Daily aspirin reduces hep B virus-related liver cancer risk

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Daily aspirin therapy was significantly associated with a reduced risk in hepatitis B virus‐related liver cancer, found a study presented this at The Liver Meeting®, held by the American Association for the Study of Liver Diseases.

Hepatitis B is a viral infection that attacks the liver. HBV can be contracted through contact with an infected person’s blood or other bodily fluid, and the infection can either be acute or chronic. According to AASLD’s Guidelines for Treatment of Chronic Hepatitis B, an estimated 240m people worldwide have chronic HBV, and the highest prevalence of the virus is in Africa and Asia. Death from HBV is commonly due to the development of cirrhosis (scaring of healthy liver tissue) or hepatocellular carcinoma (liver cancer).

Past research suggests that daily aspirin therapy – which is often prescribed to prevent cardiovascular disease – may also prevent the development of cancer. However, clinical evidence is lacking for the effectiveness of aspirin therapy in preventing HBV‐related liver cancer.

Researchers at Taichung Veterans General Hospital in Taichung, Taiwan; E‐Da Hospital in Kaohsiung, Taiwan; Fu Jen Catholic University in New Taipei City, Taiwan; and National Taiwan University Hospital in Taipei conducted a nationwide cohort study to determine if aspirin therapy could, indeed, reduce liver cancer risk.

“Liver cancer is the second leading cause of cancer death worldwide, and HBV is the most prevalent risk factor in our region, says Dr Teng‐Yu Lee, a researcher in the department of gastroenterology at Taichung Veterans General Hospital and lead investigator in the study. “HBV‐related liver cancer is therefore a major public health issue with a severe socioeconomic impact.”

Although current antiviral medicines such as nucleos(t)ide analogue therapy could significantly reduce liver cancer risk, Lee notes these therapies do not completely eliminate the risk. Additionally, Lee says most HBV carriers are not indicated for antiviral therapy, so another effective way of reducing liver cancer risk needs to be developed.

“Aspirin has been investigated to explore its chemo-preventive effect in cancers that are related to chronic inflammation, particularly in the prevention of colo-rectal cancer. However, clinical evidence supporting the chemo-preventive effect of aspirin therapy on liver cancer remains limited. Therefore, we conducted a large‐scale cohort study to evaluate the association of aspirin therapy with HBV‐related liver cancer.”

The researchers retrieved medical records from the National Health Insurance Research Database between 1998 and 2012 for their study. They screened records of 204,507 patients with chronic hepatitis B, and excluded patients with other forms of infectious hepatitis. After excluding patients with liver cancer before the follow‐up index dates, 1,553 patients who had continuously received daily aspirin for at least 90 days were randomly matched 1:4 with 6,212 patients who had never received anti‐ platelet therapy by means of propensity scores consisting of baseline characteristics, the index date and nucleos(t)ide analogue (NA) use during follow‐up. The researchers analysed both cumulative incidents of and hazard ratios for HCC development after adjusting for competing mortality.

Cumulative incidence of liver cancer in the group treated with aspirin therapy was significantly lower than that in the untreated group in five years. In their multivariate regression analysis, the researchers found aspirin therapy was independently associated with reduced liver cancer risk. Sensitivity subgroup analyses also verified this association. Older age, male gender, cirrhosis and diabetes also were independently associated with an increased risk, but nucleos(t)ide analogue or statin use was associated with a decreased risk.

“For effectively preventing HBV‐related liver cancer, the findings of this study may help hepatologists treat patients with chronic HBV infection in the future, particularly for those who are not indicated for antiviral therapy. We are pursuing prospective investigations for further confirming the findings,” says Lee.

Abstract
Background: Aspirin may prevent cancer development, but clinical evidences in HBV-related HCC remain lacking. We aimed to investigate the association of aspirin therapy with HBV-related HCC risk.
Methods: In this nationwide cohort study, medical records were retrieved from the National Health Insurance Research Database between years 1998 and 2012. We screened 204,507 patients with chronic hepatitis B, and patients with other infectious hepatitis were excluded. After excluding patients with HCC before the follow-up index dates, 1,553 patients who continuously received daily aspirin ≥ 90 days were randomly matched 1: 4 with 6,212 patients who never received anti-platelet therapy by means of propensity scores, consisted of baseline characteristics, the index date, and nucelos(t)ide analogue (NA) use during follow-up. Both cumulative incidences of and hazard ratios (HRs) for HCC development were analyzed after adjusting for competing mortality.
Results: The cumulative incidence of HCC in the treated group was significantly lower than that in the untreated group in 5 years (2.86%, 95% CI: 1.89-3.83 vs. 5.59%, 95% CI: 4.91-6.27; P < 0.001). In the multivariable regression analysis, aspirin therapy was independently associated with a reduced HCC risk (HR 0.63, 95% CI: 0.47-0.85; P = 0.002). Sensitivity subgroup analyses also verified this association. In addition, older age (HR 1.03 per year), male gender (HR 2.65), cirrhosis (HR 1.89), and diabetes mellitus (HR 1.51) were independently associated with an increased HCC risk, but NA (HR 0 57) or statin (HR 0 57) use was with a decreased HCC risk.
Conclusion: Aspirin therapy is significantly associated with a reduced risk of HBV-related HCC.

Authors
Teng-Yu Lee, Yao-Chun Hsu, Shi-Hang Yu, Jaw-Town Lin, Ming-Shiang Wu, Chun-Ying Wu

American Association for the Study of Liver Diseases material
Hepatology abstract 223


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