TITLE

TREATMENT WITH ANTI-TUMOUR NECROSIS FACTOR α (TNFα) ANTIBODY IMPROVES CLINICAL PARAMETERS AND LOWERS PORTAL PRESSURE IN ALCOHOLIC HEPATITIS

AUTHOR(S)
Mookerjee, R.P.; Sen, S.; Davies, N.A.; Hodges, S.J.; Williams, R.; Jalan, R.
PUB. DATE
April 2003
SOURCE
Gut;Apr2003 Supplement 1, Vol. 52, pA1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Patients with alcoholic hepatitis (AH) and cirrhosis exhibit an inflammatory state in addition to a hyperdynamic circulation and portal hypertension. TNFα is a key mediator in AH, promoting a cascade of inflammatory activity. In this study we addressed the effects of the chimeric anti-TNFα antibody, infliximab, on clinical parameters and portal haemodynamics, and tested the hypothesis that the development of portal hypertension in AH is associated with inflammation. Methods: Sixteen patients with biopsy proven AH (mean age 57 ± 4 and discriminant function 52.4 ± 6.8) were treated with the chimeric, monoclonal anti-TNFα antibody, infliximab (5 mg/kg lean body weight). Ten of these patients had assessment of their wedged hepatic venous pressure (WHVP) before, 24 hours, and 28 days after infliximab treatment. Patients' clinical and biochemical profiles were monitored during the study period. Results: Significant improvements were noted by 28 days in bilirubin (293±33 to 130±21; p<0.001), CRP (73±10.9 to 36.1 ± 12.7; p <0.01), white cell count (15.9 ± 2.1 to 10.51 ± 1.5; p < 0.05) and SIRS score (2.6 ± 0.4 to 0.23 ± 0.12; p < 0.01 ). Three patients died during the study period, with two developing sepsis, both from Staphylococcus aureus. No patient developed renal failure or hepatorenal syndrome, or required intensive care support. WHVP reduced significantly from 38.63 ± 2.39 to 29.14 ± 1.42 mm Hg at 24 hours, and the reduction was sustained at 28 days (27.4 ± 2.82 mm Hg; p < 0.01) with no significant differences in free HVP or CVP. Mean arterial pressure (MAP) increased significantly (71.6 ± 1.72 to 81.1 ± 3.15 mm Hg; p < 0.05 at28 days). Conclusion: Anti-TNFα treatment results in a significant reduction in bilirubin, white blood cell count, CRP, and SIRS score, coupled with an apparent improved clinical outcome. This...
ACCESSION #
9747245

 

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