Prednisolone with vs without pentoxifylline and survival of patients with severe alcoholic hepatitis: a randomized clinical trial.
نویسندگان
چکیده
IMPORTANCE Prednisolone or pentoxifylline is recommended for severe alcoholic hepatitis, a life-threatening disease. The benefit of their combination is unknown. OBJECTIVE To determine whether the addition of pentoxifylline to prednisolone is more effective than prednisolone alone. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized, double-blind clinical trial conducted between December 2007 and March 2010 in 1 Belgian and 23 French hospitals of 270 patients aged 18 to 70 years who were heavy drinkers with severe biopsy-proven alcoholic hepatitis, as indicated by recent onset of jaundice in the prior 3 months and a Maddrey score of at least 32. Duration of follow-up was 6 months. The last included patient completed the study in October 2010. None of the patients were lost to follow-up for the main outcome. INTERVENTION Patients were randomly assigned to receive either a combination of 40 mg of prednisolone once a day and 400 mg of pentoxifylline 3 times a day (n=133) for 28 days, or 40 mg of prednisolone and matching placebo (n=137) for 28 days. MAIN OUTCOMES AND MEASURES Six-month survival, with secondary end points of development of hepatorenal syndrome and response to therapy based on the Lille model, which defines treatment nonresponders after 7 days of initiation of treatment. RESULTS In intention-to-treat analysis, 6-month survival was not different in the pentoxifylline-prednisolone and placebo-prednisolone groups (69.9% [95% CI, 62.1%-77.7%] vs 69.2% [95% CI; 61.4%-76.9%], P = .91), corresponding to 40 vs 42 deaths, respectively. In multivariable analysis, only the Lille model and the Model for End-Stage Liver Disease score were independently associated with 6-month survival. At 7 days, response to therapy assessed by the Lille model was not significantly different between the 2 groups (Lille model score, 0.41 [95% CI, 0.36-0.46] vs 0.40 [95% CI, 0.35-0.45], P = .80). The probability of being a responder was not different in both groups (62.6% [95% CI, 53.9%-71.3%] vs 61.9% [95% CI, 53.7%-70.3%], P = .91). The cumulative incidence of hepatorenal syndrome at 6 months was not significantly different in the pentoxifylline-prednisolone and the placebo-prednisolone groups (8.4% [95% CI, 4.8%-14.8%] vs 15.3% [95% CI, 10.3%-22.7%], P = .07). CONCLUSION AND RELEVANCE In patients with alcoholic hepatitis, 4-week treatment with pentoxifylline and prednisolone, compared with prednisolone alone, did not result in improved 6-month survival. The study may have been underpowered to detect a significant difference in incidence of hepatorenal syndrome, which was less frequent in the group receiving pentoxifylline. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01214226.
منابع مشابه
Pentoxifylline Plus Prednisolone versus Pentoxifylline Only for Severe Alcoholic Hepatitis: A Randomized Controlled Clinical Trial
BACKGROUND Prednisolone and pentoxifylline (PTX) have been shown to be individually useful in severe alcoholic hepatitis with Maddrey discriminant function (MDF) score ≥32. Previous report suggests that PTX is probably superior to prednisolone alone. However the efficacy of PTX and prednisolone combination over PTX alone in the management of acute alcoholic hepatitis (MDF score ≥32) is yet unre...
متن کاملPrednisolone and Pentoxifylline Combination in Patients with Severe Acute Alcoholic Hepatitis
Clinical manifestation of alcoholic hepatitis is a serious and adverse sign of progression of alcoholic liver disease. Therapy of acute alcoholic hepatitis is currently limited to symptomatic therapy and prednisolone. The aim of our study was to analyze pentoxifylline and prednisolone combination in patients with severe acute alcoholic hepatitis. 136 patients with severe acute alcoholic hepatit...
متن کاملTreatment of severe alcoholic hepatitis with corticosteroids and pentoxifylline.
Despite being themost frequently abused drug for centuries, alcohol was not recognized as a direct hepatotoxin until the 1960s.1 Alcohol abuse accounts for the third leading preventable causeofdeath and the secondmost commoncauseof cirrhosis after hepatitis C virus infection in the United States.2,3 Alcoholichepatitis is a commoncomplicationofalcohol abuse; its severity can range frommild to se...
متن کاملTreatment of alcoholic hepatitis: is this a “dead-end”?
Alcoholic hepatitis (AH) is a clinical syndrome characterized by jaundice and liver failure that develops in subjects with chronic and active alcohol abuse [1]. The shortterm mortality in patients with severe disease, as defined by the Maddrey’s discriminant function, exceeds 30% [2]. Up to now, only two drugs, prednisolone and pentoxifylline, have shown some efficacy for the treatment of this ...
متن کاملPrednisolone or pentoxifylline for alcoholic hepatitis.
BACKGROUND Alcoholic 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. ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- JAMA
دوره 310 10 شماره
صفحات -
تاریخ انتشار 2013