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BACKGROUND & AIMS: The liver is the main organ of ketogenesis, while ketones are mainly metabolized in peripheral tissues via the critical enzyme 3-oxoacid CoA-transferase 1 (OXCT1). We previously found that ketolysis is reactivated in hepatocellular carcinoma (HCC) cells through OXCT1 expression to promote tumor progression; however, whether OXCT1 regulates antitumor immunity remains unclear. METHODS: To investigate the expression pattern of OXCT1 in HCC in vivo, we conducted multiplex immunohistochemistry experiments on human HCC specimens. To explore the role of OXCT1 in mouse HCC tumor-associated macrophages (TAMs), we generated LysMcreOXCT1f/f (OXCT1 conditional knockout in macrophages) mice. RESULTS: Here, we found that inhibiting OXCT1 expression in tumor-associated macrophages reduced CD8+ T-cell exhaustion through the succinate-H3K4me3-Arg1 axis. Initially, we found that OXCT1 was highly expressed in liver macrophages under steady state and that OXCT expression was further increased in TAMs. OXCT1 deficiency in macrophages suppressed tumor growth by reprogramming TAMs toward an antitumor phenotype, reducing CD8+ T-cell exhaustion and increasing CD8+ T-cell cytotoxicity. Mechanistically, high OXCT1 expression induced the accumulation of succinate, a byproduct of ketolysis, in TAMs, which promoted Arg1 transcription by increasing the H3K4me3 level in the Arg1 promoter. In addition, pimozide, an inhibitor of OXCT1, suppressed Arg1 expression as well as TAM polarization toward the protumor phenotype, leading to decreased CD8+ T-cell exhaustion and slower tumor growth. Finally, high expression of OXCT1 in macrophages was positively associated with poor survival in patients with HCC. CONCLUSIONS: In conclusion, our results demonstrate that OXCT1 epigenetically suppresses antitumor immunity, suggesting that suppressing OXCT1 activity in TAMs could be an effective approach for treating liver cancer. IMPACT AND IMPLICATIONS: The intricate metabolism of liver macrophages plays a critical role in shaping hepatocellular carcinoma progression and immune modulation. Targeting macrophage metabolism to counteract immune suppression presents a promising avenue for hepatocellular carcinoma treatment. Herein, we found that the ketogenesis gene OXCT1 was highly expressed in tumor-associated macrophages (TAMs) and promoted tumor growth by reprogramming TAMs toward a protumor phenotype. Pharmacological targeting or genetic downregulation of OXCT1 in TAMs enhances antitumor immunity and slows tumor growth. Our results suggest that suppressing OXCT1 activity in TAMs could be an effective approach for treating liver cancer.
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BACKGROUND: Integrator complex subunit 6 (INTS6) was found to play a tumour suppressing role in certain types of solid tumours. In this study, we wanted to determine the expression level of INTS6 in hepatocellular carcinoma (HCC) and evaluate its clinical characteristics and mechanisms in HCC patients (Lui and Lu, European Journal of Cancer, 51:S94, 2015). METHODS: First, we used a microarray analysis to explore the mRNA expression levels in HCC and paired normal liver tissues; second, we used qRT-PCR to measure the INTS6 mRNA levels in a cohort of 50 HCC tissues and adjacent normal liver tissues; third, we used Western blot analyses to detect the INTS6 protein levels in 20 paired HCC and normal liver tissues; fourth, we used immunohistochemistry to determine the INTS6 expression levels in 70 archived paraffin-embedded HCC samples. Finally, we investigated the suppressive function of INTS6 in the Wnt pathway. RESULTS: Herein, according to the microarray data analysis, the expression levels of INTS6 were dramatically down-regulated in HCC tissues vs. those in normal liver tissues (p<0.05). qRT-PCR and Western blot analyses showed that the INTS6 mRNA and protein expression was significantly down-regulated in tumour tissues compared to the adjacent normal liver tissues (p<0.05). Immunohistochemical assays revealed that decreased INTS6 expression was present in 62.9% (44/70) of HCC patients. Correlation analyses showed that INTS6 expression was significantly correlated with serum alpha-fetoprotein levels (AFP, p =0.004), pathology grade (p =0.005), and tumour recurrence (p =0.04). Kaplan-Meier analysis revealed that patients with low INTS6 expression levels had shorter overall and disease-free survival rates than patients with high INTS6 expression levels (p =0.001 and p =0.001). Multivariate regression analysis indicated that INTS6 was an independent predictor of overall survival and disease-free survival rates. Mechanistically, INTS6 increased WIF-1 expression and then inhibited the Wnt/ß-catenin signalling pathway. CONCLUSION: The results of our study show that down-regulated INTS6 expression is associated with a poorer prognosis in HCC patients. This newly identified INTS6/WIF-1 axis indicates the molecular mechanism of HCC and may represent a therapeutic target in HCC patients.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteínas Repressoras/genética , Proteínas Ribossômicas/genética , Proteínas Supressoras de Tumor/genética , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Proliferação de Células/genética , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas de Ligação a RNA , Via de Sinalização WntRESUMO
In this study, we aimed to determine whether the pseudogene integrator complex subunit 6 pseudogene 1 (INTS6P1) in plasma could be used as a novel approach to screen for and detect hepatocellular carcinoma (HCC). We explored the clinical role of INTS6P1: First, the expression level of INTS6P1 was measured in a cohort of 33 HCC tissue samples and adjacent normal liver tissue, next, the INTS6P1 expression was detected in the culture medium and tumor cells in a cellular experiment, and last, the diagnostic performance of INTS6P1 was examined in an independent cohort of 100 people. The expression level of INTS6P1 was remarkably downregulated in the HCC tissues compared with that in the normal liver tissues (p = 0.0066). In plasma, the INTS6P1 levels were significantly decreased in HCC patients compared with non-HCC patients (p < 0.01). Additionally, we inferred that INTS6P1 might be a prospective biomarker for screening HCC patients in which the serum-AFP levels were lower than 20 ng/ml by the area under the curve-receiver operating characteristic (AUC-ROC) analysis (p < 0.05). Pseudogene INTS6P1 could be used as a novel HCC plasma-based biomarker and might improve the accuracy of HCC screening.
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Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Fígado/metabolismo , Pseudogenes , Proteínas Ribossômicas/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Adulto , Idoso , Área Sob a Curva , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Estudos de Coortes , Meios de Cultura/química , Feminino , Células Hep G2 , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , RNA Neoplásico/sangue , Proteínas de Ligação a RNA , Curva ROC , Sensibilidade e EspecificidadeRESUMO
AIM: Although perioperative short-term administration of steroids can attenuate surgical stress response following liver resection, there is no consensus concerning the effect on postoperative complications. This study aims to use meta-analysis to quantitatively investigate the effect of perioperative short-term administration of steroids on postoperative complications following liver resection. METHODS: A systematic published work search was performed to detect randomized controlled trials (RCT) assessing the effect of perioperative short-term administration of steroids on outcomes following liver resection. Parameters of surgical stress, hospital stay and postoperative complications were analyzed. Two authors independently assessed study quality and extracted data. All data were analyzed using RevMan version 5 and meta-analyses were performed using a random-effects model. RESULTS: Five RCT published between 2001 and 2011 containing a total of 379 patients were eligible for final analysis. Serum total bilirubin, interleukin-6 and C-reactive protein were significantly lower in the steroid than in the control group on postoperative day 1 (P = 0.02, 0.004 and 0.02, respectively). There was no difference in duration of hospital stay between the steroid and control group (P = 0.37). The analysis of end-points including infective complications (odds ratio [OR], 0.95), wound complications (OR, 0.67), bile leakage (OR, 0.58) and overall complications (OR, 0.50) revealed no difference between steroid administration and no treatment. There was no postoperative death or adverse effect attributable to steroid treatment in all patients. CONCLUSION: On currently available evidence, short-term administration of steroids does not increase incidence of complications in patients undergoing liver resection.
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Retinoic acid receptor-related receptor alpha (RORalpha) has been proven to play a tumor suppressive role in certain types of solid tumors. However, the clinical characteristic of RORalpha has not been reported by far. This study investigated the expression of RORalpha in hepatocellular carcinoma (HCC) and evaluated its relationship with clinical parameters and prognosis in HCC patients. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blot analyses were performed to detect RORalpha expression levels in 20 paired HCC and corresponding adjacent non-cancerous tissues. Immunohistochemistry was performed on 100 archived paraffin-embedded HCC samples. Statistical analyses evaluated the correlations between RORalpha expression and clinicopathological features. qRT-PCR showed that RORalpha mRNA expression was significantly down-regulated in tumors compared to the adjacent non-cancerous tissues, and Western blots found that RORalpha protein expression was also reduced in tumor tissues. Immunohistochemical assays revealed that decreased RORalpha expression was present in 65 % of HCC patients. Correlation analyses showed that RORalpha expression was significantly correlated with serum alpha fetoprotein (AFP, p = 0.005), pathology grade (p < 0.001), tumor recurrence (p = 0.008), and vascular invasion (p < 0.001). Kaplan-Meier analysis revealed that patients with low RORalpha expression levels had a shorter overall and disease-free survival than patients with high expression (p < 0.001 and p = 0.002, respectively). Multivariate regression analysis indicated that RORalpha was an independent predictor for overall survival and disease-free survival. In conclusion, the results of our study showed that down-regulated RORalpha expression was associated with poorer prognosis in HCC patients. RORalpha may be a new potential prognostic marker for HCC patients.
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Biomarcadores Tumorais/fisiologia , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/fisiologia , Adulto , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/análise , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Prognóstico , Proteína Supressora de Tumor p53/fisiologia , alfa-Fetoproteínas/análiseRESUMO
AIM: To investigate the anti-hepatofibrotic effects of Gardenia jasminoides in liver fibrosis. METHODS: Male Sprague-Dawley rats underwent common bile duct ligation (BDL) for 14 d and were treated with Gardenia jasminoides by gavage. The effects of Gardenia jasminoides on liver fibrosis and the detailed molecular mechanisms were also assessed in human hepatic stellate cells (LX-2) in vitro. RESULTS: Treatment with Gardenia jasminoides decreased serum alanine aminotransferase (BDL vs BDL + 100 mg/kg Gardenia jasminoides, 146.6 ± 15 U/L vs 77 ± 6.5 U/L, P = 0.0007) and aspartate aminotransferase (BDL vs BDL + 100 mg/kg Gardenia jasminoides, 188 ± 35.2 U/L vs 128 ± 19 U/L, P = 0.005) as well as hydroxyproline (BDL vs BDL + 100 mg/kg Gardenia jasminoides, 438 ± 40.2 µg/g vs 228 ± 10.3 µg/g liver tissue, P = 0.004) after BDL. Furthermore, Gardenia jasminoides significantly reduced liver mRNA and/or protein expression of transforming growth factor ß1 (TGF-ß1), collagen typeâ Iâ (Colâ I) and α-smooth muscle actin (α-SMA). Gardenia jasminoides significantly suppressed the upregulation of TGF-ß1, Colâ Iâ and α-SMA in LX-2 exposed to recombinant TGF-ß1. Moreover, Gardenia jasminoides inhibited TGF-ß1-induced Smad2 phosphorylation in LX-2 cells. CONCLUSION: Gardenia jasminoides exerts antifibrotic effects in the liver fibrosis and may represent a novel antifibrotic agent.
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Ductos Biliares/efeitos dos fármacos , Gardenia/química , Regulação da Expressão Gênica , Células Estreladas do Fígado/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Animais , Colestase/tratamento farmacológico , Humanos , Cirrose Hepática Experimental/tratamento farmacológico , Masculino , Fosforilação , Extratos Vegetais/uso terapêutico , Ratos , Ratos Sprague-Dawley , Proteína Smad2/metabolismo , Fator de Crescimento Transformador beta1/metabolismoRESUMO
PURPOSE: This aims to evaluate the effects of lamivudine (LAM) and entecavir (ETV) in preventing hepatitis B virus (HBV) re-infection after liver transplantation (LT). METHODS: A retrospective matched case-control method was used in this study. From June 2005 to May 2007, the patients who received LAM (100 mg qd) or ETV (0.5 mg qd) were chosen. The LAM and ETV groups were matched using a 3:1 ratio based on the factors, such as age, gender, LAM or ETV antiviral duration, primary disease, and HBV DNA levels at the initiation of antiviral therapy. Data on serum HBV markers, HBV DNA, and cumulative recurrence were collected. RESULTS: Two hundred and fifty-two patients were enrolled. The average duration of follow-up was 38.5 and 41.2 months (LAM and ETV groups) (p>0.05). Duration of pre-operative antiviral therapy was 30.3 and 25.8 d (LAM and ETV groups) (p>0.05). The HBV DNA level decreased from 3.89×10(6) to 5.31×10(5) copies/mL before LT in the LAM group, and decreased from 8.74×10(6) to 5.49×10(4) copies/mL in the ETV group (p<0.05). Eighteen patients in LAM group developed HBV re-infection and 0 in ETV group. CONCLUSION: ETV is superior to LAM for preventing HBV re-infection following LT.
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Antivirais/uso terapêutico , Doença Hepática Terminal/cirurgia , Guanina/análogos & derivados , Hepatite B Crônica/prevenção & controle , Lamivudina/uso terapêutico , Transplante de Fígado , Adulto , Idoso , Estudos de Casos e Controles , DNA Viral/sangue , Doença Hepática Terminal/virologia , Feminino , Guanina/uso terapêutico , Anticorpos Anti-Hepatite B/sangue , Antígenos da Hepatite B/sangue , Vírus da Hepatite B/imunologia , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Prevenção SecundáriaRESUMO
AIM: Laparoscopic hepatectomy has become a common method for treatment of hepatocellular carcinoma (HCC) nowadays, but the oncologic risks of laparoscopic liver resection for HCC are still under investigation. We performed a meta-analysis to quantitatively compare surgical and oncologic outcomes of patients with HCC undergoing laparoscopic versus open hepatectomy. METHODS: Systematic review and meta-analysis of studies comparing laparoscopic with open liver resection for HCC. Two authors independently assessed study quality and extracted data. All data were analyzed using RevMan 5. RESULTS: Ten studies comprising 627 patients were eligible for inclusion. The overall rate of conversion to open surgery was 6.6%. The laparoscopic group had significantly less blood loss by 223.17 mL (95% confidence interval [CI]: -331.81, -114.54; P < 0.0001), fewer need for transfusions (odds ratio [OR]: 0.42, 95% CI: 0.22, .079; P = 0.007), shorter hospital stay by 5.05 days (95% CI: -7.84, -2.25; P = 0.0004) and fewer postoperative complications (OR: 0.50; 95% CI: 0.32, 0.77; P = 0.002). No significant differences were found concerning surgery margin (weighted mean differences [WMD], 0.55; 95% CI: -0.71, 1.80; P = 0.39), resection margin positive rate (OR, 0.63; 95% CI: 0.25, 1.54; P = 0.31) and tumor recurrence (OR, 0.79; 95% CI: 0.49, 1.27; P = 0.33). In the 244 patients that underwent laparoscopic hepatectomy of all 10 studies included, no patients developed tumor recurrence at the site of resection margin, peritoneal dissemination or trocar-site metastases. CONCLUSIONS: On currently available evidence, laparoscopic resection appears not to affect oncologic outcomes and increase tumor recurrence. It also offers less blood loss, decreased rate of intraoperative transfusion and shorter lengths of hospital stay. Laparoscopic resection is a safe and feasible choice for selected patients with HCC.
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BACKGROUND: In addition to suprahepatic vena cava anastomosis in two-cuff rat liver transplantation, recipient portal vein revascularization is one of the most difficult procedures that must be performed, especially for beginners. MATERIALS AND METHODS: A total of 43 cases of liver transplantation were performed. Rats in Group 1 and Group 2 were subjected to transplant procedures that used the conventional and portal venoplasty techniques, respectively. The portal vein anastomosis duration, anhepatic phase length, portal vein surgical complications, and 1 wk post-transplant survival rates were recorded for each group. RESULTS: The portal revascularization duration was statistically significantly less for Group 2 versus Group 1 (1.50 ± 0.61 min and 4.32 ± 0.67 min, respectively, P < 0.05). The anhepatic phase length of Groups 1 and 2 were 21.79 ± 1.27 min and 18.55 ± 1.47 min, respectively (P < 0.05). No significant differences between the groups were observed in relation to either portal vein surgery complications or 1-week survival rates. CONCLUSIONS: The recipient portal venoplasty and cuff insertion technique is a safe and fast alternative surgical option for portal revascularization in two-cuff rat liver transplantations performed by a single trainee.
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Anastomose Cirúrgica/métodos , Transplante de Fígado/métodos , Veia Porta/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Animais , Sobrevivência de Enxerto/fisiologia , Circulação Hepática/fisiologia , Transplante de Fígado/fisiologia , Masculino , Modelos Animais , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To analyze the negative impact of preoperative neutrophil-lymphocyte ratio (NLR) on the tumor recurrence of hepatocellular carcinoma (HCC) after orthotopic liver transplantation. METHODS: The clinical data of HBV (hepatitis B virus)-associated HCC patients undergoing liver transplantation were retrospectively analyzed. Their clinical and pathological risk factors for tumor-free survival were evaluated by univariate analysis. The analysis of Cox multiple regression was performed to determine the parameters of predicting the HCC recurrence. NLR ≥ 2.5 was considered to be elevated. RESULTS: A total of 76 patients were identified. Among them, 37 had an elevated NLR. The 1, 3 and 5-year tumor-free survival rates were 69.2%, 52.7% and 50.9% respectively. The disease-free survival for patients with high NLR was significantly worse than that for those with normal NLR (1, 3, and 5 year survivals at 56.3%, 37.6% and 37.6% vs 81.1%, 66.9% and 63.3% respectively; P = 0.011). Univariate analysis of factors revealed that tumor size > 5 cm, tumor number > 3, vascular invasion, serum α-fetoprotein level ≥ 400 µg/L and NLR ≥ 2.5 were preoperative predictors of disease-free survival. Cox regression analysis showed that the presence of vascular invasion, tumor number > 3 and NLR ≥ 2.5 were independent prognostic factors of worse disease-free survival. CONCLUSION: An elevated NLR significantly increases the risk for tumor recurrence in HCC patients undergoing liver transplantation.
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Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Recidiva Local de Neoplasia/patologia , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/mortalidade , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: There are increasing numbers of patients who survive more than one year after liver transplantation. Many studies have focused on the early mortality of these patients. However, the factors affecting long-term survival are not fully understood. This study aims to evaluate prognostic factors predicting long-term survival and to explore measures for improving the survival outcomes of patients who underwent liver transplantation for benign end-stage liver diseases. METHODS: The causes of late death after liver transplantation and potential prognostic factors were retrospectively analyzed for 221 consecutive patients who underwent liver transplantation from October 2003 to June 2008. Twenty-seven variables were assessed using the Kaplan-Meier method, and those variables found to be univariately significant at P < 0.10 were entered into a backward step-down Cox proportional hazard regression analysis to identify the independent prognostic factors influencing the recipients' long-term survival. RESULTS: Twenty-eight recipients died one year after liver transplantation. The major causes of late mortality were infectious complications, biliary complications, and Hepatitis B virus recurrence/reinfection. After Cox analysis, the five remaining co-variables were: age, ABO blood group, cold ischemia time, post-infection region, and biliary complications. CONCLUSIONS: The major causes of late mortality were infection, biliary complications and Hepatitis B virus recurrence/reinfection. Five variables (Age, ABO blood group, cold ischemia time, infection, and biliary complications) had significant impacts on patient survival.
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Doença Hepática Terminal/mortalidade , Doença Hepática Terminal/cirurgia , Hepatite B/mortalidade , Humanos , Transplante de Fígado , Complicações Pós-Operatórias/mortalidade , Estudos RetrospectivosRESUMO
OBJECTIVE: To compare early and late orthotopic liver retransplantation (re-OLT) for patients with poor graft function after primary transplantation at our center and sum up our clinical experience in re-OLT. METHODS: The clinical data of 36 re-OLTs from January 2004 to July 2009 were analyzed retrospectively, consisting of the first group with 17 cases of early re-OLT and the second group with 19 cases of late re-OLT. The average ages were (45 ± 13) years and (48 ± 10) years, and the time intervals were (49 ± 54) days and (514 ± 342) days in early re-OLT group and late re-OLT group, respectively. RESULTS: Biliary tract complications were the main indications for early re-OLT and late re-OLT. Other common indications were vascular complications in early re-OLT and recurrence of primary diseases in late re-OLT. No significant differences were found between the groups with regard to the volume of bleeding during operation, cold ischemia time, operative duration and perioperative mortality except the MELD score. Outcome was fatal for 8 patients in early re-OLT and 10 patients in late re-OLT. Three deaths were due to severe sepsis-related disease, 3 deaths due to multiple organ failure in early re-OLT and 4 deaths due to severe sepsis-related disease, 3 deaths due to recurrence of HCC in late re-OLT. One and 2-year actuarial survival rates after re-OLT were 52.9% and 41.2%, respectively, for patients in early re-OLT, and 63.2% and 52.6%, respectively, for patients in late re-OLT. No significant differences were found regarding survival rates between the two groups (P > 0.05). CONCLUSIONS: The similar clinical results can be achieved in early and late re-OLT. Proper indications and optimal operation timing, experienced surgical procedures and effective perioperative anti-infection strategy contribute to the improvement of the overall survival rate of the patients after re-OLT.
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Transplante de Fígado , Reoperação , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVES: To find out the risk factors predicting long-term survival, and to explore the measures for further improving the survival outcome of whom underwent liver transplantation (LT) for benign end-stage liver disease. METHODS: The common causes of late death after LT and risk factors were retrospectively analyzed in 221 consecutive patients, who underwent LT from October 2003 to June 2007 and survived more than one year. Twenty-six potential risk factors were assessed by the Kaplan-Meier method, and those variables found to be univariately significant at P < 0.10 were entered into a backward step down Cox proportional hazard regression analysis to screen the independent risk factors influencing the recipient's long-term survival. RESULTS: There were 28 recipients died one year later after LT during the follow-up period. The major causes of late mortality were related to infectious complications 5.0% (11/221), biliary complications 3.6% (8/221) and HBV recurrence/reinfection 1.4% (3/221). After Cox proportional hazard regression analysis, 5 covariables finally retained in the formula were: age (RR = 2.325, P = 0.009), ABO blood group (RR = 2.206, P = 0.015), cold ischemia time (RR = 3.001, P = 0.000), post-infection region (RR = 1.665, P = 0.007) and biliary complications (RR = 2.655, P = 0.004). CONCLUSION: Age (≥ 60 years), ABO blood group (incompatible), cold ischemia time (> 12 h), infectious complications (lung infection) and biliary complications (diffuse biliary stricture) significantly impact patient's survival time.
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Transplante de Fígado/mortalidade , Adulto , Idoso , Feminino , Seguimentos , Humanos , Hepatopatias/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Análise de SobrevidaRESUMO
Accurate assessment of the biliary anatomy is important for the safety of liver donors in living donor liver transplantation (LDLT). We evaluated the biliary anatomy and variations of 12 living liver donors with 3-D contrast-enhanced ultrasonic cholangiography (3-D CEUSC) by injecting microbubble contrast agents into the common hepatic ducts intraoperatively. Two radiologists assessed the diagnostically adequate, delineation of biliary branch orders, visibility scores (grades 0 to 3) and anatomical patterns of the intrahepatic biliary tree by consensus. The results were compared with findings on intraoperative cholangiography (IOC) and surgery. 3-D CEUSC successfully demonstrated the spatial structure of the intrahepatic biliary tree in all 12 donors. The maximum branching order of intrahepatic bile ducts displayed on 3-D CEUSC was the fifth order in the right lobe and fourth order in the left lobe of the liver, respectively. The visibility scores of the first-order (3.00 +/- 0.00) and second-order (2.67 +/- 0.69) branches were significantly (p < 0.001) higher than that of the third-order (1.98 +/- 1.13) branches, whereas visibility scores of the second-order (2.88 +/- 0.34) and third-order (2.44 +/- 1.01) branches in the right lobe were significantly (p = 0.040 and p < 0.001, respectively) higher than those in the left lobe (2.46 +/- 0.88 and 1.33 +/- 0.99). The 3-D CEUSC images of the 12 donors were diagnostically adequate for evaluating the biliary anatomy. Normal biliary pattern in nine donors and biliary variations in three donors were confirmed by both IOC and surgical findings. 3-D CEUSC may be a potential alternative to IOC in the evaluation of biliary anatomical variation before graft harvesting in LDLT.
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Algoritmos , Ductos Biliares/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Transplante de Fígado/diagnóstico por imagem , Doadores Vivos , Ultrassonografia Doppler em Cores/métodos , Adulto , Colangiografia , Meios de Contraste , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Pessoa de Meia-Idade , Reconhecimento Automatizado de Padrão/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
BACKGROUND: The aim of this study was to analyze the combination with long-term, low-dose hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogs as prophylaxis for hepatitis B virus (HBV) recurrence and to assess the risk factors of HBV recurrence after orthotopic liver transplantation (OLT). METHODS: One hundred sixty patients undergoing OLT with HBV-related liver disease make up the cohort studied. Long-term, low dosage of HBIG in combination with nucleos(t)ide analogs were used as prophylaxis for HBV recurrence after OLT. Patient preoperative data were collected by a retrospective method, and the rate and risk factors of HBV recurrence post-OLT after a long-term follow-up were analyzed. RESULTS: Nineteen patients developed hepatitis B recurrence for a rate of recurrence of 11.88% (19/160). There was no significant correlation between HBV recurrence after OLT and the level of HBV DNA, HBeAg state pre-OLT, or the use of nucleoside analog drug therapy pre-OLT (P>0.05). Of 19 patients with HBV recurrence, 17 patients used Lamivudine, and HBV YMDD mutants were detected in nine cases. The HBV-YMDD mutation was the major reason for recurrence of HBV in our study (P<0.001). CONCLUSIONS: Long-term use of combination prophylaxis with nucleoside analogs and low-dose HBIG can effectively prevent hepatitis B recurrence after OLT, and that a positive preoperative serum HBV DNA status did not affect the recurrence rate of HBV post-OLT. Preoperative nucleoside analogs therapy is unlikely to be obligatory if the patients received effective combination prophylaxis postoperatively. HBV YMDD mutation is the primary reason for HBV recurrence in patients treated with Lamivudine after OLT.
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Hepatite B/cirurgia , Transplante de Fígado/estatística & dados numéricos , Adolescente , Adulto , Idoso , Antivirais/uso terapêutico , Carcinoma Hepatocelular/cirurgia , DNA Viral/sangue , DNA Viral/genética , Feminino , Seguimentos , Hepatite B/tratamento farmacológico , Hepatite B/imunologia , Hepatite B/prevenção & controle , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Hepatite C/complicações , Humanos , Imunoglobulinas/uso terapêutico , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Prevenção SecundáriaRESUMO
There has been a gradual increase in the number of patients with end-stage alcoholic liver disease (ALD) undergoing liver transplantation (LT) in mainland China. However, few studies have focused on the post-transplant outcomes of this population. The aim of this study was to evaluate the efficacy of LT in patients with ALD, mainly focusing on survival rates, complications, and alcohol recidivism. The results were retrospectively analyzed from 20 patients, who underwent LT for ALD from December 2003 to September 2007 at Liver Transplant Center of Third Affiliated Hospital of Sun Yat-sen University. The 1-, 2-, and 3-year survival rates of the ALD group and non-ALD group were 90.0, 80.0, 80.0% and 90.3, 84.7, 79.8%, respectively. There was no significant difference in 1-, 2-, and 3-year survival rates between these two groups (P=.909). No significant difference was observed in complications such as pulmonary infection (50.0 vs. 31.9%, P=.137), biliary complications (15.0 vs. 27.4%, P=.297), hepatic arterial complications (10.0 vs. 6.9%, P=.641), and rejection (15.0 vs. 8.1%, P=.394) after LT between the ALD group and non-ALD group. There was only one person who resumed mild, intermittent drinking after LT. End-stage ALD is a good indication for LT, with similar results in non-ALD patients. The major cause of death in ALD patients after LT was infectious complications. More attention is needed for the prophylaxis of infectious complications after LT.
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Hepatopatias Alcoólicas/cirurgia , Transplante de Fígado , Adulto , Idoso , China , Comorbidade , Progressão da Doença , Humanos , Hepatopatias Alcoólicas/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva , Taxa de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
Hepatic artery stenosis (HAS) is a common complication in liver transplant patients. Conventional angiography remains the gold standard for diagnosis. Recently, contrast-enhanced ultrasound (CEUS) has begun providing real-time angiographic-like images of vessels and allowing the accurate diagnosis of arterial diseases such as hepatic artery thrombosis. The purpose of this study was to evaluate the efficacy of CEUS in depicting HAS after liver transplantation. Forty-seven liver transplant recipients underwent CEUS examinations with the intravenous injection of microbubble contrast agents. The reference standard was conventional angiography for 15 patients and computed tomographic angiography for 32 patients. The presence, degree, location, and type of HAS were evaluated. For the detection of HAS by CEUS, the following was found: an accuracy of 91.5% (43/47), a sensitivity of 92.3% (36/39), a specificity of 87.5% (7/8), a positive predictive value of 97.3% (36/37), and a negative predictive value of 70% (7/10). CEUS corrected false-positive findings on color Doppler ultrasound in 7 of 47 cases (14.9%). The accuracy of CEUS in identifying the location and type of HAS was 92.3% (36/39) and 84.6% (33/39), respectively. CEUS is a useful noninvasive technique for the detection of HAS in liver transplant patients because it provides comprehensive information, including the presence, location, degree, and type. A positive CEUS finding suggests angiography as the next step rather than a computed tomography scan and may thereby alter the clinical imaging algorithm.
Assuntos
Algoritmos , Arteriopatias Oclusivas/diagnóstico por imagem , Protocolos Clínicos , Meios de Contraste , Artéria Hepática/diagnóstico por imagem , Transplante de Fígado/efeitos adversos , Fosfolipídeos , Hexafluoreto de Enxofre , Adulto , Idoso , Arteriopatias Oclusivas/etiologia , Constrição Patológica , Meios de Contraste/administração & dosagem , Feminino , Humanos , Injeções Intravenosas , Masculino , Microbolhas , Pessoa de Meia-Idade , Fosfolipídeos/administração & dosagem , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Hexafluoreto de Enxofre/administração & dosagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Ultrassonografia Doppler em CoresRESUMO
OBJECTIVE: To investigate the role of lipopolysaccharides (LPS), toll-like receptor 2 (TLR2) and inducible nitric oxide synthase (iNOS) in the development of hepatopulmonary syndrome (HPS). METHODS: Seventy-one patients were divided into 3 groups: end-stage liver disease with HPS (HPS group, n = 31), end-stage liver disease without HPS (non-HPS group, n = 30) and healthy volunteers (n = 10). Blood was collected at pre-OLT and Days 3, 7, 14, 21 and 28 post-OLT to detect the plasma LPS level, TLR2mRNA and iNOSmRNA in peripheral blood monocytes. RESULTS: The LPS, TLR2mRNA and iNOSmRNA at pre-OLT in HPS group were 4.31 +/- 3.267 ng/L, 336,594.10 +/- 366,901.14 and 63,982.24 +/- 74,127.47 copies/microg RNA respectively; 1.62 +/- 1.34 ng/L, 336,321.53 +/- 222,317.17 and 44,169.9 +/- 24,993.00 copies/microg RNA respectively in non-HPS group and 0.94 +/- .69 ng/L, 10,338.28 +/- 3,814.64 and 19,168.49 +/- 2,417.35 copies/microg RNA in normal control group. LPS, TLR2mRNA and iNOSmRNA at pre-OLT in HPS group were higher than those in non-HPS group without significance (P > 0.05), but significantly higher than those in control group (P < 0.05). The TLR2mRNA decreased in all end-stage liver disease patients at post-OLT with the improvement of liver function and oxygenation. CONCLUSION: The dysfunction of intestinal barrier and intestinal endotoxemia may be the important mechanisms of HPS through the elevation of LPS level and the expressions of TLR2mRNA and iNOSmRNA.
Assuntos
Síndrome Hepatopulmonar/sangue , Lipopolissacarídeos/metabolismo , Monócitos/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Receptor 2 Toll-Like/metabolismo , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA Mensageiro/metabolismoRESUMO
OBJECTIVE: To investigate the effects of dendritic cells (DCs) infected with adenovirus vector encoding mTERT on induction of mTERT antigen specific immunity against H22 hepatoma in vivo. METHODS: Forty Bal B/c mice were subcutaneously immunized with Ad-mTERT infected DC. Cytotoxicity of mTERT specific CTL was determined by 51Cr release assay. IL-2 and IFN-gamma were tested by ELISA. IFN-gamma ELISPOT assays were performed for measuring antigen specific IFN-gamma production by T cells. Tumor size and survival of the immunized mice were recorded and evaluated whether preexisting hepatoma metastases could be supressed after immunization with mTERT-expressing DCs. RESULTS: The lytic activity of CTL, IL-2 (871.25 pg/ml), IFN-gamma (169.15 ng/ml) and IFN-gamma secreting cells (378/10(6) spleen cells) elicited by the Ad-mTERT infected DCs were much stronger and higher than that by Ad-GFP group (131.6 pg/ml, 15.4 ng/ml, 36/10(6) spleen cells, P<0.05), DC group (71.3 pg/ml, 10.5 ng/ml, 21/10(6) spleen cells, P<0.05), PBS group (65.8 pg/ml, 7.4 ng/ml, 18/10(6) spleen cells, P<0.05). In prophylaxis and treatment experiment the Ad-mTERT/DCs immunized mice lived significantly longer than other groups, demonstrating that primary DCs were genetically modified to express the mTERT antigen and could suppress the tumor growth. CONCLUSION: Adenovirus vector mediated mTERT infected DCs can effectively induce mTERT antigen specific antitumor activity, and can induce protective and therapeutic antitumor immunity.
Assuntos
Células Dendríticas/imunologia , Imunização , Neoplasias Hepáticas Experimentais/imunologia , Linfócitos T Citotóxicos/imunologia , Telomerase/imunologia , Adenoviridae/genética , Animais , Linhagem Celular Tumoral , Células Dendríticas/metabolismo , Feminino , Vetores Genéticos , Interferon gama , Interleucina-2 , Neoplasias Hepáticas Experimentais/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Telomerase/metabolismo , Carga TumoralRESUMO
The aim of this study was to determine the efficacy of contrast-enhanced ultrasound for depicting the perfusion of hilar bile ducts in ischemic-type biliary lesions after orthotopic liver transplantation. Thirteen transplant recipients with ischemic-type biliary lesions and 12 patients without ischemic-type biliary lesions underwent ultrasound examinations after the injection of 1.5 mL of an intravenous contrast agent. The enhancement of the hilar bile duct wall in the arterial, portal venous, and late phases was qualitatively graded as higher, equal, lower, or none with respect to that of the adjacent liver parenchyma. No or low contrast enhancement was seen in 10 of 13 patients (76.90%) with biliary ischemia, whereas increased contrast enhancement with respect to the normal liver parenchyma was found in all 12 patients without biliary ischemia. The difference in the enhancement patterns between the 2 groups was significant (P = 0.0001). In conclusion, contrast-enhanced ultrasound is a new imaging modality to depict perfusion of the hilar bile duct. No or low contrast enhancement of the bile duct wall in the arterial phase may reflect the microcirculatory disturbance of biliary ischemia and may contribute to its early diagnosis.