Skip to main content
Download PDF

The relationship between aspirin consumption and hepatocellular carcinoma: a systematic review and meta-analysis

European Journal of Medical Research volume 28, Article number: 226 (2023) Cite this article

Abstract

Background

Recent studies have shown that aspirin consumption may reduce the risk of hepatocellular carcinoma (HCC), but their correlation is still not fully understood. This meta-analysis aimed to investigate the correlation between aspirin consumption and HCC.

Methods

A systematic literature search was conducted on PubMed, Scopus, Cochrane Library, EMBASE, and Web of Science databases. The search period was from the establishment of the database to July 1, 2022 with no language restrictions.

Results

A total of 19 studies including three prospective studies and 16 retrospective ones with 2,217,712 patients were included. Compared with those who did not take aspirin, those who took aspirin had a 30% lower risk of HCC (hazard ratio [HR] = 0.70, 95% confidence interval [CI] 0.63–0.76, I2 = 84.7%, P < 0.001). Subgroup analysis showed that aspirin significantly reduced the risk of HCC by 19% in Asia (HR = 0.81, 95% CI 0.80–0.82, I2 = 85.2%, P < 0.001) and by 33% (HR = 0.67, 95% CI 0.61–0.73, I2 = 43.6%, P = 0.150) in Europe and the U.S with no significant difference. Moreover, in patients with HBV or HCV infection, aspirin reduced 19% and 24% of the risk of HCC, respectively. However, aspirin administration might increase risks of gastrointestinal bleeding in patients with chronic liver disease (HR = 1.14, 95% CI 0.99–1.31, I2 = 0.0%, P = 0.712). Sensitivity analysis showed no significant difference of results after excluding individual studies, suggesting that the results were robust.

Conclusion

Aspirin may reduce the risk of HCC in both healthy population and patients with chronic liver disease. However, attention should be paid to adverse events such as gastrointestinal bleeding in patients with chronic liver disease.

Introduction

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy that accounts for 75–85% of liver cancers. Patients with HCC have poor prognoses and the onset of HCC is insidious. Risk factors of HCC include chronic liver inflammation and liver fibrosis or cirrhosis. In recent years, the global incidence of HCC has increased and it is estimated that more than 1 million patients will die from HCC in 2030.

Most HCC patients don’t have the opportunity for surgery because of advanced stages. Only a small number of patients that are diagnosed at an early stage can receive radical resection [2]. Other therapies such as transcatheter arterial chemoembolization, targeted therapy, or immunotherapy also had limited efficacy [3]. Therefore, there is an urgent need for effective therapies to control the progression of HCC.

Aspirin is a classical non-steroidal anti-inflammatory drug (NSAIDs) that exerts antiplatelet effects by acetylating platelet cyclooxygenase (COX), thereby reducing the risk of myocardial infarction and stroke [4]. Therefore, it is widely used in the prevention and treatment of cardiovascular diseases. In the last few decades, much evidence has shown the potential of aspirin in the prevention and treatment of cancer [5,6,7]. A randomized trial including 25,570 participants showed that aspirin reduced the risk of death from gastrointestinal cancers, including esophageal, colorectal, and pancreatic cancers, as well as from non-gastrointestinal solid cancers, such as lung, prostate, bladder, and kidney cancers, especially colorectal cancers [8]. Studies have demonstrated that aspirin can reduce the risk of HCC, whereas non-aspirin NSAID does not have this effect [9, 10]. Moreover, compared with irregular aspirin administration, the risk-reducing effect of aspirin is dose- and duration dependent [6]. In in vitro and in vivo experiments, the combination of aspirin and other drugs exhibited a promising efficacy to suppress HCC progression [11,12,13,14].

However, a randomized controlled trial showed that long-term administration of low-dose aspirin did not reduce the risk of overall cancer, breast cancer, colorectal cancer, or other site-specific cancers [15]. Therefore, it remains controversial whether aspirin can reduce the risk of HCC. This study aimed to investigate the association between aspirin use and HCC through a meta-analysis.

Materials and methods

Literature retrieval strategy

A systematic literature search was conducted on PubMed, Scopus, Cochrane Library, EMBASE and Web of Science databases from the establishment of the database to July 1, 2022, with no language restrictions. A combination of subject terms and free words were used for literature search using Boolean logic operator grouping (Additional file 1).

Inclusion and exclusion criteria

Inclusion criteria were as follows: (1) retrospective or prospective cohort studies that explored the relationship between aspirin and the risk of HCC (from 2015 to 2022); (2) reporting the hazard ratio (HR) and 95% confidence interval (CI) of HCC based on different administration of aspirin; (3) the diagnosis of HCC was made based on the diagnostic criteria. Exclusion criteria were as follows: (1) reviews, case reports, meta-analyses, conference abstracts, redundant publications, ecological studies, animal studies, and case–control studies; (2) studies on patients who have been diagnosed with HCC before aspirin use; (3) studies that did not explicitly report any HR or 95% CI.

Evaluation of literature quality

The Newcastle–Ottawa scale (NOS) was used to evaluate literature quality in terms of study population selection, comparability between groups, and outcome measures, with a maximum score of 9. We included high-quality literature with scores greater than or equal to 7 in this study.

Data extraction

Two investigators independently screened the literature and extracted data according to the criteria. In case of disagreements, they discussed or consulted a third party to reach the consensus. During literature screening, the title was first read to exclude irrelevant literature, then the abstract and full text were read to include relevant studies. Corresponding authors were contacted by email to obtain necessary information if needed. The extracted information included (1) first author, year of publication, study region, and study type; (2) study population and whether they had liver disease; (3) the number of participants and cases; (4) reported outcomes, including HR and 95% CI and (5) study-adjusted confounding factors, etc.

Statistical analysis

Stata 14.2 software was used for meta-analysis, and the statistics were presented by HR and 95% CI, with a preference for the corrected values if they were provided in the literature. The Cochran q test (P heterogeneity) and the I2 value were used to evaluate the heterogeneity of the included studies. P ≥ 0.05, 0 ≤ I2 ≤ 50% indicated low heterogeneity, and a fixed effect model was used for analysis; P < 0.05 and I2 > 50% indicated significant heterogeneity, so that a random effect model was used to identify the source of heterogeneity and perform subgroup and sensitivity analyses. Publication bias was evaluated using a funnel plot, Beggs test, and Eggers. P < 0.05 indicated that the difference was statistically significant.

Results

Literature screening process

We retrieved 35, 221, 103, 419, and 19 papers from Pubmed, Scopus, Web of Science, EMBASE, and Cochrane Library, respectively. 240 duplicate papers were excluded. After reading the titles and abstracts and excluding irrelevant literature such as reviews, case reports, meta-analyses, conference abstracts, animal experimental studies, 49 articles were selected for full-text reading. Finally, 18 articles with a total of 2,217,712 participants were enrolled based on the criteria. The literature screening process is shown in Fig. 1.

Fig. 1
figure 1

Literature selection process

Full size image

Basic characteristics and quality evaluation of the included literature

This article included 18 articles containing 19 studies published from 2015 to 2022, in which 13 studies focused on patients with liver disease, 4 studies focused on general population, and the remaining 2 studies focused on specific patients with type 2 diabetes or head and neck squamous cell carcinoma (HNSCC); 3 were prospective studies and 16 were retrospective studies (Table 1). Based on NOS results, all included literature had high quality (Table 2).

Table 1 Basics features of the included literature
Full size table
Table 2 Literature quality evaluation
Full size table

Aspirin was associated with reduced risk of HCC

The 19 included studies showed a high heterogeneity, therefore, random effect model was adopted and showed that the risk of HCC was 30% lower in those taking aspirin compared with those not taking aspirin (HR = 0.70, 95% CI 0.63–0.76, I2 = 84.7%, P < 0.001) (Fig. 2). The results showed that there was no significant difference of HR after excluding individual studies (Fig. 3), suggesting that the results were robust.

Fig. 2
figure 2

Forest plot of correlation between aspirin and the risk of hepatocellular carcinoma

Full size image
Fig. 3
figure 3

Sensitivity analysis results

Full size image

Subgroup analysis of the association between aspirin and the risk of HCC

Subgroup analysis based on regions

Since aspirin and the risk of HCC. The studies were divided into two subgroups based on regions: the Asia group contained 15 studies whereas the Europe and the United States group had 4 studies. The results showed that aspirin reduced the risk of HCC by 19% in Asia (HR = 0.81, 95% CI 0.80–0.82, I2 = 85.2%, P < 0.001) and by 33% in Europe and the U.S. (HR = 0.67, 95% CI 0.61–0.73, I2 = 43.6%, P = 0.150) (Fig. 4).

Fig. 4
figure 4

Subgroup analysis of forest plots based on regions

Full size image

Subgroup analysis based on study design

Moreover, based on study design, these studies were classified into prospective (n = 3) and retrospective (n = 16) studies. The results showed that aspirin reduced the risk of HCC in the retrospective studies (HR = 0.81, 95% CI 0.80–0.82, I2 = 84.8%, P < 0.001) (Fig. 5).

Fig. 5
figure 5

Subgroup analysis of forest plots based on study design

Full size image

Subgroup analysis based on gender

According to genders, studies were divided into female and male groups, with a total of five papers reporting the HR for both female and male. The results showed that aspirin reduced the risk of HCC by 33% in female (HR = 0.67, 95% CI 0.59–0.75, I2 = 21.3%, P = 0.274) and by 21% in male (HR = 0.79, 95% CI 0.72–0.86, I2 = 56.5%, P = 0.042) (Fig. 6).

Fig. 6
figure 6

Subgroup analysis of forest plots based on gender

Full size image

Subgroup analysis based on whether results were adjusted by statins and metformin

Then we categorized studies according to whether the results were adjusted by statins and metformin. There were 5 papers with 6 studies adjusted results for both statins and metformin and 11 papers without adjustment. The remaining two papers only adjusted results for glucose-lowering drugs, so that they were excluded. The results showed that aspirin was associated with reduced risks of HCC when the results were adjusted for statins and metformin (HR = 0.78, 95% CI 0.73–0.83, I2 = 67.4%, P = 0.009) or not (HR = 0.81, 95% CI 0.80–0.82, I2 = 88.7%, P < 0.001); however, there was no no significant difference between the two groups (P = 0.257) (Fig. 7).

Fig. 7
figure 7

Subgroup analysis of forest plots depending on whether statins and metformin were adjusted

Full size image

Subgroup analysis based on study population

Based on different populations, divided into two subgroups: patients with chronic liver disease (n = 13) and general population (n = 4). The remaining two studies were excluded. The results showed that aspirin reduced the risk of HCC in patients with chronic liver disease (HR = 0.81, 95% CI 0.80–0.82, I2 = 87.2%, P < 0.001) (Fig. 8).

Fig. 8
figure 8

Subgroup analysis of forest plots based on the study population

Full size image

Subgroup analysis based on hepatitis subtypes

Further, in patients with liver disease, we divided studies into HBV (n = 7) and HCV (n = 4) groups based on different hepatitis viruses. The results showed that the risk of HCC was reduced by 19% in HBV-infected patients (HR = 0.81, 95% CI 0.80–0.82, I2 = 62.8%, P = 0.013) and by 24% in HCV-infected patients (HR = 0.76, 95% CI 0.70–0.83, I2 = 80.2%, P = 0.002). There was no significant difference between the two groups (P = 0.201) (Fig. 9).

Fig. 9
figure 9

Subgroup analysis of forest plots depending on the type of infected virus

Full size image

Subgroup analysis based on liver cirrhosis status

Also, we divided patients with liver disease into liver cirrhosis and non-cirrhosis groups. The results showed that aspirin was a protective factor in either cirrhosis (HR = 0.78, 95% CI 0.69–0.88, I2 = 64.9%, P = 0.023) and non-cirrhosis (HR = 0.86, 95% CI 0.78–0.94, I2 = 0.0%, P = 0.495) groups (Fig. 10).

Fig. 10
figure 10

Subgroup analysis of forest plots depending on presence or absence of cirrhosis

Full size image

Subgroup analysis based on whether results were adjusted by antiviral drugs

When studies were classified based on whether the results were adjusted by antiviral drugs, we found that aspirin remained to be a protective factor in either adjusted (HR = 0.75, 95% CI 0.70–0.80, I2 = 53.4%, P = 0.092) and 0.81 (95% CI 0.80–0.82, I2 = 78.2%, P < 0.001) respectively. There was a significant difference between groups (P = 0.027) (Figs. 11).

Fig. 11
figure 11

Subgroup analysis of forest plots depending on whether results were adjusted based on antiviral drugs

Full size image

Analysis of bleeding risk associated with aspirin

To determine whether aspirin increased the risk of bleeding, we analyzed 5 papers and found that aspirin was associated with an increased risk of gastrointestinal bleeding in patients with chronic liver disease (HR = 1.14, 95% CI 0.99–1.31, I2 = 0.0%, P = 0.712) (Fig. 12).

Fig. 12
figure 12

Forest plot of aspirin use and bleeding risk

Full size image

Publication bias analysis

Funnel plots were drawn and exhibited asymmetric, indicating the existence of publication bias. The Beggs and Eggers tests showed consistent results (Beggs: P = 0.093; Eggers: P = 0.011) (Fig. 13).

Fig. 13
figure 13

Funnel plot of the association between aspirin and the risk of hepatocellular carcinoma

Full size image

Discussion

In recent years, many studies have demonstrated the anti-HCC effect of aspirin, which is believed to reduce the incidence of HCC [2]. However, the mechanism through which aspirin inhibits the development of HCC remains unclear. Aspirin may exert anti-HCC activity by several mechanisms [33]. For example, aspirin is able to inhibit pro-inflammatory molecule COX-2, whose inhibitor is shown to reduced liver fibrosis, portal hypertension, and hepatoma cell proliferation [37]. Also, aspirin can inhibit the activation of NF-κB pathway [34,35,36]. Moreover, as aspirin may induce autophagy-related cell death and interference with glucose uptake by downregulating the expression of glucose transporter protein 1 and activating Bcl-2/Bax signaling pathway [38]. In addition, aspirin can reverse sorafenib resistance in HCC and has a synergistic antitumor effect in combination with sorafenib [14].

This meta-analysis including 2,217,714 participants provides a systematic evaluation of the relationship between aspirin and the risk of HCC. Our results indicated that aspirin reduced the risk of HCC by 30% compared with that in patients who did not use aspirin. Since considerable heterogeneity was detected in the included study, we performed subgroup analyses according to study region, study type, sex, adjusted medication, and study population. Results indicated that use was associated with a reduced risk of HCC independent of these factors. As for patients with liver disease, we concluded consistent results regardless of the presence or absence of cirrhosis and adjustment for administration of antiviral drugs. In addition, the adjusted results showed a diminished effect of aspirin in reducing the risk of HCC compared with that in aspirin users who were not adjusted for both statins and metformin, suggesting that the combination of aspirin and these drugs may have a synergistic anti-HCC effect. Our results also suggest that aspirin is associated with an increased risk of gastrointestinal bleeding in patients with chronic liver disease.

Compared with previous studies, our study has a large sample size with a long follow-up period. However, there are several limitations. First, the heterogeneity of included studies was obvious, which may be due to different study designs, different and highly variable sample sizes across studies, different inclusion and exclusion criteria, the presence of more confounding factors, inconsistent control of confounding factors across studies, and varied lengths of follow-up. In addition, the presence of confounding factors in this study should be considered. For example, aspirin is often concomitantly administered with statins, lipid-lowering agents, and clopidogrel. Studies suggested that statin and clopidogrel may reduce the risk of HCC [39, 40]. Therefore, additional studies are needed to exclude the influence of confounding factors when exploring the benefit of aspirin in HCC. In addition, although aspirin has some potential benefits for patients with liver disease, its consistent use may cause some adverse events, such as gastrointestinal and intracranial hemorrhage. Therefore, it remains controversial whether aspirin should be advocated in high-risk patients such as those with peptic ulcers and esophagogastric fundic varices. Simon et al. showed that the administration of low-dose aspirin did not increase the risk of gastrointestinal bleeding [6]. Therefore, additional studies are required to determine the optimal dose and duration of aspirin to exert clinical benefit for HCC patients without increasing risks of adverse events.

Conclusion

Aspirin may reduce the risk of HCC in both healthy population and patients with chronic liver disease. However, attention should be paid to adverse events such as gastrointestinal bleeding in patients with chronic liver disease.

Availability of data and materials

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.

    Article  PubMed  Google Scholar 

  2. Villanueva A. Hepatocellular carcinoma. N Engl J Med. 2019;380(15):1450–62.

    Article  CAS  PubMed  Google Scholar 

  3. Galle PR, Tovoli F, Foerster F, et al. The treatment of intermediate stage tumours beyond TACE: from surgery to systemic therapy. J Hepatol. 2017;67(1):173–83.

    Article  PubMed  Google Scholar 

  4. Xia H, Hui KM. Emergence of aspirin as a promising chemopreventive and chemotherapeutic agent for liver cancer. Cell Death Dis. 2017;8(10):e3112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Sahasrabuddhe VV, Gunja MZ, Graubard BI, et al. Nonsteroidal anti-inflammatory drug use, chronic liver disease, and hepatocellular carcinoma. J Natl Cancer Inst. 2012;104(23):1808–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Simon TG, Ma Y, Ludvigsson JF, et al. Association between aspirin use and risk of hepatocellular carcinoma. JAMA Oncol. 2018;4(12):1683–90.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Li JH, Wang Y, Xie XY, et al. Aspirin in combination with TACE in treatment of unresectable HCC: a matched-pairs analysis. Am J Cancer Res. 2016;6(9):2109–16.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Rothwell PM, Fowkes FGR, Belch JFF, et al. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet. 2011;377(9759):31–41.

    Article  CAS  PubMed  Google Scholar 

  9. Sahasrabuddhe VV, Gunja MZ, Graubard BI, et al. Nonsteroidal anti-inflammatory drug use, chronic liver disease, and hepatocellular carcinoma. J Natl Cancer Inst. 2012;104(23):1808–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hossain MA, Kim DH, Jang JY, et al. Aspirin induces apoptosis in vitro and inhibits tumor growth of human hepatocellular carcinoma cells in a nude mouse xenograft model. Int J Oncol. 2012;40(4):1298–304.

    Article  CAS  PubMed  Google Scholar 

  11. Sitia G, Aiolfi R, Di Lucia P, et al. Antiplatelet therapy prevents hepatocellular carcinoma and improves survival in a mouse model of chronic hepatitis B. Proc Natl Acad Sci USA. 2012;109(32):E2165–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Gao M, Kong Q, Hua H, et al. AMPK-mediated up-regulation of mTORC2 and MCL-1 compromises the anti-cancer effects of aspirin. Oncotarget. 2016;7(13):16349–61.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Liu YX, Feng JY, Sun MM, et al. Aspirin inhibits the proliferation of hepatoma cells through controlling GLUT1-mediated glucose metabolism. Acta Pharmacol Sin. 2019;40(1):122–32.

    Article  CAS  PubMed  Google Scholar 

  14. Li S, Dai W, Mo W, et al. By inhibiting PFKFB3, aspirin overcomes sorafenib resistance in hepatocellular carcinoma. Int J Cancer. 2017;141(12):2571–84.

    Article  CAS  PubMed  Google Scholar 

  15. Cook NR, Lee IM, Gaziano JM, et al. Low-dose aspirin in the primary prevention of cancer: the women’s health study: a randomized controlled trial. JAMA. 2005;294(1):47–55.

    Article  CAS  PubMed  Google Scholar 

  16. Yun B, Ahn SH, Yoon JH, et al. Clinical indication of aspirin associated with reduced risk of liver cancer in chronic hepatitis B: a nationwide cohort study. Am J Gastroenterol. 2022;117(5):758–68.

    Article  CAS  PubMed  Google Scholar 

  17. Singh J, Wozniak A, Cotler SJ, et al. Combined use of aspirin and statin is associated with a decreased incidence of hepatocellular carcinoma. J Clin Gastroenterol. 2022;56(4):369–73.

    Article  CAS  PubMed  Google Scholar 

  18. Choi Won-Mook, Kim Hyo Jeong, Jo Ae Jeong, et al. Association of aspirin and statin use with the risk of liver cancer in chronic hepatitis B: a nationwide population-based study. Liver Int. 2021;41(11):2777–85.

    Article  CAS  PubMed  Google Scholar 

  19. Hui Vicki Wing-Ki, Yip Terry Cheuk-Fung, Wong Vincent Wai-Sun, et al. Aspirin reduces the incidence of hepatocellular carcinoma in patients with chronic hepatitis B receiving oral nucleos(t)ide analog. Clin Transl Gastroenterol. 2021;12(3):e00324.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Simon TG, Duberg AS, Aleman S, et al. Association of aspirin with hepatocellular carcinoma and liver-related mortality. N Engl J Med. 2020;382(11):1018–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Shin S, Lee SH, Lee M, et al. Aspirin and the risk of hepatocellular carcinoma development in patients with alcoholic cirrhosis. Medicine. 2020;99(9):e19008.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Liao YH, Hsu RJ, Wang TH, et al. Aspirin decreases hepatocellular carcinoma risk in hepatitis C virus carriers: a nationwide cohort study [J]. BMC Gastroenterol. 2020;20(1):6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lee TY, Hsu YC, Tseng HC, et al. Association of daily aspirin therapy with hepatocellular carcinoma risk in patients with chronic hepatitis C virus infection. Clin Gastroenterol Hepatol. 2020;18(12):2784–92.

    Article  CAS  PubMed  Google Scholar 

  24. Sung JJ, Ho JM, Lam AS, et al. Use of metformin and aspirin is associated with delayed cancer incidence. Cancer Epidemiol. 2020;69:101808.

    Article  PubMed  Google Scholar 

  25. Lee TY, Hsu YC, Tseng HC, et al. Association of daily aspirin therapy with risk of hepatocellular carcinoma in patients with chronic hepatitis B. JAMA Intern Med. 2019;179(5):633–40.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Hwang IC, Chang J, Kim K, et al. Aspirin use and risk of hepatocellular carcinoma in a national cohort study of Korean adults. Sci Rep. 2018;8(1):4968.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Ho CM, Lee CH, Lee MC, et al. Comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in chemoprevention of hepatocellular carcinoma: a nationwide high-risk cohort study. BMC Cancer. 2018;18(1):401.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Tseng CH. Metformin and risk of hepatocellular carcinoma in patients with type 2 diabetes. Liver Int. 2018;38(11):2018–27.

    Article  CAS  PubMed  Google Scholar 

  29. Lin YS, Yeh CC, Huang SF, et al. Aspirin associated with risk reduction of secondary primary cancer for patients with head and neck cancer: a population-based analysis. PLoS ONE. 2018;13(8):e0199014.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Lee M, Chung GE, Lee JH, et al. Antiplatelet therapy and the risk of hepatocellular carcinoma in chronic hepatitis B patients on antiviral treatment. Hepatology. 2017;66(5):1556–69.

    Article  CAS  PubMed  Google Scholar 

  31. Lee TY, Wu JC, Yu SH, et al. The occurrence of hepatocellular carcinoma in different risk stratifications of clinically noncirrhotic nonalcoholic fatty liver disease. Int J Cancer. 2017;141(7):1307–14.

    Article  CAS  PubMed  Google Scholar 

  32. Petrick JL, Sahasrabuddhe VV, Chan AT, et al. NSAID use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: the liver cancer pooling project. Cancer Prev Res. 2015;8(12):1156–62.

    Article  CAS  Google Scholar 

  33. Alfonso L, Ai G, Spitale RC, et al. Molecular targets of aspirin and cancer prevention. Br J Cancer. 2014;111(1):61–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Chen H, Cai W, Chu ESH, et al. Hepatic cyclooxygenase-2 overexpression induced spontaneous hepatocellular carcinoma formation in mice. Oncogene. 2017;36(31):4415–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Paik YH, Kim JK, Lee JI, et al. Celecoxib induces hepatic stellate cell apoptosis through inhibition of Akt activation and suppresses hepatic fibrosis in rats. Gut. 2009;58(11):1517–27.

    Article  CAS  PubMed  Google Scholar 

  36. Kern MA, Schubert D, Sahi D, et al. Proapoptotic and antiproliferative potential of selective cyclooxygenase-2 inhibitors in human liver tumor cells. Hepatology. 2002;36(4 Pt 1):885–94.

    CAS  PubMed  Google Scholar 

  37. Gao JH, Wen SL, Yang WJ, et al. Celecoxib ameliorates portal hypertension of the cirrhotic rats through the dual inhibitory effects on the intrahepatic fibrosis and angiogenesis. PLoS ONE. 2013;8(7):e69309.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Li X, Yu Y, Liu L. Influence of aspirin use on clinical outcomes of patients with hepatocellular carcinoma: a meta-analysis. Clin Res Hepatol Gastroenterol. 2021;45(6):101545.

    Article  CAS  PubMed  Google Scholar 

  39. Kim G, Jang SY, Nam CM, et al. Statin use and the risk of hepatocellular carcinoma in patients at high risk: a nationwide nested case-control study [J]. J Hepatol. 2018;68(3):476–84.

    Article  CAS  PubMed  Google Scholar 

  40. Lee M, Chung GE, Lee JH, et al. Antiplatelet therapy and the risk of hepatocellular carcinoma in chronic hepatitis B patients on antiviral treatment [J]. Hepatology. 2017;66(5):1556–69.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

This work was supported by the Jilin Province Finance Department Project, No.2021SCZ32.

Author information

Author notes

  1. Shuai Wang and Lijuan Zuo are contributed equally to this work.

Authors and Affiliations

  1. Department of Gastroenterology, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun, 130033, Jilin, China

    Shuai Wang, Zhiqin Yang, Ran Chen & Yan Xu

  2. Department of Gastroenterology, The First Affiliated Hospital of Weifang Medical University, Weifang, China

    Lijuan Zuo

  3. Department of Anesthesiology, The First Affiliated Hospital of Weifang Medical University, Weifang, China

    Zhaojin Lin

Authors
  1. Shuai Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lijuan Zuo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhaojin Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhiqin Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ran Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yan Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SW and LZ participated in the study design and coordination and the manuscript preparation. ZL, ZY, and RC were involved in the study design and conducted the search. YX critically reviewed the manuscript and provided valuable discussions and criticisms. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Yan Xu.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1.

: A combination of subject terms and free words were used for literature search using Boolean logic operator grouping.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, S., Zuo, L., Lin, Z. et al. The relationship between aspirin consumption and hepatocellular carcinoma: a systematic review and meta-analysis. Eur J Med Res 28, 226 (2023). https://doi.org/10.1186/s40001-023-01204-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s40001-023-01204-5

Keywords

European Journal of Medical Research

ISSN: 2047-783X

Contact us