Pennsylvania University. US: Study Upends Common Belief that Prescription Drugs are Prime Culprits in Causing Liver Failure.
Drug-induced acute liver failure is uncommon, and over-the-counter
medications and dietary and herbal supplements -- not prescription
drugs -- are its most common causes, according to new research from the
Perelman School of Medicine at the University of Pennsylvania. The findings are published in the current issue of Gastroenterology.
One of the most feared complications of drugs and medications
is acute liver failure, traditionally associated with a greater than 50
percent chance of dying without a liver transplant. Drug-induced liver
injury, known as hepatotoxicity, is the second most common reason drugs
are withdrawn from the market, behind cardiac toxicity, according to
the U.S. Food and Drug Administration (FDA). The Penn authors, however,
say this is based solely on abnormal liver tests, not actual liver
damage. The real risk of acute liver failure that the researchers
calculated was 1.61 per million people per year.
“Despite widely publicized cases of drug-induced acute liver failure
related to acetaminophen and other medications, there are, until now,
no studies to specifically evaluate the incidence of acute liver
failure arising from drug-induced liver injury in the broader
population,” says senior author Vincent Lo Re, MD, MSCE, assistant professor of Medicine in the division of Infectious Diseases and assistant professor of Epidemiology in the Perelman School of Medicine at the University of Pennsylvania.
Lo Re and his team, including lead author, David Goldberg, MD, MSCE,
assistant professor of Medicine and medical director of Living Donor
Liver Transplantation at Penn, set out to uncover the incidence and
outcomes of drug-induced acute liver failure in the United States
through the analysis of data from an integrated healthcare system that
is representative of the broader U.S. population.
They looked at data from Kaiser Permanente Northern California
between January 1, 2004 and December 31, 2010, to assess the true impact
of acute liver failure in the U.S.
Among the 5,484,224 patients evaluated, 62 were identified with
acute liver failure, nearly half of which were drug-induced.
Acetaminophen was implicated in 56 percent of cases, dietary/herbal
supplements in 19 percent, antibiotics in 6 percent and miscellaneous
medications in 18 percent.
Despite hepatotoxicity being the second most common cause of drug
withdrawal from the market, acute liver failure, the most severe form of
liver injury, from prescription drugs was rare, the team found. “We
discovered that 75 percent of acute liver failure cases resulting from
prescribed medication use were derived from over-the-counter products
such as acetaminophen or herbal supplements,” says Goldberg.
“Prescription medications are an exceedingly rare cause of acute liver
failure.”
Given that one half of acetaminophen-induced acute liver failure
was from unintentional overdoses, consideration should be given to laws
to limit the size of packs of acetaminophen and/or require
acetaminophen packages to use individually-packaged drugs in “blister
packs,” as has been required in the United Kingdom since 1988, the
researchers suggest. In addition, the researchers believe these
findings could inform more aggressive regulation of the dietary and
herbal supplements industry, which has been linked to other toxicities,
including kidney toxicity induced by some herbs and heart problems,
which have been associated with the herb ephedra, making it no longer
available in the U.S.. “Perhaps this gives cause for consideration for
additional regulatory oversight of dietary supplements and herbal
products,” Lo Re says.
This study was funded by the Agency for Healthcare Research and Quality (R01 HS018372).
Additional Penn researchers include: Kimberly A. Forde, MD, MHS;
Dena M, Carbonari, MS; James D. Lewis, MD, MSCE; Kimberly B.F. Leidl,
MPH; K. Rajender Reddy, MD; Kevin Hayes, PharmD, MSCE; Brian L. Strom,
MD, MPH; Jason Roy, PhD; and Daohang Sha, PhD.