RESUMO
Interactions between communities of the gut microbiome and with the host could affect the onset and progression of metabolic associated fatty liver disease (MAFLD), and can be useful as new diagnostic and prognostic biomarkers. In this study, we performed a multi-omics approach to unravel gut microbiome signatures from 32 biopsy-proven patients (10 simple steatosis -SS- and 22 steatohepatitis -SH-) and 19 healthy volunteers (HV). Human and microbial transcripts were differentially identified between groups (MAFLD vs. HV/SH vs. SS), and analyzed for weighted correlation networks together with previously detected metabolites from the same set of samples. We observed that expression of Desulfobacteraceae bacterium, methanogenic archaea, Mushu phage, opportunistic pathogenic fungi Fusarium proliferatum and Candida sorbophila, protozoa Blastocystis spp. and Fonticula alba were upregulated in MAFLD and SH. Desulfobacteraceae bacterium and Mushu phage were hub species in the onset of MAFLD, whereas the activity of Fonticula alba, Faecalibacterium prausnitzii, and Mushu phage act as key regulators of the progression to SH. A combination of clinical, metabolomic, and transcriptomic parameters showed the highest predictive capacity for MAFLD and SH (AUC = 0.96). In conclusion, faecal microbiome markers from several community members contribute to the switch in signatures characteristic of MAFLD and its progression towards SH.
Assuntos
Aciltransferases , Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Fosfolipases A2 Independentes de Cálcio , Humanos , Microbioma Gastrointestinal/genética , Genótipo , Metaboloma , Transcriptoma/genética , Aciltransferases/genética , Fosfolipases A2 Independentes de Cálcio/genética , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/microbiologiaRESUMO
INTRODUCTION AND OBJECTIVES: With the advent of new therapeutic options for patients with hepatocellular carcinoma (HCC) for intermediate or advanced stages of the Barcelona Clinic Liver Cancer (BCLC), regional real-world data regarding prognostic survival factors are of significant importance. PATIENTS AND METHODS: A multicenter prospective cohort study was conducted in Latin America including BCLC B or C patients since 15th May 2018. We report here the second interim analysis focusing on prognostic variables and causes of treatment discontinuation. Cox proportional hazard survival analysis was performed, estimating hazard ratios (HR) and 95% confidence intervals (95% CI). RESULTS: Overall, 390 patients were included, 55.1% and 44.9% were BCLC B and C at the time of study enrollment. Cirrhosis was present in 89.5% of the cohort. Among the BCLC-B group, 42.3% were treated with TACE with a median survival since the first session of 41.9 months. Liver decompensation before TACE was independently associated with increased mortality [HR 3.22 (CI 1.64;6.33); P<.001]. Systemic treatment was initiated in 48.2% of the cohort (n=188), with a median survival of 15.7 months. Of these, 48.9% presented first-line treatment discontinuation (44.4% tumor progression, 29.3% liver decompensation, 18.5% symptomatic deterioration, and 7.8% intolerance), and only 28.7% received second-line systemic treatments. Liver decompensation [HR 2.9 (1.64;5.29); P<.0001], and symptomatic progression [HR 3.9 (1.53;9.78); P=0.004] were independently associated with mortality after first-line systemic treatment discontinuation. CONCLUSIONS: The complexity of these patients, with one-third presenting liver decompensation after systemic therapies, underlines the need for multidisciplinary team management and the central role of hepatologists.
Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Prognóstico , Estudos Prospectivos , Quimioembolização Terapêutica/efeitos adversos , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do TratamentoRESUMO
INTRODUCTION: Non-invasive biomarkers are needed for metabolic dysfunction-associated fatty liver disease (MAFLD), especially for patients at risk of disease progression in high-prevalence areas. The microbiota and its metabolites represent a niche for MAFLD biomarker discovery. However, studies are not reproducible as the microbiota is variable. OBJECTIVES: We aimed to identify microbiota-derived metabolomic biomarkers that may contribute to the higher MAFLD prevalence and different disease severity in Latin America, where data is scarce. METHODS: We compared the plasma and stool metabolomes, gene patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 single nucleotide polymorphism (SNP), diet, demographic and clinical data of 33 patients (12 simple steatosis and 21 steatohepatitis) and 19 healthy volunteers (HV). The potential predictive utility of the identified biomarkers for MAFLD diagnosis and progression was evaluated by logistic regression modelling and ROC curves. RESULTS: Twenty-four (22 in plasma and 2 in stool) out of 424 metabolites differed among groups. Plasma triglyceride (TG) levels were higher among MAFLD patients, whereas plasma phosphatidylcholine (PC) and lysoPC levels were lower among HV. The PNPLA3 risk genotype was related to higher plasma levels of eicosenoic acid or fatty acid 20:1 (FA(20:1)). Body mass index and plasma levels of PCaaC24:0, FA(20:1) and TG (16:1_34:1) showed the best AUROC for MAFLD diagnosis, whereas steatosis and steatohepatitis could be discriminated with plasma levels of PCaaC24:0 and PCaeC40:1. CONCLUSION: This study identified for the first time MAFLD potential non-invasive biomarkers in a Latin American population. The association of PNPLA3 genotype with FA(20:1) suggests a novel metabolic pathway influencing MAFLD pathogenesis.
Assuntos
Microbiota , Hepatopatia Gordurosa não Alcoólica , Biomarcadores , Genótipo , Humanos , Lipase/genética , Proteínas de Membrana/genética , Metabolômica , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/genéticaRESUMO
INTRODUCTION AND OBJECTIVES: Failures at any step in the hepatocellular carcinoma (HCC) surveillance process can result in HCC diagnostic delays and associated worse prognosis. We aimed to estimate the prevalence of surveillance failure and its associated risk factors in patients with HCC in Argentina, considering three steps: 1) recognition of at-risk patients, 2) implementation of HCC surveillance, 3) success of HCC surveillance. METHODS: We performed a multi-center cross-sectional study of patients at-risk for HCC in Argentina seen between10.01.2018 and 10.30.2019. Multivariable logistic regression analysis was used to identify correlates of surveillance failure. RESULTS: Of 301 included patients, the majority were male (74.8%) with a mean age of 64 years old. At the time of HCC diagnosis, 75 (25%) patients were unaware of their diagnosis of chronic liver disease, and only 130 (43%) patients were under HCC surveillance. Receipt of HCC surveillance was significantly associated with follow-up by a hepatologist. Of 119 patients with complete surveillance, surveillance failure occurred in 30 (25%) patients. Surveillance failure was significantly associated with alpha fetoprotein ≥20â¯ng/mL (OR 4.0, CI 95% 1.43-11.55). CONCLUSIONS: HCC surveillance failure was frequent in all the evaluated steps. These data should help guide strategies to improve the implementation and results of HCC surveillance in our country.
Assuntos
Carcinoma Hepatocelular/diagnóstico , Detecção Precoce de Câncer , Neoplasias Hepáticas/diagnóstico , Idoso , Argentina , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/terapia , Estudos Transversais , Diagnóstico Tardio , Feminino , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/terapia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Determinantes Sociais da Saúde , Falha de Tratamento , alfa-Fetoproteínas/metabolismoRESUMO
Relative adrenal insufficiency (RAI) is a common finding in cirrhotic patients with severe sepsis, and increased mortality. Its significance is unknown in stable conditions. The aim of this study was to evaluate the prevalence of RAI in stable cirrhotic patients at different stages of the disease. Also, the impact of RAI on the survival was evaluated and basal cortisol levels between plasma and saliva was correlated in control subjects and cirrhotic patients. Forty seven ambulatory patients and 16 control subjects were studied. RAI was defined as a serum cortisol increase of less than 9 υg/dl from baseline after the stimulation with 250 mg of synthetic ACTH. Twenty two had Child-Pugh = 8 and 25 = 9. The prevalence of RAI in patients with stable cirrhosis was 22%. A higher incidence of RAI was observed in patients with a Child-Pugh = 9 (8/32) than in those with = 8 (3/13, p < 0.05). A correlation between salivary cortisol and basal plasma cortisol (r = 0.6, p < 0.0004) was observed. Finally, survival at 1 year (97%) and 3 years (91%) was significantly higher without RAI than those who developed this complication (79% and 51%, p < 0.05, respectively). In summary, the prevalence of RAI is frequent in patients with stable cirrhosis and that it is related to the severity of liver diseaseand increased mortality.
Assuntos
Insuficiência Adrenal/epidemiologia , Cirrose Hepática/complicações , Insuficiência Adrenal/mortalidade , Estudos de Casos e Controles , Feminino , Humanos , Hidrocortisona/análise , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/metabolismo , Fígado/fisiopatologia , Cirrose Hepática/metabolismo , Cirrose Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/metabolismo , Prevalência , Prognóstico , Estudos Prospectivos , Saliva/química , SepseRESUMO
INTRODUCTION: The introduction of noninvasive liver stiffness (LS) determination has heralded a new stage in the diagnosis and treatment of liver fibrosis. AIM: We evaluated the effect of food intake on LS in patients with different degrees of liver disease. PATIENTS AND METHODS: We evaluated 24 patients (F≤1, n=11 and F> 1, n=13). LS (Fibroscan®) and portal blood flow (PBF) (Doppler ultrasound) were studied before and 30min after ingestion of a standard liquid meal. RESULTS: Food intake increased PBF (51±10%, p<0.001). Splanchnic hyperemia was accompanied by a significant rise in LS (from 7.8±3.3 to 10.3±4.1kPa, p<0.001). These increases were similar in patients with minimal fibrosis(F≤1) and in those with more advanced fibrosis or cirrhosis (F>1). Hemodynamic and LS values returned to baseline pre-meal levels within 2hours. CONCLUSION: LS increases markedly after ingestion of a standard meal, irrespective of the degree of fibrosis. Our results strongly suggest that LS should be measured in fasting conditions.
Assuntos
Ingestão de Alimentos/fisiologia , Jejum/fisiologia , Cirrose Hepática/diagnóstico por imagem , Fígado/fisiopatologia , Adulto , Idoso , Tomada de Decisão Clínica , Elasticidade , Feminino , Hemodinâmica , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico por imagem , Humanos , Hiperemia/etiologia , Fluxometria por Laser-Doppler , Circulação Hepática , Cirrose Hepática/etiologia , Masculino , Refeições , Pessoa de Meia-Idade , Estudos Prospectivos , Circulação Esplâncnica , Ultrassonografia DopplerRESUMO
The aim of the present study was to evaluate the incidence and clinical features of de novo tumors in patients undergoing liver transplantation in our center as well as to assess survival. We retrospectively analyzed 168 liver transplantations (159 patients) performed from May 2006 to May 2014. The incidence of de novo tumors was 7.5% (n = 12). The mean age at diagnosis was 63 ± 7 years. The most frequent neoplasms were non melanoma skin tumors and adenocarcinomas. Fifty percent of the tumors developed in the second and third year after transplantation. Type of immunosuppression did not influence tumoral type, although most patients receive tacrolimus in combination with mycofenolate and/or corticoids. The mean duration of follow-up after diagnosis of the tumor was 25 ± 29 months (range 0-76) and the mortality was 41%. The actuarial probability of survival at 1 and 5 years was 83 and 55%, respectively. De novo tumors are frequent after liver transplantation and their clinical course differs from that in the general population. Because their clinical course is more aggressive, regular follow up of these patients is essential for early diagnosis.
Assuntos
Adenocarcinoma/epidemiologia , Neoplasias do Colo/epidemiologia , Transplante de Fígado/efeitos adversos , Neoplasias da Próstata/epidemiologia , Neoplasias Cutâneas/epidemiologia , Adenocarcinoma/etiologia , Idoso , Argentina/epidemiologia , Combinação de Medicamentos , Feminino , Humanos , Imunossupressores/efeitos adversos , Incidência , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Cutâneas/etiologia , Análise de SobrevidaRESUMO
Pancreatic panniculitis is an uncommon condition that can occur in association with pancreatic disease. Most of the cases reported to date were associated with acute or chronic pancreatitis and pancreas cancer. Recently, development has been described in kidney transplant patients and secondarily to allograft pancreatitis in a pancreas-kidney transplant recipient. Both findings suggest that immunological processes may be involved in the pathogenesis of this entity. We report for the first time a case of acute pancreatitis associated with pancreatic panniculitis in a patient who underwent a liver transplant 10 months before. A 69-year-old man with a history of epigastric pain of a few days of evolution was presented with painful subcutaneous nodules on both legs. Blood chemistry showed raised serum amylase and lipase levels. Ultrasonography and multislice CT scan were suggestive of an acute pancreatitis. A skin biopsy showed typical features of pancreatic panniculitis which included lobular panniculitis with lipocyte degeneration with ghost cells. The administration of octreotide resulted in both a rapid improvement of symptoms and a disappearance of skin lesions. Liver transplant specialists should be aware that the pancreatic panniculitis could be a manifestation ofpancreas disease in patients who have undergone l ver transplantation.
Assuntos
Transplante de Fígado/efeitos adversos , Pancreatite/etiologia , Paniculite Nodular não Supurativa/etiologia , Doença Aguda , Idoso , Amilases/sangue , Humanos , Terapia de Imunossupressão/efeitos adversos , Lipase/sangue , Masculino , Pancreatite/patologia , Paniculite Nodular não Supurativa/patologia , Pele/patologiaRESUMO
INTRODUCTION: The aim of the present study was to investigate the impact of the Model for End-stage Liver Disease (MELD) on transplantation costs. MATERIAL AND METHODS: We included all patients who received a liver transplant for end-stage liver disease between 2006 and 2010. The study period encompassed the day of transplantation until hospital discharge. The patients were classified into two groups: those with a MELD score of 6-19 and those with a score of 20-40. RESULTS: The mean MELD score at transplantation was 19.2±7.0 (mean±SD). The mean cost per procedure in the study period was USD 33,461 per patient (range 21,795-104,629). The cost of transplantation was USD 30,493±8,825 in patients with a MELD score of 6-19 and was USD 36,506±15,833 in those with a score of 20-40; this difference was statistically significant (P=.04). In a stepwise logistic regression analysis, the only independent predictor of high cost was having a MELD score of 20 (OR 11.8; CI 1.6-87). In the linear regression model, the most important predictor of cost was the length of hospital stay (r(2)=43%). DISCUSSION: Our results demonstrate that the MELD score directly affects transplantation costs. We suggest that reimbursement systems compensate the distinct financing bodies according to the severity of the underlying disease, evaluated with the MELD.
Assuntos
Doença Hepática Terminal , Transplante de Fígado/economia , Modelos Estatísticos , Adolescente , Adulto , Idoso , Criança , Custos e Análise de Custo , Feminino , Hospitais Comunitários , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Índice de Gravidade de Doença , Adulto JovemRESUMO
The present study reports the effectiveness of the association of a single dose of hepatitis B immunoglobulin (HBIg) associated to entecavir in the prophylaxis of hepatitis B in patients who have undergone liver transplantation. Six patients that had been transplanted because of hepatitis B liver disease were retrospectively evaluated. Three of them developed non-oncological complications related to liver cirrhosis, two had hepatocellular carcinoma and another one had fulminant HBV hepatitis. The mean follow-up was 22 months (range: 7-52 months). The 6 patients received entecavir as prophylactic treatment before transplantation. The pretransplant viral load was undetectable in all patients. HBsAg seroconversion was observed in four of the six patients. Three patients died during follow-up, two because of recurrent hepatocellular carcinoma, none of them had detectable HBV serum viral load. In a small series of patients we could demonstrate that a regimen with a single dose of gamma globulin entecavir is effective in the post-transplant management of patients with liver disease associated with HBV. Future studies will be able to demonstrate the effectiveness of specific gamma globulin-free regimens.
Assuntos
Antivirais/administração & dosagem , Guanina/análogos & derivados , Hepatite B/prevenção & controle , Imunoglobulinas/administração & dosagem , Cirrose Hepática/cirurgia , Transplante de Fígado , Adulto , Idoso , Argentina , Quimioterapia Combinada , Feminino , Guanina/administração & dosagem , Humanos , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Prevenção SecundáriaRESUMO
UNLABELLED: After the introduction of high active antiretroviral therapy (HAART), the human immunodeficiency virus (HIV) was no longer considered a contraindication for transplantation. Yet, liver disease in this population is characterized by an accelerated course that may impact on the waiting list. OBJECTIVE: To evaluate the experience in Argentina with HIV positive patients listed for liver transplantation. PATIENTS AND METHODS: We analyzed 52 HIV positive patients listed between July 2005 and March 2010 (Group HIV positive). Results were compared with 462 HIV negative patients included during the same period (Group HIV negative). Data were obtained from INCUCAI, the Argentinian procurement organism and from the Transplantation Centers. RESULTS: The etiology of liver disease in the Group HIV positive was hepatitis C 40, HBV 3, fulminant hepatitis 3, alcohol 2, retrasplant 2 and others 2. The mean MELD at the time of listing was 1615 (lower than 19 in 40 cases, higher than 19 in 8, emergency in 3) in the group HIV positive and 16.64 in the group HIV negative (NS). The outcome in the waiting list for HIV positive and negative patients respectively was: death 14 (27%) vs 61 (18.7%) (P < 0.05), cadaveric donor transplant 10 (13%) vs 95 (29.4%) (P < 0.001), living donor transplant 0 (0%) vs 5 (1.1%) (NS), mean time from listing to death 270.70 298.11 days vs 267.29 266.53 days (NS), mean time from listing to transplant 70.26 74.05 vs 261 187.6 days (P < 0.01), mean MELD at the time of death 12.54 (13 cases lower than 15, 1 higher than 19) vs 19.6 9.7 (P < 0.05), mean MELD at the time of transplantation 24.33 vs 24.1 7.6 (NS). CONCLUSION: HIV positive patients have high mortality in the waiting list and low access to liver transplantation. MELD score underscores the severity of liver disease in this population when compared to HIV negative patients.
Assuntos
Soropositividade para HIV/virologia , Falência Hepática/cirurgia , Transplante de Fígado , Listas de Espera , Adolescente , Adulto , Idoso , Argentina , Feminino , Humanos , Falência Hepática/complicações , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Adulto JovemRESUMO
The prognosis and management of chronic liver disease largely depends on the extent and progression of liver fibrosis. Unfortunately, liver biopsy, an invasive and painful technique with several limitations, continues to be the gold standard for the staging and grading of fibrosis. Therefore, accurate noninvasive tests for liver injury are urgently needed. During the last years, transient elastography (Fibroscan®) has been proposed for the assessment of hepatic fibrosis in patients with chronic liver disease, by measuring liver stiffness. The aim of this study was to evaluate the effectiveness, objectivity and safety of this technique. We included 68 patients who underwent a liver biopsy in the last 18 months with a wide spectrum of chronic liver diseases. All procedures as well as the liver biopsies according to the METAVIR scoring system were analyzed by the same sonographer and the same specialist in pathology, respectively. Median value of stiffness with none or mild fibrosis (F0 and FI), and severe fibrosis or cirrhosis (F3 and F4) was 6.8 ± 3.0 kPa and 21.0 ± 15.1 kPa, respectively, with a significant difference between them (p < 0.01). The areas under the receiver operating characteristic curves showed the optimal liver stiffness cut-off values for each group. We found also a positive correlation between liver stiffness found by transient elastography and fibrosis stage on biopsy in all patients, independently of the liver disease etiology. Fibroscan® is an easy, quick to perform and safe non-invasive method, reliable for assessing liver fibrosis.
Assuntos
Técnicas de Imagem por Elasticidade/métodos , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Fígado/patologia , Biomarcadores/análise , Biópsia , Doença Crônica , Estudos Transversais , Técnicas de Imagem por Elasticidade/normas , Feminino , Fibrose , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND AIMS: Surveillance during liver transplantation (LT) waiting list has scarcely been reported in South America. We aimed to describe hepatocellular carcinoma (HCC) surveillance during the LT waiting list in the daily practice. PATIENTS AND METHODS: A multicenter retrospective analysis in cirrhotic patients was carried out. All patients underwent an ultrasound (US) every 6 months and the last pre-LT US was compared with explanted liver findings. A false-negative case was considered when incidentally found HCC (iHCC) was detected, whereas a false-positive case was considered when HCC diagnosed before LT (cHCC) was not confirmed in the explanted liver. US performance was assessed after excluding cHCC patients referred to transplant evaluation. RESULTS: Of 643 patients, 129 had HCC, of whom 92 had cHCC (71.3%) and 37 had iHCC (28.7%). Five patients (5.4%) had nonconfirmed cHCC (n=3 regenerative nodules, n=1 biliary hamartoma, and n=1 cholangiocarcinoma). Patients with iHCC had a higher MELD score (23±10 vs. 15±10; P<0.0001), and were more frequently Child-Pugh C (62.2 vs. 36.6%; P=0.006) compared with patients with cHCC. The number of US performed during waiting list was 1.7±1.6 (median 1.0). During transplant waiting list, the sensitivity and specificity of US were 33 and 99%, with positive and negative predictive values of 0.89 and 0.93, respectively. Multivariate analysis showed that the strongest variable related to iHCC finding was pre-LT Child-Pugh C status (OR 3.5; P=0.004). CONCLUSION: Screening for liver cancer remains an important issue during transplant waiting list. However, the US screening method should be reviewed particularly for Child-Pugh C patients.
Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Detecção Precoce de Câncer/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Transplante de Fígado , Listas de Espera , Adolescente , Adulto , Idoso , Argentina/epidemiologia , Carcinoma Hepatocelular/epidemiologia , Humanos , Neoplasias Hepáticas/epidemiologia , Pessoa de Meia-Idade , Vigilância da População/métodos , Valor Preditivo dos Testes , Estudos Retrospectivos , Ultrassonografia , Adulto JovemRESUMO
Background. Significant amounts of red blood cells (RBCs) transfusions are associated with poor outcome after liver transplantation (LT). We report our series of LT without perioperative RBC (P-RBC) transfusions to evaluate its influence on early and long-term outcomes following LT. Methods. A consecutive series of LT between 2006 and 2011 was analyzed. P-RBC transfusion was defined as one or more RBC units administrated during or ≤48 hours after LT. We divided the cohort in "No-Transfusion" and "Yes-Transfusion." Preoperative status, graft quality, and intra- and postoperative variables were compared to assess P-RBC transfusion risk factors and postoperative outcome. Results. LT was performed in 127 patients ("No-Transfusion" = 39 versus "Yes-Transfusion" = 88). While median MELD was significantly higher in Yes-Transfusion (11 versus 21; P = 0.0001) group, platelet count, prothrombin time, and hemoglobin were significantly lower. On multivariate analysis, the unique independent risk factor associated with P-RBC transfusions was preoperative hemoglobin (P < 0.001). Incidence of postoperative bacterial infections (10 versus 27%; P = 0.03), median ICU (2 versus 3 days; P = 0.03), and hospital stay (7.5 versus 9 days; P = 0.01) were negatively influenced by P-RBC transfusions. However, 30-day mortality (10 versus 15%) and one- (86 versus 70%) and 3-year (77 versus 66%) survival were equivalent in both groups. Conclusions. Recipient MELD score was not a predictive factor for P-RBC transfusion. Patients requiring P-RBC transfusions had worse postoperative outcome. Therefore, maximum efforts must be focused on improving hemoglobin levels during waiting list time to prevent using P-RBC in LT recipients.
RESUMO
La insuficiencia suprarrenal relativa (ISR) es frecuente en pacientes cirróticos con sepsis grave, asociándose a un pobre pronóstico. Se desconoce su importancia en condiciones de enfermedad estable. El objetivo del trabajo ha sido evaluar la prevalencia de la ISR en una serie de pacientes cirróticos estables y su relación con el deterioro de la función hepática. Se determinó el impacto de la ISR en la supervivencia y se correlacionaron los niveles entre el cortisol basal en plasma y saliva en sujetos controles y cirróticos. Fueron incluidos 47 pacientes ambulatorios y 16 controles. La funcionalidad del eje hipotalámico-pituitario-suprarrenal se valoró mediante la prueba de estimulación con 250 μg de ACTH sintética EV, definiendo la ISR como delta cortisol < 9 μg/dl. Respecto al grado de deterioro de la función hepática, 22 tenían un Child-Pugh ≤ 8 y 25 pacientes = 9. La prevalencia de ISR fue de un 22%, siendo significativamente más elevada en aquellos con mayor deterioro de la función hepática (8/32 vs. 3/13, p < 0.05). Se observó correlación entre el cortisol salival y el plasmático basal (r = 0.6, p < 0.0004). Por último, la supervivencia fue más elevada en los pacientes sin ISR al año (97%) y a los tres años (91%) que aquellos que desarrollaron esta complicación (79 % y 51%, p < 0.05, respectivamente). En resumen, la prevalencia de ISR es elevada en los pacientes con cirrosis estable y se relaciona con un deterioro de la función hepática y una mayor mortalidad.
Relative adrenal insufficiency (RAI) is a common finding in cirrhotic patients with severe sepsis, and increased mortality. Its significance is unknown in stable conditions. The aim of this study was to evaluate the prevalence of RAI in stable cirrhotic patients at different stages of the disease. Also, the impact of RAI on the survival was evaluated and basal cortisol levels between plasma and saliva was correlated in control subjects and cirrhotic patients. Forty seven ambulatory patients and 16 control subjects were studied. RAI was defined as a serum cortisol increase of less than 9 μg/dl from baseline after the stimulation with 250 mg of synthetic ACTH. Twenty two had Child-Pugh ≤ 8 and 25 = 9. The prevalence of RAI in patients with stable cirrhosis was 22%. A higher incidence of RAI was observed in patients with a Child-Pugh = 9 (8/32) than in those with ≤ 8 (3/13, p < 0.05). A correlation between salivary cortisol and basal plasma cortisol (r = 0.6, p < 0.0004) was observed. Finally, survival at 1 year (97%) and 3 years (91%) was significantly higher without RAI than those who developed this complication (79% and 51%, p < 0.05, respectively). In summary, the prevalence of RAI is frequent in patients with stable cirrhosis and that it is related to the severity of liver diseaseand increased mortality.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Insuficiência Adrenal/epidemiologia , Cirrose Hepática/complicações , Sistema Hipófise-Suprarrenal/metabolismo , Prognóstico , Saliva/química , Hidrocortisona/análise , Hidrocortisona/sangue , Estudos de Casos e Controles , Prevalência , Estudos Prospectivos , Insuficiência Adrenal/mortalidade , Sepse , Sistema Hipotálamo-Hipofisário/metabolismo , Fígado/fisiopatologia , Cirrose Hepática/metabolismo , Cirrose Hepática/mortalidadeRESUMO
Introduction: The introduction of noninvasive liver stiffness (LS) determination has heralded a new stage in the diagnosis and treatment of liver fibrosis. Aim: We evaluated the effect of food intake on LS in patients with different degrees of liver disease. Patients and methods: We evaluated 24 patients (F≤1, n = 11 and F> 1, n = 13). LS (Fibroscan®) and portal blood flow (PBF) (Doppler ultrasound) were studied before and 30 min after ingestion of a standard liquid meal. Results: Food intake increased PBF (51 ± 10%, p < 0.001). Splanchnic hyperemia was accompanied by a significant rise in LS (from 7.8 ± 3.3 to 10.3 ± 4.1 kPa, p < 0.001). These increases were similar in patients with minimal fibrosis(F≤1) and in those with more advanced fibrosis or cirrhosis (F > 1). Hemodynamic and LS values returned to baseline pre-meal levels within 2 hours. Conclusion: LS increases markedly after ingestion of a standard meal, irrespective of the degree of fibrosis. Our results strongly suggest that LS should be measured in fasting conditions (AU)
Introducción: El desarrollo de nuevos métodos que permiten la determinación no invasiva de la rigidez hepática ha abierto una nueva era en el manejo de la fibrosis hepática. Objetivo: El objetivo del trabajo fue evaluar el efecto de ingesta de una comida sobre la rigidez hepática en pacientes con diferentes grados de fibrosis. Pacientes y métodos: Se evaluaron 24 pacientes (F ≤ 1, n = 11, y F > 1, n = 13), que fueron estudiados basalmente y 30 min después de la ingesta de una comida estándar (Ensure Plus®). La rigidez hepática se midió por Fibroscan®, y los parámetros hemodinámicos portales, mediante Doppler. La ingesta de una comida ocasionó un aumento del flujo sanguíneo portal (51 ± 10%, p < 0,001). La hiperemia esplácnica fue acompañada por un marcado incremento en la rigidez hepática (7,8 ± 3,3 a 10,3 ± 4,1 kPa, p < 0,001). Este efecto fue similar en pacientes con fibrosis mínima (F ≤ 1) y con fibrosis significativa (F > 1). Los valores de ambos parámetros retornaron a niveles similares a los basales a las 2 h luego de la ingesta. Conclusión: Este estudio demuestra que la respuesta vascular posprandial se acompaña de aumento de la rigidez hepática. Los cambios son independientes del grado de fibrosis. Nuestros resultados sugieren fuertemente que los estudios deben realizarse en condiciones de ayuno (AU)
Assuntos
Humanos , Ingestão de Alimentos/fisiologia , Cirrose Hepática/fisiopatologia , Jejum/fisiologia , Hiperemia/fisiopatologia , Fibrose , Ultrassonografia Doppler , Período Pós-Prandial/fisiologiaRESUMO
El objetivo del presente trabajo ha sido evaluar la incidencia y las características clínicas de los tumores aparecidos de novo en los pacientes sometidos a trasplante hepático, como así también su supervivencia. Para ello, analizamos en forma retrospectiva los 168 trasplantes hepáticos realizados en 159 pacientes adultos en el período mayo 2006 hasta mayo 2014, encontrando una incidencia de neoplasia de novo de 7.5% (n = 12). La edad media en el momento del diagnóstico fue de 63 ± 7 años. Las neoplasias más frecuentes fueron las de piel no melanoma y adenocarcinomas. El 50% de las neoplasias se desarrollaron en el segundo y tercer año postrasplante. El tipo de inmunosupresión no influyó en el tipo de tumor; sin embargo, debemos destacar que la mayor parte de los pacientes recibieron tacrolimus, micofenolato y/o corticoides. El tiempo medio de seguimiento tras el diagnóstico del tumor fue 25 ± 29 meses (0-76), y la tasa de mortalidad fue de un 41% (5/12 pacientes IC95%,15-72).La supervivencia global luego del trasplante a 1 y 5 años, calculada por análisis de Kaplan-Meier, fue de 83 y 55%, respectivamente. Los tumores de novo son frecuentes luego del trasplante hepático y presentan un patrón evolutivo diferente al de la población general. Teniendo en cuenta esta evolución más agresiva, es fundamental el seguimiento periódico en estos pacientes para realizar un diagnóstico lo más precoz posible.(AU)
The aim of the present study was to evaluate the incidence and clinical features of de novo tumors in patients undergoing liver transplantation in our center as well as to assess survival. We retrospectively analyzed 168 liver transplantations (159 patients) performed from May 2006 to May 2014. The incidence of de novo tumors was 7.5% (n = 12). The mean age at diagnosis was 63 ± 7 years. The most frequent neoplasms were non melanoma skin tumors and adenocarcinomas. Fifty percent of the tumors developed in the second and third year after transplantation. Type of immunosuppression did not influence tumoral type, although most patients receive tacrolimus in combination with mycofenolate and/or corticoids. The mean duration of follow-up after diagnosis of the tumor was 25 ± 29 months (range 0-76) and the mortality was 41%. The actuarial probability of survival at 1 and 5 years was 83 and 55%, respectively. De novo tumors are frequent after liver transplantation and their clinical course differs from that in the general population. Because their clinical course is more aggressive, regular follow up of these patients is essential for early diagnosis.(AU)
RESUMO
El objetivo del presente trabajo ha sido evaluar la incidencia y las características clínicas de los tumores aparecidos de novo en los pacientes sometidos a trasplante hepático, como así también su supervivencia. Para ello, analizamos en forma retrospectiva los 168 trasplantes hepáticos realizados en 159 pacientes adultos en el período mayo 2006 hasta mayo 2014, encontrando una incidencia de neoplasia de novo de 7.5% (n = 12). La edad media en el momento del diagnóstico fue de 63 ± 7 años. Las neoplasias más frecuentes fueron las de piel no melanoma y adenocarcinomas. El 50% de las neoplasias se desarrollaron en el segundo y tercer año postrasplante. El tipo de inmunosupresión no influyó en el tipo de tumor; sin embargo, debemos destacar que la mayor parte de los pacientes recibieron tacrolimus, micofenolato y/o corticoides. El tiempo medio de seguimiento tras el diagnóstico del tumor fue 25 ± 29 meses (0-76), y la tasa de mortalidad fue de un 41% (5/12 pacientes IC95%,15-72).La supervivencia global luego del trasplante a 1 y 5 años, calculada por análisis de Kaplan-Meier, fue de 83 y 55%, respectivamente. Los tumores de novo son frecuentes luego del trasplante hepático y presentan un patrón evolutivo diferente al de la población general. Teniendo en cuenta esta evolución más agresiva, es fundamental el seguimiento periódico en estos pacientes para realizar un diagnóstico lo más precoz posible.
The aim of the present study was to evaluate the incidence and clinical features of de novo tumors in patients undergoing liver transplantation in our center as well as to assess survival. We retrospectively analyzed 168 liver transplantations (159 patients) performed from May 2006 to May 2014. The incidence of de novo tumors was 7.5% (n = 12). The mean age at diagnosis was 63 ± 7 years. The most frequent neoplasms were non melanoma skin tumors and adenocarcinomas. Fifty percent of the tumors developed in the second and third year after transplantation. Type of immunosuppression did not influence tumoral type, although most patients receive tacrolimus in combination with mycofenolate and/or corticoids. The mean duration of follow-up after diagnosis of the tumor was 25 ± 29 months (range 0-76) and the mortality was 41%. The actuarial probability of survival at 1 and 5 years was 83 and 55%, respectively. De novo tumors are frequent after liver transplantation and their clinical course differs from that in the general population. Because their clinical course is more aggressive, regular follow up of these patients is essential for early diagnosis.
Assuntos
Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adenocarcinoma/epidemiologia , Neoplasias do Colo/epidemiologia , Transplante de Fígado/efeitos adversos , Neoplasias da Próstata/epidemiologia , Neoplasias Cutâneas/epidemiologia , Adenocarcinoma/etiologia , Argentina/epidemiologia , Combinação de Medicamentos , Incidência , Imunossupressores/efeitos adversos , Transplante de Fígado/mortalidade , Estudos Retrospectivos , Análise de Sobrevida , Neoplasias Cutâneas/etiologiaRESUMO
El pronóstico de la enfermedad crónica hepática depende de la extensión y la progresión de la fibrosis hepática. Actualmente la biopsia hepática es la técnica de elección para determinar el grado de fibrosis, pero es una prueba invasiva, no exenta de complicaciones. Por ello, el desarrollo de marcadores no invasivos de fibrosis hepática se convirtió en una necesidad indiscutible. Se propuso la elastografýa por transición (Fibroscan«) para valorar la fibrosis hepática en pacientes con enfermedad crónica hepática, mediante la medición de la rigidez hepática. Nuestro objetivo fue evaluar la efectividad, la objetividad y la seguridad de esta técnica. Se estudiaron 68 pacientes a los que se les realizó una biopsia hepática en los 18 meses previos al estudio. Todos los procedimientos de elastografia y biopsia hepática fueron analizados por un mismo profesional (DA y MA, respectivamente). Para la valoración de la biopsia hepática se utilizó la escala METAVIR. El valor medio de rigidez en pacientes sin fibrosis o con fibrosis leve (F0-F1) y en los pacientes con fibrosis avanzada o cirrosis (F3-F4) fue 6.8 ± 3.0 kPa y 21.0 ± 15.1 kPa, respectivamente (con diferencia significativa, p < 0.01). Las áreas debajo de la curva ROC definieron los niveles de corte en cada grupo. Con independencia del diagnóstico etiológico de enfermedad hepática, hallamos una correlación positiva, en todos los pacientes, entre rigidez hepática medida por elastografýa y grado de fibrosis hepática en la biopsia. En conclusión, podemos considerar que el Fibroscan« es un método no invasivo, seguro, fácil y rápido, que lo convierte en la alternativa a la biopsia para identificar fibrosis significativa o cirrosis.(AU)
The prognosis and management of chronic liver disease largely depends on the extent and progression of liver fibrosis. Unfortunately, liver biopsy, an invasive and painful technique with several limitations, continues to be the gold standard for the staging and grading of fibrosis. Therefore, accurate noninvasive tests for liver injury are urgently needed. During the last years, transient elastography (Fibroscan«) has been proposed for the assessment of hepatic fibrosis in patients with chronic liver disease, by measuring liver stiffness. The aim of this study was to evaluate the effectiveness, objectivity and safety of this technique. We included 68 patients who underwent a liver biopsy in the last 18 months with a wide spectrum of chronic liver diseases. All procedures as well as the liver biopsies according to the METAVIR scoring system were analyzed by the same sonographer and the same specialist in pathology, respectively. Median value of stiffness with none or mild fibrosis (F0 and FI), and severe fibrosis or cirrhosis (F3 and F4) was 6.8 ± 3.0 kPa and 21.0 ± 15.1 kPa, respectively, with a significant difference between them (p < 0.01). The areas under the receiver operating characteristic curves showed the optimal liver stiffness cut-off values for each group. We found also a positive correlation between liver stiffness found by transient elastography and fibrosis stage on biopsy in all patients, independently of the liver disease etiology. Fibroscan« is an easy, quick to perform and safe non-invasive method, reliable for assessing liver fibrosis.(AU)