Infection in Patients With Severe Alcoholic Hepatitis Treated With Steroids: Early Response to Therapy Is the Key Factor

Louvet, Alexandre; Wartel, F.; Castel, Hélène; Dharancy, Sébastien; Hollebecque, Antoine; Canva-Delcambre, V.; Deltenre, Pierre; Mathurin, Philippe

doi:10.1053/j.gastro.2009.04.062

Cited by 312 publications

(358 citation statements)

References 31 publications

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“…13,15,20 There was a lower incidence of infection and acute kidney injury in STOPAH than in some previous trials, a factor that may have contributed to the lower mortality. 21 A comparison of the baseline characteristics of the patients in our study with those of patients in other trials conducted in the past 4 years shows that in our trial, the mean age was slightly younger and the rate of encephalopathy lower; both characteristics have been consistently shown to influence mortality. 15,20 However, the bilirubin, creatinine, and albumin levels observed in patients in STOPAH were similar to those seen in patients in other studies.…”

Section: Discussionmentioning

confidence: 97%

Prednisolone or Pentoxifylline for Alcoholic Hepatitis

Thursz¹,

Forrest²,

Ryder³

2015

N Engl J Med

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BACKGROUNDAlcoholic hepatitis is a clinical syndrome characterized by jaundice and liver impairment that occurs in patients with a history of heavy and prolonged alcohol use. The short-term mortality among patients with severe disease exceeds 30%. Prednisolone and pentoxifylline are both recommended for the treatment of severe alcoholic hepatitis, but uncertainty about their benefit persists. METHODSWe conducted a multicenter, double-blind, randomized trial with a 2-by-2 factorial design to evaluate the effect of treatment with prednisolone or pentoxifylline. The primary end point was mortality at 28 days. Secondary end points included death or liver transplantation at 90 days and at 1 year. Patients with a clinical diagnosis of alcoholic hepatitis and severe disease were randomly assigned to one of four groups: a group that received a pentoxifylline-matched placebo and a prednisolone-matched placebo, a group that received prednisolone and a pentoxifylline-matched placebo, a group that received pentoxifylline and a prednisolone-matched placebo, or a group that received both prednisolone and pentoxifylline. RESULTSA total of 1103 patients underwent randomization, and data from 1053 were available for the primary end-point analysis. Mortality at 28 days was 17% (45 of 269 patients) in the placebo-placebo group, 14% (38 of 266 patients) in the prednisolone-placebo group, 19% (50 of 258 patients) in the pentoxifylline-placebo group, and 13% (35 of 260 patients) in the prednisolone-pentoxifylline group. The odds ratio for 28-day mortality with pentoxifylline was 1.07 (95% confidence interval [CI], 0.77 to 1.49; P = 0.69), and that with prednisolone was 0.72 (95% CI, 0.52 to 1.01; P = 0.06). At 90 days and at 1 year, there were no significant between-group differences. Serious infections occurred in 13% of the patients treated with prednisolone versus 7% of those who did not receive prednisolone (P = 0.002). CONCLUSIONSPentoxifylline did not improve survival in patients with alcoholic hepatitis. Prednisolone was associated with a reduction in 28-day mortality that did not reach significance and with no improvement in outcomes at 90 days or 1 year.

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Section: Discussionmentioning

confidence: 97%

Prednisolone or Pentoxifylline for Alcoholic Hepatitis

Thursz¹,

Forrest²,

Ryder³

2015

N Engl J Med

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“…Los estudios con esteroides, específicamente, incluyeron pacientes con diagnóstico confirmado por biopsia hepática, una estrategia difícilmente aplicable hoy en día (14)(15)(16)(17). Adicionalmente, los conocidos efectos adversos de los esteroides pueden ser de mayor relevancia clínica en una población particularmente susceptible a las infecciones como son los alcohólicos con afección hepática (18,19). Este estudio no demostró ninguna utilidad para la pentoxifilina y el dudoso efecto a corto plazo de los glucocorticoides es sobrepasado por el aumento significativo en el riesgo de infección (13).…”

Section: Período De Seguimiento: 12 Mesesunclassified

Ronda clínica y epidemiológica Club de revistas

Caraballo¹,

Hincapié-Osorno²,

Marín-Díaz

et al. 2015

iatreia

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RESUMENEn esta nueva edición de Ronda Clínica y Epidemiológica analizamos cinco estudios que consideramos importantes para la actualidad de la práctica clínica. El estudio RENALRIPC en el cual Zarbock y colaboradores sugieren que el acondicionamiento isquémico remoto previo a cirugía cardiovascular reduce el riesgo de presentar lesión renal aguda. El estudio CAP-START en el que Postma y colaboradores muestran que el uso de monoterapia con betalactámicos no es inferior a la combinación de estos con macrólidos o a las fluoroquinolonas para prevenir mortalidad a 90 días en pacientes con neumonía adquirida en la comunidad. El estudio STOPAH revela que ni la pentoxifilina ni la prednisolona parecen tener efecto significativo en la mortalidad a 28 días de los pacientes con hepatitis alcohólica grave. Andersson y colaboradores presentan un estudio en el cual se evidencia que postergar al menos 3 minutos el pinzamiento del cordón umbilical al nacimiento puede significar un mejor desarrollo cognitivo a los 4 años de edad, en comparación con el pinzamiento temprano. Finalizamos con una nota de prensa del Instituto de Alergias y Enfermedades Infecciosas de Estados Unidos sobre el estudio START, mostrando que el inicio de la terapia antirretroviral en pacientes con infección por VIH cuando el recuento de CD4+ es mayor de 500 células/μL reduce significativamente el riesgo de desenlaces adversos, comparado con aquellos en los que se inicia cuando el recuento de CD4+ es de 350 células/μL o menos.

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“…Second, alcohol intake directly affects the alterations of gut permeability and gut microbiomes, resulting in the translocation of microbial products, especially endotoxin, via the portal circulation to the liver. As a consequence, it activates innate immunity, causing an increased release of proinflammatory cytokines (e.g., tumor necrosis factoralpha, interleukin-1, interleukin-6), which leads to not only the progression of liver injury but also the systemic involvement resulting in SIRS (25,26). Third, the use of mouse models for alcoholic hepatitis-essentially molecules termed "damage-associated molecular patterns" (DAMPs) released from damaged hepatic cells-can act as a molecular trigger for inflammation, resulting in a wide range of immune responses, including the production of proinflammatory cytokine or the localization of immune cells to the site of injury, subsequently initiating SIRS (6,26).…”

Section: Original Article Jaruvongvanich Et Al Sirs In Alcoholic Hepmentioning

confidence: 99%