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1.
Am J Gastroenterol ; 115(3): 398-405, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31985531

RESUMO

OBJECTIVES: Severe alcoholic hepatitis (sAH) confers substantial mortality, but the disease course is difficult to predict. As iron parameters are attractive outcome predictors in other liver diseases, we tested their prognostic ability in sAH. METHODS: Serum ferritin, transferrin, iron, transferrin saturation, nontransferrin-bound iron, soluble transferrin receptor, and hepcidin were measured in 828 patients with sAH recruited prospectively through the STOPAH trial. The cohort was randomly divided into exploratory (n = 200) and validation sets (n = 628). RESULTS: Patients with sAH had diminished serum transferrin but increased transferrin saturation. Among iron parameters, baseline transferrin was the best predictor of 28-day (area under the receiver operated characteristic 0.72 [95% confidence interval 0.67-0.78]) and 90-day survival (area under the receiver operated characteristic 0.65 [0.61-0.70]). Transferrin's predictive ability was comparable with the composite scores, namely model of end-stage liver disease, Glasgow alcoholic hepatitis score, and discriminant function, and was independently associated with survival in multivariable analysis. These results were confirmed in a validation cohort. Transferrin did not correlate with markers of liver synthesis nor with non-transferrin-bound iron or soluble transferrin receptor (as markers of excess unbound iron and functional iron deficiency, respectively). DISCUSSION: In patients with sAH, serum transferrin predicts mortality with a performance comparable with commonly used composite scoring systems. Hence, this routinely available parameter might be a useful marker alone or as a component of prognostic models.


Assuntos
Hepatite Alcoólica/mortalidade , Índice de Gravidade de Doença , Transferrina/metabolismo , Adulto , Biomarcadores/sangue , Feminino , Seguimentos , Hepatite Alcoólica/sangue , Hepatite Alcoólica/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Reprodutibilidade dos Testes
2.
World J Gastroenterol ; 25(35): 5388-5402, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31558881

RESUMO

BACKGROUND: Abnormal liver chemistry is a common problem in human immunodeficiency virus (HIV)-infected patients. Common causes of abnormal liver enzymes in this population include viral hepatitis B/C or opportunistic infection, drug toxicity, and neoplasm. Autoimmune hepatitis is a rare cause of hepatitis in HIV-infected individuals; however, this condition has been increasingly reported over the past few years. CASE SUMMARY: We present 13 HIV-infected patients (5 males and 8 females) who developed autoimmune hepatitis (AIH) after their immune status was restored, i.e. all patients had stable viral suppression with undetectable HIV viral loads, and median CD4+ counts of 557 cells/× 106 L. Eleven patients presented with chronic persistent elevation of aminotransferase enzyme levels. One patient presented with acute hepatitis and the other patient presented with jaundice. The median levels of aspartate aminotransferase and alanine aminotransferase enzymes were 178 and 177 U/mL, respectively. Elevation of immunoglobulin G levels was present in 11 (85%) patients. Antinuclear antibody and anti-smooth muscle antibody were positive in 11 (85%) and 5 (38%) patients. Liver biopsy was performed in all patients. They had histopathological findings compatible with AIH. The patients were started on prednisolone for remission induction, with good response. After improvement of the liver chemistry, the dose of prednisolone was tapered, and azathioprine was added as life-long maintenance therapy. At the last follow-up visit, all were doing well, without HIV viral rebound or infectious complications. CONCLUSION: This report underscores the emergence of autoimmune hepatitis in the context of HIV infection.


Assuntos
Carga Global da Doença , Infecções por HIV/complicações , Hepatite Autoimune/epidemiologia , Adulto , Alanina Transaminase/sangue , Fármacos Anti-HIV/uso terapêutico , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Aspartato Aminotransferases/sangue , Biópsia , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Diagnóstico Diferencial , Feminino , Glucocorticoides/uso terapêutico , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Hepatite Alcoólica/diagnóstico , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/tratamento farmacológico , Hepatite Autoimune/imunologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Incidência , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Prevalência , Indução de Remissão/métodos , Resultado do Tratamento
3.
Alcohol Alcohol ; 54(4): 408-416, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31219169

RESUMO

Alcoholic liver disease (ALD) represents a spectrum of injury, ranging from simple steatosis to alcoholic hepatitis to cirrhosis. Regular alcohol use results in fatty changes in the liver which can develop into inflammation, fibrosis and ultimately cirrhosis with continued, excessive drinking. Alcoholic hepatitis (AH) is an acute hepatic inflammation associated with significant morbidity and mortality that can occur in patients with steatosis or underlying cirrhosis. The pathogenesis of ALD is multifactorial and in addition to genetic factors, alcohol-induced hepatocyte damage, reactive oxygen species, gut-derived microbial components result in steatosis and inflammatory cell (macrophage and neutrophil leukocyte) recruitment and activation in the liver. Continued alcohol and pro-inflammatory cytokines induce stellate cell activation and result in progressive fibrosis. Other than cessation of alcohol use, medical therapy of AH is limited to prednisolone in a subset of patients. Given the high mortality of AH and the progressive nature of ALD, there is a major need for new therapeutic intervention for this underserved patient population.


Assuntos
Hepatite Alcoólica/sangue , Hepatite Alcoólica/diagnóstico , Hepatite Alcoólica/terapia , Humanos , Mediadores da Inflamação/sangue , Macrófagos do Fígado/metabolismo , Espécies Reativas de Oxigênio/sangue
4.
Dig Dis Sci ; 64(7): 1878-1892, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31076986

RESUMO

BACKGROUND: Alcohol-related liver disease is one of the most prevalent chronic liver diseases worldwide. Mechanisms involved in the pathogenesis of alcohol-related liver disease are not well understood. Oxylipins play a crucial role in numerous biological processes and pathological conditions. Nevertheless, oxylipins are not well studied in alcohol-related liver disease. AIMS: (1) To characterize the patterns of bioactive ω-3 and ω-6 polyunsaturated fatty acid metabolites in alcohol use disorder and alcoholic hepatitis patients and (2) to identify associations of serum oxylipins with clinical parameters in patients with alcohol-related liver disease. METHODS: We performed a comprehensive liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis of serum and fecal oxylipins derived from ω-6 arachidonic acid, ω-3 eicosapentaenoic acid, and docosahexaenoic acid in a patient cohort with alcohol-related liver disease. RESULTS: Our results show profound alterations in the serum oxylipin profile of patients with alcohol use disorder and alcoholic hepatitis compared to nonalcoholic controls. Spearman correlation of the oxylipins with clinical parameters shows a link between different serum oxylipins and intestinal permeability, aspartate aminotransferase, bilirubin, albumin, international normalized ratio, platelet count, steatosis, fibrosis and model for end-stage liver disease score. Especially, higher level of serum 20-HETE was significantly associated with decreased albumin, increased hepatic steatosis, polymorphonuclear infiltration, and 90-day mortality. CONCLUSIONS: Patients with alcohol-related liver disease have different oxylipin profiles. Future studies are required to confirm oxylipins as disease biomarker or to connect oxylipins to disease pathogenesis.


Assuntos
Alcoolismo/sangue , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Fezes/química , Hepatite Alcoólica/sangue , Oxilipinas/sangue , Adulto , Idoso , Alcoolismo/diagnóstico , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão , Cromatografia de Fase Reversa , Feminino , Hepatite Alcoólica/diagnóstico , Humanos , Masculino , Metabolômica/métodos , Pessoa de Meia-Idade , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem
5.
BMJ Case Rep ; 12(5)2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31142491

RESUMO

We present a teetotaler with compensated non-alcoholic fatty-liver-disease related cirrhosis who presented with acute worsening of his chronic liver disease. The acute event was not discernible even after extensive work up and finally a transjugular liver biopsy revealed features suggestive of severe alcoholic hepatitis. The patient and the family denied occult alcohol use when questioned over multiple times and finally, the culprit 'alcohol' was found to be the homoeopathy medicines that the patient was consuming over a month for treatment of Gilbert's syndrome. We retrieved and tested the homoeopathy drug for alcohol content and found an alarming 18% ethanol in the same, confirming our diagnosis.


Assuntos
Abstinência de Álcool , Hepatite Alcoólica/etiologia , Homeopatia/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/complicações , Adulto , Etanol/efeitos adversos , Etanol/análise , Doença de Gilbert/tratamento farmacológico , Hepatite Alcoólica/diagnóstico , Humanos , Hiperbilirrubinemia/tratamento farmacológico , Cirrose Hepática/complicações , Masculino , Materia Medica/efeitos adversos , Materia Medica/química , Obesidade/complicações
6.
Gastroenterology ; 157(2): 472-480.e5, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30998988

RESUMO

BACKGROUND & AIMS: Early liver transplantation (without requiring a minimum period of sobriety) for severe alcohol-associated hepatitis (AH) is controversial: many centers delay eligibility until a specific period of sobriety (such as 6 months) has been achieved. To inform ongoing debate and policy, we modeled long-term outcomes of early vs delayed liver transplantation for patients with AH. METHODS: We developed a mathematical model to simulate early vs delayed liver transplantation for patients with severe AH and different amounts of alcohol use after transplantation: abstinence, slip (alcohol use followed by sobriety), or sustained use. Mortality of patients before transplantation was determined by joint-effect model (based on Model for End-Stage Liver Disease [MELD] and Lille scores). We estimated life expectancies of patients receiving early vs delayed transplantation (6-month wait before placement on the waitlist) and life years lost attributable to alcohol use after receiving the liver transplant. RESULTS: Patients offered early liver transplantation were estimated to have an average life expectancy of 6.55 life years, compared with an average life expectancy of 1.46 life years for patients offered delayed liver transplantation (4.49-fold increase). The net increase in life expectancy from offering early transplantation was highest for patients with Lille scores of 0.50-0.82 and MELD scores of 32 or more. Patients who were offered early transplantation and had no alcohol use afterward were predicted to survive 10.85 years compared with 3.62 years for patients with sustained alcohol use after transplantation (7.23 life years lost). Compared with delayed transplantation, early liver transplantation increased survival times in all simulated scenarios and combinations of Lille and MELD scores. CONCLUSIONS: In a modeling study of assumed carefully selected patients with AH, early vs delayed liver transplantation (6 months of abstinence from alcohol before transplantation) increased survival times of patients, regardless of estimated risk of sustained alcohol use after transplantation. These findings support early liver transplantation for patients with severe AH. The net increase in life expectancy was maintained in all simulated extreme scenarios but should be confirmed in prospective studies. Sustained alcohol use after transplantation significantly reduced but did not eliminate the benefits of early transplantation. Strategies are needed to prevent and treat posttransplantation use of alcohol.


Assuntos
Doença Hepática Terminal/cirurgia , Hepatite Alcoólica/cirurgia , Transplante de Fígado/métodos , Modelos Biológicos , Tempo para o Tratamento , Adulto , Abstinência de Álcool , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/prevenção & controle , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/etiologia , Doença Hepática Terminal/mortalidade , Feminino , Hepatite Alcoólica/complicações , Hepatite Alcoólica/diagnóstico , Hepatite Alcoólica/mortalidade , Humanos , Expectativa de Vida , Transplante de Fígado/normas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco/métodos , Índice de Gravidade de Doença , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Listas de Espera
8.
Dig Liver Dis ; 51(6): 761-768, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31010745

RESUMO

Alcoholic hepatitis (AH) is a unique clinical syndrome that affects patients with chronic and active harmful alcohol consumption, and is associated with a high mortality of up to 40% at 1 month from presentation. It is important to assess disease severity and prognosis at time of presentation to identify patients at risk for high mortality and potential candidates for specific therapies. The cornerstone therapy for AH is enteral nutrition and abstinence. Steroids remain the only pharmacological option for severe AH however, adverse effects and lack of long-term benefit limit their routine use. Early liver transplantation is a potential salvage therapy for select severe AH patients. This review article comprehensively covers recent advances on the clinical unmet needs in the field including newer therapies and therapeutic targets, role of liver transplantation, and emerging biomarkers throughout the disease process from diagnosis, assessing prognosis and disease severity, and predicting responsiveness to medical therapies for severe AH.


Assuntos
Alcoolismo/terapia , Hepatite Alcoólica/diagnóstico , Hepatite Alcoólica/terapia , Transplante de Fígado , Abstinência de Álcool , Alcoolismo/complicações , Progressão da Doença , Nutrição Enteral , Humanos , Prognóstico , Esteroides/efeitos adversos , Esteroides/uso terapêutico , Resultado do Tratamento
10.
Clin Liver Dis ; 23(1): 81-98, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30454835

RESUMO

Alcoholic hepatitis is a unique type of alcohol-associated liver disease characterized by acute liver inflammation caused by prolonged heavy alcohol use. Treatment is mostly supportive. The short-term prognosis of acute alcoholic hepatitis depends on liver recovery, and ranges widely from rapid improvement to grim multiorgan failure despite treatment. Refinement of scoring systems have enhanced prognostication to guide clinical decision making in alcoholic hepatitis. Recent advances in the treatment of alcoholic hepatitis have solidified corticosteroids as the cornerstone of treatment to enhance short-term survival, but not intermediate or long-term survival.


Assuntos
Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Hepatite Alcoólica/metabolismo , Icterícia/metabolismo , Doença Aguda , Biópsia , Técnicas de Imagem por Elasticidade , Glucocorticoides/uso terapêutico , Hepatite Alcoólica/diagnóstico , Hepatite Alcoólica/tratamento farmacológico , Hepatite Alcoólica/patologia , Humanos , Fígado/patologia , Prednisolona/uso terapêutico , Prognóstico , Índice de Gravidade de Doença
12.
Trials ; 19(1): 696, 2018 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-30577864

RESUMO

BACKGROUND: Alcoholic hepatitis (AH) has the most severe presentation among alcohol-related liver diseases. Corticosteroids are the most widely recommended treatment for severe AH. However, more innovative, refined treatment measures are required because of its high mortality despite corticosteroid treatment. This study aims to determine whether granulocyte colony stimulating factor (G-CSF) treatment increases short-term survival in patients with severe AH refractory to corticosteroid treatment. METHODS/DESIGN: Patients with severe AH whose Maddrey's discriminant function (MDF) score is ≥ 32 and who will be treated with prednisolone (40 mg/day) for 1 week will be screened. Among them, 190 subjects with a partial response (PR) (Lille score 0.16-0.56), and 78 subjects with a null response (NR) (Lille score ≥ 0.56) will be enrolled. Subjects with PR will be randomized to steroid plus placebo or steroid plus 12 G-CSF injections (5 µg/kg/day for 5 days followed by every 3 days) at a ratio of 1:1. Subjects with a NR will be randomized to the placebo or G-CSF group (1:1). Study subjects in the PR group will be treated with prednisolone for 28 days followed by dose tapering for an additional 2 weeks. The primary endpoint is the 2-month survival rate in the NR group and the 6-month survival rate in the PR group. Child-Turcotte-Pugh, model for end-stage liver disease score, and the change in the proportion of peripheral circulating CD34-positive cells will be analyzed as risk factors for mortality. Preliminary safety data for the initial 10 study subjects enrolled in the PR study will be assessed to determine whether the PR study would be continued, according to the G-CSF-mobilized, peripheral-blood stem cell donor assessment protocol of the National Marrow Donor Program. DISCUSSION: We hypothesized that G-CSF would prolong short-term survival of patients with severe AH refractory to corticosteroid treatment. This is a proof-of-concept trial designed to assess the efficacy of Lille-score-guided G-CSF treatment. This trial is also designed to identify a special subgroup in whom G-CSF rescue treatment would improve liver function and prolong survival. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02442180 . Prospectively registered on 13 May 2015.


Assuntos
Corticosteroides/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Hepatite Alcoólica/tratamento farmacológico , Prednisolona/administração & dosagem , Corticosteroides/efeitos adversos , Adulto , Idoso , Método Duplo-Cego , Esquema de Medicação , Resistência a Medicamentos , Feminino , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Hepatite Alcoólica/diagnóstico , Hepatite Alcoólica/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Prednisolona/efeitos adversos , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , República da Coreia , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
13.
Langenbecks Arch Surg ; 403(7): 825-836, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30349998

RESUMO

PURPOSE: This review investigated survival and alcoholic relapse following liver transplantation (LT) in patients with severe acute alcoholic hepatitis (AH) without 6 months of alcohol abstinence. METHODS: All studies comparing acute AH patients undergoing LT with a control group were included. CENTRAL, MEDLINE, and Web of Science databases were searched. Survival benefits or odds ratios (OR) and 95% confidence intervals (CI) were assessed by meta-analyses using a random effects model. The study was registered in PROSPERO (CRD42017057971). According to the search results, two separate meta-analyses were performed: meta-analysis A compared early LT with medical therapy alone in patients with severe AH that were not responding to medical therapy and meta-analysis B compared LT outcome in patients with AH and chronic alcoholic cirrhosis (AC). RESULTS: The search yielded 2232 articles. Eight studies were included in the two meta-analyses-two studies in meta-analysis A and six studies in meta-analysis B. The two studies (n = 70) included in meta-analysis A revealed that 1-year patient survival was significantly higher in the LT group compared with the medical therapy-alone group (survival benefit, 15.88; 95% CI, 3.98-63.35; p < 0.0001). The six studies in meta-analysis B (including 1091 patients) showed that 1-year (survival benefit, 1.65; 95% CI, 0.95-2.89; p = 0.08), 3-year (survival benefit, 1.31; 95% CI, 0.79-2.18; p = 0.30), and 5-year survival (survival benefit, 1.54; 95% CI, 0.92-2.56; p = 0.10) were not significantly different between AH and AC groups. There was no significant difference in the rate of alcohol relapse between the groups (OR, 1.26; 95% CI, 0.53-2.96; p = 0.60). CONCLUSIONS: Early LT is a life-saving treatment for AH patients that do not respond to medical therapy. The chance of alcohol relapse after LT is not increased in selected patients.


Assuntos
Abstinência de Álcool , Hepatite Alcoólica/mortalidade , Hepatite Alcoólica/cirurgia , Transplante de Fígado/métodos , Doença Aguda , Feminino , Sobrevivência de Enxerto , Hepatite Alcoólica/diagnóstico , Humanos , Cirrose Hepática Alcoólica/diagnóstico , Cirrose Hepática Alcoólica/mortalidade , Cirrose Hepática Alcoólica/cirurgia , Transplante de Fígado/mortalidade , Masculino , Prognóstico , Recidiva , Medição de Risco , Análise de Sobrevida , Fatores de Tempo
14.
Ann Hepatol ; 17(5): 752-755, 2018 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-30145576

RESUMO

Malnutrition is a common cause of impeding recovery in patients with acute alcoholic hepatitis (AAH). Previous reports have shown that appropriate nutritional supplementation reduce short and long-term mortality in patients with AAH. Despite these clear recommendations, the element of nutrition in AAH is often neglected. We designed a quality improvement project to evaluate and improve compliance with appropriate nutrition in patients presenting with AAH at our institution. Patients admitted with AAH between December 2015 to December 2016 were included. Our primary outcome was compliance with appropriate nutrition. Secondary outcomes included nutrition consultation and hepatology consultation. A total of fifty-four patients were included. Nine of the 53 patients (17%) received high calorie and high protein diets. Hepatology was consulted in 72% (38/53) of the patients, and 21% (8/38) of these patients received appropriate nutrition as compared to only 8.3% (1/12) in whom hepatology was not consulted. Nutrition was consulted in 55% (29/53) of these patients and 67% (19/28) of those patients received appropriate nutrition. In conclusion, our compliance of appropriate nutrition in AAH is low. Our initial investigation suggests that hepatology and nutrition consultation improved compliance with appropriate nutrition. The next step will be to implement protocolized care for appropriate nutrition in AAH by incorporating consultation of hepatology and nutrition services, assess the effect on adherence to appropriate nutrition, and determine the impact on patient outcomes.


Assuntos
/normas , Gastroenterologistas/normas , Hepatite Alcoólica/dietoterapia , Desnutrição/dietoterapia , Estado Nutricional , Nutricionistas/normas , Padrões de Prática Médica/normas , Doença Aguda , Dieta Rica em Proteínas/normas , Ingestão de Energia , Feminino , Hepatite Alcoólica/complicações , Hepatite Alcoólica/diagnóstico , Hepatite Alcoólica/fisiopatologia , Humanos , Masculino , Desnutrição/diagnóstico , Desnutrição/etiologia , Desnutrição/fisiopatologia , Pessoa de Meia-Idade , Valor Nutritivo , Melhoria de Qualidade/normas , Indicadores de Qualidade em Assistência à Saúde/normas , Encaminhamento e Consulta/normas , Fatores de Tempo , Resultado do Tratamento
15.
Ann Hepatol ; 17(5): 759-768, 2018 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-30145578

RESUMO

Alcoholic hepatitis (AH) is a condition of acute liver inflammation in the setting of heavy alcohol use that is often managed with corticosteroids in severe cases. Among non-responders to steroids, however, prognosis is poor with up to 75% mortality within 6 months after treatment failure. Early liver transplantation (LT) can achieve an acceptable short-term survival, and initial studies have demonstrated 3-year survival rates of up to 84%. However, the practice of early LT in severe AH remains controversial with concerns over the 6-month rule of sobriety and risk of alcohol relapse post-transplant. Proponents of LT advocate for better understanding of alcohol use as a disorder rather than self-inflicted cause of illness, aim to redefine the misguided application of the 6-month rule, and point out similar relapse rates among patients with early LT and those with greater than 6 months abstinence before transplant. Opponents of LT emphasize the correlation between alcohol relapse and graft failure and mortality, public resistance and potential for distrust among donors, and arguments that transplant centers need to establish improved models to predict relapse and standardize candidate selection criteria across centers. Here we review recent literature on this controversy and provide recommendations for moving forward to consensus.


Assuntos
Hepatite Alcoólica/cirurgia , Transplante de Fígado , Abstinência de Álcool , Tomada de Decisão Clínica , Técnicas de Apoio para a Decisão , Sobrevivência de Enxerto , Hepatite Alcoólica/diagnóstico , Hepatite Alcoólica/mortalidade , Humanos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Seleção de Pacientes , Complicações Pós-Operatórias/etiologia , Recidiva , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
16.
Aliment Pharmacol Ther ; 48(9): 961-974, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30144108

RESUMO

BACKGROUND: Intestinal microbiota plays an important role in bile acid homeostasis. AIM: To study the structure of the intestinal microbiota and its function in bile acid homeostasis in alcoholic patients based on the severity of alcoholic liver disease. METHODS: In this prospective study, we included four groups of active alcoholic patients (N = 108): two noncirrhotic, with (noCir_AH, n = 13) or without alcoholic hepatitis (noCir_noAH, n = 61), and two cirrhotic, with (Cir_sAH, n = 17) or without severe alcoholic hepatitis (Cir_noAH, n = 17). Plasma and faecal bile acid profiles and intestinal microbiota composition were assessed. RESULTS: Plasma levels of total bile acids (84.6 vs 6.8 µmol/L, P < 0.001) and total ursodeoxycholic acid (1.3 vs 0.3 µmol/L, P = 0.03) were higher in cirrhosis with severe alcoholic hepatitis (Cir_sAH) than Cir_noAH, whereas total faecal (2.4 vs 11.3, P = 0.01) and secondary bile acids (0.7 vs 10.7, P < 0.01) levels were lower. Cir_sAH patients had a different microbiota than Cir_noAH patients: at the phyla level, the abundance of Actinobacteria (9 vs 1%, P = 0.01) was higher and that of Bacteroidetes was lower (25 vs 40%, P = 0.04). Moreover, the microbiota of Cir_sAH patients showed changes in the abundance of genes involved in 15 metabolic pathways, including upregulation of glutathione metabolism, and downregulation of biotin metabolism. CONCLUSIONS: Patients with Cir_sAH show specific changes of the bile acid pool with a shift towards more hydrophobic and toxic species that may be responsible for the specific microbiota changes. Conversely, the microbiota may also alter the bile acid pool by transforming primary to secondary bile acids, leading to a vicious cycle.


Assuntos
Ácidos e Sais Biliares/fisiologia , Disbiose/epidemiologia , Microbioma Gastrointestinal/fisiologia , Hepatite Alcoólica/epidemiologia , Hepatite Alcoólica/microbiologia , Homeostase/fisiologia , Adulto , Idoso , Diarreia/diagnóstico , Diarreia/epidemiologia , Diarreia/microbiologia , Disbiose/diagnóstico , Fezes/microbiologia , Feminino , França/epidemiologia , Hepatite Alcoólica/diagnóstico , Humanos , Cirrose Hepática Alcoólica/diagnóstico , Cirrose Hepática Alcoólica/epidemiologia , Cirrose Hepática Alcoólica/microbiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
17.
Alcohol Clin Exp Res ; 42(10): 1933-1938, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30080255

RESUMO

BACKGROUND: Lifetime prevalence of posttraumatic stress disorder (PTSD) in the general population is reported to be 6.8%. Individuals with alcohol dependence and substance abuse have high prevalence of PTSD. However, the prevalence of PTSD in heavy drinkers with alcoholic hepatitis (AH) is not known.The study's aim was to determine the prevalence of PTSD in heavy drinkers with and without AH. METHODS: We screened for PTSD using the Primary Care-PTSD questionnaire among heavy drinkers with (n = 115) and without (n = 64) AH participating in a multicenter observational study in which participants were followed up to 12 months following their enrollment. RESULTS: The prevalence of PTSD in heavy drinkers with AH was 34% and was not different from heavy drinking controls without liver disease (34%). In the entire group screened for PTSD, the presence of PTSD was associated with higher alcohol consumption as reported by average drinks per last 30 days and average grams of alcohol consumed per day (p = 0.047 for both tests), but not associated with relapse of heavy drinking or mortality. Similarly, patients with AH and PTSD did not have higher relapse rate or higher mortality compared to patients with AH but no PTSD. CONCLUSIONS: Compared to previously reported prevalence in general population, heavy drinking individuals with or without AH have significantly higher prevalence of PTSD. However, PTSD was not associated with higher relapse rate or higher mortality in this population.


Assuntos
Alcoolismo/diagnóstico , Alcoolismo/epidemiologia , Hepatite Alcoólica/diagnóstico , Hepatite Alcoólica/epidemiologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/psicologia , Consumo de Bebidas Alcoólicas/tendências , Alcoolismo/psicologia , Estudos de Coortes , Feminino , Seguimentos , Hepatite Alcoólica/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transtornos de Estresse Pós-Traumáticos/psicologia
18.
Liver Transpl ; 24(12): 1655-1664, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30153377

RESUMO

Identifying patients at high risk for acute kidney injury (AKI) during hospitalization among patients admitted with severe alcoholic hepatitis (AH) is an unmet clinical need. We performed a multicentric prospective cohort study using data from 4 different cohorts on well-characterized patients hospitalized with severe AH. Data collected on 773 AH patients from 4 cohorts across the globe were randomly split into test (n = 390) and validation (n = 383) cohorts. We found that 32% of the patients developed inpatient AKI in the test cohort. Approximately 60% of patients met criteria for systemic inflammatory response syndrome (SIRS) at admission. Hepatic encephalopathy, SIRS, and Model for End-Stage Liver Disease score at admission predicted inpatient AKI with odds ratios of 3.86, 2.24, and 1.14, respectively. The AKI risk score developed using these predictors stratified risk of inpatient AKI to low (score <3), moderate (3-4), and high (>4). These findings were replicated in the validation cohort. In the whole study cohort, patients with AKI had a lower 90-day survival (53% versus 77%; P < 0.001). Those with AKI risk score of >4 had significantly lower 90-day survival as compared with those with risk scores between 3 and 4 and <3 (47% versus 68% versus 88%; P < 0.001). In conclusion, AKI occurs frequently in AH patients and negatively impacts short-term mortality. The AKI risk score is useful in identifying patients at high risk for inpatient AKI and may be useful for developing new therapeutic strategies to prevent AKI in patients with AH.


Assuntos
Lesão Renal Aguda/diagnóstico , Hepatite Alcoólica/complicações , Índice de Gravidade de Doença , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/mortalidade , Adulto , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/etiologia , Doença Hepática Terminal/mortalidade , Feminino , Encefalopatia Hepática/diagnóstico , Encefalopatia Hepática/etiologia , Encefalopatia Hepática/mortalidade , Hepatite Alcoólica/diagnóstico , Hepatite Alcoólica/mortalidade , Hepatite Alcoólica/terapia , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Curva ROC , Medição de Risco/métodos , Fatores de Risco , Análise de Sobrevida , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Síndrome de Resposta Inflamatória Sistêmica/mortalidade
19.
Alcohol Alcohol ; 53(6): 716-718, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30099535

RESUMO

Liver transplantation is lifesaving for patients with severe acute alcoholic hepatitis (SAH) with preliminary data demonstrating favorable early post-transplant outcomes. Using the United Network for Organ Sharing database, we demonstrate that liver transplantation for SAH in the USA has steadily increased and is associated with similar 1- and 3-year post-transplant survival as well as comparable 30-day waitlist mortality to acute liver failure due to drug-induced liver injury.


Assuntos
Hepatite Alcoólica/cirurgia , Transplante de Fígado/tendências , Índice de Gravidade de Doença , Tempo para o Tratamento/tendências , Listas de Espera , Adulto , Bases de Dados Factuais/tendências , Feminino , Hepatite Alcoólica/diagnóstico , Hepatite Alcoólica/mortalidade , Humanos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Listas de Espera/mortalidade
20.
Presse Med ; 47(7-8 Pt 1): 655-666, 2018.
Artigo em Francês | MEDLINE | ID: mdl-30032921

RESUMO

All chronic and excessive consumer of alcohol with recent jaundice should be assessed using a Maddrey's score for severe acute alcoholic hepatitis. Corticosteroids are the first line of treatment, associated with an appropriate nutritional support and alcohol abstinence. Corticosteroids plus N-acetylcysteine combination improves short-term survival over corticosteroids alone, and could be proposed as a first line therapy. The response to treatment is evaluated at the 7th day of treatment, with the Lille model≤0.45. Prognostic of non-responders to corticosteroids with Lille model>0.45 is dramatically low with 23% survival at 6 month. Early liver transplantation in a selected group of patients with non-response to corticosteroids significantly improves 6th month and long-term survival.


Assuntos
Doença Aguda , Hepatite Alcoólica , Algoritmos , Hepatite Alcoólica/diagnóstico , Hepatite Alcoólica/fisiopatologia , Hepatite Alcoólica/terapia , Humanos , Prognóstico , Índice de Gravidade de Doença
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