Theophylline improves steroid sensitivity in acute alcoholic hepatitis

Area of Science:

• Hepatology
• Immunology
• Pharmacology

Background:

• Corticosteroid therapy offers limited benefit in severe acute alcoholic hepatitis (AAH) due to variable patient response and selection challenges.
• Theophylline may enhance corticosteroid efficacy by improving steroid sensitivity, as observed in chronic obstructive pulmonary disease.

Purpose of the Study:

• To investigate the mechanisms behind variable corticosteroid response in AAH patients.
• To determine if theophylline can improve corticosteroid response in AAH.

Main Methods:

• Assessed dexamethasone's inhibition of lymphocyte proliferation (using 3H-thymidine incorporation) in 12 severe AAH patients and controls.
• Measured steroid sensitivity via I(max) (maximum inhibition of proliferation).
• Observed the effect of 10(-5) M theophylline and changes in I(max) during recovery in survivors.

Main Results:

• Lymphocyte steroid sensitivity was significantly reduced in AAH patients (I(max) 67%) compared to controls (I(max) 95%, P=0.0002).
• Reduced sensitivity correlated with clinical markers of steroid responsiveness.
• Theophylline (10(-5) M) significantly increased lymphocyte steroid sensitivity (I(max) 86%, P=0.027).
• In survivors, I(max) increased during recovery.

Conclusions:

• Severe AAH is linked to significant lymphocyte steroid insensitivity.
• This insensitivity improves during recovery and can be enhanced ex vivo by theophylline.
• Theophylline may help rationalize corticosteroid prescribing in AAH and warrants further investigation.