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1.
Nutrients ; 13(10)2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34684371

RESUMO

BACKGROUND: Excessive intake of fructose, glucose and alcohol is associated with the development of non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). At the same time, these dietetic factors create an environment favorable for the generation of advanced glycation end-products. For this reason, advanced glycation end-products (AGEs) are hypothesized to play role in the development of NAFLD and ALD. In this systematic review and meta-analysis, we explore the relationship between NAFLD and ALD with AGE levels, including their diagnostic accuracy. METHODS: The systematic review and meta-analysis has been pre-registered with PROSPERO (CRD42021240954) and was performed in accordance with the PRISMA guidelines. Meta-analyses were performed using the meta R package. RESULTS: We have obtained 11 studies meeting our inclusion criteria, reporting data on 1844 participants (909 with NAFLD, 169 with ALD and 766 healthy controls). NAFLD was associated with significantly higher AGE fluorescence and serum N-(carboxyethyl)lysine (CEL) levels. Patients with alcoholic cirrhosis had significantly higher levels of N-(carboxymethyl)lysine (CML). Only individual studies examined AGEs in the context of their diagnostic accuracy. AGE fluorescence distinguished low and moderate steatosis with an AUC of 0.76. The ratio of CML, CEL and pentosidine to a soluble variant of the AGE receptor differentiated patients with NAFLD from healthy controls with high AUC (0.83-0.85). Glyceraldehyde-derived AGE separated non-alcoholic fatty liver (NAFL) from non-alcoholic steatohepatitis (NASH) with acceptable performance (AUC 0.78). CONCLUSIONS: In conclusion, NAFLD and ALD are associated with significantly higher levels of several AGEs. More research is needed to examine the diagnostic accuracy of AGEs, however individual studies show that AGEs perform well in distinguishing NAFL from NASH.


Assuntos
Produtos Finais de Glicação Avançada/metabolismo , Hepatopatias/metabolismo , Animais , Estudos de Casos e Controles , Produtos Finais de Glicação Avançada/sangue , Humanos , Hepatopatias/sangue , Hepatopatias/diagnóstico , Viés de Publicação , Risco
2.
Nutrients ; 13(9)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34578865

RESUMO

The association between bone mineral density (BMD) and hepatic glycogen storage diseases (GSDs) is still unclear. To evaluate the BMD of patients with GSD I, IIIa and IXα, a cross-sectional study was performed, including 23 patients (GSD Ia = 13, Ib = 5, IIIa = 2 and IXα = 3; median age = 11.9 years; IQ = 10.9-20.1) who underwent a dual-energy X-ray absorptiometry (DXA). Osteocalcin (OC, n = 18), procollagen type 1 N-terminal propeptide (P1NP, n = 19), collagen type 1 C-terminal telopeptide (CTX, n = 18) and 25-OH Vitamin D (n = 23) were also measured. The participants completed a 3-day food diary (n = 20). Low BMD was defined as a Z-score ≤ -2.0. All participants were receiving uncooked cornstarch (median dosage = 6.3 g/kg/day) at inclusion, and 11 (47.8%) presented good metabolic control. Three (13%) patients (GSD Ia = 1, with poor metabolic control; IIIa = 2, both with high CPK levels) had a BMD ≤ -2.0. CTX, OC and P1NP correlated negatively with body weight and age. 25-OH Vitamin D concentration was decreased in seven (30.4%) patients. Our data suggest that patients with hepatic GSDs may have low BMD, especially in the presence of muscular involvement and poor metabolic control. Systematic nutritional monitoring of these patients is essential.


Assuntos
Doenças Ósseas Metabólicas/epidemiologia , Doença de Depósito de Glicogênio/epidemiologia , Hepatopatias/epidemiologia , Absorciometria de Fóton , Adolescente , Adulto , Densidade Óssea , Doenças Ósseas Metabólicas/sangue , Brasil/epidemiologia , Criança , Pré-Escolar , Colágeno Tipo I/sangue , Comorbidade , Estudos Transversais , Feminino , Doença de Depósito de Glicogênio/sangue , Humanos , Hepatopatias/sangue , Masculino , Osteocalcina/sangue , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Vitamina D/sangue , Adulto Jovem
3.
Medicine (Baltimore) ; 100(30): e26719, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34397705

RESUMO

ABSTRACT: Liver dysfunction in patients with COVID-19 (coronavirus disease 2019) has been described. However, it is not clear if the presence of abnormal liver function tests at presentation was related to underlying undiagnosed liver disease, or a result of the viral infection.We retrospectively examined the first 554 consecutive polymerase chain reaction positive SARS-CoV-2 patients admitted from February 2020 to April 2020 to our academic medical centre. We reviewed their clinical data, chest radiography and laboratory studies obtained within 24 hour of admission.Despite similar hemodynamic parameters, we found significant aspartate transaminase elevation (64 ±â€Š141 vs 35 ±â€Š23 U/L, P < .001) in those with pneumonia compared to those without. Elevated liver enzymes were seen in 102 patients (18.4%). They presented with higher temperatures (38.5 ±â€Š0.9 vs 37.5 ±â€Š0.8 degC, P = .011), higher total white cell counts (6.95 ±â€Š2.29 vs 6.39 ±â€Š2.19 x109/L, P = .021), serum ferritin (240 ±â€Š274 vs 165 ±â€Š198 ng/ml, P = .002) and lactate dehydrogenase (632 ±â€Š912 vs 389 ±â€Š107 U/L, P < .001). These patients were more likely to require intensive care (6.9% vs 2.7% P = .036) and mechanical ventilation (5.9% vs 2.2%, P = .046). Migrant workers from dormitories had a higher rate of baseline liver function test abnormalities (88/425 vs 14/129, P = .01), which were more likely to persist at the time of discharge.Despite relatively mild COVID-19 disease, there was a significant prevalence of liver dysfunction, particularly amongst migrant workers. Elevated liver enzymes were associated with more severe disease, despite similar haemodynamic characteristics. Future studies should explore whether pre-existing liver disease may predispose to more severe COVID-19 disease.


Assuntos
Aspartato Aminotransferases/sangue , COVID-19/complicações , L-Lactato Desidrogenase/sangue , Hepatopatias/etiologia , Adulto , COVID-19/sangue , Feminino , Ferritinas/sangue , Humanos , Contagem de Leucócitos , Hepatopatias/sangue , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Singapura
4.
Sci Rep ; 11(1): 16982, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34417517

RESUMO

HBV infection is recognized as a serious global health problem, and hepatitis B virus infection is a complicated chronic disease leading to liver cirrhosis (LC) and hepatocellular carcinoma (HCC). New biochemical serum markers could be used to advance the diagnosis and prognosis of HBV-associated liver diseases during the progression of chronic hepatitis B into cirrhosis and HCC. We determined whether the 4210 Da and 1866 Da polypeptides are serum metabolite biomarkers of hepatopathy with hepatitis B virus. A total of 570 subjects were divided into five groups: healthy controls, those with natural clearance, and patients with CHB, LC, and HCC. The 1866 Da and 4210 Da polypeptides were measured by Clin-ToF II MALDI-TOF-MS. There were significant differences in 4210 Da and 1866 Da levels among the five groups (P < 0.001). For the differential diagnosis of CHB from normal liver, the areas under the receiver operating characteristic (ROC) curve of 4210 Da and 1866 Da and their combination via logistic regression were 0.961, 0.849 and 0.967. For the differential diagnosis of LC from CHB, the areas under the ROC curve were 0.695, 0.841 and 0.826. For the differential diagnosis of HCC from CHB, the areas under the ROC curve were 0.744, 0.710 and 0.761, respectively. For the differential diagnosis of HCC from LC, the areas under the ROC curve of 4210 Da and 1866 Da were 0.580 and 0.654. The positive rate of 1866 Da was 45.5% and 69.0% in AFP-negative HCC patients and that of 4210 Da was 60.6% 58.6% in AFP-negative HCC patients of the study HCC vs. CHB and HCC vs. LC. The 4210 Da and 1866 Da polypeptide levels were positively correlated with HBV DNA levels (P < 0.001, r = 0.269; P < 0.001, r = 0.285). The 4210 Da and 1866 Da polypeptides had good diagnostic value for the occurrence and progression of HBV-related chronic hepatitis, liver cirrhosis and hepatocellular carcinoma and could serve to accurately guide treatment management and predict clinical outcomes.


Assuntos
Progressão da Doença , Vírus da Hepatite B/fisiologia , Hepatopatias/patologia , Hepatopatias/virologia , Peptídeos/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/virologia , DNA Viral/sangue , Feminino , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Humanos , Hepatopatias/sangue , Hepatopatias/diagnóstico , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Peso Molecular , Peptídeos/sangue , Curva ROC , alfa-Fetoproteínas/metabolismo
5.
BMC Cardiovasc Disord ; 21(1): 352, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34311708

RESUMO

BACKGROUND: We examined the relationship between ratios of select biomarkers of kidney and liver function on all-cause and coronary heart disease (CHD) mortality, both in isolation, and in combination with metabolic syndrome (MetS), among adults (20 + years, n = 10,604). METHODS: Data was derived from the U.S. National Health and Nutrition Examination Survey (1999-2016) including public-use linked mortality follow-up files through December 31, 2015. RESULTS: Select biomarker ratios of kidney (UACR or albuminuria and BUN-CR) and liver (AST-ALT and GGT-ALP) function in isolation and in combination with MetS were associated with all-cause and CHD mortality. Compared to individuals with neither elevated biomarker ratios nor MetS (HR = 1.00, referent), increased risk of all-cause mortality was observed in the following groups: MetS with elevated UACR (HR, 95% CI = 2.57, 1.99-3.33), MetS with elevated AST-ALT (HR = 2.22, 1.61-3.07), elevated UACR without MetS (HR = 2.12, 1.65-2.72), and elevated AST-ALT without MetS (HR = 1.71, 1.35-2.18); no other biomarker ratios were associated with all-cause mortality. For cause-specific deaths, elevated risk of CHD mortality was associated with MetS with elevated UACR (HR = 1.67, 1.05-2.67), MetS with elevated AST-ALT (HR = 2.80, 1.62-4.86), and elevated BUN-CR without MetS (HR = 2.12, 1.12-4.04); no other biomarker ratios were associated with CHD mortality. CONCLUSION: Future longitudinal studies are necessary to examine the utility of these biomarker ratios in risk stratification for chronic disease management.


Assuntos
Doença das Coronárias/sangue , Nefropatias/sangue , Hepatopatias/sangue , Síndrome Metabólica/sangue , Adulto , Biomarcadores/sangue , Causas de Morte , Doença das Coronárias/diagnóstico , Doença das Coronárias/mortalidade , Estudos Transversais , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Nefropatias/diagnóstico , Nefropatias/mortalidade , Testes de Função Renal , Hepatopatias/diagnóstico , Hepatopatias/mortalidade , Testes de Função Hepática , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/mortalidade , Pessoa de Meia-Idade , Inquéritos Nutricionais , Valor Preditivo dos Testes , Prevalência , Prognóstico , Medição de Risco , Estados Unidos/epidemiologia
6.
Commun Biol ; 4(1): 731, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34127764

RESUMO

Human serum albumin (HSA) constitutes the primary transporter of fatty acids, bilirubin, and other plasma compounds. The binding, transport, and release of its cargos strongly depend on albumin conformation, which is affected by bound ligands induced by physiological and pathological conditions. HSA is both highly oxidized and heavily loaded with fatty acids and bilirubin in chronic liver disease. By employing small-angle X-ray scattering we show that HSA from the plasma of chronic liver disease patients undergoes a distinct opening compared to healthy donors. The extent of HSA opening correlates with clinically relevant variables, such as the model of end-stage liver disease score, bilirubin, and fatty acid levels. Although the mild oxidation of HSA in vitro does not alter overall structure, the alteration of patients' HSA correlates with its redox state. This study connects clinical data with structural visualization of albumin dynamicity in solution and underlines the functional importance of albumin's inherent flexibility.


Assuntos
Hepatopatias/metabolismo , Albumina Sérica/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Bilirrubina/sangue , Estudos de Casos e Controles , Doença Hepática Terminal/metabolismo , Ácidos Graxos/sangue , Humanos , Hepatopatias/sangue , Masculino , Pessoa de Meia-Idade , Oxirredução , Estrutura Terciária de Proteína , Adulto Jovem
7.
Pancreas ; 50(3): 393-398, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33835971

RESUMO

OBJECTIVE: The clinical significance of increased serum pancreatic enzymes (PEs) in coronavirus disease 2019 (COVID-19) patients has not yet been fully understood. We aimed to investigate the frequency and the impact on clinical outcome of PE elevation and acute pancreatitis in such patients. METHODS: Clinical data, laboratory tests, and cross-sectional images were analyzed from COVID-19 patients admitted to the Tor Vergata Hospital in Rome. Variables associated with PE abnormalities, intensive care unit (ICU) admission, or death were investigated through univariate and multivariate analyses and Cox proportional hazard model. RESULTS: Pancreatic enzymes were available in 254 of 282 COVID-19 patients. Among these, 66 patients (26%) showed mild elevation of PE, and 11 patients (4.3%) had severe elevation (>3 times of the upper limit of normal). Overall, 2 patients met the diagnostic criteria for acute pancreatitis. Hepatic and renal involvements were associated with PE elevation. Multivariate analysis showed that mild and severe PE elevations were significantly associated with ICU admission (odds ratios, 5.51 [95% confidence interval, 2.36-12.89; P < 0.0001] and 26.2 [95% confidence interval, 4.82-142.39; P < 0.0001]). CONCLUSIONS: Increase in serum PE, but not acute pancreatitis, is frequent in hospitalized COVID-19 patients and associates with ICU admission.


Assuntos
COVID-19/epidemiologia , Hospitalização/estatística & dados numéricos , Unidades de Terapia Intensiva , Pâncreas/enzimologia , Pancreatite/epidemiologia , Idoso , Idoso de 80 Anos ou mais , COVID-19/sangue , COVID-19/enzimologia , COVID-19/mortalidade , Feminino , Humanos , Nefropatias/sangue , Nefropatias/enzimologia , Nefropatias/epidemiologia , Hepatopatias/sangue , Hepatopatias/enzimologia , Hepatopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Pancreatite/sangue , Pancreatite/enzimologia , Prognóstico , Modelos de Riscos Proporcionais
8.
Mol Genet Metab ; 133(2): 148-156, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33846069

RESUMO

BACKGROUND: Urea cycle disorders (UCDs) are among the most common inborn errors of liver metabolism. As therapies for hyperammonemia associated with urea cycle dysfunction have improved, chronic complications, such as liver disease, have become increasingly apparent in individuals with UCDs. Liver disease in UCDs may be associated with hepatic inflammation, hepatic fibrosis, portal hypertension, liver cancer and even liver failure. However, except for monitoring serum aminotransferases, there are no clear guidelines for screening and/or monitoring individuals with UCDs for liver disease. Thus, we systematically evaluated the potential utility of several non-invasive biomarkers for liver fibrosis in UCDs. METHODS: We evaluated grey-scale ultrasonography, liver stiffness obtained from shear wave elastography (SWE), and various serum biomarkers for hepatic fibrosis and necroinflammation, in a cohort of 28 children and adults with various UCDs. RESULTS: Overall, we demonstrate a high burden of liver disease in our participants with 46% of participants having abnormal grey-scale ultrasound pattern of the liver parenchyma, and 52% of individuals having increased liver stiffness. The analysis of serum biomarkers revealed that 32% of participants had elevated FibroTest™ score, a marker for hepatic fibrosis, and 25% of participants had increased ActiTest™ score, a marker for necroinflammation. Interestingly, liver stiffness did not correlate with ultrasound appearance or FibroTest™. CONCLUSION: Overall, our results demonstrate the high overall burden of liver disease in UCDs and highlights the need for further studies exploring new tools for identifying and monitoring individuals with UCDs who are at risk for this complication. TRIAL REGISTRATION: This study has been registered in ClinicalTrials.gov (NCT03721367).


Assuntos
Argininossuccinato Liase/sangue , Doenças Genéticas Inatas/sangue , Cirrose Hepática/sangue , Hepatopatias/sangue , Distúrbios Congênitos do Ciclo da Ureia/sangue , Adolescente , Adulto , Biomarcadores/sangue , Criança , Pré-Escolar , Técnicas de Imagem por Elasticidade , Feminino , Doenças Genéticas Inatas/diagnóstico por imagem , Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/patologia , Humanos , Hiperamonemia/sangue , Hiperamonemia/genética , Hiperamonemia/metabolismo , Hiperamonemia/patologia , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/genética , Cirrose Hepática/patologia , Hepatopatias/genética , Hepatopatias/metabolismo , Hepatopatias/patologia , Masculino , Erros Inatos do Metabolismo/genética , Pessoa de Meia-Idade , Ultrassonografia , Distúrbios Congênitos do Ciclo da Ureia/genética , Distúrbios Congênitos do Ciclo da Ureia/metabolismo , Distúrbios Congênitos do Ciclo da Ureia/patologia , Adulto Jovem
9.
Int Immunopharmacol ; 97: 107701, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33930704

RESUMO

SARS-CoV-2 or Coronavirus disease 2019 (COVID-19) outbreak which caused by the severe acute respiratory syndrome, has rapidly spread over the world. The exact mechanism how this virus will affect the liver remained elusive. The aim of this study was to evaluate the liver function in patients with severe acute respiratory syndrome coronavirus 2 and potential causes of hepatic enzymes disease in these patients. Clinical characteristics and laboratory findings were collected from patients with COVID-19 who were admitted to the corona center in Erbil city/Kurdistan region of Iraq, from March 10 to July 10, 2020. Serum was collected from patients with COVID-19 and liver enzyme tests were measured. Liver alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBIL) were analyzed in these patients. Of the 74 patients, 25 (34.7%) had abnormal ALT activity, 28 (40%) had abnormal AST activity, 12 (20.3%) had abnormal ALP activity, and 39 (52.7%) had abnormal total bilirubin P-value < 0.05. The inflammatory biomarkers CRP and IL-6 in COVID-19 patients with abnormal liver function test (4.9 ± 1.0 mg/dl) and (231.2 ± 35.7 pg/ml) respectively. The levels of both biomarkers were statistically significantly higher than COVID-19 patients with normal liver function test (2.1 ± 0.5 mg/dl) and (2.1 ± 0.5 mg/dl) respectively, P-value < 0.05. However, CRP and IL-6 were not statistically significant different between male and female COVID-19 patients P-value < 0.05. In conclusion, we found that most of the patients with SARS-CoV-2 have abnormal hepatic enzyme activities and that is might related to virus replication in the liver.


Assuntos
COVID-19/enzimologia , COVID-19/virologia , Fígado/enzimologia , Fígado/virologia , Adolescente , Adulto , Idoso , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Biomarcadores/sangue , COVID-19/sangue , COVID-19/complicações , Portador Sadio/sangue , Criança , Feminino , Humanos , Interleucina-6/sangue , Hepatopatias/sangue , Hepatopatias/enzimologia , Hepatopatias/etiologia , Hepatopatias/virologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Receptores Imunológicos/sangue , Adulto Jovem
11.
Nutr Metab Cardiovasc Dis ; 31(5): 1416-1426, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33814235

RESUMO

BACKGROUND AND AIMS: CA.ME.LI.A (CArdiovascular risks, MEtabolic syndrome, LIver and Autoimmune disease) is a cross-sectional, epidemiological study performed between 2009-2011 in Abbiategrasso (Milan, Italy) to estimate the prevalence of cardiovascular risk factors, metabolic syndrome, liver and autoimmune diseases in the general adult population. This report focuses on the description and presentation of baseline characteristics of the population. METHODS AND RESULTS: Citizens were randomly selected from the city electoral registers (n = 30903), yielding a sample of 2554 subjects (M = 1257, F = 1297; age, 47 ± 15 yrs; range 18-77 yrs). Men had higher prevalence of overweight or obesity (60.8% vs 41.6%; p < 0.0001) and greater thickness of visceral adipose tissue (40 ± 19 vs 27 ± 17 mm; p < 0.0001); no gender difference was found in subcutaneous adipose tissue thickness. Men also showed higher levels of serum triglycerides, γ-GT, fasting blood glucose, insulin and Homa-IR Index, while HDL, CRP, and prevalence of elevated (>5.0 mg/L) CRP were lower. Compared to normal weight men, risk-ratio (RR) of CRP elevation was 1.32 (ns) in overweight and 2.68 (p < 0.0001) in obese subjects. The corresponding figures in females were 2.68 (p < 0.0001) and 5.18 (p < 0.0001). Metabolic syndrome was more frequent in men (32.7% vs 14.5%; RR: 2.24, p < 0.0001). Interadventitia common carotid artery diameter was higher in men and increased with age and BMI. CONCLUSIONS: The present study reports on the overall characteristics of a large population from Northern Italy. It aims to identify the associations among cardiovascular risk factors to prevent their development and progression, improve healthy lifestyle and identify subjects liable to pharmacological interventions.


Assuntos
Doenças Autoimunes/epidemiologia , Doenças Cardiovasculares/epidemiologia , Hepatopatias/epidemiologia , Síndrome Metabólica/epidemiologia , Adolescente , Adulto , Idoso , Doenças Autoimunes/sangue , Doenças Autoimunes/diagnóstico , Biomarcadores/sangue , Glicemia/análise , Proteína C-Reativa/análise , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Estudos Transversais , Dislipidemias/sangue , Dislipidemias/epidemiologia , Feminino , Transtornos do Metabolismo de Glucose/sangue , Transtornos do Metabolismo de Glucose/epidemiologia , Humanos , Itália/epidemiologia , Lipídeos/sangue , Hepatopatias/sangue , Hepatopatias/diagnóstico , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Obesidade/epidemiologia , Prevalência , Medição de Risco , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Adulto Jovem , gama-Glutamiltransferase/sangue
12.
PLoS One ; 16(4): e0249728, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33798236

RESUMO

AIM: Osteoporotic fractures negatively impact health-related quality of life and prognosis. Advanced glycation end products (AGEs) impair bone quality and reduce bone strength. The aim of this study was to determine the relationship between plasma levels of pentosidine, a surrogate marker for AGEs, and prevalent fractures in patients with chronic liver disease (CLD). METHODS: This cross-sectional study included 324 patients with CLD. Vertebral fractures were evaluated using lateral thoracolumbar spine radiographs. Information on prevalent fractures was obtained through a medical interview, medical records, and/or radiography. The patients were classified into low (L), intermediate (I), and high (H) pentosidine (Pen) groups based on baseline plasma pentosidine levels. RESULTS: Of the 324 patients, 105 (32.4%) had prevalent fractures. The prevalence of liver cirrhosis (LC) and prevalent fractures significantly increased stepwise with elevated pentosidine levels. The H-Pen group had the highest prevalence of LC (88.6%, p < 0.001) and prevalent fractures (44.3%, p = 0.007), whereas the L-Pen group had the lowest prevalence of LC (32.1%, p < 0.001) and prevalent fractures (21.0%, p = 0.007). Multiple logistic regression analysis identified pentosidine as a significant independent factor related to prevalent fractures (odds ratio = 1.069, p < 0.001). Pentosidine levels increased stepwise and correlated with liver disease severity. They were markedly high in patients with decompensated LC. In multiple regression analysis, liver functional reserve factors (total bilirubin, albumin, and prothrombin time-international normalized ratio) significantly and independently correlated with pentosidine levels. CONCLUSIONS: Plasma pentosidine was significantly associated with prevalent fractures and liver functional reserve in patients with CLD. Pentosidine may be useful in predicting fracture risk and should be closely followed in CLD patients with advanced disease.


Assuntos
Arginina/análogos & derivados , Fraturas Ósseas/sangue , Hepatopatias/sangue , Lisina/análogos & derivados , Idoso , Arginina/sangue , Biomarcadores/sangue , Doença Crônica , Estudos Transversais , Feminino , Fraturas Ósseas/diagnóstico , Fraturas Ósseas/epidemiologia , Humanos , Japão/epidemiologia , Hepatopatias/epidemiologia , Lisina/sangue , Masculino , Pessoa de Meia-Idade , Prevalência
13.
Biopharm Drug Dispos ; 42(6): 263-284, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33904202

RESUMO

Renal (RIP) and hepatic (HIP) impairments are prevalent conditions in cancer patients. They can cause changes in gastric emptying time, albumin levels, hematocrit, glomerular filtration rate, hepatic functional volume, blood flow rates, and metabolic activity that can modify drug pharmacokinetics. Performing clinical studies in such populations has ethical and practical issues. Using predictive physiologically-based pharmacokinetic (PBPK) models in the evaluation of the PK of alectinib, ruxolitinib, and panobinostat exposures in the presence of cancer, RIP, and HIP can help in using optimal doses with lower toxicity in these populations. Verified PBPK models were customized under scrutiny to account for the pathophysiological changes induced in these diseases. The PBPK model-predicted plasma exposures in patients with different health conditions within average 2-fold error. The PBPK model predicted an area under the curve ratio (AUCR) of 1, and 1.8, for ruxolitinib and panobinostat, respectively, in the presence of severe RIP. On the other hand, the severe HIP was associated with AUCR of 1.4, 2.9, and 1.8 for alectinib, ruxolitinib, and panobinostat, respectively, in agreement with the observed AUCR. Moreover, the PBPK model predicted that alectinib therapeutic cerebrospinal fluid levels are achieved in patients with non-small cell lung cancer, moderate HIP, and severe HIP at 1-, 1.5-, and 1.8-fold that of healthy subjects. The customized PBPK models showed promising ethical alternatives for simulating clinical studies in patients with cancer, RIP, and HIP. More work is needed to quantify other pathophysiological changes induced by simultaneous affliction by cancer and RIP or HIP.


Assuntos
Antineoplásicos/farmacocinética , Carbazóis/farmacocinética , Hepatopatias/sangue , Modelos Biológicos , Neoplasias/sangue , Nitrilas/farmacocinética , Panobinostat/farmacocinética , Piperidinas/farmacocinética , Inibidores de Proteínas Quinases/farmacocinética , Pirazóis/farmacocinética , Pirimidinas/farmacocinética , Insuficiência Renal/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/sangue , Área Sob a Curva , Carbazóis/sangue , Jejum/metabolismo , Feminino , Humanos , Hepatopatias/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias/metabolismo , Nitrilas/sangue , Panobinostat/sangue , Piperidinas/sangue , Inibidores de Proteínas Quinases/sangue , Pirazóis/sangue , Pirimidinas/sangue , Insuficiência Renal/metabolismo
14.
BMC Cardiovasc Disord ; 21(1): 145, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33740888

RESUMO

BACKGROUND: Inconsistent results were found in the association between serum alanine aminotransferase (ALT) and hypertension among population-based studies. This study evaluated the association between ALT and hypertension among Chinese reproductive-age population by utilizing registration data from National Free Pre-pregnancy Checkups Project in 2016-2017. METHODS: The 21,103,790 registered participants were eligible for analysis, including women who were 20-49 years old and men who were 20-59 years old with available data for ALT and blood pressure (BP). Logistic regression was conducted to estimate odds ratio (OR) for the association between ALT and hypertension as a binary outcome. Linear regression was used to examine the association between ALT and BP as a continuous outcome. RESULTS: In total, 4.21% of the participants were hypertensive, and 11.67% had elevated ALT (> 40 U/L). Hypertension prevalence was 3.63% and 8.56% among participants with normal and elevated ALT levels. A strong linear relationship was found between serum ALT levels and the odds of hypertension after adjustment for potential confounders. The multivariable-adjusted ORs for hypertension were 1, 1.22 (1.21, 1.22), 1.67 (1.65 1.68), 1.78 (1.76, 1.80), and 1.92 (1.90, 1.94) in participants with ALT levels of ≤ 20, 20.01-40, 40.01-60, 60.01-80, and > 80 U/L, respectively. Systolic and diastolic BPs rose by 1.83 and 1.20 mmHg on average, for each 20 U/L increase in ALT (P for trend < 0.001). The association was consistent among subgroups and tended to be stronger among populations who are overweight (body mass index ≥ 24 kg/m2) (χ2 = 52,228, P < 0.001), alcohol drinking (χ2 = 100,730, P < 0.001) and cigarette smoking (χ2 = 105,347, P < 0.001). CONCLUSIONS: Our cross-sectional analysis suggested a linear association between serum ALT and hypertension or BP, which indicated that abnormal liver metabolism marked by elevated serum ALT could play a role in hypertension or elevated BP condition.


Assuntos
Alanina Transaminase/sangue , Pressão Sanguínea , Hipertensão/fisiopatologia , Hepatopatias/sangue , Adulto , Biomarcadores/sangue , China/epidemiologia , Ensaios Enzimáticos Clínicos , Estudos Transversais , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hepatopatias/diagnóstico , Hepatopatias/epidemiologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Medição de Risco , Fatores de Risco , Adulto Jovem
15.
Front Immunol ; 12: 627944, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33763072

RESUMO

Sickle cell disease (SCD) is an inherited hemolytic disorder, defined by a point mutation in the ß-globin gene. Stress conditions such as infection, inflammation, dehydration, and hypoxia trigger erythrocyte sickling. Sickled red blood cells (RBCs) hemolyze more rapidly, show impaired deformability, and increased adhesive properties to the endothelium. In a proinflammatory, pro-coagulative environment with preexisting endothelial dysfunction, sickled RBCs promote vascular occlusion. Hepatobiliary involvement related to the sickling process, such as an acute sickle hepatic crisis, is observed in about 10% of acute sickle cell crisis incidents. In mice, ligation of CD40 with an agonistic antibody leads to a macrophage activation in the liver, triggering a sequence of systemic inflammation, endothelial cell activation, thrombosis, and focal ischemia. We found that anti-CD40 antibody injection in sickle cell mice induces a systemic inflammatory and hemodynamic response with accelerated hemolysis, extensive vaso-occlusion, and large ischemic infarctions in the liver mimicking an acute hepatic crisis. Administration of the tumor necrosis factor-α (TNF-α) blocker, etanercept, and the heme scavenger protein, hemopexin attenuated end-organ damage. These data collectively suggest that anti-CD40 administration offers a novel acute liver crisis model in humanized sickle mice, allowing for evaluation of therapeutic proof-of-concept.


Assuntos
Anemia Falciforme/complicações , Anticorpos/toxicidade , Antígenos CD40/agonistas , Inflamação/etiologia , Hepatopatias/etiologia , Anemia Falciforme/sangue , Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/imunologia , Animais , Antígenos CD40/imunologia , Antígenos CD40/metabolismo , Citocinas/sangue , Modelos Animais de Doenças , Etanercepte/farmacologia , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/imunologia , Hemólise , Hemopexina/farmacologia , Humanos , Inflamação/sangue , Inflamação/imunologia , Inflamação/prevenção & controle , Mediadores da Inflamação/sangue , Hepatopatias/sangue , Hepatopatias/imunologia , Hepatopatias/prevenção & controle , Camundongos Transgênicos , Inibidores do Fator de Necrose Tumoral/farmacologia , Disfunção Ventricular Direita/sangue , Disfunção Ventricular Direita/etiologia , Disfunção Ventricular Direita/imunologia
16.
J Clin Lab Anal ; 35(5): e23758, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33720453

RESUMO

BACKGROUND: To establish a time-resolved fluorescence immunoassay of interleukin (IL)-18 (IL-18-TRFIA) and detect its concentration in different liver disease serum samples. METHODS: The IL-18 coating antibody and the Eu3+ -labeled detection antibody were used for the IL-18-TRFIA to detect serum IL-18 concentration in patients with liver cancer, hepatitis B, hepatitis C, autoimmune hepatitis, fatty liver disease, and healthy controls. The double-antibody sandwich method was used and methodological evaluation was performed. RESULTS: The average intra- and inter-assay coefficient of variation for IL-18-TRFIA was 4.80% and 5.90%, respectively. The average recovery rate was 106.19 ± 3.44%. The sensitivity (10.96 pg/mL) was higher than that obtained using the ELISA method (62.5 pg/mL). The detection range was 10.96-1000 pg/mL. IL-6 and galectin-3 did not cross-react with IL-18-TRFIA. The serum concentration of IL-18 was (776.99; 653.48-952.39 pg/mL) in hepatitis C, (911; 775.55-1130.03 pg/mL) in fatty liver, (1048.88; 730.04-1185.10 pg/mL) in liver cancer, and (949.12; 723.70-1160.28 pg/mL) in hepatitis B. Moreover, IL-18 serum levels were significantly higher in patients than the healthy controls (483.09; 402.52-599.70/mL) (p < 0.0001). Autoimmune hepatitis with a serum IL-18 concentration of 571.62; 502.47-730.31 pg/mL was not significantly different from the healthy controls (p > 0.05). CONCLUSION: We established a highly sensitive IL-18-TRFIA method that successfully detected serum IL-18 concentrations in different liver diseases. Furthermore, IL-18 serum concentration was higher in patients with liver cancer, hepatitis C, hepatitis B, and fatty liver disease compared to healthy controls.


Assuntos
Fluorimunoensaio/métodos , Interleucina-18/sangue , Hepatopatias/sangue , Estudos de Casos e Controles , Fluorescência , Humanos , Limite de Detecção , Neoplasias Hepáticas/sangue , Curva ROC , Padrões de Referência , Sensibilidade e Especificidade , Fatores de Tempo
17.
Hepatol Int ; 15(2): 493-501, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33534084

RESUMO

BACKGROUND/PURPOSE: The relationship between liver injury and mortality remains unclear in patients with COVID-19. We aimed to evaluate the prognostic value of aminotransferases levels at hospital admission to predict mortality in patients with COVID-19. METHODS AND RESULTS: This prospective study included 406 patients [57% male, aged 56 years] with COVID-19 hospitalized in 26 centers in Brazil. Overall, 36.7% (95% CI 32.1-41.5) presented at admission with severe disease requiring respiratory support. The prevalence of elevated ALT and AST levels at admission [> 2 × ULN] was 14.0% (95% CI 11.0-17.8) and 12.9% (95% CI 10.0-16.6), respectively. Sixty-two patients [15.3% (95% CI 12.1-19.1)] died during hospitalization and the overall mortality rate was 13.4 (10.5-17.2) deaths per 1000 persons-years. The 15-day-overall survival (95% CI) was significantly lower in patients with ALT levels ≥ 2 × ULN compared to those with ALT < 2 × ULN [67.1% (48.4-80.2) vs 83.4% (76.1-88.6), p = 0.001] and in those with AST levels ≥ 2 × ULN compared to those with AST < 2 × ULN [61.5% (44.7-74.6) vs 84.2% (76.5-89.5), p < 0.001]. The presence of elevated aminotransferases levels at hospital admission significantly increased the risk of in-hospital all-cause mortality adjusted for age-and-sex. Those findings were present in the subgroup of critically ill patients already admitted in need of respiratory support (n = 149), but not in patients without that requirement at admission (n = 257). CONCLUSIONS: Elevated aminotransferases at hospital admission predicted in-hospital all-cause mortality in patients with COVID-19, especially in those with severe disease. Measurement of transaminases levels at hospital admission should be integrated to the care of patients with COVID-19 as an auxiliary strategy to identify patients at higher death risk.


Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , COVID-19/complicações , COVID-19/mortalidade , Hepatopatias/sangue , Adulto , Idoso , Brasil/epidemiologia , Feminino , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Hepatopatias/virologia , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Admissão do Paciente , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , SARS-CoV-2 , Taxa de Sobrevida
18.
Nat Commun ; 12(1): 816, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33547301

RESUMO

Serum liver enzyme concentrations are the most frequently-used laboratory markers of liver disease, a major cause of mortality. We conduct a meta-analysis of genome-wide association studies of liver enzymes from UK BioBank and BioBank Japan. We identified 160 previously-unreported independent alanine aminotransferase, 190 aspartate aminotransferase, and 199 alkaline phosphatase genome-wide significant associations, with some affecting multiple different enzymes. Associated variants implicate genes that demonstrate diverse liver cell type expression and promote a range of metabolic and liver diseases. These findings provide insight into the pathophysiology of liver and other metabolic diseases that are associated with serum liver enzyme concentrations.


Assuntos
Alanina Transaminase/genética , Fosfatase Alcalina/genética , Aspartato Aminotransferases/genética , Genoma Humano , Hepatopatias/genética , Fígado/enzimologia , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Aspartato Aminotransferases/sangue , Bancos de Espécimes Biológicos , Células Endoteliais/enzimologia , Células Endoteliais/patologia , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Hepatócitos/enzimologia , Hepatócitos/patologia , Humanos , Japão , Células Matadoras Naturais/enzimologia , Células Matadoras Naturais/patologia , Macrófagos do Fígado/enzimologia , Macrófagos do Fígado/patologia , Fígado/patologia , Hepatopatias/sangue , Hepatopatias/classificação , Hepatopatias/patologia , Locos de Características Quantitativas , Característica Quantitativa Herdável , Análise de Célula Única , Reino Unido
19.
Trop Doct ; 51(2): 228-231, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33612084

RESUMO

In Scrunb Typhus, hepatotoxicity is an important, yet understudied, manifestation. We reviewed studies on scrub typhus, published in the last five years (2014-2019), which evaluated its clinico-epidemiological factors in India, and concentrated on its hepatic involvement. Nine studies were found, and no Indian study exclusively evaluated hepatic dysfunction. Thus, comments from a few international studies were also included. We conclude that liver dysfunction in the form of elevated serum transaminase levels is a common manifestation of scrub typhus, which may herald progress to fulminant hepatic failure.


Assuntos
Hepatopatias/etiologia , Tifo por Ácaros/complicações , Humanos , Índia , Hepatopatias/sangue , Hepatopatias/fisiopatologia , Falência Hepática Aguda/etiologia , Falência Hepática Aguda/fisiopatologia , Tifo por Ácaros/sangue , Tifo por Ácaros/fisiopatologia , Transaminases/sangue
20.
Mol Med ; 27(1): 18, 2021 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-33632134

RESUMO

BACKGROUND: Hepatic ischemia/reperfusion (I/R) injury can be a major complication following liver surgery contributing to post-operative liver dysfunction. Maresin 1 (MaR1), a pro-resolving lipid mediator, has been shown to suppress I/R injury. However, the mechanisms that account for the protective effects of MaR1 in I/R injury remain unknown. METHODS: WT (C57BL/6J) mice were subjected to partial hepatic warm ischemia for 60mins followed by reperfusion. Mice were treated with MaR1 (5-20 ng/mouse), Boc2 (Lipoxin A4 receptor antagonist), LY294002 (Akt inhibitor) or corresponding controls just prior to liver I/R or at the beginning of reperfusion. Blood and liver samples were collected at 6 h post-reperfusion. Serum aminotransferase, histopathologic changes, inflammatory cytokines, and oxidative stress were analyzed to evaluate liver injury. Signaling pathways were also investigated in vitro using primary mouse hepatocyte (HC) cultures to identify underlying mechanisms for MaR1 in liver I/R injury. RESULTS: MaR1 treatment significantly reduced ALT and AST levels, diminished necrotic areas, suppressed inflammatory responses, attenuated oxidative stress and decreased hepatocyte apoptosis in liver after I/R. Akt signaling was significantly increased in the MaR1-treated liver I/R group compared with controls. The protective effect of MaR1 was abrogated by pretreatment with Boc2, which together with MaR1-induced Akt activation. MaR1-mediated liver protection was reversed by inhibition of Akt. CONCLUSIONS: MaR1 protects the liver against hepatic I/R injury via an ALXR/Akt signaling pathway. MaR1 may represent a novel therapeutic agent to mitigate the detrimental effects of I/R-induced liver injury.


Assuntos
Ácidos Docosa-Hexaenoicos/uso terapêutico , Hepatopatias/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Formil Peptídeo/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Sobrevivência Celular/efeitos dos fármacos , Citocinas/sangue , Ácidos Docosa-Hexaenoicos/farmacologia , Glutationa Peroxidase/metabolismo , Hepatócitos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Hepatopatias/sangue , Hepatopatias/metabolismo , Hepatopatias/patologia , Masculino , Malondialdeído/metabolismo , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Receptores de Formil Peptídeo/genética , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Transdução de Sinais/efeitos dos fármacos
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