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1.
Am J Gastroenterol ; 116(3): 568-575, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33657042

RESUMEN

INTRODUCTION: There are limited data on the incidence, predictors, and time to future liver abnormalities in patients with intrahepatic cholestasis of pregnancy (ICP). METHODS: Single-center retrospective study of pregnant women with and without ICP who delivered from 2005 to 2009 evaluating incidence and time to future liver abnormalities. Women returning for care with liver function tests at a minimum of 6 months postpartum were included. Liver disease diagnoses and liver functions test abnormalities were compared. Time to development of alanine aminotransferase (ALT) >25 U/L, alkaline phosphatase (ALP) >140 U/L, and diagnosis of liver disease (through imaging or clinical evaluation) were compared between women with and without ICP using Kaplan-Meier methods and Cox regression models. RESULTS: A total of 255 women with ICP and 131 age-matched control subjects with delivery during the same period were identified. Subjects in both groups were similar in follow-up time, age at pregnancy, prepregnancy body mass index, and ethnicity (≥75% were Hispanic in both groups). On univariate analyses, ICP was associated with increased incidence of ALT >25 U/L P < 0.01 ALP >140 U/L (P < 0.01) and liver disease (P = 0.03). Adjusting for metabolic factors, ICP diagnosis was associated with risk of future liver abnormalities: postpartum ALT >25 U/L (hazard ratio [HR] 1.9, P < 0.01), ALP >140 U/L (HR 3.4, P < 0.01), and liver disease (HR 1.5, P = 0.05). DISCUSSION: In our cohort of urban women, ICP diagnosis predicted risk of future liver disease and abnormal liver tests. Women with pregnancies complicated by ICP may benefit from surveillance for postpartum liver abnormalities.


Asunto(s)
Colestasis Intrahepática/diagnóstico , Hepatopatías/epidemiología , Complicaciones del Embarazo/diagnóstico , Adulto , Colestasis Intrahepática/fisiopatología , Femenino , Humanos , Incidencia , Hepatopatías/fisiopatología , Pruebas de Función Hepática , Embarazo , Complicaciones del Embarazo/fisiopatología , Resultado del Embarazo , Estudios Retrospectivos , Riesgo , Adulto Joven
2.
Medicine (Baltimore) ; 100(8): e24155, 2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33663045

RESUMEN

BACKGROUND: The aim of this study was to systematically evaluate and compare the effectiveness and safety of laparoscopic versus open resection (LR vs OR) in the treatment of hepatic hemangioma. METHODS: We searched PubMed, the Cochrane Library, Web of Science, Medline, EMBASE, and the Chinese Biomedicine Database from January 2000 to April 2020 for studies comparing the outcomes of laparoscopic versus open surgery in hepatic hemangioma treatment. RESULTS: Based on the preset criteria, 12 randomized clinical trials (RCTs) and 12 observational clinical studies (OCSs) were selected for analysis. Our results showed that laparoscopic surgery was more effective than open surgery in terms of reducing operation time, intraoperative blood loss, postoperative exhaust time, postoperative complications, postoperative bile leak, postoperative intra-abdominal infection, postoperative alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values, postoperative visual analog scale (VAS) scores, and hospitalize length. No significant differences were found between the 2 groups in hepatectomy time, hospitalized cost, intra-abdominal hemorrhage, and the postoperative recurrence of hemangioma. CONCLUSION: While similar therapeutic effect was achieved by the compared herein surgical methods, the findings of our analysis revealed that laparoscopic surgery is superior over open surgery in terms of less trauma, faster recovery, less postoperative pain, shorter hospitalize length, and reduced postoperative complications. Therefore, laparoscopic resection of hepatic hemangioma is a safe, effective, and feasible surgical method that is worth considering in clinical applications.


Asunto(s)
Hemangioma/cirugía , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Pérdida de Sangre Quirúrgica , Humanos , Laparoscopía/métodos , Tiempo de Internación , Pruebas de Función Hepática , Recurrencia Local de Neoplasia , Estudios Observacionales como Asunto , Tempo Operativo , Complicaciones Posoperatorias/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto
3.
Medicine (Baltimore) ; 100(8): e24576, 2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33663065

RESUMEN

BACKGROUND: Diabetes is a chronic metabolic disease characterized by elevated blood glucose levels due to insulin resistance and ß-cell dysfunction. In China, Huangyusang decoction (HYS) has been widely used to treat Type 2 diabetes. However, there is no systematic review found. In order to evaluate the efficacy and safety of HYS in the treatment of Type 2 diabetes, we need to conduct a meta-analysis and systematic evaluation. METHODS: We will enroll the randomized controlled trials (RCTs) evaluating the effectiveness and safety of HYS in the treatment of Type 2 diabetes. Data come mainly from 4 Chinese databases (CNKI, Wanfang, CBM, and VIP Database) and 4 English databases (PubMed, Embase, Cochrane Library, and Web of science). The enrollment of RCTs is from the starting date of database establishment till January 30, 2021. Fasting blood glucose is considered as the main indicator of the dyslipidemia, while the body mass index, glycated hemoglobin, fasting insulin, triglycerides, and cholesterol are regarded as the secondary indicators. There are safety indicators including liver enzyme and kidney function. The work such as selection of literature, data collection, quality evaluation of included literature, and assessment of publication bias will be conducted by 2 independent researchers. Meta-analysis will be performed by RevMan 5.0 software. RESULTS: This study will provide high-quality evidence for the effectiveness and safety of HYS in the treatment of type 2 diabetes. CONCLUSION: The results of the study will help us determine whether HYS can effectively treat type 2 diabetes. ETHICS AND DISSEMINATION: This study does not require ethical approval. We will disseminate our findings by publishing results in a peer-reviewed journal. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/AXBRV.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Glucemia , Índice de Masa Corporal , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/efectos adversos , Hemoglobina A Glucada , Humanos , Pruebas de Función Renal , Lípidos/sangre , Pruebas de Función Hepática , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación
4.
Yi Chuan ; 43(3): 249-260, 2021 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-33724209

RESUMEN

Liver function tests (LFTs) measure a series of complex traits that are affected by genetic and environmental factors. Previous studies demonstrated that there exist significant differences in LFTs across individuals, which may be the results of the unique genetic profile of each individual. Therefore, we performed a genome-wide association study (GWAS) to evaluate the influence of single nucleotide polymorphisms (SNPs) in LFTs and identify the significant association between genotypes and phenotypes using 1653 Chinese subjects from the UK Biobank database. We successfully identified 229 SNPs significantly associated with total bilirubin (TB) levels, 27 SNPs significantly associated with alkaline phosphatase (ALP), and 36 SNPs significantly associated with γ-glutamyl transpeptidase (GGT) in serum. In addition, one SNP significantly associated with aspartate transaminase (AST) in serum was also found. Among the most significant ones, the topmost 11 SNPs were found to be associated with LFTs for the first time. Through functional genomic analysis, the clinical significance of these SNPs could be associated with diseases (e.g. Gilbert's syndrome) and the respective candidate genes (UGT1A, ABO, GGT1). This study provides a preliminary rationale for research to understand the associations of individual genetic differences and clinical liver functions in the Chinese population.


Asunto(s)
Estudio de Asociación del Genoma Completo , gamma-Glutamiltransferasa , Aspartato Aminotransferasas , China , Humanos , Hígado , Pruebas de Función Hepática , Polimorfismo de Nucleótido Simple , gamma-Glutamiltransferasa/genética
7.
Eur Rev Med Pharmacol Sci ; 25(4): 2146-2151, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33660834

RESUMEN

OBJECTIVE: COVID-19, the newly emerging infectious disease, has been associated with acute liver injury, often related to progression to severe pneumonia. The association between moderate-severe liver injury and more severe clinical course of COVID-19 has suggested that liver injury is prevalent in severe than in mild cases of COVID-19, while no difference in liver involvement has been reported between survivors and non-survivors. The spectrum of liver involvement during COVID-19 ranges from an asymptomatic elevation of liver enzymes to severe hepatitis. Only rarely, cases with acute hepatitis have been reported in the absence of respiratory symptoms. Both epithelial and biliary cells possess the angiotensin-converting enzyme-2 receptors that SARS-CoV-2 uses to be internalized. However, to our knowledge, no ultrastructural identification of the virus in liver cells has been reported to date. Here we provide evidence of SARS-CoV-2 in the liver of two patients, a 34-year-old woman and a 60-year-old man with COVID-19. PATIENTS AND METHODS: We investigated two patients with COVID-19 showing several virions within cytoplasmic vacuoles of cholangiocytes and in endothelial cells of hepatic sinusoids. In both patients, we performed histological and ultrastructural examinations by liver biopsy. After two months, both patients were free of symptoms, and the SARS-CoV-2 infection had resolved. RESULTS: Liver biopsy histological and ultrastructural examination showed liver injury and several virions within cytoplasmic vacuoles of cholangiocytes and in endothelial cells of hepatic sinusoids. CONCLUSIONS: Although most studies in COVID-19 have been focused on the lungs, recently, cholestatic liver pathology has been introduced in the spectrum of pathological changes related to COVID-19. To the best of our knowledge, those presented in this paper are the first images of hepatic SARS-CoV-2 infected liver cells. Our findings suggest a role for cholangiocytes and biliary structures in the COVID-19.


Asunto(s)
/complicaciones , Hepatopatías/complicaciones , Hígado/virología , /aislamiento & purificación , Adulto , Biopsia , /virología , Células Epiteliales/virología , Femenino , Humanos , Hígado/diagnóstico por imagen , Hepatopatías/diagnóstico por imagen , Hepatopatías/virología , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Virión/aislamiento & purificación
8.
Medicine (Baltimore) ; 100(11): e24476, 2021 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-33725934

RESUMEN

ABSTRACT: The platelet-albumin-bilirubin (PALBI) grade plays critical role in evaluating liver function. However, the change of PALBI grade from the preoperative to postoperative period in predicting patient outcomes after hepatectomy remains unclear.A total of 489 HCC patients who underwent hepatectomy in West China Hospital between January, 2010 and June, 2016 were analyzed retrospectively.ΔPALBI grade was calculated by PALBI grade at the first postoperative month - preoperative PALBI grade.ΔPALBI >0 was considered as stable; otherwise, worse PALBI grade was considered. Kaplan- Meier method and Cox proportional hazard regression analyses were performed for survival analysis. Prognostic model was constructed by nomogram method.Three hundred forty two patients and 147 patients were classified into training group and validation group, respectively. In the training group, results from Cox model suggested that worse PALBI grade (HR 1.328, 95% CI 1.010-1.746, P = .042), tumor size (HR 1.460, 95% CI 1.058-2.015, P = .021), microvascular invasion (MVI, HR 1.802, 95% CI 1.205-2.695, P < .001), and high alpha-fetoprotein level (AFP, HR 1.364, 95% CI 1.044-1.781, P = .023) negatively influenced postoperative recurrence. Similarly, worse PALBI grade (HR 1.403, 95% CI 1.020-1.930, P = .038), tumor size (HR 1.708, 95% CI 1.157-2.520, P = .007), MVI (HR 1.914, 95% CI 1.375-2.663, P < .001), and presence of cirrhosis (HR 1.773, 95% CI 1.226-2.564, P = .002) had negatively impacts on overall survival. Patients with worse PALBI grade had worse recurrence free (RFS) and overall survival (OS). The prognostic model incorporating the change of PALBI grade constructed in training group and tested in the validation group could perform well in predicting the outcomes.Postoperative change of PALBI grade was independently risk factor related with prognosis. Prognostic model incorporating the change of PALBI grade might be a useful index to predict the prognosis of HCC patients following hepatectomy.


Asunto(s)
Bilirrubina/sangre , Carcinoma Hepatocelular/sangre , Hepatectomía/mortalidad , Pruebas de Función Hepática/métodos , Neoplasias Hepáticas/sangre , Recuento de Plaquetas , Albúmina Sérica/análisis , Adulto , Anciano , Biomarcadores de Tumor , Plaquetas , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/cirugía , Femenino , Humanos , Estimación de Kaplan-Meier , Cirrosis Hepática/sangre , Cirrosis Hepática/etiología , Cirrosis Hepática/mortalidad , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Nomogramas , Periodo Posoperatorio , Valor Predictivo de las Pruebas , Periodo Preoperatorio , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Análisis de Supervivencia
9.
Eur J Drug Metab Pharmacokinet ; 46(2): 185-203, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33538960

RESUMEN

Coronavirus Disease 2019 (COVID-19) has been a global health crisis since it was first identified in December 2019. In addition to fever, cough, headache, and shortness of breath, an intense increase in immune response-based inflammation has been the hallmark of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) virus infection. This narrative review summarizes and critiques pathophysiology of COVID-19 and its plausible effects on drug metabolism and disposition. The release of inflammatory cytokines (e.g., interleukins, tumor necrosis factor α), also known as 'cytokine storm', leads to altered molecular pathophysiology and eventually organ damage in the lung, heart, and liver. The laboratory values for various liver function tests (e.g., alanine aminotransferase, aspartate aminotransferase, total bilirubin, albumin) have indicated potential hepatocellular injury in COVID-19 patients. Since the liver is the powerhouse of protein synthesis and the primary site of cytochrome P450 (CYP)-mediated drug metabolism, even a minor change in the liver function status has the potential to affect the hepatic clearance of xenobiotics. It has now been well established that extreme increases in cytokine levels are common in COVID-19 patients, and previous studies with patients infected with non-SARS-CoV-2 virus have shown that CYP enzymes can be suppressed by an infection-related cytokine increase and inflammation. Alongside the investigational COVID-19 drugs, the patients may also be on therapeutics for comorbidities; especially epidemiological studies have indicated that individuals with hypertension, hyperglycemia, and obesity are more vulnerable to COVID-19 than the average population. This complicates the drug-disease interaction profile of the patients as both the investigational drugs (e.g., remdesivir, dexamethasone) and the agents for comorbidities can be affected by compromised CYP-mediated hepatic metabolism. Overall, it is imperative that healthcare professionals pay attention to the COVID-19 and CYP-driven drug metabolism interactions with the goal to adjust the dose or discontinue the affected drugs as appropriate.


Asunto(s)
/fisiopatología , Sistema Enzimático del Citocromo P-450/metabolismo , Preparaciones Farmacéuticas/metabolismo , Animales , Citocinas/metabolismo , Humanos , Inflamación/patología , Inflamación/virología , Hígado/patología , Hígado/virología , Pruebas de Función Hepática , Preparaciones Farmacéuticas/administración & dosificación , Factores de Riesgo
10.
Int J Nanomedicine ; 16: 951-976, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33603362

RESUMEN

Purpose: Lipoparticles are the core-shell type lipid-polymer hybrid systems comprising polymeric nanoparticle core enveloped by single or multiple pegylated lipid layers (shell), thereby melding the biomimetic properties of long-circulating vesicles as well as the mechanical advantages of the nanoparticles. The present study was aimed at the development of such an integrated system, combining the photodynamic and chemotherapeutic approaches for the treatment of multidrug-resistant cancers. Methods: For this rationale, two different sized Pirarubicin (THP) loaded poly lactic-co-glycolic acid (PLGA) nanoparticles were prepared by emulsion solvent evaporation technique, whereas liposomes containing Temoporfin (mTHPC) were prepared by lipid film hydration method. Physicochemical and morphological characterizations were done using dynamic light scattering, laser doppler anemometry, atomic force microscopy, and transmission electron microscopy. The quantitative assessment of cell damage was determined using MTT and reactive oxygen species (ROS) assay. The biocompatibility of the nanoformulations was evaluated with serum stability testing, haemocompatibility as well as acute in vivo toxicity using female albino (BALB/c) mice. Results and Conclusion: The mean hydrodynamic diameter of the formulations was found between 108.80 ± 2.10 to 405.70 ± 10.00 nm with the zeta (ζ) potential ranging from -12.70 ± 1.20 to 5.90 ± 1.10 mV. Based on the physicochemical evaluations, the selected THP nanoparticles were coated with mTHPC liposomes to produce lipid-coated nanoparticles (LCNPs). A significant (p< 0.001) cytotoxicity synergism was evident in LCNPs when irradiated at 652 nm, using an LED device. No incidence of genotoxicity was observed as seen with the comet assay. The LCNPs decreased the generalized in vivo toxicity as compared to the free drugs and was evident from the serum biochemical profile, visceral body index, liver function tests as well as renal function tests. The histopathological examinations of the vital organs revealed no significant evidence of toxicity suggesting the safety and efficacy of our lipid-polymer hybrid system.


Asunto(s)
Lípidos/química , Nanopartículas/química , Neoplasias Ováricas/tratamiento farmacológico , Fotoquimioterapia , Animales , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/análogos & derivados , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Liberación de Fármacos , Femenino , Humanos , Concentración 50 Inhibidora , Cinética , Liposomas , Pruebas de Función Hepática , Mesoporfirinas/farmacología , Mesoporfirinas/uso terapéutico , Ratones , Ratones Endogámicos BALB C , Nanopartículas/ultraestructura , Neoplasias Ováricas/patología , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Especies Reactivas de Oxígeno/metabolismo , Pruebas de Toxicidad Aguda
11.
Medicine (Baltimore) ; 100(7): e24653, 2021 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-33607801

RESUMEN

ABSTRACT: The objective of this registry is to collect data on real-life treatment conditions for patients for whom multiple organ dialysis with Advanced Organ Support (ADVOS) albumin hemodialysis is indicated.This registry was performed under routine conditions and without any study-specific intervention, diagnostic procedures, or assessments. Data on clinical laboratory tests, health status, liver function, vital signs, and examinations were collected (DRKS-ID: DRKS00017068). Mortality rates 28 and 90 days after the first ADVOS treatment, adverse events and ADVOS treatment parameters, including treatment abortions, were documented.This analysis was performed 2 years after the first patient was included on January 18, 2017. As of February 20, 2019, 4 clinical sites in Germany participated and enrolled 118 patients with a median age of 60 (IQR: 45, 69) of whom 70 were male (59.3%). Patients had a median SOFA Score of 14 (IQR: 11, 16) and a predicted mortality of 80%. The median number of failing organs was 3 (IQR: 2, 4).Four hundred twenty nine ADVOS treatments sessions were performed with a median duration of 17 hours (IQR: 6, 23). A 5.8% of the ADVOS sessions (25 of 429) were aborted due to device related errors, while 14.5% (62 of 429) were stopped for other reasons. Seventy nine adverse events were documented, 13 of them device related (all clotting, and all recovered without sequels).A significant reduction in serum creatinine (1.5 vs 1.2 mg/dl), blood urea nitrogen (24 vs 17 mg/dl) and bilirubin (6.9 vs 6.5 mg/dl) was observed following the first ADVOS treatment session. Blood pH, bicarbonate (HCO3-) and base excess returned to the physiological range, while partial pressure of carbon dioxide (pCO2) remained unchanged. At the time of the analysis, 28- and 90-day mortality were 60% and 65%, respectively, compared to an expected ICU-mortality rate of 80%. SOFA score was an independent predictor for outcome in a multivariable logistic regression analysis.The reported data show a high quality and completion of all participating centers. Data interpretation must be cautious due to the small number of patients, and the nature of the registry, without a control group. However, the data presented here show an improvement of expected mortality rates. Minor clotting events similar to other dialysis therapies occurred during the treatments.


Asunto(s)
Insuficiencia Multiorgánica/terapia , Sistema de Registros , Terapia de Reemplazo Renal/instrumentación , Anciano , Femenino , Alemania , Humanos , Pruebas de Función Renal , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Vigilancia de Productos Comercializados
12.
BMJ Case Rep ; 14(2)2021 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-33547097

RESUMEN

Iatrogenic iron overload, which is not uncommon in patients undergoing long-term haemodialysis, arises from a combination of multiple red cell transfusions and parenteral iron infusions that are administered to maintain a haemoglobin concentration of approximately 10 g/dL. Although iron overload due to genetic haemochromatosis is conventionally managed by phlebotomy, patients with haemoglobinopathies and chronic transfusion-induced iron overload are treated with iron-chelation therapy. However, the management of iron overload in our patient who presented with hepatic dysfunction and immunosuppressive drug-induced mild anaemia in the post-renal transplant setting posed unique challenges. We report on the decision-making process used in such a case that led to a successful clinical resolution of hepatic iron overload through the combined use of phlebotomy and erythropoiesis stimulating agents, while avoiding use of iron-chelating agents that could potentially compromise both hepatic and renal function.


Asunto(s)
Sobrecarga de Hierro/etiología , Sobrecarga de Hierro/terapia , Trasplante de Riñón , Biopsia , Transfusión de Eritrocitos , Femenino , Hematínicos/administración & dosificación , Humanos , Hierro/administración & dosificación , Sobrecarga de Hierro/diagnóstico , Pruebas de Función Hepática , Imagen por Resonancia Magnética , Persona de Mediana Edad , Factores de Riesgo
13.
Scand J Gastroenterol ; 56(4): 453-457, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33590789

RESUMEN

OBJECTIVES: Coronavirus disease 2019 (COVID-19) is an ongoing major health emergency, but its occurrence and clinical impact on patients withliver cirrhosis is unknown. Therefore, we conducted a population-based study of 2.6 million Danish citizens investigating the occurrence and impact of COVID-19 in patients with liver cirrhosis. MATERIALS AND METHODS: A prospective population-based cohort study was conducted in the Capital Region of Denmark and Region Zealand in the study period between 1 March 2020 up until 31 May 2020, with the only eligibility criteria being a reverse-transcriptase polymerase chain reaction for presence of viral genomic material confirming COVID-19. The patients were subsequently stratified according to presence of pre-existing liver cirrhosis. RESULTS: Among 575,935 individuals tested, 1713 patients had a diagnosis of cirrhosis. COVID-19 occurredsignificantly lessamongpatients with cirrhosis (n = 15; 0.9%, p < .01) compared with the population without cirrhosis (n = 10,593; 1.8%). However, a large proportion (n = 6;40.0%) required a COVID-19 related hospitalization which was correlated with higher values of alanine aminotransferase (p < .01) and lactate dehydrogenase (p = .04). In addition, one-in-three (n = 2; 13.3%) required intensive therapy. Four patients died (26.7%) and mortality was associated with higher MELD scores, co-existing type 2 diabetes, and bacterial superinfections. CONCLUSION: In conclusion, patientswith cirrhosis may have a lower risk of COVID-19; but a higher risk of complications hereto and mortality.


Asunto(s)
Cirrosis Hepática , Pruebas de Función Hepática , /aislamiento & purificación , Alanina Transaminasa/sangre , /prevención & control , Estudios de Cohortes , Dinamarca/epidemiología , Femenino , Hospitalización/estadística & datos numéricos , Humanos , L-Lactato Deshidrogenasa/sangre , Cirrosis Hepática/sangre , Cirrosis Hepática/epidemiología , Cirrosis Hepática/terapia , Pruebas de Función Hepática/métodos , Pruebas de Función Hepática/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Mortalidad , Medición de Riesgo , Factores de Riesgo
14.
Ann Hematol ; 100(4): 979-986, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33608849

RESUMEN

High-dose methotrexate (HD-MTX) at 3 g/m2 is one of the strategies for central nervous system (CNS) prophylaxis in the first-line treatment of aggressive lymphomas, especially in diffuse large B cell lymphoma patients with high-risk CNS-International Prognostic Index. The objective of our study was to retrospectively analyze the safety of 2 cycles of systemic HD-MTX administered as an ambulatory regimen. Between January 2013 and December 2016, 103 patients were carefully selected on 6 criteria, including age < 60, albumin > 34, performance status 0 or 1, normal renal and hepatic functions, good understanding of practical medical guidance, and no loss of weight. Strict procedures of HD-MTX infusion were observed including alkalinization, urine pH monitoring, and leucovorin rescue. Renal and hepatic functions were monitored at days 2 and 7. MTX clearance was not monitored. Toxicities and grades of toxicity were collected according to the NCI-CTCAE (version 4.0). Among the 103 selected patients, 92 (89%) patients successfully completed the planned 2 cycles of HD-MTX on an outpatient basis. Eleven patients completed only 1 cycle, 3 because of lymphoma progression and 8 because of toxicity including 3 grade II hepatotoxicity, 2 grade I/II renal toxicity, 1 grade III neutropenia, 1 active herpetic infection, and 1 grade III ileus reflex. Reported adverse events (AE) included 92 (84%) grade I/II and 18 (16%) grade III/IV. Grade III hepatotoxicity, mostly cytolysis, was the most frequent AE observed with 8 (8%) events. Grade III/IV hematologic toxicities concerned 9 patients with 8 grade III/IV neutropenia and 1 thrombocytopenia. Renal toxicity was rare, mild, and transient, observed with 4 (4%) grade I/II events. Ambulatory administration of HD-MTX at 3 g/m2 without MTX clearance monitoring is safe with strict medical guidance. It requires careful selection of patients before administration, and a renal and hepatic monitoring after the administration.


Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Sistema Nervioso Central/patología , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Metotrexato/uso terapéutico , Adolescente , Adulto , Atención Ambulatoria , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bleomicina/administración & dosificación , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Enfermedades Hematológicas/inducido químicamente , Humanos , Infusiones Intravenosas , Enfermedades Renales/inducido químicamente , Pruebas de Función Renal , Leucovorina/uso terapéutico , Pruebas de Función Hepática , Linfoma de Células B Grandes Difuso/patología , Linfoma no Hodgkin/patología , Masculino , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Persona de Mediana Edad , Invasividad Neoplásica , Servicio Ambulatorio en Hospital , Prednisona/administración & dosificación , Estudios Retrospectivos , Rituximab/administración & dosificación , Vincristina/administración & dosificación , Vindesina/administración & dosificación , Adulto Joven
15.
Nat Commun ; 12(1): 613, 2021 01 27.
Artículo en Inglés | MEDLINE | ID: mdl-33504774

RESUMEN

Induction of intrinsic liver regeneration is an unmet need that can be achieved by temporally activating key hepatocyte regenerative pathways. Here, we establish an efficient, safe, non-integrative method to transiently express hepatocyte-growth-factor (HGF) and epidermal-growth-factor (EGF) in hepatocytes via nucleoside-modified, lipid-nanoparticle-encapsulated mRNA (mRNA-LNP) delivery in mice. We confirm specific hepatotropism of mRNA-LNP via intravenous injection of firefly luciferase encoding mRNA-LNP, with protein expression lasting about 3 days. In the liver, virtually all hepatocytes are transfected along with a subpopulation of endothelial and Kupffer cells. In homeostasis, HGF mRNA-LNP efficiently induce hepatocyte proliferation. In a chronic liver injury mouse model recapitulating non-alcoholic fatty liver disease, injections of both HGF and EGF mRNA-LNP sharply reverse steatosis and accelerate restoration of liver function. Likewise, HGF and EGF mRNA-LNP accelerate liver regeneration after acetaminophen-induced acute liver injury with rapid return to baseline ALT levels. This study introduces mRNA-LNP as a potentially translatable safe therapeutic intervention to harness liver regeneration via controlled expression of endogenous mitogens in vivo.


Asunto(s)
Hepatocitos/patología , Lípidos/química , Regeneración Hepática/fisiología , Hígado/patología , Nanopartículas/química , Nucleósidos/metabolismo , ARN Mensajero/metabolismo , Acetaminofén , Animales , Proliferación Celular/efectos de los fármacos , Enfermedad Crónica , Modelos Animales de Enfermedad , Factor de Crecimiento Epidérmico/farmacología , Femenino , Proteínas Fluorescentes Verdes/metabolismo , Factor de Crecimiento de Hepatocito/farmacología , Hepatocitos/efectos de los fármacos , Homeostasis/efectos de los fármacos , Inyecciones , Hígado/efectos de los fármacos , Hígado/lesiones , Hígado/fisiopatología , Pruebas de Función Hepática , Regeneración Hepática/efectos de los fármacos , Ratones Endogámicos C57BL
17.
Ecotoxicol Environ Saf ; 208: 111610, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33396130

RESUMEN

Hepatic oxidative stress, as one important mechanism of cadmium (Cd)-induced hepatic toxicity, could, as known, be ameliorated by vitamin E (VE). However, the underlying mechanism remains to be elucidated. To investigate whether the antioxidant vitamin E can protect against Cd-induced sub-chronic liver injury associated with oxidative stress and nuclear factor erythrocyte 2-related factor 2 (Nrf2) pathway, male Sprague-Dawley rats (nine-week-old) were randomly divided into four groups (eight rats/group), namely, control, VE (100 mg/kg VE), Cd (5 mg/kg CdCl2) and VE+Cd (100 mg/kg VE+5 mg/kg CdCl2), and received intragastric administration of Cd and/or VE for four weeks. Cd-exposure alone resulted in reduced liver weight, liver histological alteration and oxidative stress, accumulation of Cd in the liver, elevated ALT and AST concentrations in serum together with decreased mRNA and protein expressions of Nrf2 pathway related molecules (Nrf2, HO-1, NQO-1, GCLC, GCLM and GST). However, the co-treatment of Cd and VE significantly ameliorated the changes mentioned above, and promoted the expression of genes and proteins of Nrf2 pathway related molecules in comparison to the Cd-exposure alone. Our results indicate that the protective effect of VE against Cd-induced sub-chronic hepatic damage in rats is associated with the inhibition of oxidative stress and activation of Nrf2 pathway.


Asunto(s)
Antioxidantes/farmacología , Cadmio/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Contaminantes Ambientales/toxicidad , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacos , Vitamina E/farmacología , Animales , Antioxidantes/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Pruebas de Función Hepática , Masculino , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Transducción de Señal
18.
Nat Commun ; 12(1): 34, 2021 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-33397947

RESUMEN

Colloidal gold nanoparticles (GNPs) serve as promising contrast agents in photoacoustic (PA) imaging, yet their utility is limited due to their absorption peak in the visible window overlapping with that of hemoglobin. To overcome such limitation, this report describes an ultrapure chain-like gold nanoparticle (CGNP) clusters with a redshift peak wavelength at 650 nm. The synthesized CGNP show an excellent biocompatibility and photostability. These nanoparticles are conjugated with arginine-glycine-aspartic acid (RGD) peptides (CGNP clusters-RGD) and validated in 12 living rabbits to perform multimodal photoacoustic microscopy (PAM) and optical coherence tomography (OCT) for visualization of newly developed blood vessels in the sub-retinal pigment epithelium (RPE) space of the retina, named choroidal neovascularization (CNV). The PAM system can achieve a 3D PAM image via a raster scan of 256 × 256 pixels within a time duration of 65 s. Intravenous injection of CGNP clusters-RGD bound to CNV and resulted in up to a 17-fold increase in PAM signal and 176% increase in OCT signal. Histology indicates that CGNP clusters could disassemble, which may facilitate its clearance from the body.


Asunto(s)
Oro/química , Nanopartículas del Metal/química , Microscopía , Imagen Molecular , Técnicas Fotoacústicas , Tomografía de Coherencia Óptica , Animales , Neovascularización Coroidal/diagnóstico por imagen , Neovascularización Coroidal/patología , Medios de Contraste/química , Femenino , Pruebas de Función Renal , Pruebas de Función Hepática , Masculino , Nanopartículas del Metal/ultraestructura , Ratones , Oligopéptidos/química , Conejos , Distribución Tisular
19.
Anticancer Res ; 41(1): 391-402, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33419836

RESUMEN

BACKGROUND/AIM: Oxaliplatin-based chemotherapy is associated with hepatic sinusoidal obstruction syndrome (SOS). PATIENTS AND METHODS: We analyzed patients from two prospective trials, in which capecitabine/oxaliplatin (XELOX, 8 cycles; n=51) and S-1/oxaliplatin [SOX, continuous (SOX-C, n=50), or intermittent (discontinuation after cycle 6 and restart on progression, SOX-I, n=50)] were administered. We compared severity (splenomegaly, thrombocytopenia, liver enzyme levels, and hepatic parenchymal heterogeneity), clinical significance (delay or dose-reduction of chemotherapy), and reversibility of SOS (splenomegaly and thrombocytopenia after stopping chemotherapy) between SOX and XELOX in gastric cancer patients. RESULTS: SOX was more likely to be associated with splenomegaly, thrombocytopenia, hyperbilirubinemia, and hepatic parenchymal heterogeneity than XELOX. Splenomegaly was partially reversible after stopping chemotherapy in both regimens, but recovery rate was lower in SOX. Proportion of delayed or dose-reduced chemotherapy cycles due to thrombocytopenia was significantly higher in SOX-C than in XELOX. CONCLUSION: S-1 combination is more likely to worsen oxaliplatin-induced hepatic sinusoidal injuries than capecitabine in gastric cancer patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad Veno-Oclusiva Hepática/etiología , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Biomarcadores , Capecitabina/administración & dosificación , Manejo de la Enfermedad , Combinación de Medicamentos , Femenino , Enfermedad Veno-Oclusiva Hepática/diagnóstico , Enfermedad Veno-Oclusiva Hepática/epidemiología , Enfermedad Veno-Oclusiva Hepática/terapia , Humanos , Incidencia , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Oxaliplatino/administración & dosificación , Ácido Oxónico/administración & dosificación , Estudios Retrospectivos , Bazo/patología , Esplenectomía , Tegafur/administración & dosificación , Resultado del Tratamiento
20.
Anticancer Res ; 41(1): 437-444, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33419841

RESUMEN

BACKGROUND/AIM: Intraarterial Technetium-99m-Macroaggregated Albumin (99mTc-MAA) administration is an established method to predict particle distribution prior to radioembolization. This study aimed to analyse the impact of intraarterial administration of 99mTc-MAA on changes in liver-specific laboratory parameters and to assess whether such changes are associated with post-radioembolization hepatotoxicity. PATIENTS AND METHODS: A total of 202 patients treated with radioembolization received prior mapping angiography with 99mTc-MAA administration. All patients underwent clinical and laboratory examinations, including liver-specific parameters at certain times before and after mapping angiography/99mTc-MAA administration, as well as before radioembolization and during follow-up. RESULTS: Bilirubin increased temporarily after 99mTc-MAA administration (p<0.001), but was not clinically relevant, and returned close to the initial value before radioembolization. These changes showed no association with subsequent postradioembolic hepatotoxicity or shortened overall survival. CONCLUSION: 99mTc-MAA administration results in a significant, however, not clinically relevant transient increase in bilirubin levels, which does not provide a predictive value for subsequent radioembolization outcome or postradioembolic hepatotoxicity.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Embolización Terapéutica/efectos adversos , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/terapia , Radiofármacos/efectos adversos , Agregado de Albúmina Marcado con Tecnecio Tc 99m/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Angiografía por Tomografía Computarizada , Manejo de la Enfermedad , Embolización Terapéutica/métodos , Femenino , Humanos , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Pronóstico , Radiofármacos/administración & dosificación , Estudios Retrospectivos , Agregado de Albúmina Marcado con Tecnecio Tc 99m/administración & dosificación , Resultado del Tratamiento
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