Short-term use of selective COX-2 inhibitors may be safe for patients with cirrhosis of the liver

Short-term use of selective COX-2 inhibitors may be safe for patients with cirrhosis of the liver, according to a recent study that compared the effects of celecoxib, naproxen, and a placebo on cirrhotic patients in a double-blind randomized controlled study.

The findings are published in the March 2005 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD). Published by John Wiley & Sons, Inc., the journal is available online via Wiley InterScience.

Previous studies in experimental cirrhosis have shown that selective COX-2 inhibitors, such as celecoxib, do not affect renal function. By contrast, nonsteroidal anti-inflammatory drugs, including naproxen, have long been associated with acute renal failure in cirrhotic patients. To further investigate these findings, researchers, led by Joan Clària of Barcelona's Hospital Clinic, sought to compare the effects of celecoxib, naproxen and a placebo on cirrhotic patients.

They recruited 28 patients who had cirrhosis and ascites and increased activity of the renin-angiotensin system. Each one was randomly assigned to a short-term course (5 doses over 60 hours) of celecoxib, naproxen or a placebo. Results from ten of the participants were not considered in the analysis due to the discovery of hepatorenal syndrome, or lack of stable serum concentrations of clearance substances needed to calculate glomerular filtration rate (GFR) and renal plasma flow (RPF.) For the remaining patients, the researchers measured and monitored platelet and renal function, as well as the diuretic and natriuretic responses to furosemide.

Celecoxib, like the placebo, did not inhibit platelet aggregation or thromboxane B2 synthesis, while naproxen did. Celecoxib also did not affect renal function, according to RPF, GFR and serum creatinine values, while naproxen reduced both RPF and GFR and increased serum creatinine levels. Neither celecoxib nor the placebo affected the diuretic or natriuretic effects of furosemide or the urinary excretion of prostaglandins. Naproxen significantly reduced both the diuretic and natriuretic responses to furosemide. Interestingly, both celecoxib and naproxen significantly reduced plasma renin activity after furosemide administration.

"These results suggest that selective COX-2 inhibitors may be safer than nonselective nonsteroidal anti-inflammatory drugs in these patients," the authors report. "Further studies using COX-2 inhibitors for a longer period of time are required to confirm this contention."

The researchers used a short-term administration of the drugs in question to prevent any significant impairment in kidney function. As a result, the study does not offer information about the safety of these drugs when administered for long-term therapeutic purposes.

"In summary," say the authors, "the current study indicates that naproxen, but not celecoxib, administered during a short period of time, adversely affects renal function and the renal response to furosemide in cirrhotic patients with ascites and increased activity of the renin-angiotensin system."