Hepatocellular Carcinoma Prevention by Aspirin: Are Platelets the Link?

Nischalke, Hans Dieter; Klüners, Alexandra; Nattermann, Jacob; Berg, Thomas; Strassburg, Christian P.; Lutz, Philipp

doi:10.1002/hep4.1769

Cited by 3 publications

(2 citation statements)

References 6 publications

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“…Because the genetic risk factors discovered so far are not sufficiently precise to define subgroups for screening in alcohol-associated cirrhosis [ 27 ], new genetic risk factors for HCC are investigated. Among others, a common variant in the toll-like receptor 5 , rs5744174, was linked to the development of HCC [ 28 ], while genetic variation in platelet receptors does not seem to play a role [ 29 ]. In the same line, we analysed two polymorphisms in SAMM50 because a recent genome-wide association study linked the genetic variation of SAMM50 to the development of HCC [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic Variation of SAMM50 Is Not an Independent Risk Factor for Alcoholic Hepatocellular Carcinoma in Caucasian Patients

Nischalke

Schmalz

Buch

et al. 2022

IJMS

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Hepatocellular carcinoma (HCC) is a severe complication of advanced alcoholic liver disease, which is modulated by genetic predisposition. Identifying new genetic loci might improve screening. Genetic variation of SAMM50 was linked to HCC. We aimed to validate this finding in a large cohort of patients with advanced alcoholic liver disease (ALD). A large, well-characterised cohort of patients with alcoholic cirrhosis without (n = 674) and with (n = 386) HCC, as well as controls with HCC due to viral hepatitis (n = 134), controls with heavy alcohol abuse without liver disease (n = 266) and healthy subjects (n = 237), were genotyped for SAMM50 rs3827385 and rs3761472 and for PNPLA3 rs738409. Genotype frequencies were compared between patients with alcohol-associated cirrhosis with and without HCC by uni- and multivariate analysis. Minor variants in both SAMM50 rs3827385 and rs3761472 were significantly more frequent in patients with alcoholic HCC versus alcoholic cirrhosis and versus the control cohorts. An even stronger association was noted for PNPLA3 rs738409. The univariate analysis resulted in an odds ratio (OR) of 1.8 for carriers of at least one minor variant of SAMM50 rs3827385 and rs3761472 (each p < 0.001), but this association was lost in multivariate analysis with age (OR 1.1/year), male sex (OR 3.2), diabetes (OR 1.9) and carriage of PNPLA3 148M (OR 2.1) remaining in the final model. Although minor variants of both SAMM50 loci are strongly associated with alcoholic HCC, this association is not independent of carriage of the well-known risk variant PNPLA3 148M.

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Section: Discussionmentioning

confidence: 99%

Genetic Variation of SAMM50 Is Not an Independent Risk Factor for Alcoholic Hepatocellular Carcinoma in Caucasian Patients

Nischalke

Schmalz

Buch

et al. 2022

IJMS

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“…Moreover, both high platelet count and platelet-to-lymphocyte ratio have been reported as negative prognostic factors in HCC patients [ 18 ]. The in vitro relationship between platelets and tumor microenvironment is complex [ 19 , 20 ]. Indeed, tumor cells enhance platelet activity through an increased adenosine diphosphate secretion, and activated platelets, in turn, release a vascular endothelial growth factor (VEGF), thus promoting neoangiogenesis and cancer cell proliferation [ 21 , 22 , 23 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

Beneficial Prognostic Effects of Aspirin in Patients Receiving Sorafenib for Hepatocellular Carcinoma: A Tale of Multiple Confounders

Ielasi

Tovoli

Tonnini

et al. 2021

Cancers

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Case–control observational studies suggested that aspirin might prevent hepatocellular carcinoma (HCC) in high-risk patients, even if randomized clinical trials are lacking. Information regarding aspirin in subjects who already developed HCC, especially in its advanced stage, are scarce. While aspirin might be a low-cost option to improve the prognosis, multiple confounders and safety concerns are to be considered. In our retrospective analyses of a prospective dataset (n = 699), after assessing the factors associated with aspirin prescription, we applied an inverse probability treatment weight analysis to address the prescription bias. Analyses of post-sorafenib survival were also performed to reduce the influence of subsequent medications. Among the study population, 133 (19%) patients were receiving aspirin at the time of sorafenib prescription. Aspirin users had a higher platelet count and a lower prevalence of esophageal varices, macrovascular invasion, and Child–Pugh B status. The benefit of aspirin was confirmed in terms of overall survival (HR 0.702, 95% CI 0.543–0.908), progression-free survival, disease control rate (58.6 vs. 49.5%, p < 0.001), and post-sorafenib survival even after weighting. Minor bleeding events were more frequent in the aspirin group. Aspirin use was associated with better outcomes, even after the correction for confounders. While safety concerns arguably remain a problem, prospective trials for patients at low risk of bleeding are warranted.

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Role of PAR1 −506 deletion/insertion polymorphism in primary sclerosing cholangitis

Langhans,

Kalthoff,

Zhou

et al. 2024

Hepatology Research

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AimPrimary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by inflammation of the intra‐ and extrahepatic bile ducts. Pathogenesis of PSC is still enigmatic but is likely to be multifactorial. Recently, we identified an interleukin‐6 (IL‐6)‐dependent signal transducer and activator of transcription 3 (STAT3) activation in CD4+ TH1 and TH17 cells in PSC. The IL‐6/STAT3 pathway was shown to be regulated by protease‐activated receptor 1 (PAR1) contributing to inflammation. The role of the PAR1 −506 deletion/insertion (Del/Ins) polymorphism in PSC has not yet been investigated.MethodsTwo hundred eighty four PSC patients (200 patients with inflammatory bowel diseases [IBD] and 84 without IBD) and 309 healthy controls were genotyped for PAR1 rs11267092 (−506 Del/Ins −13 bp). Results were correlated with clinical characteristics and transplant‐free survival.ResultsThe frequency of PAR1 –506 Ins allele carriers (Del/Ins and Ins/Ins) was significantly higher in PSC patients (57.0%) compared to healthy controls (39.8%). Furthermore, carriers of PAR1 −506 Ins allele were more likely to have PSC than noncarriers (odds ratio 2.01; 95% confidence interval, 1.45–2.79). Patients with PSC carrying the PAR1 −506 Ins allele showed significantly higher alanine aminotransferase serum levels (p = 0.0357) and a trend toward shorter transplant‐free survival time compared to noncarriers (8.9 ± 6.6 years vs. 10.5 ± 7.1 years; p = 0.076).ConclusionsOur study shows that PAR1 −506 Ins is significantly more frequent in people with PSC. As PAR1 −506 Ins allele carriers tended to have a shorter transplant‐free survival, PAR1 might play a role in the development and course of PSC.

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Hepatocellular Carcinoma Prevention by Aspirin: Are Platelets the Link?

Cited by 3 publications

References 6 publications

Genetic Variation of SAMM50 Is Not an Independent Risk Factor for Alcoholic Hepatocellular Carcinoma in Caucasian Patients

Genetic Variation of SAMM50 Is Not an Independent Risk Factor for Alcoholic Hepatocellular Carcinoma in Caucasian Patients

Beneficial Prognostic Effects of Aspirin in Patients Receiving Sorafenib for Hepatocellular Carcinoma: A Tale of Multiple Confounders

Role of PAR1 −506 deletion/insertion polymorphism in primary sclerosing cholangitis

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