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1.
Hepatology ; 2020 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-32418225

RESUMO

We would like to thank Selck et al. for their letter. The issue they raise has both methodological and scientific interest. We clearly acknowledge in our discussion the limitations of our approach to estimate the causal impact of cold weather on alcoholic cirrhosis at a population level. In addition, as highlighted in the accompanying editorial, these associations at a population level might not hold at an individual level, and the causes of differences in alcohol intake between populations and individuals might not be the same.

2.
Hepatology ; 2020 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-32246544

RESUMO

BACKGROUND & AIMS: Alcoholic hepatitis (AH) is diagnosed by clinical criteria, although several objective scores facilitate risk stratification. Extracellular vesicles (EVs) have emerged as novel biomarkers for many diseases and are also implicated in the pathogenesis of AH. Therefore, we investigated whether plasma EV concentration and sphingolipid cargo could serve as diagnostic biomarkers for AH and inform prognosis to permit dynamic risk profiling of AH subjects. APPROACH & RESULTS: EVs were isolated and quantified from plasma samples from healthy controls, heavy drinkers, and subjects with end-stage liver disease (ESLD) due to cholestatic liver diseases and non-alcoholic steatohepatitis, decompensated alcoholic cirrhosis (AC) and AH. Sphingolipids were quantified by tandem mass spectroscopy. The median plasma EV concentration was significantly higher in AH subjects (5.38X1011 /ml) compared to healthy controls (4.38X1010 /ml, p<0.0001), heavy drinkers (1.28X1011 /ml, p<0.0001), and ESLD (5.35X1010 /ml, p<0.0001) and decompensated AC (9.2X1010 /ml, p<0.0001) disease controls. Among AH subjects, EV concentration correlated with MELD score. When EV counts were dichotomized at the median, survival probability for AH subjects at 90 days was 63.0% in the high EV group and 90.0% in the low EV group (logrank p-value=0.015). Interestingly, EV sphingolipid cargo was significantly enriched in AH when compared with healthy controls, heavy drinkers, ESLD and decompensated AC (p=0.0001). Multiple sphingolipids demonstrated good diagnostic and prognostic performance as biomarkers for AH. CONCLUSIONS: Circulating EV concentration and sphingolipid cargo signature can be used in the diagnosis and differentiation of AH from heavy drinkers, decompensated alcoholic cirrhosis, and other etiologies of end-stage liver disease and predict 90-day survival permitting dynamic risk profiling.

3.
Hepatology ; 71(2): 522-538, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31228214

RESUMO

Chronic alcohol consumption causes increased intestinal permeability and changes in the intestinal microbiota composition, which contribute to the development and progression of alcohol-related liver disease. In this setting, little is known about commensal fungi in the gut. We studied the intestinal mycobiota in a cohort of patients with alcoholic hepatitis, patients with alcohol use disorder, and nonalcoholic controls using fungal-specific internal transcribed spacer amplicon sequencing of fecal samples. We further measured serum anti-Saccharomyces cerevisiae antibodies (ASCA) as a systemic immune response to fungal products or fungi. Candida was the most abundant genus in the fecal mycobiota of the two alcohol groups, whereas genus Penicillium dominated the mycobiome of nonalcoholic controls. We observed a lower diversity in the alcohol groups compared with controls. Antibiotic or steroid treatment was not associated with a lower diversity. Patients with alcoholic hepatitis had significantly higher ASCA levels compared to patients with alcohol use disorder and to nonalcoholic controls. Within the alcoholic hepatitis cohort, patients with levels of at least 34 IU/mL had a significantly lower 90-day survival (59%) compared with those with ASCA levels less than 34 IU/mL (80%) with an adjusted hazard ratio of 3.13 (95% CI, 1.11-8.82; P = 0.031). Conclusion: Patients with alcohol-associated liver disease have a lower fungal diversity with an overgrowth of Candida compared with controls. Higher serum ASCA was associated with increased mortality in patients with alcoholic hepatitis. Intestinal fungi may serve as a therapeutic target to improve survival, and ASCA may be useful to predict the outcome in patients with alcoholic hepatitis.

4.
Gastroenterol. hepatol. (Ed. impr.) ; 42(10): 657-676, dic. 2019. ilus, graf, tab
Artigo em Espanhol | IBECS | ID: ibc-188200

RESUMO

La enfermedad hepática alcohólica (EHA) es la causa más prevalente de enfermedad hepática avanzada y cirrosis hepática en Europa incluyendo a España. De acuerdo con la Organización Mundial de la Salud la fracción de cirrosis hepática atribuible al uso de alcohol en España es del 73,8% entre varones y del 56,3% entre mujeres. La EHA incluye diversos estadios como la esteatohepatitis, la cirrosis y el cáncer hepatocelular. Además, enfermos con EHA de base e ingesta abundante de alcohol pueden desarrollar hepatitis alcohólica, que cursa con una elevada mortalidad. Hasta la fecha, el único tratamiento efectivo para tratar la EHA es la abstinencia prolongada. No existen tratamientos específicos, y el único tratamiento que aumenta la esperanza de vida en la hepatitis alcohólica es la prednisolona. Para enfermos con hepatitis alcohólica que no responden al tratamiento, algunos centros ofrecen la posibilidad de un trasplante precoz. Estas guías de práctica clínica tienen como objetivo proponer recomendaciones sobre la EHA teniendo en cuenta su relevancia como causa de hepatopatía crónica avanzada y cirrosis hepática en nuestro medio. En el presente trabajo se propone como objetivo responder las preguntas claves para la práctica clínica de Gastroenterología, Hepatología, así como de Medicina Interna y centros de salud primaria, poniendo al servicio del profesional de la salud la información más actualizada respecto al manejo y tratamiento de la EHA. Estas guías proporcionan recomendaciones basadas en la evidencia para el manejo clínico de esta enfermedad


Alcohol-related liver disease (ARLD) is the most prevalent cause of advanced liver disease and liver cirrhosis in Europe, including Spain. According to the World Health Organization the fraction of liver cirrhosis attributable to alcohol use in Spain is 73.8% among men and 56.3% among women. ARLD includes various stages such as steatohepatitis, cirrhosis and hepatocellular cancer. In addition, patients with underlying ARLD and heavy alcohol intake may develop alcoholic hepatitis, which is associated with high mortality. To date, the only effective treatment to treat ARLD is prolonged withdrawal. There are no specific treatments, and the only treatment that increases life expectancy in alcoholic hepatitis is prednisolone. For patients with alcoholic hepatitis who do not respond to treatment, some centres offer the possibility of an early transplant. These clinical practice guidelines aim to propose recommendations on ARLD taking into account their relevance as a cause of advanced chronic liver disease and liver cirrhosis in our setting. This paper aims to answer the key questions for the clinical practice of Gastroenterology, Hepatology, as well as Internal Medicine and Primary Health Centres, making the most up-to-date information regarding the management and treatment of ARLD available to health professionals. These guidelines provide evidence-based recommendations for the clinical management of this disease


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Hepatite Alcoólica/epidemiologia , Consenso , Hepatopatias/epidemiologia , Alcoolismo/epidemiologia , Espanha/epidemiologia , Hepatopatias/diagnóstico , Hepatopatias/terapia , Saúde Pública , História Natural , Cirrose Hepática/complicações , Fatores de Risco
5.
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
6.
Gastroenterol Hepatol ; 42(10): 657-676, 2019 Dec.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31771785

RESUMO

Alcohol-related liver disease (ARLD) is the most prevalent cause of advanced liver disease and liver cirrhosis in Europe, including Spain. According to the World Health Organization the fraction of liver cirrhosis attributable to alcohol use in Spain is 73.8% among men and 56.3% among women. ARLD includes various stages such as steatohepatitis, cirrhosis and hepatocellular cancer. In addition, patients with underlying ARLD and heavy alcohol intake may develop alcoholic hepatitis, which is associated with high mortality. To date, the only effective treatment to treat ARLD is prolonged withdrawal. There are no specific treatments, and the only treatment that increases life expectancy in alcoholic hepatitis is prednisolone. For patients with alcoholic hepatitis who do not respond to treatment, some centres offer the possibility of an early transplant. These clinical practice guidelines aim to propose recommendations on ARLD taking into account their relevance as a cause of advanced chronic liver disease and liver cirrhosis in our setting. This paper aims to answer the key questions for the clinical practice of Gastroenterology, Hepatology, as well as Internal Medicine and Primary Health Centres, making the most up-to-date information regarding the management and treatment of ARLD available to health professionals. These guidelines provide evidence-based recommendations for the clinical management of this disease.

7.
Nat Commun ; 10(1): 3126, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31311938

RESUMO

Alcoholic hepatitis (AH) is a life-threatening condition characterized by profound hepatocellular dysfunction for which targeted treatments are urgently needed. Identification of molecular drivers is hampered by the lack of suitable animal models. By performing RNA sequencing in livers from patients with different phenotypes of alcohol-related liver disease (ALD), we show that development of AH is characterized by defective activity of liver-enriched transcription factors (LETFs). TGFß1 is a key upstream transcriptome regulator in AH and induces the use of HNF4α P2 promoter in hepatocytes, which results in defective metabolic and synthetic functions. Gene polymorphisms in LETFs including HNF4α are not associated with the development of AH. In contrast, epigenetic studies show that AH livers have profound changes in DNA methylation state and chromatin remodeling, affecting HNF4α-dependent gene expression. We conclude that targeting TGFß1 and epigenetic drivers that modulate HNF4α-dependent gene expression could be beneficial to improve hepatocellular function in patients with AH.


Assuntos
Hepatite Alcoólica/genética , Fator 4 Nuclear de Hepatócito/metabolismo , Hepatócitos/patologia , Fígado/patologia , Fator de Crescimento Transformador beta1/metabolismo , Adulto , Idoso , Animais , Biópsia , Montagem e Desmontagem da Cromatina , Metilação de DNA , Progressão da Doença , Epigênese Genética , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Hepatite Alcoólica/patologia , Fator 4 Nuclear de Hepatócito/genética , Humanos , Fígado/citologia , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Análise de Sequência de RNA , Fator de Crescimento Transformador beta1/genética
8.
Clin Gastroenterol Hepatol ; 17(11): 2320-2329.e12, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30708110

RESUMO

BACKGROUND & AIMS: Despite recent advances in treatment of viral hepatitis, liver-related mortality is high, possibly owing to the large burden of advanced alcohol-related liver disease (ALD). We investigated whether patients with ALD are initially seen at later stages of disease development than patients with hepatitis C virus (HCV) infection or other etiologies. METHODS: We performed a cross-sectional study of 3453 consecutive patients with either early or advanced liver disease (1699 patients with early and 1754 with advanced liver disease) seen at 17 tertiary care liver or gastrointestinal units worldwide, from August 2015 through March 2017. We collected anthropometric, etiology, and clinical information, as well as and model for end-stage liver disease scores. We used unconditional logistic regression to estimate the odds ratios for evaluation at late stages of the disease progression. RESULTS: Of the patients analyzed, 81% had 1 etiology of liver disease and 17% had 2 etiologies of liver disease. Of patients seen at early stages for a single etiology, 31% had HCV infection, 21% had hepatitis B virus infection, and 17% had nonalcoholic fatty liver disease, whereas only 3.8% had ALD. In contrast, 29% of patients seen for advanced disease had ALD. Patients with ALD were more likely to be seen at specialized centers, with advanced-stage disease, compared with patients with HCV-associated liver disease (odds ratio, 14.1; 95% CI, 10.5-18.9; P < .001). Of patients with 2 etiologies of liver disease, excess alcohol use was associated with 50% of cases. These patients had significantly more visits to health care providers, with more advanced disease, compared with patients without excess alcohol use. The mean model for end-stage liver disease score for patients with advanced ALD (score, 16) was higher than for patients with advanced liver disease not associated with excess alcohol use (score, 13) (P < .01). CONCLUSIONS: In a cross-sectional analysis of patients with liver disease worldwide, we found that patients with ALD are seen with more advanced-stage disease than patients with HCV-associated liver disease. Of patients with 2 etiologies of liver disease, excess alcohol use was associated with 50% of cases. Early detection and referral programs are needed for patients with ALD worldwide.

9.
Hepatology ; 69(5): 1916-1930, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30324707

RESUMO

Risk of alcoholic cirrhosis is determined by genetic and environmental factors. We aimed to investigate if climate has a causal effect on alcohol consumption and its weight on alcoholic cirrhosis. We collected extensive data from 193 sovereign countries as well as 50 states and 3,144 counties in the United States. Data sources included World Health Organization, World Meteorological Organization, and the Institute on Health Metrics and Evaluation. Climate parameters comprised Koppen-Geiger classification, average annual sunshine hours, and average annual temperature. Alcohol consumption data, pattern of drinking, health indicators, and alcohol-attributable fraction (AAF) of cirrhosis were obtained. The global cohort revealed an inverse correlation between mean average temperature and average annual sunshine hours with liters of annual alcohol consumption per capita (Spearman's rho -0.5 and -0.57, respectively). Moreover, the percentage of heavy episodic drinking and total drinkers among population inversely correlated with temperature -0.45 and -0.49 (P < 0.001) and sunshine hours -0.39 and -0.57 (P < 0.001). Importantly, AAF was inversely correlated with temperature -0.45 (P < 0.001) and sunshine hours -0.6 (P < 0.001). At a global level, all included parameters in the univariable and multivariable analysis showed an association with liters of alcohol consumption and drinkers among population once adjusted by potential confounders. In the multivariate analysis, liters of alcohol consumption associated with AAF. In the United States, colder climates showed a positive correlation with the age-standardized prevalence of heavy and binge drinkers. Conclusion: These results suggest that colder climates may play a causal role on AAF mediated by alcohol consumption.

12.
J Hepatol ; 69(2): 396-405, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29654817

RESUMO

BACKGROUND & AIMS: The degree of cholestasis is an important disease driver in alcoholic hepatitis, a severe clinical condition that needs new biomarkers and targeted therapies. We aimed to identify the largely unknown mechanisms and biomarkers linked to cholestasis in alcoholic hepatitis. METHODS: Herein, we analyzed a well characterized cohort of patients with alcoholic hepatitis and correlated clinical and histological parameters and outcomes with serum bile acids and fibroblast growth factor 19 (FGF19), a major regulator of bile acid synthesis. RESULTS: We found that total and conjugated bile acids were significantly increased in patients with alcoholic hepatitis compared with controls. Serum FGF19 levels were strongly increased and gene expression of FGF19 was induced in biliary epithelial cells and ductular cells of patients with alcoholic hepatitis. De novo bile acid synthesis (CYP7A1 gene expression and C4 serum levels) was significantly decreased in patients with alcoholic hepatitis. Importantly, total and conjugated bile acids correlated positively with FGF19 and with disease severity (model for end-stage liver disease score). FGF19 correlated best with conjugated cholic acid, and model for end-stage liver disease score best with taurine-conjugated chenodeoxycholic acid. Univariate analysis demonstrated significant associations between FGF19 and bilirubin as well as gamma glutamyl transferase, and negative correlations between FGF19 and fibrosis stage as well as polymorphonuclear leukocyte infiltration, in all patients with alcoholic hepatitis. CONCLUSION: Serum FGF19 and bile acids are significantly increased in patients with alcoholic hepatitis, while de novo bile acid synthesis is suppressed. Modulation of bile acid metabolism or signaling could represent a promising target for treatment of alcoholic hepatitis in humans. LAY SUMMARY: Understanding the underlying mechanisms that drive alcoholic hepatitis is important for the development of new biomarkers and targeted therapies. Herein, we describe a molecule that is increased in patients with alcoholic hepatitis. Modulating the molecular pathway of this molecule might lead to promising targets for the treatment of alcoholic hepatitis.


Assuntos
Ácidos e Sais Biliares , Colestase , Fatores de Crescimento de Fibroblastos/sangue , Hepatite Alcoólica , Neutrófilos/patologia , Ácidos e Sais Biliares/biossíntese , Ácidos e Sais Biliares/sangue , Ácidos e Sais Biliares/metabolismo , Biomarcadores/sangue , Colestase/etiologia , Colestase/metabolismo , Correlação de Dados , Feminino , Hepatite Alcoólica/sangue , Hepatite Alcoólica/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Infiltração de Neutrófilos , Índice de Gravidade de Doença , Transdução de Sinais/fisiologia
13.
Therap Adv Gastroenterol ; 11: 1756283X17743419, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29383024

RESUMO

Background: Episodes of hepatic encephalopathy (HE) have been related to low survival rate. However, the relation between its clinical evolution and mortality has not been assessed. Methods: A retrospective analysis of 245 cirrhotic patients admitted for an acute episode of HE (⩾grade 2) or who developed an HE episode after an upper gastrointestinal bleeding (UGIB) event was performed to assess the relation between time in HE and transplant-free survival. Results: Median (IQR25-75) time in HE was 48 h (24-96 h) in the whole cohort. Patients who presented a longer time in HE (>48 h; n = 89) exhibited a lower transplant-free survival at 28 days (67.2% versus 88.9%, p < 0.001), 90 days (48.7% versus 73.8%, p < 0.001) and 365 days (30.3% versus 53.2%, p < 0.001), as compared to those with less time in HE (⩽48 h; n = 156). Survival rates remained significantly different, with lower percentages in the group with time in HE >48 h, when comparing patients according to baseline HE grade (2 versus ⩾3) or model for end-stage liver disease (MELD) function (⩽15 versus >15). Time in HE was also an independent risk factor for mortality at each time point, hazard ratio (HR) (95 CI%) 28 days 2.59 (1.39-4.84); 90 days 1.98 (1.28-3.1) and 365 days 1.5 (1.08-2.19). Conclusions: The duration of the acute HE episode determines survival in cirrhotic patients independently of liver function and baseline HE grade.

15.
Therap Adv Gastroenterol ; 10(8): 619-629, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28835776

RESUMO

BACKGROUND: We aimed to investigate the early changes in liver and spleen stiffness measurement (LSM, SSM) in hepatitis C virus (HCV) patients with compensated advanced chronic liver disease (cACLD) treated with new antivirals (DAA) to elucidate factors determining the initial change in stiffness and its implications for the long-term follow up of HCV-cured patients. METHODS: A total of 41 patients with cACLD who started DAA therapy underwent LSM and SSM at baseline, week 4, end of treatment (EOT), 24 and 48 weeks of follow up using transient elastography. RESULTS: LSM improved rapidly during the first 4 weeks of treatment (baseline: 20.8kPa; week 4: 17.5kPa, p = 0.002), with no significant changes between week 4 and EOT (18.3kPa, p = 0.444) and between EOT and 48-week follow up (14.3kPa, p = 0.148). Likewise, SSM improved rapidly (baseline: 45.7kPa; week 4: 33.8kPa, p = 0.047), with no significant changes between week 4 and EOT (30.8kPa, p = 0.153) and between EOT and 48-week follow up (31.2kPa, p = 0.317). A higher decrease in LSM was observed in patients with baseline ALT ⩾ twofold upper limit normal (2 × ULN) than in those with ALT < 2 × ULN (-5.7kPa versus -1.6kPa). Patients who presented a decrease in LSM ⩾ 10% during treatment compared with those with LSM < 10% decrease, showed lower SSM values, higher platelet counts and lower bilirubin levels at 24-week follow up. Those with decrease in SSM ⩾ 10%, presented a higher increase in platelets than those with SSM < 10% change (p = 0.015). CONCLUSIONS: LSM and SSM decrease very rapidly during DAA treatment in cACLD patients suggesting that it most probably reflects a reduction in inflammation rather than in fibrosis. cACLD patients should be maintained under surveillance independently of stiffness changes, because advanced fibrosis can still be present.

16.
Therap Adv Gastroenterol ; 9(6): 823-835, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27803737

RESUMO

BACKGROUND: Ornithine phenylacetate (OP) has been proven effective in lowering ammonia plasma levels in animals, and to be well tolerated in cirrhotic patients. A trial to assess OP efficacy in lowering plasma ammonia levels versus placebo in cirrhotic patients after an upper gastrointestinal bleeding was performed. The primary outcome was a decrease in venous plasma ammonia at 24 hours. METHODS: A total of 38 consecutive cirrhotic patients were enrolled within 24 hours of an upper gastrointestinal bleed. Patients were randomized (1:1) to receive OP (10 g/day) or glucosaline for 5 days. RESULTS: The primary outcome was not achieved. A progressive decrease in ammonia was observed in both groups, being slightly greater in the OP group, with significant differences only at 120 hours. The subanalysis according to Child-Pugh score showed a statistically significant ammonia decrease in Child-Pugh C-treated patients at 36 hours, as well as in the time-normalized area under the curve (TN-AUC) 0-120 hours in the OP group [40.16 µmol/l (37.7-42.6); median (interquartile range) (IQR)] versus placebo group [65.5 µmol/l (54-126);p = 0.036]. A decrease in plasma glutamine levels was observed in the treated group compared with the placebo group, and was associated with the appearance of phenylacetylglutamine in urine. Adverse-event frequency was similar in both groups. No differences in hepatic encephalopathy incidence were observed. CONCLUSIONS: OP failed to significantly decrease plasma ammonia at the given doses (10 g/day). Higher doses of OP might be required in Child-Pugh A and B patients. OP appeared well tolerated.

17.
Dig Liver Dis ; 48(10): 1214-9, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27388262

RESUMO

BACKGROUND AND AIMS: Transient elastography has been proposed as a tool to predict the risk of decompensation in patients with chronic liver disease. We aimed to identify risk groups of disease progression, using a combination of baseline liver stiffness measurement (LSM) and its change over time (delta-LSM) in patients with compensated advanced chronic liver disease (cACLD). METHODS: Ninety-four patients with baseline LSM ≥10kPa, Child-Pugh score 5 and without previous decompensation were included. A second LSM was performed during follow-up and data on liver function and liver-related events were collected. The primary endpoint was a composite that included death, liver decompensation and impairment in at least 1 point in Child-Pugh score. RESULTS: After a median follow-up of 43.6 months, 15% of patients presented the primary endpoint. Multivariate analysis identified baseline LSM (OR 1.12, P=0.002) and delta-LSM (OR 1.02, P=0.048) as independent predictors of the primary endpoint. A high risk group represented by patients with baseline LSM ≥21kPa and delta-LSM ≥10% (risk of progression 47.1%, 95% CI: 23-71%) was identified, while patients with LSM <21kPa and delta-LSM <10% presented zero risk of progression (P=0.03). CONCLUSIONS: Simple classification rules using baseline LSM and delta-LSM identify cACLD patients at low or high risk of disease progression.


Assuntos
Progressão da Doença , Técnicas de Imagem por Elasticidade , Elasticidade , Hepatopatias/diagnóstico por imagem , Fígado/fisiopatologia , Idoso , Doença Crônica , Feminino , Humanos , Fígado/diagnóstico por imagem , Hepatopatias/fisiopatologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Espanha
19.
Liver Int ; 36(7): 994-1001, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26643867

RESUMO

BACKGROUND & AIMS: Antibiotic prophylaxis is a cornerstone in the management of acute variceal bleeding. However, emergence of multiresistant bacteria and antibiotic-associated complications is a growing problem in cirrhosis. It has been proposed that certain low-risk populations may have good outcomes without antibiotic. We aimed to analyse the stratified risk of bacterial infection after a variceal bleeding in previously considered low-risk patients. METHODS: We analysed prospective data from all consecutive cirrhotic patients with acute variceal bleeding admitted to our tertiary hospital between 2004 and 2012. All patients received somatostatin, variceal ligation and antibiotic prophylaxis. Patients were followed until day 42 or death. Patients were stratified based on Child-Pugh class. Within the low-risk strata, further one-step stratification was performed using baseline risk factors identified through logistic regression multivariate adjustment. RESULTS: Two hundred and fifteen patients were included. Twenty-seven patients (12.5%) developed 32 bacterial infections within 6 weeks after the index bleeding. Multivariate adjustment identified alcohol consumption as a significant risk factor for infection. Within previously considered low-risk patients (Child-Pugh A), the risk of infection was significantly higher in patients with active alcohol consumption (21.4% vs. 0% in non-drinkers, P = 0.015). The risk of infection in Child-Pugh A and B patients with non-alcohol cirrhosis receiving antibiotics was very low (2/81, 2.5%). CONCLUSIONS: Alcohol consumption significantly increased the risk of infection after a variceal bleeding in previously considered low-risk patients. Within Child-Pugh A class, patients with active alcohol consumption should not be considered at low risk of infection.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Antibacterianos/uso terapêutico , Infecções Bacterianas/epidemiologia , Varizes Esofágicas e Gástricas/complicações , Hemorragia Gastrointestinal/complicações , Cirrose Hepática/complicações , Idoso , Antibioticoprofilaxia/métodos , Infecções Bacterianas/tratamento farmacológico , Varizes Esofágicas e Gástricas/terapia , Feminino , Hemorragia Gastrointestinal/terapia , Humanos , Ligadura , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Fatores de Risco , Somatostatina/uso terapêutico , Espanha , Centros de Atenção Terciária
20.
J Hepatol ; 60(2): 275-81, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24128414

RESUMO

BACKGROUND & AIMS: In spite of the high incidence of hepatic encephalopathy (HE) in cirrhosis, there are few observational studies. METHODS: We performed an analysis to define the characteristics of HE and associated features using the database of the Canonic Study. Clinical, laboratory and survival data of 1348 consecutive cirrhotic patients admitted with an acute decompensation were compared according to the presence (n=406) or absence of HE and of acute-on-chronic liver failure (ACLF) (n=301). RESULTS: HE development was independently associated with previous HE episodes; survival probabilities worsen in relation to the presence and grade of HE. There were marked differences between HE associated (n=174) and not associated (n=286) to ACLF. HE not associated with ACLF occurred in older cirrhotics, inactive drinkers, without severe liver failure or systemic inflammatory reaction and in relation to diuretic use. In contrast, HE associated with ACLF occurred in younger cirrhotics, more frequently alcoholics, with severe liver failure and systemic inflammatory reaction, and in relation to bacterial infections, active alcoholism and/or dilutional hyponatremia. Prognosis was relatively preserved in the first and extremely poor in the second group. Independent risk factors of mortality in patients with HE were age, bilirubin, INR, creatinine, sodium, and HE grade. CONCLUSIONS: In cirrhosis, previous HE identifies a subgroup of patients that is especially vulnerable for developing new episodes of HE. The course of HE appears to be different according to the presence of ACLF.


Assuntos
Encefalopatia Hepática/etiologia , Encefalopatia Hepática/mortalidade , Cirrose Hepática/complicações , Cirrose Hepática/mortalidade , Falência Hepática Aguda/complicações , Falência Hepática Aguda/mortalidade , Idoso , Doença Hepática Terminal/complicações , Doença Hepática Terminal/mortalidade , Feminino , Humanos , Cirrose Hepática Alcoólica/complicações , Cirrose Hepática Alcoólica/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologia , Fatores de Tempo
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