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2.
Arq Bras Cir Dig ; 33(3): e1549, 2021.
Artigo em Inglês, Português | MEDLINE | ID: mdl-33470379

RESUMO

BACKGROUND: Strongly associated with obesity, non-alcoholic fatty liver disease is considered the hepatic manifestation of the metabolic syndrome. It presents as simple steatosis and steatohepatitis, which can progress to cirrhosis and its complications. Among the therapeutic alternatives is bariatric surgery. AIM: To compare the effect of the two most frequent bariatric procedures (sleeve and bypass) on liver disease regarding to epidemiological, demographic, clinical and laboratory parameters. METHODS: The results of intraoperative and 12 months after surgery liver biopsies were used. The NAFLD activity score (NAS) was used to assess and compare the stages of liver disease. RESULTS: Sixteen (66.7%) patients underwent Bypass procedure and eight (33.3%) Sleeve. It was observed that the variation in the NAFLD activity score was significantly greater in the Bypass group than in Sleeve (p=0.028) and there was a trend regarding the variation in fibrosis (p=0.054). CONCLUSION: Both surgical techniques were effective in improving the hepatic histology of most operated patients. When comparing sleeve and bypass groups, bypass showed better results, according to the NAS score.


Assuntos
Cirurgia Bariátrica/métodos , Derivação Gástrica/métodos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Obesidade Mórbida/cirurgia , Perda de Peso , Adulto , Biópsia , Feminino , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/cirurgia , Obesidade Mórbida/complicações , Fatores de Risco , Resultado do Tratamento
3.
Food Chem ; 340: 128169, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33007695

RESUMO

Polyphenols from cambuci (CBC) (Campomanesia phaea (O. Berg.)), a Brazilian native fruit, were investigated on therapeutic actions mitigating insulin resistance and hepatic steatosis in high-fat-sucrose diet (HFS) induced obese mice. For this, C57BL/6J mice fed with a obesogenic and diabetogenic HFS diet were administered with either water or two CBC doses (36 or 74 mg gallic acid equivalent (GAE)/kg body weight) by gavage from week 6 to week 14 (end-point) of HFS feeding. CBC reduced body weight gain, inflammation, hepatic steatosis, hyperglycemia, glucose intolerance, and insulin resistance in liver and skeletal muscle of obese mice, and such effects were associated with activation of Akt and AMPK in these tissues. In conclusion, polyphenols from CBC show important therapeutic actions ameliorating obesity-associated complications.


Assuntos
Resistência à Insulina , Myrtaceae/química , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Obesidade/complicações , Polifenóis/farmacologia , Animais , Dieta Hiperlipídica/efeitos adversos , Frutas/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/induzido quimicamente , Obesidade/metabolismo , Polifenóis/uso terapêutico
4.
Ann Pharmacother ; 55(1): 65-79, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32571083

RESUMO

OBJECTIVE: To evaluate glucagon-like peptide 1 receptor agonists (GLP-1 RAs), dipeptidyl-peptidase IV (DPP-4) inhibitors, and sodium-glucose cotransporter 2 (SGLT) inhibitors to treat nondiabetic and type 2 diabetes mellitus (T2DM) nonalcoholic fatty liver disease (NAFLD) as it relates to improvement in hepatosteatosis (HS) or steatohepatitis (SH). DATA SOURCES: MEDLINE and CINAHL were searched from inception through May 1, 2020. Search terms included nonalcoholic steatohepatitis, nonalcoholic fatty liver disease, fatty liver, dipeptidyl-peptidase IV inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose transporter 2 inhibitors. STUDY SELECTION AND DATA EXTRACTION: Full-text observational and randomized controlled studies in English were included. Patients diagnosed with NAFLD, treated with GLP-1 RAs, DPP-4 inhibitors, and SGLT2 inhibitors, with measures to evaluate HS or SH were evaluated. DATA SYNTHESIS: Eight GLP-1 RA trials were reviewed; 7 GLP-1 RA trials showed improvement in HS. Two studies demonstrated improvement in liver histology in patients with SH. Seven SGLT2 inhibitor studies were reviewed; 6 studies demonstrated improvements in NAFLD. Five studies showed improvements in HS, whereas 1 displayed improvement in liver histology in NASH. Six studies that included DPP-4 inhibitors were evaluated, and only 2 demonstrated improvement in NASH. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Based on evidence reviewed, GLP-1 RAs and SGLT2 inhibitors decreased HS and SH in NAFLD patients, whereas DPP-4 inhibitor therapy was not effective for patients with HS. CONCLUSIONS: Based on study data utilizing imaging studies and biopsy results, GLP-1 RAs or SGLT2 inhibitors can benefit NAFLD T2DM patients. Clinical trials with larger patient populations may augment these results.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Humanos , Hipoglicemiantes/administração & dosagem , Hepatopatia Gordurosa não Alcoólica/complicações , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
5.
Arq Gastroenterol ; 57(4): 471-476, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33331479

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver disease worldwide. Approximately 20% of individuals with NAFLD develop nonalcoholic steatohepatitis (NASH), which is associated with increased risk of cirrhosis, portal hypertension, and hepatocellular carcinoma. Intestinal microflora, including small intestinal bacterial overgrowth (SIBO), appear to play an important role in the pathogenesis of the disease, as demonstrated in several clinical and experimental studies, by altering intestinal permeability and allowing bacterial endotoxins to enter the circulation. OBJECTIVE: To determine the relationship between SIBO and endotoxin serum levels with clinical, laboratory, and histopathological aspects of NAFLD and the relationship between SIBO and endotoxin serum levels before and after antibiotic therapy. METHODS: Adult patients with a histological diagnosis of NAFLD, without cirrhosis were included. A comprehensive biochemistry panel, lactulose breath test (for diagnosis of SIBO), and serum endotoxin measurement (chromogenic LAL assay) were performed. SIBO was treated with metronidazole 250 mg q8h for 10 days and refractory cases were given ciprofloxacin 500 mg q12h for 10 days. RESULTS: Overall, 42 patients with a histopathological diagnosis of NAFLD were examined. The prevalence of SIBO was 26.2%. Comparison of demographic and biochemical parameters between patients with SIBO and those without SIBO revealed no statistically significant differences, except for use of proton pump inhibitors, which was significantly more frequent in patients with positive breath testing. The presence of SIBO was also associated with greater severity of hepatocellular ballooning on liver biopsy. Although the sample, as a whole, have elevated circulating endotoxin levels, we found no significant differences in this parameter between the groups with and without SIBO. Endotoxin values before and after antibiotic treatment did not differ, even on paired analysis, suggesting absence of any relationship between these factors. Serum endotoxin levels were inversely correlated with HDL levels, and directly correlated with triglyceride levels. CONCLUSION: Serum endotoxin levels did not differ between patients with and without SIBO, nor did these levels change after antibacterial therapy, virtually ruling out the possibility that elevated endotoxinemia in non-cirrhotic patients with NAFLD is associated with SIBO. Presence of SIBO was associated with greater severity of ballooning degeneration on liver biopsy, but not with a significantly higher prevalence of NASH. Additional studies are needed to evaluate the reproducibility and importance of this finding in patients with NAFLD and SIBO.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Adulto , Endotoxinas , Humanos , Intestino Delgado , Cirrose Hepática , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica/complicações , Reprodutibilidade dos Testes
6.
Medicine (Baltimore) ; 99(50): e22867, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327227

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has emerged as a major health problem worldwide; according to statistics, 10% to 25% of patients with NAFLD can progress to nonalcoholic steatohepatitis (NASH). A link between the composition and metabolites of intestinal microbiota and the development of NAFLD is becoming clearer. It is believed that microbiota factors are driving forces of hepatic steatosis and inflammation. The formulated food that contains prebiotics and dietary fiber may improve NAFLD by altering the intestinal flora and its metabolites. METHODS: The study plan to recruit adult patients (18-75 years, n = 120) with NAFLD, range of alanine aminotransferase is 1.5 to 5 times upper limit of normal (ULN) or liver biopsy is confirmed as NASH. Participants will be randomly allocated into 2 groups: formulated food (n = 80) and a placebo group (n = 40) for 24 weeks. Both groups will receive lifestyle and nutritional advice. The primary endpoint is a decrease in MRS-PDFF by more than 30% from baseline at 24 weeks. The secondary endpoints include the change of anthropometric, liver function, glycolipid metabolism, and systemic inflammation at 4, 12, and 24 weeks. In addition, we consider the changes in intestinal microbiota as an exploration to assess the abundance and diversity at 24 weeks. Weeks 24 to 36 are the follow-up period of drug withdrawal. DISCUSSION: This clinical trial will provide evidence of efficacy and safety of formulated food as a potential new therapeutic agent for NAFLD patients. TRIAL REGISTRATION: The trial is registered in the China Clinical Trial Center (ChiCTR1800016178).


Assuntos
Alimentos Formulados/efeitos adversos , Microbioma Gastrointestinal/fisiologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Adulto , Idoso , Alanina Transaminase/análise , Bactérias/metabolismo , Estudos de Casos e Controles , China/epidemiologia , Fígado Gorduroso/dietoterapia , Fígado Gorduroso/microbiologia , Feminino , Seguimentos , Alimentos Formulados/microbiologia , Alimentos Formulados/provisão & distribução , Humanos , Inflamação/dietoterapia , Inflamação/microbiologia , Metabolismo dos Lipídeos/fisiologia , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Hepatopatia Gordurosa não Alcoólica/patologia , Segurança , Resultado do Tratamento
7.
PLoS One ; 15(12): e0243846, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33315911

RESUMO

Hypertension is an important risk factor for nonalcoholic steatohepatitis. We have previously demonstrated that hypertensive rats fed a high fat and cholesterol (HFC) diet incurred a more severe hepatic inflammatory response and fibrosis. Here we investigated the role of hypertension in NASH by comparing HFC-induced hepatic fibrogenesis between spontaneously hypertensive rats (SHRs) and their normotensive Wistar Kyoto counterpart. Compared to the counterpart, the HFC diet led to stronger aggregation of CD68-positive macrophages in SHRs. HFC feeding also resulted in significantly higher upregulation of the fibrosis-related gene alpha-smooth muscle actin in SHR. The HFC diet induced higher overexpression of serum tissue inhibitor of metalloproteinase-1 (TIMP1) and greater suppression of matrix metalloproteinase-2 (MMP2):TIMP1, MMP8:TIMP1, and MMP9:TIMP1 ratios, as a proxy of the activities of these MMPs in SHR. Administration of the antihypertensive agent hydralazine to SHRs significantly ameliorated HFC-induced liver fibrosis; it suppressed the aggregation of CD68-positive macrophages and the upregulation of platelet-derived growth factor receptor beta, and collagen, type 1, alpha-1 chain. In conclusion, a hypertensive environment exacerbated the hepatic fibrogenetic effects of the HFC diet; while the effects were partially reversed by the antihypertensive agent hydralazine. Our data suggest that antihypertensive drugs hold promise for treating NASH exacerbated by hypertension.


Assuntos
Anti-Hipertensivos/uso terapêutico , Progressão da Doença , Matriz Extracelular/metabolismo , Hidralazina/uso terapêutico , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Colesterol na Dieta , Citocinas/sangue , Dieta Hiperlipídica , Regulação da Expressão Gênica/efeitos dos fármacos , Hidralazina/administração & dosagem , Hidralazina/farmacologia , Hipertensão/fisiopatologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Metaloproteinases da Matriz/sangue , Modelos Biológicos , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologia , Tamanho do Órgão/efeitos dos fármacos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Inibidor Tecidual de Metaloproteinase-1/sangue
8.
PLoS One ; 15(10): e0240400, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33031439

RESUMO

BACKGROUND & AIMS: Although metabolic risk factors are associated with more severe COVID-19, there is little evidence on outcomes in patients with non-alcoholic fatty liver disease (NAFLD). We here describe the clinical characteristics and outcomes of NAFLD patients in a cohort hospitalised for COVID-19. METHODS: This study included all consecutive patients admitted for COVID-19 between February and April 2020 at Imperial College Healthcare NHS Trust, with either imaging of the liver available dated within one year from the admission or a known diagnosis of NAFLD. Clinical data and early weaning score (EWS) were recorded. NAFLD diagnosis was based on imaging or past medical history and patients were stratified for Fibrosis-4 (FIB-4) index. Clinical endpoints were admission to intensive care unit (ICU)and in-hospital mortality. RESULTS: 561 patients were admitted. Overall, 193 patients were included in the study. Fifty nine patients (30%) died, 9 (5%) were still in hospital, and 125 (65%) were discharged. The NAFLD cohort (n = 61) was significantly younger (60 vs 70.5 years, p = 0.046) at presentation compared to the non-NAFLD (n = 132). NAFLD diagnosis was not associated with adverse outcomes. However, the NAFLD group had higher C reactive protein (CRP) (107 vs 91.2 mg/L, p = 0.05) compared to non-NAFLD(n = 132). Among NAFLD patients, male gender (p = 0.01), ferritin (p = 0.003) and EWS (p = 0.047) were associated with in-hospital mortality, while the presence of intermediate/high risk FIB-4 or liver cirrhosis was not. CONCLUSION: The presence of NAFLD per se was not associated with worse outcomes in patients hospitalised for COVID-19. Though NAFLD patients were younger on admission, disease stage was not associated with clinical outcomes. Yet, mortality was associated with gender and a pronounced inflammatory response in the NAFLD group.


Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Hepatopatia Gordurosa não Alcoólica/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Fatores Etários , Idoso , Betacoronavirus , Estudos de Coortes , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Feminino , Mortalidade Hospitalar , Humanos , Fígado/patologia , Londres/epidemiologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/mortalidade , Hepatopatia Gordurosa não Alcoólica/patologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Estudos Retrospectivos , Fatores Sexuais
9.
Rev Med Suisse ; 16(711): 1965-1969, 2020 Oct 21.
Artigo em Francês | MEDLINE | ID: mdl-33085251

RESUMO

Cirrhosis results from chronic liver disease and is associated with a high mortality. The most frequent causes for chronic liver disease include alcoholic liver disease, non-alcoholic fatty liver disease and viral hepatitis B and C. Bacterial infections often complicate decompensated cirrhosis. It is estimated that up to 35% of patients with decompensated cirrhosis have an infection at admission or during hospital stay. There are considerable consequences to these bacterial infections. Whilst evidence supports the use of prophylactic antibiotics, the emergence of multi-resistant bacteria is changing the spectrum of antibiotics that have to be used.


Assuntos
Infecções Bacterianas , Cirrose Hepática , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Bacterianas/complicações , Infecções Bacterianas/tratamento farmacológico , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Humanos , Cirrose Hepática/complicações , Hepatopatias Alcoólicas/complicações , Hepatopatia Gordurosa não Alcoólica/complicações
10.
Clín. investig. arterioscler. (Ed. impr.) ; 32(5): 200-205, sept.-oct. 2020. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-196743

RESUMO

ANTECEDENTES: La esteatosis hepática es un problema de salud pública de incidencia y prevalencia crecientes en nuestra sociedad. OBJETIVO: Determinar si la esteatosis hepática, medida mediante el Fatty Liver Index (FLI), se relaciona con el riesgo metabólico y vascular y, de ser así, identificar qué factor clínico-metabólico explica el mayor riesgo vascular de estos pacientes. MÉTODOS: Estudio transversal que incluye una muestra de 531 varones que acudieron a la unidad de chequeos de la Clínica Universitaria de Navarra. Se determinó el grado de esteatosis mediante el FLI. El riesgo metabólico fue evaluado mediante una escala basada en determinaciones de HDL, LDL, triglicéridos, glucemia, HOMA-IR, índice neutrófilo/linfocitario y presión sistólica; el riesgo vascular, mediante la presencia de placas ateromatosas en carótidas y/o femorales. La asociación dosis-respuesta entre el FLI y ambos riesgos se analizó mediante modelos no paramétricos (splines) y regresión logística. RESULTADOS: La muestra estudiada presenta una edad media de 52,70años, con el 49,3% de ellos presentando un FLI≥60, el 33,6% con síndrome metabólico y el 43,9% con placas ateromatosas en carótidas o femorales. La relación entre el FLI y el riesgo metabólico y vascular fue lineal (metabólico: valor de p no lineal=0,097; valor de p lineal <0,001; vascular: valor de p no lineal=1,000; valor de p lineal=0,028). Por cada 10unidades de incremento del FLI la odds de presentar placas de ateroma aumentaba en un 9,7% (OR=1,097; intervalo de confianza al 95%: 1,010-1,191). Al ajustar por trigliceridemia la asociación desaparecía (OR=1,001). CONCLUSIONES: Los pacientes con esteatosis hepática presentan un mayor riesgo metabólico y vascular. El mayor riesgo vascular está asociado con el nivel de triglicéridos. A nivel clínico, este estudio sugiere que estos pacientes podrían beneficiarse del tratamiento de la hipertrigliceridemia


BACKGROUND: Hepatic steatosis is a public health problem with increased incidence and prevalence. OBJECTIVE: To determine whether the liver steatosis, as measured by the Fatty Liver Index (FLI), is related to metabolic risk and vascular factors and, if so, to identify the clinical-metabolic factor that explains the higher vascular risk. METHODS: Cross-sectional study including a sample of 531 men who came to the University of Navarra Clinic Check-up Unit. The degree of steatosis was determined by the FLI. The metabolic risk was assessed using a scale based on determinations of HDL, LDL, triglycerides, blood glucose, HOMA-IR, neutrophil/lymphocyte index, and systolic blood pressure. The vascular risk was assessed by the presence of carotid and/or femoral atheromatous plaques. The dose-response association between FLI and both risks was analysed using non-parametric models (splines) and logistic regression. RESULTS: The sample studied had a mean age of 52.70years, with 49.3% having an FLI ≥60, as well as 33.6% with metabolic syndrome, and 43.9% with carotid and/or femoral atheromatous plaques. The relationship between FLI and metabolic risk and vascular was linear (metabolic: non-linear P=.097; linear P<.001; vascular: non-linear P=1.000; linear P=.028). For every 10 units of increase in FLI, the odds of presenting with atheroma plaques increased by 9.7% (OR=1.097; 95% confidence interval 1.010-1.191). When adjusting for triglyceridaemia, the association disappeared (OR=1.001). CONCLUSIONS: Patients with fatty liver disease had an increased metabolic and vascular risk. The increased vascular risk is associated with the triglyceride level. On a clinical level, this study suggests that these patients could benefit from treatment of hypertriglyceridaemia


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Hepatopatia Gordurosa não Alcoólica/complicações , Doenças Vasculares/etiologia , Fatores de Risco , Estudos Transversais , Hipertrigliceridemia/terapia , Triglicerídeos/análise , Indicadores Básicos de Saúde , Medição de Risco , Modelos Logísticos
12.
Scand J Immunol ; 92(5): e12971, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32892401

RESUMO

With an increase in sedentary lifestyle and dietary over nutrition, obesity has become one of the major public health problems worldwide and is a prevalent predisposing risk factor to non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease in Western developed countries. NAFLD represents a series of diseased states ranging from non-alcoholic fatty liver (NAFL) to steatohepatitis (NASH), which can lead to fibrosis and eventually to cirrhosis and hepatocellular carcinoma. Currently, the only effective treatment to cure end-stage liver disease is liver transplantation. Macrophages have been reported to play a crucial role in the progression of NAFLD, thereby are a potential target for therapy. In this review, we discuss the current knowledge on the role of macrophages and inflammatory signalling pathways associated with obesity and chronic liver inflammation, and their contribution to NAFLD development and progression.


Assuntos
Fígado Gorduroso/imunologia , Cirrose Hepática/imunologia , Macrófagos/imunologia , Hepatopatia Gordurosa não Alcoólica/imunologia , Obesidade/imunologia , Receptores Depuradores/imunologia , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/metabolismo , Progressão da Doença , Fígado Gorduroso/complicações , Fígado Gorduroso/metabolismo , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/metabolismo , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/metabolismo , Macrófagos/metabolismo , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/complicações , Obesidade/metabolismo , Receptores Depuradores/metabolismo
13.
Hepatol Int ; 14(5): 701-710, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32734407

RESUMO

BACKGROUND AND AIM: Cytokine storm has been reported in patients with coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. We examine the incidence of acute on chronic liver failure (ACLF) in COVID-19 patients with pre-existing compensated chronic liver disease (CLD). METHODS: From 20 Jan 2020 to 7 Feb 2020, we studied 140 consecutive COVID-19 patients admitted to either Fuyang Second People's Hospital (FYSPH), Anhui or the Fifth Medical Center of Chinese PLA General Hospital (PLAGH) in Beijing, China. Pre-existing CLD includes those with liver cirrhosis assessed by APRI/FIB-4 score and /or ultrasound; NAFLD as identified by either ultrasound or hepatic steatosis index with significant liver fibrosis and chronic hepatitis B (CHB) or hepatitis C (CHC) infection. The diagnosis, grading of severity and clinical management of COVID-19 patients complied to the guideline and clinical protocol issued by the China National Health Commission. All patients had liver function test at least twice weekly till discharge with full recovery or death. RESULTS: In total, 3 had liver cirrhosis, 6 patients had CHB, 13 had NAFLD with significant liver fibrosis (one also had CHB). On admission, none had liver decompensation. COVID-19 disease progression was significantly less frequent in non-CLD patients (10/118 8.5%) than CLD patients (13/22 59.1%, p < 0.001). One patient with CLD had acute-on-chronic liver failure (ACLF). CONCLUSION: Disease progression is significantly higher in those COVID-19 patients with CLD as compared to those with no CLD. ACLF can also occur in patient with pre-existing compensated CLD who had severe COVID-19.


Assuntos
Insuficiência Hepática Crônica Agudizada , Infecções por Coronavirus , Hepatite B Crônica , Cirrose Hepática , Hepatopatia Gordurosa não Alcoólica , Pandemias , Pneumonia Viral , Insuficiência Hepática Crônica Agudizada/diagnóstico , Insuficiência Hepática Crônica Agudizada/epidemiologia , Insuficiência Hepática Crônica Agudizada/etiologia , Betacoronavirus/isolamento & purificação , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Progressão da Doença , Feminino , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Humanos , Incidência , Fígado/diagnóstico por imagem , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Cirrose Hepática/etiologia , Testes de Função Hepática/métodos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Ultrassonografia/métodos
14.
Lancet Gastroenterol Hepatol ; 5(11): 996-1007, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32805205

RESUMO

BACKGROUND: The laxative drug lubiprostone improves intestinal permeability in healthy volunteers. We aimed to assess efficacy and safety of lubiprostone in patients with non-alcoholic fatty liver disease (NAFLD) with constipation via attenuation of intestinal permeability. METHODS: This randomised, double-blind, placebo-controlled, phase 2a study in Yokohama City University Hospital, Japan, recruited patients (aged 20-85 years) with NAFLD and constipation, alanine aminotransferase (ALT) at least 40 U/L, liver stiffness (≤6·7 kPa), and hepatic fat fraction at least 5·2% when assessed by MRI-proton density fat fraction. Eligible patients were randomly assigned (11:10:9) by a computer-based system and stratified by age and sex to receive 24 µg lubiprostone, 12 µg lubiprostone, or placebo, orally, once per day for 12 weeks. The primary endpoint was the absolute changes in ALT at 12 weeks. Efficacy analysis was done by intention to treat. Safety was assessed in all treated patients. This trial was registered with University Hospital Medical Information Network Clinical Trials Registry (UMIN000026635). FINDINGS: Between March 24, 2017, and April 3, 2018, we screened 288 patients, of whom 150 (52%) were randomly assigned to treatment: 55 patients were assigned to receive 24 µg lubiprostone, 50 to receive 12 µg lubiprostone, and 45 to receive placebo. A greater decrease in the absolute ALT levels from baseline to 12 weeks was seen in the 24 µg lubiprostone group (mean -13 U/L [SD 19]) than in the placebo group (1 U/L [24]; mean difference -15 U/L [95% CI -23 to -6], p=0·0007) and in the 12 µg lubiprostone group (-12 U/L [21]) than in the placebo group (mean difference -13 U/L [-22 to -5], p=0·0023). 18 (33%) of 55 patients in the 24 µg group had at least one adverse event, as did three (6%) of 47 patients in the 12 µg group and three (7%) of 43 in the placebo group. The most common adverse event was diarrhoea (17 [31%] of patients in the 24 µg group, three [6%] in the 12 µg group, none in the placebo group). No life-threatening events or treatment-related deaths occurred. INTERPRETATION: Lubiprostone was well tolerated and reduced the levels of liver enzymes in patients with NAFLD and constipation. Further studies are necessary to better define the efficacy and tolerability of lubiprostone in patients with NAFLD without constipation. FUNDING: Mylan EPD G.K.


Assuntos
Alanina Transaminase/sangue , Diarreia , Fígado , Lubiprostona , Hepatopatia Gordurosa não Alcoólica , Constipação Intestinal/tratamento farmacológico , Constipação Intestinal/etiologia , Diarreia/induzido quimicamente , Diarreia/diagnóstico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Monitoramento de Medicamentos/métodos , Técnicas de Imagem por Elasticidade/métodos , Feminino , Humanos , Laxantes/administração & dosagem , Laxantes/efeitos adversos , Fígado/diagnóstico por imagem , Fígado/metabolismo , Testes de Função Hepática , Lubiprostona/administração & dosagem , Lubiprostona/efeitos adversos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Resultado do Tratamento
15.
Chem Biol Interact ; 330: 109199, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32805210

RESUMO

Obesity is characterized by the deposition of excessive body fat, and is caused by energy imbalance, especially when consuming fat-rich diets. High fat diet (HFD)-associated obesity is greatly common in patients with non-alcoholic fatty liver disease (NAFLD) that is emerging as one of the most universal causes of liver disease worldwide, especially in Western countries. In spite of its high prevalence, only a small proportion of affected individuals will become inflamed, followed by fibrosis and chronic liver diseases, and most patients only show simple steatosis. In this case, the full comprehension of the mechanisms underlying the progression of NAFLD is of extreme significance; in spite of progress in this field, awareness on the development of NAFLD is still incomplete. Traditionally, liver steatosis is commonly connected with HFD, obesity, and insulin resistance (IR). Recently, various possible mechanisms have been put forward for liver damage, including endoplasmic reticulum stress, perturbation of autophagy, mitochondrial dysfunction, hepatocellular apoptosis, gut microbiota imbalance, dysregulation of microRNAs, and genetic/epigenetic risk factors, as well as an increase in inflammatory responses, among many others. Collectively, these proposed mechanisms allow for a variety of hits acting together on subjects to mediated NAFLD and will offer a more accurate explanation for progression of NAFLD. Therefore, this review summarizes the present information concerning NAFLD after HFD exposure, as well as discusses possible mechanisms through which it may arise.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/complicações
16.
PLoS One ; 15(8): e0236977, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822391

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is increasingly widespread with an overall global estimated prevalence of 25%. Type 2 diabetes Mellitus (T2DM) is a key contributor to NAFLD progression and predicts moderate-severe liver fibrosis and mortality. However, there is currently no uniform consensus on routine NAFLD screening among T2DM patients, and the risk factors of NAFLD and advanced fibrosis among T2DM patients remain to be clarified fully. AIM: We explored the prevalence, clinical spectrum, and risk factors of NAFLD and liver fibrosis among T2DM patients. METHODS: This is a cross-sectional study that enrolled subjects from a primary care clinic and a diabetes centre in Singapore. Subjects aged 21 to 70 years of all ethnic groups with an established T2DM diagnosis were included. Subjects with chronic liver diseases of other aetiologies were excluded. All subjects underwent transient elastography for hepatic steatosis and fibrosis assessment. Their demographics, anthropometric measurements and clinical parameters were collected. Statistical analysis was performed using STATA/SE16.0 software. RESULTS: Among 449 enrolled T2DM subjects, 436 with complete data and valid transient elastography results were analysed. Overall, 78.72% (344/436) of the T2DM subjects had NAFLD, of which 13.08% (45/344) had increased liver stiffness. Higher ALT level (OR = 1.08; 95% CI: 1.03-1.14; p = 0.004), obesity (BMI ≥ 27.5 kg/m2, OR = 2.64; 95% CI: 1.28-5.44; p = 0.008) and metabolic syndrome (OR = 4.36; 95% CI 1.40-13.58; p = 0.011) were independent factors associated with increased CAP (NAFLD). Higher AST level (OR = 1.06; 95% CI: 1.02-1.11; p = 0.008), CAP value (OR = 1.02; 95% CI: 1.00-1.03; p = 0.003), lower platelet count (OR = 0.99; 95% CI: 0.98-1.00; p = 0.009) and concomitant hypertension (OR = 4.56; 95% CI: 1.18-17.62; p = 0.028) were independent factors associated with increased liver stiffness. CONCLUSIONS: Our study demonstrated a considerably high prevalence of NAFLD among T2DM patients, with the proportion of advanced liver fibrosis among T2DM NAFLD patients much higher than the general population. Given that NAFLD is largely asymptomatic, increased awareness and vigilance for identifying NAFLD and increased liver stiffness among T2DM patients should be advocated.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Hepatopatia Gordurosa não Alcoólica/complicações , Adulto , Idoso , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Técnicas de Imagem por Elasticidade , Feminino , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/epidemiologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Prevalência , Fatores de Risco , Singapura/epidemiologia , Adulto Jovem
17.
Aliment Pharmacol Ther ; 52(4): 619-636, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32638417

RESUMO

BACKGROUND: Patients with non-alcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease, are at higher risk of cardiovascular disease (CVD) and associated mortality. Therefore, it is important to understand how new therapies for non-alcoholic steatohepatitis (NASH) may impact CVD risk factors in these patients. AIMS: To summarise the effects of drug therapies on lipid and lipoprotein levels in patients with NASH and provide insight into the potential mechanisms for the observed changes. METHODS: PubMed searches of the literature were performed and results were compiled. RESULTS: Recent clinical trials have highlighted the safety and efficacy of drug candidates for the treatment of NASH. Several agents have shown improvements in the histological features of NASH and liver function. Pioglitazone, a drug that is currently available for type 2 diabetes and may be useful for NASH, exhibits beneficial effects on lipids. However, agents such as farnesoid X receptor agonists, which are in development for NASH, may adversely affect circulating lipids and lipoproteins. CONCLUSIONS: NASH is a multi-system disease with a disproportionate CVD burden. Current and future drugs for NASH have had variable impact on the atherogenic risk profile. Potential co-administration of a statin may help mitigate the negative impact of some of these therapies on lipid and lipoprotein levels.


Assuntos
Aterosclerose/etiologia , Hipolipemiantes/uso terapêutico , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Aterosclerose/epidemiologia , Aterosclerose/prevenção & controle , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Desenvolvimento de Medicamentos/métodos , Desenvolvimento de Medicamentos/tendências , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/fisiologia , Testes de Função Hepática , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Pioglitazona/uso terapêutico , Fatores de Risco
18.
Am J Surg Pathol ; 44(10): 1406-1412, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32618599

RESUMO

Steatohepatitic hepatocellular carcinoma (SH-HCC) is a variant of hepatocellular carcinoma (HCC) with established association with nonalcoholic steatohepatitis (NASH), while its association with alcoholic steatohepatitis (ASH) is unclear. We studied 2 cohorts of patients who underwent resection for HCC in the setting of steatohepatitis. In our Mount Sinai (New York) cohort, we found SH-HCC in 17/24 (71%) patients with NASH and in 14/19 (74%) patients with ASH, while SH-HCC was the predominant tumor morphology in 12/24 (50%) in the NASH group and 9/19 (47%) in the ASH group. Upon review, 12/19 patients diagnosed with ASH also had diabetes and/or a body mass index >30. When these patients were removed, we still found similar rates of SH-HCC (6/7 [86%] showed SH-HCC, while SH-HCC was predominant in 3/7 [43%]. Interestingly, glycogenated hepatocyte nuclei were seen in the nontumor liver in 4/7 (57%) of these cases. In our Japan cohort, we also found similar rates of SH-HCC in NASH and ASH patients with HCC, 15/58 (26%), and 16/45 (36%), respectively. We determined molecular subclassification of tumors from the Japan cohort and found no difference in the distribution of S1, S2 and S3 subclasses among the ASH and NASH groups, though, among cases of SH-HCC, there was a trend toward an association of ASH with S1 (P=0.054) and NASH with S3 (P=0.052). Our study shows that SH-HCC is common in both ASH and NASH and that both underlying liver diseases produce tumors with similar molecular profiles, though different pathways may underlie the development of SH-HCC in ASH versus NASH.


Assuntos
Carcinoma Hepatocelular/patologia , Fígado Gorduroso Alcoólico/complicações , Neoplasias Hepáticas/patologia , Hepatopatia Gordurosa não Alcoólica/complicações , Idoso , Carcinoma Hepatocelular/etiologia , Estudos de Coortes , Feminino , Humanos , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade
19.
Arch Biochem Biophys ; 690: 108505, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32679195

RESUMO

Obesity has major adverse consequences on human health contributing to the development of, among others, insulin resistance and type 2 diabetes, cardiovascular disease, non-alcoholic fatty liver disease, altered behavior and cognition, and cancer. Changes in dietary habits and lifestyle could contribute to mitigate the development and/or progression of these pathologies. This review will discuss current evidence on the beneficial actions of the flavan-3-ol (-)-epicatechin (EC) on obesity-associated comorbidities. These benefits can be in part explained through EC's capacity to mitigate several common events underlying the development of these pathologies, including: i) high circulating levels of glucose, lipids and endotoxins; ii) chronic systemic inflammation; iii) tissue endoplasmic reticulum and oxidative stress; iv) insulin resistance; v) mitochondria dysfunction and vi) dysbiosis. The currently known underlying mechanisms and cellular targets of EC's beneficial effects are discussed. While, there is limited evidence from human studies supplementing with pure EC, other studies involving cocoa supplementation in humans, pure EC in rodents and in vitro studies, support a potential beneficial action of EC on obesity-associated comorbidities. This evidence also stresses the need of further research in the field, which would contribute to the development of human dietary strategies to mitigate the adverse consequences of obesity.


Assuntos
Catequina/farmacologia , Obesidade/tratamento farmacológico , Animais , Glicemia/efeitos dos fármacos , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/tratamento farmacológico , Comorbidade , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Disbiose/metabolismo , Dislipidemias/metabolismo , Retículo Endoplasmático/metabolismo , Endotoxinas/metabolismo , Flavonoides/farmacologia , Humanos , Inflamação/metabolismo , Resistência à Insulina , Metabolismo dos Lipídeos , Transtornos Mentais/complicações , Transtornos Mentais/tratamento farmacológico , Mitocôndrias/metabolismo , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Estresse Oxidativo
20.
J Pediatr ; 223: 93-99.e2, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32711755

RESUMO

OBJECTIVE: To investigate the association between muscle mass and liver disease severity in pediatric patients with non-alcoholic fatty liver disease (NAFLD). STUDY DESIGN: This was a retrospective study of patients aged <20 years followed from 2009 to 2018. Muscle mass was estimated in all patients by measuring magnetic resonance imaging-based total psoas muscle surface area (tPMSA) and correcting for height (tPMSA index = tPMSA/height2). Two cohorts were studied, one with histological confirmation of NAFLD (n = 100) and the other with magnetic resonance imaging (MRI) evidence of hepatic steatosis (n = 236). Histology was scored using Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) criteria. MRI-measured proton density fat fraction (PDFF) and liver stiffness were collected. Demographic, clinical, and socioeconomic status (using a validated Community Deprivation Index [CDI]) were assessed as covariates. Univariate regression analyses, followed by multivariable regression analyses, were used to determine the relationships between tPMSA index and NAS, MRI-PDFF, and liver stiffness, adjusting for clinical, demographic, and CDI variables. RESULTS: In the multivariable regression analyses, higher steatosis score was associated with a lower tPMSA index (OR, 0.73; 95% CI, 0.56-0.96) and younger age (OR, 0.84; 95% CI, 0.73-0.97). Liver PDFF was also significantly associated with the tPMSA index (P = .029), sex (P = .019), and CDI (P = .005). In contrast, liver stiffness was not associated with tPMSA in multivariable analyses. CONCLUSIONS: tPMSA index was independently associated with both imaging and histological features of hepatic steatosis severity in children. Future studies should directly explore the presence and directionality of causative links between muscle mass and steatosis, as well as whether interventions that enhance muscle mass can reduce disease severity in children with NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica/patologia , Músculos Psoas/patologia , Sarcopenia/diagnóstico , Adolescente , Adulto , Criança , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Músculos Psoas/diagnóstico por imagem , Estudos Retrospectivos , Sarcopenia/etiologia , Sarcopenia/patologia , Índice de Gravidade de Doença , Adulto Jovem
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