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BACKGROUND AND AIMS: Most patients with decompensated cirrhosis fail to meet their nutrition targets. The impact of nasogastric feeding (NGF) on malnutrition in cirrhosis remains unknown. This study aims to assess the impact of pretransplant NGF on pre-liver transplant and post-liver transplant outcomes. APPROACH AND RESULTS: This single-center, prospective randomized controlled trial of 55 patients with severe malnutrition and low handgrip strength (HGS) compared a standard high-energy high-protein diet to diet plus supplemental nocturnal NGF while awaiting transplant. The primary outcome was a change in HGS. The median age was 58.5 years (IQR: 51.1-64), median MELD was 24 (20-28.5), and 32 (58%) patients were male. The median duration of NGF was 63.0 days (34.5-127), following which time the median between-group difference in HGS was 3.6 kg (95% CI: 1.7-5.2, p <0.001), an increase of 20% from baseline. Mid-upper-arm circumference, triceps skinfold, and immune function all increased significantly with NGF. Muscle and nutritional parameters continued to improve with increasing duration of feeding. NGF significantly increased daily energy intake between groups by 1285 kcal (95% CI: 860-1677) and protein intake by 51 g (95% CI: 32-71) (both p <0.001). All NGF patients met >100% of their measured nutritional requirements. Posttransplant clinical outcomes were similar between groups. CONCLUSIONS: Targeted enteral feeding before liver transplant improves HGS, anthropometry, and immune function in severely malnourished patients with cirrhosis. These findings provide a strong rationale for early consideration of NGF to reverse malnutrition and improve muscle strength. Appropriately powered studies should explore whether NGF can also impact clinically relevant outcomes including pretransplant and posttransplant mortality.
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BACKGROUND AND AIMS: Observational studies suggest a beneficial effect of continuous terlipressin infusion (CTI) on ascites and sarcopenia in decompensated cirrhosis with portal hypertension. APPROACH AND RESULTS: This single-center, prospective, cross-over study randomized 30 patients with cirrhosis, ascites, and sarcopenia to commence on 12 weeks of home CTI or 12 weeks of observation prior to cross-over. The co-primary outcomes were change in handgrip strength and paracentesis volume. Secondary outcomes included quality of life, sarcopenia measures, renal function, safety, and hospitalization. The median age of participants was 62 years (IQR: 57-64), the median Model for End-Stage Liver Disease-Sodium was 16 (12.3-20.8), and 22 (73%) were male. Handgrip strength increased by a mean adjusted difference (MAD) of 3.09 kg (95% CI: 1.11-5.08 kg) between CTI and observation ( p =0.006); an 11.8% increase from baseline. The total volume of ascites drained decreased by a MAD of 11.39L (2.99-19.85, p =0.01), with 1.75 fewer episodes of paracentesis (0.925-2.59, p <0.001) on CTI. Serum creatinine decreased, urinary sodium excretion increased, and quality of life was significantly higher on CTI (all p <0.001), with an increase in Chronic Liver Disease Questionnaire score of 0.41 points (0.23-0.59). There were 7 minor line-related complications but no cardiac events or pulmonary edema. CONCLUSIONS: This novel study demonstrates a significant increase in handgrip strength, reduction in paracentesis volume, and improved quality of life in patients with decompensated cirrhosis treated with continuous terlipressin infusion. These findings provide a strong rationale for the use of ambulatory CTI in appropriately selected patients with cirrhosis.
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Computed tomography coronary angiography (CTCA) is increasingly utilized for preoperative risk stratification before liver transplantation (LT). We sought to assess the predictors of advanced atherosclerosis on CTCA using the recently developed Coronary Artery Disease-Reporting and Data System (CAD-RADS) score and its impact on the prediction of long-term major adverse cardiovascular events (MACE) following LT. We conducted a retrospective cohort study of consecutive patients who underwent CTCA for LT work-up between 2011 and 2018. Advanced atherosclerosis was defined as coronary artery calcium scores > 400 or CAD-RADS score ≥ 3 (≥50% coronary artery stenosis). MACE was defined as myocardial infarction, heart failure, stroke, or resuscitated cardiac arrest. Overall, 229 patients underwent CTCA (mean age 66 ± 5 y, 82% male). Of these, 157 (68.5%) proceeded with LT. The leading etiology of cirrhosis was hepatitis (47%), and 53% of patients had diabetes before transplant. On adjusted analysis, male sex (OR 4.6, 95% CI 1.5-13.8, p = 0.006), diabetes (OR 2.2, 95% CI 1.2-4.2, p = 0.01) and dyslipidemia (OR 3.1, 95% CI 1.3-6.9, p = 0.005) were predictors of advanced atherosclerosis on CTCA. Thirty-two patients (20%) experienced MACE. At a median follow-up of 4 years, CAD-RADS ≥ 3, but not coronary artery calcium scores, was associated with a heightened risk of MACE (HR 5.8, 95% CI 1.6-20.6, p = 0.006). Based on CTCA results, 71 patients (31%) commenced statin therapy which was associated with a lower risk of all-cause mortality (HR 0.48, 95% CI 0.24-0.97, p = 0.04). The standardized CAD-RADS classification on CTCA predicted the occurrence of cardiovascular outcomes following LT, with a potential to increase the utilization of preventive cardiovascular therapies.
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Aterosclerose , Doença da Artéria Coronariana , Diabetes Mellitus , Transplante de Fígado , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Angiografia Coronária/métodos , Estudos Retrospectivos , Transplante de Fígado/efeitos adversos , Cálcio , Fatores de Risco , Medição de Risco/métodos , Prognóstico , Valor Preditivo dos Testes , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/etiologia , Angiografia por Tomografia Computadorizada , Tomografia Computadorizada por Raios X/métodos , Aterosclerose/complicaçõesRESUMO
OBJECTIVE: Extracellular volume fraction (fECV) and liver and spleen size have been correlated with liver fibrosis stages and cirrhosis. The purpose of the current study was to determine the predictive value of fECV alone and in conjunction with measurement of liver and spleen size for severity of liver fibrosis. METHODS: This was a retrospective study of 95 subjects (65 with liver biopsy and 30 controls). Spearman rank correlation coefficient was used to assess correlation between radiological markers and fibrosis stage. Receiver operating characteristic analysis was performed to assess the discriminative ability of radiological markers for significant (F2+) and advanced (F3+) fibrosis and cirrhosis (F4), by reporting the area under the curve (AUC). RESULTS: The cohort had a mean age of 51.4 ± 14.4 years, and 52 were female (55%). There were 36, 5, 6, 9, and 39 in fibrosis stages F0, F1, F2, F3, and F4, respectively. Spleen volume alone showed the highest correlation (r = 0.552, P < 0.001) and AUCs of 0.823, 0.807, and 0.785 for identification of significant and advanced fibrosis and cirrhosis, respectively. Adding fECV to spleen length improved AUCs (0.764, 0.745, and 0.717 to 0.812, 0.781, and 0.738, respectively) compared with splenic length alone. However, adding fECV to spleen volume did not improve the AUCs for significant or advanced fibrosis or cirrhosis. CONCLUSIONS: Spleen size (measured in length or volume) showed better correlation with liver fibrosis stages compared with fECV. The combination of fECV and spleen length had higher accuracy compared with fECV alone or spleen length alone.
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Graft-derived cell-free DNA (gdcfDNA) quantification is a promising, minimally invasive tool for detecting acute T cell-mediated rejection (ATCMR) following liver transplantation (LT). We investigated the utility of measuring hepatocyte-specific methylation in cfDNA (HS-cfDNA) to quantify gdcfDNA, examining its accuracy in detecting ATCMR in a prospective, cross-sectional study. Blood was collected from LT recipients immediately prior to graft biopsy for suspected rejection. HS-cfDNA was quantified using droplet-digital polymerase chain reaction. Prebiopsy liver function tests (LFTs) and HS-cfDNA levels were correlated with biopsy results and the primary outcome of treated biopsy-proven acute rejection (tBPAR). A total of 51 patients were recruited; 37 had evidence of rejection on biopsy and 20 required treatment. As much as 11 patients needed inpatient treatment for rejection. HS-cfDNA significantly outperformed LFTs in identifying patients with tBPAR, particularly those needing inpatient treatment (area under the curve, 73.0%; 95% confidence interval, 55.4%-90.6%; P = 0.01). At a threshold of <33.5% of the total cfDNA fraction, HS-cfDNA had a specificity of 97%, correctly excluding tBPAR in 30/31 patients. Quantifying graft-specific methylation in cfDNA has a major advantage over previous gdcfDNA techniques: it does not require genotyping/sequencing, lending it greater feasibility for translation into transplantation care. Low levels of HS-cfDNA were a strong negative predictor for tBPAR (negative predictive value, 86%) and may have a future role in triaging patients prior to invasive graft biopsies.
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Ácidos Nucleicos Livres , Transplante de Fígado , Biomarcadores , Estudos Transversais , Rejeição de Enxerto , Hepatócitos , Humanos , Transplante de Fígado/efeitos adversos , Metilação , Estudos Prospectivos , Linfócitos T , Doadores de TecidosRESUMO
BACKGROUND AND AIMS: The 30-day hospital readmission rate in cirrhotic patients has been demonstrated to be up to 40% in international studies, but is not well studied in Australia. The aim of the current study was to report on the rate and cause of 30-day hospital readmission from a single liver transplant referral centre, including a cost analysis of readmissions. METHODS: This was a retrospective study of consecutive cirrhotic patients admitted to a liver transplant centre in Victoria, Australia, between 1 January 2019 and 31 December 2019. Cases were identified through International Classification of Diseases, Tenth Revision, 10 coding for cirrhosis and its complications. Baseline demographic data, liver-related complications and unrelated extra-hepatic comorbidities, laboratory values and prognostic scores were collected from the electronic medical record. RESULTS: One hundred seventy-nine (63% men; median age at index admission, 59 years) patients who were admitted 427 times during the study period were included in the final analysis. The 30-day hospital readmission rate was 46%, with the majority of readmissions attributable to fluid overload (29%), miscellaneous reasons (27%) and infection (20%). One fifth of readmissions were considered preventable. History of variceal haemorrhage was found to be an independent predictor of 30-day hospital readmission. The annual cost of readmission is over AU$2.7 million and the median cost of hospital readmission was about AU$9000. CONCLUSIONS: The 30-day hospital readmission rate of 46% is higher than previously reported and almost half of cases were caused by either fluid overload or infection.
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Varizes Esofágicas e Gástricas , Transplante de Fígado , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Readmissão do Paciente , Fatores de Risco , Estudos Retrospectivos , Hemorragia Gastrointestinal , Cirrose Hepática/epidemiologia , Cirrose Hepática/cirurgia , Vitória/epidemiologiaRESUMO
BACKGROUND AND PURPOSE: Postoperative atrial fibrillation (POAF) is the commonest cardiovascular complication following liver transplantation (LT). This study sought to assess a possible association of POAF with subsequent thromboembolic events in patients undergoing LT. METHODS: A retrospective cohort study of consecutive adults undergoing LT between 2010 and 2018 was undertaken. Patients were classified as POAF if atrial fibrillation (AF) was documented within 30 days of LT without a prior history of AF. Cases of ischemic stroke or systemic embolism were adjudicated by a panel of 2 independent physicians. RESULTS: Among the 461 patients included, POAF occurred in 47 (10.2%) a median of 3 days following transplantation. Independent predictors of POAF included advancing age, postoperative sepsis and left atrial enlargement. Over a median follow-up of 4.9 (interquartile range, 2.9-7.2) years, 21 cases of stroke and systemic embolism occurred. Rates of thromboembolic events were significantly higher in patients with POAF (17.0% versus 3.1%; P<0.001). After adjustment, POAF remained a strong independent predictor of thromboembolic events (hazard ratio, 8.36 [95% CI, 2.34-29.79]). Increasing CHA2DS2VASc score was also an independent predictor of thromboembolic events (hazard ratio, 1.58 [95% CI, 1.02-2.46]). A model using POAF and a CHA2DS2VASc score ≥2 alone yielded a C statistic of 0.77, with appropriate calibration for the prediction of thromboembolic events. However, POAF was not an independent predictor of long-term mortality. CONCLUSIONS: POAF following LT is associated with an 8-fold increased risk of thromboembolic events and the use of the CHA2DS2VASc score may facilitate risk stratification of these patients. Prospective studies are warranted to assess whether the use of oral anticoagulants can reduce the risk of thromboembolism following LT.
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Fibrilação Atrial/epidemiologia , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Adulto , Idoso , Fibrilação Atrial/etiologia , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologiaRESUMO
Liver transplantation (LT) has a 4-fold higher risk of periprocedural cardiac arrest and ventricular arrhythmias (CA/VAs) compared with other noncardiac surgeries. Prolongation of the corrected QT interval (QTc) is common in patients with liver cirrhosis. Whether it is associated with an increased risk of CA/VAs following LT is unclear. Rates of 30-day CA/VAs post-LT were assessed in consecutive adults undergoing LT between 2010 and 2017. Pretransplant QTc was measured by a cardiologist blinded to clinical outcomes. Among 408 patients included, CA/VAs occurred in 26 patients (6.4%). QTc was significantly longer in CA/VA patients (475 ± 34 vs 450 ± 34 ms, P < .001). Optimal QTc cut-off for prediction of CA/VAs was ≥480 ms. After adjustment, QTc ≥480 ms remained the strongest predictor for the occurrence of CA/VAs (odds ratio [OR] 5.2, 95% confidence interval [CI] 2.2-12.6). A point-based cardiac arrest risk index (CARI) was derived with the bootstrap method for yielding optimism-corrected coefficients (2 points: QTc ≥480, 1 point: Model for End-Stage Liver Disease [MELD] ≥30, 1 point: age ≥65, and 1 point: male). CARI score ≥3 demonstrated moderate discrimination (c-statistic 0.79, optimism-corrected c-statistic 0.77) with appropriate calibration. QTc ≥480 ms was associated with a 5-fold increase in the risk of CA/VAs. The CARI score may identify patients at higher risk of these events. Whether heightened perioperative cardiac surveillance, avoidance of QT prolonging medications, or beta blockers could mitigate the risk of CA/VAs in this population merits further study.
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Doença Hepática Terminal , Parada Cardíaca , Transplante de Fígado , Síndrome do QT Longo , Adulto , Doença Hepática Terminal/cirurgia , Parada Cardíaca/etiologia , Humanos , Transplante de Fígado/efeitos adversos , Síndrome do QT Longo/etiologia , Masculino , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
It is postulated that cardiac structural abnormalities observed in cirrhotic cardiomyopathy (CCM) contribute to the electrophysiologic abnormality of QT interval (QTc) prolongation. We sought to evaluate whether QTc prolongation is associated with intrinsic abnormalities in cardiac structure and function that characterize CCM. Consecutive patients undergoing liver transplant work-up between 2010 and 2018 were included. Measures of cardiac function on stress testing including cardiac reserve and chronotropic incompetence were collected prospectively and a corrected QTc ≥ 440 ms was considered prolonged. Overall, 439 patients were included and 65.1% had a prolonged QTc. There were no differences in markers of left ventricular and atrial remodeling, or resting systolic and diastolic function across QTc groups. The proportion of patients that met the criteria for a low cardiac reserve (39.2 vs 36.6%, p = .66) or chronotropic incompetence (18.1 vs 21.3%, p = .52) was not different in those with a QTc ≥ 440 vs <440 ms. Further, there was no association between QTc prolongation and CCM by either the 2005 World College of Gastroenterology or modified 2020 Cirrhotic Cardiomyopathy Consortium criteria. QT interval prolongation was not associated with structural or functional cardiac abnormalities that characterize CCM. These findings suggest that CCM and QT interval prolongation in cirrhosis may be two separate entities with distinct pathophysiological origins.
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Cardiomiopatias , Transplante de Fígado , Síndrome do QT Longo , Cardiomiopatias/etiologia , Ventrículos do Coração , Humanos , Cirrose Hepática/complicações , Síndrome do QT Longo/etiologiaRESUMO
BACKGROUND: Despite high rates of infection and malignancy post-solid organ transplant, there are little data on patient participation in preventative health care. METHODS: We conducted a cross-sectional survey of post-liver transplant patients to evaluate insight into transplant-associated infective and neoplastic risks, and receipt of vaccination and cancer surveillance in accordance with Australian and local institution-specific guidelines. Descriptive analyses were used to assess characteristics potentially influencing adherence. RESULTS: Of 219 patients surveyed, adherence to bowel cancer surveillance was significantly reduced in those distant from transplantation compared with those recently transplanted (95.8% if transplanted ≤ 5 years ago vs. 68.3% if transplanted > 5 years ago, P < .001). Skin cancer surveillance participation with annual physician-directed examination was low (42.9%), particularly in younger patients (29.5% in < 50yo vs. 48.1% in ≥ 50yo, P = .01), who were also less adherent to vaccination recommendations (72.1% in < 50yo vs. 87.3% in ≥ 50yo, P = .008). CONCLUSIONS: This is the first analysis of preventative healthcare participation in a cohort of Australian liver transplant recipients, revealing concerning adherence to bowel and skin cancer surveillance recommendations. Major interventions to avoid preventable disease in this high-risk cohort are warranted.
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Transplante de Fígado , Transplante de Órgãos , Austrália , Estudos de Coortes , Estudos Transversais , Humanos , TransplantadosRESUMO
Reduction in muscle mass is a highly prevalent phenomenon in cirrhosis and is now well-documented to be associated with significant morbidity and mortality. Research into muscle loss in cirrhosis remains limited by an ongoing poor understanding of its relationship with muscle function, physical activity, and aerobic capacity. Alterations in exercise physiology have been documented in studies of individuals with cirrhosis that provide important information on physical function that is not captured by simple quantification of muscle mass. Despite expert consensus recommending regular exercise in end-stage liver disease to maintain muscle mass and function, there is little evidence guiding clinicians as to which form of exercise or delivery mechanism is most effective. It also remains unproven whether any specific intervention can alter clinically relevant outcomes. This review article summarizes the available literature regarding the changes in exercise physiology observed in cirrhosis, the associated impact on physical capacity, and the results of existing trials that examine the potential benefits of exercise delivery in patients with cirrhosis, particularly pertaining to their impact on exercise physiology.
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Terapia por Exercício , Cirrose Hepática , Sarcopenia , Composição Corporal , Dietoterapia , Doença Hepática Terminal/etiologia , Doença Hepática Terminal/metabolismo , Doença Hepática Terminal/terapia , Exercício Físico/fisiologia , Teste de Esforço , Terapia por Exercício/métodos , Tolerância ao Exercício , Fragilidade/etiologia , Fragilidade/terapia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/metabolismo , Cirrose Hepática/terapia , Força Muscular , Qualidade de Vida , Sarcopenia/etiologia , Sarcopenia/metabolismo , Sarcopenia/terapiaRESUMO
OBJECTIVES: Cardiac dysfunction has been implicated in the genesis of hepatorenal syndrome (HRS). It is unclear whether a low cardiac output (CO) or attenuated contractile response to hemodynamic stress can predict its occurrence. We studied cardiovascular hemodynamics in cirrhosis and assessed whether a diminished cardiac reserve with stress testing predicted the development of HRS on follow-up. METHODS: Consecutive patients undergoing liver transplant workup with dobutamine stress echocardiography (DSE) were included. CO was measured at baseline and during low-dose dobutamine infusion at 10 µg/kg/min. HRS was diagnosed using guideline-based criteria. RESULTS: A total of 560 patients underwent DSE, of whom 488 were included after preliminary assessment. There were 64 (13.1%) patients with established HRS. The HRS cohort had a higher baseline CO (8.0 ± 2 vs 6.9 ± 2 L/min; P < 0.001) and demonstrated a blunted response to low-dose dobutamine (ΔCO 29 ± 22% vs 44 ± 32%, P < 0.001) driven primarily by inotropic incompetence. Optimal cutpoint for ΔCO in patients with HRS was determined to be <25% and was used to define a low cardiac reserve. Among the 424 patients without HRS initially, 94 (22.1%) developed HRS over a mean follow-up of 1.5 years. Higher proportion with a low cardiac reserve developed HRS (52 [55.0%] vs 56 [16.9%]; hazard ratio 4.5; 95% confidence interval 3.0-6.7; P < 0.001). In a Cox multivariable model, low cardiac reserve remained the strongest predictor for the development of HRS (hazard ratio 3.9; 95% confidence interval 2.2-7.0; P < 0.001). DISCUSSION: Patients with HRS demonstrated a higher resting CO and an attenuated cardiac reserve on stress testing. On longitudinal follow-up, low cardiac reserve was an independent predictor for the development of HRS. Assessment of cardiac reserve with DSE may provide a novel noninvasive risk marker for developing HRS in patients with advanced liver disease.HRS is a life-threatening complication of liver disease. We studied whether an inability to increase cardiac contraction in response to stress can assist in the prediction of HRS. We demonstrate that patients with liver disease who exhibit cardiac dysfunction during stress testing had a 4-fold increased risk of developing HRS. This may improve our ability for early diagnosis and treatment of patients at a higher risk of developing HRS.
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Débito Cardíaco , Cardiotônicos , Dobutamina , Ecocardiografia sob Estresse/métodos , Síndrome Hepatorrenal/diagnóstico , Síndrome Hepatorrenal/etiologia , Cirrose Hepática/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Regras de Decisão Clínica , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Recent studies reveal substantial species and regional differences in enteroendocrine cell (EEC) populations, including differences in patterns of hormone coexpression, which limit extrapolation between animal models and human. In this study, jejunal samples, with no histologically identifiable pathology, from patients undergoing Whipple's procedure were investigated for the presence of gastrointestinal hormones using double- and triple-labelling immunohistochemistry and high-resolution confocal microscopy. Ten hormones (5-HT, CCK, secretin, proglucagon-derived peptides, PYY, GIP, somatostatin, neurotensin, ghrelin and motilin) were localised in EEC of the human jejunum. If only single staining is considered, the most numerous EEC were those containing 5-HT, CCK, ghrelin, GIP, motilin, secretin and proglucagon-derived peptides. All hormones had some degree of colocalisation with other hormones. This included a population of EEC in which GIP, CCK and proglucagon-derived peptides are costored, and four 5-HT cell populations, 5-HT/GIP, 5-HT/ghrelin, 5-HT/PYY, and 5-HT/secretin cell groups, and a high degree of overlap between motilin and ghrelin. The presence of 5-HT in many secretin cells is consistent across species, whereas lack of 5-HT and CCK colocalisation distinguishes human from mouse. It seems likely that the different subclasses of 5-HT cells subserve different roles. At a subcellular level, we examined the vesicular localisation of secretin and 5-HT, and found these to be separately stored. We conclude that hormone-containing cells in the human jejunum do not comply with a one-cell, one-hormone classification and that colocalisations of hormones are likely to define subtypes of EEC that have different roles.
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Células Enteroendócrinas/metabolismo , Jejuno/citologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Contagem de Células , Feminino , Hormônios Gastrointestinais/metabolismo , Humanos , Jejuno/metabolismo , Masculino , Serotonina/metabolismoRESUMO
Antibody-mediated rejection, whereby transplant recipient B cells and/or plasma cells produce alloreactive anti-human leukocyte antigen (HLA) antibodies, negatively influences transplant outcomes and is a major contributor to graft loss. An early humoral immune response is suggested by the production of anti-HLA donor-specific antibodies (DSA) that can be measured using solid phase assays. We report the early posttransplant coexistence of a shared anti-HLA antibody profile in 5 solid organ transplant recipients who received organs from the same donor. Retrospective analysis of the donor's serum confirmed the presence of the same anti-HLA profile, suggesting the transfer of donor-derived anti-HLA antibodies, or the cells that produce them, to multiple solid organ transplant recipients. The time frame and extent of transfer suggest a novel variant of the passenger lymphocyte syndrome. These findings have important implications for the consideration of all posttransplant antibody measurements, particularly the interpretation of non-DSAs in the sera of transplant recipients.
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Antígenos HLA/imunologia , Imunidade Humoral/imunologia , Isoanticorpos/imunologia , Transplante de Pulmão/métodos , Linfócitos/imunologia , Complicações Pós-Operatórias/imunologia , Doadores de Tecidos/provisão & distribuição , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Órgãos , Prognóstico , Estudos Retrospectivos , SíndromeRESUMO
Sarcopenia is associated with mortality in cirrhosis, but there is no gold standard for its diagnosis. The comparative utility of different diagnostic methods is unknown. This single-center observational cohort study followed 145 men referred for liver transplant evaluation between 2005 and 2012. Muscle mass was estimated by handgrip strength, dual energy X-ray absorptiometry (DEXA) lean mass, and single-slice computed tomography (CT) scan at the fourth lumbar vertebra. Recorded outcomes included time to death or liver transplantation. The median (interquartile range [IQR]) age was 54 years (47-59 years), and Model for End-Stage Liver Disease (MELD) score was 17 (14-23). Of 145 men, 56 died with a median (IQR) time to death of 7.44 months (3.48-14.16 months). In total, 79 men underwent transplantation with median (IQR) time to transplant of 7.20 months (3.96-12.84 months). The prevalence of sarcopenia differed between diagnostic modalities with 70.3% using CT muscle mass, 45.9% using handgrip strength, and 38.7% using DEXA. Muscle mass was inversely associated with wait-list mortality for measured CT muscle mass (hazard ratio [HR], 0.94; 95% confidence interval (CI), 0.90-0.98; P = 0.002), DEXA muscle mass (HR, 0.99; 95% CI, 0.99-0.99; P = 0.003), and handgrip strength (HR, 0.94; 95% CI, 0.91-0.98; P = 0.002). These results retained significance independent of the MELD score. In predicting mortality, the MELD-handgrip strength bivariate Cox model was superior to a MELD-CT muscle Cox model (P < 0.001). In conclusion, handgrip strength combined with MELD score was the superior predictive model in this novel study examining 3 commonly employed techniques to diagnose sarcopenia in cirrhosis. Handgrip strength has additional potential clinical benefits because it can be performed serially without the radiation dose, cost, and access issues attributable to CT and DEXA.
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Doença Hepática Terminal/mortalidade , Força da Mão/fisiologia , Cirrose Hepática/mortalidade , Transplante de Fígado , Sarcopenia/diagnóstico , Absorciometria de Fóton , Progressão da Doença , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/patologia , Doença Hepática Terminal/cirurgia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Cirrose Hepática/cirurgia , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiopatologia , Prevalência , Prognóstico , Estudos Retrospectivos , Sarcopenia/epidemiologia , Sarcopenia/etiologia , Sarcopenia/fisiopatologia , Índice de Gravidade de Doença , Análise de Sobrevida , Tomografia Computadorizada por Raios XRESUMO
Erythropoietic protoporphyria (EPP) is an inherited metabolic disorder of heme synthesis resulting from overproduction of protoporphyrin IX (PPIX), which can lead to progressive liver disease characterized by recurrent EPP crises and end-stage liver disease. We used the Australian Transplant Registry to identify 5 patients referred for liver transplantation between 2008 and 2017. A total of 4 patients had EPP secondary to ferrochelatase deficiency, and 1 patient had X-linked EPP. No patient had follow-up with a specialist prior to the diagnosis of progressive liver disease. There were 3 patients who underwent orthotopic liver transplantation, whereas 2 died while on the transplant waiting list. Parenteral PPIX-lowering therapy was used in 4 patients and was effective in 3 patients, although 2 of these had rebound porphyria and worsening liver function following a decrease in the intensity of therapy. Early disease recurrence in the allograft following transplantation occurred in 2 patients requiring red cell exchange (RCE) to successfully attain and maintain low PPIX levels, but RCE was associated with hemosiderosis in 1 patient. Allogeneic stem cell transplantation (AlloSCT) was performed in 2 patients. One failed engraftment twice, whereas the second rejected the first graft but achieved full donor chimerism with a second graft and increased immunosuppression. In conclusion, our observations suggest that progressive liver disease needs parenteral PPIX-lowering treatment with the intensity adjusted to achieve a target Erc-PPIX level. Because EPP liver disease is universally recurrent, AlloSCT should be considered in all patients with adequate immunosuppression to facilitate engraftment. RCE appears to be effective for recurrent EPP liver disease but is associated with an increased risk of iron overload.
Assuntos
Doença Hepática Terminal/terapia , Rejeição de Enxerto/epidemiologia , Transplante de Fígado , Protoporfiria Eritropoética/patologia , Transplante de Células-Tronco , Listas de Espera/mortalidade , Adolescente , Adulto , Aloenxertos/patologia , Progressão da Doença , Doença Hepática Terminal/mortalidade , Doença Hepática Terminal/patologia , Feminino , Rejeição de Enxerto/patologia , Humanos , Lactente , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Protoporfiria Eritropoética/mortalidade , Protoporfiria Eritropoética/terapia , Recidiva , Sistema de Registros/estatística & dados numéricos , Transplante Homólogo , Adulto JovemRESUMO
INTRODUCTION: Reduced muscle area on CT scan is an independent predictor of mortality in cirrhosis. We examine for the first time the relationship between dual energy x-ray absorptiometry (DEXA) lean mass parameters on outcomes in cirrhotic men awaiting liver transplantation. MATERIALS AND METHODS: We retrospectively reviewed DEXA scans performed during transplant assessment between 2001 and 2016. Baseline data including the presence of ascites and MELD score were recorded. DEXA lean mass measures were adjusted for height. The primary outcome was 12-month wait-list mortality. RESULTS: Four hundred twenty men with median age 55.4 years [interquartile range 49.2; 59.4] and MELD 16 [12; 20] were studied. Median follow-up was 58.5 [28.8; 109] months. 12-month wait-list mortality was 12.4%. Appendicular lean mass was inversely associated with mortality (HR 0.78 [0.62; 0.98], P = 0.03). Lean mass of arms (HR 0.37 [0.16; 0.83], P = 0.02) rather than legs (HR 0.77 [0.58; 1.03], P = 0.08) was responsible for this association. Upper limb lean mass showed a significant interaction with MELD score in predicting wait-list mortality, particularly within 4 months. Total lean mass was not associated with mortality but increased in conjunction with increasing ascites (OR for ascites 1.20 [1.15; 1.25], P < 0.001 for each unit increase in MELD). CONCLUSION: Upper limb lean mass by DEXA is strongly associated with mortality in men awaiting liver transplantation. The superiority of upper limb lean mass probably relates to confounding of lower limb measures by fluid retention. This DEXA parameter represents a novel and reproducible measure of sarcopenia in cirrhosis.
Assuntos
Absorciometria de Fóton , Cirrose Hepática/mortalidade , Transplante de Fígado , Sarcopenia/mortalidade , Listas de Espera , Austrália , Humanos , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/cirurgia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Análise de SobrevidaRESUMO
The development of antiviral-resistant cytomegalovirus (CMV) infection complicates the management of transplant recipients. We describe the case of a 65-year-old male who developed CMV disease on valganciclovir prophylaxis (donor CMV IgG positive, recipient CMV IgG indeterminate) 30 days after combined liver-kidney transplantation for alcoholic cirrhosis and hepato-renal syndrome. After an initial complete response to treatment dose oral valganciclovir, he developed recurrent CMV viraemia. Resistance testing revealed a UL97 mutation with in-frame deletions of codons 595-596. He was treated successfully with foscarnet and reduction in immunosuppression. This mutation has not been described previously and was suspected to confer ganciclovir resistance. Ganciclovir resistance occurs most commonly due to mutations in the UL97 or UL54 genes, which encode a protein kinase and a DNA polymerase, respectively. The UL97-encoded protein kinase phosphorylates ganciclovir to ganciclovir triphosphate, which competitively inhibits viral replication. Mutations in the UL97 gene are typically point mutations or deletions. We describe a new mutation, del595-596 in the CMV UL97 gene, occurring in the context of clinical treatment failure with standard and double-dose ganciclovir, and successful virological control achieved with foscarnet. This mutation is likely to result in ganciclovir resistance, although recombinant phenotyping is required for confirmation.