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1.
Am J Physiol Gastrointest Liver Physiol ; 318(3): G410-G418, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31905026

RESUMO

Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are common causes of chronic liver disease. The overlap between ALD and NAFLD suggests the existence of metabolic steatohepatitis. Development of in vivo models that reflect various aspects of human steatohepatitis is essential for drug discovery. We aimed to characterize several models of steatohepatitis (SH) and to investigate whether the pathology could be modulated. Sprague-Dawley rats were fed a high-fat diet (HFD) for 9 wk, followed by either a high-fat, high-cholesterol and cholate diet (HFC) or a HFC diet containing 13% trans fat (HFC-TF). A subset received 15% ethanol-water twice a week for 12 wk. Serum triglycerides, cholesterol, LDL, HDL, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and rodent NH2-terminal propeptide of type III collagen (rPRO-C3) were assessed. The liver was weighed and evaluated using modified Nonalcoholic Steatohepatitis Clinical Research Network histological score system criteria. All diets induced hepatomegaly, but only HFC-TF increased the size of visceral adipose tissue. Trans fat augmented HFC-induced dyslipidemia, and cholesterol was higher and HDL was lower in the HFC-TF groups. Alcohol lowered triglycerides in both dietary groups. HFC elevated ALT and AST, which were lowered by trans fat. All diets induced histological SH, addition of trans fat induced more steatosis but less inflammation. Inclusion of alcohol augmented the HFC-induced inflammation. All diets induced mild fibrosis. Inclusion of trans fat and alcohol significantly increased rPRO-C3. The addition of trans fat reduced the HFC-induced inflammation but augmented steatosis and dyslipidemia. Inclusion of alcohol induced a more inflammatory and fibrogenic phenotype.NEW & NOTEWORTHY Alcoholic liver disease and nonalcoholic liver disease share significant overlap, which suggests the existence of metabolic steatohepatitis. Trans fat has been implicated in steatohepatitis development. Here, we show that the addition of trans fat to an atherogenic diet results in a more steatotic but less inflammatory phenotype, whereas the addition of alcohol to an atherogenic diet augments the inflammatory and fibrogenic properties of the diet.


Assuntos
Bebedeira/complicações , Dieta Aterogênica , Fígado Gorduroso Alcoólico/etiologia , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Ácidos Graxos Trans , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Modelos Animais de Doenças , Dislipidemias/etiologia , Dislipidemias/metabolismo , Dislipidemias/patologia , Fígado Gorduroso Alcoólico/metabolismo , Fígado Gorduroso Alcoólico/patologia , Hepatomegalia/etiologia , Hepatomegalia/metabolismo , Hepatomegalia/patologia , Metabolismo dos Lipídeos , Fígado/metabolismo , Cirrose Hepática Alcoólica/etiologia , Cirrose Hepática Alcoólica/metabolismo , Cirrose Hepática Alcoólica/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/patologia , Estresse Oxidativo , Fragmentos de Peptídeos/metabolismo , Pró-Colágeno/metabolismo , Ratos Sprague-Dawley
3.
J Nepal Health Res Counc ; 17(3): 357-361, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31735932

RESUMO

BACKGROUND: The clinical picture in cirrhosis is dominated by the classical complications such as ascites, bleeding varices, portal hypertension and encephalopathy. Cardiac dysfunction in patients with cirrhosis, which contributes significantly to the morbidity and, mortality though prevalent, is less studied and not widely recognized entity since it is largely asymptomatic at rest, with overt heart failure seen mainly during pharmacological stress, transjugular intrahepatic portosystemic shunt, liver transplantation. METHODS: It is a cross sectional study done on patients admitted in wards or attending to outpatient department of Liver unit, Bir Hospital, between May 2015 to May 2016. Diagnosis of cirrhosis was based on clinical examination, lab parameters, ultrasound examination, endoscopy and/or liver biopsy. Cirrhotic patients after assessing the exclusion criteria were recruited for the study. Child Pugh and model for end stage liver disease scores were calculated to assess the liver function. Cardiac function was evaluated by resting pulse, mean arterial pressure, electrocardiography, and 2 dimensional echocardiography. RESULTS: Diastolic dysfunction was seen in 61.9%(48) and was more common in alcoholic group (63.2% Vs 58.6%). Systolic dysfunction was seen in 6.6% of alcoholic patients only. 51.4% had cirrhotic cardiomyopathy according to the criteria (proposed by World congress of gastroenterology in 2005). Prolonged QTc of >0.44 seconds was noted in 79%, mainly in child pugh C, with model for end stage liver disease score >10. CONCLUSIONS: Cardiac dysfunction is prevalent with sizeable number of patients with cirrhosis especially in the form of diastolic dysfunction independent of etiology. QTc prolongation might be an early indicator of cardiac dysfunction and is directly correlated with child pugh and model for end stage liver disease scores.


Assuntos
Cardiopatias/etiologia , Cirrose Hepática/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/etiologia , Estudos Transversais , Ecocardiografia , Feminino , Cardiopatias/diagnóstico por imagem , Cardiopatias/patologia , Humanos , Cirrose Hepática/patologia , Cirrose Hepática Alcoólica/complicações , Cirrose Hepática Alcoólica/patologia , Masculino , Pessoa de Meia-Idade , Nepal , Adulto Jovem
4.
Int. j. morphol ; 37(3): 872-876, Sept. 2019. graf
Artigo em Espanhol | LILACS | ID: biblio-1012368

RESUMO

Miguel Ángel Buonarroti (1475 - 1564) es considerando uno de los más grandes artistas de la historia. Estudió en detalle la anatomía humana a través de la disección de cadáveres, práctica hasta entonces relegada por motivos religiosos. Desde que en el año 1990 el médico Frank Lynn Meshberger publicara su interpretación del fresco "La Creación de Adán" basada en la neuroanatomía, en donde comparaba la imagen de Dios con la de una sección sagital del cerebro humano, muchos autores han encontrado diversas referencias anatómicas ocultas en la obra de Miguel Ángel. En el presente trabajo exponemos el hallazgo de una inédita lección de anatomía hepática oculta en el fresco La Embriaguez de Noé de la Capilla Sixtina.


Michelangelo Buonarroti (1475 - 1564) is considered one of the greatest artists in history. He studied in detail the human anatomy through corpses dissection, practice until then relegated for religious reasons. Since the physician Frank Lynn Meshberger published in 1990 his interpretation of the fresco "The Creation of Adam" based on neuroanatomy, where he compared the image of God with a sagittal section of the human brain, many authors have found various hidden anatomical references in the work of Michelangelo. In the present paper we expose the finding of a hidden lesson on liver anatomy in the fresco The Drunkenness of Noah of the Sistine Chapel.


Assuntos
Humanos , História do Século XVI , Anatomia/história , Cirrose Hepática Alcoólica/patologia , Medicina nas Artes/história , Intoxicação Alcoólica/patologia
5.
Int J Mol Sci ; 20(14)2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340446

RESUMO

Alcoholic liver disease (ALD) is a highly prevalent spectrum of pathologies caused by alcohol overconsumption. Morbidity and mortality related to ALD are increasing worldwide, thereby demanding strategies for early diagnosis and detection of ALD predisposition. A potential candidate as a marker for ALD susceptibility is the transcription factor nuclear factor erythroid-related factor 2 (Nrf2), codified by the nuclear factor erythroid 2-related factor 2 gene (NFE2L2). Nrf2 regulates expression of proteins that protect against oxidative stress and inflammation caused by alcohol overconsumption. Here, we assessed genetic variants of NFE2L2 for association with ALD. Specimens from patients diagnosed with cirrhosis caused by ALD were genotyped for three NFE2L2 single nucleotide polymorphisms (SNP) (SNPs: rs35652124, rs4893819, and rs6721961). Hematoxylin & eosin and immunohistochemistry were performed to determine the inflammatory score and Nrf2 expression, respectively. SNPs rs4893819 and rs6721961 were not specifically associated with ALD, but analysis of SNP rs35652124 suggested that this polymorphism predisposes to ALD. Furthermore, SNP rs35652124 was associated with a lower level of Nrf2 expression. Moreover, liver samples from ALD patients with this polymorphism displayed more severe inflammatory activity. Together, these findings provide evidence that the SNP rs35652124 variation in the Nrf2-encoding gene NFE2L2 is a potential genetic marker for susceptibility to ALD.


Assuntos
Predisposição Genética para Doença , Cirrose Hepática Alcoólica/genética , Fator 2 Relacionado a NF-E2/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Adulto , Estudos de Casos e Controles , Etanol/farmacologia , Feminino , Expressão Gênica , Hepacivirus/crescimento & desenvolvimento , Hepacivirus/patogenicidade , Hepatite C/patologia , Hepatite C/virologia , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática Alcoólica/metabolismo , Cirrose Hepática Alcoólica/patologia , Cirrose Hepática Alcoólica/cirurgia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo
6.
Int Immunopharmacol ; 75: 105759, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31325729

RESUMO

This study aimed to investigate the effect and underlying mechanism of Methyl helicterilate from Helicteres angustifolia (MHHA) on alcohol-induced hepatic fibrosis. The results showed that MHHA treatment markedly alleviated alcohol-induced liver injury and notably reduced collagen deposition in liver tissue. It significantly enhanced the activity of alcohol dehydrogenase and aldehyde dehydrogenase. Moreover, MHHA treatment markedly decreased the content of inflammatory cytokines, alleviated collagen accumulation, and inhibited the expression of TGF-ß1 and Smad2/3 in liver tissue. The experiments in cells showed that MHHA significantly inhibited HSC activation by blocking TGF-ß1/Smads signaling pathway. Additionally, it notably induced HSC apoptosis by modulating the mitochondria-dependent pathway. The present study demonstrates that MHHA treatment significantly ameliorates alcoholic hepatic fibrosis and the underlying mechanism may be ascribed to the inhibition of the TGF-ß1/Smads pathway and regulation of the mitochondria-mediated apoptotic pathway.


Assuntos
Cirrose Hepática Alcoólica/tratamento farmacológico , Proteína Smad2/imunologia , Proteína Smad3/imunologia , Fator de Crescimento Transformador beta1/imunologia , Triterpenos/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Colágeno/metabolismo , Células Estreladas do Fígado/efeitos dos fármacos , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/patologia , Cirrose Hepática Alcoólica/imunologia , Cirrose Hepática Alcoólica/metabolismo , Cirrose Hepática Alcoólica/patologia , Masculino , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Triterpenos/farmacologia
7.
Gastroenterology ; 157(5): 1352-1367.e13, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31362006

RESUMO

BACKGROUND & AIMS: Activation of TGFB (transforming growth factor ß) promotes liver fibrosis by activating hepatic stellate cells (HSCs), but the mechanisms of TGFB activation are not clear. We investigated the role of ECM1 (extracellular matrix protein 1), which interacts with extracellular and structural proteins, in TGFB activation in mouse livers. METHODS: We performed studies with C57BL/6J mice (controls), ECM1-knockout (ECM1-KO) mice, and mice with hepatocyte-specific knockout of EMC1 (ECM1Δhep). ECM1 or soluble TGFBR2 (TGFB receptor 2) were expressed in livers of mice after injection of an adeno-associated virus vector. Liver fibrosis was induced by carbon tetrachloride (CCl4) administration. Livers were collected from mice and analyzed by histology, immunohistochemistry, in situ hybridization, and immunofluorescence analyses. Hepatocytes and HSCs were isolated from livers of mice and incubated with ECM1; production of cytokines and activation of reporter genes were quantified. Liver tissues from patients with viral or alcohol-induced hepatitis (with different stages of fibrosis) and individuals with healthy livers were analyzed by immunohistochemistry and in situ hybridization. RESULTS: ECM1-KO mice spontaneously developed liver fibrosis and died by 2 months of age without significant hepatocyte damage or inflammation. In liver tissues of mice, we found that ECM1 stabilized extracellular matrix-deposited TGFB in its inactive form by interacting with αv integrins to prevent activation of HSCs. In liver tissues from patients and in mice with CCl4-induced liver fibrosis, we found an inverse correlation between level of ECM1 and severity of fibrosis. CCl4-induced liver fibrosis was accelerated in ECM1Δhep mice compared with control mice. Hepatocytes produced the highest levels of ECM1 in livers of mice. Ectopic expression of ECM1 or soluble TGFBR2 in liver prevented fibrogenesis in ECM1-KO mice and prolonged their survival. Ectopic expression of ECM1 in liver also reduced the severity of CCl4-induced fibrosis in mice. CONCLUSIONS: ECM1, produced by hepatocytes, inhibits activation of TGFB and its activation of HSCs to prevent fibrogenesis in mouse liver. Strategies to increase levels of ECM1 in liver might be developed for treatment of fibrosis.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Proteínas da Matriz Extracelular/metabolismo , Células Estreladas do Fígado/metabolismo , Cirrose Hepática Experimental/prevenção & controle , Fígado/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Animais , Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Proteínas da Matriz Extracelular/deficiência , Proteínas da Matriz Extracelular/genética , Células Estreladas do Fígado/patologia , Hepatite Alcoólica/metabolismo , Hepatite Alcoólica/patologia , Hepatite Viral Humana/metabolismo , Hepatite Viral Humana/patologia , Humanos , Fígado/patologia , Cirrose Hepática Alcoólica/metabolismo , Cirrose Hepática Alcoólica/patologia , Cirrose Hepática Experimental/genética , Cirrose Hepática Experimental/metabolismo , Cirrose Hepática Experimental/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de Sinais
8.
Biomed Res Int ; 2019: 3646975, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31192254

RESUMO

The aim of this study was to evaluate the diagnostic values of noninvasive indirect markers of liver fibrosis: APRI, GAPRI, Forns, FIB-4, Age-Platelet, and Hepascore in alcoholics. Blood samples were collected from a randomized group of 142 alcohol-dependent patients. The diagnosis of dependency was made according to the ICD-10 WHO criteria. The values of noninvasive markers were calculated with specific algorithms. The fibrosis stage was evaluated on the basis of FibroTest. The values of APRI, Forns, FIB-4, GAPRI, AP, and Hepascore differ between various stages of liver fibrosis. Patients with fibrosis stage F0 present lower values of APRI, Forns, FIB-4, GAPRI, and Hepascore in comparison to the patients with stages F1 and F0-F1. Patients with fibrosis stages < F2 have lower values of all noninvasive markers than patients with stages ≥F2. Patients with fibrosis stages ≥F2 but

Assuntos
Alcoolismo/sangue , Cirrose Hepática Alcoólica/sangue , Adulto , Alcoolismo/patologia , Biomarcadores/sangue , Feminino , Humanos , Cirrose Hepática Alcoólica/patologia , Masculino , Pessoa de Meia-Idade
9.
Ann Agric Environ Med ; 26(1): 143-147, 2019 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-30922045

RESUMO

INTRODUCTION: In Poland, an increasing number of patients are hospitalized due to liver diseases. One of the common liver diseases is cirrhosis, which can be caused by alcohol, viral hepatitis, autoimmune processes and metabolic diseases. MATERIAL AND METHODS: The study included 99 patients with alcoholic cirrhosis from the Lublin region of Eastern Poland. The control group consisted of 20 healthy individuals without liver disease who did not abuse alcohol. The concentrations of serum kallistatin and chemerin were determined using ELISA kits. OBJECTIVE: The aim of the study is to evaluate serum levels of kallistatin and chemerin in patients with different stages of alcoholic liver cirrhosis. RESULTS: The highest chemerin level was found in the control group - 182.6±80.4 ng/ml. In other stages of liver cirrhosis, the following levels were observed: 175.7±62.7 ng/ml in Child-Pugh stage A (Ch-P A), 150.2±59.7 ng/ml in Ch-P B and 110.3±73.6 ng/ml in Ch-P C. Significant differences in chemerin levels between controls and Ch-P C patients (p=0.01), as well as between the Ch-P A patients and Ch-P C patients (p=0.02), were demonstrated. The highest kallistatin level was demonstrated in the control group - 8.2±3.5 µg/ml. In other stages of liver cirrhosis, the following concentrations were found: 7.2±27 µg/ml in Ch-P A, 4.4±2.2 µg/ml in Ch-P B and 3.5±1.9 µg/ml in Ch-P C. Statistically significant differences were observed between controls and Ch-P B patients (p<0.001), controls and Ch-P C patients (p<0.001), Ch-P A and Ch-P B patients (p=0.01), as well as Ch-P A and Ch-P C patients (<0.001). CONCLUSIONS: The levels of chemerin and kallistatin decrease with progression of liver damage during alcoholic liver cirrhosis. The impairment of its synthetic function leads to reductions in levels of the adipokines studied.


Assuntos
Quimiocinas/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Cirrose Hepática Alcoólica/sangue , Serpinas/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Cirrose Hepática Alcoólica/patologia , Masculino , Pessoa de Meia-Idade , Polônia , Índice de Gravidade de Doença
10.
J Cancer Res Ther ; 15(1): 255-257, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30880788

RESUMO

This case report demonstrates successful concurrent chemoradiotherapy for esophageal cancer without severe adverse events in a patient with cirrhotic disease. A 63-year-old Japanese male with alcoholic liver cirrhosis was referred to our hospital for treatment of superficial esophageal cancer. Endoscopic submucosal dissection was performed and the patient was diagnosed as having squamous cell carcinoma of the esophagus that was pathologically staged as pT1bN0M0. When a superficial tumor involves the submucosa, esophagectomy is usually recommended. However, the patient was at high risk of perioperative morbidity and mortality because of impaired liver function. As an alternative to esophagectomy, the patient received concurrent chemoradiotherapy, comprising nedaplatin 64 mg/m2 on days 1 and 34 and S-1 80 mg/body orally on days 1-14 and 34-47 with concurrent radiotherapy of 50 Gy in daily fractions of 2 Gy. He has shown no signs of recurrence in the 30 months since his treatment.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Cirrose Hepática Alcoólica/patologia , Quimiorradioterapia/métodos , Progressão da Doença , Ressecção Endoscópica de Mucosa , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/complicações , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Esofagectomia , Esofagoscopia , Humanos , Cirrose Hepática Alcoólica/complicações , Cirrose Hepática Alcoólica/diagnóstico , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/uso terapêutico , Planejamento da Radioterapia Assistida por Computador , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Resultado do Tratamento
11.
Osteoporos Int ; 30(6): 1195-1204, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30788527

RESUMO

Liver cirrhosis leads to bone loss. To date, information on bone quality (three-dimensional microarchitecture) and, thus, bone strength is scarce. We observed decreased bone quality at both assessed sites, independent of disease severity. Therefore, all patients should undergo early-stage screening for osteoporosis. INTRODUCTION: Recent studies found low bone mineral density in cirrhosis, but data on bone microstructure are scarce. This study assessed weight-bearing and non-weight-bearing bones in patients with cirrhosis and healthy controls. The primary objective was to evaluate trabecular and cortical microarchitecture. METHODS: This was a single-center study in patients with recently diagnosed hepatic cirrhosis. Thirty-two patients and 32 controls participated in this study. After determining the type of cirrhosis, the parameters of bone microarchitecture were assessed by high-resolution peripheral quantitative computed tomography. RESULTS: Both cortical and trabecular microarchitectures showed significant alterations. At the radius, trabecular bone volume fraction was 17% lower (corrected p = 0.028), and, at the tibia, differences were slightly more pronounced. Trabecular bone volume fraction was 19% lower (p = 0.024), cortical bone mineral density 7% (p = 0.007), and cortical thickness 28% (p = 0.001), while cortical porosity was 32% higher (p = 0.023), compared to controls. Areal bone mineral density was lower (lumbar spine - 13%, total hip - 11%, total body - 9%, radius - 17%, and calcaneus - 26%). There was no correlation between disease severity and microarchitecture. Areal bone mineral density (aBMD) measured by dual-energy X-ray absorptiometry (DXA) correlated well with parameters of cortical and trabecular microarchitecture. CONCLUSIONS: Hepatic cirrhosis deteriorates both trabecular and cortical microarchitecture, regardless of disease severity. Areal bone mineral density is diminished at all sites as a sign of generalized affection. In patients with hepatic cirrhosis, regardless of its origin or disease severity, aBMD measurements are an appropriate tool for osteologic screening.


Assuntos
Remodelação Óssea/fisiologia , Cirrose Hepática/patologia , Cirrose Hepática/fisiopatologia , Rádio (Anatomia)/patologia , Tíbia/patologia , Idoso , Biomarcadores/sangue , Densidade Óssea , Osso Esponjoso/diagnóstico por imagem , Osso Esponjoso/patologia , Estudos de Casos e Controles , Osso Cortical/diagnóstico por imagem , Osso Cortical/patologia , Feminino , Humanos , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática Alcoólica/diagnóstico por imagem , Cirrose Hepática Alcoólica/patologia , Cirrose Hepática Alcoólica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Porosidade , Rádio (Anatomia)/diagnóstico por imagem , Tíbia/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Suporte de Carga/fisiologia
12.
Clin Liver Dis ; 23(1): 11-23, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30454825

RESUMO

Excessive alcohol consumption can lead to a spectrum of liver histopathology, including steatosis, steatohepatitis, foamy degeneration, fatty liver with cholestasis, and cirrhosis. Although variability in sampling and pathologist interpretation are of some concern, liver biopsy remains the gold standard for distinguishing between steatohepatitis and noninflammatory histologic patterns of injury that can also cause the clinical syndrome of alcohol-related hepatitis. Liver biopsy is not routinely recommended to ascertain a diagnosis of alcohol-related liver disease in patients with an uncertain alcohol history, because the histologic features of alcohol-related liver diseases can be found in other diseases, including nonalcoholic steatohepatitis and drug-induced liver injury.


Assuntos
Hepatopatias Alcoólicas/patologia , Fígado/patologia , Biópsia , Colestase/patologia , Fígado Gorduroso Alcoólico/patologia , Hepatite Alcoólica/patologia , Humanos , Cirrose Hepática Alcoólica/patologia
13.
Liver Int ; 39(1): 168-176, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30188604

RESUMO

BACKGROUND & AIMS: Familial aggregation of metabolic traits in NAFLD is well documented. However, relevance of these traits in alcoholic cirrhosis is not well studied. We aimed to explore the association of family history of metabolic traits with age at diagnosis, severity and complications of alcoholic cirrhosis. METHODS: In a cross-sectional study, all consecutive patients with alcoholic cirrhosis presenting to our tertiary care centre were included. Family and personal history, demographic characteristics, medical history, anthropometric measurements and laboratory data were recorded. The amount and duration of alcohol consumption were also carefully recorded. RESULTS: Out of 1084 alcoholic cirrhotics (age 48.5 ± 10.1 years, all males), family history for metabolic traits was documented in 688 (63.5%) patients. These patients had younger age at diagnosis, increased incidence of jaundice, ascites, variceal bleed and hepatic encephalopathy with consequently higher MELD and CTP score. These patients developed cirrhosis despite shorter median duration (13 years, IQR 7-20 vs 21, IQR 18-25) and lesser amount of alcohol consumption (74 g/d, IQR 24-96 vs 144, IQR 100-148). Patients with both family and personal history of metabolic traits had a higher risk by 3.3 times (95% CI 2.2-4.8) of an early age at diagnosis, 13.2 times (95% CI 8.7-20.1) of progression to cirrhosis with lesser amount of alcohol consumption and 4.6 times (95% CI 3.1-6.9) with lesser duration of alcohol consumption. CONCLUSIONS: Positive family and personal history of metabolic traits predispose to alcoholic cirrhosis with an earlier age at onset and more severity despite lesser exposure to alcohol.


Assuntos
Cirrose Hepática Alcoólica/complicações , Anamnese , Síndrome Metabólica/complicações , Hepatopatia Gordurosa não Alcoólica/complicações , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Ascite/etiologia , Estudos Transversais , Progressão da Doença , Feminino , Predisposição Genética para Doença , Encefalopatia Hepática/complicações , Humanos , Cirrose Hepática Alcoólica/diagnóstico , Cirrose Hepática Alcoólica/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Índice de Gravidade de Doença , Centros de Atenção Terciária
14.
Gut ; 68(6): 1099-1107, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30068662

RESUMO

OBJECTIVE: Homozygous alpha1-antitrypsin (AAT) deficiency increases the risk for developing cirrhosis, whereas the relevance of heterozygous carriage remains unclear. Hence, we evaluated the impact of the two most relevant AAT variants ('Pi*Z' and 'Pi*S'), present in up to 10% of Caucasians, on subjects with non-alcoholic fatty liver disease (NAFLD) or alcohol misuse. DESIGN: We analysed multicentric case-control cohorts consisting of 1184 people with biopsy-proven NAFLD and of 2462 people with chronic alcohol misuse, both cohorts comprising cases with cirrhosis and controls without cirrhosis. Genotyping for the Pi*Z and Pi*S variants was performed. RESULTS: The Pi*Z variant presented in 13.8% of patients with cirrhotic NAFLD but only in 2.4% of counterparts without liver fibrosis (p<0.0001). Accordingly, the Pi*Z variant increased the risk of NAFLD subjects to develop cirrhosis (adjusted OR=7.3 (95% CI 2.2 to 24.8)). Likewise, the Pi*Z variant presented in 6.2% of alcohol misusers with cirrhosis but only in 2.2% of alcohol misusers without significant liver injury (p<0.0001). Correspondingly, alcohol misusers carrying the Pi*Z variant were prone to develop cirrhosis (adjusted OR=5.8 (95% CI 2.9 to 11.7)). In contrast, the Pi*S variant was not associated with NAFLD-related cirrhosis and only borderline with alcohol-related cirrhosis (adjusted OR=1.47 (95% CI 0.99 to 2.19)). CONCLUSION: The Pi*Z variant is the hitherto strongest single nucleotide polymorphism-based risk factor for cirrhosis in NAFLD and alcohol misuse, whereas the Pi*S variant confers only a weak risk in alcohol misusers. As 2%-4% of Caucasians are Pi*Z carriers, this finding should be considered in genetic counselling of affected individuals.


Assuntos
Predisposição Genética para Doença/epidemiologia , Heterozigoto , Cirrose Hepática Alcoólica/genética , alfa 1-Antitripsina/genética , Distribuição por Idade , Áustria , Biópsia por Agulha , Estudos de Casos e Controles , Intervalos de Confiança , Feminino , Triagem de Portadores Genéticos , Variação Genética , Alemanha , Humanos , Imuno-Histoquímica , Incidência , Cirrose Hepática Alcoólica/epidemiologia , Cirrose Hepática Alcoólica/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Razão de Chances , Polimorfismo de Nucleotídeo Único , Prognóstico , Medição de Risco , Distribuição por Sexo
15.
BMC Gastroenterol ; 20(1): 1, 2019 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-31892306

RESUMO

BACKGROUND: The multifactorial mechanisms driving negative health outcomes among risky drinkers with HIV may include immunosenescence. Immunosenescence, aging of the immune system, may be accentuated in HIV and leads to poor outcomes. The liver regulates innate immunity and adaptive immune tolerance. HIV-infected people have high prevalence of liver-related comorbidities. We hypothesize that advanced liver fibrosis/cirrhosis is associated with alterations in T-cell subsets consistent with immunosenescence. METHODS: ART-naïve people with HIV with a recent history of heavy drinking were recruited into a clinical trial of zinc supplementation. Flow cytometry was used to characterize T-cell subsets. The two primary dependent variables were CD8+ and CD4+ T-cells expressing CD28-CD57+ (senescent cell phenotype). Secondary dependent variables were CD8+ and CD4+ T-cells expressing CD45RO + CD45RA- (memory phenotype), CD45RO-CD45RA+ (naïve phenotype), and the naïve phenotype to memory phenotype T-cell ratio (lower ratios associated with immunosenescence). Advanced liver fibrosis/cirrhosis was defined as FIB-4 > 3.25, APRI≥1.5, or Fibroscan measurement ≥10.5 kPa. Analyses were conducted using multiple linear regression adjusted for potential confounders. RESULTS: Mean age was 34 years; 25% female; 88% hepatitis C. Those with advanced liver fibrosis/cirrhosis (N = 25) had higher HIV-1 RNA and more hepatitis C. Advanced liver fibrosis/cirrhosis was not significantly associated with primary or secondary outcomes in adjusted analyses. CONCLUSIONS: Advanced liver fibrosis/cirrhosis was not significantly associated with these senescent T-cell phenotypes in this exploratory study of recent drinkers with HIV. Future studies should assess whether liver fibrosis among those with HIV viral suppression and more advanced, longstanding liver disease is associated with changes in these and other potentially senescent T-cell subsets.


Assuntos
Alcoolismo/complicações , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Infecções por HIV/imunologia , Imunossenescência , Cirrose Hepática Alcoólica/imunologia , Adulto , Antígenos CD28/metabolismo , Linfócitos T CD4-Positivos/imunologia , Antígenos CD57/metabolismo , Linfócitos T CD8-Positivos/imunologia , Estudos Transversais , Feminino , Infecções por HIV/complicações , Hepatite C/imunologia , Humanos , Memória Imunológica , Antígenos Comuns de Leucócito/metabolismo , Modelos Lineares , Cirrose Hepática Alcoólica/diagnóstico por imagem , Cirrose Hepática Alcoólica/enzimologia , Cirrose Hepática Alcoólica/patologia , Masculino , Fenótipo , Ensaios Clínicos Controlados Aleatórios como Assunto , Federação Russa , Zinco/administração & dosagem
16.
Korean J Gastroenterol ; 72(1): 37-41, 2018 Jul 25.
Artigo em Coreano | MEDLINE | ID: mdl-30049177

RESUMO

Ectopic varices are rare among patients with portal hypertension, especially in the ascending colon. It is difficult to evaluate massive lower gastrointestinal bleeding in patients with liver cirrhosis by colonoscopy due to hemodynamic instability and poor bowel preparation. In Korea, there has only been one case report about ascending colon variceal bleeding, in which hemostasis was performed by venous coil embolization. We report another rare case of ascending colon variceal bleeding in a patient with alcoholic cirrhosis, who was successfully treated via two sessions of N-butyl-2-cyanoacrylate injection through colonoscopy. This case suggests that the careful endoscopic approach and hemostasis with glue injection might be an option for treating massive bleeding in the lower gastrointestinal varix.


Assuntos
Embucrilato/uso terapêutico , Hemorragia Gastrointestinal/prevenção & controle , Cirrose Hepática Alcoólica/patologia , Adesivos Teciduais/uso terapêutico , Colo Ascendente/irrigação sanguínea , Colo Ascendente/diagnóstico por imagem , Colonoscopia , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
17.
Georgian Med News ; (278): 98-103, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29905553

RESUMO

The concept of acute-on-chronic liver failure (ACLF) covers acute deterioration of the liver function in patients with alcoholic cirrhosis (ALC) caused by secondary or extra-hepatic provoking factors (PF) leading to dysfunction of target organs. CLIF-C-ACLF score refers to the number of decompensated organs/systems and is recommended for predicting outcome in patients with ALC. Objective - to compare the diagnostic value of the Child-Pugh score and the CLIF-C-ACLF score for predicting short-term mortality in patients with ALC. The clinical data of 150 patients with ALC were retrospectively analyzed. Enrolled patients were divided into 2 groups according to the presence / absence of PF 3 months before the death: I group (n = 83) - without PF (CLF), group II (n= 67) - with PF (ACLF). To assess the severity of ALC we used the Child-Pugh score and the CLIF-C-ACLF score. Infectious complications were considered as PF. The sensitivity of the STMP by Child-Pugh score in group 1 was 100% (95% CI 58.9-100), specificity was 38.9% (95% CI 30.9-47.4). The sensitivity for the CLIF-C-ACLF score was 100% (95% CI 58.9-100), specificity-93.75% (95% CI 88.5-97.1).A. The sensitivity of STMP by Child-Pugh score in group II was 100% (95% CI 54.1-100), specificity was 29.5% (95% CI -42.6 to 18.5). The sensitivity of STMP by CLIF-C-ACLF in score II was 100% (95% CI 58.9-100), specificity was 88.5% (95% CI 77.8-95.2). The CLIF-C-ACLF corresponded to the model of excellent quality in groups I (0.99) and II (0.97) and was higher than the Child-Pugh score in both groups (p = 0.012 and p = 0.015 respectively). The diagnostic value of the CLIF-C-ACLF score for predicting short-term mortality in patients with ALC is higher than Child-Pugh, especially for acute decompensation of ALC caused by precipitating factors.


Assuntos
Insuficiência Hepática Crônica Agudizada/diagnóstico , Cirrose Hepática Alcoólica/diagnóstico , Peritonite/diagnóstico , Pneumonia Bacteriana/diagnóstico , APACHE , Insuficiência Hepática Crônica Agudizada/mortalidade , Insuficiência Hepática Crônica Agudizada/patologia , Adulto , Progressão da Doença , Feminino , Humanos , Fígado/patologia , Cirrose Hepática Alcoólica/mortalidade , Cirrose Hepática Alcoólica/patologia , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Peritonite/mortalidade , Peritonite/patologia , Pneumonia Bacteriana/mortalidade , Pneumonia Bacteriana/patologia , Fatores Desencadeantes , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
18.
J Vasc Interv Radiol ; 29(8): 1194-1202.e1, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29887183

RESUMO

PURPOSE: This study used the Oncopig Cancer Model (OCM) to develop alcohol-induced fibrosis in a porcine model capable of developing hepatocellular carcinoma. MATERIALS AND METHODS: Liver injury was induced in 8-week-old Oncopigs (n = 10) via hepatic transarterial infusion of 0.75 mL/kg ethanol-ethiodized oil (1:3 v/v). Feasibility was assessed in an initial Oncopig cohort (n = 5) by histologic analysis at 8 weeks after induction, and METAVIR results were compared to age- and sex-matched healthy controls (n = 5). Liver injury was then induced in a second OCM cohort (n = 5) for a time-course study, with post-induction disease surveillance via biweekly physical exam, lab analysis, and liver biopsies until 20 weeks after induction. RESULTS: In Cohort 1, 8-week post-induction liver histologic analysis revealed median METAVIR F3 (range, F3-F4) fibrosis, A2 (range, A2-A3) inflammation, and 15.3% (range, 5.0%-22.9%) fibrosis. METAVIR and inflammation scores were generally elevated compared to healthy controls (F0-F1, P = 0.0013; A0-A1, P = .0013; median percent fibrosis 8.7%, range, 5.8%-12.1%, P = .064). In Cohort 2, histologic analysis revealed peak fibrosis severity of median METAVIR F3 (range, F2-F3). However, lack of persistent alcohol exposure resulted in liver recovery, with median METAVIR F2 (range, F1-F2) fibrosis at 20 weeks after induction. No behavioral or biochemical abnormalities were observed to indicate liver decompensation. CONCLUSIONS: This study successfully validated a protocol to develop METAVIR F3-F4 fibrosis within 8 weeks in the OCM, supporting its potential to serve as a model for hepatocellular carcinoma in a fibrotic liver background. Further investigation is required to determine if repeated alcohol liver injury is required to develop an irreversible METAVIR grade F4 porcine cirrhosis model.


Assuntos
Carcinoma Hepatocelular/etiologia , Transformação Celular Neoplásica/patologia , Etanol , Óleo Etiodado , Cirrose Hepática Alcoólica/etiologia , Neoplasias Hepáticas/etiologia , Fígado/patologia , Animais , Animais Geneticamente Modificados , Biópsia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Transformação Celular Neoplásica/genética , Modelos Animais de Doenças , Progressão da Doença , Feminino , Genes p53 , Genes ras , Cirrose Hepática Alcoólica/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Índice de Gravidade de Doença , Sus scrofa , Fatores de Tempo
19.
Cell Biol Int ; 42(10): 1330-1339, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29935035

RESUMO

The regulatory roles of lncRNAs in the development of alcoholic hepatic fibrosis (AHF) have not been revealed. Here, we found lncRNA Gm5091 was being downregulated in mouse hepatic stellate cells (HSCs) during AHF. Then, Gm5091 was, respectively, overexpressed and knocked down in alcohol-treated primary HSCs. Our results showed that Gm5091 negatively regulated cell migration, ROS content, IL-1ß secretion, and expression of Collagen I and markers of HSC activation including α-SMA and Desmin. Furthermore, bioinformatics analysis showed that Gm5091 sequence contained binding sites of miR-27b, miR-23b, and miR-24, and we proved that miR-27b/23b/24 all bound to Gm5091 by using RNA pull-down assay. Full-length Gm5091 could decrease the miR-27b/23b/24 levels, but the truncated Gm5091 deleting the binding sites could not. Finally, we confirmed that full-length Gm5091 could alleviate AHF in vivo, but the truncated Gm5091 could not. In conclusion, lncRNA Gm5091 alleviates mouse AHF by sponging miR-27b/23b/24.


Assuntos
Cirrose Hepática Alcoólica/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Animais , Movimento Celular/fisiologia , Regulação para Baixo , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Cirrose Hepática Alcoólica/metabolismo , Cirrose Hepática Alcoólica/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , RNA Longo não Codificante/biossíntese , RNA Longo não Codificante/metabolismo
20.
Med Sci Law ; 58(3): 186-188, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29783922

RESUMO

A 52-year-old man died soon after admission to hospital with a severe metabolic acidosis and likely sepsis. He had a past history of alcohol abuse with withdrawal seizures. An abdominal computed tomography scan showed thickened bowel loops but no obvious ischaemic changes, and a blood culture yielded a pure growth of Escherichia coli. At autopsy, the liver showed well-established micro-nodular cirrhosis with steatosis. The peritoneal cavity contained 200 mL of turbid yellow-brown fluid, and the caecum and ascending colon were unusually thickened. Microscopy of the caecum and ascending colon showed oedema, with a florid submucosal acute inflammatory infiltrate and large numbers of rod-shaped bacilli typical of phlegmonous colitis. This rare acute infectious condition predominately involves the caecum and ascending colon and is associated with liver cirrhosis. It should therefore always be considered at autopsy in individuals with cirrhosis, with careful examination and microscopic sampling of the caecum and proximal ascending colon, including ancillary blood/fluid bacterial cultures if the condition is suspected based on the macroscopic findings and/or history.


Assuntos
Colite/microbiologia , Colite/patologia , Escherichia coli/isolamento & purificação , Cirrose Hepática Alcoólica/patologia , Sepse/microbiologia , Infecções por Escherichia coli/diagnóstico , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade
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