205 One potential approach to resolve this is the use of individual patient data across clinical trials, which represents the “gold standard” approach to meta-analysis.206 Although it is impractical to retrieve and combine primary data from all the clinical trials in this field, where large variation in studies over time exists, this approach was pursued with the use of a combined dataset, using pooled primary data from three placebo controlled trials in patients with comparable
measures of disease severity (i.e., an MDF ≥32). The result showed a significant increase in short-term selleck survival among treated patients compared to control patients: 84.6% versus 65%.207 This represents a modest absolute reduction in risk, but a 30% relative risk reduction, and translates into a number needed to treat of 5, i.e., five patients need to
be treated to avert one death. This last meta-analysis also excluded a recent trial comparing steroids to a combination of antioxidants, which showed a similar protective effect of corticosteroids among treated patients.208 Although it is possible that antioxidants themselves may be detrimental,209 the doses used seem unlikely to account for the differences in survival, and the consistency of the data suggest a protective effect of steroids. Although the doses and durations BVD-523 mouse of steroid treatment used in the clinical trials were variable, the best available evidence suggests a dose of prednisolone (40 mg/day MCE公司 for 4 weeks then tapered over 2-4 weeks, or stopped, depending on the clinical situation) should be used in favor of prednisone.210 It is important to recognize that the efficacy of steroids
has not been evaluated in patients with severe alcoholic hepatitis and concomitant pancreatitis, gastrointestinal bleeding, renal failure, or active infection, which were exclusion criteria in many of the early studies of alcoholic hepatitis. An important issue in all studies of medical therapy, and one that has been recognized for some time in this literature, is the possibility that these therapies may not be effective at an advanced stage of disease. Just as there is a threshold for the use of steroids (i.e., identifying patients at high risk of mortality defined by a MDF score ≥32), there may also be a ceiling beyond which medical therapies aimed at decreasing the inflammatory cascade may cause more harm than benefit. One study examined this issue, and suggested that patients with a MDF > 54 were at a higher mortality risk from use of steroids than from not being treated.211 This cutoff, however, needs to be confirmed. One recently derived model used six variables to predict 6-month mortality in patients who were universally treated with steroids (including age, renal insufficiency (serum creatinine > 1.