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1.
Lancet Gastroenterol Hepatol ; 5(5): 494-506, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32277902

RESUMO

Alcoholic hepatitis is an acute, inflammatory liver disease associated with high morbidity and mortality both in the short term and long term. Alcoholic hepatitis often arises in patients with a background of chronic liver disease and it is characterised by the rapid onset of jaundice and the development of myriad complications. Medical therapy for severe alcoholic hepatitis relies on corticosteroids, which have modest effectiveness. Abstinence from alcohol is critically important in patients with alcoholic hepatitis, but recidivism is high. Because of the absence of effective medical treatments for alcoholic hepatitis and alcohol dependency, there is a pressing need to develop new and effective therapeutics. Supported by promising preliminary and preclinical studies, many ongoing clinical trials of new therapies for alcoholic hepatitis are currently underway and are discussed further in this Series paper.


Assuntos
Corticosteroides/uso terapêutico , Alcoolismo/terapia , Anti-Inflamatórios/uso terapêutico , Hepatite Alcoólica/terapia , Abstinência de Álcool , Alcoolismo/complicações , Antibacterianos/uso terapêutico , Antioxidantes/uso terapêutico , Suplementos Nutricionais , Hepatite Alcoólica/diagnóstico , Hepatite Alcoólica/etiologia , Humanos , Ácidos Pentanoicos/uso terapêutico , Probióticos/uso terapêutico , Receptores de Interleucina-1/antagonistas & inibidores , Transdução de Sinais , Fator de Necrose Tumoral alfa/antagonistas & inibidores
2.
PLoS One ; 15(2): e0228889, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32045450

RESUMO

Mesenchymal stem cells (MSCs) are a population of pluripotent cells that have been tested for the treatment of many inflammatory diseases. It remains unclear whether MSCs were effective in treating mice with alcoholic hepatitis (AH) and its underlying mechanism. In the present study, MSCs were isolated from bone marrow of 4-6 week-old C57BL/6N male mice. AH was induced in female mice by chronic-binge ethanol feeding for 10 days. Intraperitoneal (i.p.) transplantation of MSCs or saline were performed in mice on day 10. Blood samples and hepatic tissues were harvested on day 11. Biochemical, liver histological and flow cytometric analyses were performed. Compared to the control mice, the AH mice had significantly increased liver/body weight ratio, serum alanine aminotransferase (ALT) and aspartate aminotransferases (AST), hepatic total cholesterol (TC), triglyceride (TG), malondialdehyde (MDA), hepatic neutrophil and macrophage infiltration (P<0.001), which were markedly reduced by i.p. transplantation of MSCs (P<0.01). Compared to the control mice, the hepatic glutathione (GSH) was prominently lower in the AH mice (P<0.001), which was markedly enhanced after i.p. injection of MSCs (P<0.001). MSCs were effective for the treatment of AH mice, which might be associated with their ability in inhibiting hepatic neutrophil and macrophage infiltration, and alleviating oxidative stress.


Assuntos
Hepatite Alcoólica/terapia , Transplante de Células-Tronco Mesenquimais , Animais , Diferenciação Celular , Modelos Animais de Doenças , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Fígado Gorduroso/terapia , Feminino , Hepatite Alcoólica/metabolismo , Hepatite Alcoólica/patologia , Metabolismo dos Lipídeos , Fígado/metabolismo , Fígado/patologia , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Infiltração de Neutrófilos , Estresse Oxidativo
3.
F1000Res ; 92020.
Artigo em Inglês | MEDLINE | ID: mdl-32089834

RESUMO

Alcoholic hepatitis is the severest clinical presentation of alcoholic liver disease. Lacking an effective pharmacologic treatment, alcoholic hepatitis is associated with a poor prognosis and its recovery relies mostly on abstinence. With alcohol use disorder being universally on the rise, the impact of alcoholic hepatitis on society and health-care costs is expected to increase significantly. Prognostic factors and liver biopsy can help with timely diagnosis, to determine eligibility and response to corticosteroids, and for prognostication and transplant referral. Although recent discoveries in the pathophysiology of alcoholic hepatitis are encouraging and could pave the way for novel treatment modalities, a multidisciplinary approach considering timely identification and treatment of liver-related complications, infectious and metabolic disease, malnutrition, and addiction counseling should be emphasized. Apart from proper selection of candidates, transplant programs should provide adequate post-transplant addiction support in order to make of early liver transplantation for alcoholic hepatitis the ultimate sobering experience in the next decade.


Assuntos
Hepatite Alcoólica , Hepatopatias Alcoólicas , Transplante de Fígado , Hepatite Alcoólica/diagnóstico , Hepatite Alcoólica/terapia , Humanos
4.
Dig Dis Sci ; 65(6): 1608-1614, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32107678

RESUMO

Although alcohol-associated liver disease has long been a major component of the liver disease landscape, it was overshadowed by chronic hepatitis C until recently. Nevertheless, with the declining incidence of hepatitis C in the wake of highly effective antiviral therapy, attention has shifted to the increasing burden of alcohol-associated liver disease. The incidence of advanced alcohol-associated liver disease, including acute alcoholic hepatitis and alcohol-associated cirrhosis, is rising in parallel with increasing rates of alcohol use disorders. As a result, alcohol-associated liver disease is now one of the most common indications for liver transplantation. Rates of liver transplantation for acute alcoholic hepatitis are rising as well in spite of the sparse guidance regarding candidate selection, counseling, postoperative care, long-term follow-up, and other best practices. To this day, liver transplant for acute alcoholic hepatitis remains a hotly debated clinical controversy.


Assuntos
Hepatite Alcoólica/patologia , Hepatite Alcoólica/terapia , Hepatopatias Alcoólicas/patologia , Hepatopatias Alcoólicas/terapia , Transplante de Fígado , Alcoolismo/complicações , Feminino , Sobrevivência de Enxerto , Humanos , Cirrose Hepática Alcoólica/complicações , Masculino , Seleção de Pacientes , Resultado do Tratamento
5.
Dig Dis Sci ; 65(1): 312-321, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31363954

RESUMO

BACKGROUND: Accurate prediction of outcomes for alcohol-associated hepatitis (AH) is critical, as prognosis determines treatment eligibility. Computed tomography (CT) features may provide prognostic information beyond traditional models. AIMS: Our aim was to identify CT features that predict outcomes in AH. METHODS: We studied 108 patients retrospectively with definite or probable AH, who underwent admission abdominal CT. A radiologist blinded to outcome evaluated eight CT features. The primary outcome was 90-day mortality. RESULTS: Twenty-five (23.2%) patients died within 90 days. While traditional prognostic tools, including Maddrey discriminant function (DF), predicted 90-day mortality (OR 1.01 [1.00, 1.03], P = 0.02), abdominal CT findings were also accurate predictors. On abdominal CT, patients with severe AH had larger volume of ascites (moderate/large volume: 34.0 vs. 8.2%, P < 0.0001), longer liver length (17.1 vs. 15.1 cm, P = 0.001), greater liver heterogeneity (moderate/severe: 21.3 vs. 8.2%, P = 0.007), and more likely to have splenomegaly (42.6 vs. 18.0%, P = 0.009) than those with mild AH. Univariate analysis revealed that ascites volume (OR 2.59 [1.35, 4.96], P = 0.004) predicted 90-day mortality. In multivariate analysis, degree of ascites predicted 90-day mortality when controlling for Maddrey DF (OR 2.36 [1.19, 4.69], P = 0.01) and trended toward significance when controlling for MELD score (OR 2.02 [0.95, 4.30], P = 0.07). CONCLUSION: CT findings in AH differentiate disease severity and predict 90-day mortality; therefore, the role of CT warrants further investigation as a tool in AH management.


Assuntos
Hepatite Alcoólica/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Feminino , Hepatite Alcoólica/complicações , Hepatite Alcoólica/mortalidade , Hepatite Alcoólica/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Valor Preditivo dos Testes , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo
6.
Dig Dis Sci ; 65(4): 990-1002, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31372912

RESUMO

BACKGROUND/AIMS: Alcoholic hepatitis (AH) can lead to sudden and severe hepatic decompensation necessitating recurrent hospitalizations. We evaluated the trends, predictors, and healthcare cost burden of AH-related readmissions in the USA. METHODS: Utilizing the National Readmissions Database 2010-2014, we performed a retrospective longitudinal analysis to identify the index readmission with AH for up to 90 days after discharge. Annual trends of 30- and 90-day AH-related readmissions were calculated. Predictors of 30- and 90-day readmission were determined by multivariate logistic regression. Annual healthcare cost burden associated with AH-linked readmissions was estimated. RESULTS: Of the 21,572 (unweighted: 50,769) AH-related hospitalizations, 4917 (22.8%) and 7890 (36.6%) were readmitted in 30 and 90 day, respectively, with rates that were statistically unchanged from 2010 to 2014. Predictors of 30-day readmissions included female gender, hepatitis C virus infection, cirrhosis, ascites, acute kidney injury, urinary tract infection, history of bariatric surgery, chronic pancreatitis, and high medical comorbidity index. Acute pancreatitis and palliative care consultation were associated with a lower risk of 30-day readmission. Predictors of 90-day readmission were similar to risk factors for 30-day readmission. From 2010 to 2014, the annual cost (and total hospitalization days) burden increased in 2014 to $164 million (22,244 days) and $321 million (42,772 days) for 30- and 90-day AH-related readmissions, respectively. CONCLUSION: Despite relatively stable trends in AH-related readmission, the total LOS and cost has been rising. A target-directed approach with a focus on high-risk subpopulations may help understand the unique challenges associated with the rising cost of AH-related readmissions.


Assuntos
Hepatite Alcoólica/epidemiologia , Hepatite Alcoólica/terapia , Readmissão do Paciente/tendências , Adulto , Estudos de Coortes , Feminino , Hepatite Alcoólica/diagnóstico , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos/epidemiologia
8.
Dig Dis Sci ; 65(1): 301-311, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31346950

RESUMO

BACKGROUND: Data on alcohol-related HCC are limited. AIMS: Our aim was to describe the incidence, management, and prognosis of alcohol compared to Hepatitis C (HCV)-related HCC at a national level. METHODS: Incident cases of HCC were identified in French healthcare databases between 2009 and 2012 and analyzed retrospectively. Demographic data, type, location, and annual HCC-caseload of the hospitals where patients were first managed were retrieved. Survival of incident cases was computed from the time of diagnosis and adjusted for potential confounding variables. RESULTS: The study population included 14,060 incident cases of alcohol and 2581 HCV-related HCC. Alcohol-related HCC was more frequent than HCV-related HCC (29.37 and 5.39/100,000 adults/year, respectively) with an heterogeneous distribution on the French territory. The optimal treatment was less frequently curative (20.5% vs 35.9%; p < 0.001), and survival was significantly shorter (9.5 [9.0-10.0] versus 16.8 [15.5-18.7] months p < 0.001) in alcohol compared to HCV-related HCC, with marked variations between regions for a given risk factor. In multivariable analysis in the whole study population, curative treatment was a strong predictor of survival (adjusted HR 0.28 [0.27-0.30] months p < 0.001). Being managed at least once in a teaching hospital during follow-up was independently associated with receiving a curative treatment and survival. CONCLUSION: In France, incidence of alcohol-related HCC is high and prognosis is poor compared to HCV-related HCC, with marked variations between regions. These results should guide future health policy initiatives pertaining to HCC care. Importantly, increasing patient' referral in expert centers could increase chances to receive curative treatment and improve outcomes.


Assuntos
Carcinoma Hepatocelular/terapia , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde , Hepatite C/terapia , Hepatite Alcoólica/terapia , Neoplasias Hepáticas/terapia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Bases de Dados Factuais , Feminino , França/epidemiologia , Hepatite C/diagnóstico , Hepatite C/mortalidade , Hepatite Alcoólica/diagnóstico , Hepatite Alcoólica/mortalidade , Humanos , Incidência , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Resultado do Tratamento
9.
Dig Liver Dis ; 52(1): 21-32, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31757596

RESUMO

Worldwide, the prevalence of alcohol use disorder (AUD) is 20-30% in men and 10-15% in women, and cirrhosis due to alcohol-related liver disease (ALD) is responsible for 0.9% of global deaths and 47.9% of cirrhosis-related deaths. End-stage ALD (ESALD) is the final condition of alcohol-related cirrhosis, and severe acute alcohol-related hepatitis (SAAH) is a distinct clinical syndrome associated with the consumption of large amounts of alcohol. In some cases, ESALD, and SAAH may need liver transplantation (LT). Thus, the management of ESALD and SAAH in patients affected by AUD may be an essential part of the clinical skills for hepatologists. For these reasons, the national board of the Italian Society on Alcohol have reviewed the most recent data on the management of ESALD, SAAH and LT for ALD in patients with AUD, formulating a position paper with related recommendations regarding four issues of specific clinical interest in this field: (a) the management of hepatic encephalopathy in patients with AUD, and LT in patients with ESALD; (b) the management of SAAH; (c) the management of AUD in patients with ESALD and SAAH; (d) special populations: polydrug addicts.


Assuntos
Alcoolismo/complicações , Doença Hepática Terminal/cirurgia , Hepatite Alcoólica/terapia , Cirrose Hepática Alcoólica/terapia , Transplante de Fígado , Abstinência de Álcool , Alcoolismo/terapia , Doença Hepática Terminal/etiologia , Hepatite Alcoólica/etiologia , Humanos , Itália , Cirrose Hepática Alcoólica/etiologia , Sociedades Médicas
10.
Nature ; 575(7783): 505-511, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31723265

RESUMO

Chronic liver disease due to alcohol-use disorder contributes markedly to the global burden of disease and mortality1-3. Alcoholic hepatitis is a severe and life-threatening form of alcohol-associated liver disease. The gut microbiota promotes ethanol-induced liver disease in mice4, but little is known about the microbial factors that are responsible for this process. Here we identify cytolysin-a two-subunit exotoxin that is secreted by Enterococcus faecalis5,6-as a cause of hepatocyte death and liver injury. Compared with non-alcoholic individuals or patients with alcohol-use disorder, patients with alcoholic hepatitis have increased faecal numbers of E. faecalis. The presence of cytolysin-positive (cytolytic) E. faecalis correlated with the severity of liver disease and with mortality in patients with alcoholic hepatitis. Using humanized mice that were colonized with bacteria from the faeces of patients with alcoholic hepatitis, we investigated the therapeutic effects of bacteriophages that target cytolytic E. faecalis. We found that these bacteriophages decrease cytolysin in the liver and abolish ethanol-induced liver disease in humanized mice. Our findings link cytolytic E. faecalis with more severe clinical outcomes and increased mortality in patients with alcoholic hepatitis. We show that bacteriophages can specifically target cytolytic E. faecalis, which provides a method for precisely editing the intestinal microbiota. A clinical trial with a larger cohort is required to validate the relevance of our findings in humans, and to test whether this therapeutic approach is effective for patients with alcoholic hepatitis.


Assuntos
Bacteriófagos/fisiologia , Enterococcus faecalis/patogenicidade , Enterococcus faecalis/virologia , Microbioma Gastrointestinal , Hepatite Alcoólica/microbiologia , Hepatite Alcoólica/terapia , Terapia por Fagos , Alcoolismo/complicações , Alcoolismo/microbiologia , Animais , Enterococcus faecalis/isolamento & purificação , Etanol/efeitos adversos , Fígado Gorduroso/complicações , Fígado Gorduroso/microbiologia , Fezes/microbiologia , Feminino , Vida Livre de Germes , Hepatite Alcoólica/complicações , Hepatite Alcoólica/mortalidade , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Perforina/metabolismo
11.
South Med J ; 112(7): 363-368, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31282964

RESUMO

OBJECTIVES: Severe acute alcoholic hepatitis is a serious condition in individuals who consume significant quantities of alcohol. We aimed to identify risk factors for short-term mortality with this illness. METHODS: Patients with severe acute alcoholic hepatitis admitted to our academic medical center from 2010 to 2012 were identified. Demographic features, laboratory values, and patient outcomes were recorded. In-hospital mortality and transfer to inpatient hospice were combined to calculate overall inpatient mortality. RESULTS: A total of 251 hospitalizations of 191 patients were identified. The average age was 43.1 years (standard deviation 9.55). Most patients were men (80.6%). Compared with all adult patients admitted to internal medicine services during the same period, patients self-reporting Native American and Hispanic race/ethnicity were overrepresented (11.1% vs 34.0% and 14.8% vs 27.7%, χ2 P < 0.0001). In-hospital mortality was 20.3%. Another 10% of patients were transferred to inpatient hospice facilities. In the multivariate analysis, higher overall inpatient mortality was associated with an admission bilirubin >20 mg/dL (odds ratio 4.59). Of the patients, 11.9% were readmitted with a complication within 30 days-most commonly septic shock. Of the readmitted patients, the overall inpatient mortality was 86.2%. CONCLUSIONS: This study confirms the severity of illness among patients with severe acute alcoholic hepatitis. Patients with the highest total bilirubin levels on admission had the highest overall inpatient mortality. Readmission was a strong predictor of overall in-hospital mortality.


Assuntos
Hepatite Alcoólica/terapia , Hospitalização , Doença Aguda , Adulto , Idoso , Feminino , Hepatite Alcoólica/mortalidade , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , New Mexico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença
12.
Aliment Pharmacol Ther ; 50(3): 249-257, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31231848

RESUMO

BACKGROUND: Alcoholic hepatitis is a serious complication of alcohol misuse. Severe alcoholic hepatitis with its high mortality, has been investigated in detail but 'nonsevere alcoholic hepatitis' is poorly characterised. Survival of this group of patients is unknown. AIM: To conduct a systematic review and meta-analysis to determine 28-day, 90-day and 1-year mortality of patients with nonsevere alcoholic hepatitis. METHODS: The protocol was registered on the PROSPERO database (CRD42018107451). Embase, Medline and Cochrane Central databases were searched until July 2018. All study designs reporting mortality rates in patients with nonsevere alcoholic hepatitis were eligible. Mortality data were extracted and meta-analysis performed using a random effects model. Risk of bias was assessed by Cochrane risk of bias or National Institutes of Health quality assessment tool for case series studies. RESULTS: Twenty-five studies (n = 1372 patients; 12 prospective) met criteria. Nonsevere was variably defined based on bilirubin, prothrombin time, and creatinine. Twenty-eight day mortality (17 studies; n = 993) was 6% (95% CI 3%-9%; I2  = 67.3%; P < 0.001), 90-day mortality (15 studies; n = 755) was 7% (4%-11%, I2  = 64.2%; P < 0.001) and 1-year mortality (five studies; n = 234) was 13% (4%-24%; I2  = 72%; P = 0.006). Subgroup analyses by method of diagnosis (histological vs clinical) or study design (prospective vs retrospective) did not reveal differences in mortality. CONCLUSION: Nonsevere alcoholic hepatitis is not benign with 6% and 13% 28-day and 1-year mortality, respectively. This systematic review demonstrates the paucity of high quality studies in patients with nonsevere alcoholic hepatitis. Our analysis suggests that patients who do not meet criteria for severe alcoholic hepatitis are an important and hitherto overlooked clinical group. Full characterisation of clinical outcome and development of treatment strategies to reduce mortality in this group is a priority.


Assuntos
Hepatite Alcoólica/mortalidade , Hepatite Alcoólica/patologia , Hepatite Alcoólica/terapia , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Índice de Gravidade de Doença
13.
Rev Med Liege ; 74(5-6): 326-331, 2019 05.
Artigo em Francês | MEDLINE | ID: mdl-31206275

RESUMO

Alcoholic hepatitis is a syndrome defined primarily by the clinical onset of jaundice in patients with a concomitant heavy consumption of alcoholic beverages. This pathology is managed by alcohol withdrawal with a 30-day survival rate of 90 %. For patients with severe alcoholic hepatitis, with a Maddrey score greater than 32 (taking into account bilirubin and prothrombin time), treatment with corticosteroids is discussed provided that a possible infection can be sufficiently excluded or adequately managed. The administration of corticosteroids is continued for 28 days if the Lille score, calculated after 7 days of treatment, is favourable (inferior to 0.45), leading to a survival rate of 80-90 %. However, if the Lille score is unfavourable (superior to 0.45), the prognosis is bad, with a survival of only 25-30 % at 6 months. Special attention needs to be paid to assure a sufficient caloric intake during the treatment period for a successful management. Liver transplantation, previously prohibited for this indication, can be discussed under certain circumstances. However, the success of treatment is contingent upon the alcohol withdrawal. Innovative drugs are currently under investigation to improve the prognosis of this condition.


Assuntos
Corticosteroides , Hepatite Alcoólica , Transplante de Fígado , Corticosteroides/uso terapêutico , Bilirrubina , Hepatite Alcoólica/terapia , Humanos , Prognóstico
14.
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
15.
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
16.
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
17.
J Psychosom Res ; 116: 75-82, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30654998

RESUMO

AIMS: Alcoholic hepatitis (AH) is a life-threatening complication of alcohol use disorder (AUD). Alcohol abstinence is the main predictor of the long-term prognosis of AH. It is unknown whether AUD treatment retention (TR) after an AH episode impacts alcohol relapse and mortality or what baseline factors influence TR. METHODS: Design: case-control study; Study population: hospitalized patients (1999-2012) with an episode of biopsy-proven AH were included (n = 120); Assessment: demographic and clinical data, the High-Risk Alcoholism Relapse (HRAR) scale, mortality and alcohol relapse were assessed through clinical records and telephone or personal interviews; Follow-up period: short-term and long-term TRs were assessed at 12 and 24 months, respectively. RESULTS: The overall short-term and long-term TRs were 37% and 27.8%, respectively. The severity of liver disease at baseline predicted both short-term and long-term TR (OR 3.7 and 3.3, respectively), whereas HRAR >3 and a history of psychiatric disorders predicted long-term TR (OR 2.9 and 2.6, respectively). Moreover, HRAR >3 (OR 3.0) and previous treatment for AUD (OR 2.9) increased the risk of relapse in the short term. Importantly, receiving alcohol therapy in a centre different from the hospital where the patient was admitted was associated with increased risk of alcohol relapse over the long term (OR 5.4). CONCLUSION: Experiencing an alcohol-related life-threatening complication is insufficient motivation to seek treatment for AUD. AUD treatment after an episode of AH is suboptimal, with a low TR rate, high risk of alcohol relapse and poor impact of treatment on alcohol relapse.


Assuntos
Alcoolismo/complicações , Alcoolismo/terapia , Hepatite Alcoólica/terapia , Estudos de Casos e Controles , Doença Crônica , Feminino , Hepatite Alcoólica/patologia , Hepatite Alcoólica/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva
18.
Alcohol ; 80: 139-148, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30217504

RESUMO

Cutaneous burn injury is one of the most devastating injuries one can obtain, with tissue damage extending beyond the skin wound to distal organs, including the gastrointestinal tract, liver, and lungs. Multiple organ failure is a leading cause of death after burn injury, resulting in excessive systemic and localized inflammation directly contributing to end organ damage. We postulated that the gut-liver-lung inflammatory axis underscores multiple organ failure in the context of burn injury and is hyper-activated when ethanol intoxication precedes burn. Mesenchymal stem cells (MSCs) are regenerative and anti-inflammatory, and MSC treatment has been shown to be beneficial in several immune disorders and injury models. Our objective was to determine whether intravenous infusion of exogenous bone marrow-derived MSCs could reduce post-burn and intoxication pulmonary, hepatic, and systemic inflammation. Vehicle- or ethanol- (1.6 g/kg) treated mice were subjected to sham or 15% total body surface area scald burn. One hour post-injury, mice were given 5 × 105 CFSE-labeled MSCs or phosphate-buffered saline intravenously (i.v.) and were euthanized 24 h later. We assessed circulating biomarkers of inflammation and liver damage, measured cytokine and chemokine production, and quantified apoptosis in lung and liver tissue. Compared to intoxicated and burned mice, those treated with MSCs had less cellularity, limited apoptosis, and a slight reduction in the pro-inflammatory cytokine interleukin-6 (IL-6) and the neutrophil chemokine, KC (CXCL1) in lung tissue. Mice with MSCs treatment had more dramatic anti-inflammatory effects on systemic and hepatic inflammation, as serum IL-6 levels were diminished by 43%, and il6 and kc expression in liver tissue were markedly reduced, as were biomarkers of liver damage, aspartate transaminase (AST) and alanine transaminase (AST), compared with intoxicated and burned mice. Taken together, our results suggest intravenous MSCs treatment can diminish systemic inflammation, lessen hepatic damage, and decrease liver and lung apoptosis and inflammation, indicating MSCs as a novel therapy for restoring homeostasis of multiple organ systems in intoxicated burn patients.


Assuntos
Queimaduras/complicações , Etanol/toxicidade , Hepatite Alcoólica/terapia , Transplante de Células-Tronco Mesenquimais , Pneumonia/terapia , Animais , Bebedeira/complicações , Quimiocinas/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Citometria de Fluxo , Hepatite Alcoólica/etiologia , Marcação In Situ das Extremidades Cortadas , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Camundongos , Camundongos Endogâmicos C57BL , Pneumonia/etiologia , Reação em Cadeia da Polimerase
19.
Curr Med Res Opin ; 35(2): 261-273, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29781336

RESUMO

Severe alcoholic hepatitis (SAH) is a costly and worldwide public health issue with high morbidity and mortality. Specific effective treatments for SAH have yet to be established. The aim of the present article is to review the current knowledge of the pathogenesis, assessment and treatment options in patients with SAH. To date, alcohol abstinence and enteral nutrition are the recommended first-line treatments. Although corticosteroids remain the preferred therapy for certain patients with a modified Maddrey discriminant function level greater than 54, they only improve short-term survival rates. New research focuses on liver inflammation, liver regeneration, the gut-liver axis, human induced pluripotent stem cells and extracorporeal albumin dialysis. Liver transplantation is considered the last medical option for patients with SAH who are nonresponsive to other medical treatments.


Assuntos
Corticosteroides/administração & dosagem , Hepatite Alcoólica/terapia , Transplante de Fígado/métodos , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Resultado do Tratamento
20.
Clin Mol Hepatol ; 24(4): 358-366, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30360030

RESUMO

Severe acute alcoholic liver disease (SAAH) unresponsive to medical therapy shows one-year-mortality rates of up to 90%. Most transplant centers request six months of alcohol abstinence prior to transplantation, the so-called "6-month rule." This regulation is not based on strong evidence, repeatedly making it a topic of controversial debates. The majority of patients with SAAH will die before fulfilling the 6-month rule. Therefore, liver transplantation (LT) protocols are becoming more flexible towards the rigid abstinence regulation, especially concerning SAAH patients. We conducted a literature review regarding LT in SAAH and its outcomes, including post-transplant mortality and recidivism. We studied available data on PubMed from 2011 and onwards whilst including articles dealing with genetic components, medical therapy and historic snapshots of alcoholism. Emerging studies recommend LT in SAAH not responding to medical therapies even without realizing the required abstinence period, since the majority of these patients would die within 6 months. SAAH without response to medical therapy has one-year-mortality rates of up to 90%. The 6-month rule is not based on strong evidence and is repeatedly a topic of controversial debates. There is genetic linkage to alcoholism and medical therapy is not as effective as estimated, yet. The 6-months-regulation has not shown to evidently decrease the risk of recidivism post-LT, which is a lifesaving treatment in SAAH patients. Insisting on rigid sobriety rules results in excluding patients with a low risk of recidivism from being transplanted. Moreover, the genetic linkage of alcoholism must be recognized.


Assuntos
Hepatite Alcoólica/terapia , Transplante de Fígado , Álcool Desidrogenase/genética , Alcoolismo/genética , Alcoolismo/patologia , Hepatite Alcoólica/tratamento farmacológico , Humanos , Pentoxifilina/uso terapêutico , Inibidores de Fosfodiesterase/uso terapêutico , Índice de Gravidade de Doença
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