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1.
Lancet Gastroenterol Hepatol ; 5(5): 485-493, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32277901

RESUMO

Alcohol-related liver disease has become the leading indication for liver transplantation in the USA, partly due to an increase in the prevalence of high-risk drinking behaviour and alcohol use disorder, particularly among young women. Achieving sustained alcohol abstinence might not only prevent the development and progression of alcohol-related liver disease, but could also lead to clinically significant improvements, even in the advanced stages of disease. In this Series paper, we discuss the diagnosis and outpatient management of alcohol-related liver disease, with an emphasis on treatment options for alcohol use disorder and the assessment of nutritional status.


Assuntos
Assistência Ambulatorial/métodos , Hepatopatias Alcoólicas/diagnóstico , Hepatopatias Alcoólicas/terapia , Abstinência de Álcool , Comorbidade , Diagnóstico Diferencial , Humanos , Hepatopatias Alcoólicas/complicações , Hepatopatias Alcoólicas/patologia , Desnutrição/etiologia , Desnutrição/terapia , Programas de Rastreamento , Avaliação Nutricional , Estado Nutricional , Apoio Nutricional
2.
J Dairy Sci ; 102(12): 10737-10747, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31521345

RESUMO

Alcoholic liver disease (ALD) is correlated with alcohol consumption, and ALD progression depends on various factors. Some lactic acid bacteria (LAB) are beneficial for mitigating ALD. However, the valuable effects of LAB-derived dairy products remain unclear. Here, we evaluated the effects of Lactococcus chungangensis CAU 1447 dry cells (CAU 1447) and cream cheese derived from CAU 1447 on ALD progression following long-term alcohol consumption in rats. Oral administration of CAU 1447 and CAU 1447 cream cheese significantly reduced alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and triglyceride levels. We found that CAU 1447 and CAU 1447 cream cheese downregulated mRNA encoding various cytokines and antioxidative factors in the liver. Oral CAU 1447 cream cheese administration increased short-chain fatty acid, butyrate, and acetate levels in feces. Thus, administration of CAU 1447 and CAU 1447 cream cheese induced hepatoprotective effects, indicating potential applications as a supplement for ALD mitigation.


Assuntos
Lactococcus , Hepatopatias Alcoólicas/terapia , Probióticos/uso terapêutico , Animais , Fatores Biológicos/uso terapêutico , Queijo/microbiologia , Suplementos Nutricionais , Fezes/química , Fermentação , Masculino , Substâncias Protetoras/uso terapêutico , Ratos , Ratos Sprague-Dawley
4.
Transpl Immunol ; 56: 101227, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31351125

RESUMO

BACKGROUND: Alcohol-related liver disease (ALD) is one of the main indications for liver transplantation (LT). For 20 years, tacrolimus (Tac) is the cornerstone immunosuppressive drug used after LT and is very efficient for the prevention of rejection. Nevertheless, the major drawback of long-term use of Tac is the risk for developing dose-dependent adverse effects. OBJECTIVE: The aim of the present study was to assess the impact of Tac exposure (trough concentrations and concentration/dose (C/D) ratio) during the first year after LT, on short- and long-term complications after LT for ALD. METHODS: All patients who underwent a LT for ALD at Lyon Edouard Herriot Hospital from October 1990 to September 2010, and who were treated with Tac for at least one year after LT, were analyzed. RESULTS: The study population consisted in 251 patients, mean age 53.4 ±â€¯7.3 years, and followed during 11.6 ±â€¯4.8 years. Post-LT complications included severe infectious events (44.6%), malignancies (41.4%), arterial hypertension (49.4%) dyslipidemia (44.2%), diabetes (18.7%) and cardiovascular events (15.5%). De novo hypertension, cardiovascular event, CMV infection, non-melanoma skin cancers and HCC recurrence after transplantation were significantly associated with higher Tac trough blood concentration. In addition, Tac fast-metabolizers (defined as C/D < 1.8) had significantly more impaired renal function at 1, 5, and 10 years and more cardiovascular events, PTLD, diabetes and hypertension than slow-metabolizers. CONCLUSION: Our results strongly support that, in addition to blood trough concentrations, Tac metabolism, as estimated by the simple C/D ratio, could be an efficient parameter in daily practice to identify LT patients at risk to develop long term general complications of Tac.


Assuntos
Infecções por Citomegalovirus/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Hipertensão/epidemiologia , Imunossupressores/uso terapêutico , Hepatopatias Alcoólicas/terapia , Transplante de Fígado , Complicações Pós-Operatórias/epidemiologia , Neoplasias Cutâneas/epidemiologia , Tacrolimo/uso terapêutico , Infecções por Citomegalovirus/etiologia , Feminino , Seguimentos , França/epidemiologia , Humanos , Hipertensão/etiologia , Hepatopatias Alcoólicas/epidemiologia , Masculino , Pessoa de Meia-Idade , Risco , Neoplasias Cutâneas/etiologia , Fatores de Tempo
5.
Int J Mol Sci ; 20(11)2019 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-31159489

RESUMO

Alcoholic liver disease (ALD) refers to the damages to the liver and its functions due to alcohol overconsumption. It consists of fatty liver/steatosis, alcoholic hepatitis, steatohepatitis, chronic hepatitis with liver fibrosis or cirrhosis, and hepatocellular carcinoma. However, the mechanisms behind the pathogenesis of alcoholic liver disease are extremely complicated due to the involvement of immune cells, adipose tissues, and genetic diversity. Clinically, the diagnosis of ALD is not yet well developed. Therefore, the number of patients in advanced stages has increased due to the failure of proper early detection and treatment. At present, abstinence and nutritional therapy remain the conventional therapeutic interventions for ALD. Moreover, the therapies which target the TNF receptor superfamily, hormones, antioxidant signals, and MicroRNAs are used as treatments for ALD. In particular, mesenchymal stem cells (MSCs) are gaining attention as a potential therapeutic target of ALD. Therefore, in this review, we have summarized the current understandings of the pathogenesis and diagnosis of ALD. Moreover, we also discuss the various existing treatment strategies while focusing on promising therapeutic approaches for ALD.


Assuntos
Hepatopatias Alcoólicas/diagnóstico , Hepatopatias Alcoólicas/terapia , Animais , Gerenciamento Clínico , Diagnóstico Precoce , Humanos , Fígado/patologia , Hepatopatias Alcoólicas/patologia , Transplante de Fígado , Terapia de Alvo Molecular
6.
World J Gastroenterol ; 25(12): 1445-1456, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30948908

RESUMO

Explosive economic growth and increasing social openness in China over the last 30 years have significantly boosted alcohol consumption, and consequently, the incidence of alcoholic liver disease (ALD) in China has increased. Because the epidemiologic and clinical features of ALD in the Chinese population may differ from those of the Caucasian population, this review describes the epidemiology, pathogenesis, genetic polymorphisms, diagnosis, and treatment of ALD in the Chinese population. This updated knowledge of ALD in China provides information needed for a global understanding of ALD and may help in the development of useful strategies for reducing the global ALD burden.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Efeitos Psicossociais da Doença , Hepatopatias Alcoólicas/epidemiologia , Fatores Socioeconômicos , Consumo de Bebidas Alcoólicas/efeitos adversos , Grupo com Ancestrais do Continente Asiático/genética , China/epidemiologia , Predisposição Genética para Doença , Humanos , Incidência , Hepatopatias Alcoólicas/diagnóstico , Hepatopatias Alcoólicas/genética , Hepatopatias Alcoólicas/terapia , Polimorfismo Genético , Fatores de Risco
7.
Int Immunopharmacol ; 70: 477-485, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30870678

RESUMO

Increased intestinal permeability and immune disorder are important mechanisms of alcoholic liver disease (ALD). Recent evidences suggest bone marrow derived mesenchymal stem cells (BMMSCs) have protective effects on end-stage liver disease and intestinal barrier injury. Moreover, the activation of toll-like receptor 3 (TLR3) has been shown enhancing therapeutic effects of BMMSCs in inflammatory bowel disease (IBD). However, the mechanism remains unclear. In current study, chronic-binge alcohol abuse model was employed to investigate the therapeutic effects of BMMSCs and BMMSCs pre-activated with TLR3 (P-BMMSCs) on alcohol-induced liver and intestine damage. C57BL/6 mice were divided into four groups with normal control, alcohol-fed model, alcohol-fed model with BMMSCs treatment and alcohol-fed model with P-BMMSCs treatment. Alcohol-fed mice were fed Lieber-DeCali diet containing 5% alcohol for four weeks and given alcohol intragastrically on the 28th day, but control group were fed isocaloric diet. BMMSCs and P-BMMSCs were injected into the treatment group three times. Results showed alcohol diet causing significant damage to intestinal barrier and liver. These were reversed by the treatment of BMMSCs, especially P-BMMSCs. Moreover, alcohol increased the expression of intestinal HIF-2α, the proportion of NKB cells and the level of serum IL-18, while BMMSCs or P-BMMSCs reduced these factors. In conclusion, BMMSCs, especially TLR3 pre-activated BMMSCs could be used to protect alcohol-induced intestine and liver injury.


Assuntos
Células da Medula Óssea/fisiologia , Intestinos/fisiologia , Células Matadoras Naturais/imunologia , Hepatopatias Alcoólicas/terapia , Fígado/fisiologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/fisiologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Células Cultivadas , Etanol/administração & dosagem , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Transdução de Sinais , Receptor 3 Toll-Like/metabolismo
8.
Nat Rev Gastroenterol Hepatol ; 16(4): 235-246, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30643227

RESUMO

Alcoholic liver disease, which ranges from mild disease to alcoholic hepatitis and cirrhosis, is a leading cause of morbidity and mortality worldwide. Alcohol intake can lead to changes in gut microbiota composition, even before liver disease development. These alterations worsen with advancing disease and could be complicit in disease progression. Microbial function, especially related to bile acid metabolism, can modulate alcohol-associated injury even in the presence of cirrhosis and alcoholic hepatitis. Microbiota changes might also alter brain function, and the gut-brain axis might be a potential target to reduce alcoholic relapse risk. Gut microbiota manipulation including probiotics, faecal microbial transplant and antibiotics has been studied in alcoholic liver disease with varying success. Further investigation of the modulation of the gut-liver axis is relevant, as most of these patients are not candidates for liver transplantation. This Review focuses on clinical studies involving the gut microbiota in patients with alcoholic liver disease across the spectrum from alcoholic fatty liver to cirrhosis and alcoholic hepatitis. Specific alterations in the gut-liver-brain axis that are complicit in the interactions between the gut microbiota and alcohol addiction are also reviewed.


Assuntos
Disbiose/complicações , Microbioma Gastrointestinal , Hepatopatias Alcoólicas/microbiologia , Antibacterianos/uso terapêutico , Disbiose/terapia , Transplante de Microbiota Fecal , Humanos , Hepatopatias Alcoólicas/fisiopatologia , Hepatopatias Alcoólicas/psicologia , Hepatopatias Alcoólicas/terapia , Probióticos
9.
Clin Med (Lond) ; 19(1): 43-46, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30651244

RESUMO

Age-standardised mortality from liver disease in the United Kingdom has risen by 400% since 1970, with three-quarters of deaths from alcohol-related liver disease (ARLD). The 2013 National Confidential Enquiry into Patient Outcome and Death report found that only 47% of the patients dying in hospital from liver disease experienced 'good' care. We discuss common complications in the care of patients with ARLD and the evidence-based best practice that can improve patient outcomes, with a focus on the initial management of patients presenting acutely to the medical take.


Assuntos
Hepatopatias Alcoólicas/terapia , Alcoolismo/terapia , Hepatite Alcoólica/terapia , Humanos
11.
Clin Liver Dis ; 23(1): 55-69, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30454833

RESUMO

Alcohol use disorder (AUD) is common in alcoholic liver disease (ALD) and intrinsic to its pathophysiology. Optimal treatment requires a multidisciplinary team approach and a working alliance between patients and providers. Diagnosing AUD involves a combination of thorough history taking, physical examination, screening questionnaires, and alcohol biomarkers. Alcohol biomarkers have advantages and limitations of use of which clinicians should be aware. AUD treatment is effective, multifaceted, and can be tailored to each individual. Available treatment modalities are myriad: motivational enhancement therapy, cognitive behavior therapy, 12-step facilitation, group therapies, intensive outpatient programs, inpatient and residential treatment, and relapse prevention medications.


Assuntos
Alcoolismo/reabilitação , Hepatopatias Alcoólicas/terapia , Abstinência de Álcool , Dissuasores de Álcool/uso terapêutico , Alcoolismo/complicações , Alcoolismo/diagnóstico , Alcoolismo/metabolismo , Biomarcadores/metabolismo , Humanos , Hepatopatias Alcoólicas/etiologia
12.
Gut ; 68(8): 1504-1515, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30448775

RESUMO

OBJECTIVE: Antimicrobial C-type lectin regenerating islet-derived 3 gamma (REG3G) is suppressed in the small intestine during chronic ethanol feeding. Our aim was to determine the mechanism that underlies REG3G suppression during experimental alcoholic liver disease. DESIGN: Interleukin 22 (IL-22) regulates expression of REG3G. Therefore, we investigated the role of IL-22 in mice subjected to chronic-binge ethanol feeding (NIAAA model). RESULTS: In a mouse model of alcoholic liver disease, we found that type 3 innate lymphoid cells produce lower levels of IL-22. Reduced IL-22 production was the result of ethanol-induced dysbiosis and lower intestinal levels of indole-3-acetic acid (IAA), a microbiota-derived ligand of the aryl hydrocarbon receptor (AHR), which regulates expression of IL-22. Importantly, faecal levels of IAA were also found to be lower in patients with alcoholic hepatitis compared with healthy controls. Supplementation to restore intestinal levels of IAA protected mice from ethanol-induced steatohepatitis by inducing intestinal expression of IL-22 and REG3G, which prevented translocation of bacteria to liver. We engineered Lactobacillus reuteri to produce IL-22 (L. reuteri/IL-22) and fed them to mice along with the ethanol diet; these mice had reduced liver damage, inflammation and bacterial translocation to the liver compared with mice fed an isogenic control strain and upregulated expression of REG3G in intestine. However, L. reuteri/IL-22 did not reduce ethanol-induced liver disease in Reg3g-/- mice. CONCLUSION: Ethanol-associated dysbiosis reduces levels of IAA and activation of the AHR to decrease expression of IL-22 in the intestine, leading to reduced expression of REG3G; this results in bacterial translocation to the liver and steatohepatitis. Bacteria engineered to produce IL-22 induce expression of REG3G to reduce ethanol-induced steatohepatitis.


Assuntos
Disbiose , Etanol , Microbioma Gastrointestinal/fisiologia , Interleucinas/imunologia , Intestino Delgado/imunologia , Lactobacillus reuteri/imunologia , Hepatopatias Alcoólicas , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Modelos Animais de Doenças , Disbiose/complicações , Disbiose/etiologia , Disbiose/imunologia , Etanol/efeitos adversos , Etanol/metabolismo , Imunidade Inata , Ácidos Indolacéticos/metabolismo , Inflamação/metabolismo , Hepatopatias Alcoólicas/imunologia , Hepatopatias Alcoólicas/microbiologia , Hepatopatias Alcoólicas/terapia , Camundongos , Camundongos Knockout , Proteínas Associadas a Pancreatite/imunologia , Receptores de Hidrocarboneto Arílico/metabolismo
13.
J Diabetes Res ; 2019: 6430486, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31915709

RESUMO

Diabetes mellitus (DM) is a common chronic disease affecting humans globally. During the last few years, the incidence of diabetes has increased and has received more attention. In addition to growing DM populations, DM complications are involving injuries to more organs, such as the heart and cerebral vessel damage. DM complications can reduce quality of life and shorten life spans and eventually also impede social and economic development. Therefore, effective measures to curb the occurrence and development of diabetes assist in improving patients' quality of life, delay the progression of DM in the population, and ease a social burden. The liver is regarded as an important link in the management and control of DM, including the alleviation of glucose metabolism and lipid metabolism and others via glucose storage and endogenous glucose generation from glycogen stored in the liver. Liver cirrhosis is a very common chronic disease, which often lowers the quality of life and decreases life expectancy. According to a growing body of research, diabetes shows a close correlation with hepatitis, liver cirrhosis, and liver cancer. Moreover, coexistence of liver complications would accelerate the deterioration of patients with diabetes. Liver cirrhosis and diabetes influence each other. Thus, in addition to pharmacological treatments and lifestyle interventions, effective control of cirrhosis might assist in a better management of diabetes. When it comes to different etiologies of liver cirrhosis, different therapeutic methods, such as antiviral treatment, may be more effective. Effective control of cirrhosis might be a strategy for better management of diabetes.


Assuntos
Complicações do Diabetes/terapia , Cirrose Hepática/terapia , Doença Crônica , Feminino , Hepatite B/complicações , Hepatite B/terapia , Hepatite C/complicações , Hepatite C/terapia , Humanos , Hepatopatias Alcoólicas/epidemiologia , Hepatopatias Alcoólicas/etiologia , Hepatopatias Alcoólicas/terapia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/terapia
14.
Cent Eur J Public Health ; 27(Supplement): S10-S14, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31901188

RESUMO

This educational article/narrative review reflects the European Association for the Study of the Liver (EASL) clinical practice guidelines: management of alcohol-related liver disease. An important change contrasting with the 2012 guidelines is the new terminology of alcohol-related liver diseases. Another important outcome is the strong emphasis on prevention of alcohol use disorder which may be performed at all stages of public health care.


Assuntos
Hepatopatias Alcoólicas/terapia , Humanos , Guias de Prática Clínica como Assunto
15.
Kobe J Med Sci ; 65(3): E80-E89, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-32029692

RESUMO

The objective of this study was to clarify the lifestyle characteristics of patients with alcoholic liver disease (ALD) who were readmitted to the hospital, and to identify the background factors associated with these characteristics. This was a prospective observational study. Over a period of 3 months following hospital discharge, we conducted structured interviews to investigate the following five lifestyle characteristics based on our previous research: dietary intake, alcohol consumption or abstinence, psycho-emotional status, regularity of life habits, adherence to treatment. We also collected data on background factors from medical records and questionnaires. The analysis was performed using conceptual cluster matrices, with participants divided into two groups (at-home recovery and readmission). Lifestyle, health status, and background factors were compared between the two groups. Of the 34 patients with ALD recruited, 21 completed the one-month follow-up and were included in the analysis-14 patients were in the at-home recovery group and 7 in the readmission group. The at-home group's lifestyle was characterized by controlled alcohol consumption, but with maintenance of regular life and eating habits and adherence to treatment. In contrast, irregular eating habits (p=0.006) and the development of irregular life habits or the discontinuation of treatment very quickly after hospital discharge characterized the readmission group's lifestyle. Experiences of loss were a lifestyle-related background factor that was associated with readmission (p=0.017). Based on these findings, supporting patients with ALD in maintaining regular eating habits and taking experiences of loss into consideration would be important in avoiding readmission over the short-term.


Assuntos
Estilo de Vida , Hepatopatias Alcoólicas/fisiopatologia , Hepatopatias Alcoólicas/psicologia , Readmissão do Paciente , Adulto , Idoso , Consumo de Bebidas Alcoólicas , Dieta , Emoções , Comportamento Alimentar , Seguimentos , Nível de Saúde , Humanos , Hepatopatias Alcoólicas/terapia , Pessoa de Meia-Idade , Cooperação do Paciente , Readmissão do Paciente/estatística & dados numéricos , Estudos Prospectivos , Psicologia
17.
J R Coll Physicians Edinb ; 48(4): 293-298, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30488881

RESUMO

BACKGROUND: National Confidential Enquiry into Patient Outcome and Death (NCEPOD) 'Measuring the Units' (June 2013) identified significant organisational and attitudinal deficits in hospital care of patients with alcohol-related liver disease (ARLD), care being recognised as good in less than 50% of patients. METHOD: We surveyed over 700 consultants and trainees in acute medical and intensive therapy specialties to examine their perceptions of the NCEPOD findings. RESULTS: A total of 178 responded. In keeping with the NCEPOD findings, their perception was of lack of 24-hour access to specialty advice for patients with liver disease and inequity of access to high-dependency units. Their explanations include lack of resources, therapeutic nihilism and prejudicial judgements that would not be made of other patient groups. CONCLUSION: There is an urgent need for robust mechanisms to ensure equity of access to specialist liver advice and intensive therapy unit resources, and to counter negative and prejudicial attitudes to these patients.


Assuntos
Atitude do Pessoal de Saúde , Acesso aos Serviços de Saúde , Hepatopatias Alcoólicas/terapia , Médicos/psicologia , Cuidados Críticos , Inglaterra , Gastroenterologia , Recursos em Saúde , Humanos , Internato e Residência , Futilidade Médica , Preconceito , Encaminhamento e Consulta , Inquéritos e Questionários
18.
World J Gastroenterol ; 24(36): 4104-4118, 2018 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-30271077

RESUMO

MicroRNAs (miRNAs) are small non-coding RNAs that regulate multiple physiological and pathological functions through the modulation of gene expression at the post-transcriptional level. Accumulating evidence has established a role for miRNAs in the development and pathogenesis of liver disease. Specifically, a large number of studies have assessed the role of miRNAs in alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD), two diseases that share common underlying mechanisms and pathological characteristics. The purpose of the current review is to summarize and update the body of literature investigating the role of miRNAs in liver disease. In addition, the potential use of miRNAs as biomarkers and/or therapeutic targets is discussed. Among all miRNAs analyzed, miR-34a, miR-122 and miR-155 are most involved in the pathogenesis of NAFLD. Of note, these three miRNAs have also been implicated in ALD, reinforcing a common disease mechanism between these two entities and the pleiotropic effects of specific miRNAs. Currently, no single miRNA or panel of miRNAs has been identified for the detection of, or staging of ALD or NAFLD. While promising results have been shown in murine models, no therapeutic based-miRNA agents have been developed for use in humans with liver disease.


Assuntos
Alcoolismo/complicações , Hepatopatias Alcoólicas/genética , MicroRNAs/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Animais , Biomarcadores/análise , Citocinas/metabolismo , Modelos Animais de Doenças , Etanol/efeitos adversos , Terapia Genética/métodos , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Hepatopatias Alcoólicas/diagnóstico , Hepatopatias Alcoólicas/patologia , Hepatopatias Alcoólicas/terapia , MicroRNAs/análise , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/terapia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
19.
Alcohol Clin Exp Res ; 42(10): 1863-1873, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30080257

RESUMO

Alcoholic liver disease (ALD), a liver function disorder caused by excessive alcohol intake, is a serious threat to global public health and social development. Toxic metabolites and reactive oxygen species produced during the metabolism of alcohol can alter the epigenetic state including DNA methylation, histone modifications, and expression of microRNAs. Epigenetic alterations can conversely involve various signaling pathways, which could contribute to the initiation and progression of ALD. To elucidate the relationship between epigenetic alterations and alcohol damage not only reinforces our understanding on pathogenesis of ALD, but also provides novel targets for clinical diagnosis, treatment, and drug research of ALD. In this review, we have summarized the research progress of epigenetic alterations and related mechanisms caused by alcohol in the pathogenesis of ALD. Considering the invertibility of epigenetic alterations, treatment of ALD through epigenetic modification with common less harmful compounds is also related.


Assuntos
Epigênese Genética/genética , Hepatopatias Alcoólicas/genética , Hepatopatias Alcoólicas/terapia , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Metilação de DNA/efeitos dos fármacos , Metilação de DNA/fisiologia , Epigênese Genética/efeitos dos fármacos , Humanos , Hepatopatias Alcoólicas/patologia , Resveratrol/farmacologia , Resveratrol/uso terapêutico
20.
Clin Med (Lond) ; 18(Suppl 2): s60-s65, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29700095

RESUMO

Decompensated cirrhosis is a common reason for admission to the acute medical unit, and such patients typically have complex medical needs and are at high risk of in-hospital death. It is therefore vital that these patients receive appropriate investigations and management as early as possible in their patient journey. Typical presenting clinical features include jaundice, ascites, hepatic encephalopathy, hepato-renal syndrome or variceal haemorrhage. A careful history, examination and investigations can help identify the precipitating cause (infections, gastrointestinal bleeding, high alcohol intake / alcohol-related hepatitis or drug-induced liver injury), so appropriate treatment can be given. A 'care bundle' that has been endorsed by the British Society of Gastroenterology is available to help guide the management of patients with decompensated cirrhosis for the first 24 hours and ensure all aspects are addressed. Specific management of complications, such as infections, gastrointestinal bleeding, hepatic encephalopathy and hepatorenal syndrome, are discussed.


Assuntos
Cirrose Hepática , Falência Hepática , Doença Aguda , Ascite , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/terapia , Hepatopatias Alcoólicas/diagnóstico , Hepatopatias Alcoólicas/terapia , Falência Hepática/diagnóstico , Falência Hepática/terapia
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