In Patients With Severe Alcoholic Hepatitis, Prednisolone Increases Susceptibility to Infection and Infection-Related Mortality, and Is Associated With High Circulating Levels of Bacterial DNA
| العنوان: | In Patients With Severe Alcoholic Hepatitis, Prednisolone Increases Susceptibility to Infection and Infection-Related Mortality, and Is Associated With High Circulating Levels of Bacterial DNA |
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| المؤلفون: | Nikhil, Vergis, Stephen R, Atkinson, Suzanne, Knapp, James, Maurice, Michael, Allison, Andrew, Austin, Ewan H, Forrest, Steven, Masson, Anne, McCune, David, Patch, Paul, Richardson, Dermot, Gleeson, Stephen D, Ryder, Mark, Wright, Mark R, Thursz |
| المصدر: | Gastroenterology |
| بيانات النشر: | W.B. Saunders, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Adult, DNA, Bacterial, Male, Prednisolone, SAH, severe alcoholic hepatitis, Infections, Severity of Illness Index, Article, MELD, Model for End-Stage Liver Disease, PCR, polymerase chain reaction, Double-Blind Method, Risk Factors, Odds Ratio, Prevalence, STOPAH Trial, Humans, Pentoxifylline, Glucocorticoids, Steroid, Liver Diseases, Alcoholic, DF, discriminant function, SAE, serious adverse event, bDNA, bacterial DNA, Hepatitis, Alcoholic, Incidence, Gastroenterology, Free Radical Scavengers, E coli, Middle Aged, United Kingdom, Anti-Bacterial Agents, MELD, CI, confidence interval, OR, odds ratio, Logistic Models, Liver, Female, STOPAH, Steroids or Pentoxifylline for Alcoholic Hepatitis, Disease Susceptibility, hibDNA, bacterial DNA >18 pg/mL |
| الوصف: | Background & Aims\ud \ud Infections are common in patients with severe alcoholic hepatitis (SAH), but little information is available on how to predict their development or their effects on patients. Prednisolone is advocated for treatment of SAH, but can increase susceptibility to infection. We compared the effects of infection on clinical outcomes of patients treated with and without prednisolone, and identified risk factors for development of infection in SAH.\ud \ud Methods\ud \ud We analyzed data from 1092 patients enrolled in a double-blind placebo-controlled trial to evaluate the efficacy of treatment with prednisolone (40 mg daily) or pentoxifylline (400 mg 3 times each day) in patients with SAH. The 2 × 2 factorial design led to 547 patients receiving prednisolone; 546 were treated with pentoxifylline. The trial was conducted in the United Kingdom from January 2011 through February 2014. Data on development of infection were collected at evaluations performed at screening, baseline, weekly during admission, on discharge, and after 90 days. Patients were diagnosed with infection based on published clinical and microbiologic criteria. Risk factors for development of infection and effects on 90-day mortality were evaluated separately in patients treated with prednisolone (n = 547) and patients not treated with prednisolone (n = 545) using logistic regression. Pretreatment blood levels of bacterial DNA (bDNA) were measured in 731 patients.\ud \ud Results\ud \ud Of the 1092 patients in the study, 135 had an infection at baseline, 251 developed infections during treatment, and 89 patients developed an infection after treatment. There was no association between pentoxifylline therapy and the risk of serious infection (P = .084), infection during treatment (P = .20), or infection after treatment (P = .27). Infections classified as serious were more frequent in patients treated with prednisolone (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.27−2.92; P = .002). There was no association between prednisolone therapy and infection during treatment (OR, 1.04; 95% CI, 0.78−1.37; P = .80). However, a higher proportion (10%) of patients receiving prednisolone developed an infection after treatment than of patients not given prednisolone (6%) (OR, 1.70; 95% CI, 1.07−2.69; P = .024). Development of infection was associated with increased 90-day mortality in patients with SAH treated with prednisolone, independent of model for end-stage liver disease or Lille score (OR, 2.46; 95% CI, 1.41−4.30; P = .002). High circulating bDNA predicted infection that developed within 7 days of prednisolone therapy, independent of Model for End-Stage Liver Disease and white blood cell count (OR, 4.68; 95% CI, 1.80−12.17; P = .001). In patients who did not receive prednisolone, infection was not independently associated with 90-day mortality (OR, 0.94; 95% CI, 0.54−1.62; P = .82) or levels of bDNA (OR, 0.83; 95% CI, 0.39−1.75; P = .62).\ud \ud Conclusions\ud \ud Patients with SAH given prednisolone are at greater risk for developing serious infections and infections after treatment than patients not given prednisolone, which may offset its therapeutic benefit. Level of circulating bDNA before treatment could identify patients at high risk of infection if given prednisolone; these data could be used to select therapies for patients with SAH. EudraCT no: 2009-013897-42; Current Controlled Trials no: ISRCTN88782125. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1528-0012 0016-5085 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::c55e3018b7a8479e7803d01c31f1d8d7Test http://europepmc.org/articles/PMC6381387Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid.dedup....c55e3018b7a8479e7803d01c31f1d8d7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15280012 00165085 |
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