Systematic Review With Meta-analysis

The Effects of Non-steroidal Anti-inflammatory Drugs and Anti-platelet Therapy on the Incidence and Recurrence of Hepatocellular Carcinoma

Regina Zi Hwei Tan; Ian Lockart; Christina Abdel Shaheed; Mark Danta


Aliment Pharmacol Ther. 2021;54(4):356-367. 

In This Article


Hepatocellular carcinoma (HCC) is the sixth most common cancer and fourth leading cause of cancer-related death worldwide.[1] HCC typically occurs in patients with chronic liver disease (CLD), with viral hepatitis being the most important cause worldwide, followed by alcohol-related liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD).[2] Despite recommendations for HCC screening in at-risk groups, HCC is usually detected late where the prognosis remains poor and the therapeutic options are limited.[3] More effective prevention strategies and novel HCC therapies are crucial to improve HCC outcomes.

There has been increasing recognition of the role of platelets in inflammation and carcinogenesis. Platelets promote cancer cell proliferation, angiogenesis and metastasis through direct interaction with leucocytes and endothelial cells, and via the release of multiple factors including TXA2, ADP, angiogenic factors (VEGF, FGF, PDGF) and growth factors (IGF-I, TGF-β1, SDF-1).[4–6] Anti-platelet agents may, therefore, have a novel role in cancer therapy.[7–10] Recent data suggest that long-term use of low-dose NSAIDs may effectively prevent several malignancies, including colon, breast, lung and prostate cancer, with notably stronger protective effects in gastrointestinal malignancies.[11–13] Increasing data suggest that NSAIDs and anti-platelet therapy (APT), especially aspirin, reduces HCC incidence. Two previous meta-analyses revealed that NSAID use reduced the risk of HCC, although results varied in subgroup analysis by drug type.[14,15] Another meta-analysis revealed that aspirin users had a reduced risk of developing HCC compared with non-users.[16] These analyses, however, were conducted in the general population, with no specific risk factors for HCC.

The primary aim of this study was to assess the impact of NSAIDs and APT on HCC incidence among at-risk individuals with chronic liver disease. The secondary aims included evaluating the impact of NSAIDs or APT on liver-related mortality; HCC recurrence; and to quantify the bleeding complications associated with long-term NSAIDs or APT use in this at-risk population. The results could inform practitioners about the benefits and risks of prescribing long-term low-dose NSAIDs or APT to patients with chronic liver disease.