Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.143
Filtrar
1.
Medicine (Baltimore) ; 98(47): e17900, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764786

RESUMO

OBJECTIVE: To observe the immediate and mid-term effects of partial spleen embolization (PSE) in reducing hepatic venous pressure gradient (HVPG) in patients with cirrhotic esophagogastric varices. METHODS: Patients diagnosed with cirrhosis and esophagogastric varices in our hospital between July 2016 and March 2018 were consecutively selected. Forty-three patients were selected based on the eligibility criteria to undergo PSE. The change in HVPG 5 minutes before and after embolization, was used to determine the immediate effect of PSE on HVPG reduction. HVPG was retested after 6 months to observe the change in the antihypertensive effect along with time. RESULTS: Forty-three patients successfully underwent PSE and HVPG measurements. The HVPG was 17.7 ±â€Š3.9 mmHg and 13.9 ±â€Š3.1 mmHg before and after PSE, respectively, showing a significant decrease (21.5%, P < .05). Among them, 18 cases were retested for HVPG at 6 months after PSE, and the results showed significant differences in the HVPG levels before, immediately and 6 months after PSE. Compared with preoperative PSE, HVPG was decreased by 22.9% and 17.7% (P < 0.05) immediately and at 6 months after operation, respectively. There was no significant change at 6 months after PSE when compared with immediate postoperative PSE. No serious complications were observed in patients during their postoperative hospital stay. CONCLUSION: PSE immediately reduced the portal pressure, and HVPG remained stable at 6 months after surgery. PSE is considered as a safe and easy to implement method, and is expected to be one of the treatments for reducing the portal pressure.


Assuntos
Embolização Terapêutica/métodos , Varizes Esofágicas e Gástricas/fisiopatologia , Varizes Esofágicas e Gástricas/terapia , Pressão na Veia Porta/fisiologia , Baço/irrigação sanguínea , Varizes Esofágicas e Gástricas/etiologia , Feminino , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
2.
Zhonghua Gan Zang Bing Za Zhi ; 27(10): 777-781, 2019 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-31734992

RESUMO

Objective: To investigate the safety, feasibility, and preliminary clinical experience of ultrasonic guided percutaneous portal vein punctures combined bi-directional angiography in the treatment by transjugular intrahepatic portosystemic shunt(TIPS). Methods: From January 2016 to June 2018, 15 patients with TIPS from our hospital who were treated by ultrasonic guided percutaneous portal vein punctures combined with bi-directional angiography were enrolled,and were recruited as experimental group. During the same period, 30 patients who were treated by TIPS combined with traditional methods were enrolled, and were recruited as control group. There was no statistical difference in baseline characteristics between the two groups (P > 0.05). The portal pressure difference in preoperative and postoperative, the fluoroscopy time, the number of puncture needles and complications were recorded. After treatment, the patients were followed up through outpatient service or telephone method. Results: The technical success rate was 100% in experimental group, and 96.7% in control group. In the experimental group, number of percutaneous transhepatic portal vein puncture by needle was 1-3 (average, 2.13 ± 0.74), and the number of portal vein puncture needles in the control group were 1-11 (average, 4.16 ± 2.13). The number of puncture needles in the experimental group were significantly decreased than in the control group (P < 0.001). In the experimental group, the fluoroscopy time was 18 ~ 46 (average 29.64 ± 8.79) minutes. In the control group, the fluoroscopy time was 12 ~ 150 (average 44.57 ± 26.84) minutes.The fluoroscopy time was significantly reduced in the experimental group compared with the control group(P = 0.023). Conclusion: Ultrasound-guided portal vein combined with bidirectional angiog-raphy is safe, feasible, and reliable in the treatment by TIPS. Compare with traditional TIPS, it can reduce the fluoroscopy time, the number of puncture needles and the liver injury.


Assuntos
Veia Porta/diagnóstico por imagem , Derivação Portossistêmica Transjugular Intra-Hepática , Angiografia , Fluoroscopia , Humanos , Agulhas , Pressão na Veia Porta , Punções , Estudos Retrospectivos , Resultado do Tratamento , Ultrassonografia
3.
World J Gastroenterol ; 25(39): 5953-5960, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31660032

RESUMO

BACKGROUND: Portal hypertension (PHT) is primarily caused by an increase in resistance to portal outflow and secondarily by an increase in splanchnic blood flow. Vascular hyporeactivity both in systemic circulation and in the mesenteric artery plays a role in the hyperdynamic circulatory syndrome. AIM: To explore gender differences and the role of endogenous sex hormones in PHT and vascular reactivity of mesenteric arterioles in rats. METHODS: Cirrhosis and PHT were established by subcutaneous injection of carbon tetrachloride (CCl4) in both male and female integral and castrated rats (ovariectomized [OVX] in female rats, orchiectomy [ORX] in male rats). The third-order branch of the mensenteric artery was divided and used to measure vascular reactivity to vasoconstrictors. RESULTS: No significant difference in portal pressure was observed between integral and castrated male PHT rats (15.2 ± 2.1 mmHg vs 16.7 ± 2.7 mmHg, P > 0.05). The portal pressure in integral female PHT rats was lower than that in OVX female PHT rats (12.7 ± 2.7 mmHg vs 16.5 ± 2.4 mmHg, P < 0.05). In PHT rats, the concentration response curves of the mesenteric arterioles to norepinephrine were shifted to the right, and the maximal responses (Emax) values were decreased and effective concentrations causing half maximum responses (EC50) values were increased, compared to those of non-PHT rats, both in male and female rats. Compared to non-PHT integral male rats, the sensitivity of the mesenteric arterioles of non-PHT ORX male rats to norepinephrine was decreased (P > 0.05). However, there was no difference between integral and ORX male rats with PHT. In integral female PHT rats, the concentration response curves were shifted to the left (P < 0.05), and the Emax values were increased and EC50 values were decreased compared to OVX female PHT rats. CONCLUSION: Clear gender differences were observed in mesenteric vascular reactivity in CCl4-induced cirrhotic and PHT rats. Conservation of estrogen can retain the sensitivity of the mesenteric arterioles to vasoconstrictors and has a protective effect on splanchnic vascular function in PHT.


Assuntos
Arteríolas/fisiologia , Hormônios Esteroides Gonadais/metabolismo , Hipertensão Portal/fisiopatologia , Cirrose Hepática Experimental/fisiopatologia , Resistência Vascular/fisiologia , Animais , Arteríolas/efeitos dos fármacos , Tetracloreto de Carbono/toxicidade , Feminino , Humanos , Hipertensão Portal/induzido quimicamente , Hipertensão Portal/metabolismo , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/metabolismo , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/fisiopatologia , Pressão na Veia Porta/efeitos dos fármacos , Pressão na Veia Porta/fisiologia , Ratos , Ratos Sprague-Dawley , Fatores Sexuais , Circulação Esplâncnica/efeitos dos fármacos , Circulação Esplâncnica/fisiologia , Resistência Vascular/efeitos dos fármacos , Vasoconstritores/administração & dosagem
4.
Ann Transplant ; 24: 401-406, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31273186

RESUMO

BACKGROUND We assessed the alterations in portal hemodynamics associated with donor right hepatectomy and its effects on functional regeneration of the remnant liver. MATERIAL AND METHODS This prospective study included 30 adult living donors who underwent right hepatectomy in the Liver Transplantation Unit, Faculty of Medicine, Cairo University from June 2015 to October 2016. During donor surgery, portal venous pressure (PVP) was measured using an antithrombotic catheter inserted into the main portal vein, and was measured before and after clamping of the right portal vein. Postoperatively, liver function tests were done daily until normalization. The outcome measures were the time to normalization of liver function tests and effect of residual volume and steatosis on PVP. RESULTS All donors had normal PVP before clamping and changed significantly after clamping (p<0.001). After clamping, 25 donors (83%) had a PVP above 12 mmHg; i.e. had high portal pressure. The median percentage of change was 55%. There were obvious increases in liver enzymes and bilirubin after surgery, but albumin and international normalized ratio showed progressive decreases postoperatively. The percent change in PVP was positively correlated with the levels of liver enzymes, time to normalization of liver enzymes, albumin, and bilirubin, and with the degree of steatosis, bit it was negatively correlated with residual liver volume. CONCLUSIONS During living donor liver transplantation, PVP increases by over 50% after clamping of the right portal vein of the donor's liver. This increase is associated with temporary delay of normalization of liver function of the donors.


Assuntos
Transplante de Fígado/métodos , Fígado/fisiologia , Doadores Vivos , Pressão na Veia Porta/fisiologia , Veia Porta/fisiologia , Adulto , Feminino , Hepatectomia , Humanos , Fígado/irrigação sanguínea , Testes de Função Hepática , Masculino , Estudos Prospectivos , Adulto Jovem
5.
Acta Med Port ; 32(6): 420-426, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31292022

RESUMO

INTRODUCTION: Excessive portal venous pressure in the liver remnant is an independent factor in the occurrence of posthepatectomy liver failure and small-for-size syndrome. The baseline portal pressure prior to hepatectomy was not considered previously. The aim of this study is to assess the impact of portal pressure change during hepatectomy on the patient outcome. MATERIAL AND METHODS: Prospective observational study including 30 patients subjected to intraoperative measurement of portal pressure before and after hepatectomy. This variation was related to the patient outcome. Control group evaluation was assessed. Patient, disease and procedure features were considered. The optimal cut-off of portal pressure variation was determined. Linear regression or logistic regression was applied to identify predictors of the outcome. RESULTS: The univariate analysis showed that portal pressure increase after hepatectomy was associated with coagulation impairment in the first 30 postoperative days (p < 0.05), and with the occurrence of major complications (p = 0.01), namely hepatic failure (p = 0.041). The multivariate analysis showed that portal venous pressure increase ≥ 2 mmHg is an independent factor for worse outcomes. DISCUSSION: As in previous studies, this study concludes that, after hepatectomy, in addition to the functional liver remnant, other factors are responsible for deterioration of liver function and patient outcome, such as the portal pressure increase and the exposure to chemotherapy prior to hepatectomy. This work may influence the definition of future indications for portal influx modulation. CONCLUSION: Patient outcomes are influenced by the portal venous pressure increase: an increment ≥ 2 mmHg after hepatectomy seems to increase the risk of major complications.


Assuntos
Transtornos da Coagulação Sanguínea/etiologia , Hepatectomia/efeitos adversos , Falência Hepática/etiologia , Pressão na Veia Porta/fisiologia , Complicações Pós-Operatórias/etiologia , Idoso , Análise de Variância , Área Sob a Curva , Determinação da Pressão Arterial/métodos , Estudos de Casos e Controles , Feminino , Hepatectomia/mortalidade , Humanos , Hipertensão , Coeficiente Internacional Normatizado , Cuidados Intraoperatórios , Modelos Lineares , Fígado/enzimologia , Falência Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Pressão na Veia Porta/efeitos dos fármacos , Cuidados Pós-Operatórios , Complicações Pós-Operatórias/mortalidade , Estudos Prospectivos , Tempo de Protrombina , Fatores de Tempo , Resultado do Tratamento
6.
Transplant Proc ; 51(6): 1946-1949, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31279408

RESUMO

BACKGROUND: The aim of the present study was to evaluate spleen volume (SV) and the factors influencing it after adult-to-adult living donor liver transplantation (A2LDLT) using a left lobe. METHODS: Pretransplant computed tomography (CT) and post-transplant CT 2 years after A2LDLT were examined by volumetric analysis in 24 patients. We divided the recipients into the following 2 groups according to the post-transplant SV: >500 mL (Group A) and ≤500 mL (Group B). The factors affecting the change in post-transplant SV were compared between the 2 groups. RESULTS: The mean pretransplant SV decreased significantly after A2LDLT. Platelet counts after living donor liver transplantation increased significantly relative to the pretransplant values. Post-transplant SV was >500 mL in 9 patients (Group A) and ≤500 mL in 15 (Group B). Pretransplant SV, platelet count, anhepatic time, operative time, intraoperative blood loss, post-transplant portal vein pressure >20 mm Hg, and post-transplant portal vein flow >250 mL/min/100 g graft weight showed significant differences between the 2 groups. Actual graft volume (GV) and GV/standard liver volume ratio showed no intergroup differences. Multivariate analysis showed that the only significant factor related to a post-transplant SV of >500 mL was the pretransplant SV. Post-transplant platelet counts were significantly increased from the pretransplant values in both Group A and Group B. CONCLUSIONS: Pretransplant SV is the only significant factor predicting a SV of >500 mL after A2LDLT. However, even in patients with a SV of >500 mL, the platelet count increased significantly from the pretransplant value.


Assuntos
Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/etiologia , Esplenomegalia/etiologia , Adulto , Peso Corporal , Feminino , Humanos , Fígado/patologia , Transplante de Fígado/métodos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Duração da Cirurgia , Tamanho do Órgão , Contagem de Plaquetas , Pressão na Veia Porta , Complicações Pós-Operatórias/sangue , Período Pré-Operatório , Fatores de Risco , Baço/patologia , Baço/cirurgia , Esplenomegalia/sangue , Tomografia Computadorizada por Raios X , Transplantes/patologia
7.
Hepatobiliary Pancreat Dis Int ; 18(4): 337-342, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31278029

RESUMO

BACKGROUND: Graft inflow modulation (GIM) during adult-to-adult living donor liver transplantation (LDLT) is a common strategy to avoid small-for-size syndrome, and some transplant surgeons attempt small size graft strategy with frequent GIM procedures, which are mostly performed by splenectomy, in LDLT. However, splenectomy can cause serious complications such as portal vein thrombosis and overwhelming postsplenectomy infection. METHODS: Forty-eight adult-to-adult LDLT recipients were enrolled in this study and retrospectively reviewed. We applied the graft selection criteria, which routinely fulfill graft-to-recipient weight ratio ≥ 0.8%, and consider GIM as a backup strategy for high portal venous pressure (PVP). RESULTS: In our current strategy of LDLT, splenectomy was performed mostly due to hepatitis C and splenic arterial aneurysms, but splenectomy for GIM was intended to only one patient (2.1%). The final PVP values ≤ 20 mmHg were achieved in all recipients, and no significant difference was observed in patient survival or postoperative clinical course based on whether splenectomy was performed or not. However, 6 of 18 patients with splenectomy (33.3%) developed postsplenectomy portal vein thrombosis (PVT), while none of the 30 patients without splenectomy developed PVT after LDLT. Splenectomy was identified as a risk factor of PVT in this study (P < 0.001). Our study revealed that a lower final PVP could be risk factor of postsplenectomy PVT. CONCLUSIONS: Using sufficient size grafts was one of the direct solutions to control PVP, and allowed GIM to be reserved as a backup procedure. Splenectomy should be avoided as much as possible during LDLT because splenectomy was found to be a definite risk factor of PVT. In splenectomy cases with a lower final PVP, a close follow-up is required for early detection and treatment of PVT.


Assuntos
Transplante de Fígado/efeitos adversos , Doadores Vivos , Veia Porta , Esplenectomia/efeitos adversos , Trombose Venosa/etiologia , Adulto , Feminino , Humanos , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Pressão na Veia Porta , Veia Porta/diagnóstico por imagem , Veia Porta/fisiopatologia , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/fisiopatologia
8.
PLoS One ; 14(5): e0217488, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31150446

RESUMO

INTRODUCTION: Despite advances in perioperative management and surgical technique, postoperative liver failure remains a feared complication after hepatic resection. Various supportive treatment options are under current discussion, but lack of structured evaluation. We therefore established a porcine model of major liver resection to study regeneration after partial hepatectomy in a reliable and well-defined pre-clinical setting. METHODS: Major hepatectomy was performed on seven minipigs with the intention to set up a non-lethal but relevant transient impairment of liver function. For steady postoperative vascular access (e.g. for blood withdrawal, measurement of venous pressure), permanent catheters were implanted into the internal jugular and portal veins, respectively. Animals were followed up for 30 days; clinical and laboratory results were recorded in detail. Monitoring was enhanced by non-invasive determination of the maximum liver function capacity (LiMAx test). RESULTS AND CONCLUSIONS: The established porcine model appeared suitable for evaluation of postoperative liver regeneration. Clinical characteristics and progression of liver function impairment as well as subsequent recovery were comparable to courses known from surgery in humans. Laboratory parameters (e.g. liver enzymes, bilirubin, INR, coagulation factor II) showed relevant derangements during postoperative days (POD) 0 to 3 followed by normalization until POD 7. Application of the LiMAx test was feasible in minipigs, again showing values comparable to humans and kinetics in line with obtained laboratory parameters. The exteriorized portal vein catheters enabled intra- and postoperative monitoring of portal venous pressures as well as easy access for blood withdrawal without relevant risk of postoperative complications.


Assuntos
Hepatectomia/efeitos adversos , Falência Hepática/diagnóstico , Regeneração Hepática/fisiologia , Complicações Pós-Operatórias/diagnóstico , Acetamidas/administração & dosagem , Acetamidas/química , Animais , Testes Respiratórios/métodos , Isótopos de Carbono/administração & dosagem , Isótopos de Carbono/análise , Isótopos de Carbono/química , Modelos Animais de Doenças , Estudos de Viabilidade , Feminino , Humanos , Injeções Intramusculares , Fígado/metabolismo , Fígado/fisiopatologia , Fígado/cirurgia , Falência Hepática/etiologia , Falência Hepática/fisiopatologia , Masculino , Pressão na Veia Porta , Veia Porta , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologia , Suínos , Porco Miniatura
9.
Dig Dis ; 37(6): 498-508, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31067534

RESUMO

BACKGROUND/AIMS: One hallmark of chronic liver disease in patients with portal hypertension is the formation of portal-systemic collaterals in which angiogenesis has a fundamental role. We studied patients with chronic liver disease undergoing liver transplantation to correlate levels of circulating angiogenic factors in portal and peripheral circulation with portal pressure and portal-systemic collaterals. METHODS: Sixteen patients who underwent liver transplantation were enrolled. During transplant surgery, we determined portal venous pressure and portal-systemic collateral formation. We determined angiogenics mediator levels in systemic and portal plasma. Peripheral plasma from healthy donors was measured as controls. RESULTS: Vascular endothelial growth factor (VEGF)-R1 and 2, Ang-1 and 2, Tie2, FGF- 1 and 2, CD163, PDGFR-ß, PDGFsRα, PDGF-AB and BB, CD163, TGF-ß VASH-1 levels were significantly different in the controls in comparison to cases. Significantly decreased portal venous levels of Ang-1, FGF-1, PDGF-AB/BB, and CC were observed in patients with higher portal pressure. Peripheral VEGF, Ang-1, pPDGF-AB, BB, and CC were significantly decreased in patients with more severe collateral formation. While peripheral VEGF-R1 was higher in patients with severe collateral formation. For portal circulation, VEGF, Ang-1, -pPDGF-AB, BB, and CC were significantly decreased in patients with more severe collateral formation Conclusions: Angiogenesis factors correlated with portal pressure and collateral formation and different patterns of circulating angiogenesis mediators were found in peripheral and portal blood of patients with chronic liver disease. These results support the importance of angiogenic pathways in cirrhosis and portal hypertension and highlight areas for further study to identify clinically useful noninvasive markers of portal pressure and collateral formation.


Assuntos
Circulação Colateral , Hepatopatias/fisiopatologia , Neovascularização Patológica/patologia , Pressão na Veia Porta , Adulto , Idoso , Animais , Doença Crônica , Feminino , Humanos , Fígado/patologia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/fisiopatologia , Doadores de Tecidos
10.
Ann Surg ; 269(6): 1025-1033, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31082898

RESUMO

OBJECTIVE: To investigate the safety and efficacy of somatostatin as liver inflow modulator in patients with end-stage liver disease (ESLD) and clinically significant portal hypertension (CSPH) undergoing liver transplantation (LT) (ClinicalTrials.gov number,01290172). BACKGROUND: In LT, portal hyperperfusion can severely impair graft function and survival, mainly in cases of partial LT. METHODS: Thirty-three patients undergoing LT for ESLD and CSPH were randomized double-blindly to receive somatostatin or placebo (2:1). The study drug was administered intraoperatively as 5-mL bolus (somatostatin: 500 µg), followed by a 2.5 mL/h infusion (somatostatin: 250 µg/h) for 5 days. Hepatic and systemic hemodynamics were measured, along with liver function tests and clinical outcomes. The ischemia-reperfusion injury (IRI) was analyzed through histological and protein expression analysis. RESULTS: Twenty-nine patients (18 receiving somatostatin, 11 placebo) were included in the final analysis. Ten patients responded to somatostatin bolus, with a significant decrease in hepatic venous portal gradient (HVPG) and portal flow of -28.3% and -29.1%, respectively. At graft reperfusion, HVPG was lower in patients receiving somatostatin (-81.7% vs -58.8%; P = 0.0084), whereas no difference was observed in the portal flow (P = 0.4185). Somatostatin infusion counteracted the decrease in arterial flow (-10% vs -45%; P = 0.0431). There was no difference between the groups in the severity of IRI, incidence of adverse events, long-term complications, graft, and patient survival. CONCLUSIONS: Somatostatin infusion during LT in patients with CSPH is safe, reduces the HVPG, and preserves the arterial inflow to the graft. This study establishes the efficacy of somatostatin as a liver inflow modulator.


Assuntos
Doença Hepática Terminal/complicações , Doença Hepática Terminal/cirurgia , Hormônios/uso terapêutico , Hipertensão Portal/tratamento farmacológico , Transplante de Fígado , Somatostatina/uso terapêutico , Idoso , Método Duplo-Cego , Doença Hepática Terminal/fisiopatologia , Feminino , Humanos , Hipertensão Portal/complicações , Masculino , Pessoa de Meia-Idade , Pressão na Veia Porta , Resultado do Tratamento
11.
Gastroenterology ; 157(1): 193-209.e9, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30872106

RESUMO

BACKGROUND & AIMS: Mechanical forces contribute to portal hypertension (PHTN) and fibrogenesis. We investigated the mechanisms by which forces are transduced by liver sinusoidal endothelial cells (LSECs) into pressure and matrix changes. METHODS: We isolated primary LSECs from mice and induced mechanical stretch with a Flexcell device, to recapitulate the pulsatile forces induced by congestion, and performed microarray and RNA-sequencing analyses to identify gene expression patterns associated with stretch. We also performed studies with C57BL/6 mice (controls), mice with deletion of neutrophil elastase (NE-/-) or peptidyl arginine deiminase type IV (Pad4-/-) (enzymes that formation of neutrophil extracellular traps [NETs]), and mice with LSEC-specific deletion of Notch1 (Notch1iΔEC). We performed partial ligation of the suprahepatic inferior vena cava (pIVCL) to simulate congestive hepatopathy-induced portal hypertension in mice; some mice were given subcutaneous injections of sivelestat or underwent bile-duct ligation. Portal pressure was measured using a digital blood pressure analyzer and we performed intravital imaging of livers of mice. RESULTS: Expression of the neutrophil chemoattractant CXCL1 was up-regulated in primary LSECs exposed to mechanical stretch, compared with unexposed cells. Intravital imaging of livers in control mice revealed sinusoidal complexes of neutrophils and platelets and formation of NETs after pIVCL. NE-/- and Pad4-/- mice had lower portal pressure and livers had less fibrin compared with control mice after pIVCL and bile-duct ligation; neutrophil recruitment into sinusoidal lumen of liver might increase portal pressure by promoting sinusoid microthrombi. RNA-sequencing of LSECs identified proteins in mechanosensitive signaling pathways that are altered in response to mechanical stretch, including integrins, Notch1, and calcium signaling pathways. Mechanical stretch of LSECs increased expression of CXCL1 via integrin-dependent activation of transcription factors regulated by Notch and its interaction with the mechanosensitive piezo calcium channel. CONCLUSIONS: In studies of LSECs and knockout mice, we identified mechanosensitive angiocrine signals released by LSECs which promote PHTN by recruiting sinusoidal neutrophils and promoting formation of NETs and microthrombi. Strategies to target these pathways might be developed for treatment of PHTN. RNA-sequencing accession number: GSE119547.


Assuntos
Capilares/metabolismo , Quimiocina CXCL1/metabolismo , Células Endoteliais/metabolismo , Hipertensão Portal/metabolismo , Fígado/irrigação sanguínea , Infiltração de Neutrófilos , Estresse Mecânico , Trombose/metabolismo , Animais , Sinalização do Cálcio , Capilares/citologia , Armadilhas Extracelulares , Hidrolases/genética , Técnicas In Vitro , Integrinas/metabolismo , Elastase de Leucócito/genética , Ligadura , Fígado/metabolismo , Mecanotransdução Celular , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pressão na Veia Porta , Receptor Notch1/genética , Veia Cava Inferior/cirurgia
12.
Front Med ; 13(3): 398-408, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30820806

RESUMO

Increased serum urotensin II (UII) levels in human cirrhotic populations have been recently shown, but the long-term effects of UII receptor antagonist on the cirrhosis have not been investigated. To investigate the therapeutic effects of urotensin II receptor (UT) antagonist palosuran on rats with carbon tetrachloride (CCl4)-induced cirrhosis, the hepatic and systemic hemodynamics, liver fibrosis, the metalloproteinase-13 (MMP-13)/tissue inhibitor of metalloproteinase-1 (TIMP-1) ratio, hepatic Rho-kinase activity, and the endothelial nitric oxide synthase (eNOS) activity are measured in CCl4-cirrhotic rats treated with palosuran or vehicle for 4 weeks. Primary hepatic stellate cells (HSCs) are used to investigate the changes in UII/UT expression and the in vitro effect of palosuran. Compared with the vehicle-treated cirrhotic rats, treatment with palosuran can reduce the portal pressure (PP), decrease the risk of liver fibrosis and the level of α smooth muscle actin, collagen-I (COL-I), and transforming growth factor ß expression. However, treatment with palosuran can increase MMP-13/TIMP-1, pvasodilator-stimulated phosphoprotein (p-VASP), and p-eNOS expression. Moreover, in vitro UII/UT mRNA expression increases during HSC activation. MMP-13/TIMP-1, COL-I, and p-VASP are inhibited after palosuran treatment. Our data indicate that long-term administration of palosuran can decrease PP in cirrhosis, which results from decreased hepatic fibrosis and enhanced eNOS-dependent HSC vasodilatation.


Assuntos
Cirrose Hepática/tratamento farmacológico , Óxido Nítrico Sintase Tipo III/metabolismo , Pressão na Veia Porta , Quinolinas/farmacologia , Receptores Acoplados a Proteínas-G/antagonistas & inibidores , Ureia/análogos & derivados , Animais , Tetracloreto de Carbono , Hemodinâmica , Células Estreladas do Fígado/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Cirrose Hepática/induzido quimicamente , Masculino , Ratos , Ratos Sprague-Dawley , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Ureia/farmacologia , Quinases Associadas a rho/metabolismo
13.
Gastroenterology ; 157(1): 149-162, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30905652

RESUMO

BACKGROUND & AIMS: We investigated the effect of albumin treatment (20% solution) on hypoalbuminemia, cardiocirculatory dysfunction, portal hypertension, and systemic inflammation in patients with decompensated cirrhosis with and without bacterial infections. METHODS: We performed a prospective study to assess the effects of long-term (12 weeks) treatment with low doses (1 g/kg body weight every 2 weeks) and high doses (1.5 g/kg every week) of albumin on serum albumin, plasma renin, cardiocirculatory function, portal pressure, and plasma levels of cytokines, collecting data from 18 patients without bacterial infections (the Pilot-PRECIOSA study). We also assessed the effect of short-term (1 week) treatment with antibiotics alone vs the combination of albumin plus antibiotics (1.5 g/kg on day 1 and 1 g/kg on day 3) on plasma levels of cytokines in biobanked samples from 78 patients with bacterial infections included in a randomized controlled trial (INFECIR-2 study). RESULTS: Circulatory dysfunction and systemic inflammation were extremely unstable in many patients included in the Pilot-PRECIOSA study; these patients had intense and reversible peaks in plasma levels of renin and interleukin 6. Long-term high-dose albumin, but not low-dose albumin, was associated with normalization of serum level of albumin, improved stability of the circulation and left ventricular function, and reduced plasma levels of cytokines (interleukin 6, granulocyte colony-stimulating factor, interleukin 1 receptor antagonist, and vascular endothelial growth factor) without significant changes in portal pressure. The immune-modulatory effects of albumin observed in the Pilot-PRECIOSA study were confirmed in the INFECIR-2 study. In this study, patients given albumin had significant reductions in plasma levels of cytokines. CONCLUSIONS: In an analysis of data from 2 trials (Pilot-PRECIOSA study and INFECIR-2 study), we found that albumin treatment reduced systemic inflammation and cardiocirculatory dysfunction in patients with decompensated cirrhosis. These effects might be responsible for the beneficial effects of albumin therapy on outcomes of patients with decompensated cirrhosis. ClinicalTrials.gov, Numbers: NCT00968695 and NCT03451292.


Assuntos
Albuminas/administração & dosagem , Infecções Bacterianas/imunologia , Citocinas/imunologia , Hipertensão Portal/fisiopatologia , Hipoalbuminemia/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Albumina Sérica/metabolismo , Infecções Bacterianas/complicações , Infecções Bacterianas/fisiopatologia , Estudos de Casos e Controles , Feminino , Hemodinâmica , Humanos , Hipertensão Portal/etiologia , Hipoalbuminemia/etiologia , Hipoalbuminemia/imunologia , Hipoalbuminemia/fisiopatologia , Inflamação , Circulação Hepática , Cirrose Hepática/complicações , Cirrose Hepática/imunologia , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pressão na Veia Porta , Sistema Porta , Estudos Prospectivos , Renina/sangue
14.
Gastrointest Endosc Clin N Am ; 29(2): 311-320, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30846155

RESUMO

The number of endoscopic ultrasound (EUS)-guided interventions is rapidly growing within advanced endoscopy. EUS offers high-resolution imaging of mediastinal and intra-abdominal vasculature, which can be targeted for various interventions, hence a growing number of studies have explored EUS-guided vascular catheterization. Potential clinical applications of EUS-guided portal venous access include angiography, measurement of the portosystemic pressure gradient, and EUS-guided transhepatic intrahepatic portosystemic shunt creation. This article reviews different devices and techniques used in these applications.


Assuntos
Angiografia/métodos , Determinação da Pressão Arterial/métodos , Endossonografia , Hipertensão Portal/diagnóstico por imagem , Hipertensão Portal/terapia , Animais , Humanos , Hipertensão Portal/fisiopatologia , Pressão na Veia Porta , Derivação Portossistêmica Cirúrgica/métodos , Ultrassonografia de Intervenção
15.
Transplant Proc ; 51(3): 919-924, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30737025

RESUMO

Small-for-size-liver grafts (SFSG) in adult transplant recipients have elevated risk of graft failure, limiting its application in clinical liver transplantation. Relevant preclinical model of SFSG is lacking. Relevant to deceased-donor split liver transplant and living-donor liver transplant in adult recipients, in this study, we present our initial characterization of SFSG model using monosegments of a discarded human donor liver.


Assuntos
Circulação Hepática/fisiologia , Transplante de Fígado/métodos , Doadores Vivos , Perfusão/métodos , Pressão na Veia Porta/fisiologia , Veia Porta/fisiopatologia , Transplantes , Adulto , Sobrevivência de Enxerto , Humanos , Veia Porta/cirurgia , Fatores de Tempo , Resultado do Tratamento
16.
Ann Vasc Surg ; 58: 378.e11-378.e15, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30802581

RESUMO

Portopulmonary hypertension (PoPH) is a well-recognized complication of portal hypertension. This study reports a case of PoPH that was secondarily caused by post-traumatic mesenteric arteriovenous fistula. A 38-year-old man with a history of knife stabbing wounds in the abdomen in 2003 was admitted to the hospital with exertional shortness of breath and a mechanic murmur over the umbilical region. Computed tomography indicated signs of PoPH and mesenteric arteriovenous fistula. Percutaneous catheter-directed embolization was first performed but failed. Subsequently, the patient was successfully treated with fistula resection and partial enterectomy. The patient had been postoperatively followed regularly, and chief symptoms had been alleviated significantly and pulmonary pressure had successfully decreased to normal range. We believe that this is the first case of PoPH caused by mesenteric arteriovenous fistula.


Assuntos
Traumatismos Abdominais/etiologia , Fístula Arteriovenosa/etiologia , Hipertensão Portal/etiologia , Hipertensão Pulmonar/etiologia , Artérias Mesentéricas/lesões , Veias Mesentéricas/lesões , Traumatismo Múltiplo/etiologia , Ferimentos Perfurantes/etiologia , Traumatismos Abdominais/diagnóstico , Adulto , Angiografia Digital , Pressão Arterial , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/fisiopatologia , Fístula Arteriovenosa/cirurgia , Angiografia por Tomografia Computadorizada , Humanos , Hipertensão Portal/diagnóstico por imagem , Hipertensão Portal/fisiopatologia , Hipertensão Portal/cirurgia , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/cirurgia , Masculino , Artérias Mesentéricas/diagnóstico por imagem , Artérias Mesentéricas/fisiopatologia , Artérias Mesentéricas/cirurgia , Veias Mesentéricas/diagnóstico por imagem , Veias Mesentéricas/fisiopatologia , Veias Mesentéricas/cirurgia , Traumatismo Múltiplo/diagnóstico , Flebografia/métodos , Pressão na Veia Porta , Artéria Pulmonar/fisiopatologia , Ferimentos Perfurantes/diagnóstico
17.
Eur Radiol ; 29(9): 5032-5041, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30796573

RESUMO

OBJECTIVES: Transjugular intrahepatic portosystemic shunt (TIPS) and partial splenic embolization (PSE) were two interventional radiological treatments for the complications of cirrhosis. This study aimed to investigate the effects of concomitant PSE on the long-term shunt patency and overall survival of TIPS-treated patients. METHODS: Forty-eight patients with TIPS insertion were enrolled and studied retrospectively. They were divided into TIPS+PSE (n = 16) and TIPS groups (n = 32), undergoing combined therapy using TIPS and PSE, and monotherapy using TIPS alone, respectively. RESULTS: The 5-year cumulative primary patency rate in the TIPS+PSE group was markedly higher than in the TIPS group (56.8% vs. 32.8%, p = 0.028), whereas the 5-year cumulative secondary patency rate (93.8% vs. 87.7%, p = 0.749) and overall survival rate (62.5% vs. 30.7%, p = 0.414) were not significantly different between the two groups. Cox-regression models revealed that group (hazard ratio [HR], 0.235; 95% CI, 0.084-0.665; p = 0.006), portal venous pressure decline (HR, 0.687; 95% CI, 0.563-0.838; p = 0.000), and baseline portal vein thrombosis (HR, 3.955; 95% CI, 1.634-9.573; p = 0.002) were significant predictors for shunt dysfunction, while only ascites (HR, 2.941; 95% CI, 1.250-6.920; p = 0.013) was a significant predictor for mortality. No severe adverse event was noted in the two groups except for the potential risk of splenic abscess development in the TIPS+PSE group. CONCLUSIONS: Concomitant PSE may help increase the long-term primary shunt patency rate, but not the overall survival of TIPS-treated patients. Further prospective studies are needed to validate these retrospective findings and to investigate the potential mechanisms. KEY POINTS: • Combined therapy using TIPS and PSE is associated with higher primary patency rates than TIPS alone. • Combined therapy using TIPS and PSE is associated with similar rates of secondary patency and overall survival of patients than TIPS alone. • Group (TIPS alone or TIPS+PSE), PVD, and baseline PVT are three independent predictors for shunt dysfunction, while ascites is the only independent predictor for mortality.


Assuntos
Embolização Terapêutica/métodos , Hemorragia Gastrointestinal/terapia , Cirrose Hepática/complicações , Derivação Portossistêmica Transjugular Intra-Hepática/métodos , Idoso , China/epidemiologia , Feminino , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/mortalidade , Humanos , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pressão na Veia Porta , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Resultado do Tratamento
18.
J Vet Med Sci ; 81(3): 361-364, 2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30674733

RESUMO

The relation between complete or partial ligation of extrahepatic portosystemic shunting and intraoperative mesenteric portovenography (IMP) was evaluated in 72 canines. Of the 72 dogs, 55 had complete ligation and 17 underwent partial ligation of abnormal vessels. IMP allowed evaluation of the number of intrahepatic portal branches and ratio of the diameter of cranial (CrPV) and caudal main portal vein (CaPV) at the shunt location. Nearly all cases in the complete ligation group and nearly half of the cases in the partial ligation group had three or more portal vein branches. CrPV/CaPV was 0.75 ± 0.24 in the complete ligation group and 0.29 ± 0.15 in the partial ligation group. CrPV/CaPV can be an effective new method for assessing IMP.


Assuntos
Cães/anormalidades , Pressão na Veia Porta , Veia Porta/anormalidades , Fístula Vascular/veterinária , Malformações Vasculares/veterinária , Animais , Cães/cirurgia , Estudos de Viabilidade , Feminino , Masculino , Flebografia/veterinária , Veia Porta/diagnóstico por imagem , Veia Porta/cirurgia , Estudos Retrospectivos , Fístula Vascular/diagnóstico por imagem , Fístula Vascular/cirurgia , Malformações Vasculares/diagnóstico por imagem , Malformações Vasculares/cirurgia
19.
J Ultrasound Med ; 38(9): 2305-2314, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30609088

RESUMO

OBJECTIVES: To analyze the clinical significance of using hepatic transit time (HTT) to evaluate portal vein pressure in gastroesophageal varices patients. METHODS: For the observation group, we enrolled 50 gastroesophageal varices patients who had received esophagogastric variceal embolization in our hospital between January 2015 and February 2018. Patients without liver disease populated the control group and were recruited during the same time period. All patients underwent contrast-enhanced sonography. In the observation group, free portal pressure (FPP) was detected during esophagogastric variceal embolization with ultrasound guidance. Differences in hepatic artery-hepatic vein transit time (HA-HVTT), portal vein-hepatic vein transit time (PV-HVTT), and parenchyma-hepatic vein transit time (PA-HVTT) were compared between groups. Correlations between HA-HVTT, PV-HVTT, PA-HVTT, and FPP in the observation group were analyzed using the Pearson coefficient and linear regression analysis. RESULTS: HA-HVTT (t = 5.078; P < .001), PV-HVTT (t = 12.163; P < .001), and PA-HVTT (t = 2.649; P = .009) within the observation group were significantly lower than those of the control group. The areas under the curve of HTT were 0.771 (HA-HVTT), 0.951 (PV-HVTT), and 0.652 (PA-HVTT), and the sensitivity and specificity of PV-HVTT at 7.99 seconds were 86.0% and 88.0%, respectively. The HA-HVTT (r = -0.799; P < .001), PV-HVTT (r = -0.554; P < .001), and PA-HVTT (r = -0.735; P < .001) negatively correlated to FPP in the observation group. Linear regression analysis showed y = -0.410x + 7.254 (HA-HVTT and FPP), y = -0.335x + 4.983 (PV-HVTT and FPP), and y = -0.566x + 4.997 (PA-HVTT and FPP) in the observation group. CONCLUSION: Compared with the control patients, the HTT of patients with portal hypertension-esophagogastric varices was significantly shorter, and showed an inverse relationship with FPP.


Assuntos
Varizes Esofágicas e Gástricas/fisiopatologia , Artéria Hepática/fisiopatologia , Veias Hepáticas/fisiopatologia , Pressão na Veia Porta/fisiologia , Ultrassonografia/métodos , Meios de Contraste , Feminino , Artéria Hepática/diagnóstico por imagem , Veias Hepáticas/diagnóstico por imagem , Humanos , Aumento da Imagem/métodos , Masculino , Pessoa de Meia-Idade , Veia Porta , Sensibilidade e Especificidade , Fatores de Tempo
20.
Clin Sci (Lond) ; 133(1): 153-166, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30606815

RESUMO

Liver failure is the major cause of death following liver resection. Post-resection portal venous pressure (PVP) predicts liver failure, is implicated in its pathogenesis, and when PVP is reduced, rates of liver dysfunction decrease. The aim of the present study was to characterize the hemodynamic, biochemical, and histological changes induced by 80% hepatectomy in non-cirrhotic pigs and determine if terlipressin or direct portacaval shunting can modulate these effects. Pigs were randomized (n=8/group) to undergo 80% hepatectomy alone (control); terlipressin (2 mg bolus + 0.5-1 mg/h) + 80% hepatectomy; or portacaval shunt (PCS) + 80% hepatectomy, and were maintained under terminal anesthesia for 8 h. The primary outcome was changed in PVP. Secondary outcomes included portal venous flow (PVF), hepatic arterial flow (HAF), and biochemical and histological markers of liver injury. Hepatectomy increased PVP (9.3 ± 0.4 mmHg pre-hepatectomy compared with 13.0 ± 0.8 mmHg post-hepatectomy, P<0.0001) and PVF/g liver (1.2 ± 0.2 compared with 6.0 ± 0.6 ml/min/g, P<0.0001) and decreased HAF (70.8 ± 5.0 compared with 41.8 ± 5.7 ml/min, P=0.002). Terlipressin and PCS reduced PVP (terlipressin = 10.4 ± 0.8 mmHg, P=0.046 and PCS = 8.3 ± 1.2 mmHg, P=0.025) and PVF (control = 869.0 ± 36.1 ml/min compared with terlipressin = 565.6 ± 25.7 ml/min, P<0.0001 and PCS = 488.4 ± 106.4 ml/min, P=0.002) compared with control. Treatment with terlipressin increased HAF (73.2 ± 11.3 ml/min) compared with control (40.3 ± 6.3 ml/min, P=0.026). The results of the present study suggest that terlipressin and PCS may have a role in the prevention and treatment of post-resection liver failure.


Assuntos
Hepatectomia , Artéria Hepática/efeitos dos fármacos , Circulação Hepática/efeitos dos fármacos , Falência Hepática/prevenção & controle , Fígado/irrigação sanguínea , Derivação Portocava Cirúrgica , Pressão na Veia Porta/efeitos dos fármacos , Veia Porta/efeitos dos fármacos , Terlipressina/farmacologia , Animais , Velocidade do Fluxo Sanguíneo , Modelos Animais de Doenças , Artéria Hepática/fisiopatologia , Fígado/patologia , Falência Hepática/etiologia , Falência Hepática/patologia , Falência Hepática/fisiopatologia , Masculino , Veia Porta/fisiopatologia , Sus scrofa
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA