RESUMEN
BACKGROUND: To determine the standard remnant liver volume (SRLV) threshold to avoid postoperative hepatic insufficiency inpatients in different stages of hepatic fibrosis who undergo right hemi-hepatectomy. METHODS: Data for 85 patients at our single medical center were analysed prospectively to examine whether the following factors differed significantly between those who experienced postoperative hepatic insufficiency and those who did not: height, prothrombin time, remnant liver volume, SRLV or hepatic fibrosis stage. RESULTS: Logistic regression showed SRLV and hepatic fibrosis stage to be independent risk factors for postoperative hepatic insufficiency. The threshold SRLV for predicting insufficiency was 203.2 ml/m2 across all patients [area under receiver operating characteristic curve (AUC) 0.778, sensitivity 66.67%, specificity 83.64%, p<0.0001), 193.8 ml/m2 for patients with severe hepatic fibrosis (AUC 0.938, sensitivity 91.30%, specificity 85.71%, p<0.0001), and 224.3 ml/m2 for patients with cirrhosis (AUC 0.888, sensitivity 100%, specificity 64.29%, p<0.0001). CONCLUSIONS: Right hemi-hepatectomy may be safer in Chinese patients when the standard remnant liver volume is more than 203.2 ml/m2 in the absence of hepatic fibrosis or cirrhosis, 193.8 ml/m2 in the presence of severe hepatic fibrosis or 224.3 ml/m2 in the presence of cirrhosis.
Asunto(s)
Carcinoma Hepatocelular , Hepatectomía/efectos adversos , Cirrosis Hepática , Neoplasias Hepáticas , Hígado , Adulto , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Simulación por Computador , Femenino , Hepatectomía/métodos , Insuficiencia Hepática/etiología , Insuficiencia Hepática/prevención & control , Humanos , Imagenología Tridimensional , Hígado/diagnóstico por imagen , Hígado/patología , Hígado/cirugía , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Estudios Prospectivos , Estándares de Referencia , Valores de Referencia , Factores de Riesgo , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Treatment of liver metastases of colorectal carcinoma is surgical resection. However, only 10-15% of the patients in this context will be candidate for curative resection arising other 10-13% after response to neoadyuvant chemotherapy. In order to perform the liver metastases surgery, it is necessary to have a sufficient remnant liver volume (RLV) which allows maintaining an optimal liver function after resection. Studies on liver regeneration have determined that CD133 + stem cells are involved in liver hypertrophy developed after an hepatectomy with encouraging results. As presented in previous studies, CD133 + stem cells can be selected from peripheral blood after stimulation with G-CSF, being able to obtain a large number of them. We propose to treat patients who do not meet criteria for liver metastases surgery because of insufficient RLV (<40%) with CD133 + cells together with portal embolization, in order to achieve enough liver volume which avoids liver failure. METHODS: /Design: The aim of this study is to evaluate the effectiveness of preoperative PVE plus the administration of CD133 + mobilized from peripheral blood with G-CSF compared to PVE only. SECONDARY AIMS ARE: to compare the grade of hypertrophy, speed and changes in liver function, anatomopathological study of hypertrophied liver, to determine the safety of the treatment and analysis of postoperative morbidity and surveillance. STUDY DESIGN: Prospective randomized longitudinal phase IIb clinical trial, open, to evaluate the efficacy of portal embolization (PVE) together with the administration of CD133 + cells obtained from peripheral blood versus PVE alone, in patients with hepatic metastasis of colorectal carcinoma (CCRHM). DISCUSSION: The number of CD133 + obtained from peripheral blood after G -CSF stimulation will be far greater than the number obtained with direct puncture of bone marrow. This will allow a greater intrahepatic infusion, which could have a direct impact on achieving a larger and quicker hypertrophy. Consequently, it will permit the treatment of a larger number of patients with an increase on their survival. TRIAL REGISTRATION: ClinicalTrials.gov, ID NCT03803241.
Asunto(s)
Neoplasias Colorrectales/patología , Embolización Terapéutica , Hepatectomía , Neoplasias Hepáticas/cirugía , Vena Porta , Cuidados Preoperatorios/métodos , Trasplante de Células Madre/métodos , Antígeno AC133 , Ensayos Clínicos Fase II como Asunto , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Insuficiencia Hepática/prevención & control , Humanos , Hígado/patología , Hígado/fisiología , Neoplasias Hepáticas/secundario , Regeneración Hepática , Metastasectomía , Tamaño de los Órganos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND AND AIMS: Hepatic crisis is an emergent complication affecting patients with sickle cell disease (SCD); however, the molecular mechanism of sickle cell hepatobiliary injury remains poorly understood. Using the knock-in humanized mouse model of SCD and SCD patient blood, we sought to mechanistically characterize SCD-associated hepato-pathophysiology applying our recently developed quantitative liver intravital imaging, RNA sequence analysis, and biochemical approaches. APPROACH AND RESULTS: SCD mice manifested sinusoidal ischemia, progressive hepatomegaly, liver injury, hyperbilirubinemia, and increased ductular reaction under basal conditions. Nuclear factor kappa B (NF-κB) activation in the liver of SCD mice inhibited farnesoid X receptor (FXR) signaling and its downstream targets, leading to loss of canalicular bile transport and altered bile acid pool. Intravital imaging revealed impaired bile secretion into the bile canaliculi, which was secondary to loss of canalicular bile transport and bile acid metabolism, leading to intrahepatic bile accumulation in SCD mouse liver. Blocking NF-κB activation rescued FXR signaling and partially ameliorated liver injury and sinusoidal ischemia in SCD mice. CONCLUSIONS: These findings identify that NF-κB/FXR-dependent impaired bile secretion promotes intrahepatic bile accumulation, which contributes to hepatobiliary injury of SCD. Improved understanding of these processes could potentially benefit the development of therapies to treat sickle cell hepatic crisis.
Asunto(s)
Anemia de Células Falciformes/complicaciones , Bilis/metabolismo , Colestasis/etiología , Insuficiencia Hepática/etiología , Hígado/patología , Adolescente , Adulto , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/genética , Animales , Conductos Biliares Intrahepáticos/diagnóstico por imagen , Conductos Biliares Intrahepáticos/patología , Colestasis/patología , Colestasis/prevención & control , Modelos Animales de Enfermedad , Femenino , Técnicas de Sustitución del Gen , Hemoglobina Falciforme/genética , Insuficiencia Hepática/patología , Insuficiencia Hepática/prevención & control , Humanos , Microscopía Intravital , Hígado/diagnóstico por imagen , Masculino , Ratones , Persona de Mediana Edad , FN-kappa B/antagonistas & inhibidores , FN-kappa B/efectos de los fármacos , FN-kappa B/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Transducción de Señal/efectos de los fármacos , Adulto JovenRESUMEN
Intrahepatic cholangiocarcinoma (iCCA) is the second most common hepatic malignancy and its incidence has been shown to increase significantly during the past decades. Complete surgical resection is currently acknowledged as the only curative treatment option able to provide adequate long-term outcomes. We herein review technical, functional and oncologic limitations for resectability, discuss current surgical aspects as well as highlight the fields in which future research and practice should focus on in order to ameliorate long-term outcomes in patients with iCCA.
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Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares Intrahepáticos , Colangiocarcinoma/cirugía , Hepatectomía/métodos , Escisión del Ganglio Linfático/métodos , Recurrencia Local de Neoplasia/cirugía , Neoplasias de los Conductos Biliares/patología , Vasos Sanguíneos/patología , Colangiocarcinoma/patología , Insuficiencia Hepática/prevención & control , Humanos , Laparoscopía , Trasplante de Hígado , Márgenes de Escisión , Terapia Neoadyuvante , Invasividad Neoplásica , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Múltiples/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & controlRESUMEN
Objective: To explore the feasibility, safety and efficacy of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and portal vein embolization (PVE) for the treatment of liver cancer with insufficient future liver remnant (FLR) . Methods: The data regarding the clinical controlled trials in comparison of ALPPS and PVE in liver surgery were collected from the both domestic and international publications searched through the datebases of PubMed, Cochrane Library, Embase, CNKI, and VIP.Meta analysis was performed by RevMan 5.3 software. Results: Total 10 studies with clinical control were analyzed (9 cohort studies and 1 randomized controlled study) .A total of 620 patients were included, with 165 cases in ALPPS group, 455 cases in PVE group.Results of Meta-analysis showed that there was statistically significant difference (P<0.05) between the two groups in the completion rate of two-steps surgery (OR=6.04, 95%CI: 2.97-12.31, Z=4.96) , FLR growth rate (MD=19.91, 95% CI: 8.64-31.18, Z=3.46) , two-steps surgical interval (MD=-30.48, 95%CI: -37.87--23.09, Z=8.09) , and R0 resection rate (OR=2.29, 95%CI=1.07-4.90, Z=2.13) .While there was no significant differences between the two groups in the mortality rate of postoperative within 90-days, postoperative the total complication rates, postoperative liver failure, and total hospital stay (all P>0.05) . Conclusions: Compared to the PVE procedures, ALPPS appears an effective treatment method for liver tumor with insufficient FLR.Therefore, the applications of ALPPS and PVE are limited and depending on further investigation.
Asunto(s)
Embolización Terapéutica , Hepatectomía/métodos , Insuficiencia Hepática/prevención & control , Neoplasias Hepáticas/cirugía , Hígado/irrigación sanguínea , Hígado/cirugía , Embolización Terapéutica/efectos adversos , Embolización Terapéutica/mortalidad , Estudios de Factibilidad , Hepatectomía/efectos adversos , Hepatectomía/mortalidad , Insuficiencia Hepática/etiología , Insuficiencia Hepática/mortalidad , Humanos , Ligadura , Hígado/anatomía & histología , Neoplasias Hepáticas/mortalidad , Vena Porta/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: Retracting the lateral liver segment during laparoscopic distal gastrectomy is important for achieving an optimal surgical field. However, excessive force may injure the liver, causing temporary abnormalities of liver function tests after laparoscopic surgery. We developed a new liver retraction method and assessed its safety and utility. PATIENTS AND METHODS: We retrospectively analyzed records in our surgical database of consecutive surgical patients who underwent laparoscopic distal gastrectomy for early gastric cancer. We divided the 229 patients into two groups based on the liver retraction method used, either flexible liver retraction with clipping and suturing (FLICS) or the Nathanson retractor (NR). One-to-one propensity score matching was performed to match patients, resulting in the records of 53 pairs of cases extracted from the database. Operative and postoperative outcomes were assessed, including following the values of serum liver enzymes, total bilirubin, and C-reactive protein until postoperative day 30. RESULTS: There were no significant differences in patient characteristics or preoperative data in the two groups. The retraction method was not changed intraoperatively for any patients. The operative time was significantly shorter in the FLICS group, but the amount of bleeding did not differ. Liver injury was not observed as a result of liver retraction during surgery. In both groups, serum liver enzymes temporarily increased after surgery but improved rapidly thereafter. The postoperative increases in aspartate transaminase, alanine transaminase, and C-reactive protein levels were significantly lower in the FLICS than in the NR group. No serious complications associated with liver retraction were observed in either group. CONCLUSIONS: Our new liver retraction technique provided an optimal surgical field without inducing liver dysfunction. It is a simple, safe, and effective liver retraction technique.
Asunto(s)
Gastrectomía/métodos , Insuficiencia Hepática/prevención & control , Laparoscopía/métodos , Complicaciones Posoperatorias/prevención & control , Neoplasias Gástricas/cirugía , Adulto , Anciano , Femenino , Insuficiencia Hepática/diagnóstico , Insuficiencia Hepática/etiología , Humanos , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Tempo Operativo , Complicaciones Posoperatorias/diagnóstico , Puntaje de Propensión , Estudios RetrospectivosRESUMEN
The purpose of this study was to determine the effect on the effectiveness of the correction of enteric insufficiency syndrome in patients with urgent surgical pathology included in the scheme of complex therapy Remaxol. The results of complex therapy of 227 patients (98 people with common peritonitis and 129 patients with acute intestinal obstruction) were analyzed. 128 patients of the main group in the postoperative period were included in the therapy scheme Remaxol: intravenously drip in a daily dose of 400 ml at a rate of 40 drops per minute, a course of -5 days. Patients of the control group (99 people) received standard treatment. The study is devoted to the role of postoperative hepatoprotective therapy in the treatment of patients with urgent surgical pathology. The main attention is paid to the hepatoenteric link of the pathogenesis of polyorganism insufficiency. This approach gives hope for a reduction in the risk of abdominal sepsis and a reduction in mortality among patients with acute abdominal pathology. The study found that in patients with acute abdominal pathology, an increase in the severity of enteric insufficiency syndrome due to toxic aggression and bacterial translocation can lead to hepatic dysfunction. Consequently, the implementation of hepatoprotective therapy is a pathogenetic link in the complex treatment of urgent surgical patients. The obtained results allowed to draw a number of conclusions. In particular, it has been established that the use of hepatoprotective therapy in the complex medical treatment of patients with acute abdominal pathology makes it possible to stop hepatorenal syndrome by the 5th day, and the syndrome of enteric insufficiency by the 7th day. Earlier relief of hepatic dysfunction and enteral insufficiency syndrome due to hepatoprotective therapy allowed to reduce the incidence of infectious complications to 9.7%, to reduce the lethality to 9.4% and to shorten hospitalization from 17.29 to 1.734 to 12.14±1.385 bed/day.
Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Insuficiencia Hepática , Obstrucción Intestinal , Intestino Delgado , Peritonitis , Succinatos/administración & dosificación , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Monitoreo de Drogas , Femenino , Insuficiencia Hepática/etiología , Insuficiencia Hepática/prevención & control , Humanos , Obstrucción Intestinal/complicaciones , Obstrucción Intestinal/cirugía , Intestino Delgado/fisiopatología , Intestino Delgado/cirugía , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/prevención & control , Peritonitis/etiología , Peritonitis/cirugía , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/fisiopatología , Complicaciones Posoperatorias/prevención & control , Sustancias Protectoras/administración & dosificación , Sepsis/etiología , Sepsis/prevención & control , Resultado del TratamientoRESUMEN
AIM: To determine ALPPS advisability in small future remnant liver. MATERIAL AND METHODS: 22 ALPPS procedures were performed at the Center for Surgery and Transplantology for the period from 2011 to 2016. Indications were both tumoral and non-tumoral unresectable liver diseases. Postoperative complications were classified according to Clavien-Dindo, ISGLS. RESULTS: According to CT-volumetry future remnant liver before the 1st stage of ALPPS was from 17 to 25%, before the 2nd stage - from 28 to 49%. Both stages were carried out in all patients with R0-resection in 100%. Postoperative complications were diagnosed in 40.9%, 1 death was caused by severe pulmonary embolism. Follow-up varied from 3 to 48 months (median 17.5), 86% of patients are alive at present. CONCLUSION: ALPPS provides rapid and effective FLR growth and can be used for both tumoral and non-tumoral unresectable liver diseases. However, ALPPS should be performed strictly according to indications and only in specialized centers with extensive experience of advanced liver resection and transplantation after previous comprehensive selection of patients.
Asunto(s)
Hepatectomía , Insuficiencia Hepática , Neoplasias Hepáticas/cirugía , Hígado , Vena Porta/cirugía , Femenino , Hepatectomía/efectos adversos , Hepatectomía/métodos , Insuficiencia Hepática/etiología , Insuficiencia Hepática/patología , Insuficiencia Hepática/fisiopatología , Insuficiencia Hepática/prevención & control , Humanos , Ligadura/métodos , Hígado/irrigación sanguínea , Hígado/patología , Hígado/fisiopatología , Neoplasias Hepáticas/patología , Regeneración Hepática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Evaluación de Procesos y Resultados en Atención de Salud , Complicaciones Posoperatorias/patología , Complicaciones Posoperatorias/fisiopatología , Complicaciones Posoperatorias/prevención & controlRESUMEN
BACKGROUND: The objective of this study was to elucidate whether the inhibition of Toll-like receptor 4 attenuates liver injury ischemia/reperfusion in the cholestatic liver. METHOD: Rats were assigned into sham, bile duct ligation, sham ischemia/reperfusion (ischemia/reperfusion after laparotomy), and bile duct ligation ischemia/reperfusion (ischemia/reperfusion after bile duct ligation) groups. In some rats, TAK-242, an inhibitor of Toll-like receptor 4, was administered 15 minutes before ischemia/reperfusion. We measured intrahepatic Toll-like receptor 4 expression, serum hepatic marker expression, liver necrosis, gene expression of inflammation-associated factors, and serum high-mobility group box protein b1 levels. RESULTS: Intrahepatic Toll-like receptor 4 expression was significantly greater in the bile duct ligation group than in the sham group. Toll-like receptor 4 expression was further increased after ischemia/reperfusion in bile duct ligation ischemia/reperfusion groups. The levels of serum hepatic markers were significantly greater in both the sham ischemia/reperfusion and bile duct ligation ischemia/reperfusion groups than in the groups without ischemia/reperfusion. Liver necrosis was greater in the bile duct ligation group than in the sham group and was further increased in the bile duct ligation ischemia/reperfusion group. Genomic expression of inflammation-associated factors was also significantly greater in the bile duct ligation ischemia/reperfusion group than in the sham group. Serum high-mobility groups box protein b1 levels were greater in the bile duct ligation ischemia/reperfusion group than in the sham group (28.1 ng/ml versus 9.2 ng/ml, P = .011) and the bile duct ligation group (28.1 ng/ml versus 10.6 ng/ml, P = .017). These changes in the bile duct ligation ischemia/reperfusion group were significantly attenuated by preconditioning with TAK242. CONCLUSIONS: Toll-like receptor 4 inhibition has a potential to minimize severe injury after ischemia/reperfusion in the cholestatic liver through inhibition of high-mobility groups box protein b1.
Asunto(s)
Insuficiencia Hepática/etiología , Precondicionamiento Isquémico , Daño por Reperfusión/etiología , Sulfonamidas/uso terapéutico , Receptor Toll-Like 4/antagonistas & inhibidores , Animales , Evaluación Preclínica de Medicamentos , Proteína HMGB1/sangre , Insuficiencia Hepática/metabolismo , Insuficiencia Hepática/prevención & control , Hígado/metabolismo , Hígado/patología , Masculino , Ratas Wistar , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & control , Sulfonamidas/farmacología , Receptor Toll-Like 4/metabolismoRESUMEN
Research findings that suggest beneficial health effects of dietary supplementation with virgin coconut oil (VCO) are limited in the published literature. This study investigated the in vivo effects of a 5-week VCO-supplemented diet on lipid profile, hepatic antioxidant status, hepatorenal function, and cardiovascular risk indices in normal rats. Rats were randomly divided into 3 groups: 1 control and 2 treatment groups (10% and 15% VCO-supplemented diets) for 5 weeks. Serum and homogenate samples were used to analyze lipid profile, hepatorenal function markers, hepatic activities of antioxidant enzymes, and malondialdehyde level. Lipid profile of animals fed VCO diets showed significant reduction in total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels; high-density lipoprotein (HDL) level increased significantly (p < .05) compared to control; and there were beneficial effects on cardiovascular risk indices. The level of malondialdehyde (MDA), a lipid peroxidation marker, remarkably reduced and activities of hepatic antioxidant enzymes-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)-were markedly increased in VCO diet-fed rats. The VCO diet significantly modulated creatinine, sodium (Na+), potassium (K+), chloride (Cl-), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) compared to control. The findings suggest a beneficial effect of VCO on lipid profile, renal status, hepatic antioxidant defense system, and cardiovascular risk indices in rats.
Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Aceite de Coco/uso terapéutico , Suplementos Dietéticos , Insuficiencia Hepática/prevención & control , Hígado/metabolismo , Estrés Oxidativo , Insuficiencia Renal/prevención & control , Animales , Biomarcadores/sangre , Biomarcadores/metabolismo , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/patología , Enfermedades Cardiovasculares/fisiopatología , Aceite de Coco/administración & dosificación , Aceite de Coco/normas , Calidad de los Alimentos , Insuficiencia Hepática/metabolismo , Insuficiencia Hepática/patología , Insuficiencia Hepática/fisiopatología , Humanos , Riñón/fisiología , Riñón/fisiopatología , Metabolismo de los Lípidos , Peroxidación de Lípido , Lípidos/sangre , Hígado/patología , Hígado/fisiología , Hígado/fisiopatología , Masculino , Tamaño de los Órganos , Oxidorreductasas/antagonistas & inhibidores , Oxidorreductasas/metabolismo , Distribución Aleatoria , Ratas Wistar , Insuficiencia Renal/metabolismo , Insuficiencia Renal/patología , Insuficiencia Renal/fisiopatologíaRESUMEN
BACKGROUND: It is not known whether simultaneous delivery of hydrogen and oxygen can reduce injury caused by hemorrhagic shock and resuscitation (HSR). This study investigated the therapeutic potential of hyperoxygenated hydrogen-rich solution (HHOS), a combined hydrogen/oxygen carrier, in a rat model of HSR-induced liver injury. MATERIALS AND METHODS: Rats (n = 60) were randomly divided into 5 groups (n = 6 per group at each time point). One group underwent sham operation, and the others were subjected to severe hemorrhagic shock and then treated with lactated Ringer's solution (LRS), hydrogen-rich solution, hyperoxygenated solution, or HHOS. At 2 and 6 h after resuscitation, blood samples (n = 6) were collected from the femoral artery and serum concentrations of alanine aminotransferase and aspartate aminotransferase (AST) were measured. Rats were then sacrificed, and histopathological changes in the liver were evaluated by quantifying the percentage of apoptotic cells by caspase-3 immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick-end labeling. Inflammation was assessed by assessing malondialdehyde content and tumor necrosis factor-α, and interleukin (IL)-6 expression. RESULTS: Compared to lactated Ringer's solution, hydrogen-rich solution, or hyperoxygenated solution groups, serum AST and alanine aminotransferase levels and IL-6, tumor necrosis factor-α, and malondialdehyde expression in liver tissue were decreased by HHOS treatment. The number of caspase-3- and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells was decreased (P < 0.05) by HHOS treatment, 2 and 6 h after resuscitation. CONCLUSIONS: HHOS has protective effects against liver injury in a rat model of HSR.
Asunto(s)
Insuficiencia Hepática/prevención & control , Resucitación/efectos adversos , Choque Hemorrágico/complicaciones , Soluciones/uso terapéutico , Animales , Citocinas/metabolismo , Modelos Animales de Enfermedad , Insuficiencia Hepática/etiología , Insuficiencia Hepática/patología , Hidrógeno/uso terapéutico , Hígado/metabolismo , Hígado/ultraestructura , Masculino , Oxígeno/uso terapéutico , Distribución Aleatoria , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To evaluate the effect of hydrogen-rich saline (HS) on hepatic ischemia-reperfusion (I/R) injury. METHODS: Forty rats were randomly allocated into five groups: one sham group (control group), one group treated with 20 min of ischemia and normal saline (NS; I/R1 + NS group), one group treated with 20 min of ischemia and HS (I/R1 + HS group), one group treated with 60 min of ischemia and NS (I/R2 + NS group), and one group treated with 60 min of ischemia and HS (I/R2 + HS group). After reperfusion for 6 h, hepatic function, oxidative stress, pathological changes, and apoptosis of hepatic cells were evaluated. Furthermore, the expression levels of endoplasmic reticulum (ER) stress-associated proteins were identified. RESULTS: Serum ALT and AST levels and tissue MDA content in the I/R + HS groups were significantly lower than those in the I/R + NS groups. Pathological changes were also significantly ameliorated in the HS groups compared with those in the NS groups. Moreover, HS appeared to significantly attenuate hepatic I/R-induced ER stress responses, as indicated by the decreased expression of C/EBP homologous protein, protein-kinase-RNA-like ER kinase, and inositol-requiring protein-1α, as well as the increased expression of GRP78 proteins. Finally, the levels of apoptotic markers such as caspase-3 and TUNEL-positive cells were significantly lower in the HS groups than in the NS control groups, whereas the level of Bcl2 protein increased in the HS groups. CONCLUSION: The protective effect of HS can be attributed to ER stress and apoptosis inhibition.
Asunto(s)
Apoptosis/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Insuficiencia Hepática/prevención & control , Hidrógeno/uso terapéutico , Daño por Reperfusión/prevención & control , Cloruro de Sodio/uso terapéutico , Animales , Hidrógeno/farmacología , Hígado/metabolismo , Masculino , Malondialdehído/metabolismo , Distribución Aleatoria , Ratas Sprague-Dawley , Cloruro de Sodio/farmacología , Superóxido Dismutasa/metabolismoRESUMEN
Parenteral nutrition-associated liver disease (PNALD) spectrum ranges from liver enzyme abnormalities to steatosis to fibrosis, and, eventually, cirrhosis from total parenteral nutrition (TPN). The pathophysiology is postulated to be multifactorial. Diagnosis in adults is primarily by exclusion, eliminating other causes of chronic liver disease or cirrhosis, and other factors seen in critically ill or postoperative patients on TPN. Principal treatment is avoiding TPN. If this is not feasible, research supports fish oil-based lipid emulsions in TPN formulations to reduce risk and progression of PNALD. With liver and intestinal failure, liver and intestine transplant is an option.
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Hepatopatías/etiología , Nutrición Parenteral Total/efectos adversos , Emulsiones Grasas Intravenosas/uso terapéutico , Hígado Graso/etiología , Hígado Graso/prevención & control , Aceites de Pescado/uso terapéutico , Insuficiencia Hepática/etiología , Insuficiencia Hepática/prevención & control , Humanos , Intestinos/trasplante , Cirrosis Hepática/etiología , Cirrosis Hepática/prevención & control , Hepatopatías/prevención & control , Hepatopatías/cirugía , Trasplante de HígadoRESUMEN
Therapeutic hypothermia (TH) is now provided as standard care to infants with moderate-severe hypoxic ischemic encephalopathy (HIE). The role of TH in limiting neuronal injury is well recognized, but its effect on hepatic injury which occurs frequently in neonatal HIE is not known. Our objective was to characterize biomarkers of liver injury and function in the setting of neonatal HIE and to describe whether HIE severity and provision of TH influence these hepatic biomarkers. We performed a multicenter retrospective study and compared hepatic biomarkers obtained during the first postnatal week, according to the severity of HIE and whether treated with TH. Of a total of 361 infants with HIE, 223 (62%) received TH and 138 (38%) were managed at normal temperature. Most hepatic biomarkers and C-reactive protein (CRP) were significantly associated with the severity of HIE (p < 0.001). Infants treated with TH had lower peak alanine aminotransferase (ALT) concentrations (p = 0.025) and a delay in reaching peak CRP concentration (p < 0.001). CONCLUSION: We observed a significant association between the clinical grade of HIE and biomarkers of liver metabolism and function. Therapeutic hypothermia was associated with delayed CRP responses and with lower ALT concentrations and so may have the potential to modulate hepatic injury. What is Known: ⢠Ischemic hepatic injury occurs frequently as a part of multiorgan dysfunction in infants with hypoxic ischemic encephalopathy (HIE). ⢠The neuroprotective role of therapeutic hypothermia in management of infants with HIE is well recognized, but the potential hepato-protective effects of hypothermia are unclear. What is New/What this study adds: ⢠Therapeutic hypothermia was associated with lower alanine aminotransferase and albumin concentrations and a delayed C-reactive protein (CRP) response and so may have the potential to modulate hepatic injury. ⢠An elevated CRP concentration during the first postnatal week may be regarded as an expected finding in moderate and severe HIE and, in the overwhelming majority of cases, occurs secondary to hepatic hypoxia-ischemia in the absence of blood culture-positive sepsis.
Asunto(s)
Biomarcadores/sangre , Insuficiencia Hepática/diagnóstico , Hipotermia Inducida , Hipoxia-Isquemia Encefálica/terapia , Proteína C-Reactiva/metabolismo , Femenino , Insuficiencia Hepática/sangre , Insuficiencia Hepática/etiología , Insuficiencia Hepática/prevención & control , Humanos , Hipoxia-Isquemia Encefálica/complicaciones , Recién Nacido , Hígado/enzimología , Hígado/fisiopatología , Masculino , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
No disponible
Asunto(s)
Humanos , Insuficiencia Hepática Crónica Agudizada/complicaciones , Insuficiencia Hepática Crónica Agudizada/epidemiología , Cirrosis Hepática/epidemiología , Cirrosis Hepática/prevención & control , Insuficiencia Hepática/epidemiología , Insuficiencia Hepática/prevención & control , BiomarcadoresRESUMEN
NOS isoform activation is related to liver failure during sepsis, but the mechanisms driving mitochondrial impairment remain unclear. We induced sepsis by LPS administration to inducible nitric oxide synthase (iNOS-/-) and neuronal nitric oxide synthase (nNOS-/-) mice and their respective wild-type controls to examine the contribution of iNOS to mitochondrial failure in the absence of nNOS. To achieve this goal, the determination of messenger RNA (mRNA) expression and protein content of iNOS in cytosol and mitochondria, the mitochondrial respiratory complex content, and the levels of nitrosative and oxidative stress (by measuring 3-nitrotyrosine residues and carbonyl groups, respectively) were examined in the liver of control and septic mice. We detected strongly elevated iNOS mRNA expression and protein levels in liver cytosol and mitochondria of septic mice, which were related to enhanced oxidative and nitrosative stress, and with fewer changes in respiratory complexes. The absence of the iNOS, but not nNOS, gene absolutely prevented mitochondrial impairment during sepsis. Moreover, the nNOS gene did not modify the expression and the effects of iNOS here shown. Melatonin administration counteracted iNOS activation and mitochondrial damage and enhanced the expression of the respiratory complexes above the control values. These effects were unrelated to the presence or absence of nNOS. iNOS is a main target to prevent liver mitochondrial impairment during sepsis, and melatonin represents an efficient antagonist of these iNOS-dependent effects whereas it may boost mitochondrial respiration to enhance liver survival (AU)
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Asunto(s)
Animales , Ratones , Antioxidantes/uso terapéutico , Modelos Animales de Enfermedad , Insuficiencia Hepática/prevención & control , Hígado , Melatonina/uso terapéutico , Sepsis/tratamiento farmacológico , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo I , Regulación Enzimológica de la Expresión Génica , Lipopolisacáridos/toxicidad , Biomarcadores/sangre , Carbonilación Proteica , Mitocondrias Hepáticas , ARN Mensajero/metabolismo , Estrés Oxidativo , Inyecciones IntraperitonealesRESUMEN
NOS isoform activation is related to liver failure during sepsis, but the mechanisms driving mitochondrial impairment remain unclear. We induced sepsis by LPS administration to inducible nitric oxide synthase (iNOS-/-) and neuronal nitric oxide synthase (nNOS-/-) mice and their respective wild-type controls to examine the contribution of iNOS to mitochondrial failure in the absence of nNOS. To achieve this goal, the determination of messenger RNA (mRNA) expression and protein content of iNOS in cytosol and mitochondria, the mitochondrial respiratory complex content, and the levels of nitrosative and oxidative stress (by measuring 3-nitrotyrosine residues and carbonyl groups, respectively) were examined in the liver of control and septic mice. We detected strongly elevated iNOS mRNA expression and protein levels in liver cytosol and mitochondria of septic mice, which were related to enhanced oxidative and nitrosative stress, and with fewer changes in respiratory complexes. The absence of the iNOS, but not nNOS, gene absolutely prevented mitochondrial impairment during sepsis. Moreover, the nNOS gene did not modify the expression and the effects of iNOS here shown. Melatonin administration counteracted iNOS activation and mitochondrial damage and enhanced the expression of the respiratory complexes above the control values. These effects were unrelated to the presence or absence of nNOS. iNOS is a main target to prevent liver mitochondrial impairment during sepsis, and melatonin represents an efficient antagonist of these iNOS-dependent effects whereas it may boost mitochondrial respiration to enhance liver survival.
Asunto(s)
Antioxidantes/uso terapéutico , Modelos Animales de Enfermedad , Insuficiencia Hepática/prevención & control , Hígado/efectos de los fármacos , Melatonina/uso terapéutico , Óxido Nítrico Sintasa de Tipo II/metabolismo , Sepsis/tratamiento farmacológico , Animales , Antioxidantes/administración & dosificación , Biomarcadores/sangre , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Insuficiencia Hepática/etiología , Inyecciones Intraperitoneales , Lipopolisacáridos/toxicidad , Hígado/inmunología , Hígado/metabolismo , Melatonina/administración & dosificación , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Noqueados , Mitocondrias Hepáticas/efectos de los fármacos , Mitocondrias Hepáticas/inmunología , Mitocondrias Hepáticas/metabolismo , Óxido Nítrico Sintasa de Tipo I/genética , Óxido Nítrico Sintasa de Tipo I/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Estrés Oxidativo/efectos de los fármacos , Carbonilación Proteica/efectos de los fármacos , ARN Mensajero/metabolismo , Sepsis/inmunología , Sepsis/metabolismo , Sepsis/fisiopatologíaRESUMEN
BACKGROUND & AIMS: Intravenous fat emulsions are associated with liver disease and there is some evidence that the administration of intravenous fish oil (FO) may be useful in reversing it. The aim of our study was to assess whether there are differences in the changes of liver function tests (LFTs) in hospitalized adult patients with parenteral nutrition (PN) with FO and vegetal lipids vs patients without FO. The secondary aim was to study the relationship between impaired LFT and FO. METHODS: This was a 4-year, propensity score-matched analysis including patients aged ≥18 years treated with PN for ≥10 days. The exclusion criteria were previous liver disease, biliary disorders or pancreatic cancer, and altered initial LFT values. Patients were classified into 2 groups: FO cohort (patients who received FO - in addition to vegetal oil - after the first week of PN) and the vegetal oil cohort (patients who received only vegetal oil). A propensity score matched cohort design was developed. Univariate analyses were used to study the changes in LFTs. To evaluate whether LFT alterations vary with FO administration, four stepwise multiple linear regression models were conducted. RESULTS: 52 patients were included, 52% men, median 66 (55-75) years and 69 kg (61.7-78.8), with 18.5 (14-31.8) days of PN treatment. Maximum FO supplementation was 23%. During the first week with PN (none of the groups receiving FO), gammaglutamyl transferase (GGT), alkaline phosphatase (AP) and total bilirubin (BIL) increased significantly. Comparing LFT values at seven days of PN with at the end of PN treatment, the univariate analysis showed a better response for the FO group. The group without FO showed a significant increase for GGT and AP. In multivariate models, the percentage of FO administered was associated with a decrease in GGT, B = -0.33 [CI 95% = -0.54/-0.12], in AP, B = -0.12 [CI 95% = -0.20/-0.03] and ALT, B = -0.12 [CI 95% = -0.21/-0.024]. CONCLUSIONS: Lipid composition plays a significant role in LFT alteration associated with PN, and FO intravenous lipid emulsions (ILEs) minimize disturbance of LFTs in hospitalized adult patients.
Asunto(s)
Emulsiones Grasas Intravenosas/uso terapéutico , Aceites de Pescado/uso terapéutico , Insuficiencia Hepática/prevención & control , Hígado/fisiopatología , Nutrición Parenteral/efectos adversos , Anciano , Biomarcadores/sangre , Estudios de Cohortes , Emulsiones Grasas Intravenosas/administración & dosificación , Emulsiones Grasas Intravenosas/efectos adversos , Femenino , Aceites de Pescado/administración & dosificación , Aceites de Pescado/efectos adversos , Estudios de Seguimiento , Insuficiencia Hepática/sangre , Insuficiencia Hepática/etiología , Insuficiencia Hepática/fisiopatología , Hospitales Universitarios , Humanos , Unidades de Cuidados Intensivos , Tiempo de Internación , Modelos Lineales , Masculino , Persona de Mediana Edad , Aceites de Plantas/administración & dosificación , Aceites de Plantas/efectos adversos , Aceites de Plantas/uso terapéutico , Índice de Severidad de la Enfermedad , EspañaRESUMEN
BACKGROUND: N-acetylcysteine (NAC) is an antioxidant with direct and indirect antioxidant actions used in the clinical setting. Oxidative stress is known to play a pivotal role in the intestinal ischemia reperfusion (IIR). Therefore, we studied the effect of different pretreatment regimens with NAC on the IIR injury in rats. MATERIALS AND METHODS: Thirty-five male Wistar rats were randomly assigned to five groups. In group sham, only laparotomy was performed. Group control underwent IIR without NAC. In the other groups, NAC was administered intraperitoneally with different regimens: 150 mg/kg before ischemia (NAC 150), 300 mg/kg before ischemia (NAC 300), and 150 mg/kg before ischemia plus 150 mg/kg 5 min before reperfusion (NAC 150 + 150). Measurements in tissues and blood were conducted at 4 h of reperfusion following exsanguination. RESULTS: Histological score of the liver was significantly improved in NAC 300 compared with control (1.7 ± 0.5 versus 2.9 ± 1.1, respectively, P = 0.05). In addition, NAC treatment significantly reduced liver transaminases in all groups of treatment, mostly in group NAC 300. Plasma malondialdehyde levels were lower with NAC treatment, although not statistically significant. Lung glutathione peroxidase was significantly increased in group NAC 300 (P = 0.04), while the other oxidation biomarkers showed no significant differences. CONCLUSIONS: NAC exerts a significant protective role in liver injury following IIR, which seems to be independent of an intestinal protective effect. Additional administration of NAC before reperfusion was of no further benefit. The most effective regimen among the compared regimens was that of 300 mg/kg before ischemia.
Asunto(s)
Acetilcisteína/uso terapéutico , Antioxidantes/uso terapéutico , Insuficiencia Hepática/prevención & control , Intestinos/irrigación sanguínea , Daño por Reperfusión/tratamiento farmacológico , Acetilcisteína/farmacología , Animales , Antioxidantes/farmacología , Biomarcadores/metabolismo , Insuficiencia Hepática/etiología , Insuficiencia Hepática/metabolismo , Insuficiencia Hepática/patología , Inyecciones Intraperitoneales , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Pruebas de Función Hepática , Masculino , Estrés Oxidativo/efectos de los fármacos , Distribución Aleatoria , Ratas , Ratas Wistar , Daño por Reperfusión/metabolismo , Daño por Reperfusión/fisiopatologíaRESUMEN
BACKGROUND: The aim of our study was to investigate the antifibrotic and antioxidant effects of Myrtus communis subsp. communis (MC) extract against liver injury and fibrosis occurring in rats with biliary obstruction. MATERIALS AND METHODS: The rats were randomized into four groups (n = 8). Control group (C), MC-administrated group (MC), the bile duct ligation (BDL), and BDL + MC groups. MC was administered at a dose of 50 mg/kg a day orally for 28 days. In blood samples, total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase levels, tumor necrosis factor-α, and interleukin-1ß measurement were measured. Oxidative injury was examined by measuring luminol and lucigenin chemiluminescence, malondialdehyde and glutathione levels, superoxide dismutase and myeloperoxidase activities. Transforming growth factor-beta and hydroxyproline levels were measured for analyzing fibrosis. The hepatic injury was also analyzed microscopically. RESULTS: Plasma total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-α, and interleukin-1ß levels were found significantly high in the BDL group, while these values significantly decreased in the BDL group treated with MC. On the other hand, the glutathione and superoxide dismutase values significantly decreased in the BDL group compared to the control group but increased markedly in BDL + MC group compared to the BDL group. Malondialdehyde levels, myeloperoxidase activity, tissue luminol, lucigenin, transforming growth factor-beta, and hydroxyproline levels when compared with the control group increased dramatically in the BDL group and reduced the MC + BDL group. CONCLUSIONS: Our results suggest that MC protects the liver tissues against oxidative damage following BDL via its radical scavenging and antioxidant activities, which appear to involve the inhibition of tissue neutrophil infiltration.