Sequential Therapy Consisting of Glucocorticoid Infusions Followed by Granulocyte-monocyte Absorptive Apheresis in Patients with Severe Alcoholic Hepatitis

Background: Activated leukocytes infiltrating the liver contribute to the provocation of alcoholic hepatitis. Glucocorticoid induces the demargination of leukocytes from the hepatic sinusoids, whereas granulocyte-monocyte absorptive apheresis (GMA) removes leukocytes from the circulation. Thus, the usefulness of a sequential therapy consisting of glucocorticoid infusions followed by GMA was evaluated in patients with severe alcoholic hepatitis.

Methods: Patients with severe alcoholic hepatitis received intravenous injections of methylprednisolone (1,000 mg/day) for 3 or 4 days, and then GMA was performed every day for 3 days. Responders were defined as those with attenuated serum C-reactive protein (CRP) levels during the GMA procedures.

Results: Ten consecutive patients were enrolled. At the baseline, the Japan alcoholic hepatitis scores were 9 in two patients and 10 or more in eight patients, and the Model for End-Stage Liver Disease scores ranged from 22 to 43. In all the patients, the peripheral neutrophil counts increased and the serum levels of CRP, aspartate aminotransferase, IL-6, IL-8, TNF-α, and intercellular adhesion molecule 1 decreased immediately after the glucocorticoid infusions. However, a rebound increase in the serum CRP levels was observed in all patients after discontinuation of glucocorticoid infusions, but the maximal values during the GMA procedures were lower than the baseline values. Six patients were rescued, whereas the remaining four patients died because of sepsis, pneumonia, pancreatitis, and renal failure.

Conclusions: Sequential therapy combining glucocorticoid infusion and GMA was useful for attenuating liver injuries in patients with severe alcoholic hepatitis by preventing rebound increases in inflammatory reactions after discontinuation of glucocorticoid infusions, except in patients with bacterial infections and/or multiple organ failure.