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Abstract

Study Objective: To determine whether elevated tumor necrosis factor levels contribute to the clinical manifestations and complications of severe acute alcoholic hepatitis and to evaluate the relation between tumor necrosis factor and plasma levels of endotoxin and interleukin-1β.

Design: Prospective, controlled study.

Setting: The liver unit of a university teaching hospital.

Patients: We studied 21 patients with acute severe alcoholic hepatitis. There were four control groups: patients with inactive alcoholic cirrhosis, alcoholic persons without liver disease, patients with impaired renal function, and normal subjects.

Measurements and Main Results: With one exception, patients with alcoholic hepatitis had higher tumor necrosis factor levels (mean, 26.3 ng/L; 95% CI, 21.7 to 30.9) than normal subjects (6.4 ng/L; CI, 5.4 to 7.4). Patients who subsequently died had a higher tumor necrosis factor level (34.7 ng/L; CI, 27.8 to 41.6) than survivors (16.6 ng/L; CI, 14.0 to 19.2). In patients with alcoholic hepatitis, tumor necrosis factor levels correlated positively with serum bilirubin (r = 0.74; P = 0.0009) and serum creatinine (r = 0.81; P = 0.0003). Patients with alcoholic hepatitis had higher tumor necrosis factor levels than patients with inactive alcoholic cirrhosis (11.1 ng/L; CI, 8.9 to 13.3) and severely alcoholic persons without liver disease (6.4 ng/L; CI, 5.0 to 7.8). Patients with abnormal renal function had lower tumor necrosis factor levels (14.1 ng/L; CI, 5.4 to 22.8) than patients with alcoholic hepatitis. Serial samples obtained during a 1-week period from patients with alcoholic hepatitis showed no significant change in tumor necrosis factor when patients who died were compared with survivors. No correlation was found between tumor necrosis factor and plasma endotoxin. Levels of interleukin-1β did not exceed 20 ng/L.

Conclusions: Elevations in tumor necrosis factor in alcoholic hepatitis are most marked in severe cases, suggesting that tumor necrosis factor plays a role in the pathogenesis.

Plasma concentrations of tumor necrosis factor (TNF) were determined in 21 consecutive patients with severe alcoholic hepatitis. 10 of these patients died within 6 weeks of admission. Controls included patients with inactive alcoholic cirrhosis, alcoholic subjects without liver disease, patients with impaired renal function, and normal subjects. Patients with alcoholic hepatitis had higher plasma TNF concentrations than all but 1 normal subject. Plasma TNF concentrations positively correlated with serum creatinine, serum bilirubin, blood neutrophil count and temperature. Alcoholic hepatitis patients having infections had higher plasma TNF concentrations than those without infection. Plasma TNF concentrations also were significantly higher in alcoholic hepatitis patients who subsequently died than those who survived. Patients with alcoholic hepatitis had significantly higher plasma TNF concentrations than did patients with inactive cirrhosis or alcoholics having no liver disease. Patients with alcoholic cirrhosis had mild elevations in their plasma TNF concentrations, and alcoholics without liver disease had no significant increase in plasma TNF concentrations above normal values. Renal failure patients had modest elevations in their plasma TNF concentrations. There was no correlation found between plasma endotoxin and plasma TNF concentrations in alcoholic hepatitis patients. It is concluded that there is elevated plasma TNF concentrations in patients with severe alcoholic hepatitis, and it is suggested that TNF may play a role in the pathogenesis of this disease process.