Long-term acid control and proton pump inhibitors: interactions and safety issues in perspective

Concerns have been raised regarding the safety of proton pump inhibitors in the long-term management of acid-related peptic disease, especially with regard to the physiological effects of prolonged hypochlorhydria. Of special consideration is the potential for development of enterochromaffin-like cell hyperplasia and gastric carcinoids, colorectal adenocarcinoma and polyps, and bacterial overgrowth as a result of achlorhydria. However, the magnitude of hypergastrinemia associated with the administration of proton pump inhibitors is comparable to that observed after vagotomy and is 3- to 6-fold lower than that observed with pernicious anemia. Only minimal morphological changes in gastric endocrine cells have been observed after the long-term daily administration of proton pump inhibitors, and these changes appear to be self-limiting, nondysplastic, and nonneoplastic. All current evidence suggests that the hypergastrinemia observed during proton pump inhibitor therapy has little clinical significance. However, longer-term results are necessary so that one can appreciate the full implications of acid suppression by proton pump inhibitors.