RESUMO
OBJECTIVES: Liver transplantation (LT) is the only available cure for end-stage liver disease and one of the best treatment options for hepatocellular carcinomas (HCC). Patients with known alcohol-associated cirrhosis (AC) are routinely assessed for alcohol dependence or abuse before LT. Patients with other liver diseases than AC may consume alcohol both before and after LT. The aim of this study was to assess the effects of alcohol drinking before and after LT on patient and graft survival regardless of the etiology of liver disease. MATERIALS AND METHODS: Between April 2012 and December 2015, 200 LT-recipients were interviewed using the Lifetime Drinking History and the Addiction Severity Index questionnaire. Patients were categorized as having AC, n = 24, HCC and/or hepatitis C cirrhosis (HCV), n = 69 or other liver diseases, n = 107. Patients were monitored and interviewed by transplantation-independent staff for two years after LT with questions regarding their alcohol consumption. Patient and graft survival data were retrieved in October 2019. RESULTS: Patients with AC had an increased hazard ratio (HR) for death after LT (crude HR: 4.05, 95% CI: 1.07-15.33, p = 0.04) and for graft loss adjusted for age and gender (adjusted HR: 3.24, 95% CI 1.08-9.77, p = 0.04) compared to the other patients in the cohort. There was no significant effect of the volume of alcohol consumed before or after LT on graft loss or overall survival. CONCLUSION: Patients transplanted for AC have a worse prognosis, but we found no correlation between alcohol consumed before or after LT and graft or patient survival.
Assuntos
Carcinoma Hepatocelular , Hepatite C , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/complicações , Suécia/epidemiologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/complicações , Fatores de Risco , Cirrose Hepática Alcoólica/cirurgia , Cirrose Hepática Alcoólica/complicações , Hepatite C/complicações , Hepacivirus , Resultado do Tratamento , Estudos RetrospectivosRESUMO
BACKGROUND AND AIM: Roux-En-Y gastric bypass (RYGB) is associated with risk of alcohol use disorder. The impact of RYGB among patients with alcohol-associated liver disease (ALD) remains unknown. METHODS: A retrospective cohort from National Inpatient Sample (01/2006-09/2015) database on 421,156 admissions with alcohol-associated cirrhosis (AC) was stratified for non-primary discharge diagnosis of previous RYGB. Admissions with RYGB (cases) were matched 1:3 to without RYGB (controls) based on propensity score on demographics, calendar year, socioeconomic status (insurance and zip code income quartile), obesity, diabetes, anxiety, and alcohol use disorder. Primary outcome was concomitant discharge diagnosis of alcoholic hepatitis (AH) or development of acute on chronic liver failure (ACLF). RESULTS: Of 10,168 admissions (mean age 49 yrs., 75% females, 79% whites), cases (N = 2542) vs. controls had higher prevalence of concomitant AH (18.8 vs. 17%, P = 0.032), hepatic encephalopathy (31 vs. 25%), infection (28 vs. 24%), and grade 3 ACLF (13 vs. 5%), P < 0.001. Conditional logistic regression models showed higher odds for AH, hepatic encephalopathy, and infection among cases. In-hospital mortality of 6.3% (43% in ACLF) was lower in cases, but similar in the sub-cohorts of AH (N = 1768) or ACLF (N = 768). Results were similar in a sensitivity analysis of matched cohort of 2016 hospitalizations (504 cases) with primary discharge diagnosis of AC. CONCLUSION: Among patients with AC, previous RYGB is associated with increased likelihood of concomitant AH, hepatic encephalopathy, and infection, but similar in-hospital mortality. Prospective studies are needed to validate, determine causality, and understand mechanisms of these findings among patients with alcohol-associated cirrhosis.
Assuntos
Alcoolismo , Derivação Gástrica , Encefalopatia Hepática , Hepatite Alcoólica , Obesidade Mórbida , Feminino , Humanos , Pessoa de Meia-Idade , Masculino , Derivação Gástrica/efeitos adversos , Derivação Gástrica/métodos , Estudos Retrospectivos , Encefalopatia Hepática/epidemiologia , Encefalopatia Hepática/etiologia , Hospitalização , Cirrose Hepática Alcoólica/epidemiologia , Cirrose Hepática Alcoólica/cirurgia , Obesidade Mórbida/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND & AIMS: In 2018, our team initiated a prospective pilot program to challenge the paradigm of the "6-month rule" of abstinence for patients with alcohol-related liver disease (ALD) requiring transplant. Our pilot involved an in-depth examination of patients' alcohol use, social support, and psychiatric comorbidity, as well as the provision of pre- and post-transplantation addiction treatment. METHODS: Patients with ALD were assessed for inclusion in the pilot by a multidisciplinary team. Relapse prevention therapy was provided directly to all patients deemed to meet the program's inclusion criteria. Random biomarker testing for alcohol was used pre and post transplantation. RESULTS: We received 703 referrals from May 1, 2018 to October 31, 2020. After fulfilling the program's criteria, 101 patients (14%) were listed for transplantation and 44 (6.2%) received transplants. There were no significant differences in survival rates between those receiving transplants through the pilot program compared with a control group with more than 6 months of abstinence (P = .07). Three patients returned to alcohol use during an average post-transplantation follow-up period of 339 days. In a multivariate analysis, younger age and lower Model for End-Stage Liver Disease scores at listing were associated with an increased likelihood of a return to alcohol use (P < .05); length of abstinence was not a predictor. CONCLUSIONS: Our prospective program provided direct monitoring and relapse prevention treatment for patients with ALD and with less than 6 months of abstinence and resulted in a reduction of post-transplantation return to drinking. This pilot study provides a framework for the future of more equitable transplant care.
Assuntos
Abstinência de Álcool , Consumo de Bebidas Alcoólicas/prevenção & controle , Alcoolismo/terapia , Cirrose Hepática Alcoólica/cirurgia , Transplante de Fígado , Psicoterapia , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/psicologia , Alcoolismo/complicações , Alcoolismo/diagnóstico , Alcoolismo/psicologia , Biomarcadores/sangue , Biomarcadores/urina , Tomada de Decisão Clínica , Ensaios Enzimáticos Clínicos , Feminino , Glucuronatos/urina , Humanos , Cirrose Hepática Alcoólica/diagnóstico , Cirrose Hepática Alcoólica/etiologia , Testes de Função Hepática , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Projetos Piloto , Valor Preditivo dos Testes , Estudos Prospectivos , Recidiva , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Acute kidney injury is seen in approximately 30% of patients with severe alcohol-associated hepatitis (AH) and is associated with increased mortality. Controversy exists surrounding initiation of renal replacement therapy (RRT) in these patients, as most are ineligible for early transplantation. AIMS: The primary aim was to identify predictors of survival and identify patients who may benefit from RRT as a bridge to transplant or recovery. METHODS: A retrospective multicenter cohort of adult patients with AH, who received RRT, was developed, including patients from two North American and one European liver transplant centers. RESULTS: Fifty-five patients were included. Survival was 26/55 (47.3%) at 30 days, 17/55 (30.9%) at 3 months, and 15/55 (27.2%) at 6 months. Of those who survived 6 months, 2/15 (13.3%) received simultaneous liver and kidney transplantation, 11/15 (73.3%) had spontaneous recovery of kidney function, and 2/15 (13.3%) remained on RRT. Of patients who survived at least 3 months, 8/17 (47%) completed addiction treatment. Predictors of mortality were pre-RRT MELD (OR 1.10, 1.02-1.19) and pre-RRT MELD-Na (OR 1.14, 1.03-1.27). Pre-RRT MELD-Na < 35 was associated with lower 6-month mortality (OR 0.23, 0.06 - 0.81). Of patients with pre-RRT MELD-Na < 35, 50% survived 6 months compared to 18% of patients with pre-RRT MELD-Na ≥ 35. CONCLUSIONS: Although RRT has a limited role in patients with decompensated cirrhosis, ineligible for transplant, it may be used in select patients with AH. This may allow for spontaneous recovery with alcohol abstinence or completion of addiction treatment prior to transplant.
Assuntos
Injúria Renal Aguda/terapia , Hepatite Alcoólica/fisiopatologia , Síndrome Hepatorrenal/terapia , Cirrose Hepática Alcoólica/fisiopatologia , Terapia de Substituição Renal , Injúria Renal Aguda/complicações , Adulto , Feminino , Hepatite Alcoólica/complicações , Síndrome Hepatorrenal/complicações , Humanos , Transplante de Rim , Cirrose Hepática Alcoólica/complicações , Cirrose Hepática Alcoólica/cirurgia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Mortalidade , Recuperação de Função Fisiológica , Estudos Retrospectivos , Índice de Gravidade de Doença , Taxa de SobrevidaRESUMO
BACKGROUND: One of the major issues related to the living donor liver transplantation recipient outcome is still the high rate of biliary complication, especially when multiple biliary ducts are present and multiple anastomoses have to be performed. CASE PRESENTATION AND CONCLUSION: We report a case of adult-to-adult right lobe living donor liver transplantation performed for a recipient affected by alcohol-related cirrhosis with MELD score of 17. End-stage liver disease was complicated by refractory ascites, portal hypertension, small esophageal varices and portal gastropathy, hypersplenism, and abundant right pleural effusion. Here in the attached video we described the adult-to-adult LDLT procedures, where a right lobe with two biliary ducts draining respectively the right anterior and the right posterior segments has been transplanted. LDLT required a biliary reconstruction using the native cystic and common bile ducts stented trans-papillary with two 5- French 6 cm long soft silastic catheter. None major complications were detected during post-operative clinical courses. Actually, the donor and the recipient are alive and well. The technique we describe in the video, allow to keep the biliary anastomoses protected and patent without having the risk of creating cholestasis and the need of invasive additional procedure. No living donor right lobe transplantation should be refused because of the presence of multiple biliary ducts.
Assuntos
Ductos Biliares/cirurgia , Ducto Cístico/cirurgia , Cirrose Hepática Alcoólica/cirurgia , Transplante de Fígado , Doadores Vivos , Stents , Anastomose Cirúrgica , Ducto Colédoco , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Alcohol-related liver disease (ALD) is one of the main indications for liver transplantation (LT). Severe alcohol relapse can rapidly lead to recurrent alcohol-related cirrhosis (RAC) for the graft. The aim of this study was to describe the natural history of RAC and the overall survival after LT and after an RAC diagnosis. From 1992 to 2012, 812 patients underwent primary LT for ALD in 5 French transplant centers. All patients with severe alcohol relapse and an RAC diagnosis on the graft were included. The diagnosis of cirrhosis was based on the analysis of liver biopsy or on the association of clinical, biological, radiological, and/or endoscopic features of cirrhosis. RAC was diagnosed in 57/162 patients (35.2%) with severe alcohol relapse, and 31 (54.4%) of those patients had at least 1 episode of liver decompensation. The main types of decompensation were ascites (70.9%), jaundice (58.0%), and hepatic encephalopathy (9.6%). The cumulative probability of decompensation was 23.8% at 5 years, 50.1% at 10 years, and 69.9% at 15 years after LT. During the follow-up, 36 (63.2%) patients died, the main cause of death being liver failure (61.1%). After diagnosis of cirrhosis, the survival rate was 66.3% at 1 year, 37.8% at 5 years, and 20.6% at 10 years. In conclusion, RAC is associated with a high risk of liver decompensation and a poor prognosis. Prevention of severe alcohol relapse after LT is a major goal to improve patient survival.
Assuntos
Transplante de Fígado , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/cirurgia , Cirrose Hepática Alcoólica/cirurgia , Transplante de Fígado/efeitos adversos , Recidiva , Fatores de RiscoRESUMO
BACKGROUND: In order to reduce alcohol relapse after liver transplantation (LT), the German national guidelines for waiting-list maintenance and organ allocation demand a minimum 6-month period of alcohol abstinence pre-LT, confirmed by measuring urinary ethyl glucuronide (uEtG). METHODS: Between January 2015 and June 2016, uEtG was measured at least once in 339 cirrhotic patients with an indication for LT at the University Medical Center Mainz. uEtG was measured with an enzyme-linked immunosorbent assay (ELISA) screening test (cutoff value: 500âµg/L). For uEtG values ≥â500âµg/L, liquid chromatography-mass spectrometry (LC-MS/MS) was performed as a confirmatory assay. Data were collected prospectively in a transplant database. RESULTS: Of the 339 potential liver transplant candidates, uEtG was negative in 86.4â%. Most patients were male (64.3â%), with an average age of 56.42â±â10.1 years. In the multivariate analysis, mean corpuscular volume (pâ=â0.001), urinary creatinine (pâ=â0.001), gamma-glutamyl transferase (pâ=â0.001), and hemoglobin (pâ=â0.003) were significantly associated with a positive uEtG test result. The sensitivity of the ELISA screening test was 100â% for uEtG values >â2000âµg/L, as confirmed by LC-MS/MS. CONCLUSION: uEtG is an effective parameter to reveal alcohol consumption by patients on the waiting list for LT. The sensitivity of the ELISA is excellent for uEtG values >â2000âµg/L, for which LC-MS/MS confirmation could be omitted.
Assuntos
Consumo de Bebidas Alcoólicas , Glucuronatos/urina , Cirrose Hepática Alcoólica/cirurgia , Cirrose Hepática Alcoólica/urina , Transplante de Fígado , Programas de Rastreamento/métodos , Idoso , Biomarcadores/urina , Cromatografia Líquida , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Etanol/sangue , Etanol/urina , Feminino , Humanos , Cirrose Hepática Alcoólica/diagnóstico , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem , Listas de EsperaRESUMO
Cancer transmission with organ donation has been previously reported with a variety of malignancies and organ transplants. The risk of transmission through organ transplantation from donors with a history of previously treated malignancies has been addressed by guidelines from transplant societies. Herein, we report a case of a patient who developed lung cancer confined to the liver after liver transplantation with no known history of malignancy in the donor. The suspicion of donor origin arose after positron emission tomography-computerized tomography scan showed metastatic lung cancer only involving the transplanted liver without a primary focus. Genetic analysis of the malignant cells confirmed donor origin of the cancer.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/etiologia , Cirrose Hepática Alcoólica/cirurgia , Transplante de Fígado/efeitos adversos , Neoplasias Pulmonares/etiologia , Idoso , Aloenxertos/diagnóstico por imagem , Aloenxertos/patologia , Biópsia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Evolução Fatal , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Neoplasias Pulmonares/diagnóstico , Masculino , Doadores de Tecidos , Tomografia Computadorizada por Raios XRESUMO
Alcohol-associated liver disease (ALD) can be coded in United Network for Organ Sharing (UNOS) as either alcoholic cirrhosis or alcoholic hepatitis (AH), without having specific criteria to assign either diagnosis. In this multicenter American Consortium of Early Liver Transplantation for Alcoholic Hepatitis (ACCELERATE-AH) study, we sought to assess the concordance of the clinician diagnosis of AH at liver transplantation (LT) listing versus UNOS data entry of AH as listing diagnosis. In a prior study, consecutive early LT recipients transplanted for AH between 2012 and 2017 were identified by chart review at 10 ACCELERATE-AH sites. In this current study, these same LT recipients were identified in the UNOS database. The primary UNOS diagnostic code was evaluated for concordance with the chart-review assignment of AH. In cases where the primary listing diagnosis in UNOS was not AH, we determined the reason for alternate classification. Among 124 ACCELERATE-AH LT recipients with a chart-review diagnosis of AH, only 43/124 (35%) had AH as listing diagnosis in UNOS; 80 (64%) were listed as alcoholic cirrhosis, and 1 (1%) as fulminant hepatic necrosis. Of the 81 patients missing AH as a UNOS listing diagnosis code, the reasons for alternate classification were 44 (54%) due to a lack of awareness of a separate diagnosis code for AH; 13 (16%) due to concomitant clinical diagnosis of AH and alcoholic cirrhosis in the chart; 12 (15%) due to clinical uncertainty regarding the diagnosis of AH versus acute decompensated alcoholic cirrhosis; and 12 (15%) due to a data entry error. In conclusion, in a large cohort of LT recipients with AH, only 35% were documented as such in UNOS. Increased education and awareness for those performing UNOS data entry, the establishment of specific criteria to define AH in the UNOS database, and the ability to document dates of alcohol use would allow future research on ALD to be more informative.
Assuntos
Codificação Clínica/estatística & dados numéricos , Bases de Dados Factuais/estatística & dados numéricos , Hepatite Alcoólica/cirurgia , Cirrose Hepática Alcoólica/cirurgia , Transplante de Fígado/estatística & dados numéricos , Adulto , Erros de Diagnóstico , Feminino , Hepatite Alcoólica/diagnóstico , Hepatite Alcoólica/epidemiologia , Humanos , Cirrose Hepática Alcoólica/diagnóstico , Cirrose Hepática Alcoólica/epidemiologia , Transplante de Fígado/normas , Masculino , Prontuários Médicos/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Liver transplant candidates undergo psychosocial assessment as a component of their pretransplant evaluation. Global psychosocial assessment scales, including the Psychosocial Assessment of Candidates for Transplantation (PACT), capture and quantify these psychiatric and social variables. OBJECTIVE: Our primary aim was to assess for an association between global PACT score and survival in liver transplant recipients. METHODS: This retrospective cohort study examined records of all liver recipients at one U.S. Transplant Center from 2000 to 2012 with outcomes monitoring until 07/01/2016. We investigated for associations between the following variables and mortality: PACT score, age, gender, marital status, race, alcoholic liver disease (ALD), and body mass index (BMI). Statistical methods included Student's t-test, Wilcoxon rank sum test, chi-square, Fisher's exact test, Kaplan-Meier curve, and Cox proportional hazard models. RESULTS: Of 1040 liver recipients, 538 had a documented PACT score. Among these, PACT score was not associated with mortality. In women, a lower PACT score was associated with mortality (pâ¯=â¯0.003) even after adjustments for age, marital status, and BMI. Women with ALD had a 2-fold increased hazard of death (pâ¯=â¯0.012). Increasing age was associated with increased risk of death for the cohort as a whole (pâ¯=â¯0.019) and for men (pâ¯=â¯0.014). In men, being married and BMI were marginally protective (pâ¯=â¯0.10 and pâ¯=â¯0.13, respectively). CONCLUSIONS: Transplant psychosocial screening scales, specifically the PACT, identify psychosocial burden and may predict post-transplant outcomes in certain populations. In female liver recipients, lower PACT scores and ALD were associated with a greater risk of post-transplant mortality.
Assuntos
Cirrose Hepática Alcoólica/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Saúde Mental , Mortalidade , Apoio Social , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Estilo de Vida , Cirrose Hepática/cirurgia , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Psicologia , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
We report a case of necrotizing skin infection caused by Yokenella regensburgei in an immunosuppressed patient with orthotopic liver transplantation. Initial bacterial culture identification was suggestive of Hafnia alvei. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) confirmed identification of Y. regensburgei. Necrotizing fasciitis is potentially fatal and requires aggressive management, including early diagnosis, appropriate antibiotic selection, and operative debridement.
Assuntos
Enterobacteriaceae/isolamento & purificação , Fasciite Necrosante/microbiologia , Hospedeiro Imunocomprometido , Pele/lesões , Ferimentos e Lesões/microbiologia , Amputação Cirúrgica , Antibacterianos/uso terapêutico , Desbridamento , Enterobacteriaceae/imunologia , Fasciite Necrosante/imunologia , Fasciite Necrosante/terapia , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/efeitos adversos , Perna (Membro) , Cirrose Hepática Alcoólica/imunologia , Cirrose Hepática Alcoólica/cirurgia , Transplante de Fígado/efeitos adversos , Pessoa de Meia-Idade , Pele/microbiologia , Pele/patologia , Resultado do Tratamento , Ferimentos e Lesões/imunologia , Ferimentos e Lesões/terapiaRESUMO
We report the case of a 53-year-old-man who developed human T-cell leukemia virus type-1-associated myelopathy (HAM) after ABO-incompatible liver transplantation for alcoholic liver cirrhosis. The living donor was seropositive for human T-cell leukemia virus type-1 (HTLV-1) and the recipient was seronegative for HTLV-1 before transplantation. After transplantation, the recipient developed steroid-resistant acute cellular rejection, which was successfully treated using anti-thymocyte globulin, and he was eventually discharged. He underwent spinal surgery twice after the transplantation for the treatment of cervical spondylosis that had been present for a period of 9 months before the transplantation. The surgery improved his gait impairment temporarily. However, his gait impairment progressed, and magnetic resonance imaging revealed multiple sites of myelopathy. He was diagnosed with HAM 16 months after the transplantation. Pulse steroid therapy (1000mg) was administered over a period of 3 days, and his limb paresis improved. Presently, steroid therapy is being continued, with a plan to eventually taper the dose, and he is being carefully followed up at our institution. Our case suggests that liver transplantation involving an HTLV-1-positive living donor carries the risk of virus transmission and short-term development of HAM after transplantation.
Assuntos
Sistema ABO de Grupos Sanguíneos , Anticorpos Antivirais/sangue , Incompatibilidade de Grupos Sanguíneos , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Cirrose Hepática Alcoólica/cirurgia , Transplante de Fígado/efeitos adversos , Doadores Vivos , Paraparesia Espástica Tropical/transmissão , Feminino , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Cirrose Hepática Alcoólica/diagnóstico , Masculino , Pessoa de Meia-Idade , Paraparesia Espástica Tropical/imunologia , Paraparesia Espástica Tropical/terapia , Paraparesia Espástica Tropical/virologia , Medição de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
INTRODUCTION AND OBJECTIVES: Non-alcoholic steatohepatitis (NASH) indication of liver transplant (LT) has increased recently, whereas alcoholic cirrhosis remains a major indication for LT. To characterize NASH-related cases and to compare the post-transplant outcome of these two conditions represents our major objective. MATERIAL AND METHODS: Patients undergoing LT for NASH between 1997 and 2016 were retrieved. Those transplanted between 1997 and 2006 were compared to an "age and LT date" matched group of patients transplanted for alcoholic cirrhosis (ratio 1:2). Baseline features and medium-term outcome measures were compared. RESULTS: Of 1986 LT performed between 1997 and 2016, 40 (2%) were labeled as NASH-related indications. NASH-related cases increased initially (from 0.8% in 1997-2001 to 2.7% in 2002-2006) but remained stable in subsequent years (2.3%). Hepatocellular carcinoma (HCC) prevalence was greater in NASH-vs alcohol-related cirrhosis (40% vs 3%, p=0.001). The incidence of overweight, obesity, arterial hypertension, dyslipidemia, diabetes, hyperuricemia, renal insufficiency and cardiovascular (CV) disease was similar in both groups at 5 years post-LT. Five-year survival was higher in NASH but without reaching statistical significance (83% vs 72%, p=0.21). The main cause of mortality in NASH-LT patients was HCC recurrence. CONCLUSION: Most previously considered cryptogenic cases are actually NASH-cirrhosis. While the incidence of this indication is increasing in many countries, it has remained relatively stable in our Unit, the largest LT center in Spain. HCC is common in these patients and represents a main cause of post-transplant mortality. Metabolic complications, CV-related disease and 5-yr survival do not differ in patients transplanted for NASH vs alcohol.
Assuntos
Carcinoma Hepatocelular/cirurgia , Cirrose Hepática Alcoólica/cirurgia , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica/cirurgia , Adulto , Idoso , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/mortalidade , Doenças Cardiovasculares/epidemiologia , Causas de Morte , Estudos de Coortes , Diabetes Mellitus/epidemiologia , Dislipidemias/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Hiperuricemia/epidemiologia , Cirrose Hepática/etiologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Hepatopatia Gordurosa não Alcoólica/complicações , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Insuficiência Renal/epidemiologia , Estudos Retrospectivos , Espanha/epidemiologia , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Alcoholic liver disease (ALD) is a highly prevalent spectrum of pathologies caused by alcohol overconsumption. Morbidity and mortality related to ALD are increasing worldwide, thereby demanding strategies for early diagnosis and detection of ALD predisposition. A potential candidate as a marker for ALD susceptibility is the transcription factor nuclear factor erythroid-related factor 2 (Nrf2), codified by the nuclear factor erythroid 2-related factor 2 gene (NFE2L2). Nrf2 regulates expression of proteins that protect against oxidative stress and inflammation caused by alcohol overconsumption. Here, we assessed genetic variants of NFE2L2 for association with ALD. Specimens from patients diagnosed with cirrhosis caused by ALD were genotyped for three NFE2L2 single nucleotide polymorphisms (SNP) (SNPs: rs35652124, rs4893819, and rs6721961). Hematoxylin & eosin and immunohistochemistry were performed to determine the inflammatory score and Nrf2 expression, respectively. SNPs rs4893819 and rs6721961 were not specifically associated with ALD, but analysis of SNP rs35652124 suggested that this polymorphism predisposes to ALD. Furthermore, SNP rs35652124 was associated with a lower level of Nrf2 expression. Moreover, liver samples from ALD patients with this polymorphism displayed more severe inflammatory activity. Together, these findings provide evidence that the SNP rs35652124 variation in the Nrf2-encoding gene NFE2L2 is a potential genetic marker for susceptibility to ALD.
Assuntos
Predisposição Genética para Doença , Cirrose Hepática Alcoólica/genética , Fator 2 Relacionado a NF-E2/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Adulto , Estudos de Casos e Controles , Etanol/farmacologia , Feminino , Expressão Gênica , Hepacivirus/crescimento & desenvolvimento , Hepacivirus/patogenicidade , Hepatite C/patologia , Hepatite C/virologia , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática Alcoólica/metabolismo , Cirrose Hepática Alcoólica/patologia , Cirrose Hepática Alcoólica/cirurgia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Estresse OxidativoRESUMO
We report cutaneous fluorescent in-situ hybridization (FISH) analysis as a useful test for earlier diagnostic confirmation in a case of acute graft-versus-host disease (GVHD) in a sex-mismatched liver transplant patient compared to the gold standard peripheral blood short tandem repeat chimerism analysis.
Assuntos
Dermatite/patologia , Doença Enxerto-Hospedeiro/diagnóstico , Transplante de Fígado , Quimerismo , Dermatite/etiologia , Diagnóstico Precoce , Feminino , Doença Enxerto-Hospedeiro/complicações , Doença Enxerto-Hospedeiro/patologia , Humanos , Imunossupressores/uso terapêutico , Hibridização in Situ Fluorescente/métodos , Cirrose Hepática Alcoólica/cirurgia , Pessoa de Meia-Idade , Pancitopenia/etiologia , Reação em Cadeia da Polimerase , Linfócitos T/metabolismoRESUMO
In Belgium as in many other countries, alcohol is one of the leading causes of adult liver transplantation. Liver transplantation for terminal liver failure due to excessive alcohol intake raises clear ethical issues concerning the use of grafts to save patients suffering from a self-inflecting affection. Alcoholic liver disease is one of the best indications for liver transplantation, with excellent results in terms of length of survival and post transplantation quality of life, if this transplantation is proposed by a multidisciplinary team in a patient able to and helped by a supporting family and social environment.
En Belgique, comme dans beaucoup d'autres pays, la maladie alcoolique constitue une des causes les plus fréquentes menant à la transplantation hépatique chez l'adulte. Or la transplantation hépatique chez des patients alcooliques pose de claires questions éthiques concernant l'utilisation de greffons pour soigner des patients souffrant d'une maladie trop souvent considérée comme étant auto-infligée. La maladie alcoolique du foie est une des meilleures indications de greffe hépatique, avec d'excellents résultats en termes de durée de survie et de qualité de vie après transplantation. Le pré-requis est que cette transplantation soit proposée par une équipe multidisciplinaire, chez un patient capable de se prendre en charge et soutenu par un environnement familial et social favorable.
Assuntos
Alcoolismo , Cirrose Hepática Alcoólica , Hepatopatias Alcoólicas , Transplante de Fígado , Adulto , Bélgica , Humanos , Cirrose Hepática Alcoólica/cirurgia , Qualidade de Vida , RecidivaRESUMO
The incidence and impact of anti-human leukocyte antigen donor-specific alloantibodies (DSAs) developing after liver transplantation (LT) remains controversial and not extensively studied. The aim of the present study was to assess the incidence of DSAs, to identify risk factors for the development of DSAs, and to understand the impact of DSAs in a large population of adult LT recipients. This single-center retrospective study included all adult patients who underwent a first LT between 2000 and 2010 in our center. The study population mainly consisted of male patients, the mean age was 52.4 years, and the main indication was alcoholic cirrhosis (54.1%). From the 297 patients included in the cross-sectional study, 14 (4.7%) had preformed DSAs, and 59 (19.9%) presented de novo DSAs (12.2% at 1 year, 13.4% at 5 years, and 19.5% at 10 years). Multivariate analysis found that female donor sex (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.12-2.01; P = 0.01) and delay between LT and DSA screening (HR, 1.10; 95% CI, 1.01-1.20; P = 0.03) were associated with occurrence of de novo DSAs. From the 190 patients included in the subgroup longitudinal analysis, exposure to tacrolimus (mean trough level during the periods 0-2 years and 0-3 years) was significantly lower for patients having DSAs at 5 years. Concerning histology, only acute rejection (P = 0.04) and portal fibrosis ≥2 (P = 0.02) were more frequent at 1 year for patients with DSAs. Patient survival and graft survival were not significantly different according to the presence or not of DSAs at 1 year. Among the 44 patients who had de novo or persistent preformed DSAs, the diagnosis of antibody-mediated rejection was made in 4 (9.1%) patients after 1, 47, 61, and 74 months following LT. In conclusion, the results of the present study suggest that DSAs are observed in a minority of LT adult patients, with limited overall impact on graft and patient outcome.
Assuntos
Rejeição de Enxerto/epidemiologia , Isoanticorpos/sangue , Cirrose Hepática Alcoólica/cirurgia , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Adulto , Estudos Transversais , Feminino , Seguimentos , Rejeição de Enxerto/sangue , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Antígenos HLA/imunologia , Humanos , Imunossupressores/uso terapêutico , Incidência , Isoanticorpos/imunologia , Isoanticorpos/isolamento & purificação , Cirrose Hepática Alcoólica/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/imunologia , Complicações Pós-Operatórias/prevenção & controle , Prevalência , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Tacrolimo/uso terapêutico , Transplantados , Resultado do TratamentoRESUMO
AIM: We performed meta-analysis to determine effect of alcohol relapse after liver transplantation (LT) for alcoholic cirrhosis on graft histology and survival. METHODS: Studies were selected using following criteria: (a) LT for alcoholic cirrhosis, (b) reporting data on liver histology and/or patient survival among relapsers and abstainers, (c) minimum follow-up of 3 years. Random effects model was used to pool data to compare relapsers and abstainers on liver histology and patient survival. RESULTS: On analysis of seven studies, pooled prevalence of self-reported alcohol relapse was 26.3% (18.0-36.7%) over median (range) follow-up of 6.0 (3.7-8.3) years, with annual alcohol relapse rate of 4.7% (3.0-6.4%) for any alcohol use and 2.9% (0.5-5.3%) for heavy alcohol use. Relapsers compared to abstainers had higher odds for graft steatosis [4.1 (2.4-6.9)], steatohepatitis [4.5 (1.4-14.2)], alcoholic hepatitis [9.3 (1.01-85)], advanced fibrosis or cirrhosis [8.4 (3.5-20)]. Relapsers were over 3-fold more likely to die at 10 years of follow-up: [3.67 (1.42-9.50)] without differences in overall or 5-year survival. Recurrent alcoholic cirrhosis occurring in 9% of biopsied patients and 2% of all transplants was responsible for about 20% of all deaths on follow-up after LT. Extra-hepatic malignancy, and cardiovascular events were common causes for patient mortality. CONCLUSION: Alcohol relapse after LT for alcoholic cirrhosis negatively impacts the graft and long-term patient survival. Studies are needed to develop strategies to reduce alcohol relapse after LT for alcoholic cirrhosis. SHORT SUMMARY: Alcohol relapse in liver transplant recipients can negatively affect graft histology and patient survival. Strategies to reduce alcohol relapse are needed to preserve graft function?