Friday, November 30, 2012

Liver Cancer - Painkillers May Protect Liver

Painkillers May Protect Liver

By Crystal Phend, Senior Staff Writer, MedPage Today
Published: November 29, 2012
Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

View Video at MedPage Today

Nonsteroidal anti-inflammatory drugs, especially aspirin, may help prevent serious liver problems, a large observational study suggested.

Aspirin users were 41% less likely to develop hepatocellular carcinoma and 45% less likely to die from chronic liver disease than non-users, both statistically significant differences, Vikrant V. Sahasrabuddhe, MBBS, DrPH, of the National Cancer Institute in Rockville, Md., and colleagues reported.

Other NSAIDs were also associated with reduced mortality from chronic liver disease, but not with less liver cancer, among the more than 300,000 middle-age and older participants in the National Institutes of Health-AARP Diet and Health Study cohort.

"These associations are prominent with the use of aspirin, and if confirmed, might open new vistas for chemoprevention of hepatocellular carcinoma and chronic liver disease," the researchers wrote in the Dec. 5 issue of the Journal of the National Cancer Institute.

The findings were not unexpected based on prior results in colorectal and other cancer types, Boris Pasche, MD, PhD, an oncologist at the University of Alabama at Birmingham, noted in an interview with MedPage Today.

"We are seeing a growing body of evidence suggesting that taking aspirin long-term prevents the development of several types of cancer" in populations taking the NSAID for cardiovascular event prevention, he explained.

However, aside from being a possible additional benefit when indicated for cardioprotection, aspirin might not be either necessary or that useful for protecting the liver, according to other experts.
For one thing, there are already good strategies that don't raise bleeding risk the way NSAIDs do, Isra G. Levy, MBBCh, MSc, and Carolyn P. Pim, MD, both of the University of Ottawa and Ottawa Public Health in Ontario, noted in an accompanying editorial.

"In practice," they wrote, "we know and understand the causes of most cases of chronic liver disease and primary liver cancer: viral infections, especially hepatitis B virus (HBV) and hepatitis C virus (HCV), and alcohol. And we already have cheap, readily available interventions to prevent a substantial majority of such diseases."

Furthermore, the risk of developing hepatocellular carcinoma is low enough in the general population that chemoprevention wouldn't make sense when weighed against the bleeding risk, commented Mary Ann Huang, MD, a hepatologist at Henry Ford Hospital in Detroit.

The higher-risk population for whom preventive strategies are needed -- those with cirrhosis -- likely wouldn't be good candidates either because they are also at higher risk of bleeding, Huang told MedPage Today in an interview.

Still the NIH-AARP study results may be good enough to warrant a prospective trial to see whether the benefit would outweigh the risk in that population, Pasche suggested.

The joint Diet and Health study included 300,504 adults ages 50 to 71 years at enrollment who reported their NSAID use on a baseline questionnaire.

The cohort was pulled from six states (California, Florida, Louisiana, New Jersey, North Carolina, and Pennsylvania) and two metropolitan areas (Atlanta and Detroit).
Among the respondents, 73% reported aspirin use and 56% used other NSAIDs.

Altogether, any aspirin or non-aspirin NSAID use was associated with reduced relative risks of:
  • 0.63 for developing hepatocellular carcinoma (95% CI 0.46 to 0.87)
  • 0.49 for risk of death due to chronic liver disease (95% CI 0.39 to 0.61)
Aspirin use specifically, regardless of other NSAID use, came out significantly protective on both counts as well, with relative risks of 0.59 for developing hepatocellular carcinoma (95% CI 0.45 to 0.77) and 0.55 for death from chronic liver disease (95% CI 0.45 to 0.67).

The effect was even greater, with relative risks of 0.51 and 0.50, when looking at those participants who exclusively used aspirin versus those who didn't take any NSAIDs.

Other NSAID use was associated with a reduced risk of chronic liver disease mortality, with a relative risk of 0.74 (95% CI 0.61 to 0.90) that dropped to 0.66 (95% CI 0.48 to 0.91) when looking at those who used only non-aspirin NSAIDs versus no NSAIDs.

But the effect on hepatocellular carcinoma incidence wasn't significant in either case with non-aspirin NSAIDs, and the effect on death from chronic liver disease was significant only in those who used it on a monthly rather than daily or weekly basis.

Aspirin's effects were independent of frequency of use.

All the results were adjusted for age, sex, race or ethnicity, body mass index, cigarette smoking, alcohol consumption, and diabetes.

The researchers suggested that the apparent advantage of NSAID use in the cohort may have been due to anti-inflammatory or other mechanisms.

They acknowledged, though, that the lack of dose response and finding of only monthly links to non-aspirin NSAID use "suggests that the findings should be interpreted with some caution, because they may also reflect an unmeasured confounder."
Huang pointed to the lack of data on cirrhosis and hepatitis status and the single time point of NSAID use ascertainment.

Although there wasn't any reporting of duration or indication for NSAID use, a sensitivity analysis excluding participants who said they had a history of heart disease or hypertension as "a proxy for cardiovascular indication and longer duration of NSAID use, particularly low-dose aspirin), yielded hazard rate ratios similar to those of the overall cohort and suggested minimal potential for confounding by indication."

Primary source: Journal of the National Cancer Institute
Source reference:
Sahasrabuddhe VV, et al "Nonsteroidal Anti-inflammatory Drug Use, Chronic Liver Disease, and Hepatocellular Carcinoma" J Natl Cancer Inst 2012: 104; 1808–1814.

Additional source: Journal of the National Cancer Institute
Source reference:
Levy IG, Pim CP "An Aspirin a Day: The Allure (and Distraction) of Chemoprevention" J Natl Cancer Inst 2012: 104.

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