泼尼松龙或己酮可可碱治疗酒精性肝炎。

Prednisolone or pentoxifylline for alcoholic hepatitis.

机构信息

From Imperial College (M.R.T., N.V.), King's College Hospital (J.O.), and the Royal Free Hospital (D.P.), London, Royal Liverpool Hospital (P. Richardson) and Aintree Hospital (S.H.), Liverpool, Addenbrookes Hospital, Cambridge (M.A.), Derby Royal Hospital, Derby (A.A.), Southampton Clinical Trials Unit, University of Southampton (M.B., N.D., J.M., I.R., P. Roderick, L.S.), and University Hospital Southampton NHS Foundation Trust (M.W.), Southampton, Faculty of Medical Sciences, Newcastle University (C.P.D.), and Newcastle upon Tyne Hospitals NHS Foundation Trust (S.M.), Newcastle upon Tyne, Sheffield Teaching Hospitals Foundation Trust, Sheffield (D.G.), Edinburgh Royal Infirmary, Edinburgh (A. MacGilchrist), Leicester Royal Infirmary, Leicester (A.G.), Bristol Royal Infirmary, Bristol (A. McCune), Nottingham University Hospitals NHS Trust and National Institute for Health Research Biomedical Research Unit, Queens Medical Centre, Nottingham (S.R.), and the Glasgow Royal Infirmary, Glasgow (E.H.F.) - all in the United Kingdom.

出版信息

N Engl J Med. 2015 Apr 23;372(17):1619-28. doi: 10.1056/NEJMoa1412278.

DOI:10.1056/NEJMoa1412278

PMID:25901427

Abstract

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.

METHODS

We 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.

RESULTS

A 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).

CONCLUSIONS

Pentoxifylline 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. (Funded by the National Institute for Health Research Health Technology Assessment program; STOPAH EudraCT number, 2009-013897-42 , and Current Controlled Trials number, ISRCTN88782125 ).

摘要

背景

酒精性肝炎是一种以黄疸和肝功能损害为特征的临床综合征，发生于大量和长期饮酒史的患者。重症患者的短期死亡率超过 30%。泼尼松龙和己酮可可碱均被推荐用于治疗重症酒精性肝炎，但对其疗效仍存在不确定性。

方法

我们进行了一项多中心、双盲、随机试验，采用 2×2 析因设计，以评估泼尼松龙或己酮可可碱治疗的效果。主要终点是 28 天死亡率。次要终点包括 90 天和 1 年时的死亡或肝移植。临床诊断为酒精性肝炎和重症疾病的患者被随机分配至四组之一：一组接受己酮可可碱匹配安慰剂和泼尼松龙匹配安慰剂，一组接受泼尼松龙和己酮可可碱匹配安慰剂，一组接受己酮可可碱和泼尼松龙匹配安慰剂，或一组接受泼尼松龙和己酮可可碱。

结果

共有 1103 名患者接受了随机分组，1053 名患者的数据可用于主要终点分析。28 天死亡率安慰剂-安慰剂组为 17%（269 例患者中 45 例），泼尼松龙-安慰剂组为 14%（266 例患者中 38 例），己酮可可碱-安慰剂组为 19%（258 例患者中 50 例），泼尼松龙-己酮可可碱组为 13%（260 例患者中 35 例）。己酮可可碱的 28 天死亡率比值比为 1.07（95%置信区间，0.77 至 1.49；P=0.69），泼尼松龙的比值比为 0.72（95%置信区间，0.52 至 1.01；P=0.06）。90 天和 1 年时，各组间无显著差异。接受泼尼松龙治疗的患者中 13%发生严重感染，而未接受泼尼松龙治疗的患者中为 7%（P=0.002）。