PMID- 19155081
OWN - NLM
STAT- MEDLINE
DCOM- 20090729
LR  - 20151119
IS  - 1600-0641 (Electronic)
IS  - 0168-8278 (Linking)
VI  - 50
IP  - 3
DP  - 2009 Mar
TI  - Infliximab monotherapy for severe alcoholic hepatitis and predictors of survival: 
      an open label trial.
PG  - 584-91
LID - 10.1016/j.jhep.2008.10.024 [doi]
AB  - BACKGROUND/AIMS: Severe alcoholic hepatitis (AH) is associated with very high 
      mortality. Tumor necrosis factor-alpha (TNF-alpha) contributes to the progression 
      of AH and TNF-alpha antagonists like infliximab may help in ameliorating the 
      severity and complications of AH. There is a scarcity of data regarding the 
      safety and efficacy of infliximab monotherapy in the treatment of AH. We 
      evaluated infliximab monotherapy in patients with severe AH. METHODS: Patients 
      with severe AH (Maddrey's score>32) received a single dose of infliximab 5 mg/kg 
      IV. The primary endpoint was survival assessed at one and two months. The 
      secondary endpoints were reduction of the Maddrey's DF and development of any 
      bacterial infections. Predictors of survival were assessed at admission and at 
      day 7. RESULTS: Nineteen patients were enrolled in the study and received 
      infliximab. By the end of one month two patients died resulting in 1-month 
      survival of 17/19 (89%). By the end of two months four additional patients died 
      resulting in 2-month survival of 68%. At the end of one and two months, compared 
      to baseline, there was significant improvement in median values of Maddrey's DF 
      (p<0.05). Median serum TNF-alpha levels decreased from 45 (range 11-19,880) at 
      baseline to 20 (range 4-8600) pg/mL at 4 weeks (p=0.001). CRP levels, MELD score, 
      and absolute neutrophil count decreased significantly. Five patients (26%) 
      developed infection: three of them had pneumonia, while two developed a flare of 
      pulmonary tuberculosis. Three patients recovered with treatment but two patients 
      (10%) died (one with pneumonia leading to sepsis and the other of disseminated 
      tuberculosis). Absence of hepatic encephalopathy at admission significantly 
      predicted survival. Among patients who survived only 1/13 (8%) had hepatic 
      encephalopathy at admission while among patients who died 4/6 (67%) had hepatic 
      encephalopathy (p=0.017). Lille score and delta bilirubin at day 7 (DBD7) 
      (defined as [baseline serum bilirubin minus serum bilirubin at day 7] x 
      100/baseline serum bilirubin), also predicted 2-month mortality. The area under 
      ROC curve of DBD7 values for predicting survival was 0.77 (95% CI 0.55-0.99). 
      DBD7 of >7.5% best predicted survival in the patients (sensitivity 85%, 
      specificity 67%, PPV 85%, NPV 67%, and overall accuracy 79%). CONCLUSIONS: In 
      severe AH, single dose infliximab is associated with improvement in parameters of 
      severity and survival. However, infection remains a concern. Hepatic 
      encephalopathy at admission, Lille score and DBD7 predicted 2-month mortality. 
      Large randomized controlled trials are needed before infliximab can be 
      recommended for AH.
FAU - Sharma, Praveen
AU  - Sharma P
AD  - Department of Gastroenterology, G B Pant Hospital, University of Delhi, New 
      Delhi, India.
FAU - Kumar, Ashish
AU  - Kumar A
FAU - Sharma, Barjesh Chander
AU  - Sharma BC
FAU - Sarin, Shiv Kumar
AU  - Sarin SK
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
DEP - 20081225
PL  - Netherlands
TA  - J Hepatol
JT  - Journal of hepatology
JID - 8503886
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Blood Proteins)
RN  - 0 (Serum Albumin)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - B72HH48FLU (Infliximab)
RN  - RFM9X3LJ49 (Bilirubin)
SB  - IM
MH  - Adult
MH  - Anti-Inflammatory Agents/*therapeutic use
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - Bacterial Infections/complications/epidemiology
MH  - Bilirubin/blood
MH  - Blood Proteins/metabolism
MH  - Disease Progression
MH  - Hepatitis, Alcoholic/complications/*drug therapy/mortality/pathology
MH  - Humans
MH  - Infliximab
MH  - International Normalized Ratio
MH  - Leukocyte Count
MH  - Male
MH  - Middle Aged
MH  - Patient Selection
MH  - Serum Albumin/metabolism
MH  - Survival Analysis
MH  - Survivors
MH  - Tumor Necrosis Factor-alpha/physiology
MH  - Young Adult
EDAT- 2009/01/22 09:00
MHDA- 2009/07/30 09:00
CRDT- 2009/01/22 09:00
PHST- 2008/02/07 00:00 [received]
PHST- 2008/10/14 00:00 [revised]
PHST- 2008/10/23 00:00 [accepted]
PHST- 2009/01/22 09:00 [entrez]
PHST- 2009/01/22 09:00 [pubmed]
PHST- 2009/07/30 09:00 [medline]
AID - S0168-8278(08)00792-7 [pii]
AID - 10.1016/j.jhep.2008.10.024 [doi]
PST - ppublish
SO  - J Hepatol. 2009 Mar;50(3):584-91. doi: 10.1016/j.jhep.2008.10.024. Epub 2008 Dec 
      25.