Aspirin cuts HCC risk in CHB patients with heavy metabolic burden

Aspirin safely lowers the risk of hepatocellular carcinoma (HCC) among chronic hepatitis B (CHB) patients suffering from a heavy burden of metabolic risk, according to a study presented at The Liver Meeting Digital Experience 2021 of the American Association for the Study of Liver Diseases (AASLD 2021).

On the other hand, CHB patients with low metabolic risk do not seem to derive much benefit from aspirin therapy, which instead heightens their risk of bleeding.

Drawing from the database of National Health Insurance Service of South Korea, the researchers enrolled 282,611 patients (median age 43 years, 65.7 percent men). Four risk factors were taken into consideration when assessing metabolic risk: high blood pressure, obesity, diabetes, and hypercholesterolaemia.

Most (n=114,457) of the participants had none of the above metabolic risk factors, while 96,651, 57,515, and 13,812 patients harboured 1, 2, and ≥3 risk factors, respectively. Compared to no-burden patients, those with ≥3 risk factors were at least 70-percent more likely to develop the primary outcome of HCC (adjusted hazard ratio [HR], 1.73, 95 percent confidence interval [CI], 1.58–1.90). [AASLD 2021, Lee CH, et al]

Similarly, having such a high burden of metabolic risk aggravated the likelihood of liver-related mortality (adjusted HR, 2.04, 95 percent CI, 1.78–2.34) and major bleeding (adjusted HR, 1.71–2.12).

The researchers then split the patients into two groups: low (≤2 risk factors; n=268,799) and high (≥3 risk factors; n=13,812) metabolic risk. After 1:1 propensity-score matching, the remaining participants in each group were further divided into two according to whether they received aspirin treatment or not.

Fine and Gray competing risk analysis showed that in the high metabolic risk group, aspirin treatment exerted a significant protective effect against HCC, reducing such risk by nearly 30 percent relative to untreated counterparts (adjusted HR, 0.72, 95 percent CI, 0.57–0.91). This benefit also occurred safely with no excess risk of major bleeding (adjusted HR, 1.02, 95 percent CI, 0.79–1.32).

In contrast, aspirin proved to be detrimental for CHB patients with low metabolic risk. Treatment had no significant impact on HCC risk (adjusted HR, 0.93, 95 percent CI, 0.84–1.03) but significantly aggravated the likelihood of major bleeding (adjusted HR, 1.22, 95 percent CI, 1.08–1.39).

“Experimental and clinical evidence suggest that aspirin may prevent progression of liver fibrosis and HCC,” the researchers said, pointing to two prior nationwide cohort studies, where aspirin treatment indeed safely suppressed HCC risk. [JAMA Intern Med 2019;179:633-640; N Engl J Med 2021;382:1018-1028]

“Considering the wide spectrum of liver diseases and lengthy treatment period, there is a strong need to elucidate the optimal candidate” for such treatment, they added.

“In this nationwide cohort study of CHB patients without cirrhosis, increasing burden of metabolic risk factors was associated with higher risk of HCC, liver-related mortality, and major bleeding,” the researchers said. However, among those suffering from a heavy burden of metabolic risk, “aspiring therapy was associated with a 28-percent reduced risk of HCC, without excess risk of bleeding.”