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1.
J Cancer Res Clin Oncol ; 148(3): 647-656, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34874490

RESUMEN

PURPOSE: Immune checkpoint inhibitor (ICI)-induced hepatitis belongs to the frequently occurring immune-related adverse events (irAEs), particularly with the combination therapy involving ipilimumab and nivolumab. However, predisposing factors predicting the occurrence of ICI-induced hepatitis are barely known. We investigated the association of preexisting autoantibodies in the development of ICI-induced hepatitis in a prospective cohort of cancer patients. METHODS: Data from a prospective biomarker cohort comprising melanoma and non-small cell lung cancer (NSCLC) patients were used to analyze the incidence of ICI-induced hepatitis, putatively associated factors, and outcome. RESULTS: 40 patients with melanoma and 91 patients with NSCLC received ICI between July 2016 and May 2019. 11 patients developed ICI-induced hepatitis (8.4%). Prior to treatment, 45.5% of patients in the hepatitis cohort and 43.8% of the control cohort showed elevated titers of autoantibodies commonly associated with autoimmune liver diseases (p = 0.82). We found two nominally significant associations between the occurrence of ICI-induced hepatitis and HLA alleles associated with autoimmune liver diseases among NSCLC patients. Of note, significantly more patients with ICI-induced hepatitis developed additional irAEs in other organs (p = 0.0001). Neither overall nor progression-free survival was affected in the hepatitis group. CONCLUSION: We found nominally significant associations of ICI-induced hepatitis with two HLA alleles. ICI-induced hepatitis showed no correlation with liver-specific autoantibodies, but frequently co-occurred with irAEs affecting other organs. Unlike other irAEs, ICI-induced hepatitis is not associated with a better prognosis.


Asunto(s)
Autoanticuerpos/inmunología , Biomarcadores de Tumor/inmunología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Hepatitis/epidemiología , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Melanoma/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Autoanticuerpos/sangre , Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/patología , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Hepatitis/sangre , Hepatitis/etiología , Hepatitis/inmunología , Humanos , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Masculino , Melanoma/inmunología , Melanoma/patología , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Suiza/epidemiología
2.
J Pediatr Hematol Oncol ; 44(1): e223-e226, 2022 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-34669357

RESUMEN

Hepatitis-associated aplastic anemia (HAA) is a form of acquired aplastic anemia (AA) in which bone marrow failure develops after an acute attack of hepatitis. Bone marrow failure leading to AA is generally severe in cases of HAA and fatal if left untreated. This retrospective multicenter study investigated clinical and laboratory characteristics, possible causes, treatment, and outcome of HAA in children. Twenty patients from 8 centers were included in the study. Aspartate aminotransferase and alanine aminotransferase were <3 to 5×upper limit of normal (ULN) in 2 patients, <5 to 10×ULN in 2 patients, and >10×ULN in 16 patients. Acute liver failure developed in 5 (29%) patients. Pancytopenia was simultaneously present in 6 of 20 (30%) patients. Eleven of the 20 patients (55%) were alive, in remission and transfusion free. Those who were alive either had undergone hematopoietic stem cell transplantation and/or immunosuppressive treatment, except 1 patient who had received no treatment. Patients with the diagnosis of acute hepatitis should be evaluated and followed up carefully for presence of cytopenia, so that definitive treatment of AA can be initiated in a timely and appropriate manner when needed.


Asunto(s)
Anemia Aplásica , Trasplante de Células Madre Hematopoyéticas , Hepatitis , Fallo Hepático Agudo , Adolescente , Alanina Transaminasa/sangre , Aloinjertos , Anemia Aplásica/sangre , Anemia Aplásica/etiología , Anemia Aplásica/mortalidad , Anemia Aplásica/terapia , Aspartato Aminotransferasas/sangre , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Hepatitis/sangre , Hepatitis/complicaciones , Hepatitis/mortalidad , Hepatitis/terapia , Humanos , Fallo Hepático Agudo/sangre , Fallo Hepático Agudo/complicaciones , Fallo Hepático Agudo/mortalidad , Fallo Hepático Agudo/terapia , Masculino , Estudios Retrospectivos , Tasa de Supervivencia
3.
Biomark Med ; 16(1): 41-50, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34784758

RESUMEN

Viral diseases remain a significant global health threat, and therefore prioritization of limited healthcare resources is required to effectively manage dangerous viral disease outbreaks. In a pandemic of a newly emerged virus that is yet to be well understood, a noninvasive host-derived prognostic biomarker is invaluable for risk prediction. Red blood cell distribution width (RDW), an index of red blood cell size disorder (anisocytosis), is a potential predictive biomarker for severity of many diseases. In view of the need to prioritize resources during response to outbreaks, this review highlights the prospects and challenges of RDW as a prognostic biomarker for viral infections, with a focus on hepatitis and COVID-19, and provides an outlook to improve the prognostic performance of RDW for risk prediction in viral diseases.


Asunto(s)
Índices de Eritrocitos , Virosis/diagnóstico , Animales , Biomarcadores/análisis , Biomarcadores/sangre , COVID-19/sangre , COVID-19/diagnóstico , Eritrocitos/citología , Hepatitis/sangre , Hepatitis/diagnóstico , Humanos , Pronóstico , Virosis/sangre
4.
Sci Rep ; 11(1): 13053, 2021 06 22.
Artículo en Inglés | MEDLINE | ID: mdl-34158543

RESUMEN

Detection of low abundance target DNA/RNA for clinical or research purposes is challenging because the target sequences can be hidden under a large background of human genomic or non-human metagenomic sequences. We describe a probe-based capture method to enrich for target sequences with DNA-clicked iron oxide nanoparticles. Our method was tested against commercial capture assays using streptavidin beads, on a set of probes derived from a common genotype of the hepatitis C virus. We showed that our method is more specific and sensitive, most likely due to the combination of an inert silica coating and a high density of DNA probes clicked to the nanoparticles. This facilitates target capture below the limits of detection for TaqMan qPCR, and we believe that this method has the potential to transform management of infectious diseases.


Asunto(s)
Química Clic , ADN/análisis , Nanopartículas Magnéticas de Óxido de Hierro/química , Oligonucleótidos/química , ARN/análisis , Genoma Viral , Hepacivirus/genética , Hepatitis/sangre , Hepatitis/virología , Humanos , Estreptavidina/química
5.
Int Immunopharmacol ; 97: 107716, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33951559

RESUMEN

Several experiments confirmed that vitamin D3 protected against acetaminophen (APAP)-induced acute liver injury (ALI). This research aimed to evaluate the influence of vitamin D deficiency (VDD) on APAP-induced ALI. In VDD and VDD + APAP groups, mice were fed with VDD diet. In APAP and VDD + APAP groups, mice were intraperitoneally injected with a sublethal dose of APAP (150 mg/kg). A sublethal dose of APAP caused a slight elevation of ALT and AST. Interestingly, APAP-induced elevation of ALT and AST was aggravated in VDD-fed mice. APAP-induced hepatic necrosis was exacerbated in VDD-fed mice. In addition, APAP-induced hepatocyte death, measured using TUNEL assay, was exacerbated in VDD-fed mice. Additional experiment showed that APAP-induced hepatic GSH depletion and lipid peroxidation were exacerbated in VDD-fed mice. Moreover, APAP-induced upregulation of antioxidant genes, such as hepatic heme oxygenase-1 (Ho-1), glutathione peroxidase (Gshpx), superoxide dismutase 1 (Sod1) and catalase enzymes (Cat), was aggravated in VDD-fed mice. Although a sublethal dose of APAP did not cause hepatic inflammation, hepatic proinflammatory cytokines and chemokines, such as Tnf-α, Kc, Mcp-1 and Mip2, were upregulated in VDD-fed mice treated with APAP. These results provide experimental data that VDD exacerbates hepatic oxidative stress and inflammation during APAP-induced ALI.


Asunto(s)
Acetaminofén/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/inmunología , Hepatitis/inmunología , Deficiencia de Vitamina D/complicaciones , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Hepatitis/sangre , Hepatitis/patología , Humanos , Hígado/efectos de los fármacos , Hígado/inmunología , Hígado/patología , Masculino , Ratones , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/inmunología , Regulación hacia Arriba/inmunología , Vitamina D/sangre , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/inmunología
6.
Sci Rep ; 11(1): 10331, 2021 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-33990635

RESUMEN

Chorioamnionitis, inflammation of fetal membranes, is an important cause of preterm birth and a risk factor for the development of adverse neonatal outcomes including sepsis and intestinal pathologies. Intestinal bile acids (BAs) accumulation and hepatic cytokine production are involved in adverse intestinal outcomes. These findings triggered us to study the liver and enterohepatic circulation (EHC) following intra-amniotic (IA) lipopolysaccharide (LPS) exposure. An ovine chorioamnionitis model was used in which circulatory cytokines and outcomes of the liver and EHC of preterm lambs were longitudinally assessed following IA administration of 10 mg LPS at 5, 12 or 24h or 2, 4, 8 or 15d before preterm birth. Hepatic inflammation was observed, characterized by increased hepatic cytokine mRNA levels (5h - 2d post IA LPS exposure) and increased erythropoietic clusters (at 8 and 15 days post IA LPS exposure). Besides, 12h after IA LPS exposure, plasma BA levels were increased, whereas gene expression levels of several hepatic BA transporters were decreased. Initial EHC alterations normalized over time. Concluding, IA LPS exposure induces significant time-dependent changes in the fetal liver and EHC. These chorioamnionitis induced changes have potential postnatal consequences and the duration of IA LPS exposure might be essential herein.


Asunto(s)
Corioamnionitis/inmunología , Circulación Enterohepática/inmunología , Feto/irrigación sanguínea , Hepatitis/inmunología , Nacimiento Prematuro/inmunología , Animales , Ácidos y Sales Biliares/sangre , Ácidos y Sales Biliares/metabolismo , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Corioamnionitis/sangre , Corioamnionitis/patología , Citocinas/sangre , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Feto/inmunología , Regulación de la Expresión Génica/inmunología , Hepatitis/sangre , Hepatitis/patología , Lipopolisacáridos/administración & dosificación , Lipopolisacáridos/inmunología , Hígado/inmunología , Hígado/patología , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Embarazo , Nacimiento Prematuro/sangre , Oveja Doméstica , Factores de Tiempo
7.
Nutrients ; 13(4)2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-33916929

RESUMEN

The impairment of liver function frequently causes various type of malnutrition, as the liver is one of the most important organs involved in maintaining nutritional homeostasis [...].


Asunto(s)
Dieta , Hepatitis/fisiopatología , Fenómenos Fisiológicos de la Nutrición , Animales , Autofagia , Modelos Animales de Enfermedad , Estrés del Retículo Endoplásmico , Hepatitis/sangre , Hepatitis/genética , Hepatitis/microbiología , Humanos , Estrés Oxidativo , Oligoelementos/análisis
8.
Br J Haematol ; 193(4): 827-840, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33899219

RESUMEN

A total of 244 patients with hereditary haemolytic anaemias (HHA) were screened for acute symptomatic human parvovirus B19 infection (HPV-B19) in a prospective study. To assess the risks associated with HPV-B19 infection, patients were classified into Group I and Group II according to presence or absence (symptoms, signs and specific serology) of acute HPV-B19 infection respectively. In all, 131 (53·7%) patients had ß-thalassaemia, 75 (30·7%) hereditary spherocytosis (HS), 27 (11·1%) sickle cell anaemia (SCA) and 11 (4·5%) glucose-6-phosphate dehydrogenase (G6PD) deficiency. Of 33 (13·5%) patients who presented with symptomatic HPV-B19 infection, 19 (57·5%) had HS, nine (27·3%) had ß-thalassaemia and five (15·2%) had SCA. In Group I, there were significant differences in the mean white blood cell, red blood cell and platelet counts, haemoglobin concentration, total bilirubin (TB), alanine aminotransferase, aspartate aminotransferase and serum creatinine (all P < 0·001) compared to Group II. In all, 27 (81·8%) patients had arthropathy and bone marrow failure (BMF); 13 (39·4%) had acute kidney injury (AKI), more in SCA (80%); and 12 (36·4%) patients had hepatitis, more in HS (66·8%). Five (15·2%) patients with HS had BMF, AKI, nervous system involvement and extreme hyperbilirubinaemia (TB range 26·3-84·7 mg/dl). Five (15·2%) patients had haemophagocytic syndrome. Two patients with HS combined with Type-I autoimmune hepatitis presented with transient BMF. Complete recovery or stabilisation was noted at 12 months in every patient except for one patient with SCA who died during the infection. HPV-B19 must be suspected and screened in patients with HHA with typical and atypical presentations with careful follow-up.


Asunto(s)
Anemia Hemolítica Congénita , Trastornos de Fallo de la Médula Ósea , Eritema Infeccioso , Hepatitis , Hiperbilirrubinemia , Parvovirus B19 Humano/metabolismo , Enfermedad Aguda , Adolescente , Adulto , Anemia Hemolítica Congénita/sangre , Anemia Hemolítica Congénita/mortalidad , Anemia Hemolítica Congénita/virología , Trastornos de Fallo de la Médula Ósea/sangre , Trastornos de Fallo de la Médula Ósea/mortalidad , Trastornos de Fallo de la Médula Ósea/virología , Niño , Eritema Infeccioso/sangre , Eritema Infeccioso/mortalidad , Femenino , Estudios de Seguimiento , Hepatitis/sangre , Hepatitis/mortalidad , Hepatitis/virología , Humanos , Hiperbilirrubinemia/sangre , Hiperbilirrubinemia/mortalidad , Hiperbilirrubinemia/virología , Masculino , Persona de Mediana Edad , Estudios Prospectivos
9.
J Cell Mol Med ; 25(2): 1140-1150, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33295107

RESUMEN

Inflammation and fibrosis are major consequences of autoimmune hepatitis, however, the therapeutic mechanism remains to be investigated. USP4 is a deubiquitinating enzyme and plays an important role in tissue fibrosis and immune disease. Vialinin A is an extract from mushroom and is a specific USP4 inhibitor. However, there is lack of evidences that Vialinin A plays a role in autoimmune hepatitis. By employing S100-induced autoimmune hepatitis in mice and AML12 cell line, therapeutic mechanism of Vialinin A was examined. Inflammation was documented by liver histological staining and inflammatory cytokines. Fibrosis was demonstrated by Masson, Sirius red staining and fibrotic cytokines with western blot and real-time RT-PCR. In experimental animal, there were increases in inflammation and fibrosis as well as USP4, and which were reduced after treatment of Vialinin A. Vialinin A also reduced Rheb and phosphorylated mTOR. Moreover, in LPS-treated AML12 cells, LPS-induced USP4, inflammatory and fibrotic cytokines, phosphorylated mTOR and Rheb. Specific inhibitory siRNA of USP4 reduced USP4 level and the parameters mentioned above. In conclusion, USP4 was significantly elevated in autoimmune hepatitis mice and Vialinin A reduced USP4 level and attenuate inflammation and fibrosis in the liver. The mechanism may be related to regulation of Rheb/mTOR signalling.


Asunto(s)
Hepatitis/tratamiento farmacológico , Inflamación/patología , Cirrosis Hepática/tratamiento farmacológico , Proteína Homóloga de Ras Enriquecida en el Cerebro/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Compuestos de Terfenilo/farmacología , Proteasas Ubiquitina-Específicas/antagonistas & inhibidores , Animales , Línea Celular , Citocinas/metabolismo , Hepatitis/sangre , Hepatitis/complicaciones , Hepatitis/genética , Humanos , Lipopolisacáridos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/genética , Masculino , Ratones Endogámicos C57BL , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas S100 , Transducción de Señal/efectos de los fármacos , Proteasas Ubiquitina-Específicas/sangre , Proteasas Ubiquitina-Específicas/genética , Proteasas Ubiquitina-Específicas/metabolismo , Ubiquitinación
10.
Biomed Pharmacother ; 132: 110890, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33080465

RESUMEN

BACKGROUND: Ambroxol hydrochloride is being used in respiratory diseases as a broncholytic therapy. Beta-Glucosylceramide (GC) is a naturally occurring glycosphingolipid that exerts an immune protective effect. The aim of the present study was to determine the synergistic immunomodulatory effect between these two compounds. METHODS: Immune-mediated hepatitis was induced in the mice by administration of Con A. Mice were treated with either Ambroxol or GC alone or with the combination of both. Mice were followed for their effect on the liver injury, cytokine profile, and the immune system. RESULTS: Coadministration of Ambroxol and GC significantly alleviated the liver injury induced by ConA, as demonstrated by the decreased liver enzymes. The combined treatment had a statistically significant synergistic effect on the suppression of intrahepatic CD8+CD25+, an increase in the CD4/CD8 lymphocyte ratio and in the CD8+ intrahepatic lymphocyte trapping, as well as on change of serum in the IL4 levels. The beneficial effect was associated with the promotion of regulatory T lymphocytes subsets, and with a trend for a pro-inflammatory to an anti-inflammatory cytokine shift. CONCLUSIONS: Coadministration of Ambroxol with GC exerted a synergistic immunoprotective effect in a model of immune-mediated acute liver damage. Considering the high safety profile of both agents, the combination may become a novel immunomodulatory non-immunosuppressive therapeutic agent. SIGNIFICANCE STATEMENT: Coadministration of Ambroxol with glucocerebroside exerted a synergistic immunoprotective effect in a model of immune-mediated acute liver damage.


Asunto(s)
Ambroxol/farmacología , Antiinflamatorios/farmacología , Glucosilceramidas/farmacología , Hepatitis/prevención & control , Factores Inmunológicos/farmacología , Hígado/efectos de los fármacos , Linfocitos T/efectos de los fármacos , Animales , Concanavalina A , Citocinas/sangre , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Quimioterapia Combinada , Hepatitis/sangre , Hepatitis/inmunología , Mediadores de Inflamación/sangre , Hígado/inmunología , Hígado/metabolismo , Masculino , Ratones Endogámicos C57BL , Linfocitos T/inmunología , Linfocitos T/metabolismo
11.
Scand J Rheumatol ; 49(6): 427-433, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32942921

RESUMEN

Systemic lupus erythematosus (SLE), a multisystem autoimmune inflammatory disease, may involve any organs, including the liver. Liver involvement in SLE is not part of the American College of Rheumatology criteria and is relatively rare. Liver disease is usually mild, manifesting as subtle elevation of liver enzymes. Jaundice and hepatomegaly can be seen in some patients; advanced liver disease with cirrhosis is extremely rare. Precise pathology remains obscure. SLE may cause non-specific changes, including hepatocellular, cholestatic, or vascular changes. Alcohol, drugs, viral infections, metabolic disorders, autoimmune hepatitis, and other common causes of liver dysfunction should be excluded. Corticosteroids may expedite the recovery process, but may lead to non-alcoholic fatty liver disease and liver damage. Several large-scale multicentre studies have shown that liver involvement is not the major cause of morbidity and mortality in SLE patients. In this review, we discuss the pathogenesis, diagnosis, differential diagnosis, clinical manifestations, management, complications, and prognosis of lupus hepatitis.


Asunto(s)
Hepatitis/etiología , Lupus Eritematoso Sistémico/complicaciones , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Hepatitis/sangre , Humanos , Lupus Eritematoso Sistémico/sangre
12.
Aliment Pharmacol Ther ; 52(8): 1399-1406, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32886813

RESUMEN

BACKGROUND: Guidelines recommend liver biopsy to rule out significant inflammatory activity in chronic hepatitis B (CHB) patients with elevated hepatitis B virus (HBV) DNA but without other indications for treatment. AIM: To study rates and determinants of clinically significant liver inflammation. METHODS: We selected patients with HBV DNA > 2000 IU/mL from the SONIC-B database. The presence of significant inflammation (METAVIR ≥ A2 or HAI ≥ 9) was assessed by liver biopsy and correlated with alanine aminotransferase (ALT) levels (according to AASLD upper limits of normal [ULN]) and stratified by the presence of significant liver fibrosis (Ishak ≥ 3 or METAVIR ≥ F2). RESULTS: The cohort included 2991 patients; 1672 were HBeAg-positive. ALT was < ULN in 270 (9%), 1-2 times ULN in 852 (29%) and > 2 times ULN in 1869 (63%). Significant fibrosis was found in 1419 (47%) and significant inflammatory activity in 630 (21%). Significant inflammatory activity was found in 34% of patients with liver fibrosis, compared to 9.5% of those without (P < 0.001). Among patients without fibrosis, significant inflammatory activity was detected in 3.6% of those with normal ALT, 5.0% of those with ALT 1-2 times ULN and in 13% of those with ALT > 2 times ULN (P < 0.001). ALT < 2 times ULN had a negative predictive value of 95% for ruling out significant inflammatory activity among patients without liver fibrosis. CONCLUSIONS: Among patients without significant fibrosis, an ALT level < 2 times ULN is associated with < 5% probability of significant inflammatory activity. If fibrosis can be ruled out using non-invasive methods, liver biopsy solely to assess inflammatory activity should be discouraged.


Asunto(s)
Alanina Transaminasa/sangre , Hepatitis B Crónica/complicaciones , Hepatitis/diagnóstico , Hepatitis/etiología , Adulto , Biopsia , Estudios de Cohortes , Femenino , Hepatitis/sangre , Hepatitis/epidemiología , Hepatitis B Crónica/sangre , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/epidemiología , Humanos , Inflamación/sangre , Inflamación/diagnóstico , Inflamación/epidemiología , Inflamación/etiología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/epidemiología , Masculino , Persona de Mediana Edad , Probabilidad , Pronóstico , Factores de Riesgo , Adulto Joven
13.
Tohoku J Exp Med ; 251(3): 183-191, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32669486

RESUMEN

Prior studies have shown an association between the incidence of diabetes with liver enzymes, such as alanine transaminase (ALT). Liver fibrosis scores, such as the Fibrosis-4 index which indicates chronic liver damage, were also associated with diabetes development. However, no literature compared predictive accuracy between ALT and Fibrosis-4 index. Thus, we aimed to determine it, and to assess its association using inverse probability of treatment weighting. This was a non-concurrent prospective cohort study of 9,748 subjects without diabetes receiving Yuport Health Checkup in Japan between 1998 and 2006. ALT was categorized into three groups: the highest ALT group (men ≥ 30 U/L and women ≥ 20 U/L), the middle (men ≥ 20 and < 30 U/L, and women ≥ 14 and < 20 U/L), and the lowest (men < 20 U/L and women < 14 U/L). The primary outcome was the new onset of diabetes. The area under the receiver operating characteristic curves (AUC) of ALT for predicting the diabetes development was higher than that of any other markers of liver damage. The AUC for ALT was 0.71, while that for the Fibrosis-4 index was 0.51 (p < 0.001 for the difference between the AUCs). The highest and middle ALT groups had a significantly higher incidence of diabetes than the lowest group: adjusted relative risk 1.79 [95% confidence interval (CI): 1.29, 2.58], and 1.64 [95% CI: 1.17, 2.38] respectively. Of the various indicators of liver function, ALT is likely to be the most accurate and associated predictor of diabetes development.


Asunto(s)
Alanina Transaminasa/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/epidemiología , Adulto , Anciano , Algoritmos , Área Bajo la Curva , Biomarcadores , Estudios de Cohortes , Femenino , Hepatitis/sangre , Hepatitis/complicaciones , Humanos , Incidencia , Japón/epidemiología , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Curva ROC , Medición de Riesgo
14.
Toxicol Lett ; 332: 1-6, 2020 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-32579995

RESUMEN

Non-alcoholic fatty liver disease (NAFLD) can be typically classified into two subgroups: non-alcoholic fatty liver and non-alcoholic steatohepatitis. Mouse models of NAFLD are useful tools for understanding the pathogenesis and progression of NAFLD and for developing drugs for its treatment. Here, we investigated the time-dependent changes in serum lipids and biochemical markers of hepatic function, hepatic inflammation, and fibrosis in mice fed a normal diet (ND) or a NAFLD diet (choline deficient, L-amino acid-defined, high-fat diet; CDAHFD) for 12 weeks. CDAHFD-fed mice showed significantly reduced serum levels of total cholesterol, triglyceride, and high-density lipoprotein cholesterol throughout the treatment period compared with ND-fed mice. The changes in aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and total bilirubin showed an inverse U-shaped curve in the CDAHFD-fed mice. The serum alkaline phosphatase levels decreased in both ND- and CDAHFD-fed mice in a time-dependent manner. Furthermore, CDAHFD-fed mice showed a significant increase in the number of inflammatory foci and hepatic fibrosis at 6-12 weeks, although inflammatory foci and hepatic fibrogenesis were observable at relatively early stages as well (1-4 weeks). In conclusion, the long-term profile of serological biomarkers, hepatic inflammation, and fibrosis in CDAHFD-fed mice identified in this study may provide a better understanding of NAFLD pathogenesis.


Asunto(s)
Hepatitis/patología , Cirrosis Hepática/patología , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico/patología , Animales , Biomarcadores/análisis , Peso Corporal/efectos de los fármacos , Colesterol/sangre , HDL-Colesterol/sangre , Dieta , Hepatitis/sangre , Hepatitis/enzimología , Metabolismo de los Lípidos , Hígado/enzimología , Hígado/metabolismo , Cirrosis Hepática/sangre , Pruebas de Función Hepática , Masculino , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/enzimología , Triglicéridos/sangre
15.
Aging (Albany NY) ; 12(12): 11843-11863, 2020 06 18.
Artículo en Inglés | MEDLINE | ID: mdl-32554864

RESUMEN

Long noncoding RNAs (lncRNAs), such as LINC00462, HOTAIR, and MALAT1, are significantly upregulated in hepatocellular carcinoma (HCC) tissues. However, lncRNA expression in the serum of HCC patients is still unclear. To identify candidate lncRNAs for HCC diagnosis, we purified exosomal total RNA from the serum of healthy volunteers (controls) and hepatitis, cirrhosis, and HCC patients. To assess the function of lncRNAs, small interfering RNAs and overexpression vectors were designed and cell viability and cell apoptosis assays conducted. The exosomes of the control group had a larger number of lncRNAs with a high amount of alternative splicing compared to hepatic disease patients. qPCR assays showed that lnc-FAM72D-3, lnc-GPR89B-15, lncZEB2-19, and lnc-EPC1-4 are differentially expressed in HCC. Furthermore, the expression level of lnc-EPC1-4 correlated with age. While the expression levels of lnc-GPR89B-15 and lnc-EPC1-4 correlated with serum alpha-fetoprotein level. lnc-FAM72D-3 knockdown decreased cell viability and promoted cell apoptosis, indicating that lnc-FAM72D-3 functions as an oncogene in HCC. In contrast, lnc-EPC1-4 overexpression inhibited cell proliferation and induced cell apoptosis, indicating that it functions as a tumor suppressor gene. Collectively, these findings show that lnc-FAM72D-3 and lnc-EPC1-4 play a novel role that might contribute to hepatocarcinogenesis and identify potential candidate biomarkers for HCC diagnosis.


Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/diagnóstico , Exosomas/metabolismo , Neoplasias Hepáticas/diagnóstico , ARN Largo no Codificante/sangre , Adolescente , Adulto , Apoptosis/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinogénesis/genética , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/genética , Estudios de Casos y Controles , Línea Celular Tumoral , Proliferación Celular/genética , Detección Precoz del Cáncer/métodos , Femenino , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Redes Reguladoras de Genes , Voluntarios Sanos , Hepatitis/sangre , Humanos , Cirrosis Hepática/sangre , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/genética , Masculino , Persona de Mediana Edad , Oncogenes , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , RNA-Seq , Adulto Joven
16.
J Clin Lab Anal ; 34(7): e23262, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32167614

RESUMEN

BACKGROUND: To evaluate the clinical diagnostic efficacy of the combination of alpha-fetoprotein (AFP) and lens culinaris agglutinin-reactive fraction of AFP/total AFP (AFP-L3%) for detecting hepatocellular carcinoma (HCC). METHODS: A comprehensive and systemic literature search was executed in Web of Science, PubMed, and the Cochrane Library websites. Then, the related articles were reviewed and the quality of included studies was evaluated with the QUADAS tool. Further, serum samples were collected from 49 HCC patients, 52 cirrhosis patients, 47 hepatitis patients, and 48 healthy controls and these samples were tested for AFP and AFP-L3% levels. RESULTS: A total of 16 eligible articles were included in our meta-analysis. The overall sensitivity (SEN) of AFP + AFP-L3% was higher than that of AFP or AFP-L3 alone; the overall specificity (SPE) of AFP + AFP-L3% was lower than that of AFP or AFP-L3 alone. In the original study, the related statistics were, respectively, SEN = 0.592 and SPE = 0.918 for AFP; SEN = 0.367 and SPE = 1.000 for AFP-L3%; and SEN = 0.592 and SPE = 0.918 for the combination. CONCLUSION: The results of meta-analysis indicate there is a beneficial effect of using the unity of AFP and AFP-L3% for HCC diagnosing. However, in the original study, just for the results of sensitivity and specificity, there is no significant difference between AFP alone and AFP + AFP-L3%.


Asunto(s)
Carcinoma Hepatocelular/sangre , Neoplasias Hepáticas/sangre , Lectinas de Plantas/inmunología , alfa-Fetoproteínas/análisis , Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/diagnóstico , Estudios de Casos y Controles , Hepatitis/sangre , Humanos , Cirrosis Hepática/sangre , Neoplasias Hepáticas/diagnóstico , Mediciones Luminiscentes , Sensibilidad y Especificidad , alfa-Fetoproteínas/inmunología
17.
BMC Nephrol ; 21(1): 38, 2020 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-32005171

RESUMEN

BACKGROUND: Chronic Kidney Disease of unknown etiology (CKDu) is prevalent in North Central Province (NCP) of Sri Lanka. Consumption of un-boiled dug well water has been identified as one of the causative factors. This in-vivo study was performed to investigate some of the suspected factors associated with the pathogenesis of CKDu mediated via ground water. METHOD: Rats were given water, collected from high and low disease prevalent areas from the NCP of Sri Lanka and the results compared with those obtained from previously identified low disease prevalent area; Colombo. Blood Urea Nitrogen, creatinine, urinary microalbumin:creatinine ratio together with ALT and AST levels were analyzed and results were compared using one-way ANOVA and paired t-Test. Histopathology was analyzed using non-parametric method. RESULTS: Rats that ingested water from New Town Medirigiriya (NTM) from high disease prevalent NCP reported significantly elevated microalbumin:creatinine ratios compared to other water sources after 8 months, whilst boiled water from NTM had been able to significantly reduce it. Histopathological findings after the 14 months experimental period revealed significantly high tubular lesion index in rats that ingested water from NCP compared to Colombo. Rats that ingested water from high disease prevalent Divuldamana (DD) from NCP showed the highest kidney lesion index though the fluoride content was relatively low in this area compared to other water sources from high disease prevalent NCP. Rats that ingested boiled and un-boiled water from NTM also developed severe lesions whilst the group from Colombo reported the lowest. Low disease prevalent area from NCP, Huruluwewa (HW) also reported elevated liver enzymes and altered renal histopathology. Association of Na+:Ca2+ ratio in the disease progression was not reflected by the current study. Compared to Colombo, high fluoride, calcium and sodium contents were observed in water from high disease prevalent areas. All the water samples were negative for heavy metals. CONCLUSIONS: Though Fluoride is a known kidney toxic agent it cannot be the sole reason for CKDu in NCP, Sri Lanka. Various toxic elements present in NCP water may contribute to different grade of kidney and liver lesions in Wistar rats.


Asunto(s)
Agua Potable/efectos adversos , Agua Potable/química , Agua Subterránea/química , Insuficiencia Renal Crónica/etiología , Alanina Transaminasa/sangre , Albuminuria/orina , Animales , Aspartato Aminotransferasas/sangre , Nitrógeno de la Urea Sanguínea , Calcio/análisis , Creatinina/sangre , Creatinina/orina , Agua Potable/administración & dosificación , Femenino , Fluoruros/análisis , Hepatitis/sangre , Hepatitis/etiología , Hepatitis/patología , Túbulos Renales/patología , Masculino , Distribución Aleatoria , Ratas , Ratas Wistar , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/patología , Insuficiencia Renal Crónica/orina , Sodio/análisis , Sri Lanka
18.
Cancer Med ; 9(4): 1451-1461, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31903730

RESUMEN

OBJECTIVE: To establish nomogram based on inflammatory indices for differentiating intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC). METHODS: A cohort of 422 patients with HCC or ICC hospitalized at Xiangya Hospital between January 2014 and December 2018 was included in the study. Univariate and multivariate analysis was performed to identify the independent differential factors. Through combining these independent differential factors, a nomogram was established for differential diagnosis between ICC and HCC. The accuracy of nomogram was evaluated by using receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). The results were validated using a prospective study on 98 consecutive patients operated on from January 2019 to November 2019 at the same institution. RESULTS: Sex (OR = 9.001, 95% CI: 3.268-24.792, P < .001), hepatitis (OR = 0.323, 95% CI: 0.121-0.860, P = .024), alpha-fetoprotein (AFP) (OR = 0.997, 95% CI: 0.995-1.000, P = .046), carbohydrate antigen 19-9 (CA199) (OR = 1.016, 95% CI: 1.007-1.025, P < .001), and aspartate transaminase-to-neutrophil ratio index (ANRI) (OR = 0.904, 95% CI: 0.843-0.969, P = .004) were the independent differential factors for ICC. Nomogram was established with well-fitted calibration curves through incorporating these 5 factors. Comparing model 1 including gender, hepatitis, AFP, and CA199 (C index = 0.903, 95% CI: 0.849-0.957) and model 2 enrolling AFP and CA199 (C index = 0.850, 95% CI: 0.791-0.908), the nomogram showed a better discrimination between ICC and HCC, with a C index of 0.920 (95% CI, 0.872-0.968). The results were consistent in the validation cohort. DCA also confirmed the conclusion. CONCLUSION: A nomogram was established for the differential diagnosis between ICC and HCC preoperatively, and better therapeutic choice would be made if it was applied in clinical practice.


Asunto(s)
Neoplasias de los Conductos Biliares/diagnóstico , Carcinoma Hepatocelular/diagnóstico , Colangiocarcinoma/diagnóstico , Hepatitis/diagnóstico , Neoplasias Hepáticas/diagnóstico , Nomogramas , Adulto , Anciano , Neoplasias de los Conductos Biliares/sangre , Neoplasias de los Conductos Biliares/inmunología , Conductos Biliares Intrahepáticos/inmunología , Conductos Biliares Intrahepáticos/patología , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/inmunología , Colangiocarcinoma/sangre , Colangiocarcinoma/inmunología , Diagnóstico Diferencial , Femenino , Hepatectomía , Hepatitis/sangre , Hepatitis/inmunología , Humanos , Hígado/inmunología , Hígado/patología , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/inmunología , Masculino , Persona de Mediana Edad , Periodo Preoperatorio , Estudios Prospectivos , Estudios Retrospectivos
19.
Front Immunol ; 10: 2827, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31849991

RESUMEN

Background: This study aimed to investigate the association of plasma levels of IL-33, a mucosal alarmin known to elicit type-2 immunity, with infection and liver fibrosis profiles of school children from an endemic area for Schistosoma mansoni, malaria and hepatitis (B & C) in rural Cameroon. Methods: A cross-sectional study enrolling schoolchildren from 5 public schools was conducted. Single schistosomiasis, malaria and hepatitis infections or co-infections were assessed by kato katz, microscopy, and rapid diagnostic tests, respectively. Hepatic fibrosis was assessed by ultrasound according to WHO Niamey guidelines and plasma levels of Interleukin 33 were determined by ELISA. All statistics were performed using R studio software. Principal findings: We found a prevalence of 13.5% (37/275), 18.2% (50/275), and 8% (22/275), respectively for schistosomiasis, malaria and hepatitis (B or C) single infections. Only 7.6% (21/275) of co-infections were reported. Although Plasma IL-33 showed a minimal negative risk for schistosomiasis infection (AOR 0.99; 95% CI 0.97-1.01), S. mansoni infected participants had lower levels of plasma IL-33 (p = 0.003) which decreased significantly as eggs burdens increased (p = 0.01) with a negative Pearson coefficient of r = -0.22. Hepatic fibrosis occurred in 47.3% (130/275) of our study population independently from plasma levels of IL-33 (AOR 1.00; 95% CI 0.99-1.01). Conclusion/Significance: Our data failed to show an association between plasma IL-33 levels and liver disease but convincingly report on a negative association between plasma IL-33 levels and schistosomiasis infection and egg burden in school children from a polyparasitic schistosomiasis endemic area.


Asunto(s)
Interleucina-33/sangre , Esquistosomiasis mansoni/sangre , Adolescente , Animales , Camerún/epidemiología , Niño , Coinfección/sangre , Coinfección/epidemiología , Femenino , Hepatitis/sangre , Hepatitis/epidemiología , Humanos , Cirrosis Hepática/sangre , Cirrosis Hepática/epidemiología , Malaria/sangre , Malaria/epidemiología , Masculino , Prevalencia , Población Rural , Schistosoma mansoni , Esquistosomiasis mansoni/epidemiología
20.
In Vivo ; 33(5): 1697-1702, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31471426

RESUMEN

BACKGROUND/AIM: Chemotherapy is often halted due to abnormal liver function resembling hepatitis. But the cause can be extrahepatic portal venous obstruction (EHPVO) with hepatic enzyme elevation rather than being an adverse effect of chemotherapy. We investigated EHPVO with hepatic enzyme elevation in patients with cancer. PATIENTS AND METHODS: Data of these hospitalized patients with solid tumors between January 2013 and September 2017 were collected. The criteria for study inclusion were: (i) Extrahepatic malignancy; (ii) computed tomographic scans showing a tumor with external compression of the extrahepatic portal vein; and (iii) serum aminotransferase (AST) or alanine transaminase (ALT) level three times above the normal value. RESULTS: Thirteen out of 377 (3%) patients developed EHPVO with hepatic enzyme elevation, as demonstrated from computed tomographic scan. Four cases (31%) also had vascular thrombosis (three portal vein and one inferior vena cava). Serum AST increased from 34±11 to 169±94 U/l. ALT increased from 9±38 to 177±104 U/l. There was no relationship of EHPVO with viral markers and cirrhosis. Six cases received chemotherapy with liver function improvement. CONCLUSION: EHPVO occurred in patients with metastatic cancer, leading to hepatic enzyme elevation resembling hepatitis without hepatitis risk factors and cirrhosis. Before withholding chemotherapy due to hepatic enzyme elevation, the possibility of EHPVO should firstly be excluded.


Asunto(s)
Constricción Patológica/diagnóstico , Hepatitis/complicaciones , Hepatitis/diagnóstico , Neoplasias/complicaciones , Vena Porta/patología , Enfermedades Vasculares/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores , Constricción Patológica/etiología , Femenino , Hepatitis/sangre , Humanos , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Neoplasias/diagnóstico , Tomografía Computarizada por Rayos X , Enfermedades Vasculares/etiología
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