RESUMO
BACKGROUND & AIMS: Liver inflammation is key in the progression of chronic viral hepatitis to cirrhosis and hepatocellular carcinoma. The magnitude of viral replication and the specific anti-viral immune responses should govern the degree of inflammation, but a direct correlation is not consistently found in chronic viral hepatitis patients. We aim to better define the mechanisms that contribute to chronic liver inflammation. METHODS: Intrahepatic CD14+ myeloid cells from healthy donors (n=19) and patients with viral-related liver cirrhosis (HBV, HBV/HDV or HCV; n=15) were subjected to detailed phenotypic, molecular and functional characterisation. RESULTS: Unsupervised analysis of multi-parametric data showed that liver disease was associated with the intrahepatic expansion of activated myeloid cells mainly composed of pro-inflammatory CD14+HLA-DRhiCD206+ cells, which spontaneously produced TNFα and GM-CSF. These cells only showed heightened pro-inflammatory responses to bacterial TLR agonists and were more refractory to endotoxin-induced tolerance. A liver-specific enrichment of CD14+HLA-DRhiCD206+ cells was also detected in a humanised mouse model of liver inflammation. This accumulation was abrogated following oral antibiotic treatment, suggesting a direct involvement of translocated gut-derived microbial products in liver injury. CONCLUSIONS: Viral-related chronic liver inflammation is driven by the interplay between non-endotoxin-tolerant pro-inflammatory CD14+HLA-DRhiCD206+ myeloid cells and translocated bacterial products. Deciphering this mechanism paves the way for the development of therapeutic strategies specifically targeting CD206+ myeloid cells in viral-related liver disease patients. Lay summary: Viral-related chronic liver disease is driven by intrahepatic pro-inflammatory myeloid cells accumulating in a gut-derived bacterial product-dependent manner. Our findings support the use of oral antibiotics to ameliorate liver inflammation in these patients.
Assuntos
Hepatite Viral Humana/etiologia , Lectinas Tipo C/fisiologia , Macrófagos/imunologia , Lectinas de Ligação a Manose/fisiologia , Receptores de Superfície Celular/fisiologia , Animais , Antibacterianos/uso terapêutico , Microbioma Gastrointestinal , Antígenos HLA-DR/análise , Hepatite Viral Humana/tratamento farmacológico , Humanos , Receptores de Lipopolissacarídeos/análise , Receptor de Manose , Camundongos , Células Mieloides/fisiologia , Fator de Necrose Tumoral alfa/biossínteseRESUMO
The ability of innate immune cells to sense and respond to impending danger varies by anatomical location. The liver is considered tolerogenic but is still capable of mounting a successful immune response to clear various infections. To understand whether hepatic immune cells tune their response to different infectious challenges, we probed mononuclear cells purified from human healthy and diseased livers with distinct pathogen-associated molecules. We discovered that only the TLR8 agonist ssRNA40 selectively activated liver-resident innate immune cells to produce substantial quantities of IFN-γ. We identified CD161(Bright) mucosal-associated invariant T (MAIT) and CD56(Bright) NK cells as the responding liver-resident innate immune cells. Their activation was not directly induced by the TLR8 agonist but was dependent on IL-12 and IL-18 production by ssRNA40-activated intrahepatic monocytes. Importantly, the ssRNA40-induced cytokine-dependent activation of MAIT cells mirrored responses induced by bacteria, i.e., generating a selective production of high levels of IFN-γ, without the concomitant production of TNF-α or IL-17A. The intrahepatic IFN-γ production could be detected not only in healthy livers, but also in HBV- or HCV-infected livers. In conclusion, the human liver harbors a network of immune cells able to modulate their immunological responses to different pathogen-associated molecules. Their ability to generate a strong production of IFN-γ upon stimulation with TLR8 agonist opens new therapeutic opportunities for the treatment of diverse liver pathologies.
Assuntos
Adjuvantes Imunológicos/farmacologia , Imunidade Inata/efeitos dos fármacos , Leucócitos Mononucleares/efeitos dos fármacos , Fígado/efeitos dos fármacos , Oligorribonucleotídeos/farmacologia , Receptor 8 Toll-Like/agonistas , Regulação para Cima/efeitos dos fármacos , Células Cultivadas , Técnicas de Cocultura , Enterococcus faecalis/imunologia , Enterococcus faecalis/metabolismo , Enterococcus faecalis/patogenicidade , Escherichia coli/imunologia , Escherichia coli/metabolismo , Escherichia coli/patogenicidade , Hepacivirus/imunologia , Hepacivirus/patogenicidade , Hepatite B/imunologia , Hepatite B/metabolismo , Hepatite B/patologia , Hepatite B/virologia , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/patogenicidade , Hepatite C/imunologia , Hepatite C/metabolismo , Hepatite C/patologia , Hepatite C/virologia , Humanos , Testes de Liberação de Interferon-gama , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/patologia , Fígado/imunologia , Fígado/microbiologia , Fígado/patologia , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Monócitos/metabolismo , Pseudomonas aeruginosa/imunologia , Pseudomonas aeruginosa/metabolismo , Pseudomonas aeruginosa/patogenicidade , Riboflavina/biossíntese , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Receptor 8 Toll-Like/metabolismoRESUMO
Human mucosal-associated invariant T (MAIT) cells are a T cell population characterized by the expression of a semi-invariant TCR capable of recognizing bacterial products in the context of MR1. MAIT cells are enriched in the human liver, which is constantly exposed to bacterial products from the intestine. Whether this specific parenchymal localization influences their function remains unknown. We analyzed MAIT cells resident in the vascular bed of livers and showed that they represented the majority of T cells expressing NK markers and the dominant IL-17A(+) T cell subset in the human liver sinusoids. In comparison with MAIT cells purified from peripheral blood, intrasinusoidal MAIT cells expressed markers of T cell activation; however, TCR-mediated cytokine production was equally suppressed in both circulating and intrasinusoidal MAIT cells. MAIT cells also expressed high levels of IL-7R, and we showed that IL-7, a cytokine produced by hepatocytes during inflammation, regulated TCR-mediated activation of MAIT cells, licensing them to dramatically increase Th1 cytokines and IL-17A production. Our quantitative and functional data indicate that MAIT cells are a specialized cell population highly adapted to exert their immune functions in the vascular network of the liver.
Assuntos
Interleucina-7/fisiologia , Fígado/imunologia , Ativação Linfocitária/imunologia , Subpopulações de Linfócitos T/imunologia , Adulto , Análise por Conglomerados , Perfilação da Expressão Gênica , Humanos , Imunofenotipagem , Interferon gama/biossíntese , Interleucina-7/metabolismo , Interleucina-7/farmacologia , Pessoa de Meia-Idade , Mitógenos/imunologia , Mucosa/imunologia , Mucosa/metabolismo , Fenótipo , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/metabolismo , Adulto JovemRESUMO
BACKGROUND & AIMS: Tumor and viral antigens are expressed by hepatocellular carcinoma (HCC) in patients with chronic hepatitis B, but little is known about the immunodominance and function of tumor- and virus-specific CD8+ T cells in these patients. METHODS: HLA-A2-restricted T-cell responses to 16 tumor antigens and hepatitis B virus (HBV) proteins were tested using 49 previously described epitopes. Cells from 30 HLA-A2+, HBV-infected patients (10 with HCC, 10 with HBV cirrhosis, and 10 HBV but no cirrhosis) were analyzed, after expansion, by enzyme-linked immunosorbent spot (ELISPOT). Interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-2 production, as well as expression of the degranulation marker CD107a on tumor-specific CD8+ T cells, were evaluated. RESULTS: Cells from all groups had tumor-specific responses. The tumor antigens NY-ESO-1 and SSX-2 were most frequently targeted and were immunogenic in the HLA-A2 subtypes that are characteristic of Asian ethnicity. Tumor-specific T cells had low affinities; T cells from non-HCC patients were polyfunctional (IFN-gamma+, TNF-alpha+, CD107a+) and those from HCC patients displayed an exhausted phenotype (IFN-gamma+, CD107a+). Programmed Death 1 (PD-1) was expressed at higher levels on T cells from tumor and liver than peripheral blood from HCC patients and might contribute to T-cell exhaustion. Blocking PD-1/PD-L1 increased the frequency of tumor-specific T cells in HCC patients but did not restore T cell function. CONCLUSIONS: Patients with or without HCC have a quantitative and functional hierarchy of tumor-specific T cells. HLA-A2-restricted T cells from HCC patients target NY-ESO-1, but exist in an exhausted state that might require additional activation to restore function.
Assuntos
Antígenos de Neoplasias/metabolismo , Linfócitos T CD8-Positivos/imunologia , Carcinoma Hepatocelular/imunologia , Hepatite B Crônica/imunologia , Cirrose Hepática/imunologia , Neoplasias Hepáticas/imunologia , Adulto , Antígenos de Neoplasias/imunologia , Biomarcadores Tumorais/metabolismo , Linfócitos T CD8-Positivos/patologia , Carcinoma Hepatocelular/virologia , Epitopos/imunologia , Feminino , Antígeno HLA-A2/imunologia , Antígeno HLA-A2/metabolismo , Hepatite B Crônica/virologia , Humanos , Cirrose Hepática/virologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Probabilidade , Valores de Referência , Sensibilidade e Especificidade , Células Tumorais CultivadasRESUMO
BACKGROUND: Although the treatment of extrahepatic metastases from primary liver tumors is essentially palliative, solitary metastasis from such tumors offers a possibility of cure by surgical resection. The adrenal gland is an uncommon site for metastasis from primary liver tumors. METHOD: We report two cases of adrenalectomy for solitary adrenal metastasis: one from intrahepatic cholangiocarcinoma and the other from hepatocellular carcinoma. RESULTS: The patient with intrahepatic cholangiocarcinoma had a synchronous adrenal metastasis and underwent simultaneous liver resection and adrenalectomy. However, he developed recurrent disease 17 months following surgery for which he is presently on palliative chemotherapy. The other patient underwent adrenalectomy for adrenal metastasis 3 months following liver transplantation for hepatocellular carcinoma. He is presently alive and disease-free 27 months after adrenalectomy. CONCLUSION: Carefully selected patients with solitary metastasis from primary liver tumors may be considered for resection.
Assuntos
Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Carcinoma Hepatocelular/cirurgia , Colangiocarcinoma/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias das Glândulas Suprarrenais/secundário , Idoso , Neoplasias dos Ductos Biliares/cirurgia , Carcinoma Hepatocelular/secundário , Colangiocarcinoma/secundário , Hepatectomia , Humanos , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Infectious complications are common during the postoperative course of a liver transplant recipient. Malaria, however, is a rare complication in such a setting. METHOD: We report post-transplantation malaria causing elevation of liver enzymes in two recipients. RESULTS: Both patients who had undergone living donor liver transplantation showed elevated levels of liver enzymes and fever during the postoperative course. Investigations (including liver biopsy in one patient) were initially inconclusive in determining the cause of liver dysfunction. The diagnosis of malaria was established in both cases by peripheral blood smear. Liver function transiently worsened with antimalarial treatment but subsequently became normal. CONCLUSION: This report highlights the importance of excluding such uncommon causes of post-transplantation liver dysfunction, especially when either the recipient or the donor comes from a region endemic for malaria.
Assuntos
Transplante de Fígado/efeitos adversos , Doadores Vivos , Malária/etiologia , Idoso , Animais , Biópsia , Feminino , Humanos , Fígado/parasitologia , Fígado/patologia , Malária/enzimologia , Malária/patologia , Masculino , Pessoa de Meia-Idade , Plasmodium vivax/isolamento & purificação , Transaminases/sangue , gama-Glutamiltransferase/sangueRESUMO
BACKGROUND: The indications of liver transplantation in hepatocellular carcinoma (HCC) are evolving. With the advent of living donor liver transplantation (LDLT), there is a renewed interest in this procedure for tumors beyond the standard Milan criteria. METHODS: We retrospectively analyzed the outcome of 28 patients who underwent LDLT for HCC in one institution. Survival analysis was done using the Kaplan-Meier method. RESULTS: Of the 28 patients, 9, 12 and 7 had Child's A, B and C cirrhosis respectively; 26 (93%) had underlying hepatitis B or C. Nineteen patients (68%) had tumors exceeding the Milan criteria. Postoperative (within 90 days) mortality and morbidity rates were 2/28 (7%) and 7/28 (25%) respectively. The actuarial overall 1-year, 2-year and 3-year survival rates were 76%, 76% and 51%, respectively. The actuarial 1-year, 2-year and 3-year recurrence free survival rates (computed by censoring the data of patients who died of causes other than HCC recurrence) were 88%, 82% and 70%, respectively. Although the survival rates were better for tumors within the Milan criteria than those exceeding them, the difference was not significant. CONCLUSIONS: LDLT is an effective modality in the treatment of HCC in patients with liver cirrhosis. It may also provide an opportunity for potential cure to patients with tumors beyond Milan criteria.
Assuntos
Carcinoma Hepatocelular/cirurgia , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/métodos , Doadores Vivos , Adulto , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/mortalidade , Intervalo Livre de Doença , Feminino , Hepatite B/complicações , Hepatite C/complicações , Humanos , Estimativa de Kaplan-Meier , Cirrose Hepática/complicações , Cirrose Hepática/mortalidade , Neoplasias Hepáticas/mortalidade , Transplante de Fígado/estatística & dados numéricos , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prevalência , Estudos Retrospectivos , Taiwan/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: Hilar cholangiocarcinoma is a devastating disease. Surgery is the only potentially curative modality. However, the results of surgical resection for hilar cholangiocarcinomas are disappointing. The introduction of liver transplantation for this condition has brought new hope for the management of this disease. The aim of this review is to discuss the role of liver transplantation in this disease. DATA SOURCES: A MEDLINE search was conducted for the articles on liver transplantation for hilar cholangiocarcinoma. Their results have been compiled and compared with the existing literature on resection for this disease. RESULTS: The earlier series on liver transplantation for hilar cholangiocarcinoma were not encouraging because of poor patient selection. The Mayo Clinic protocol of neoadjuvant chemoradiation followed by liver transplantation has shown remarkable success (survival at 1-, 3-, and 5-year post-transplantation being 92%, 82%, and 82%, respectively). With better patient selection and integration of neoadjuvant chemoradiation, the long-term survival is superior to that of the patients who undergo resection, as shown by the published literature on resection. The limitations of organ availability can be overcome by the living donor liver transplantation programme. This review article discusses the rationale, pros and cons of liver transplantation vis-á-vis resection for hilar cholangiocarcinoma. CONCLUSIONS: Liver transplantation, especially living donor liver transplantation, is a new and exciting alternative to resection for hilar cholangiocarcinoma. Integration of neoadjuvant chemoradiation has the potential to further improve the curative potential of liver transplantation. The strategy of combining neoadjuvant chemoradiation and liver transplantation brings new hope for the treatment of this difficult disease.
Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/cirurgia , Transplante de Fígado , Terapia Combinada , HumanosRESUMO
BACKGROUND: The outcome of liver transplantation (LT) is influenced by the recipient's clinical condition. In a retrospective observational study, we evaluated the role of pre-LT Molecular Adsorbent Recirculating System (MARS) treatment in improving the clinical status and thereby the outcome of patients with chronic liver disease and severe hepatic decompensation. METHODS: Between March 2002 and September 2006, 70 patients with end-stage chronic liver disease underwent living-donor LT (LDLT). Of these, 9 (13%) patients with severely decompensated liver function (serum bilirubin> 350 micromol/L [20 mg/dL] and/or hepatic encephalopathy > or = grade 2) received pre-LT MARS treatment. RESULTS: The median MELD score was 33 (range, 26-47). A median of 2 (range, 1-6) sessions (8 hour/session) of MARS dialysis was performed per patient. MARS treatment was associated with reduction in serum bilirubin, creatinine and ammonia levels and no procedure-related complications. CONCLUSION: Pre-LT MARS is well tolerated and results in reduction of jaundice and improvement in renal function and may be useful in the management of patients with severe hepatic decompensation.
Assuntos
Hepatopatias/terapia , Transplante de Fígado , Adulto , Feminino , Humanos , Hepatopatias/fisiopatologia , Fígado Artificial , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
INTRODUCTION: Living donor liver transplantation (LDLT) has progressed dramatically in Asia due to the scarcity of cadaver donors and is increasingly performed in Singapore. The authors present their experience with adult LDLT. MATERIALS AND METHODS: Adult LDLTs performed at the Asian Centre for Liver Diseases and Transplantation, Singapore from 20 April 2002 until 20 March 2006 were reviewed. All patients received right lobe grafts and were managed by the same team throughout this period. Data were obtained by chart review. This study presents both recipient and donor outcomes in a single centre. RESULTS: A total of 65 patients underwent LDLT. Forty-three were genetically related while 22 were from emotionally-related donors. The majority were chronic liver failure while 14% were acute. The most common indication for LDLT was end-stage liver disease due to hepatitis B virus. A total of 22 patients with hepatoma were transplanted and overall 1-year disease specific survival was 94.4%. The mean model for end-stage liver disease (MELD) score was 17.4 +/- 9.4 (range, 6 to 40). Six patients had preoperative molecular adsorbent recycling system (MARS) dialysis with 83% transplant success rate. The mean follow-up was 479.2 days with a median of 356 days. One-year overall survival was 80.5%. There was 1 donor mortality and morbidity rate was 17%. Our series is in its early stage with good perioperative survival outcome with 1-month and 3-month actuarial survival rates of 95.4% and 87.3% respectively. CONCLUSION: The study demonstrates that LDLT can be done safely with good results for a variety of liver diseases. However, with dynamically evolving criteria and management strategies, further studies are needed to maximise treatment outcome.
Assuntos
Transplante de Fígado , Doadores Vivos , Avaliação de Resultados em Cuidados de Saúde , Adulto , Feminino , Hospitais Especializados , Humanos , Transplante de Fígado/mortalidade , Transplante de Fígado/estatística & dados numéricos , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Enfermagem Perioperatória , Singapura/epidemiologia , Taxa de SobrevidaRESUMO
Liver transplantation is an established treatment modality for patients with hepatocellular carcinoma (HCC), creating a potential for disease-free, long-term survival. In Asia, due to a severe shortage of donors, resection remains the treatment of choice for patients with HCC and good liver functional reserve. The use of marginal donors, split liver grafts and grafts from living donors are potential solutions that are best performed in experienced liver transplant centres to ensure an optimal outcome. Ethical issues relating to living donor liver transplantation have yet to be fully addressed. The roles of therapies to limit tumour progression during the waiting period, such as transarterial chemoembolization, need to be further investigated in the setting of a prospective trial and their benefits better defined.
Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Ásia/epidemiologia , Humanos , Transplante de Fígado/estatística & dados numéricos , Doadores Vivos , Prognóstico , Obtenção de Tecidos e ÓrgãosRESUMO
Biliary complication is the Achilles' heel for live donor liver transplant. Bile leak is particularly difficult to manage as the anastomotic site was often angled acutely. We described a patient with bile leak managed by a modified rendezvous technique whereby the endoscopist and radiologist work simultaneously under fluoroscopy. Unlike the traditionally described rendezvous technique where the grasping of guidewire occurred at the duodenum, the grasping of guidewire occurred at the biloma in this modified technique. Insertion of biliary stent could then be performed over the guidewire through the duodenoscope. The bile leak resolved after keeping the biliary stents in situ for 12 months.
Assuntos
Ductos Biliares/cirurgia , Bile , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/efeitos adversos , Doadores Vivos , Anastomose Cirúrgica/efeitos adversos , Carcinoma Hepatocelular/etiologia , Duodenoscopia , Hepatite B/complicações , Humanos , Fígado , Cirrose Hepática/etiologia , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/terapia , StentsRESUMO
Spontaneous bacterial peritonitis (SBP) is a common cause of morbidity and mortality in patients with advanced cirrhosis and portal hypertension. While gram-negative rods and Enterococcus species are the common offending organisms, Salmonella has also been recognized as a rare and atypical offending organism. Atypical features of Salmonella SBP include both its occurrence in cirrhotic patients with immunosuppressive state and its lack of typical neutroascitic response. Diagnosis is often delayed as it requires confirmation from ascitic fluid culture. We report a case of Salmonella SBP occurring in a patient with decompensated cryptogenic cirrhosis with concurrent low-grade non-Hodgkin lymphoma and prior treatment with rituximab. Physicians should be aware of the atypical presentation, especially in cirrhotic patients who are immunosuppressed.
RESUMO
BACKGROUND: Surgical resection is the standard treatment for hepatocellular carcinoma (HCC). However, the role of surgery in treatment of large tumors (10 cm or more) is controversial. We have analyzed, in a single centre, the long-term outcome associated with surgical resection in patients with such large tumors. METHODS: We retrospectively investigated 166 patients who had undergone surgical resection between July 1995 and December 2006 because of large (10 cm or more) HCC. Survival analysis was done using the Kaplan-Meier method. Prognostic factors were evaluated using univariate and multivariate analyses. RESULTS: Of the 166 patients evaluated, 80% were associated with viral hepatitis and 48.2% had cirrhosis. The majority of patients underwent a major hepatectomy (48.2% had four or more segments resected and 9% had additional organ resection). The postoperative mortality was 3%. The median survival in our study was 20 months, with an actuarial 5-year and 10-year overall survival of 28.6% and 25.6%, respectively. Of these patients, 60% had additional treatment in the form of transarterial chemoembolization, radiofrequency ablation or both. On multivariate analysis, vascular invasion (P < 0.001), cirrhosis (P = 0.028), and satellite lesions/multicentricity (P = 0.006) were significant prognostic factors influencing survival. The patients who had none of these three risk factors had 5-year and 10-year overall survivals of 57.7% each, compared with 22.5% and 19.3%, respectively, for those with at least one risk factor (P < 0.001). CONCLUSIONS: Surgical resection for those with large HCC can be safely performed with a reasonable long-term survival. For tumors with poor prognostic factors, there is a pressing need for effective adjuvant therapy.
Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Análise Atuarial , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica , Criança , Terapia Combinada , Eletrocoagulação , Feminino , Seguimentos , Humanos , Fígado/patologia , Testes de Função Hepática , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , Retratamento , Singapura , Análise de SobrevidaRESUMO
Extracorporeal albumin dialysis with the molecular adsorbent recirculating system (MARS) machine is a new supportive intervention for patients with liver failure. It removes bilirubin and other albumin-bound toxins from the patient and has been shown by preliminary studies of liver failure patients to be beneficial. Our study examines the ability of predialysis molar ratio of bilirubin to albumin to predict the decrease of bilirubin by MARS. We had 5 patients and results from 29 treatments. The results showed a significant correlation between the predialysis molar ratio of bilirubin (total and conjugated) to albumin to the reduction in bilirubin (total and conjugated): R(2) = 0.27 and 0.62 respectively, P <.005 for both. There was no significant correlation with the predialysis molar ratio of unconjugated bilirubin to albumin to the reduction in unconjugated bilirubin. The ratio of change in total bilirubin (micromol/L) to the predialysis molar ratio of total bilirubin to albumin and the ratio of change in conjugated bilirubin (micromol/L) to the predialysis molar ratio of conjugated bilirubin to albumin were 6.2 (+/- 4.2) and 10.8 (+/- 4.3), respectively (mean (+/- SD)). The results enable us to predict the likely reduction in bilirubin (especially conjugated) after each MARS treatment and also suggest to us that albumin infusion before MARS treatment may reduce the efficacy of bilirubin removal. Whether this ratio applies to other albumin-bound toxins remains open for investigation.
Assuntos
Bilirrubina/sangue , Falência Hepática/terapia , Diálise Renal/métodos , Albumina Sérica/análise , Humanos , Falência Hepática/sangueRESUMO
BACKGROUND: The indications of liver transplantation in hepatocellular carcinoma (HCC) are evolving. With the advent of living donor liver transplantation (LDLT), there is a renewed interest in this procedure for tumors beyond the standard Milan criteria. METHODS: We retrospectively analyzed the outcome of 28 patients who underwent LDLT for HCC in one institution. Survival analysis was done using the Kaplan-Meier method. RESULTS: Of the 28 patients, 9, 12 and 7 had Child's A, B and C cirrhosis respectively; 26 (93%) had underlying hepatitis B or C. Nineteen patients (68%) had tumors exceeding the Milan criteria. Postoperative (within 90 days) mortality and morbidity rates were 2/28 (7%) and 7/28 (25%) respectively. The actuarial overall 1-year, 2-year and 3-year survival rates were 76%, 76% and 51%, respectively. The actuarial 1-year, 2-year and 3-year recurrence free survival rates (computed by censoring the data of patients who died of causes other than HCC recurrence) were 88%, 82% and 70%, respectively. Although the survival rates were better for tumors within the Milan criteria than those exceeding them, the difference was not significant. CONCLUSIONS: LDLT is an effective modality in the treatment of HCC in patients with liver cirrhosis. It may also provide an opportunity for potential cure to patients with tumors beyond Milan criteria.
Assuntos
Adulto , Idoso , Carcinoma Hepatocelular/complicações , Intervalo Livre de Doença , Feminino , Hepatite B/complicações , Hepatite C/complicações , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/mortalidade , Transplante de Fígado/métodos , Doadores Vivos , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prevalência , Estudos Retrospectivos , Taiwan/epidemiologia , Resultado do TratamentoAssuntos
Neoplasias das Glândulas Suprarrenais/secundário , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/secundário , Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/cirurgia , Hepatectomia , Humanos , Masculino , Resultado do TratamentoRESUMO
BACKGROUND: The outcome of liver transplantation (LT) is influenced by the recipient's clinical condition. In a retrospective observational study, we evaluated the role of pre-LT Molecular Adsorbent Recirculating System (MARS) treatment in improving the clinical status and thereby the outcome of patients with chronic liver disease and severe hepatic decompensation. METHODS: Between March 2002 and September 2006, 70 patients with end-stage chronic liver disease underwent living-donor LT (LDLT). Of these, 9 (13%) patients with severely decompensated liver function (serum bilirubin> 350 micromol/L [20 mg/dL] and/or hepatic encephalopathy > or = grade 2) received pre-LT MARS treatment. RESULTS: The median MELD score was 33 (range, 26-47). A median of 2 (range, 1-6) sessions (8 hour/session) of MARS dialysis was performed per patient. MARS treatment was associated with reduction in serum bilirubin, creatinine and ammonia levels and no procedure-related complications. CONCLUSION: Pre-LT MARS is well tolerated and results in reduction of jaundice and improvement in renal function and may be useful in the management of patients with severe hepatic decompensation.