Effect of long-term, continuous versus alternate-day omeprazole therapy on serum gastrin in patients treated for reflux esophagitis.

摘要

BACKGROUND: Proton pump inhibitors have been proven to have a major role in the management of peptic diseases, especially the long-term control of reflux esophagitis. The potent inhibitory effect of omeprazole on gastric acid secretion is frequently associated with hypergastrinemia, and gastrin and its intermediates have been reported to promote gastrointestinal cellular functions and cell growth. Experimental data suggest that gastrin may affect the proliferation of colon cells and some other cancer cells. However, so far the direct role of gastrin in tumorigenesis is unclear. Although most clinical studies on long-term treatment with omeprazole or other proton pump inhibitors do not report serious adverse effects, the issue of prolonged hypergastrinemia and tissue growth is unsettled, and many clinicians are reluctant to recommend long-term use of omeprazole or of other proton pump inhibitors. STUDY: We examined the effect of long-term omeprazole treatment on serum gastrin levels in patients with reflux esophagitis when given either 20 mg daily (group 1) or on alternate days (group 2). During the follow-up period, clinical remission was monitored and maintained in all patients in group 1 and in the majority of patients in group 2. RESULTS: The mean serum gastrin level was significantly elevated in group 1 (mean +/- SE, 159 +/- 23.6 pg/mL; range, 45-620 pg/mL; n = 31) as compared with the alternate-day treatment group (group 2) (66 +/- 4.8 pg/mL; range, 37-115 pg/mL; n = 21) (p < 0.005). In controls, serum gastrin levels showed similar values to those found in group 2 (54 +/- 4.3 pg/mL; range, 27-94 pg/mL; n = 20). Fourteen patients (45%) in group 1 had serum gastric ranging from 140 to 620 pg/mL, and 8 (25%) had a 6-fold or greater increase in serum gastrin. The follow-up treatment period ranged between 3 and 60 months (mean +/- SE, 16.1 +/- 2.1 months) for group 1 and 3-36 months (9.7 +/- 1.4 months) for group 2. Upon multivariate adjustment for age and duration of treatment, a significantly lower mean serum gastrin level was observed in the alternate-day group as compared with the daily treated group. CONCLUSION: Alternate-day, long-term treatment with omeprazole may be adequate to maintain remission in patients with reflux esophagitis. This regimen can assure serum gastrin levels within the normal range, thus reducing the potential risk of prolonged, sustained hypergastrinemia and profound hypochlorhydria.