Pentoxifylline vs. corticosteroid to treat severe alcoholic hepatitis: a randomised, non-inferiority, open trial.
OBJECTIVE
Both corticosteroid and pentoxifylline reduce short-term mortality in severe alcoholic hepatitis. However, few studies have directly compared the efficacy of pentoxifylline and corticosteroid in patients with this condition.


METHODS
In this multicentre, open-labelled, randomised non-inferiority trial, we assigned 121 patients with severe alcoholic hepatitis (Maddrey's discriminant function ⩾32) to receive either pentoxifylline (400 mg, 3 times daily, in 62 subjects) or prednisolone (40 mg daily, in 59 subjects). The primary end point was non-inferiority in survival at the 1 month time point for the pentoxifylline treatment compared with prednisolone.


RESULTS
The 1-month survival rate of patients receiving pentoxifylline was 75.8% (15 deaths) compared with 88.1% (7 deaths) in those, taking prednisolone, for a treatment difference of 12.3% (95% confidence interval, -4.2% to 28.7%; p = 0.08). The 95% confidence interval for the observed difference exceeded the predefined margin of non-inferiority (Δ15%) and included zero. The 6-month survival rate was not significantly different between the pentoxifylline and prednisolone groups (64.5% vs. 72.9%; p = 0.23). At 7 days, the response to therapy assessed by the Lille model was significantly lower in the prednisolone group (n = 58) than in the pentoxifylline group (n = 5 9): 0.35 vs. 0.50 (p = 0.012). Hepatitis complications, including hepatorenal syndrome and side effects, such as infection and gastrointestinal bleeding, were similar in the two groups.


CONCLUSIONS
The findings demonstrate that the efficacy of the pentoxifylline is not statistically equivalent to the efficacy of prednisolone, supporting the use of prednisolone as a preferred treatment option in patients with severe alcoholic hepatitis.
Department of Internal Medicine, Inje University Haeundae Paik-Hospital, Inje University College of Medicine, Busan, Republic of Korea.
Seung Ha
SH
Park
Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Republic of Korea. Electronic address: djkim@hallym.ac.kr.
Dong Joon
DJ
Kim
Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Republic of Korea.
Young Seok
YS
Kim
Department of Internal Medicine, Korea University College of Medicine, Ansan, Republic of Korea.
Hyung Joon
HJ
Yim
Department of Internal Medicine, Kyungpook National University College of Medicine, Daegu, Republic of Korea.
Won Young
WY
Tak
Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Republic of Korea.
Heon Ju
HJ
Lee
Department of Internal Medicine, Hanyang University College of Medicine, Guri, Republic of Korea.
Joo Hyun
JH
Sohn
Department of Internal Medicine, Pusan National University School of Medicine, Yangsan, Republic of Korea.
Ki Tae
KT
Yoon
Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea.
In Hee
IH
Kim
Department of Internal Medicine, Hallym University College of Medicine, Seoul, Republic of Korea.
Hyoung Su
HS
Kim
Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
Soon Ho
SH
Um
Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
Soon Koo
SK
Baik
Department of Internal Medicine, Inje University College of Medicine, Goyang, Republic of Korea.
June Sung
JS
Lee
Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Republic of Korea.
Ki Tae
KT
Suk
Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Republic of Korea.
Sang Gyune
SG
Kim
Department of Internal Medicine, Korea University College of Medicine, Ansan, Republic of Korea.
Sang Jun
SJ
Suh
Department of Internal Medicine, Kyungpook National University College of Medicine, Daegu, Republic of Korea.
Soo Young
SY
Park
Department of Internal Medicine, Hanyang University College of Medicine, Guri, Republic of Korea.
Tae Yeob
TY
Kim
Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Republic of Korea.
Jae Young
JY
Jang
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects; D016903:Drug Monitoring; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000209:etiology; D006519:Hepatitis, Alcoholic / Q000150:complications / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology; D006530:Hepatorenal Syndrome / Q000209:etiology; D006801:Humans; D007239:Infections / Q000209:etiology; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D010431:Pentoxifylline / Q000008:administration & dosage / Q000009:adverse effects; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D011239:Prednisolone / Q000008:administration & dosage / Q000009:adverse effects; D012720:Severity of Illness Index; D015996:Survival Rate; D013812:Therapeutics
D000893:Anti-Inflammatory Agents; D010726:Phosphodiesterase Inhibitors; D011239:Prednisolone; D010431:Pentoxifylline
Alcoholic hepatitis; Corticosteroid; Non-inferiority trial; Pentoxifylline