RESUMO
The osmotic demyelination syndrome (ODS) is a serious neurologic condition that occurs in the setting of rapid correction of hyponatremia. It presents with protean manifestations, from encephalopathy to the "locked-in" syndrome. ODS can complicate liver transplantation (LT), and its incidence may increase with the inclusion of serum sodium as a factor in the Mayo End-Stage Liver Disease score. A comprehensive understanding of risk factors for the development of ODS in the setting of LT, along with recommendations to mitigate the risk of ODS, are necessary. The literature to date on ODS in the setting of LT was reviewed. Major risk factors for the development of ODS include severe pretransplant hyponatremia (serum sodium [SNa] < 125 mEq/L), the magnitude of change in SNa pre- versus posttransplant, higher positive intraoperative fluid balance, and the presence of postoperative hemorrhagic complications. Strategies to reduce the risk of ODS include correcting hyponatremia pretransplant via fluid restriction and/or ensuring an appropriate rate of increase from the preoperative SNa via close attention to fluid and electrolyte management both during and after surgery. Multidisciplinary management involving transplant hepatology, nephrology, neurology, surgery, and anesthesiology/critical care is key to performing LT safely in patients with hyponatremia.
Assuntos
Doenças Desmielinizantes/prevenção & controle , Hiponatremia/complicações , Transplante de Fígado/efeitos adversos , Doenças Desmielinizantes/complicações , Doenças Desmielinizantes/etiologia , Feminino , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/cirurgia , Masculino , Fatores de Risco , SíndromeRESUMO
Patients with active hepatitis C virus (HCV) infection at transplantation experience rapid allograft infection, increased risk of graft failure and accelerated fibrosis. MBL-HCV1, a neutralizing human monoclonal antibody (mAb) targeting the HCV envelope, was combined with a licensed oral direct-acting antiviral (DAA) to prevent HCV recurrence post-transplant in an open-label exploratory efficacy trial. Eight subjects received MBL-HCV1 beginning on the day of transplant with telaprevir initiated between days 3 and 7 post-transplantation. Following FDA approval of sofosbuvir, two subjects received MBL-HCV1 starting on the day of transplant with sofosbuvir initiated on day 3. Combination treatment was administered for 8-12 weeks or until the stopping rule for viral rebound was met. The primary endpoint was undetectable HCV RNA at day 56 with exploratory endpoints of sustained virologic response (SVR) at 12 and 24 weeks post-treatment. Both subjects receiving mAb and sofosbuvir achieved SVR24. Four of eight subjects in the mAb and telaprevir group met the primary endpoint; one subject achieved SVR24 and three subjects relapsed 2-12 weeks post-treatment. The other four subjects experienced viral breakthrough. There were no serious adverse events related to study treatment. This proof-of-concept study demonstrates that peri-transplant immunoprophylaxis combined with a single oral direct-acting antiviral in the immediate post-transplant period can prevent HCV recurrence.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Antivirais/administração & dosagem , Anticorpos Anti-Hepatite C/administração & dosagem , Hepatite C/prevenção & controle , Transplante de Fígado , Prevenção Secundária , Aloenxertos , Anticorpos Monoclonais/efeitos adversos , Antivirais/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Anticorpos Anti-Hepatite C/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/administração & dosagem , Oligopeptídeos/efeitos adversos , Estudo de Prova de Conceito , RNA Viral/sangue , Sofosbuvir/administração & dosagem , Sofosbuvir/efeitos adversos , Resposta Viral Sustentada , Transplantados , Resultado do TratamentoRESUMO
Early liver transplantation (LT) in European centers reportedly improved survival in patients with severe alcoholic hepatitis (AH) not responding to medical therapy. Our aim was to determine if a strategy of early LT for severe AH could be applied successfully in the United States. We reviewed 111 patients with severe AH at our center from January 2012 to January 2015. The primary end point was mortality at 6 months or early LT, with a secondary end point of alcohol relapse after LT. Survival was compared between those receiving early LT and matched patients who did not. Using a process similar to the European trial, 94 patients with severe AH not responding to medical therapy were evaluated for early LT. Overall, 9 (9.6%) candidates with favorable psychosocial profiles underwent early LT, comprising 3% of all adult LT during the study period. The 6-month survival rate was higher among those receiving early LT compared with matched controls (89% vs 11%, p<0.001). Eight recipients are alive at a median of 735 days with 1 alcohol relapse. Early LT for severe AH can achieve excellent clinical outcomes with low impact on the donor pool and low rates of alcohol relapse in highly selected patients in the United States.
Assuntos
Hepatite Alcoólica/cirurgia , Transplante de Fígado , Seleção de Pacientes , Índice de Gravidade de Doença , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Recidiva , Fatores de Risco , Taxa de Sobrevida , Fatores de TempoRESUMO
The Banff Working Group on Liver Allograft Pathology reviewed and discussed literature evidence regarding antibody-mediated liver allograft rejection at the 11th (Paris, France, June 5-10, 2011), 12th (Comandatuba, Brazil, August 19-23, 2013), and 13th (Vancouver, British Columbia, Canada, October 5-10, 2015) meetings of the Banff Conference on Allograft Pathology. Discussion continued online. The primary goal was to introduce guidelines and consensus criteria for the diagnosis of liver allograft antibody-mediated rejection and provide a comprehensive update of all Banff Schema recommendations. Included are new recommendations for complement component 4d tissue staining and interpretation, staging liver allograft fibrosis, and findings related to immunosuppression minimization. In an effort to create a single reference document, previous unchanged criteria are also included.
Assuntos
Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Isoanticorpos/imunologia , Transplante de Fígado/efeitos adversos , Aloenxertos , Humanos , Relatório de PesquisaRESUMO
To conduct surveillance and determine the safety profile of new hepatitis C virus treatments in real-world clinical practice. Hepatic decompensation and other serious adverse events were investigated in an observational cohort study of 511 patients treated with regimens containing sofosbuvir, December 2013-June 2014. Among 499 previously stable patients (no history of hepatic decompensation during the previous 12 months), a nested case-control study was performed to identify predictors of decompensation/serious adverse event. Cases and controls were matched 1:5 based on treatment regimen and duration. Matched conditional logistic regression was used for analysis. Providers scored the likelihood that events were treatment-related (scale = 0-4). The cumulative incidence of decompensation/events was 6.4% for the total cohort. Among 499 previously stable patients, the incidence of decompensation/events was 4.5%; the mortality rate was 0.6%. Sixteen of the 499 experienced one or more serious complications considered to be at least potentially treatment-related, and the sustained virological response rate was 7/16 (44%). Two cases, both on sofosbuvir/simeprevir (without interferon or ribavirin), had complications consistent with autoimmune events (score 3, 'likely treatment-related'), and one experienced a flare of autoimmune hepatitis. Compared to controls, cases had higher baseline median model for end-stage liver disease scores (14 vs 8, P < 0.01). Decompensation/events was independently associated with lower baseline albumin (OR = 0.12/g/dL, P = 0.01) and higher total bilirubin (OR = 4.31/mg/dL, P = 0.01). Reduced hepatic function at baseline increased the risk of liver decompensation/events.
Assuntos
Antivirais/uso terapêutico , Bilirrubina/sangue , Insuficiência Hepática/epidemiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Albumina Sérica/análise , Sofosbuvir/uso terapêutico , Idoso , Estudos de Casos e Controles , Técnicas de Apoio para a Decisão , Feminino , Hepatite C Crônica/patologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Albumina Sérica Humana , Simeprevir/uso terapêutico , Análise de SobrevidaRESUMO
BACKGROUND: Spontaneous bacterial peritonitis (SBP) carries appreciable morbidity and mortality in the pre-liver transplant (LT) setting. However, the occurrence of SBP and its consequences in the post-LT setting have not been well characterized. METHODS: This is a retrospective study of SBP occurring in post-LT patients between January 2007 and December 2012. Outcomes were compared to a cohort of post-LT patients with allograft failure and ascites without SBP. RESULTS: The most common indication for liver transplantation in this cohort was hepatitis C. A total of 29 episodes of SBP in 21 patients were identified. Escherichia coli (19%) and Klebsiella pneumoniae (10%) were the most frequent pathogens identified. Six patients died during their first episode of SBP. Ten patients were eventually listed for liver re-transplantation (re-LT) after their first episode of SBP; 5 of these patients were transplanted and the other 5 died. Of the 5 who were transplanted, 2 died shortly after re-transplant, and 3 are still alive. The cause of death in the majority of patients was infection (83.3%). The median time from onset of ascites to death was 214 days (range: 10-1085 days) and from the first episode of SBP to death was 50.5 days (range: 4-549 days). In contrast, the median time from onset of ascites to death in patients with allograft failure and ascites without SBP was 331.5 days (45-2400 days). CONCLUSIONS: Allograft failure with ascites is a poor prognostic factor and these patients should be considered high risk for re-LT. SBP may accelerate the time to mortality.
Assuntos
Infecções Bacterianas/mortalidade , Rejeição de Enxerto/epidemiologia , Hepatite C Crônica/cirurgia , Cirrose Hepática/complicações , Transplante de Fígado/efeitos adversos , Peritonite/mortalidade , Adolescente , Adulto , Idoso , Ascite/etiologia , Infecções Bacterianas/microbiologia , Escherichia coli/isolamento & purificação , Feminino , Rejeição de Enxerto/virologia , Humanos , Klebsiella pneumoniae/isolamento & purificação , Cirrose Hepática/cirurgia , Masculino , Pessoa de Meia-Idade , Peritonite/microbiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Transplante Homólogo/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: Liver transplantation (LT) is a treatment option for select human immunodeficiency virus (HIV)-infected patients with advanced liver disease. The aim of this study was to describe LT evaluation outcomes in HIV-infected patients. METHODS: All HIV-infected patients referred for their first LT evaluation at the Mount Sinai Medical Center were included in this retrospective, descriptive cohort study. Multivariable logistic regression was used to identify factors independently associated with listing. RESULTS: Between February 2000 and April 2012, 366 patients were evaluated for LT, with 66 (18.0%) listed for LT and 300 (82.0%) not listed. Fifty-one patients (13.9%) died before completing evaluation and 85 (23.2%) were too early for listing. Reasons patients were declined for listing were psychosocial (15.8%), HIV-related (10.4%), loss to follow-up (9.6%), surgical/medical (6.0%), liver-related (4.4%), patient choice (3.4%), and financial (1.6%). Listed patients were more likely to have hepatocellular carcinoma (HCC) (43.1% vs. 17.1%; P < 0.0001) and less likely to have hepatitis B (6.2% vs. 15.7%; P = 0.04) or a psychiatric history (19.7% vs. 35.2%; P = 0.02) than those not listed. In multivariable analysis, HCC (odds ratio [OR] 5.79; 95% confidence interval [95% CI]: 2.97-11.28), model for end-stage liver disease (MELD) score at referral (OR 1.06; 95% CI 1.01-1.11), and hepatitis B (OR 0.26; 95% CI 0.08-0.79) were associated with listing. CONCLUSION: MELD score and HCC were positive predictors of listing in HIV-infected patients referred for LT evaluation and, therefore, timely referrals are vital in these patients. As MELD is a predictor for death while undergoing evaluation, rapid evaluation should be performed in HIV-infected patients with a higher MELD score.
Assuntos
Doença Hepática Terminal/cirurgia , Infecções por HIV/complicações , Transplante de Fígado , Seleção de Pacientes , Listas de Espera , Adulto , Idoso , Doença Hepática Terminal/complicações , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/mortalidade , Feminino , Infecções por HIV/mortalidade , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Encaminhamento e Consulta , Estudos Retrospectivos , Índice de Gravidade de Doença , Listas de Espera/mortalidadeRESUMO
Achievement of a sustained virologic response (SVR) with antiviral therapy significantly improves graft survival in hepatitis C virus (HCV) monoinfected liver transplant (LT) patients. Risks and benefits of HCV therapy in HCV-human immunodeficiency virus (HIV) coinfected LT recipients are not well established. Among 89 HCV-HIV LT recipients in the HIVTR cohort, 39 (23% Black, 79% genotype 1, 83% fibrosis stage ≤ 1) were treated with peginterferon-a2a or a2b plus ribavirin for a median 363 days (14-1373). On intent-to-treat basis, 22% (95% CI: 10-39) and 14% (95% CI: 5-30) achieved an end-of-treatment response (EOTR) and SVR, respectively. By per-protocol analysis (completed 48 weeks of therapy ± dose reductions), 42% and 26% had EOTR and SVR, respectively. Severe adverse events occurred in 85%, with 26% hospitalized with infections and 13% developing acute rejection. Early discontinuations and dose reductions occurred in 38% and 82%, respectively, despite use of growth factors in 85%. Eighteen of 39 treated patients (46%) subsequently died/had graft loss, with 10 (26%) attributed to recurrent HCV. In conclusion, SVR rates are low and tolerability is poor in HCV-HIV coinfected transplant recipients treated with peginterferon and ribavirin. These results highlight the critical need for better tolerated and more efficacious HCV therapies for HCV-HIV coinfected transplant recipients.
Assuntos
Antivirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Transplante de Fígado/efeitos adversos , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Transplantados , Adolescente , Adulto , Idoso , Criança , DNA Viral/genética , Quimioterapia Combinada , Feminino , Seguimentos , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/mortalidade , HIV/genética , HIV/isolamento & purificação , Infecções por HIV/complicações , Infecções por HIV/mortalidade , Infecções por HIV/virologia , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/complicações , Hepatite C Crônica/mortalidade , Hepatite C Crônica/virologia , Humanos , Hepatopatias/complicações , Hepatopatias/mortalidade , Hepatopatias/cirurgia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prognóstico , Estudos Prospectivos , Proteínas Recombinantes/uso terapêutico , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Rapid allograft infection complicates liver transplantation (LT) in patients with hepatitis C virus (HCV). Pegylated interferon-α and ribavirin therapy after LT has significant toxicity and limited efficacy. The effect of a human monoclonal antibody targeting the HCV E2 glycoprotein (MBL-HCV1) on viral clearance was examined in a randomized, double-blind, placebo-controlled pilot study in patients infected with HCV genotype 1a undergoing LT. Subjects received 11 infusions of 50 mg/kg MBL-HCV1 (n=6) or placebo (n=5) intravenously with three infusions on day of transplant, a single infusion on days 1 through 7 and one infusion on day 14 after LT. MBL-HCV1 was well-tolerated and reduced viral load for a period ranging from 7 to 28 days. Median change in viral load (log10 IU/mL) from baseline was significantly greater (p=0.02) for the antibody-treated group (range -3.07 to -3.34) compared to placebo group (range -0.331 to -1.01) on days 3 through 6 posttransplant. MBL-HCV1 treatment significantly delayed median time to viral rebound compared to placebo treatment (18.7 days vs. 2.4 days, p<0.001). As with other HCV monotherapies, antibody-treated subjects had resistance-associated variants at the time of viral rebound. A combination study of MBL-HCV1 with a direct-acting antiviral is underway.
Assuntos
Anticorpos Monoclonais/farmacologia , Hepacivirus/fisiologia , Hepatite C/tratamento farmacológico , Transplante de Fígado , Idoso , Biópsia , Método Duplo-Cego , Feminino , Genótipo , Hepatite C/virologia , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , RNA Viral/análise , Fatores de Tempo , Proteínas do Envelope Viral/imunologiaRESUMO
An algorithm is presented for restoration of colour microscopic images with distortions from imperfect microscope lenses having transverse chromatic aberrations, resulting in a magnification that slightly varies with wavelengths or colours. The differential of each colour component image is computed as the difference between the component image and its slightly magnified version. The absolute values in the differential component images are generally higher at the edges where greater discontinuities occur. The two cross-correlation functions of the absolute differentials between red and green colours and between red and blue colours are then computed. The maximum in the two cross-correlation functions were sought, respectively, and the cross-correlation delays were then calculated. The two cross-correlation delays were used to determine dispersions and to realign the three colour components. Results of real microscopic images are provided. The restored image and the original are compared both visually and quantitatively in terms of the estimated entropies measured for the degree of concentrations using vector distributions.
Assuntos
Processamento de Imagem Assistida por Computador/métodos , Microscopia/métodos , Patologia/métodos , Encéfalo/patologiaRESUMO
We herein report a patient with decompensated cirrhosis secondary to autoimmune hepatitis, who presented with pneumatosis intestinalis (PI) and portal venous gas. Mesenteric ischemia has been recognized as a common and life-threatening cause of PI which portends a grave prognosis. The patient was found to have bacterascites and recovered after appropriate antibiotic therapy. Spontaneous bacterial peritonitis/bacterascites with gas-forming organisms manifesting as PI has not been previously reported.
Assuntos
Embolia Aérea/diagnóstico por imagem , Infecções por Haemophilus/diagnóstico , Haemophilus parainfluenzae/isolamento & purificação , Veias Mesentéricas/diagnóstico por imagem , Pneumatose Cistoide Intestinal/diagnóstico por imagem , Antibacterianos/uso terapêutico , Embolia Aérea/complicações , Feminino , Fibrose/complicações , Gases , Infecções por Haemophilus/tratamento farmacológico , Infecções por Haemophilus/microbiologia , Humanos , Pessoa de Meia-Idade , Pneumatose Cistoide Intestinal/etiologia , Pneumatose Cistoide Intestinal/terapia , Veia Porta/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
We describe a case of nevirapine-induced Stevens-Johnson Syndrome (SJS) and fulminant hepatic failure (FHF) requiring liver transplantation. Five weeks prior to admission, a 57-year-old female with HIV infection had been switched to a nevirapine-based regimen of highly active antiretroviral therapy (HAART) with a CD4 cell count of 695/mm(3). Examination of the explanted native liver at initial transplantation revealed massive hepatic necrosis consistent with drug-induced liver injury. Primary graft nonfunction complicated the early postoperative course and liver retransplantation was required. On follow-up 2 years later, she remains in good health with an undetectable viral load on an efavirenz-based regimen of HAART. To our knowledge, this is the first report of successful liver transplantation following SJS and FHF.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Falência Hepática Aguda/induzido quimicamente , Transplante de Fígado , Nevirapina/efeitos adversos , Síndrome de Stevens-Johnson/induzido quimicamente , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Terapia Antirretroviral de Alta Atividade/métodos , Feminino , Infecções por HIV/tratamento farmacológico , Hemofiltração , Humanos , Falência Hepática Aguda/cirurgia , Pessoa de Meia-Idade , Nevirapina/uso terapêutico , Síndrome de Stevens-Johnson/cirurgia , Resultado do TratamentoRESUMO
As substance abusers need to demonstrate abstinence prior to transplant, valid/reliable drug tests are needed. Patients may deny use, fearing surgery will be delayed. Breath, blood and urine tests have brief detection windows that allow patients to evade detection. Routine laboratory tests do not include all substances of abuse. Hair analysis overcomes these barriers, increasing the likelihood that active users will be identified. This study compared results for alcohol, opioids and cocaine based on 445 self-report, breath, urine and hair samples from 42 patients who had been denied a transplant due to recent substance abuse. Compared to hair toxicology, sensitivity for conventional drug tests was moderate for cocaine and opioids, but poor for alcohol. Of positive hair tests, only half were corroborated through other tests. In contrast, specificity was high across tests and substances, with positive findings from conventional tests confirmed through hair toxicology. Based on a 90-day detection window for hair analysis, two negative tests suggest 6 months of continuous abstinence. Hair testing should be considered as an alternative approach for monitoring substance use in the transplant population, either as a routine procedure or when the veracity of findings from conventional tests is in doubt.
Assuntos
Cabelo/química , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Adulto , Analgésicos Opioides/análise , Técnicas de Laboratório Clínico , Cocaína/análise , Cocaína/urina , Usuários de Drogas , Etanol/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Urinálise/métodosRESUMO
Quantitation of connective tissue versus parenchymal tissue compartments is important in assessment of fibrosis (scarring) and its progression in liver disease. This paper presents a two-step algorithm for quantifying fibrosis in liver biopsies stained with Sirius red. With this staining technique, collagen and cell nuclei appear similarly stained, whereas cytoplasm appears pale. The first step of the algorithm is to separate similarly stained areas occupied by collagen and hepatocyte nuclei. Since the total area of the combined collagen and cell nuclei is usually much smaller than the remaining liver parenchyma, a non-linear intensity mapping is applied to enhance the smaller cluster in order to match the larger one in both intensity and size. The second step is to differentiate the fibrotic areas usually having irregular shapes from hepatocyte nuclei that have relatively uniform size and have circular shape. The proposed algorithm has been applied to quantify the development of progressive fibrosis and its possible regression in liver biopsy specimens from patients with parenteral-induced liver injury undergoing intestinal transplantation.
Assuntos
Algoritmos , Diagnóstico por Imagem/métodos , Cirrose Hepática/patologia , Coloração e Rotulagem/métodos , Compostos Azo , Biópsia , Núcleo Celular/metabolismo , Colágeno/metabolismo , Hepatócitos/metabolismo , Humanos , Processamento de Imagem Assistida por Computador , Fígado/citologia , Fígado/patologiaRESUMO
UNLABELLED: Infrequently, hepatitis C (HCV) appears to be the cause of hepatic granulomas. Interferon therapy for HCV has been increasingly associated with the development of sarcoidosis. AIMS: We sought to determine the incidence of hepatic granulomas in patients with recurrent HCV post liver transplantation (LT). METHODS: Between 1994 and 2005, 820 patients were transplanted for HCV at our institution. The pathology database was searched for patients having recurrent HCV and granulomas. At Mount Sinai Medical Center, protocol biopsies have been performed for the last 2 years in patients receiving pegylated interferon-alpha2b and ribavirin (PEG) for recurrent HCV. Review of slides from explanted livers, pre- and post-perfusion biopsies, and all allograft biopsies were evaluated. Lipogranulomas were excluded because of their frequent association with steatosis. RESULTS: A total of 10,225 liver biopsies were performed on HCV patients, and 25 (0.24%) showed non-caseating epithelioid granulomas. Hepatic granulomas were detected in 14 post-LT HCV patients; 9 patients received PEG. Typically, only 1 lobular granuloma was found. None of these patients had granulomas in the native liver or in any biopsy before interferon therapy; 6/9 patients had undetectable HCV-RNA levels, and 4 had sustained viral response. No other cause for granuloma formation was identified in the 6 patients. CONCLUSIONS: Hepatic granulomas are infrequently found in HCV liver biopsies and rarely found in post-LT biopsies with recurrent HCV. When present, they occur more commonly in patients receiving and virologically responding to PEG therapy. The presence of granulomas in patients with HCV being treated with PEG may not warrant an extensive etiologic work-up for granulomatous hepatitis unless otherwise clinically indicated.
Assuntos
Antivirais/uso terapêutico , Granuloma/etiologia , Hepatite C/tratamento farmacológico , Interferon-alfa/uso terapêutico , Hepatopatias/etiologia , Transplante de Fígado/efeitos adversos , Adulto , Idoso , Biópsia , Feminino , Hepatite C/complicações , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Recidiva , Estudos Retrospectivos , Ribavirina/uso terapêutico , Sarcoidose/induzido quimicamenteRESUMO
BACKGROUND: Chronic kidney disease (CKD) is an important risk factor for morbidity and mortality post-liver transplantation (OLT). This study focused on investigating the incidence and risk factors associated with the development CKD after OLT. METHODS: We performed a retrospective cohort study of recipients followed at least 5 years at our institution. CKD was diagnosed and classified according to National Kidney Foundation and the Kidney Disease Outcomes Quality Initiative guidelines. RESULTS: There were 231 patients, 64% men, 67% Caucasian, 16% African-American, and 17% others, with a mean age of 56 +/- 13 years. The mean glomerular filtration rate (GFR) of the population was 56 +/- 28 mL/min/1.73 m2. CKD was defined as GFR less than 60 mL/min; 144 patients (61%) were identified as having CKD. When these patients were compared to the non-CKD group, the former were significantly older (62 +/- 9 vs 52 +/- 12 years, P = .03), more likely to be hypertensive (59% vs 38%, P = .003), and required more antihypertensive medications (0.83 +/- 0.81 vs 0.52 +/- 0.77, P = .02); 26% of all patients had diabetes. However, the incidence of diabetes (43.3% vs 19.3%, P = .02) as well as the incidence of insulin dependency (21.6% vs 12.5%, P = .001) was significantly higher in the CKD population. Mean uric acid levels were higher in CKD patients compared to non-CKD patients (8.00 +/- 2.00 mg/dL vs 6.70 +/- 1.99 mg/dL respectively, P = .001); patients with uric acid more than 6.0 had a 1.7 risk of having CKD. CONCLUSIONS: CKD defined as GFR < 60 mL/min is highly prevalent in long-term OLT survivors. Older age, elevated systolic blood pressure, insulin-dependent diabetes mellitus, and elevated uric acid levels are independently associated with CKD.
Assuntos
Falência Renal Crônica/epidemiologia , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Estudos de Coortes , Efeitos Psicossociais da Doença , Creatinina/metabolismo , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Because of a critical shortage of deceased donor (DD) livers, more extended criteria allografts are being utilized; these allografts are at increased risk for ischemia-reperfusion injury (IRI). We assessed whether, in a large cohort of patients transplanted for hepatitis C virus (HCV) either via a DD or live donor (LD), there was a relationship between the degree of IRI and the frequency and timing of acute cellular rejection (ACR) and histologic HCV recurrence. METHODS: During an 8-year study, patients were separated into four groups based on peak alanine aminotransferase (ALT) levels and three groups based on severity of IRI on postreperfusion liver biopsy. RESULTS: The mean follow-up time of 433 DD and 44 LD recipients was 1212 days. We noted a strong correlation in DD between peak ALT and the histologic degree of IRI (P = .01). There was no difference in the incidence or grade of ACR among the four groups. There was no correlation between the severity of IRI and the incidence or time to histologic recurrence of HCV. CONCLUSIONS: The magnitude of peak ALT correlated with the severity of IRI on postreperfusion liver biopsy. Among this large HCV cohort, there was no correlation between the severity of IRI and the incidence or timing of histologic HCV recurrence or incidence of ACR.
Assuntos
Rejeição de Enxerto/epidemiologia , Hepatite C/cirurgia , Transplante de Fígado , Complicações Pós-Operatórias/epidemiologia , Traumatismo por Reperfusão/complicações , Doença Aguda , Adulto , Alanina Transaminase/sangue , Humanos , Incidência , Doadores Vivos , Pessoa de Meia-Idade , Seleção de Pacientes , Complicações Pós-Operatórias/classificação , Recidiva , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Doadores de Tecidos , Transplante HomólogoRESUMO
BACKGROUND: Drug toxicity is the leading cause of acute liver failure in the United States. Further understanding of hepatotoxicity is becoming increasingly important as more drugs come to market. AIMS: (i) To provide an update on recent advances in our understanding of hepatotoxicity of select commonly used drug classes. (ii) To assess the safety of these medications in patients with pre-existing liver disease and in the post-liver transplant setting. (iii) To review relevant advances in toxicogenomics which contribute to the current understanding of hepatotoxic drugs. METHODS: A Medline search was performed to identify relevant literature using search terms including 'drug toxicity, hepatotoxicity, statins, thiazolidinediones, antibiotics, antiretroviral drugs and toxicogenomics'. RESULTS: Amoxicillin-clavulanic acid is one of the most frequently implicated causes of drug-induced liver injury worldwide. Statins rarely cause clinically significant liver injury, even in patients with underlying liver disease. Newer thiazolidinediones are not associated with the degree of liver toxicity observed with troglitazone. Careful monitoring for liver toxicity is warranted in patients who are taking antiretrovirals, especially patients who are co-infected with hepatitis B and C. Genetic polymorphisms among enzymes involved in drug metabolism and HLA types may account for some of the differences in individual susceptibility to drug hepatotoxicity. CONCLUSIONS: Drug-induced hepatotoxicity will remain a problem that carries both clinical and regulatory significance as long as new drugs continue to enter the market. Future results from ongoing multicentre collaborative efforts may help contribute to our current understanding of hepatotoxicity associated with drugs.
Assuntos
Antibacterianos/efeitos adversos , Antivirais/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Fígado/metabolismo , Tiazolidinedionas/efeitos adversos , Humanos , Hepatopatias/metabolismoRESUMO
INTRODUCTION: Controversy exists as to whether there is an increased severity or frequency of recurrent hepatitis C viral (HCV) infection in recipients of adult living donor liver transplantation (LDLT) grafts. We sought to examine the time to histological recurrence and survival in HCV (+) patients who underwent split liver transplantation (SLT), which is technically similar to what occurs in the LDLT procedure. METHODS: Twenty four HCV (+) adult recipients were identified through the UNOS database as having had SLT procedures at three centers: Mount Sinai Medical Center, University of Chicago, and University of California at Los Angeles. Of these, 17 patients with comprehensive data were matched to 32 HCV (+) patients who underwent whole deceased donor liver transplantation (DDLT) during the same time period. Outcome and time to initial HCV recurrence as documented by liver biopsy were assessed. Liver biopsy was performed when clinically indicated. RESULTS: Patients who had SLT were significantly older (P=.01). There was no difference in number of rejection episodes (P=.40). Fifteen of 17 SLT (88%) versus 24/32 DDLT (75%) patients had documented HCV recurrence by biopsy (P=.46). The time to median cumulative incidence of recurrence of HCV post-liver transplantation was 12.6 months (SLT) versus 39.8 months (DDLT) patients. There was no difference in survival between SLT and DDLT patients (47 vs 70 months, P=.62) nor in cumulative incidence of histological HCV recurrence at 1, 2, and 3 years (P=.198, .919, and .806, respectively). CONCLUSION: There is no difference in the cumulative incidence of histological recurrence of HCV post-liver transplant or in survival between recipients of deceased donor and split liver transplants.
Assuntos
Hepatite C/epidemiologia , Transplante de Fígado/fisiologia , Adulto , Cadáver , Feminino , Hepatectomia/métodos , Hepatite C/mortalidade , Humanos , Imunossupressores/uso terapêutico , Incidência , Transplante de Fígado/imunologia , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Doadores de Tecidos , Coleta de Tecidos e Órgãos/métodosRESUMO
BACKGROUND: Non-alcoholic steatohepatitis (NASH) and resultant liver fibrosis is a major health problem without approved pharmacotherapy. Pre-clinical results of GR-MD-02, a galectin-3 inhibitor, suggested potential efficacy in NASH with advanced fibrosis/cirrhosis and prompted initiation of a clinical development programme in NASH with advanced fibrosis. AIM: To evaluate the safety, pharmacokinetics and exploratory pharmacodynamic markers of GR-MD-02 in subjects having NASH with bridging fibrosis. METHODS: The GT-020 study was a first-in-human, sequential dose-ranging, placebo controlled, double-blinded study with the primary objective to assess the safety, tolerability and dose limiting toxicity of GR-MD-02, in subjects with biopsy-proven NASH with advanced fibrosis (Brunt stage 3). The secondary objectives were to characterise first-dose and multiple-dose pharmacokinetic profiles and to evaluate changes in potential serum biomarkers and liver stiffness as assessed by FibroScan. RESULTS: GR-MD-02 single and three weekly repeated of 2, 4 and 8 mg/kg revealed no meaningful clinical differences in treatment emergent adverse events, vital signs, electrocardiographic findings or laboratory tests. Pharmokinetic parameters showed a dose-dependent relationship with evidence of drug accumulation following 8 mg/kg (~twofold). CONCLUSIONS: GR-MD-02 doses were in the upper range of the targeted therapeutic dose determined from pre-clinical data and were safe and well tolerated with evidence of a pharmacodynamic effect. These results provide support for a Phase 2 development programme in advanced fibrosis due to NASH.