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Does aspirin reduce the incidence, recurrence, and mortality of hepatocellular carcinoma? A GRADE-assessed systematic review and dose–response meta-analysis

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Abstract

Purpose

Aspirin has been suggested to reduce the risk of cancer. However, previous studies have been inconsistent regarding the relationship between aspirin use and the risk of occurrence of hepatocellular carcinoma (HCC). The purpose of this study was to assess the effect of aspirin on clinical outcomes in patients with HCC in a meta-analysis and to explore the possible dose–response relationship.

Methods

A systematic literature search was conducted in 10 electronic databases and 4 registries. The combined hazard ratios (HRs) were calculated using a random-effects model with 95% confidence interval (CIs) to assess the effect of aspirin on the risk of HCC. Relevant subgroup analyses and sensitivity analyses were performed.

Results

The results show that aspirin use correlated with lower incidence of HCC (HR: 0.75, 95% CI: 0.71–0.80), decreased risk of HCC recurrence (HR: 0.79, 95% CI: 0.65–0.96), and reduced mortality (HR: 0.72, 95% CI: 0.60–0.87). The results of the subgroup analysis showed that aspirin use was consistently associated with reduced incidence of HCC across different regions, study designs, and populations. A linear relationship was found for both dosage and duration of aspirin use. An increased of bleeding with aspirin use among patients was also observed (HR 1.10, 95% CI: 1.02–1.20).

Conclusions

This meta-analysis found that aspirin use was independently associated with a reduced risk of HCC incidence, recurrence, and death. Furthermore, aspirin use influenced HCC occurrence in a dose-dependent and duration-dependent manner. However, an increased risk of bleeding with aspirin use was noted.

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Acknowledgements

We appreciate all authors for their contributions, and support from AMITA Health Saint Joseph Hospital Chicago, the First Affiliated Hospital of Anhui Medical University, Kansas City University, Duke University, Mayo Clinic and Anhui Medical University.

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  1. Shaodi Ma and Guangbo Qu contributed equally to this work and should be considered as co-first authors.

Authors and Affiliations

  1. Department of Epidemiology and Health Statistics, School of Public, Health Anhui Medical University, No. 81 Meishan Road, Hefei, 230032, Anhui, People’s Republic of China

    Shaodi Ma, Guangbo Qu, Haixia Liu, Ning Li, Birong Wu, Juan Gao, Linya Feng, Peng Xie, Weihang Xia & Yehuan Sun

  2. AMITA Health Saint Joseph Hospital Chicago, 2900 N. Lake Shore Drive, Chicago, Illinois, 60657, USA

    Chenyu Sun & Na Hyun Kim

  3. Department of Infectious Diseases, the First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230032, Anhui, China

    Yuemeng Jiang

  4. College of Osteopathic Medicine, Kansas City University, 1750 Independence Ave, Kansas City, MO, 64106, USA

    Scott Lowe & Rachel Bentley

  5. Trinity College of Arts & Sciences, Duke University, 102 Wannamaker Drive, Durham, NC, 27708, USA

    Yike Zhu

  6. Radiation Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Qin Zhou

  7. Center for Evidence-Based Practice, Anhui Medical University, No. 81 Meishan Road, Hefei, 230032, Anhui, China

    Yehuan Sun

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Contributions

Shaodi Ma and Yehuan Sun designed research; Shaodi Ma, Guangbo Qu, Chenyu Sun, and Haixia Liu conducted literature search; Haixia Liu participated and assisted in literature search and data collection; Shaodi Ma, Chenyu Sun, Guangbo Qu, Haixia Liu, and Yehuan Sun analyzed and interpreted data; Shaodi Ma and Chenyu Sun wrote the paper. Yehuan Sun, Chenyu Sun, Yuemeng Jiang, Birong Wu, Juan Gao, Ning Li, Na Hyun Kim, Scott Lowe, and Rachel Bentley provided critical opinion. Yehuan Sun, Linya Feng, Peng Xie, Weihang Xia, Yike Zhue, and Qin Zhou revised the paper. Shaodi Ma, Chenyu Sun, Guangbo Qu, and Haixia Liu had primary responsibility for final content. Yehuan Sun is the corresponding author. All authors read and approved the final manuscript. All individuals gave written informed consent for publication. The authors are responsible for the reported research, have participated in the concept and design, analysis, and interpretation of data, drafting, or revising of the manuscript, and have approved the manuscript as submitted.

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Correspondence to Yehuan Sun.

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This article does not contain any studies with human participants or animals performed by any of the authors. We did not use individual data but published data. These data have been widely utilized in research and are generally available. Therefore, we confirm that any aspect of the work covered in this manuscript has been conducted with ethical approval. And this study has been registered (registration number: CRD42021256093) with the PROSPERO (International Prospective Register of Systematic Reviews) and was conducted according to the Preferred Reporting Items for Systemic Reviews and Meta-Analysis (PRISMA) statement.

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Ma, S., Qu, G., Sun, C. et al. Does aspirin reduce the incidence, recurrence, and mortality of hepatocellular carcinoma? A GRADE-assessed systematic review and dose–response meta-analysis. Eur J Clin Pharmacol 79, 39–61 (2023). https://doi.org/10.1007/s00228-022-03414-y

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