Non-steroidal anti-inflammatory drugs – potential risks and benefits in the gastrointestinal tract distal to the ligament of Treitz

The toxicity of non-steroidal anti-inflammatory drugs (NSAIDs) related to the upper gastrointestinal (GI) tract is well established. However, they may cause injury distal to the duodenum as well – to the small and large intestine and/or to other organs of the digestive system. Non-steroidal anti-inflammatory drugs induce small intestinal perforation, ulcers or strictures requiring surgery and inflammation with blood and protein loss called NSAID enteropathy. These drugs can exacerbate pre-existing large bowel disease (e.g. ulcerative colitis, diverticular disease) and precipitate relapse of inactive disease or the new onset of inflammatory bowel disease (IBD) with rapid resolution of symptoms on their withdrawal. They have been implicated in the development of microscopic colitis. Non-steroidal anti-inflammatory drugs-associated toxicity of the small and large bowel is increasingly recognized in clinical practice, as enteroscopic procedures become more frequently used. Liver injury is an uncommon, but potentially lethal complication. It can occur with all NSAIDs, but diclofenac and sulindac seem to be most commonly associated with the problem. These drugs may contribute to acute fatty liver of pregnancy. Hepatotoxicity is likely due to an idiosyncratic reaction resulting from an immunological response or altered metabolic pathways. The major benefits of NSAIDs relate to reports of possible prevention, delay or regression of progress towards cancer of the colon, oesophagus, stomach as well as of cancer of the breast, lung, prostate and skin. Despite their promise, NSAIDs are not yet recommended for prevention or treatment of any cancer, because the balance of hazards and benefits from the treatment must be resolved in the designated patient population.