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1.
J Hepatocell Carcinoma ; 10: 863-881, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37313303

RESUMEN

Purpose: As the major subtype of liver cancer, hepatocellular carcinoma (HCC) suffers from high mortality and is prone to recurrence. Long non-coding RNAs (lncRNAs) are well characterized to be pivotal players contributing to HCC pathogenesis and progression. Therefore, this study intended to probe the biological functions of LINC00886 in hepatocarcinogenesis. Patients and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to analysis of LINC00886, microRNA-409-3p (miR-409-3p), microRNA-214-5p (miR-214-5p), RAB10 and E2F2 expression. Subcellular localization of LINC00886 was identified through a fluorescent in situ hybridization (FISH) kit and a subcellular assay. Additionally, proliferated cells were determined with EdU as well as cell counting kit-8 (CCK-8) assays. Scratch and Transwell assays were applied to detect migratory and invasive cells. Apoptotic cells were measured via TUNEL staining assay. Furthermore, targeted binding between LINC00886 and miR-409-3p or miR-214-5p was validated utilizing dual-luciferase reporter assays. RAB10, E2F2 and NF-κB signaling-associated protein levels were evaluated utilizing Western blot. Results: LINC00886, RAB10 and E2F2 levels were aberrantly increased, with the abnormal expressed decline of miR-409-3p and miR-214-5p, in HCC tissues, cells and peripheral blood mononuclear cells (PBMCs). Silencing LINC00886 attenuated the proliferative, migratory, invasive, and anti-apoptotic potential of HCC cells, while LINC00886 overexpression proceeded in the contrary direction. Mechanistically, miR-409-3p and miR-214-5p were validated as binding targets for LINC00886 and inverted the biological functions of LINC00886 during HCC progression. Furthermore, the LINC00886-miR-409-3p/miR-214-5p axis could regulate RAB10 and E2F2 expression via mediating NF-κB pathway activation in hepatocarcinogenesis. Conclusion: Our findings indicated that LINC00886 facilitated HCC progression via absorbing miR-409-3p or miR-214-5p to upregulate RAB10 and E2F2 through activation of NF-κB pathway, offering a promising novel target for HCC therapy.

2.
Lab Med ; 54(5): 507-511, 2023 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-36810696

RESUMEN

OBJECTIVE: The presence of red blood cell (RBC) irregular antibodies can severely jeopardize mother and child and bring trouble to the treatment of anemia. The aim of this study was to analyze the specificity of RBC irregular antibody in inpatients. METHODS: An analysis was performed on samples from patients with RBC irregular antibodies. Antibody screening positive samples were analyzed. RESULTS: Among the 778 cases of irregular antibody positive samples, 214 were from males and 564 from females. History of blood transfusion accounted for 13.1% of the total. Of the women, 96.8% had a pregnancy. A total of 131 antibodies were identified. The antibodies included 68 Rh systematic antibodies, 6 MNS systematic antibodies, 6 Lewis systematic antibodies, 2 Kidd systematic antibodies, 10 autoantibodies, and 39 antibodies of uncertain specificity. CONCLUSION: Patients with blood transfusion or pregnancy history are prone to produce RBC irregular antibodies.


Asunto(s)
Transfusión Sanguínea , Eritrocitos , Masculino , Niño , Embarazo , Humanos , Femenino , Autoanticuerpos , Isoanticuerpos
3.
Acta Haematol ; 146(3): 214-219, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36758527

RESUMEN

INTRODUCTION: The aims of this study were to observe the therapeutic effect of platelet (PLT) transfusion and to analyze influencing factors for the sake of providing useful clues for improving the efficacy of PLT transfusion. METHODS: Included in this study were patients who received PLT transfusion in the affiliated hospital of Nantong University. Patients' sex, age, height, weight, PLT transfusion status, and 20-24-h PLT count before and after PLT transfusion were collected to calculate the PLT corrected count increment values before and after PLT transfusion. Solid-phase red cell adherence assay was used to determine PLT antibody. Statistical analysis was performed using SPSS25.0 Software. RESULTS: A total of 364 patients received 1,060 PLT transfusions, including 728 successful transfusions and 332 unsuccessful transfusions. When the patients were grouped according to different etiologies, significant differences in PLT transfusion effectiveness were observed between these groups (χ2 = 15.070, p < 0.05). Grouping of the 364 patients according to sex, blood type, and PLT transfusion frequency showed no significant difference in PLT transfusion refractoriness (PTR) between different age-groups and sexes (p > 0.05). With the number of PLT transfusions increasing, PTR increased gradually. PLT antibodies were detected of 364 patients, 67 of them were positive. Among them, 63 cases (94.02%) were positive for HLA class I antibody. CONCLUSION: To reduce PTR, multiple factors should be considered comprehensively when PLT transfusion therapy is to be implemented in clinical practice. PLT antibody is the main immune factor causing PTR.


Asunto(s)
Transfusión de Plaquetas , Trombocitopenia , Humanos , Trombocitopenia/terapia , Recuento de Plaquetas
4.
Pathogens ; 11(12)2022 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-36558760

RESUMEN

Grapevine is one of the earliest domesticated fruit crops and prized for its table fruits and wine worldwide. However, the concurrence of a number of biotic/abiotic stresses affects their yield. Stress-associated proteins (SAPs) play important roles in response to both biotic and abiotic stresses in plants. Despite the growing number of studies on the genomic organisation of SAP gene family in various species, little is known about this family in grapevines (Vitis vinifera L.). In this study, a total of 15 genes encoding proteins possessing A20/AN1 zinc-finger were identified based on the analysis of several genomic and proteomic grapevine databases. According to their structural and phylogenetics features, the identified SAPs were classified into three main groups. Results from sequence alignments, phylogenetics, genomics structure and conserved domains indicated that grapevine SAPs are highly and structurally conserved. In order to shed light on their regulatory roles in growth and development, as well as the responses to biotic/abiotic stresses in grapevine, the expression profiles of SAPs were examined in publicly available microarray data. Bioinformatics analysis revealed distinct temporal and spatial expression patterns of SAPs in various tissues, organs and developmental stages, as well as in response to biotic/abiotic stresses. This study provides insight into the evolution of SAP genes in grapevine and may aid in efforts for further functional identification of A20/AN1-type proteins in the signalling cross-talking induced by biotic/abiotic stresses.

5.
Transfus Apher Sci ; 61(6): 103509, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35842292

RESUMEN

OBJECTIVE: To analyze the molecular mechanism of rare Bweak subgroup in the ABO blood group system and conduct pedigree investigations. METHODS: The blood group was detected by conventional serological method, and ABO gene of proband and her family was amplified and sequenced by polymerase chain reaction method. RESULTS: The study showed that the proband was a Bweak phenotype by conventional serological method. Her family's serological results were as follows, her father and eldest brother were Bweak subgroup while her mother and second eldest brother were O group. The proband's ABO gene sequencing result was ABO*BW.27/ABO*O.01.02. Her father, mother and two elder brothers were ABO*BW.27/ABO*O.01.01, ABO*O.01.01/ABO*O.01.02, ABO*BW.27/ABO*O.01.02, ABO*O.01.01/ABO*O.01.02. CONCLUSION: Conventional blood group serology combined with molecular diagnostic technology can accurately identify the Bweak subgroup, and the pedigree investigation analysis showed that the proband's allelic mutation came from her father. She has gained a point mutation of c.905A>G on the basis of ABO*B.01.


Asunto(s)
Sistema del Grupo Sanguíneo ABO , Biología Molecular , Masculino , Femenino , Animales , Linaje , Genotipo , Alelos , Fenotipo , Sistema del Grupo Sanguíneo ABO/genética
6.
J Hepatocell Carcinoma ; 9: 389-403, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35592243

RESUMEN

Purpose: The aim of this study was to identify and validate novel biomarkers for distinguishing among hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), liver fibrosis/liver cirrhosis (LF/LC) and chronic hepatitis B (CHB). Patients and Methods: Transcriptomic sequencing was conducted on the liver tissues of 5 patients with HCC, 5 patients with LF/LC, 5 patients with CHB, and 4 healthy controls. The expression levels of selected mRNAs and proteins were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical (IHC) staining, and were verified in validation set (n=200) and testing set (n=400) via enzyme-linked immunosorbent assay (ELISA). Results: A total of 9 hub mRNAs were identified by short time-series expression miner and weighted gene co-expression network analysis. Of note, the results of qRT-PCR and IHC staining demonstrated that SHC adaptor protein 1 (SHC1), SLAM family member 8 (SLAMF8), and interleukin-32 (IL-32) exhibited gradually increasing trends in the four groups. Subsequent ELISA tests on the validation cohort indicated that the plasma levels of SHC1, SLAMF8 and IL-32 also gradually increased. Furthermore, a diagnostic model APFSSI (age, PLT, ferritin, SHC1, SLAMF8 and IL-32) was established to distinguish among CHB, LF/LC and HCC. The performance of APFSSI model for discriminating CHB from healthy subjects (AUC=0.966) was much greater compared to SHC1 (AUC=0.900), SLAMF8 (AUC=0.744) and IL-32 (AUC=0.821). When distinguishing LF/LC from CHB, APFSSI was the most outstanding diagnostic parameter (AUC=0.924), which was superior to SHC1, SLAMF8 and IL-32 (AUC=0.812, 0.684 and 0.741, respectively). Likewise, APFSSI model with the greatest AUC value displayed an excellent performance for differentiating between HCC and LF/LC than other variables (SHC1, SLAMF8 and IL-32) via ROC analysis. Finally, the results in the test set were consistent with those in the validation set. Conclusion: SHC1, SLAMF8 and IL-32 can differentiate among patients with HCC, LF/LC, CHB and healthy controls. More importantly, the APFSSI model greatly improves the diagnostic accuracy of HBV-associated liver diseases.

7.
Lab Med ; 53(1): 65-70, 2022 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-34388244

RESUMEN

The purpose of this study was to determine whether circular RNA hsa_circ_0002874 could serve as a novel biomarker for the diagnosis of gastric cancer (GC). The expression level of hsa_circ_0002874 mean (interquartile range [IQR]) in the plasma of patients with GC, patients with benign gastric lesions, and healthy individuals was 3.482 (IQR, 1.524-9.048), 1.261 (IQR, 0.817-2.000), and 1.00 (IQR, 0.726-1.382), respectively, whereas there was no significant difference between the latter 2 groups. The plasma expression level of hsa_circ_0002874 was significantly correlated with tumor stage (U = 234.0; P < .001) and lymph node metastasis (U = 240.0; P < .001). The receiver operating characteristic (ROC) curve showed that the sensitivity of the combined determination of hsa_circ_0002874 and the serum markers CEA and CA19-9 was 95.8% in patients with GC compared with that of the healthy group and 93.0% compared with that of patients with benign gastric tumor lesions. The specificity of hsa_circ_0002874 in differentiating GC from benign lesions was 98.3%. The results showed that plasma hsa_circ_0002874 may prove to be a useful biomarker for auxiliary diagnosis, the grading of malignant neoplasms, and the prognostic prediction of GC.


Asunto(s)
Neoplasias Gástricas , Biomarcadores de Tumor , Humanos , Pronóstico , ARN Circular , Curva ROC , Neoplasias Gástricas/diagnóstico
8.
Blood Transfus ; 20(5): 414-419, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-34967725

RESUMEN

BACKGROUND: The para-Bombay phenotype is a rare red blood cell phenotype characterised by the lack of ABH antigens on red blood cells, but ABH substances can be found in saliva. The aim of this research was to study the mechanism of mutation of FUT1 and FUT2 genes and the pedigree of a family with the para-Bombay phenotype. MATERIAL AND METHODS: The blood group was detected by a conventional serological method, H antigen adsorption-elution test, and testing saliva for A, B, and H antigens. We amplified and sequenced the ABO, FUT1, and FUT2 genes of the proband and her family using a polymerase chain reaction method, and performed TA cloning and sequencing on the amplified products of the FUT1 gene to determine its genotype. RESULTS: With the conventional serological method, it was found that the red blood cell phenotype of the proband and her sister lacked H antigen, while the adsorption-elution test of H antigen could detect weak H antigen. Through FUT1 cloning and sequencing, it was found that the proband had a compound heterozygous mutation of c.649G>T and c.768delC, and the genotype was FUT1*01W.24/FUT1*01N.20; the proband's father and mother had heterozygous mutations of c.768delC and c.649G>T, and their genotypes were FUT1*01N.20/FUT1*01 and FUT1*01W.24/FUT1*01. The sister's FUT1 mutation site and genotype were the same as the those of the proband. FUT2 gene sequencing revealed that the proband and sister had a synonymous mutation of c.357C>T, while their parents both had a synonymous mutation of c.357C>T and a missense mutation of c.385A>T. The Lewis blood types of the four samples all showed Le (a-b+), all of which were secretory. CONCLUSION: Blood group serology and molecular diagnostic techniques showed that the compound heterozygous mutations of the proband and her sister were inherited from their father and mother.


Asunto(s)
Sistema del Grupo Sanguíneo ABO , Fucosiltransferasas , Sistema del Grupo Sanguíneo ABO/genética , Alelos , Femenino , Fucosiltransferasas/genética , Genotipo , Humanos , Mutación , Linaje , Fenotipo
9.
Onco Targets Ther ; 12: 6639-6651, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31695405

RESUMEN

BACKGROUND: Increasing evidence suggests that glutathione peroxidase 2 (GPX2) plays important roles in the tumorigenesis and progression of various human cancers, such as colorectal carcinomas and lung adenocarcinomas. However, the role of GPX2 in cervical cancer is unclear. In this study, we identified the role of GPX2 in cervical cancer tissues and cell lines. MATERIALS AND METHODS: The basal mRNA and protein expression of GPX2 in cervical cancer cells and a series of key molecules in the epithelial to mesenchymal transition (EMT) and WNT/ß-catenin pathways were examined via real time fluorescence quantitative PCR (qRT-PCR) and Western blot assays. The biological phenotype of the cervical cancer cell lines was detected by the cloning formation and transwell assays, and intracellular reactive oxygen species (ROS) levels were detected by flow cytometry. Finally, the GPX2 expression level in 100 clinical cervical tissues was examined by immunohistochemistry. RESULTS: We found that GPX2 was highly expressed in cervical cancer tissues compared to normal individuals and promoted the proliferation and metastasis of cervical cancer cells, and this promotion correlated with the activation of EMT and WNT/ß-catenin signaling in vitro. GPX2 was determined to reduce apoptotic damage by reducing hydroperoxides. According to the characteristics and verification of GPX2, this series of phenotypes is clearly related to oxidative stress in cells. Furthermore, we verified that GPX2 was highly expressed in cervical cancer tissues and promoted the metastasis of cervical cancer. CONCLUSION: In summary, we found that GPX2 was highly expressed in cervical cancer cells and promoted the proliferation and metastasis of cervical cancer by affecting oxidative stress. Our study provides a new target for the clinical treatment of cervical cancer.

10.
Mol Med Rep ; 17(3): 4567-4572, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29328470

RESUMEN

The aim of the present study was to investigate the preconditioning effect and underlying mechanisms of cobalt-protoporphyrin (CoPP) in a mouse model of liver ischemia­reperfusion (I/R) injury. Mice were divided into five groups: Sham­operated (control), I/R, I/R + CoPP, I/R + CoPP and zinc­protoporphyrin (ZnPP) and I/R + ZnPP. Serum levels of aspartate transaminase (AST) and alanine aminotransferase (ALT) were detected using commercial kits. The expression of the pro­apoptotic protein caspase­3 was detected by immunohistochemistry and the expression levels of the anti­apoptotic protein B­cell lymphoma 2 (Bcl­2) and heme oxygenase 1 (HO­1) were analyzed by western blotting. Sections of liver tissue were stained with hematoxylin and eosin to observe pathologic alterations. Furthermore, hepatocyte apoptosis was detected using a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. AST and ALT levels of the CoPP preconditioned group were significantly reduced compared with the IR injury group (P<0.05) and liver damage was attenuated. The expression levels of the pro­apoptotic protein caspase3 was inhibited and those of HO­1 and Bcl­2 were increased in the CoPP group compared with the I/R group; the opposite results were observed in the ZnPP group. Furthermore, the percentage of apoptotic cells as detected by TUNEL was significantly decreased in the CoPP group compared with the I/R group (P<0.05); these protective effects were abrogated by ZnPP. In conclusion, the results of the present study suggested that CoPP may induce HO­1 overexpression and produce anti­apoptotic effects in liver I/R injury.


Asunto(s)
Apoptosis/efectos de los fármacos , Hemo-Oxigenasa 1/metabolismo , Hígado/metabolismo , Protoporfirinas/farmacología , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Caspasa 3/metabolismo , Modelos Animales de Enfermedad , Inmunohistoquímica , Hígado/patología , Ratones , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Regulación hacia Arriba/efectos de los fármacos
11.
Sci Rep ; 7(1): 3762, 2017 06 19.
Artículo en Inglés | MEDLINE | ID: mdl-28630433

RESUMEN

The characteristics of intestinal microbial communities may be affected by changes in the pathophysiology of patients with end-stage liver disease. Here, we focused on the characteristics of intestinal fecal microbial communities in post-liver transplantation (LT) patients in comparison with those in the same individuals pre-LT and in healthy individuals. The fecal microbial communities were analyzed via MiSeq-PE250 sequencing of the V4 region of 16S ribosomal RNA and were then compared between groups. We found that the gut microbiota of patients with severe liver disease who were awaiting LT was significantly different from that of healthy controls, as represented by the first principal component (p = 0.0066). Additionally, the second principal component represented a significant difference in the gut microbiota of patients between pre-LT and post-LT surgery (p = 0.03125). After LT, there was a significant decrease in the abundance of certain microbial species, such as Actinobacillus, Escherichia, and Shigella, and a significant increase in the abundance of other microbial species, such as Micromonosporaceae, Desulfobacterales, the Sarcina genus of Eubacteriaceae, and Akkermansia. Based on KEGG profiles, 15 functional modules were enriched and 21 functional modules were less represented in the post-LT samples compared with the pre-LT samples. Our study demonstrates that fecal microbial communities were significantly altered by LT.


Asunto(s)
Bacterias , Enfermedad Hepática en Estado Terminal/microbiología , Microbioma Gastrointestinal , Trasplante de Hígado , ARN Bacteriano/genética , ARN Ribosómico 16S/genética , Adulto , Bacterias/clasificación , Bacterias/genética , Bacterias/crecimiento & desarrollo , Enfermedad Hepática en Estado Terminal/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad
12.
Medicine (Baltimore) ; 96(5): e5790, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28151854

RESUMEN

RATIONALE: Postliver transplant periampullary carcinoma is an extremely uncommon disease. PATIENT CONCERNS: Cutaneous jaundice in a patient who had received a liver transplant 4 years earlier. DIAGNOSIS: Periampullary carcinoma. INTERVENTIONS: Radiofrequency ablation plus fully covered self-expanding metal stents (FCSEMS). OUTCOMES: The treatment of malignant neoplasm of the ampulla of Vater is the patient by radiofrequency ablation plus FCSEMS placement was successful. No complications occurred. LESSONS: This is the first reported case of a liver transplant patient with inoperable periampullary carcinoma successfully treated by radiofrequency ablation plus FCSEMS placement. Our experience will be useful to other surgeons in managing similar patients in the future.


Asunto(s)
Técnicas de Ablación/métodos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Neoplasias del Conducto Colédoco/cirugía , Trasplante de Hígado , Stents Metálicos Autoexpandibles , Ampolla Hepatopancreática , Humanos , Masculino , Persona de Mediana Edad
13.
World J Gastroenterol ; 21(20): 6409-16, 2015 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-26034379

RESUMEN

Mesenchymal hamartomas of the liver (MHLs) in adults are rare and potentially premalignant lesions, which present as solid/cystic neoplasms. We report a rare case of orthotopic liver transplantation in a patient with a giant MHL. In 2013, a 34-year-old female sought medical advice after a 2-year history of progressive abdominal distention and respiratory distress. Physical examination revealed an extensive mass in the abdomen. Computed tomography (CT) of her abdomen revealed multiple liver cysts, with the diameter of largest cyst being 16 cm × 14 cm. The liver hilar structures were not clearly displayed. The adjacent organs were compressed and displaced. Initial laboratory tests, including biochemical investigations and coagulation profile, were unremarkable. Tumor markers, including levels of AFP, CEA and CA19-9, were within the normal ranges. The patient underwent orthotopic liver transplantation in November 2013, the liver being procured from a 40-year-old man after cardiac death following traumatic brain injury. Warm ischemic time was 7.5 min and cold ischemic time was 3 h. The recipient underwent classical orthotopic liver transplantation. The recipient operative procedure took 8.5 h, the anhepatic phase lasting for 1 h without the use of venovenous bypass. The immunosuppressive regimen included intraoperative induction with basiliximab and high-dose methylprednisolone, and postoperative maintenance with tacrolimus, mycophenolate mofetil, and prednisone. The recipient's diseased liver weighed 21 kg (dry weight) and measured 41 cm × 32 cm × 31 cm. Histopathological examination confirmed the diagnosis of an MHL. The patient did not experience any acute rejection episode or other complication. All the laboratory tests returned to normal within one month after surgery. Three months after transplantation, the immunosuppressive therapy was reduced to tacrolimus monotherapy, and the T-tube was removed after cholangiography showed no abnormalities. Twelve months after transplantation, the patient remains well and is fulfilling all normal activities. Adult giant MHL is extremely rare. Symptoms, physical signs, laboratory results, and radiographic imaging are nonspecific and inconclusive. Surgical excision of the lesion is imperative to make a definite diagnosis and as a cure. Liver transplantation should be considered as an option in the treatment of a non-resectable MHL.


Asunto(s)
Hamartoma/cirugía , Neoplasias Hepáticas/cirugía , Trasplante de Hígado , Adulto , Biomarcadores de Tumor/análisis , Biopsia , Femenino , Supervivencia de Injerto , Hamartoma/química , Hamartoma/patología , Humanos , Inmunohistoquímica , Inmunosupresores/administración & dosificación , Neoplasias Hepáticas/química , Neoplasias Hepáticas/patología , Masculino , Mesodermo/patología , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Carga Tumoral
14.
World J Gastroenterol ; 21(7): 2236-41, 2015 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-25717264

RESUMEN

Although the development of de novo autoimmune liver disease after liver transplantation (LT) has been described in both children and adults, autoimmune hepatitis (AIH)-primary biliary cirrhosis (PBC) overlap syndrome has rarely been seen in liver transplant recipients. Here, we report a 50-year-old man who underwent LT for decompensated liver disease secondary to alcoholic steatohepatitis. His liver function tests became markedly abnormal 8 years after LT. Standard autoimmune serological tests were positive for anti-nuclear and anti-mitochondrial antibodies, and a marked biochemical response was observed to a regimen consisting of prednisone and ursodeoxycholic acid added to maintain immunosuppressant tacrolimus. Liver biopsy showed moderate bile duct lesions and periportal lymphocytes infiltrating along with light fibrosis, which confirmed the diagnosis of AIH-PBC overlap syndrome. We believe that this may be a case of post-LT de novo AIH-PBC overlap syndrome; a novel type of autoimmune overlap syndrome.


Asunto(s)
Colestasis/etiología , Hígado Graso Alcohólico/cirugía , Hepatitis Autoinmune/etiología , Cirrosis Hepática Biliar/etiología , Trasplante de Hígado/efectos adversos , Colagogos y Coleréticos/uso terapéutico , Colestasis/diagnóstico , Colestasis/terapia , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/tratamiento farmacológico , Humanos , Inmunosupresores/uso terapéutico , Cirrosis Hepática Biliar/diagnóstico , Cirrosis Hepática Biliar/tratamiento farmacológico , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Tacrolimus/uso terapéutico , Resultado del Tratamiento , Ácido Ursodesoxicólico/uso terapéutico
15.
Int J Clin Pharmacol Ther ; 53(1): 75-83, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25207550

RESUMEN

OBJECTIVE: The purpose of this study was to describe the population pharmacokinetics (PK) of tacrolimus (TAC) in 52 Chinese pediatric patients early after liver transplantation. METHODS: Details of drug dose, sampling times and concentrations were collected retrospectively from routine therapeutic drug monitoring data from the first day after surgery. A total of 488 concentration data were obtained and analyzed by a nonlinear mixed-effect modeling (NONMEM) method. A number of demographic and clinical variables were tested for their influence on TAC PK parameters. RESULTS: The PK of TAC were best described by a one-compartment model with first-order absorption and elimination. Apparent clearance (CL/F) and apparent volumes of distribution (V/F) in final population model were 5.72 L/h and 131 L, respectively. The absorption rate constant (Ka) was fixed in 4.48 h-1. The inter-individual variabilities in CL/F and V/F were 13.5% and 78.1%. In the final analysis performed in all 52 patients, the post-operation day (POD) and alanine aminotransferase (ALT) influenced TAC CL/F and V/F, and total protein (TP) was the only covariate retained on V/F. CONCLUSION: A population PK model of TAC was developed in Chinese pediatric patients early after liver transplantation. It identified significant relationships between the PK of TAC and the characteristics of the patients. POD, ALT, and TP were identified as the main factors influencing the PK of TAC. The developed model could be useful to optimize individual pediatric TAC dosing regimen in routine clinical practice.


Asunto(s)
Rechazo de Injerto/prevención & control , Inmunosupresores/farmacocinética , Trasplante de Hígado , Modelos Biológicos , Tacrolimus/farmacocinética , Administración Oral , Adolescente , Factores de Edad , Área Bajo la Curva , Pueblo Asiatico , Niño , Preescolar , China , Esquema de Medicación , Monitoreo de Drogas , Femenino , Rechazo de Injerto/sangre , Rechazo de Injerto/etnología , Rechazo de Injerto/inmunología , Supervivencia de Injerto/efectos de los fármacos , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/sangre , Lactante , Trasplante de Hígado/efectos adversos , Masculino , Tasa de Depuración Metabólica , Dinámicas no Lineales , Reproducibilidad de los Resultados , Estudios Retrospectivos , Tacrolimus/administración & dosificación , Tacrolimus/sangre , Resultado del Tratamiento
16.
Clin Res Hepatol Gastroenterol ; 38(4): e65-7, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24836842

RESUMEN

Acquired inhibitors against coagulation factor V (FV) occur rarely, the clinical symptoms vary to a great extent, from asymptomatic laboratory abnormalities to life-threatening bleeding. Coagulation factor V (FV) is a plasma-cofactor mostly existing in the plasma, and approximately 20-25% (Tracy et al. (1982), Kane (2006)) of FV exist in platelet granules. Patients' reaction is the prolonging of prothrombin time (PT) and activated partial thromboplastin time (APTT), but there is no exact reason, and that can not be corrected after normal plasma transfusion (Morris and Curris (2009), Lucia and Aguilar (2005)). We report here a case of the occurrence of FV inhibitors after orthotopic liver transplantation (OLT). With gastrointestinal bleeding, patient's haemostatic response was not achieved after using fresh frozenplasma (FFP), platelet concentrates (PC), prothrombin complex concentrates (PCC) or recombinant activated FVII (rFVIIa). After using high-dose intravenous immunoglobulin (IVIg) and change of immunosuppressant from tacrolimus (FK506) to cyclosporine, the bleeding stopped and better laboratory examination results was achieved thereafter.


Asunto(s)
Inhibidores de Factor de Coagulación Sanguínea , Factor V , Hemorragia Gastrointestinal/etiología , Trasplante de Hígado , Complicaciones Posoperatorias/etiología , Humanos , Masculino , Persona de Mediana Edad
17.
J Pharm (Cairo) ; 2014: 713650, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-26556199

RESUMEN

Aim. The aim of this study was to establish population pharmacokinetic models of tacrolimus in Chinese adult liver transplantation patients. Methods. Tacrolimus dose and concentration data (n = 435) were obtained from 47 Chinese adult liver transplant recipients, and the data were analyzed using a nonlinear mixed-effect modeling (NONMEM) method. Results. The structural model was a two-compartment model with first-order absorption. The typical population values of tacrolimus for the pharmacokinetic parameters of apparent clearance (CL/F), apparent distribution volume of the central compartment (V 2/F), intercompartmental clearance (Q/F), apparent distribution volume of the peripheral compartment (V 3/F), and absorption rate (k a ) were 11.2 L/h, 406 L, 57.3 L/h, 503 L, and 0.723 h(-1), respectively. The interindividual variabilities of these parameters were 16.2%, 163%, 19.7%, 199%, and 74.3%, respectively, and the intraindividual variability of observed concentration was 26.54%. The covariates retained in the final models were postoperative days (POD) and dosage per day (DOSE) on CL/F. Conclusion. Population pharmacokinetic models of tacrolimus were developed in Chinese adult liver transplant patients. These results could provide the interpretation of the outcome of pharmacokinetics modeling and the impact of covariate tested on individualized tacrolimus therapy.

18.
Hepatogastroenterology ; 61(135): 2047-51, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25713909

RESUMEN

BACKGROUND/AIMS: To analyze the data from hepatitis B virus (HBV) infected patients with HBV recurrence after orthotopic liver transplantation (OLT) to determine their prognosis and survival. METHODOLOGY: We retrospectively analyzed data from patients who experienced HBV recurrence following OLT at our center between January 2000 and September 2011. All patients were monitored until June 2012 or their death. RESULTS: The total number of cases of HBV recurrence after liver transplantation was 56. Of these cases, 21 had benign liver disease and 35 had hepatocellular carcinoma (HCC). The median follow-up time was 48.8 months (range: 5.0-138.1 months). The median time to recurrence following transplantation was 44.4 months (range: 0.3-116.3 months) and 12.2 months (range: 0.3-135.1 months) for patients with benign liver disease and HCC, respectively. Nine patients were diagnosed with HBV recurrence first (1.2-8.2 months prior to HCC recurrence), seven patients showed HCC recurrence first (0.4-27.1 months prior to HBV recurrence), and the remaining 5 patients had HBV and HCC recurrence at the same time. Correlation analysis demonstrated a strong correlation between HBV and HCC recurrence times. Of the 56 patients with HBV recurrence, 24 had died at the time of data cut off, and the main cause of death was HCC recurrence. In patients with malignant liver disease, the survival rates were 78.8%, 48.8%, and 40.1% at 1, 3, and 5 years, respectively, which were lower than those in patients with benign liver disease, which were 94.7%, 89.5%, and 77.5% at 1, 3, and 5 years, respectively, P=0.001. CONCLUSION: Patients with HBV recurrence and benign liver disease have a better prognosis than HCC patients. Treatment with the addition of adefovir and/or entecavir is necessary for patients with HBV recurrence. A correlation between HBV and HCC recurrence times was observed. Hepatitis B recurrence can be used as a warning signal for tumor recurrence.


Asunto(s)
Carcinoma Hepatocelular/cirugía , Hepatitis B/complicaciones , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/efectos adversos , Adulto , Anciano , Antivirales/uso terapéutico , Biomarcadores/sangre , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/virología , Causas de Muerte , ADN Viral/sangre , Femenino , Hepatitis B/diagnóstico , Hepatitis B/tratamiento farmacológico , Hepatitis B/mortalidad , Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/virología , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Mutación , Recurrencia Local de Neoplasia , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Carga Viral
19.
Hepatobiliary Pancreat Dis Int ; 12(2): 143-8, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23558067

RESUMEN

BACKGROUND: Congenital biliary atresia is a rare condition characterized by idiopathic dysgenesis of the bile ducts. If untreated, congenital biliary atresia leads to liver cirrhosis, liver failure and premature death. The present study aimed to evaluate the outcomes of orthotopic liver transplantation in children with biliary atresia. METHOD: We retrospectively analyzed 45 patients with biliary atresia who had undergone orthotopic liver transplantation from September 2006 to August 2012. RESULTS: The median age of the patients was 11.0 months (5-102). Of the 45 patients, 41 were younger than 3 years old. Their median weight was 9.0 kg (4.5-29.0), 34 of the 45 patients were less than 10 kg. Thirty-one patients had undergone Kasai portoenterostomy prior to orthotopic liver transplantation. We performed 30 living donor liver transplants and 15 split liver transplants. Six patients died during a follow-up. The median follow-up time of surviving patients was 11.4 months (1.4-73.7). The overall 1-, 2- and 3-year survival rates were 88.9%, 84.4% and 84.4%, respectively. CONCLUSION: With advances in surgical techniques and management, children with biliary atresia after liver transplantation can achieve satisfactory survival in China, although there remains a high risk of complications in the early postoperative period.


Asunto(s)
Atresia Biliar/cirugía , Trasplante de Hígado , Factores de Edad , Atresia Biliar/mortalidad , Niño , Preescolar , China , Femenino , Humanos , Inmunosupresores/uso terapéutico , Lactante , Estimación de Kaplan-Meier , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Donadores Vivos , Masculino , Portoenterostomía Hepática , Complicaciones Posoperatorias/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
20.
Hepatol Res ; 43(12): 1321-6, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23489344

RESUMEN

AIM: Whether percutaneous transluminal balloon dilatation (PTBD) or stent placement should be used in children with hepatic venous outflow obstruction (HVOO) is still controversial. The aim of the present study was to retrospectively describe experience in diagnosis and treatment of HVOO and to evaluate the outcome of PTBD in HVOO patients after pediatric liver transplantation (P-LT). METHODS: From January 2001 to January 2011, 54 children received P-LT at our center. The clinical features of children with HVOO analyzed included demography, type of donor and liver transplant, the new-onset symptoms, liver function test, interventional examination, and treatment and outcome. RESULTS: Three children were treated successfully with PTBD without stenting. All patients received percutaneous interventional management successfully. In the total of eight episodes of PTBD across the stenosis, the mean pressure gradient ± standard deviation was 16.6 ± 7.90 mmHg before PTBD and 6.8 ± 2.27 mmHg after PTBD. The difference was significant (P < 0.05). All of the three HVOO patients were still surviving with primary graft functioning normally until the last follow up. CONCLUSION: HVOO after P-LT should be taken seriously. PTBD is an effective and safe treatment for HVOO in younger patients subjected to P-LT and re-venoplasty is recommended even in patients with recurrent HVOO.

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