (28.6 %) patients died from complications related to the double lumen catheter used for TPE. CONCLUSION: This pilot study of TPE in patients with ACLF grade 2 and 3 showed a marked but transient improvement in liver function tests. TPE worth to be evaluated in large trials in ACLF patients, with a liver transplant project, and less organ failure.

15.
Clin Res Hepatol Gastroenterol ; 46(1): 101768, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34332127

RESUMO

Rare genetic liver diseases can result in multi-systemic damage, which may compromise the patient's prognosis. Wilson's disease and alpha-1 antitrypsin deficiency must be investigated in any patient with unexplained liver disease. Cystic fibrosis screening of new-borns is now implemented in most high-prevalence countries. The diagnosis of these diseases can be strongly suggested with specific non-invasive tests. Molecular analysis gene for these diseases is long and tedious but is recommended to confirm the diagnosis and help for the family screening. Liver biopsy is not systematic and is discussed when it helps diagnosis. Currently, for these three diseases, non-invasive fibrosis markers could identify patients with risk of cirrhosis and complications. Rare genetic liver diseases can result in multi-systemic damage, which may compromise the patient's prognosis. Wilson's disease, must be investigated in any patient with unexplained liver disease and/or unexplained neurological or neuropsychiatric disorders. The diagnosis is based on a combination of clinical, biological features, including copper balance. The exchangeable copper/total copper ratio is a new sensible and specific biological marker, useful for the diagnosis of the disease. Timely diagnosis and treatment will prevent serious complications from the disease. Neurological evaluation and familial screening are essential in patients with Wilson's disease.


Assuntos
Degeneração Hepatolenticular , Deficiência de alfa 1-Antitripsina , Biomarcadores , Cobre , Seguimentos , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/genética , Humanos , Fígado , Doenças Raras , Deficiência de alfa 1-Antitripsina/complicações , Deficiência de alfa 1-Antitripsina/diagnóstico , Deficiência de alfa 1-Antitripsina/genética
16.
Liver Transpl ; 17 Suppl 2: S6-13, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21858912

RESUMO

KEY POINTS: 1. Liver transplantation is currently an effective therapy for patients with HCC who meet the Milan criteria. 2. The proportion of patients on waiting lists for liver transplantation who have HCC has increased substantially in recent years. HCC is currently one of the major indications for liver transplantation; it is the indication for approximately one-third of liver transplants. 3. If the Milan criteria are not met, the survival rates after liver transplantation for HCC tend to decrease, mainly because of the catastrophic consequences of HCC recurrence. 4. A few studies have supported liver transplantation when the Milan criteria are exceeded, but extensions beyond the Milan criteria remain controversial. Even if an individual patient with HCC who does not meet the Milan criteria might benefit from liver transplantation, the limited number of currently available donor organs limits the indications for liver transplantation to those patients with HCC who have the greatest likelihood of survival after the procedure. 5. To patients with early-stage HCC, surgical resection can be offered if the hepatocellular function is well maintained and severe portal hypertension is not present. 6. To enable patients with HCC to have access to liver transplantation that is similar to the access for other patients without HCC in the MELD allocation system, additional points based on the number and size of HCC lesions are assigned to patients on the waiting list. However, this system requires further refinement to ensure that it is as fair as possible. 7. Liver transplantation for HCC should be restricted to those patients who are expected to have the same posttransplant survival as that of patients with nonneoplastic end-stage chronic liver disease. 8. On the basis of these considerations, a 5-year survival rate of 50% after liver transplantation for HCC seems too low.


Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/normas , Seleção de Pacientes , Doadores de Tecidos/provisão & distribuição , Listas de Espera , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Medicina Baseada em Evidências , Acessibilidade aos Serviços de Saúde/normas , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Guias de Prática Clínica como Assunto , Medição de Risco , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Obtenção de Tecidos e Órgãos/normas , Resultado do Tratamento , Listas de Espera/mortalidade
17.
Hepatobiliary Surg Nutr ; 10(5): 598-609, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34760964

RESUMO

BACKGROUND: Obesity is associated with increased oncological risk and outcomes but the evidence surrounding the effect of body mass index (BMI) on increased risk of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) is still questionable. The purpose of this retrospective study of a large cohort of adult patients transplanted for HCC was to investigate the effect of BMI on the incidence of HCC recurrence and outcome. METHODS: Data from 427 adult recipients transplanted for HCC between 2000 and 2017 were collected. Patients were classified at time of LT according to the World Health Organization BMI classification into 3 groups; group 1: BMI <25 (n=166), group 2: BMI 25-29.9 (n=150) and group 3: BMI ≥30 (n=111). RESULTS: There were no significant changes of mean BMI overtime 26.8±5.0 kg/m2 at time of LT and 28.8±23.1 at 5 years. The recurrence rates of HCC after LT in the three groups were 19%, 16% and 17% respectively. The 5, 10 and 15-year recurrence free survival (RFS) rates were respectively 68.6%, 47.3% and 40.8% in group 1, 73.3%, 66.2% and 49.5% in group 2 and 68.8%, 57.5% and 47.7% in group 3 (log rank P=0.47). CONCLUSIONS: Recipient BMI at time of transplant and during follow-up didn't impact the incidence of HCC recurrence nor long-term patient survival, irrespective to the status of the patients and their tumor characteristic at time of LT. The present study clearly confirms that obesity should not be considered, when selecting patients with HCC to LT, as a predictive factor of recurrence.

18.
Transplantation ; 105(8): 1778-1790, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32890134

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is currently the first indication of liver transplantation (LT) in Europe and Asia-Pacific region and the third in the United States. HCC recurrence is the main complication affecting short- and medium-term outcomes after LT. METHODS: A total of 433 consecutive adult recipients transplanted for HCC between 2000 and 2017 (mean age: 57.8 ± 8.5 y; 83.8% were males) with a mean follow-up of 74.6 ± 58.6 months were included. Patients had to meet Milan criteria and, since 2014, alpha-fetoprotein score to be listed. Patients with HCC recurrence were classified into early (≤2 y) and late recurrence (>2 y) and were retrospectively reviewed. RESULTS: Patients who developed recurrence (75 patients, 17%) had more tumors outside Milan and University of California San Francisco criteria, high alpha-fetoprotein score, and microvascular invasion at pathology. Early recurrence developed in 46 patients (61.3%); the overall 5- and 10-year survival rates of these patients from time of LT were 6.7% and 0%, which were significantly lower than those with late recurrence 64.0% and 27.1%, respectively (P < 0.001). The median survival times from the diagnosis of HCC recurrence were 15 and 17 months, respectively, in the 2 groups (P < 0.001). Multivariable Cox regression analysis identified alcoholic cirrhosis as etiology of the underlying liver disease (hazard ratio [HR] = 3.074; P = 0.007), bilobar tumor at time of LT (HR = 2.001; P = 0.037), and a tumor size (>50 mm) in the explant (HR = 1.277; P = 0.045) as independent predictors of early recurrence. CONCLUSIONS: Improving the prediction of early HCC recurrence could optimize patient selection for LT, potential adjuvant therapy with new targeted drugs and hence, improve long-term survival.


Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Recidiva Local de Neoplasia/etiologia , Idoso , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Modelos de Riscos Proporcionais , Estudos Retrospectivos
19.
Eur J Med Genet ; 64(10): 104305, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34400371

RESUMO

BACKGROUND/AIM: The spectrum of ATP7B variants varies significantly according to geographic distribution, and there is insufficient data on the variants observed in the French population. METHODS: Clinical data of 113 children included in the French WD national registry were gathered from March 01, 1995 to July 01, 2020. Data included epidemiological, clinical, laboratory, genetics. RESULTS: Diagnosis was made at a mean age of 11.0 ± 4.1 years (range 1-18 years). At diagnosis, 91 patients (79.8 %) had hepatic manifestations, 18 (15.8 %) presented neurological manifestations, and 4 patients (3.5 %) were asymptomatic. Only 29 patients (25 %) were homozygous for a variant. We have found a total of 102 different variants including 14 novel variants. Recurrent variant p.His1069Gln was the most prevalent, n = 31 alleles (14,2%), with only seven homozygous; in contrast 55% of variants are identified in only one family. 45% were truncating variants. In respect of mutated exon, the three most prevalent were exon 14 (16.5%), exon 8 (13.8%), and exon 3 (11.5%). When considering patients with two Nonsense / Frameshift variants as a group and those with two Missense variants, we found significantly lower ceruloplasmin for the former: 2.8 ± 0.7 mg/dl vs 8.4 ± 5mg/dl (p<0.05). CONCLUSION: p.His1069Gln is the most frequent variant (14,2%) and exons 14, 8, and 2 of the ATP7B gene account for 41.7% of total variants. However, there is significant heterogeneity in the French population concerning the other ATP7B variants. Nonsense / Frameshift variants were associated with lower ceruloplasmin levels.


Assuntos
ATPases Transportadoras de Cobre/genética , Degeneração Hepatolenticular/genética , Fenótipo , Adolescente , Ceruloplasmina/análise , Criança , Pré-Escolar , Feminino , Frequência do Gene , Degeneração Hepatolenticular/sangue , Degeneração Hepatolenticular/patologia , Humanos , Masculino , Mutação
20.
Neurology ; 94(21): e2189-e2202, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32398357

RESUMO

OBJECTIVE: To evaluate the effect of liver transplantation (LT) in patients with Wilson disease (WD) with severe neurologic worsening resistant to active chelation. METHODS: French patients with WD who underwent LT for pure neurologic indication were retrospectively studied. Before LT and at the last follow-up, neurologic impairment was evaluated with the Unified Wilson's Disease Rating Scale (UWDRS) score, disability with the modified Rankin Scale (mRS) score, and hepatic function with the Model for End-stage Liver Disease score, together with the presence of a Kayser-Fleischer ring (KFR), brain MRI scores, and copper balance. The survival rate and disability at the last follow-up were the coprimary outcomes; evolution of KFR and brain MRI were the secondary outcomes. Prognosis factors were further assessed. RESULTS: Eighteen patients had LT. All were highly dependent before LT (median mRS score 5). Neurologic symptoms were severe (median UWDRS score 105), dominated by dystonia and parkinsonism. The cumulated survival rate was 88.8% at 1 year and 72.2% at 3 and 5 years. At the last follow-up, 14 patients were alive. Their mRS and UWDRS scores improved (p < 0.0001 and p = 0.0003). Eight patients had a major improvement (78% decrease of the UWDRS score), 4 a moderate one (41% decrease), and 2 a stable status. KFR and brain MRI scores improved (p = 0.0007). Severe sepsis (p = 0.011) and intensive care unit admission (p = 0.001) before LT were significantly associated with death. CONCLUSIONS: LT is a rescue therapeutic option that should be carefully discussed in selected patients with neurologic WD resistant to anticopper therapies (chelators or zinc salts) as it might allow patients to gain physical independency with a reasonable risk. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with WD with severe neurologic worsening resistant to active pharmacologic therapy, LT might decrease neurologic impairment.


Assuntos
Degeneração Hepatolenticular/cirurgia , Transplante de Fígado/estatística & dados numéricos , Adolescente , Avaliação da Deficiência , Resistência a Medicamentos , Feminino , Humanos , Testes de Função Hepática , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Taxa de Sobrevida , Adulto Jovem
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