Short-term use of anti-inflammatory drugs known as COX-2 inhibitors may be safe in people with liver cirrhosis, says a new study from Spain.¹

COX inhibitors are a class of anti-inflammatory medications that inhibit the activity of two types of enzymes known as cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). COX-1 is necessary for maintaining the body's internal stability, such as protecting the lining of the stomach. But COX-2 is involved in inflammatory processes. Thus, drugs that inhibited both COX enzymes created unwanted side effects like stomach ulcers. In 1999, the first drug to inhibit only COX-2, celecoxib (Celebrex/Pfizer) entered the market. Celecoxib and other medications in the same class reduce the unwanted side effects that nonselective COX inhibitors may create.²

Risks of Some NSAIDs in Liver Disease
In their small analysis involving 18 patients with cirrhosis and ascites, Vicente Arroyo, MD, at the Hospital Clinic in Barcelona, Spain wanted to find out if COX inhibitors caused kidney failure in people with advanced liver disease. Previous studies had suggested it.³

"The most important conclusion of these studies was that NSAIDs [non-steroidal anti-inflammatory drugs] should be used with great caution, if ever, in patients with cirrhosis and ascites," Arroyo and his colleagues noted. "This represents an important limitation because these patients may present complications requiring anti-inflammatory therapy."

But other preclinical studies suggested that COX-1, not COX-2 inhibitors negatively affected the kidneys related to liver disease.⁴ To answer this question in people, Arroyo and his team initiated a double-blind, randomized controlled study.

Which COX Inhibitor is More Risky?
Each patient was randomly assigned to receive a short-term course of celecoxib, a COX-2 inhibitor; naproxen, a non-selective COX inhibitor; or a placebo. Treatment consisted of five doses of medication or placebo for 60 hours. The study length was shortened to reduce the risk of kidney failure, if it occurred, in any of the patients.

The researchers measured and monitored platelet and kidney function. (Inhibiting the activity of COX-1 also tends to block normal blood clotting, or platelet aggregation, as it's known in medical terms.)

After 60 hours of treatment, the researchers found that naproxen, but not celecoxib or placebo, significantly inhibited normal blood clotting. Naproxen also negatively affected kidney function, while celecoxib and placebo did not.

Arroyo's team noted previous studies that suggested that the use of COX-2 inhibitors was toxic to the liver, but they found no changes in liver function in this study.

"These results suggest that selective COX-2 inhibitors may be safer than nonselective NSAIDs in these patients," Arroyo and his colleagues wrote. "Further studies using COX-2 inhibitors for a longer period are required, however, to confirm this contention."

1. Claria J, Kent JD, Lopez-Parra M et al. Effects of celecoxib and naproxen on renal function in nonazotemic patients with cirrhosis and ascites. Hepatology 2005 Mar;41(3):579-87.
2. American College of Rheumatology. COX-2 agents have dramatically changed the NSAID landscape. Available at: http://www.rheumatology.org/press/2004/fedutes_nsaid.asp. Accessed March 2, 2005.
3. Boyer TD, Zia P, Reynolds TB. Effect of indomethacin and prostaglandin A1 on renal function and plasma renin activity in alcoholic liver disease. Gastroenterology 1979;77:215-22.
4. Bosch-Marce M, Claria J, Titos E et al. Selective inhibition of cyclooxygenase-2 spares renal function and prostaglandin synthesis in cirrhotic rats with ascites. Gastroenterology 1999;116:1167-75.

John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.