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Clinical question
Does the combination of prednisolone and pentoxifylline improve survival in patients with severe alcoholic hepatitis?
Bottom line
Although pentoxifylline and prednisolone have both been demonstrated to be effective individual treatments for alcoholic hepatitis, the combination of both did not improve survival more than prednisolone alone. (LOE = 1b)
Reference
Mathurin P, Louvet A, Duhamel A, et al. Prednisolone with vs without pentoxifylline and survival of patients with severe alcoholic hepatitis: A randomized clinical trial. JAMA 2013;310(10):1033-1041.
Study design
Randomized controlled trial (double-blinded)
Funding source
Government
Allocation
Concealed
Setting
Inpatient (any location) with outpatient follow-up
Synopsis
Current guidelines recommend the use of either prednisolone or pentoxifylline for the treatment of severe alcoholic hepatitis. The benefit of the combination of these 2 medications in this setting is unclear. These investigators enrolled patients who were current heavy alcohol users and who had biopsy-proven alcoholic hepatitis with a Maddrey score of 32 or more. Patients were randomized, using concealed allocation, to receive prednisolone 40 mg daily plus pentoxifylline 400 mg 3 times daily (n = 133) or prednisolone 40 mg daily plus placebo (n = 137). Treatment lasted for 28 days and follow-up was 100% at 6 months. The patients had a mean age of 51 years and an average Maddrey score in the 50s (indicating severe disease). No significant difference was detected in 6-month survival between the 2 groups in either the intention-to-treat or per-protocol analyses. Overall, there were 82 deaths in the cohort at 6 months -- 40 in the pentoxifylline-prednisolone group and 42 in the placebo-prednisolone group. The risk of hepatorenal syndrome was decreased at 1 month in the combination therapy group as compared with the placebo group (3.1% vs 11.7%; P = .007), but this difference did not remain significant at 6 months. It is important to note, however, that this study was not powered to detect a difference in the incidence of hepatorenal syndrome.
Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.
Clinical question
Does the combination of prednisolone and pentoxifylline improve survival in patients with severe alcoholic hepatitis?
Bottom line
Although pentoxifylline and prednisolone have both been demonstrated to be effective individual treatments for alcoholic hepatitis, the combination of both did not improve survival more than prednisolone alone. (LOE = 1b)
Reference
Mathurin P, Louvet A, Duhamel A, et al. Prednisolone with vs without pentoxifylline and survival of patients with severe alcoholic hepatitis: A randomized clinical trial. JAMA 2013;310(10):1033-1041.
Study design
Randomized controlled trial (double-blinded)
Funding source
Government
Allocation
Concealed
Setting
Inpatient (any location) with outpatient follow-up
Synopsis
Current guidelines recommend the use of either prednisolone or pentoxifylline for the treatment of severe alcoholic hepatitis. The benefit of the combination of these 2 medications in this setting is unclear. These investigators enrolled patients who were current heavy alcohol users and who had biopsy-proven alcoholic hepatitis with a Maddrey score of 32 or more. Patients were randomized, using concealed allocation, to receive prednisolone 40 mg daily plus pentoxifylline 400 mg 3 times daily (n = 133) or prednisolone 40 mg daily plus placebo (n = 137). Treatment lasted for 28 days and follow-up was 100% at 6 months. The patients had a mean age of 51 years and an average Maddrey score in the 50s (indicating severe disease). No significant difference was detected in 6-month survival between the 2 groups in either the intention-to-treat or per-protocol analyses. Overall, there were 82 deaths in the cohort at 6 months -- 40 in the pentoxifylline-prednisolone group and 42 in the placebo-prednisolone group. The risk of hepatorenal syndrome was decreased at 1 month in the combination therapy group as compared with the placebo group (3.1% vs 11.7%; P = .007), but this difference did not remain significant at 6 months. It is important to note, however, that this study was not powered to detect a difference in the incidence of hepatorenal syndrome.
Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.
Clinical question
Does the combination of prednisolone and pentoxifylline improve survival in patients with severe alcoholic hepatitis?
Bottom line
Although pentoxifylline and prednisolone have both been demonstrated to be effective individual treatments for alcoholic hepatitis, the combination of both did not improve survival more than prednisolone alone. (LOE = 1b)
Reference
Mathurin P, Louvet A, Duhamel A, et al. Prednisolone with vs without pentoxifylline and survival of patients with severe alcoholic hepatitis: A randomized clinical trial. JAMA 2013;310(10):1033-1041.
Study design
Randomized controlled trial (double-blinded)
Funding source
Government
Allocation
Concealed
Setting
Inpatient (any location) with outpatient follow-up
Synopsis
Current guidelines recommend the use of either prednisolone or pentoxifylline for the treatment of severe alcoholic hepatitis. The benefit of the combination of these 2 medications in this setting is unclear. These investigators enrolled patients who were current heavy alcohol users and who had biopsy-proven alcoholic hepatitis with a Maddrey score of 32 or more. Patients were randomized, using concealed allocation, to receive prednisolone 40 mg daily plus pentoxifylline 400 mg 3 times daily (n = 133) or prednisolone 40 mg daily plus placebo (n = 137). Treatment lasted for 28 days and follow-up was 100% at 6 months. The patients had a mean age of 51 years and an average Maddrey score in the 50s (indicating severe disease). No significant difference was detected in 6-month survival between the 2 groups in either the intention-to-treat or per-protocol analyses. Overall, there were 82 deaths in the cohort at 6 months -- 40 in the pentoxifylline-prednisolone group and 42 in the placebo-prednisolone group. The risk of hepatorenal syndrome was decreased at 1 month in the combination therapy group as compared with the placebo group (3.1% vs 11.7%; P = .007), but this difference did not remain significant at 6 months. It is important to note, however, that this study was not powered to detect a difference in the incidence of hepatorenal syndrome.
Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.