Association of perioperative use of statins, metformin, and aspirin with recurrence after curative liver resection in patients with hepatocellular carcinoma: A propensity score matching analysis

Khajeh, Elias; Aminizadeh, Ehsan; Moghadam, Arash Dooghaie; Ramouz, Ali; Klotz, Rosa; Golriz, Mohammad; Merle, Uta; Springfeld, Christoph; Chang, De‐Hua; Longerich, Thomas; Büchler, Markus W.; Mehrabi, Arianeb

doi:10.1002/cam4.6569

Cited by 3 publications

(2 citation statements)

References 51 publications

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“…169 Perioperative use of statin may decrease HCC recurrence by up to 80% and increase recurrence-free survival by up to 20% after resection. [220][221][222][223][224][225][226][227] However, overall survival and mortality benefits of perioperative statin is controversial with significant variability. 191,[220][221][222][223][224][225]228,229 In liver transplantation, postoperative statin use lowered recurrent risk of HCC by up to 68% (HR=0.32, 95% CI 0.11-0.89), mortality by up to 65% (HR=0.35, 95% CI 0.12-0.98), and reduced risk of re-transplantation (p=0.004).…”

Section: Statin and Surgical Intervention In Hccmentioning

confidence: 99%

“…[220][221][222][223][224][225][226][227] However, overall survival and mortality benefits of perioperative statin is controversial with significant variability. 191,[220][221][222][223][224][225]228,229 In liver transplantation, postoperative statin use lowered recurrent risk of HCC by up to 68% (HR=0.32, 95% CI 0.11-0.89), mortality by up to 65% (HR=0.35, 95% CI 0.12-0.98), and reduced risk of re-transplantation (p=0.004). 230,231 In at least one prospective cohort study, combination of pravastatin and transarterial chemoembolization (TACE) increased median survival by 8.9-months compared to TACE alone (20.9 months, 95%CI 15.5-26.3 vs 12.0 months, 95%CI 10.3-13.7).…”

Section: Statin and Surgical Intervention In Hccmentioning

confidence: 99%

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Statins in Chronic Liver Disease: Review of the Literature and Future Role

Pham,

Benhammou

2024

Semin Liver Dis

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Chronic liver disease (CLD) is a major contributor to global mortality, morbidity, and healthcare burden. Progress in pharmacotherapeutic for CLD management is lagging given its impact on the global population. While statins are indicated for the management of dyslipidemia and cardiovascular disease, their role in CLD prevention and treatment is emerging. Beyond their lipid lowering effects, their liver-related mechanisms of action are multifactorial and include anti-inflammatory, anti-proliferative, and immune-protective effects. In this review, we highlight what is known about the clinical benefits of statins in viral and non-viral etiologies of CLD and HCC, and explore key mechanisms and pathways targeted by statins. While their benefits may span the spectrum of CLD and potentially HCC treatment, their role in CLD chemoprevention is likely to have the largest impact. As emerging data suggest that genetic variants may impact their benefits, the role of statins in precision hepatology will need to be further explored.

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Section: Statin and Surgical Intervention In Hccmentioning

confidence: 99%

Section: Statin and Surgical Intervention In Hccmentioning

confidence: 99%

Statins in Chronic Liver Disease: Review of the Literature and Future Role

Pham,

Benhammou

2024

Semin Liver Dis

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Does metformin really reduce prostate cancer risk: an up-to-date comprehensive genome-wide analysis

Zhang,

2024

Diabetol Metab Syndr

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Background The relationship between metformin use and prostate cancer (PCa) risk has yet to be clear despite more than a decade of debate on this topic. Hence, we aimed to investigate the causal role of metformin in reducing PCa risk through an up-to-date comprehensive genome-wide analysis. Methods We employed validated instrument variables of metformin use derived from a prior high-quality study, including five potential targets (AMPK, GCG, GDF15, MCI and MG3). Mendelian randomization (MR) analysis was performed to harmonize genetically predicted metformin use and PCa phenotypes. PCa phenotypes were from two large genome-wide association studies (GWAS), the Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome (PRACTICAL) and the FinnGen cohort. Seven methods were applied to generate MR results: the inverse variance weighted (IVW), IVW with multiplicative random effects, MR-Egger, MR-Egger (bootstrap), weighted median, simple mode and weighted mode. Strict sensitivity analysis was conducted to satisfy core assumptions of MR design. Results We enrolled 32 significant single nucleotide polymorphisms (SNPs) that involved with metformin use. Nearly all targets yielded insignificant primary results (IVW with multiplicative random effects), except that AMPK target posed a positive effect on PCa risk from FinnGen cohort [odds ratio (OR): 6.09, 95% confidence interval (CI): 1.10-33.53, P value: 0.038]. The general effect of metformin use, comprising all 5 targets, also yielded negative results (random-effect meta-analysis with OR: 1.09, 95% CI: 0.76–1.58, P value: 0.637 for PRACTICAL; OR: 2.55, 95% CI: 0.58–11.16, P value: 0.215 for FinnGen). None of the sensitivity analyses provided support for a causal association between metformin use and PCa risk. Conclusion This up-to-date study did not support the protective role of metformin in reducing PCa risk, considering each target, overall effect, and sensitivity analysis. It is imperative to reflect on the presumed “almighty medicine” and ongoing phase III trials are anticipated to assess the anti-neoplasm effect of metformin.

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Preoperative serum glutathione reductase activity and alpha-fetoprotein level are associated with early postoperative recurrence of hepatocellular carcinoma

Shen,

Shao,

Feng

2024

Journal of Laboratory Medicine

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Objectives The aim of this study is to investigate the correlation between preoperative serum glutathione reductase (GR) activity, alpha-fetoprotein (AFP) level, and early postoperative recurrence in patients diagnosed with hepatocellular carcinoma (HCC). Methods The data of 91 patients with HCC who underwent hepatectomy at Jinhua Hospital from January 2020 to December 2021 were retrospectively analyzed. A comparison of clinical characteristics between Non-Recurrent group and Recurrence group was conducted, and the association between GR activity, AFP levels, and early postoperative recurrence in HCC was investigated. Results Recurrence group (n=50) had a significantly higher AFP levels (median: 226.7 vs. 99.7 μg/L, p<0.001) and significantly lower GR activity (median: 55.0 vs. 68.0 U/L, p<0.0001) compared with Non-Recurrent group (n=41). The GR activity was negatively correlated with the AFP level (r=−0.4275, p<0.01). Low GR activity (OR=0.948; 95 % CI: 0.910–0.988; p=0.011) and high AFP levels (OR=1.003; 95 % CI: 1.000–1.006; p=0.036) independently contribute to an increased risk of early postoperative recurrence in HCC patients. The area under receiver operating characteristic curve of GR activity and AFP level for predicting early postoperative recurrence of HCC was 0.790 and 0.708, respectively. Patients with GR >60U/L had a higher early postoperative non-recurrence rate than patients with GR ≤60U/L (71.4 % [30/42] vs. 22.4 % [11/49]; HR=4.026; 95 % CI: 2.254–7.188; p<0.01); Patients with AFP ≤100 μg/L had a higher early postoperative non-recurrence rate than patients with AFP >100 μg/L (65.6 % [21/32] vs. 33.9 % [20/59]; HR=2.490; 95 % CI: 1.397–4.438; p<0.01). Conclusions The preoperative serum GR activity and AFP level hold significant predictive value for early postoperative recurrence in HCC patients.

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Association of perioperative use of statins, metformin, and aspirin with recurrence after curative liver resection in patients with hepatocellular carcinoma: A propensity score matching analysis

Cited by 3 publications

References 51 publications

Statins in Chronic Liver Disease: Review of the Literature and Future Role

Statins in Chronic Liver Disease: Review of the Literature and Future Role

Does metformin really reduce prostate cancer risk: an up-to-date comprehensive genome-wide analysis

Preoperative serum glutathione reductase activity and alpha-fetoprotein level are associated with early postoperative recurrence of hepatocellular carcinoma

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