Corticosteroids reduce alcoholic hepatitis mortality short-term
Corticosteroid therapy reduced mortality risk within 28 days of treatment among patients with severe alcoholic hepatitis compared with pentoxifylline or placebo, although the effect did not remain in the following 6 months, according to a recently published meta-analysis.
“Corticosteroids improve liver function, response to therapy, and 28-day survival as compared to the other tested options,” Alexandre Louvet, MD, PhD, from the Université Lille in France, and colleagues wrote. “The lack of statistical interaction between treatment response and baseline disease severity does not support not treating the most severely ill patient ... with corticosteroids.”
Louvet and colleagues analyzed the results of 11 randomized controlled trials, in which researchers compared corticosteroids vs. placebo (n = 6), corticosteroids vs. pentoxifylline (n = 2), combination corticosteroids and pentoxifylline vs. corticosteroids alone (n = 3), and pentoxifylline vs. placebo (n =2) among a total of 2,111 patients.
Corticosteroid use correlated with a significant decrease in mortality at 28 days compared with pentoxifylline (HR = 0.64; 95% CI, 0.43-0.95) and placebo (HR = 0.64; 95% CI, 0.48-0.95), with no evidence of heterogeneity between trials.
The reduced mortality risk from corticosteroid use remained significant compared with pentoxifylline in complete case-adjusted analysis (HR = 0.66; 95% CI, 0.43-0.98) but not in multiple-imputation adjusted analysis.
The researchers observed no significant difference in 28-day mortality after comparing combination corticosteroids and pentoxifylline vs. corticosteroids alone or between pentoxifylline vs. placebo. There was also no significant difference in 6-month mortality between any comparison.
“Pooling arms drawn from trials involving different comparators makes it possible to make indirect comparisons without respecting the methodology of a randomized controlled trial,” Louvet and colleagues wrote. “If we combined the 11 trials together, we could estimate the effect of the combination of corticosteroids and pentoxifylline compared to controls while none of the trials performed this comparison.”
Through pooled analysis, the researchers confirmed the effect of corticosteroids compared with pentoxifylline and compared with controls in 28-day mortality.
“We suggest that future studies evaluate 3 or 6 months of drug exposure and consider 3- or 6-month survival as end-points to test the impact of molecules targeting liver injury,” Louvet and colleagues concluded. “Such loss of efficacy over the time highlights the urgent need for clinicians to focus on new therapeutic strategies aiming to improve medium-term outcome.” – by Talitha Bennett
Disclosure: The authors report no relevant financial disclosures.