Serious liver toxicity associated with the use of nonsteroidal anti-inflammatory drugs showed a sevenfold jump in incidence in a recent 10-year period in California.
The explanation for this alarming trend is speculative, but one key factor might be the steady growth in concomitant use of other potentially hepatotoxic drugs, such as statins, Dr. Gurkirpal Singh observed at the annual European Congress of Rheumatology.
Another potential contributing factor could be the background rise in nonalcoholic fatty liver disease, added Dr. Singh of Stanford (Calif.) University.
Acute liver failure and other serious hepatotoxicity related to nonsteroidal anti-inflammatory drugs have not gotten much clinical and media attention, in contrast to NSAID-related cardiovascular toxicity and the more common problem of NSAID-related gastrointestinal bleeding.
But nevertheless, the liver toxicity carries high morbidity and mortality.
In the California study, 19% of individuals with NSAID-associated acute liver failure died, and 4% of the population requried a liver transplant.
Dr. Singh analyzed 1995–2005 data from MediCal, California's Medicaid program, which covers more than 7 million patients per year. Among 1.6 million MediCal participants with more than 3 million person-years of NSAID use, there were 1,648 cases of serious liver toxicity (defined by a blinded adjudication panel comprising three hepatologists as hospitalization for hepatitis, acute liver failure, jaundice, hepatorenal syndrome, or hepatic coma). Any cases of alcohol-related liver injury and viral hepatitis were excluded.
The overall incidence of serious liver toxicity associated with the use of NSAIDs was found to be 55 cases per 100,000 person-years of exposure. The rate increased steadily from 23 cases per 100,000 person-years in 1995 to 142 in 2005.
The fatality rate was 12%.
The incidence of acute liver failure climbed from 3.1 cases per 100,000 years of nonsteroidal anti-inflammatory drug exposure in 1995 to 17.8 per 100,000 person-years in 2005.
Dr. Singh recommended careful monitoring with periodic liver function tests in chronic nonsteroidal anti-inflammatory drug users.
Indeed, this is particularly important in those patients who are taking other potentially hepatotoxic drugs or who have additional risk factors for fatty liver or other liver disorders, Dr. Singh commented.