Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 10.459
Filtrar
1.
Medicine (Baltimore) ; 100(22): e26207, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087892

RESUMO

ABSTRACT: Terry nails and Lindsay nails are similar forms of proximal apparent leukonychia (PAL). A change in nail bed vascularity is thought to be responsible for PAL. The study was aimed at investigating the frequency of PAL in patients attending a liver disease clinic, the factors associated with its presence, its value for detecting cirrhosis, its prognostic value for mortality, and associated capillaroscopic findings.A total of 521 patients were included (age range, 18-94 years; 69% men). Systematic nail photographs were evaluated by 2 independent investigators. Disease-related data were obtained from the medical records. Mortality was evaluated after 7 years of follow-up. Nailfold capillaroscopy was performed on a subset of 80 patients.PAL was present in 228 patients (43.8%; Terry nails in 205, Lindsay nails in 20, and both in 3). The kappa-coefficient of interobserver agreement was 0.82. The presence of PAL was associated with cirrhosis and, accordingly, with portal hypertension and hepatocellular dysfunction. The positive likelihood ratio of PAL for the diagnosis of cirrhosis was 1.6 (95% CI 1.3-1.92). PAL was independently associated with chronic alcohol abuse and was not a significant predictor of mortality. Venous loop dilatation and prominence of the venous plexus were observed on capillaroscopy in patients with cirrhosis but were not significantly associated with PAL.In summary, PAL is a common finding in patients from a liver clinic; it is associated with liver cirrhosis and with alcohol abuse. PAL is not associated with specific capillaroscopic findings. We propose the generic term proximal apparent leukonychia instead of classic eponymous titles to avoid confusion in the literature.


Assuntos
Hipopigmentação/diagnóstico , Cirrose Hepática/diagnóstico , Hepatopatias/patologia , Angioscopia Microscópica/métodos , Doenças da Unha/congênito , Adulto , Idoso , Alcoolismo/complicações , Capilares/patologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Hipopigmentação/etiologia , Cirrose Hepática/mortalidade , Hepatopatias/complicações , Masculino , Angioscopia Microscópica/estatística & dados numéricos , Pessoa de Meia-Idade , Doenças da Unha/diagnóstico , Doenças da Unha/etiologia , Unhas/irrigação sanguínea , Unhas Malformadas/diagnóstico , Unhas Malformadas/patologia , Fotografação/métodos , Prognóstico
2.
Liver Int ; 41 Suppl 1: 1-8, 2021 06.
Artigo em Inglês | MEDLINE | ID: covidwho-1280355

RESUMO

Liver involvement, indicated by elevated liver function test results, is common in hospitalized patients with coronavirus disease 2019 (COVID-19) and has been linked to disease severity and outcome. A dual pattern of elevated liver function tests can be observed especially in patients with severe or critical COVID-19, characterized by an increase in aminotransferases early in the course of this disease, followed by an increase in cholestasis-associated biochemistry markers at later stages. This dual pattern is associated with inflammatory response markers and poor outcome. Current notions on the mechanisms of liver injury in COVID-19 include direct cytopathic effects of the virus on hepatocytes and cholangiocytes, ischemic and hypoxic liver damage, drug-induced liver injury, activation of hepatic immune cells by excess cytokine production and exacerbation of pre-existing liver disease. Patients with obesity-related non-alcoholic fatty liver disease and, in particular, patients with cirrhosis are at high risk of liver injury and a fatal outcome from COVID-19. In contrast, individuals receiving stable immunosuppressive medication for autoimmune liver diseases or during long-term follow-up after liver transplantation do not have a higher case-to-infection ratio and have a fairly favourable outcome. The present review describes the epidemiology, characteristics and potential pathological mechanisms of COVID-19-related liver injury. Moreover, the influence of pre-existing liver disease on the susceptibility and severity of liver injury in COVID-19 are discussed.


Assuntos
COVID-19 , Hepatopatias , Hepatopatia Gordurosa não Alcoólica , Humanos , Fígado/patologia , Cirrose Hepática/patologia , Hepatopatias/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , SARS-CoV-2
3.
Sci Rep ; 11(1): 11734, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: covidwho-1258596

RESUMO

To explore the role of chronic liver disease (CLD) in COVID-19. A total of 1439 consecutively hospitalized patients with COVID-19 from one large medical center in the United States from March 16, 2020 to April 23, 2020 were retrospectively identified. Clinical characteristics and outcomes were compared between patients with and without CLD. Postmortem examination of liver in 8 critically ill COVID-19 patients was performed. There was no significant difference in the incidence of CLD between critical and non-critical groups (4.1% vs 2.9%, p = 0.259), or COVID-19 related liver injury between patients with and without CLD (65.7% vs 49.7%, p = 0.065). Postmortem examination of liver demonstrated mild liver injury associated central vein outflow obstruction and minimal to moderate portal lymphocytic infiltrate without evidence of CLD. Patients with CLD were not associated with a higher risk of liver injury or critical/fatal outcomes. CLD was not a significant comorbid condition for COVID-19.


Assuntos
COVID-19/epidemiologia , Hepatopatias/epidemiologia , Lesão Pulmonar Aguda/epidemiologia , Lesão Pulmonar Aguda/patologia , Idoso , COVID-19/mortalidade , Doença Crônica , Comorbidade , Feminino , Humanos , Hepatopatias/patologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estados Unidos/epidemiologia
4.
Cell Mol Life Sci ; 78(14): 5631-5646, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34110423

RESUMO

Peroxisomes play an essential role in the ß-oxidation of dicarboxylic acids (DCAs), which are metabolites formed upon ω-oxidation of fatty acids. Genetic evidence linking transporters and enzymes to specific DCA ß-oxidation steps is generally lacking. Moreover, the physiological functions of DCA metabolism remain largely unknown. In this study, we aimed to characterize the DCA ß-oxidation pathway in human cells, and to evaluate the biological role of DCA metabolism using mice deficient in the peroxisomal L-bifunctional protein (Ehhadh KO mice). In vitro experiments using HEK-293 KO cell lines demonstrate that ABCD3 and ACOX1 are essential in DCA ß-oxidation, whereas both the bifunctional proteins (EHHADH and HSD17B4) and the thiolases (ACAA1 and SCPx) have overlapping functions and their contribution may depend on expression level. We also show that medium-chain 3-hydroxydicarboxylic aciduria is a prominent feature of EHHADH deficiency in mice most notably upon inhibition of mitochondrial fatty acid oxidation. Using stable isotope tracing methodology, we confirmed that products of peroxisomal DCA ß-oxidation can be transported to mitochondria for further metabolism. Finally, we show that, in liver, Ehhadh KO mice have increased mRNA and protein expression of cholesterol biosynthesis enzymes with decreased (in females) or similar (in males) rate of cholesterol synthesis. We conclude that EHHADH plays an essential role in the metabolism of medium-chain DCAs and postulate that peroxisomal DCA ß-oxidation is a regulator of hepatic cholesterol biosynthesis.


Assuntos
Colesterol/metabolismo , Ácidos Dicarboxílicos/urina , Erros Inatos do Metabolismo Lipídico/patologia , Hepatopatias/patologia , Mitocôndrias/patologia , Enzima Bifuncional do Peroxissomo/fisiologia , Animais , Feminino , Células HEK293 , Homeostase , Humanos , Erros Inatos do Metabolismo Lipídico/etiologia , Hepatopatias/etiologia , Hepatopatias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/metabolismo
5.
FASEB J ; 35(7): e21497, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34152015

RESUMO

Despite the increasing understanding of the pathophysiology of hepatic fibrosis, the therapies to combat it remain inadequate. Fluorofenidone (AKF-PD) is a novel pyridone agent able to ameliorate hepatic fibrosis in an experimental hepatic fibrosis model induced by dimethylnitrosamine. However, the underlying mechanism remains to be further elucidated. In light of the critical role of the NF-κB pathway in inflammation and hepatic fibrosis, together with the preliminary finding that AKF-PD decreases the release of proinflammatory cytokines in the endotoxemia and unilateral ureteral occlusion model, the aim of this study was to explore whether AKF-PD exerts an antifibrotic effect in hepatic fibrosis by inhibiting inflammation and suppressing the activation of the NF-κB pathway in vivo and in vitro. To test this possibility, the effect of AKF-PD on hepatic fibrosis models induced by both carbon tetrachloride (CCL4 ) and porcine serum (PS) was investigated. Our results showed that AKF-PD treatment ameliorated hepatic injury and fibrosis in both models. Furthermore, the administration of AKF-PD induced a robust anti-inflammatory reaction revealed by the downregulation of the proinflammatory cytokines as well as the suppression of the infiltration of inflammatory cells in the fibrotic liver. The analysis of the mechanism of action demonstrated that the attenuation of the production of proinflammatory cytokines and chemokines mediated by AKF-PD in vivo and in vitro were accompanied by the suppression in the activation of the NF-κB signaling pathway. In conclusion, AKF-PD might be considered as an antifibrotic agent attenuating hepatic inflammation and fibrosis potentially through the suppression of the NF-κB pathway.


Assuntos
Anti-Inflamatórios/farmacologia , Fibrose/tratamento farmacológico , Inflamação/tratamento farmacológico , Hepatopatias/prevenção & controle , NF-kappa B/antagonistas & inibidores , Substâncias Protetoras/farmacologia , Piridonas/farmacologia , Animais , Células Cultivadas , Fibrose/metabolismo , Fibrose/patologia , Inflamação/metabolismo , Inflamação/patologia , Hepatopatias/metabolismo , Hepatopatias/patologia , Masculino , Ratos , Ratos Sprague-Dawley
6.
Sci Rep ; 11(1): 11734, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34083670

RESUMO

To explore the role of chronic liver disease (CLD) in COVID-19. A total of 1439 consecutively hospitalized patients with COVID-19 from one large medical center in the United States from March 16, 2020 to April 23, 2020 were retrospectively identified. Clinical characteristics and outcomes were compared between patients with and without CLD. Postmortem examination of liver in 8 critically ill COVID-19 patients was performed. There was no significant difference in the incidence of CLD between critical and non-critical groups (4.1% vs 2.9%, p = 0.259), or COVID-19 related liver injury between patients with and without CLD (65.7% vs 49.7%, p = 0.065). Postmortem examination of liver demonstrated mild liver injury associated central vein outflow obstruction and minimal to moderate portal lymphocytic infiltrate without evidence of CLD. Patients with CLD were not associated with a higher risk of liver injury or critical/fatal outcomes. CLD was not a significant comorbid condition for COVID-19.


Assuntos
COVID-19/epidemiologia , Hepatopatias/epidemiologia , Lesão Pulmonar Aguda/epidemiologia , Lesão Pulmonar Aguda/patologia , Idoso , COVID-19/mortalidade , Doença Crônica , Comorbidade , Feminino , Humanos , Hepatopatias/patologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estados Unidos/epidemiologia
7.
BMC Gastroenterol ; 21(1): 268, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34182924

RESUMO

BACKGROUND: Alcohol is the main cause of chronic liver disease. The Enhanced Liver Fibrosis (ELF) test is a serological biomarker for fibrosis staging in chronic liver disease, however its utility in alcohol-related liver disease warrants further validation. We assessed the diagnostic and prognostic performance of ELF in alcohol-related liver disease. METHODS: Observational cohort study assessing paired ELF and histology from 786 tertiary care patients with chronic liver disease due to alcohol (n = 81) and non-alcohol aetiologies (n = 705). Prognostic data were available for 64 alcohol patients for a median of 6.4 years. Multiple ELF cut-offs were assessed to determine diagnostic utility in moderate fibrosis and cirrhosis. Survival data were assessed to determine the ability of ELF to predict liver related events and all-cause mortality. RESULTS: ELF identified cirrhosis and moderate fibrosis in alcohol-related liver disease independently of aminotransferase levels with areas under receiver operating characteristic curves of 0.895 (95% CI 0.823-0.968) and 0.923 (95% CI 0.866-0.981) respectively, which were non-inferior to non-alcohol aetiologies. The overall performance of ELF was assessed using the Obuchowski method: in alcohol = 0.934 (95% CI 0.908-0.960); non-alcohol = 0.907 (95% CI 0.895-0.919). Using ELF < 9.8 to exclude and ≧ 10.5 to diagnose cirrhosis, 87.7% of alcohol cases could have avoided biopsy, with sensitivity of 91% and specificity of 85%. A one-unit increase in ELF was associated with a 2.6 (95% CI 1.55-4.31, p < 0.001) fold greater odds of cirrhosis at baseline and 2.0-fold greater risk of a liver related event within 6 years (95% CI 1.39-2.99, p < 0.001). CONCLUSIONS: ELF accurately stages liver fibrosis independently of transaminase elevations as a marker of inflammation and has superior prognostic performance to biopsy in alcohol-related liver disease.


Assuntos
Cirrose Hepática , Hepatopatias , Biomarcadores , Biópsia , Estudos de Coortes , Humanos , Fígado/patologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Hepatopatias/patologia , Testes de Função Hepática , Prognóstico
8.
Liver Int ; 41 Suppl 1: 1-8, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34155789

RESUMO

Liver involvement, indicated by elevated liver function test results, is common in hospitalized patients with coronavirus disease 2019 (COVID-19) and has been linked to disease severity and outcome. A dual pattern of elevated liver function tests can be observed especially in patients with severe or critical COVID-19, characterized by an increase in aminotransferases early in the course of this disease, followed by an increase in cholestasis-associated biochemistry markers at later stages. This dual pattern is associated with inflammatory response markers and poor outcome. Current notions on the mechanisms of liver injury in COVID-19 include direct cytopathic effects of the virus on hepatocytes and cholangiocytes, ischemic and hypoxic liver damage, drug-induced liver injury, activation of hepatic immune cells by excess cytokine production and exacerbation of pre-existing liver disease. Patients with obesity-related non-alcoholic fatty liver disease and, in particular, patients with cirrhosis are at high risk of liver injury and a fatal outcome from COVID-19. In contrast, individuals receiving stable immunosuppressive medication for autoimmune liver diseases or during long-term follow-up after liver transplantation do not have a higher case-to-infection ratio and have a fairly favourable outcome. The present review describes the epidemiology, characteristics and potential pathological mechanisms of COVID-19-related liver injury. Moreover, the influence of pre-existing liver disease on the susceptibility and severity of liver injury in COVID-19 are discussed.


Assuntos
COVID-19 , Hepatopatias , Hepatopatia Gordurosa não Alcoólica , Humanos , Fígado/patologia , Cirrose Hepática/patologia , Hepatopatias/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , SARS-CoV-2
9.
Pathol Res Pract ; 221: 153451, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33932720

RESUMO

Few studies have focused on COVID-19 patients' hepatic histopathological features. Many of the described morphological landscapes are non-specific and possibly due to other comorbidities or to Sars-CoV-2-related therapies. We describe the hepatic histopathological findings of 3 liver biopsies obtained from living COVID-19 patients in which active SARS-CoV-2 infection was molecularly confirmed and biopsied because of significant alterations of liver function tests and 25 livers analyzed during COVID-19-related autopsies. Main histopathological findings were (i) the absence of significant biliary tree or vascular damages, (ii) mild/absent lymphocytic hepatitis; (iii) activation of (pigmented) Kupffer cells, (iv) hepatocellular regenerative changes, (v) the presence of steatosis, (vi) sinusoidal ectasia, micro-thrombosis and acinar atrophy in autopsy specimens No viral particle actively infecting the hepatic or endothelial cells was detected at in situ hybridization. The morphological features observed within the hepatic parenchyma are not specific and should be considered as the result of an indirect insult resulting from the viral infection or the adopted therapeutic protocols.


Assuntos
COVID-19/complicações , Hepatopatias/patologia , Hepatopatias/virologia , Idoso , Idoso de 80 Anos ou mais , Autopsia , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2
10.
Sci Rep ; 11(1): 10599, 2021 05 19.
Artigo em Inglês | MEDLINE | ID: covidwho-1236092

RESUMO

Emerging evidence suggest association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with the development of many liver abnormalities. The overarching aim of this study was therefore to assess the available evidence on the clinical effects of SARS-CoV-2 on the profiles of liver chemistries and coagulation in COVID-19 diagnosed patients. We considered all study designs including epidemiological and observational that reported liver function test abnormalities in patients confirmed with SARS-CoV-2 infection. Medline, Embase databases and Google Scholar as well as relevant reviews were searched to identify appropriate studies from inception to 31st of August 2020. We calculated the pooled mean with 95% confidence intervals (95% CI) through a random-effect model meta-analysis. A total of 35 studies with 10,692 participants were considered for the review from which 23 studies with sufficient quantitative data were included in the meta-analysis. The pooled mean for liver enzymes and coagulation parameters did not significantly change in patients diagnosed with COVID-19 and remained within normal range. Notwithstanding potential bias from confounding factors in interpretation of data in this review, findings from the observational studies and case reports suggest that COVID-19 does not appear to have a significant impact on the transaminases or total bilirubin levels of patients with confirmed SARS-CoV-2 infection. Further controlled studies and larger sample size observational studies are needed with adequate reporting of other liver function parameters are warranted.


Assuntos
COVID-19/patologia , Hepatopatias/patologia , Hepatopatias/virologia , COVID-19/virologia , Humanos , Hepatopatias/epidemiologia , Testes de Função Hepática , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/patogenicidade
11.
Pathol Res Pract ; 221: 153451, 2021 May.
Artigo em Inglês | MEDLINE | ID: covidwho-1209485

RESUMO

Few studies have focused on COVID-19 patients' hepatic histopathological features. Many of the described morphological landscapes are non-specific and possibly due to other comorbidities or to Sars-CoV-2-related therapies. We describe the hepatic histopathological findings of 3 liver biopsies obtained from living COVID-19 patients in which active SARS-CoV-2 infection was molecularly confirmed and biopsied because of significant alterations of liver function tests and 25 livers analyzed during COVID-19-related autopsies. Main histopathological findings were (i) the absence of significant biliary tree or vascular damages, (ii) mild/absent lymphocytic hepatitis; (iii) activation of (pigmented) Kupffer cells, (iv) hepatocellular regenerative changes, (v) the presence of steatosis, (vi) sinusoidal ectasia, micro-thrombosis and acinar atrophy in autopsy specimens No viral particle actively infecting the hepatic or endothelial cells was detected at in situ hybridization. The morphological features observed within the hepatic parenchyma are not specific and should be considered as the result of an indirect insult resulting from the viral infection or the adopted therapeutic protocols.


Assuntos
COVID-19/complicações , Hepatopatias/patologia , Hepatopatias/virologia , Idoso , Idoso de 80 Anos ou mais , Autopsia , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2
12.
FASEB J ; 35(6): e21672, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34042221

RESUMO

Strong inflammatory response triggered by the activation of the innate immune system is one typical characteristic of sepsis-associated liver injury (SALI). Guanylate-binding protein 5 (GBP-5) is a component of cell-autonomous immunity and known to be associated with inflammation. Currently, whether GBP-5 participates in SALI and its roles in this disease are yet to be investigated. Using a lipopolysaccharide (LPS)-induced SALI mouse model, we found GBP-5 was highly expressed in LPS-treated mice, and its expression was tightly related to the serum concentrations of live injury markers and inflammatory cytokines, liver damage scores by H&E staining, and amounts of apoptotic hepatocytes by TUNEL staining. Moreover, GBP-5 overexpression was found to aggravate LPS-induced SALI by promoting the activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome, then facilitated the production of pro-inflammatory cytokines, eventually induced hepatocyte cell death. Direct transcriptional activation of GBP-5 by basic leucine zipper ATF-like transcription factor (BATF) was identified and further validated. This study unveils a transcriptional upregulation of GBP-5 by interacting with BATF, which promotes the progression of LPS-induced SALI through NLRP3 inflammasome activation, and provides novel therapeutic insights for halting the progression of liver injury in various liver diseases.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Proteínas de Ligação ao GTP/genética , Inflamassomos/imunologia , Inflamação/patologia , Hepatopatias/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sepse/complicações , Animais , Fatores de Transcrição de Zíper de Leucina Básica/genética , Inflamação/etiologia , Inflamação/metabolismo , Hepatopatias/etiologia , Hepatopatias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética
13.
Sci Rep ; 11(1): 10599, 2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-34012016

RESUMO

Emerging evidence suggest association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with the development of many liver abnormalities. The overarching aim of this study was therefore to assess the available evidence on the clinical effects of SARS-CoV-2 on the profiles of liver chemistries and coagulation in COVID-19 diagnosed patients. We considered all study designs including epidemiological and observational that reported liver function test abnormalities in patients confirmed with SARS-CoV-2 infection. Medline, Embase databases and Google Scholar as well as relevant reviews were searched to identify appropriate studies from inception to 31st of August 2020. We calculated the pooled mean with 95% confidence intervals (95% CI) through a random-effect model meta-analysis. A total of 35 studies with 10,692 participants were considered for the review from which 23 studies with sufficient quantitative data were included in the meta-analysis. The pooled mean for liver enzymes and coagulation parameters did not significantly change in patients diagnosed with COVID-19 and remained within normal range. Notwithstanding potential bias from confounding factors in interpretation of data in this review, findings from the observational studies and case reports suggest that COVID-19 does not appear to have a significant impact on the transaminases or total bilirubin levels of patients with confirmed SARS-CoV-2 infection. Further controlled studies and larger sample size observational studies are needed with adequate reporting of other liver function parameters are warranted.


Assuntos
COVID-19/patologia , Hepatopatias/patologia , Hepatopatias/virologia , COVID-19/virologia , Humanos , Hepatopatias/epidemiologia , Testes de Função Hepática , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/patogenicidade
14.
Int J Mol Sci ; 22(9)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946468

RESUMO

Mitochondria are the major source of intercellular bioenergy in the form of ATP. They are necessary for cell survival and play many essential roles such as maintaining calcium homeostasis, body temperature, regulation of metabolism and apoptosis. Mitochondrial dysfunction has been observed in variety of diseases such as cardiovascular disease, aging, type 2 diabetes, cancer and degenerative brain disease. In other words, the interpretation and regulation of mitochondrial signals has the potential to be applied as a treatment for various diseases caused by mitochondrial disorders. In recent years, mitochondrial transplantation has increasingly been a topic of interest as an innovative strategy for the treatment of mitochondrial diseases by augmentation and replacement of mitochondria. In this review, we focus on diseases that are associated with mitochondrial dysfunction and highlight studies related to the rescue of tissue-specific mitochondrial disorders. We firmly believe that mitochondrial transplantation is an optimistic therapeutic approach in finding a potentially valuable treatment for a variety of mitochondrial diseases.


Assuntos
Mitocôndrias/transplante , Doenças Mitocondriais/terapia , Animais , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/terapia , Cardiopatias/metabolismo , Cardiopatias/patologia , Cardiopatias/terapia , Humanos , Hepatopatias/metabolismo , Hepatopatias/patologia , Hepatopatias/terapia , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Doenças Mitocondriais/metabolismo , Doenças Mitocondriais/patologia , Dinâmica Mitocondrial , Doenças do Sistema Nervoso/metabolismo , Doenças do Sistema Nervoso/patologia , Doenças do Sistema Nervoso/terapia
15.
Anticancer Res ; 41(5): 2727-2732, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33952504

RESUMO

BACKGROUND: Hepatic inflammatory pseudotumor (HIPT) is an uncommon benign tumor-like mass that mimics malignant tumors. CASE REPORT: A 73-year-old man was admitted with severe epigastric pain and high fever. He had received choledocojejunostomy. Enhanced computed tomography showed a 76 mm, heterogeneous, gradual enhanced low-density mass in the caudate lobe and hyperdense fluid was detected around the mass. Based on the diagnosis of hemorrhage from a hypervascular malignant liver tumor, chemoembolization was conducted. Antibiotics (Meropenem) were administered for 2 weeks, and methylprednisolone (125 mg) was administered twice as a premedication for chemoembolization. After the 2nd chemoembolization, rapid tumor shrinkage was observed and the inflammatory changes gradually disappeared. The tumor was finally diagnosed as fibrohistiocytic type HIPT with an ultrasound-guided percutaneous tumor biopsy. The diameter of the liver tumor decreased to 15 mm and intra-abdominal hemorrhage disappeared in 3 months. CONCLUSION: Development of HIPT can be associated with intra-abdominal hemorrhage.


Assuntos
Granuloma de Células Plasmáticas/diagnóstico , Hemorragia/diagnóstico , Hepatopatias/diagnóstico , Idoso , Animais , Antibacterianos/administração & dosagem , Granuloma de Células Plasmáticas/diagnóstico por imagem , Granuloma de Células Plasmáticas/tratamento farmacológico , Granuloma de Células Plasmáticas/patologia , Hemorragia/tratamento farmacológico , Hemorragia/patologia , Humanos , Hepatopatias/diagnóstico por imagem , Hepatopatias/tratamento farmacológico , Hepatopatias/patologia , Masculino
16.
Pan Afr Med J ; 38: 142, 2021.
Artigo em Inglês | MEDLINE | ID: covidwho-1264677

RESUMO

Hemorrhagic manifestations during COVID-19 infections are increasingly described in the literature. We report the first case of spontaneous subcapsular hematoma of the liver revealing a COVID-19 infection in a 44-year-old woman with no underlying health condition history, a computerized tomography evaluation showed an aspect of lung ground-glass opacities, with moderate impairment estimated at about 20%. Reverse transcription-polymerase chain reaction confirmed the diagnosis of COVID-19 infection. During the COVID-19 pandemic, non-traumatic bleeding such as spontaneous hematomas in patients with no coagulation disorder could be a manifestation of COVID-19 infection.


Assuntos
COVID-19/diagnóstico , Hematoma/diagnóstico , Hepatopatias/diagnóstico , Adulto , COVID-19/complicações , Feminino , Hematoma/patologia , Hematoma/virologia , Humanos , Hepatopatias/patologia , Hepatopatias/virologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tomografia Computadorizada por Raios X
17.
Int J Mol Sci ; 22(9)2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33919123

RESUMO

In liver surgery, biliary obstruction can lead to secondary biliary cirrhosis, a life-threatening disease with liver transplantation as the only curative treatment option. Mesenchymal stromal cells (MSC) have been shown to improve liver function in both acute and chronic liver disease models. This study evaluated the effect of allogenic MSC transplantation in a large animal model of repeated biliary obstruction followed by partial hepatectomy. MSC transplantation supported the growth of regenerated liver tissue after 14 days (MSC group, n = 10: from 1087 ± 108 (0 h) to 1243 ± 92 mL (14 days); control group, n = 11: from 1080 ± 95 (0 h) to 1100 ± 105 mL (14 days), p = 0.016), with a lower volume fraction of hepatocytes in regenerated liver tissue compared to resected liver tissue (59.5 ± 10.2% vs. 70.2 ± 5.6%, p < 0.05). Volume fraction of connective tissue, blood vessels and bile vessels in regenerated liver tissue, serum levels of liver enzymes (AST, ALT, ALP and GGT) and liver metabolites (albumin, bilirubin, urea and creatinine), as well as plasma levels of IL-6, IL-8, TNF-α and TGF-ß, were not affected by MSC transplantation. In our novel, large animal (pig) model of repeated biliary obstruction followed by partial hepatectomy, MSC transplantation promoted growth of liver tissue without any effect on liver function. This study underscores the importance of translating results between small and large animal models as well as the careful translation of results from animal model into human medicine.


Assuntos
Colestase/complicações , Modelos Animais de Doenças , Hepatopatias/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Animais , Hepatopatias/etiologia , Hepatopatias/patologia , Células-Tronco Mesenquimais , Suínos
18.
Biomed Res Int ; 2021: 6612477, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33860040

RESUMO

Myeloid-derived suppressor cells (MDSCs) have attracted attention due to their important role in inflammation. Several studies have investigated the involvement of MDSCs in chronic liver disease. However, due to the difference of MDSC phenotypes, patient types, and sample sources among the studies, the results are inconsistent and controversial. We took advantage of a large well-defined cohort of 98 (24 patients with CHB, 18 with NAFLD, 13 with HCC, 16 with PBC, and 27 with AIH) patients with liver inflammation and 12 healthy controls to investigate the expression of MDSCs, and the relationships between the expression of hepatic MDSCs and the clinical characteristics were analyzed. We found that the expression of CD11b+CD33+ MDSCs is closely related to chronic liver disease and positively correlated with clinical parameters such as ALT, AST, and globulin. Ultimately, the present study suggests that hepatic CD11b+CD33+ MDSCs are increased in HCC and AIH and positively correlate with the liver stages of hepatitis activity and liver fibrosis stage.


Assuntos
Hepatopatias/patologia , Células Supressoras Mieloides/patologia , Adulto , Antígenos CD/metabolismo , Doença Crônica , Feminino , Humanos , Fígado/metabolismo , Fígado/patologia , Hepatopatias/genética , Masculino , Pessoa de Meia-Idade , Regulação para Cima/genética
19.
Int J Mol Sci ; 22(6)2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33803718

RESUMO

Platelets are tightly connected with the liver, as both their production and their clearance are mediated by the liver. Platelets, in return, participate in a variety of liver diseases, ranging from non-alcoholic fatty liver diseases, (viral) hepatitis, liver fibrosis and hepatocellular carcinoma to liver regeneration. Due to their versatile functions, which include (1) regulation of hemostasis, (2) fine-tuning of immune responses and (3) release of growth factors and cellular mediators, platelets quickly adapt to environmental changes and modulate disease development, leading to different layers of complexity. Depending on the (patho)physiological context, platelets exert both beneficial and detrimental functions. Understanding the precise mechanisms through which platelet function is regulated at different stages of liver diseases and how platelets interact with various resident and non-resident liver cells helps to draw a clear picture of platelet-related therapeutic interventions. Therefore, this review summarizes the current knowledge on platelets in acute and chronic liver diseases and aims to shed light on how the smallest cells in the circulatory system account for changes in the (patho)physiology of the second largest organ in the human body.


Assuntos
Plaquetas/patologia , Hepatopatias/patologia , Humanos , Fígado/patologia , Regeneração Hepática
20.
Int J Mol Sci ; 22(5)2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33807573

RESUMO

The prevalence of osteoporosis and sarcopenia is significantly higher in patients with liver disease than in those without liver disease and osteoporosis and sarcopenia negatively influence morbidity and mortality in liver disease, yet these musculoskeletal disorders are frequently overlooked in clinical practice for patients with chronic liver disease. The objective of this review is to provide a comprehensive understanding of the molecular mechanisms of musculoskeletal disorders accompanying the pathogenesis of liver disease. The increased bone resorption through the receptor activator of nuclear factor kappa (RANK)-RANK ligand (RANKL)-osteoprotegerin (OPG) system and upregulation of inflammatory cytokines and decreased bone formation through increased bilirubin and sclerostin and lower insulin-like growth factor-1 are important mechanisms for osteoporosis in patients with liver disease. Sarcopenia is associated with insulin resistance and obesity in non-alcoholic fatty liver disease, whereas hyperammonemia, low amount of branched chain amino acids, and hypogonadism contributes to sarcopenia in liver cirrhosis. The bidirectional crosstalk between muscle and bone through myostatin, irisin, ß-aminoisobutyric acid (BAIBA), osteocalcin, as well as the activation of the RANK and the Wnt/ß-catenin pathways are associated with osteosarcopenia. The increased understandings for these musculoskeletal disorders would be contributes to the development of effective therapies targeting the pathophysiological mechanism involved.


Assuntos
Hepatopatias/patologia , Doenças Musculoesqueléticas/patologia , Osteoporose/patologia , Sarcopenia/patologia , Animais , Doença Crônica , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...