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1.
Liver Transpl ; 30(4): 421-430, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38240612

RESUMO

The term "futility" in liver transplantation is used inappropriately and inaccurately, as it is frequently applied to patient populations with suboptimal outcomes that are often not truly "futile." The term "futile" is used interchangeably with poor outcomes. Not all poor outcomes fulfill a definition of futility when considering all viewpoints. Definitions of "futility" are variable throughout the medical literature. We review futility in the context of liver transplantation, encompassing various viewpoints, with a goal to propose focused outcome definitions, including futility, that encompass broader viewpoints, and improve the utilization of "futility" to truly futile situations, and improve communication between providers and patients/families. Focused, appropriate definitions will help the transplant community develop better models to more accurately predict and avoid futile transplants, and better predict an individual patient's posttransplant outcome.


Assuntos
Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Futilidade Médica
2.
Liver Transpl ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38535627

RESUMO

Sleep disturbances are common in chronic liver disease and significantly impact patient outcomes and quality of life. The severity and nature of sleep disturbances vary by liver disease etiology and severity. While there is ongoing research into the association between liver disease and sleep-wake dysfunction, the underlying pathophysiology varies and, in many cases, is poorly understood. Liver disease is associated with alterations in thermoregulation, inflammation, and physical activity, and is associated with disease-specific complications, such as HE, that may directly affect sleep. In this article, we review the relevant pathophysiologic processes, disease-specific sleep-wake disturbances, and clinical management of CLD-associated sleep-wake disturbances.

3.
Hepatology ; 2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37725761

RESUMO

Obesity is highly prevalent in hepatology clinics and has a significant impact on chronic liver disease and patient management. Hepatologists and gastroenterologists need to be actively engaged in the management of obesity. This review provides a detailed approach to this challenging comorbidity.

4.
Hepatology ; 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38088872

RESUMO

Occurrence of metabolic dysfunction-associated steatotic liver disease (MASLD) is common following liver transplantation (LT). MASLD can be classified as a recurrent disease when it occurs in patients receiving LT for metabolic dysfunction-associated steatohepatitis (MASH) or as de novo when it occurs in patients undergoing transplantation for non-metabolic dysfunction-associated steatohepatitis etiologies of liver disease. Fibrosis progression in patients with MASLD is accelerated, with progression to cirrhosis occurring more rapidly compared with the general (ie, non-LT) population. Moreover, the metabolic burden in LT recipients with MASLD is high and synergizes with liver disease to negatively affect the clinical course. Despite the oversized clinical burden of MASLD among LT recipients, there is currently a lack of regulatory approach and pathway for therapeutics development in this patient population. The present document, thus, provides guidance for therapeutics development that incorporates nuances of transplant care in patients with post-LT MASLD to facilitate drug development.

5.
Clin Transplant ; 38(7): e15389, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38952185

RESUMO

INTRODUCTION: Hepatitis B virus reactivation (HBVr) can occur in solid organ transplant (SOT) recipients with previously inactive hepatitis B virus (HBV) infection. Previous studies have reported that HBVr is generally less than 10% in nonliver SOT recipients with past HBV infection. METHODS: We conducted a retrospective study from January 2018 to August 2023 at Mayo Clinic sites in Arizona, Florida, and Minnesota. We examined the antiviral prophylaxis strategy used and the characteristics of HBVr in hepatitis B core antibody-positive (HBcAb +) nonliver SOT adult recipients. Past HBV infection was defined as HBcAb + / hepatitis B surface antigen (HBsAg) -. Chronic HBV infection was defined as HBcAb + / HBsAg +. RESULTS: A total of 180 nonliver SOT recipients were identified during the study period. Indefinite antiviral prophylaxis was utilized in 77 recipients, and none developed HBVr after transplantation. In 103 recipients without antiviral prophylaxis, the incidence of HBVr was 12% (12/97) and 33% (2/6) in those with past HBV infection and chronic HBV infection. The incidence of HBVr in patients with past HBV infection is 16% (8/50), 15% (3/20), and 5% (1/22) in kidney, heart, and lungs, respectively. HBVr was more frequent in those who received alemtuzumab. Among 14 recipients with HBVr, none had HBV-associated liver failure or death. CONCLUSIONS: Our study observed a higher rate of HBVr (12%) in nonliver SOT recipients with past HBV infection compared to the previous studies. Further studies are needed to identify predictors of HBVr in nonliver SOT recipients and optimize antiviral prophylaxis guidance.


Assuntos
Antivirais , Vírus da Hepatite B , Hepatite B , Transplante de Órgãos , Ativação Viral , Humanos , Estudos Retrospectivos , Masculino , Feminino , Vírus da Hepatite B/isolamento & purificação , Incidência , Pessoa de Meia-Idade , Transplante de Órgãos/efeitos adversos , Hepatite B/virologia , Hepatite B/epidemiologia , Seguimentos , Fatores de Risco , Antivirais/uso terapêutico , Prognóstico , Adulto , Medição de Risco , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/virologia , Idoso
6.
Clin Transplant ; 38(2): e15263, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38375953

RESUMO

Liver transplantation (LT) with hepatitis B core antibody (anti-HBc) positive grafts to hepatitis B surface-antigen (HBsAg) negative recipients is safe and has likely contributed to improvements in organ access over the years. The incidence of de novo hepatitis B infection (HBV) in these instances is low with appropriate prophylaxis and is affected by recipient immunologic status. There is debate as to whether hepatitis B surface antibody (anti-HBs) positivity may safely inform prophylaxis discontinuation post-LT. In this retrospective study of all hepatitis B surface antigen (HBsAg) negative recipients of anti-HBc positive organs at three large academic centers between January 2014 and December 2019, nine LT recipients discontinued prophylaxis after developing anti-HBs antibodies 1 year or later post-LT. Three of the nine patients (33%) developed de novo HBV, defined by positive HBsAg or hepatitis B virus (HBV) DNA, during the study period. The remaining six patients had no evidence of HBV infection after a mean follow-up of 37 months. The patients without de novo HBV had higher anti-HBs titers at the time of prophylaxis discontinuation and were less likely to have negative anti-HBs at the time of transplant or negative anti-HBc at any time point. These results suggest that quantitative anti-HBs titer thresholds rather than qualitative anti-HBs positivity at 1 year or later after LT should be used to identify patients at decreased risk of de novo infection and help guide prophylaxis duration.


Assuntos
Hepatite B , Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Antígenos de Superfície da Hepatite B , Estudos Retrospectivos , Antivirais/uso terapêutico , Antígenos do Núcleo do Vírus da Hepatite B , Hepatite B/etiologia , Vírus da Hepatite B , Anticorpos Anti-Hepatite B
7.
J Hepatol ; 78(6): 1089-1104, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37208096

RESUMO

Liver transplant(ation) (LT) is the most effective treatment for patients with decompensated liver disease. The increasing prevalence of obesity and type 2 diabetes and the growing number of patients with non-alcoholic fatty liver disease being evaluated for LT, have resulted in a greater proportion of LT candidates presenting with a higher risk of cardiovascular disease. As cardiovascular disease is a major cause of morbidity and mortality after LT, a thorough cardiovascular evaluation pre-LT is crucial. In this review, we discuss the latest evidence on the cardiovascular evaluation of LT candidates and we focus on the most prevalent conditions, namely ischaemic heart disease, atrial fibrillation and other arrhythmias, valvular heart disease, and cardiomyopathies. LT candidates undergo an electrocardiogram, a resting transthoracic echocardiography and an assessment of their cardiopulmonary functional ability as part of their standardised pre-LT work-up. Further diagnostic work-up is undertaken based on the results of the baseline evaluation and may include a coronary computed tomography angiography in patients with cardiovascular risk factors. The evaluation of potential LT candidates for cardiovascular disease requires a multidisciplinary approach, with input from anaesthetists, cardiologists, hepatologists and transplant surgeons.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Humanos , Doenças Cardiovasculares/epidemiologia , Fatores de Risco , Diabetes Mellitus Tipo 2/epidemiologia , Comorbidade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia
8.
Clin Gastroenterol Hepatol ; 21(2): 445-455.e2, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35189388

RESUMO

BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) is the leading indication for liver transplant (LT) in women and the elderly. Granular details into factors impacting survival in this population are needed to optimize management and improve outcomes. METHODS: Patients receiving LT for NASH cirrhosis from 1997 to 2017 across 7 transplant centers (NailNASH consortium) were analyzed. The primary outcome was all-cause mortality, and causes of death were enumerated. All outcomes were cross referenced with United Network for Organ Sharing and adjudicated at each individual center. Cox regression models were constructed to elucidate clinical factors impacting mortality. RESULTS: Nine hundred thirty-eight patients with a median follow-up of 3.8 years (interquartile range, 1.60-7.05 years) were included. The 1-, 3-, 5-, 10-, and 15-year survival of the cohort was 93%, 88%, 83%, 69%, and 46%, respectively. Of 195 deaths in the cohort, the most common causes were infection (19%), cardiovascular disease (18%), cancer (17%), and liver-related (11%). Inferior survival was noted in patients >65 years. On multivariable analysis, age >65 (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.04-2.77; P = .04), end-stage renal disease (HR, 1.55; 95% CI, 1.04-2.31; P = .03), black race (HR, 5.25; 95% CI, 2.12-12.96; P = .0003), and non-calcineurin inhibitors-based regimens (HR, 2.05; 95% CI, 1.19-3.51; P = .009) were associated with increased mortality. Statin use after LT favorably impacted survival (HR, 0.38; 95% CI, 0.19-0.75; P = .005). CONCLUSIONS: Despite excellent long-term survival, patients transplanted for NASH at >65 years or with type 2 diabetes mellitus at transplant had higher mortality. Statin use after transplant attenuated risk and was associated with improved survival across all subgroups, suggesting that careful patient selection and implementation of protocol-based management of metabolic comorbidities may further improve clinical outcomes.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores de Hidroximetilglutaril-CoA Redutases , Hepatopatia Gordurosa não Alcoólica , Humanos , Feminino , Idoso , Hepatopatia Gordurosa não Alcoólica/complicações , Fatores de Risco , Diabetes Mellitus Tipo 2/complicações , Resultado do Tratamento , Estudos Retrospectivos , Cirrose Hepática/complicações
9.
Clin Transplant ; 37(10): e15050, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37329298

RESUMO

BACKGROUND: Liver transplant (LT) recipients with untreated hepatitis C (HCV) are at risk for cirrhosis graft failure. The advent of direct acting antiviral agents (DAA) has improved outcomes in HCV. AIMS: We aim to examine liver transplant outcomes and allograft fibrosis development/progression after sustained virologic response (SVR). METHODS: We performed a retrospective cohort study of 226 consecutive liver transplant recipients with HCV from 2007 to 2018. The cohort was split into transplants pre (Group A) and post (Group B) 2014 to reflect the introduction of DAAs. Fibrosis was monitored with liver biopsy and non-invasive imaging. RESULTS: Group B had significantly improved HCV treatment rates and earlier SVR compared to Group A, with a cumulative incidence rate of SVR at 2 years of 86.7% versus 15.4% (HR = .11, p < .001). Prior to achieving SVR, Group A demonstrated worsening of fibrosis stage per year (+.21, p < .001) whereas Group B showed minimal change on protocol annual biopsy (-.02, p = .80). After SVR, most patients were followed non-invasively and demonstrated stable or improved fibrosis stage over time. Patients undergoing transient elastography showed regression in fibrosis stage per year (-.19, p < .001). CONCLUSION: HCV patients undergoing LT after 2014 had higher rates of SVR and improved clinically relevant transplant outcomes, namely less graft loss and death relating to HCV. Fibrosis progression halted or improved after SVR in both cohorts, suggesting that LT recipients with SVR do not require fibrosis monitoring even with established fibrosis prior to SVR.


Assuntos
Hepatite C Crônica , Hepatite C , Transplante de Fígado , Humanos , Antivirais/uso terapêutico , Transplante de Fígado/efeitos adversos , Resposta Viral Sustentada , Estudos Retrospectivos , Hepatite C Crônica/tratamento farmacológico , Hepatite C/tratamento farmacológico , Cirrose Hepática/patologia , Hepacivirus
10.
BMC Med ; 20(1): 429, 2022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-36348343

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) can lead to pulmonary dysfunction that is associated with pulmonary inflammation. Moreover, little is known regarding the therapeutic role of exercise training on pulmonary pathophysiology in NAFLD. The present study aimed to investigate the effect of exercise training on high-fat high-carbohydrate (HFHC)-induced pulmonary dysfunction in C57BL/6 mice. METHODS: Male C57BL/6 mice (N = 40) were fed a standard Chow (n = 20) or an HFHC (n = 20) diet for 15 weeks. After 8 weeks of dietary treatment, they were further assigned to 4 subgroups for the remaining 7 weeks: Chow (n = 10), Chow plus exercise (Chow+EX, n = 10), HFHC (n = 10), or HFHC plus exercise (HFHC+EX, n = 10). Both Chow+EX and HFHC+EX mice were subjected to treadmill running. RESULTS: Chronic exposure to the HFHC diet resulted in obesity with hepatic steatosis, impaired glucose tolerance, and elevated liver enzymes. The HFHC significantly increased fibrotic area (p < 0.001), increased the mRNA expression of TNF-α (4.1-fold, p < 0.001), IL-1ß (5.0-fold, p < 0.001), col1a1 (8.1-fold, p < 0.001), and Timp1 (6.0-fold, p < 0.001) in the lung tissue. In addition, the HFHC significantly altered mitochondrial function (p < 0.05) along with decreased Mfn1 protein levels (1.8-fold, p < 0.01) and increased Fis1 protein levels (1.9-fold, p < 0.001). However, aerobic exercise training significantly attenuated these pathophysiologies in the lungs in terms of ameliorating inflammatory and fibrogenic effects by enhancing mitochondrial function in lung tissue (p < 0.001). CONCLUSIONS: The current findings suggest that exercise training has a beneficial effect against pulmonary abnormalities in HFHC-induced NAFLD through improved mitochondrial function.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Pneumonia , Camundongos , Masculino , Animais , Hepatopatia Gordurosa não Alcoólica/terapia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Modelos Animais de Doenças , Carboidratos/farmacologia , Mitocôndrias/metabolismo
11.
Liver Transpl ; 28(8): 1367-1375, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35289056

RESUMO

Liver transplantation (LT) is the definitive treatment for end-stage liver disease. Unfortunately, women are disadvantaged at every stage of the LT process. We conducted a literature review to increase the understanding of this disparity. Hormonal differences, psychological factors, and Model for End-Stage Liver Disease (MELD) score inequalities are some pretransplantation factors that contribute to this disparity. In the posttransplantation setting, women have differing risk than men in most major outcomes (perioperative complications, rejection, long-term renal dysfunction, and malignancy) and assessing the two groups together is disadvantageous. Herein, we propose interventions including standardized criteria for LT referral, using an alternate MELD, education for support of women, and motivating women to seek living donors. Understanding sex-based differences will allow us to improve access, tailor management, and improve overall outcomes for all patients, particularly women.


Assuntos
Doença Hepática Terminal , Transplante de Fígado , Doença Hepática Terminal/etiologia , Feminino , Humanos , Transplante de Fígado/efeitos adversos , Doadores Vivos , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença
12.
Hepatology ; 74(2): 1003-1013, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33544906

RESUMO

BACKGROUND AND AIMS: Gastrointestinal (GI) malignancies are common after liver transplantation. The aim of this study was to identify the risk and timing of the more common GI malignancies, colorectal and pancreatic cancer, to aid in optimizing potential posttransplant screening practices. APPROACH AND RESULTS: Data from the United Network for Organ Sharing database of all adult liver-transplant recipients from 1997 to 2017 were analyzed and a comparison made with cancer incidence from general population data using Surveillance, Epidemiology, and End Results data. Of 866 de novo GI malignancies, 405 colorectal and 216 pancreas were identified. The highest cumulative incidence for colorectal cancer occurred in recipients with primary sclerosing cholangitis (PSC), recipients over the age of 50 with non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC)/cholangiocarcinoma (CCA), and females >50 years with alcohol-associated liver disease and HCC/CCA, with risk increasing above the general population within 5 years of transplant. Patients with PSC and HCC/CCA or NASH and HCC/CCA have the highest cumulative incidence of pancreatic cancer also rising within 5 years following transplant, with those patients >50 years old conferring the highest risk. CONCLUSIONS: These data identify a high-risk cohort that warrants consideration for intensified individualized screening practices for colorectal cancer after liver transplantation. In addition to recipients with PSC, further study of recipients with NASH and HCC/CCA and females with alcohol-associated liver disease and HCC/CCA may be better tailored to colorectal cancer screening ideals. Higher-risk patient populations for pancreatic cancer (PSC and NASH with HCC/CCA) would benefit from further study to determine potential screening practices. GI malignancies occur at higher rates in liver-transplant patients compared with the general population. In the era of individualized medicine, this study identifies the highest-risk transplant recipients (PSC and NASH cirrhosis with coexisting HCC/CCA) who may benefit from altered screening practices for these malignancies.


Assuntos
Neoplasias Colorretais/epidemiologia , Doença Hepática Terminal/cirurgia , Transplante de Fígado/efeitos adversos , Neoplasias Pancreáticas/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Adulto , Fatores Etários , Idoso , Neoplasias dos Ductos Biliares/epidemiologia , Neoplasias dos Ductos Biliares/patologia , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/patologia , Colangiocarcinoma/epidemiologia , Colangiocarcinoma/patologia , Colangite Esclerosante/epidemiologia , Colangite Esclerosante/patologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/prevenção & controle , Detecção Precoce de Câncer/normas , Doença Hepática Terminal/etiologia , Feminino , Humanos , Incidência , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/prevenção & controle , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Programa de SEER/estatística & dados numéricos , Transplantados/estatística & dados numéricos
13.
Hepatology ; 73(5): 2051-2062, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33047343

RESUMO

BACKGROUND AND AIMS: Thirty percent of patients with cirrhosis are obese and the prevalence of obesity increases after transplant to >40% post-transplant. There are currently four weight loss medications approved by the FDA for treatment of obesity (orlistat, phentermine-topiramate, naltrexone-bupropion, and liraglutide). The aim of this review was to investigate the data on the use of these weight loss medications and alternative medicines in patients with cirrhosis and in liver transplant recipients (LTRs). APPROACH AND RESULTS: While there is paucity of data for these medications in patients with cirrhosis and LTRs, Liraglutide appears to be generally safe in view of its pharmacokinetic properties. Phentermine-topiramate seems to have the highest weight loss potential but special consideration should be given to neuropsychiatric disorders, cardiovascular comorbidities, and drug interactions. There are emerging data on use of alternative medicines for weight loss but more data are needed. CONCLUSIONS: The use of weight loss medications is feasible in this patient population but the decision of which medication to prescribe should be individualized based on the degree of renal and hepatic impairment, other co-morbidities, and concomitant medications.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Cirrose Hepática/complicações , Transplante de Fígado/efeitos adversos , Obesidade/complicações , Bupropiona/administração & dosagem , Bupropiona/efeitos adversos , Bupropiona/uso terapêutico , Quimioterapia Combinada , Humanos , Liraglutida/efeitos adversos , Liraglutida/uso terapêutico , Transplante de Fígado/métodos , Naltrexona/administração & dosagem , Naltrexona/efeitos adversos , Naltrexona/uso terapêutico , Obesidade/tratamento farmacológico , Orlistate/efeitos adversos , Orlistate/uso terapêutico , Fentermina/administração & dosagem , Fentermina/efeitos adversos , Fentermina/uso terapêutico , Topiramato/administração & dosagem , Topiramato/efeitos adversos , Topiramato/uso terapêutico , Ciência Translacional Biomédica
14.
Hepatology ; 73(2): 571-585, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32246544

RESUMO

BACKGROUND AND AIMS: Alcoholic hepatitis (AH) is diagnosed by clinical criteria, although several objective scores facilitate risk stratification. Extracellular vesicles (EVs) have emerged as biomarkers for many diseases and are also implicated in the pathogenesis of AH. Therefore, we investigated whether plasma EV concentration and sphingolipid cargo could serve as diagnostic biomarkers for AH and inform prognosis to permit dynamic risk profiling of AH subjects. APPROACH AND RESULTS: EVs were isolated and quantified from plasma samples from healthy controls, heavy drinkers, and subjects with end-stage liver disease (ESLD) attributed to cholestatic liver diseases and nonalcoholic steatohepatitis, decompensated alcohol-associated cirrhosis (AC), and AH. Sphingolipids were quantified by tandem mass spectroscopy. The median plasma EV concentration was significantly higher in AH subjects (5.38 × 1011 /mL) compared to healthy controls (4.38 × 1010 /mL; P < 0.0001), heavy drinkers (1.28 × 1011 /mL; P < 0.0001), ESLD (5.35 × 1010 /mL; P < 0.0001), and decompensated AC (9.2 × 1010 /mL; P < 0.0001) disease controls. Among AH subjects, EV concentration correlated with Model for End-Stage Liver Disease score. When EV counts were dichotomized at the median, survival probability for AH subjects at 90 days was 63.0% in the high-EV group and 90.0% in the low-EV group (log-rank P value = 0.015). Interestingly, EV sphingolipid cargo was significantly enriched in AH when compared to healthy controls, heavy drinkers, ESLD, and decompensated AC (P = 0.0001). Multiple sphingolipids demonstrated good diagnostic and prognostic performance as biomarkers for AH. CONCLUSIONS: Circulating EV concentration and sphingolipid cargo signature can be used in the diagnosis and differentiation of AH from heavy drinkers, decompensated AC, and other etiologies of ESLD and predict 90-day survival permitting dynamic risk profiling.


Assuntos
Alcoolismo/diagnóstico , Doença Hepática Terminal/diagnóstico , Hepatite Alcoólica/diagnóstico , Cirrose Hepática/diagnóstico , Esfingolipídeos/sangue , Adulto , Idoso , Alcoolismo/sangue , Alcoolismo/complicações , Biomarcadores/sangue , Biópsia , Estudos de Casos e Controles , Diagnóstico Diferencial , Doença Hepática Terminal/sangue , Vesículas Extracelulares , Feminino , Hepatite Alcoólica/sangue , Hepatite Alcoólica/epidemiologia , Hepatite Alcoólica/patologia , Humanos , Fígado/patologia , Cirrose Hepática/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco/métodos , Índice de Gravidade de Doença
15.
Clin Transplant ; 36(8): e14714, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35594161

RESUMO

BACKGROUND AND AIMS: Nonalcoholic steatohepatitis (NASH) is associated with metabolic conditions that increase the risk of de novo malignancy following transplant. Patients often have more than one underlying liver disease, which could change the risk of de novo malignancy. This study assessed the incidence of NASH overlap and its effect on de novo malignancy in liver transplant recipients. METHODS: Data was analyzed from the United Network for Organ Sharing database for all liver transplant recipients from 1997 to 2017 for NASH alone or in combination with another liver disease. RESULTS: There is an increasing prevalence of NASH overlap. Of the 98,679 patients included in the analysis, 1238 had a de novo malignancy identified (7.4% by 5 years post-transplant). The cumulative incidence of de novo malignancy increases in primary sclerosing cholangitis (PSC)/NASH overlap after 5 years and was increased in alcohol-related liver disease (ALD)/NASH through 10 years compared to ether disease alone. NASH overlaps with "other" diseases experience a cumulative incidence similar to NASH and not the "other" disease. An increased risk of de novo solid organ malignancy was associated with older age, male gender, previous malignancy, and multiorgan transplant. CONCLUSION: The prevalence of liver transplant recipients with NASH overlap is increasing. These patients may experience different long-term outcomes than patients with either diagnosis alone. De novo malignancy risk can be influenced by multiple factors and metabolic comorbidities. Further study of patients with overlap diagnoses is important moving forward to guide individualized care and cancer screening programs.


Assuntos
Transplante de Fígado , Neoplasias , Hepatopatia Gordurosa não Alcoólica , Humanos , Incidência , Transplante de Fígado/efeitos adversos , Masculino , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/etiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Fatores de Risco , Transplantados
16.
Clin Transplant ; 36(2): e14538, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34787329

RESUMO

BACKGROUND: Hypertrophic cardiomyopathy (HCM) presents with a hypertrophied left ventricle (LV). It is often associated with LV outflow tract obstruction (LVOTO) and a risk for sudden death. This study aimed to describe outcomes of patients with HCM who underwent liver transplant (LT). METHODS: A retrospective review was conducted for patients diagnosed with HCM undergoing LT. Patient characteristics, preoperative echocardiography results, HCM risk of sudden cardiac death prediction model score, and 5-year mortality were examined. A univariable Cox proportional hazards model was used to evaluate the association between risk factors and 5-year mortality. All tests were two-sided with the alpha level set at .05. RESULTS: Twenty-nine patients were included in the analysis. Six patients (21%) had a perioperative cardiopulmonary complication. The 5-year survival rate was 61% (95% CI, 45-82). The analyzed risk factors showed that 5-year post-LT survival was significantly predicted by maximal LV outflow tract gradient at rest > 60 mmHg (hazard ratio, 1.04 [95% CI, 1.01-1.06]). CONCLUSIONS: Preoperative LV outflow tract resting gradient > 60 mmHg was associated with 5-year post-LT mortality. The results suggest the severity of LVOTO identified by echocardiography is a prognostic tool for patients with HCM after LT.


Assuntos
Cardiomiopatia Hipertrófica , Transplante de Fígado , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/cirurgia , Morte Súbita Cardíaca/etiologia , Ecocardiografia , Humanos , Transplante de Fígado/efeitos adversos , Prognóstico , Estudos Retrospectivos
17.
Transpl Infect Dis ; 24(4): e13843, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35596686

RESUMO

Graft-versus-hostdisease (GVHD) following liver transplantation (LT) is rare but can lead tosignificant mortality. The leading cause of death following GVHD diagnosis isinfectious complications. However, there is a lack of clear descriptions concerning infection and antimicrobial management patterns. Our study aims toprovide the focused details of all infectious complications of acute GVHDfollowing LT. We retrospectively reviewed all adult LT recipients with acute GVHD at Mayo Clinic's Transplant Centers from January 1, 2010, to December 31, 2021. Detailed characteristics of infection in each case were described. Among 4,585 LTs performed during this period, 12 (0.3%) patients developed acuteGVHD. The median time from transplantation to GVHD diagnosis was 49.0 days [IQR 31.5-99.0]. Ten (83.3%) patients developed severe infections leading tomortality. The most common cause of infection was nosocomial bacteremia fromenteric bacteria such as vancomycin-resistant enterococci and gram-negative bacilli. Other infections included breakthrough invasive fungal infections,cytomegalovirus (CMV) reactivation, and Clostridioides difficile colitis. Antimicrobial prophylaxis strategies in most cases were based on the degree of neutropenia-these include levofloxacin for bacterial prophylaxis, nebulized pentamidine for Pneumocystis jiroveci pneumonia prophylaxis, posaconazole for invasive fungal prophylaxis, and valganciclovir based on CMVstatus. All GVHD patients with severe infections succumbed to thesecomplications. Ourstudy reiterates that despite prophylaxis, infectious complications in GVHDfollowing LT are common and lead to exceptionally high mortality. Individualizedantimicrobial treatment, prophylaxis and monitoring strategies remain a criticalcomponent of GVHD management. Further study to optimize these practices isrequired.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante de Fígado , Pneumonia por Pneumocystis , Doença Aguda , Adulto , Antibacterianos/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Transplante de Fígado/efeitos adversos , Pneumonia por Pneumocystis/tratamento farmacológico , Estudos Retrospectivos , Valganciclovir/uso terapêutico
18.
Semin Liver Dis ; 41(4): 448-460, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34243194

RESUMO

The burden of obesity and metabolic syndrome has determined a sharp increase in bariatric surgery (BS) procedures, which lead to marked weight loss, improved metabolic syndrome, reduced cardiovascular risk, and even improvement in nonalcoholic steatohepatitis (NASH). Despite these promising results, BS in patients with chronic liver disease can rarely lead to worsening of liver function, progression to cirrhosis and its complications, and even liver transplantation. On the other hand, since obesity in patients with cirrhosis is a major cofactor for progression to a decompensated stage of the disease and a risk factor for hepatocellular carcinoma, BS has been used to achieve weight loss in this population. In this review, we critically analyze the existing data on outcomes of BS in patients with cirrhosis and the possible mechanisms leading to fibrosis progression and worsening liver function in patients undergoing BS. Finally, we propose a set of measures that could be taken to improve the multidisciplinary management of liver disease in patients undergoing BS, including early recognition of malnutrition and alcohol misuse.


Assuntos
Cirurgia Bariátrica , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Cirurgia Bariátrica/efeitos adversos , Humanos , Fígado/patologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/patologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/patologia , Recompensa
19.
Am J Transplant ; 21(8): 2890-2894, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33792185

RESUMO

Current guidelines recommend deferring liver transplantation (LT) in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection until clinical improvement occurs and two PCR tests collected at least 24 hours apart are negative. We report a case of an 18-year-old, previously healthy African-American woman diagnosed with COVID-19, who presents with acute liver failure (ALF) requiring urgent LT in the context of SARS-CoV-2 polymerase chain reaction (PCR) positivity. The patient was thought to have acute Wilsonian crisis on the basis of hemolytic anemia, alkaline phosphatase:bilirubin ratio <4, AST:ALT ratio >2.2, elevated serum copper, and low uric acid, although an unusual presentation of COVID-19 causing ALF could not be excluded. After meeting criteria for status 1a listing, the patient underwent successful LT, despite ongoing SARS-CoV-2 PCR positivity. Remdesivir was given immediately posttransplant, and mycophenolate mofetil was withheld initially and the SARS-CoV-2 PCR test eventually became negative. Three months following transplantation, the patient has made a near-complete recovery. This case highlights that COVID-19 with SARS-CoV-2 PCR positivity may not be an absolute contraindication for transplantation in ALF. Criteria for patient selection and timing of LT amid the COVID-19 pandemic need to be validated in future studies.


Assuntos
COVID-19 , Falência Hepática Aguda , Transplante de Fígado , Adolescente , Feminino , Humanos , Falência Hepática Aguda/etiologia , Falência Hepática Aguda/cirurgia , Transplante de Fígado/efeitos adversos , Pandemias , Reação em Cadeia da Polimerase , SARS-CoV-2
20.
Am J Transplant ; 21(2): 460-474, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32969590

RESUMO

Patients undergoing evaluation for solid organ transplantation (SOT) often have a history of malignancy. Although the cancer has been treated in these patients, the benefits of transplantation need to be balanced against the risk of tumor recurrence, especially in the setting of immunosuppression. Prior guidelines of when to transplant patients with a prior treated malignancy do not take in to account current staging, disease biology, or advances in cancer treatments. To develop contemporary recommendations, the American Society of Transplantation held a consensus workshop to perform a comprehensive review of current literature regarding cancer therapies, cancer stage-specific prognosis, the kinetics of cancer recurrence, and the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis based on contemporary treatment and transplant recommendations for breast, colorectal, anal, urological, gynecological, and nonsmall cell lung cancers. This conference and consensus documents aim to provide recommendations to assist in the evaluation of patients for SOT given a history of a pretransplant malignancy.


Assuntos
Prova Pericial , Transplante de Órgãos , Consenso , Humanos , Recidiva Local de Neoplasia , Prognóstico
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