Antioxidants versus corticosteroids in the treatment of severe alcoholic hepatitis—A randomised clinical trial

Phillips, M; Curtis, Howard; Portmann, Bernard; Donaldson, Nora; Bomford, Adrian; O’Grady, John

doi:10.1016/j.jhep.2005.11.039

Cited by 186 publications

(117 citation statements)

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“…[7][8][9] In patients with DF Ն 32, several RCTs and a recent meta-analysis showed that corticosteroids improve shortterm survival. 1,5,[10][11][12][13][14] However, novel strategies or molecules are required, in light of the fact that approximately 40% of patients die at 6 months. 15 Therefore, improvement in the prediction of mortality in severe AH is warranted.…”

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confidence: 99%

The Lille model: A new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids

et al. 2007

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Early identification of patients with severe (discriminant function > 32) alcoholic hepatitis (AH) not responding to corticosteroids is crucial. We generated a specific prognostic model (Lille model) to identify candidates early on for alternative therapies. Three hundred twenty patients with AH prospectively treated by corticosteroids were included in the development cohort and 118 in its validation. Baseline data and a change in bilirubin at day 7 were tested. The model was generated by logistic regression. The model combining six reproducible variables (age, renal insufficiency, albumin, prothrombin time, bilirubin, and evolution of bilirubin at day 7) was highly predictive of death at 6 months (P < 0.000001). The area under the receiver operating characteristic (AUROC) curve of the Lille model was 0.89 ؎ 0.02, higher than the Child-Pugh (0.62 ؎ 0.04, P < 0.00001) or Maddrey scores (0.66 ؎ 0.04, P < 0.00001). In the validation cohort, its AUROC was 0.85 ؎ 0.04, still higher than the other models, including MELD (0.72 ؎ 0.05, P ‫؍‬ 0.01) and Glasgow scores (0.67 ؎ 0.05, P ‫؍‬ 0.0008). Patients above the ideal cutoff of 0.45 showed a marked decrease in 6-month survival as compared with others: 25% ؎ 3.8% versus 85% ؎ 2.5%, P < 0.0001. This cutoff was able to identify approximately 75% of the observed deaths. Conclusion: In the largest cohort to date of patients with severe AH, we demonstrate that the term "nonresponder" can now be extended to patients with a Lille score above 0.45, which corresponds to 40% of cases. Early identification of subjects with substantial risk of death according to the Lille model will improve management of patients suffering from severe AH and will aid in the design of future studies for alternative therapies. (HEPATOLOGY 2007;45:1348-1354 T he treatment of severe forms of alcoholic hepatitis (AH) constitutes a major challenge in management of severe alcoholic liver disease. Before the era of the Maddrey function (DF), 1,2 clinicians faced substantial difficulties in identifying subgroups of patients with high risk of death over a short term; as a consequence, survival of untreated patients enrolled in randomized controlled trials (RCTs) ranged from 0 to 81%. 3 Since the use of DF (DF Ն 32) in several RCTs, 1,4-6 spontaneous 2-month survival has been approximately 50%. The DF clearly demonstrates the tremendous progress provided by elaborating specific prognostic functions for AH. The advantage of accurate models has been confirmed by the growing importance of the MELD score in the selection of candidates for liver transplantation. [7][8][9] In patients with DF Ն 32, several RCTs and a recent meta-analysis showed that corticosteroids improve shortterm survival. 1,5,10-14 However, novel strategies or molecules are required, in light of the fact that approximately 40% of patients die at 6 months. 15 Therefore, improvement in the prediction of mortality in severe AH is warranted. However, we lack evidence supporting the higher efficacy of new models such as MELD and Glasgow scores compa...

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The Lille model: A new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids

et al. 2007

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“…This study strongly suggests that replenishing GSH could be beneficial in patients with severe AH receiving prednisolone. Whether the use of antioxidants alone is able to improve survival in patients with AH is controversial [19,20]. While the study by Phillips et al [19] showed no beneficial effect, a clinical trial by Stewart et al [20] showed improved short-term outcome.…”

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“…Whether the use of antioxidants alone is able to improve survival in patients with AH is controversial [19,20]. While the study by Phillips et al [19] showed no beneficial effect, a clinical trial by Stewart et al [20] showed improved short-term outcome. Further studies including end-points other than survival are clearly needed to assess the efficacy of antioxidants in alcoholic liver disease including AH.…”

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Alcoholic hepatitis: should we combine old drugs for better results?

Cabezas

Bataller

2016

Hepatol Int

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Alcoholic liver disease (ALD) is the main cause of cirrhosis worldwide [1]. Despite its high prevalence, ALD has received little attention in the liver community and there is a clear lack of programs for early detection and novel targeted therapies for advanced forms. ALD encloses a wide spectrum of features, ranging from simple steatosis, steatohepatitis, and cirrhosis to hepatocellular carcinoma [2]. Patients with underlying ALD and heavy alcohol intake can develop an episode of alcoholic hepatitis (AH), the most severe form of ALD [3]. AH is characterized by an abrupt onset of jaundice and/or liver decompensation. Patients with AH often show signs of systemic inflammation at admission, and are prone to infections and kidney injury, which can lead to multi-organ dysfunction within a few days [4]. In its severe form, AH can result in 20-50 % mortality at 3 months. The only available therapies that improve survival are corticosteroids and liver transplantation [5,6]. The efficacy of pentoxifylline is debatable, based on recent large clinical trials [6]. The efficacy of prednisolone has been shown in meta-analyses of individual data and was partially confirmed in the recent STOPAH trial [6,7]. Unfortunately, many patients do not respond to prednisolone and performing salvage liver transplantation is not feasible in most centers. Therefore, there is an urgent need to provide these patients with novel targeted therapies. In the last two decades, there have been several attempts to test old and novel drugs in patients with severe AH, ranging from classic drugs [8] to monoclonal antibodies [9] or stimulating factors [10]

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“…This may be the case for some of the patients in this study as Table 2 indicated that some patients had serum bilirubin values as low as 44lmol/L, well below the threshold for inclusion in recent clinical trials of alcoholic hepatitis. 8,9 Thus, while reassuring us that the available prognostic scores have excellent negative predictive values, the testing of such scores on a treated population may underestimate the utility of those scores which can direct clinical treatment, and the use of a biopsy-proven cohort might still lead to the inclusion of patients without clinical alcoholic hepatitis. With regard to his comments, we would like to reiterate that all patients included in our study had a clinical diagnosis of alcoholic hepatitis that was confirmed by a liver biopsy.…”

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Letter: prognostic scores in alcoholic hepatitis

Forrest

2014

Aliment Pharmacol Ther

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Antioxidants versus corticosteroids in the treatment of severe alcoholic hepatitis—A randomised clinical trial

Cited by 186 publications

References 38 publications

The Lille model: A new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids

The Lille model: A new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids

Alcoholic hepatitis: should we combine old drugs for better results?

Letter: prognostic scores in alcoholic hepatitis

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