Higher cholesterol levels, not statin use, are associated with a lower risk of hepatocellular carcinoma.
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ABSTRACT:
SUBMITTER: Yi SW
PROVIDER: S-EPMC7054540 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundUse of statins is associated with a reduced risk of hepatocellular carcinoma (HCC). However, the effect of statin use on HCC recurrence is unclear. This study aimed to evaluate the effect of statin use on recurrence after curative resection among patients with HCC.MethodsWe retrospectively assessed 820 patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A HCC who underwent primary resection between January 2001 and June 2016 at Kaohsiung Chang Gung Memorial Hospital. Exposure to statins was defined as use of a statin for at least 3 months before HCC recurrence. Factors that influenced overall survival (OS) and recurrence-free survival (RFS) were analyzed using Cox proportional hazards models.ResultsOf the 820 patients, 46 (5.6%) used statins (statin group) and 774 (94.4%) did not (non-statin group). During the mean follow-up of 76.5 months, 440 (53.7%) patients experienced recurrence and 146 (17.8%) patients died. The cumulative incidence of HCC recurrence was significantly lower in the statin group than the non-statin group (p = 0.001); OS was not significantly different between groups. In multivariate analysis, age (hazard ratio [HR]: 1.291; p = 0.010), liver cirrhosis (HR: 1.743; p < 0.001), diabetes (HR:1.418; p = 0.001), number of tumors (HR: 1.750; p < 0.001), tumor size (HR: 1.406; p = 0.004) and vascular invasion (HR: 1.659; p < 0.001) were independent risk factors for HCC recurrence, whereas statin use (HR: 0.354; p < 0.001) and antiviral therapy (HR: 0.613; p < 0.001) significantly reduced the risk of HCC recurrence. The statin group still had lower RFS than the non-statin group after one-to-four propensity score matching.ConclusionStatins may exert a chemo-preventive effect on HCC recurrence after curative resection.
| S-EPMC7808883 | biostudies-literature
Project description:PURPOSE:Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are medications widely prescribed to reduce cholesterol levels. Observational studies in high-risk populations, mostly in Asia, have suggested that statins are associated with a reduced risk of hepatocellular carcinoma (HCC). The current study sought to evaluate the association of statin use and HCC in a U.S.-based, low-risk, general population. METHODS:A nested case-control study was conducted among members of the Health Alliance Plan HMO of the Henry Ford Health System enrolled between 1999 and 2010. Electronic pharmacy records of statin use were compared among tumor registry-confirmed cases of HCC (n=94) and controls (n=468) matched on age, sex, diagnosis date, and length of HMO enrolment. RESULTS:In multivariate analyses, ever-use of statins was significantly inversely associated with development of HCC (Odds ratio (OR): 0.32, 95%CI: 0.15-0.67). No clear dose-response relationship was evident as statin use for <2 years (OR=0.32, 95%CI=0.13-0.83) and >2 years (OR=0.31, 95CI%=0.12-9.81) resulted in very similar ORs. CONCLUSIONS:The use of statins among populations in low-risk HCC areas may be associated with decreased risk of HCC.
| S-EPMC4188715 | biostudies-literature
Project description:BACKGROUND & AIMS:Statin use is associated with a lower risk of developing hepatocellular carcinoma (HCC). However, it is unclear whether postdiagnosis statin use is associated with a reduced risk of death in patients with HCC. METHODS:We performed a retrospective analysis of data from 15,422 patients with HCC in the Veterans Administration Central Cancer Registry, diagnosed from 2002 through 2016. We identified statin prescriptions that were filled before and after the cancer diagnosis and used time-dependent Cox regression models to calculate adjusted hazard ratios (HRs) and 95% CIs for risk of death. We used a time-varying exposure to avoid immortal time bias, and a 3-month lag (following up patients from 3 months after the cancer diagnosis) to reduce reverse causation. A sensitivity analysis was conducted varying the lag duration between date of cancer diagnosis and start of follow-up evaluation. RESULTS:Statin use after diagnosis was recorded for 14.9% of patients with HCC. We found that postdiagnosis statin use was associated with a decreased risk of cancer-specific death (adjusted HR, 0.85; 95% CI, 0.77-0.93) and all-cause mortality (HR, 0.89; 95% CI, 0.83-0.95). The magnitudes of these inverse associations were consistent for patients who used high or low doses of statins, and the inverse associations remained across a range of lag periods (from 0 months to 12 months after HCC diagnosis). We found no evidence for effect modification by prediagnosis statin use, or by presentation- or treatment-related factors, and no independent association with prediagnosis statin use. CONCLUSIONS:In a retrospective analysis of data from veterans with HCC, use of statins (high or low doses) after a diagnosis of HCC was associated with reduced mortality.
| S-EPMC6612541 | biostudies-literature
Project description:Statins have been reported to prevent the development of hepatocellular carcinoma (HCC). We examined whether statin therapy is associated with decreased HCC recurrence in patients who underwent liver transplantation for HCC. Three hundred forty-seven patients???20 years old who underwent liver transplantation for HCC from 2006 to 2016 were enrolled in this study. Statin therapy was defined as the administration of statins for more than 30 days after liver transplantation. One hundred twelve (32.3%) patients treated with statins over 30 days were defined as the statin group, and the remaining 235 (67.7%) were defined as the non-statin group. Several risk factors reported to be associated with HCC recurrence, such as proportion of underlying liver disease, above Milan criteria, differentiation of HCC, vascular invasion, and preoperative alpha-fetoprotein level were not different between the two groups. Time-dependent Cox regression analysis showed that statin treatment was associated with significantly lower recurrence risk of HCC after adjusting for other risk factors (hazard ratio?=?0.32, 95% CI?=?0.11-0.89).
| S-EPMC6365496 | biostudies-literature
Project description:Background and Aims: Statins are the first-line medication to treating hypercholesterolemia. Several studies have investigated the impact of statins on the risk of hepatocellular carcinoma (HCC). However, the extent to which statins may prevent HCC remains uncertain. Therefore, we performed a meta-analysis of relevant studies to quantify the magnitude of the association between statins use and the risk of HCC. Methods: A systematic literature search of PubMed, EMBASE, Google Scholar, Web of Science, and Scopus was performed for studies published between January 1, 1990, and September 1, 2019, with no restriction of language. Two reviewers independently evaluated the literature and included observational and experimental studies that reported the association between statin use and HCC risk. The random-effect model was used to calculate the overall risk ratio (RR) with a 95% confidence interval (CI), and the heterogeneity among the studies was assessed using the Q statistic and I2 statistic. The Newcastle Ottawa Scale (NOS) was also used to evaluate the quality of the included studies. Results: A total of 24 studies with 59,073 HCC patients was identified. Statin use was associated with a reduced risk of HCC development (RR: 0.54, 95% CI: 0.47-0.61, I2 = 84.39%) compared with nonusers. Moreover, the rate of HCC reduction was also significant among patients with diabetes (RR: 0.44, 95% CI: 0.28-0.70), liver cirrhosis (RR: 0.36, 95% CI: 0.30-0.42), and antiviral therapy (RR: 0.21, 95% CI: 0.08-0.59) compared with nonusers. Conclusion: This study serves as additional evidence supporting the beneficial inhibitory effect of statins on HCC incidence. The subgroup analyses of this study also highlight that statins are significantly associated with a reduced risk of HCC and may help to direct future prevention efforts. Additional large clinical studies are needed to determine whether statins are associated with a lower risk of HCC.
| S-EPMC7139959 | biostudies-literature
Project description:Importance:The use of statins (hydroxymethylglutaryl coenzyme A inhibitors) has been associated with a lower risk of primary open-angle glaucoma (POAG); however, results have been conflicting, and little is known about the association between high cholesterol levels and POAG. Objective:To assess the association of elevated cholesterol levels and statin use with incident POAG. Design, Setting, and Participants:This study used data collected biennially from participants aged 40 years or older who were free of glaucoma and reported eye examinations, within 3 population-based cohorts: the Nurses' Health Study (N?=?50?710; followed up from 2000 to 2014), the Nurses' Health Study 2 (N?=?62?992; 1999-2015), and the Health Professionals Follow-up Study (N?=?23?080; 2000-2014). Incident cases of POAG were confirmed by medical record review. The analyses were performed in January 2019. Exposures:Biennially updated self-reported information on elevated cholesterol level status, serum cholesterol levels, and duration of statin use. Main Outcomes and Measures:Multivariable-adjusted relative risks (RRs) and 95% CIs were estimated using Cox proportional hazards regression models on pooled data, with stratification by cohort. Results:Among the 136?782 participants in the 3 cohorts (113?702 women and 23?080 men), 886 incident cases of POAG were identified. Every 20-mg/dL increase in total serum cholesterol was associated with a 7% increase in risk of POAG (RR, 1.07 [95% CI, 1.02-1.11]; P?=?.004). Any self-reported history of elevated cholesterol was also associated with a higher risk of POAG (RR, 1.17 [95% CI, 1.00-1.37]). A history of any statin use was associated with a 15% lower risk of POAG (RR, 0.85 [95% CI, 0.73-0.99]). Use of statins for 5 or more years vs never use of statins was associated with a 21% lower risk of POAG (RR, 0.79 [95% CI, 0.65-0.97]; P?=?.02 for linear trend). The association between use of statins for 5 or more years vs never use of statins and risk of POAG was more inverse in those who were older (?65 years: RR, 0.70 [95% CI, 0.56-0.87] vs <65 years: RR, 1.05 [95% CI, 0.68-1.63]; P?=?.01 for interaction). Conclusions and Relevance:Among adults aged 40 years or older, higher serum cholesterol levels were associated with higher risk of POAG, while 5 or more years of statin use compared with never use of statins was associated with a lower risk of POAG.
| S-EPMC6499123 | biostudies-literature
Project description:PurposeStatins are associated with lower risk of aggressive prostate cancer, but lethal prostate cancer is understudied and contributing mechanisms are unclear. We prospectively examined statins and lethal prostate cancer risk in the Health Professionals Follow-up Study (HPFS), tested associations with molecular subtypes, and integrated gene expression profiling to identify putative mechanisms.Experimental designOur study included 44,126 men cancer-free in 1990, followed for prostate cancer incidence through 2014, with statin use recorded on biennial questionnaires. We used multivariable Cox regression to examine associations between statins and prostate cancer risk overall, by measures of clinically significant disease, and by ERG and PTEN status. In an exploratory analysis, age-adjusted gene set enrichment analysis identified statin-associated pathways enriched in tumor and adjacent normal prostate tissue.ResultsDuring 24 years of follow-up, 6,305 prostate cancers were diagnosed and 801 (13%) were lethal (metastatic at diagnosis or metastatic/fatal during follow-up). Relative to never/past use, current statin use was inversely associated with risk of lethal prostate cancer [HR, 0.76; 95% confidence interval (CI), 0.60-0.96] but not overall disease. We found a strong inverse association for risk of PTEN-null cancers (HR, 0.40; 95% CI, 0.19-0.87) but not PTEN-intact cancers (HR, 1.18; 95% CI, 0.95-1.48; P heterogeneity = 0.01). Associations did not differ by ERG. Inflammation and immune pathways were enriched in normal prostate tissue of statin ever (n = 10) versus never users (n = 103).ConclusionsMolecular tumor classification identified PTEN and inflammation/immune activation as potential mechanisms linking statins with lower lethal prostate cancer risk. These findings support a potential causal association and could inform selection of relevant biomarkers for statin clinical trials.
| S-EPMC7056554 | biostudies-literature
Project description:AIMS:To examine the association between statin use before and after intracranial haemorrhage (ICH) and the risk of poststroke epilepsy (PSE). METHODS:Patients with new-onset ICH between 2004 and 2012 were identified from the Taiwan National Health Insurance Research Database. The main outcome was the occurrence of epilepsy after stroke. Multivariable Cox regression modelling was used to estimate the association between statin use and the risk of PSE, with poststroke medication exposures being treated as time-dependent variables. RESULTS:A total of 7435 patients with ICH were enrolled with a median follow-up of 17.6 months. Within the study cohort, 709 patients developed PSE. Poststroke, but not prestroke, stain use was associated with a reduced risk of PSE (adjusted hazard ratio 0.62, 95% confidence interval 0.42-0.90, P = 0.01). In subanalyses, a trend of a dose-response relationship was observed. A significant PSE risk reduction was correlated with a higher cumulative statin dose. Moreover, the risk of PSE was lower in patients receiving moderate-to-high-intensity statin therapy (adjusted hazard ratio 0.37, 95% confidence interval 0.18-0.75, P = 0.01). Lipophilic and hydrophilic statins were similar with regard to their associations with the reduced risk of PSE. CONCLUSIONS:Statin therapy may reduce the risk of PSE after ICH, especially with moderate-to-high therapy intensity. Further research is needed to understand the mechanisms underlying the potential protective effects of statins against PSE in this patient population.
| S-EPMC6089806 | biostudies-other
Project description:To examine the association between use of statin and nonstatin cholesterol-lowering medications and risk of nontraumatic major lower extremity amputations (LEAs) and treatment failure (LEA or death).A retrospective cohort of patients with Type I and Type 2 diabetes mellitus (diabetes) was followed for 5 years between 2004 and 2008. The follow-up exposure duration was divided into 90-day periods. Use of cholesterol-lowering agents, diabetic medications, hemoglobin A1c, body mass index, and systolic and diastolic blood pressures were observed in each period. Demographic factors were observed at baseline. Major risk factors of LEA including peripheral neuropathy, peripheral artery disease, and foot ulcers were observed at baseline and were updated for each period. LEA and deaths were assessed in each period and their hazard ratios (HRs) were estimated. The study took place in the U.S. Department of Veterans Affairs Healthcare system, and the subjects consisted of cholesterol drug-naïve patients with Type I or II diabetes who were treated in the U.S. Department of Veterans Affairs Healthcare system in 2003 and were <65 years old at the end of follow-up.Of 83,953 patients in the study cohort, 217 (0.3%) patients experienced a major LEA and 11,716 (14.0%) patients experienced an LEA or death (treatment failure) after a mean follow-up of 4.6 years. Compared with patients who did not use cholesterol-lowering agents, statin users were 35% to 43% less likely to experience an LEA (HR, 0.65; 95% confidence interval [CI], 0.42-0.99) and a treatment failure (HR, 0.57; 95% CI, 0.54-0.60). Users of other cholesterol-lowering medications were not significantly different in LEA risk (HR, 0.95; 95% CI, 0.35-2.60) but had a 41% lower risk of treatment failure (HR, 0.59; 95% CI, 0.51-0.68).This is the first study to report a significant association between statin use and diminished amputation risk among patients with diabetes. In this nonrandomized cohort, beneficial effects of statin therapy were similar to that seen in large-scale clinical trial experience. For LEA risk, those given nonstatins did not have a statistically significant benefit and its effect on LEA risk was much smaller compared with statins. Unanswered questions to be explored in future studies include a comparison of statins of moderate vs high potency in those with high risk of coronary heart disease and an exploration of whether the effects seen in this study are simply effects of cholesterol-lowering or possibly pleiotropic effects.
| S-EPMC3844128 | biostudies-other
Project description:Hepatocellular carcinoma (HCC) commonly develops in patients with liver fibrosis; in these patients, the blood levels of lysophosphatidic acid (LPA) and its generating enzyme autotaxin (ATX) increase with the liver fibrosis stage. We aimed to examine the potential relevance of ATX and LPA in HCC. Fifty-eight HCC patients who underwent surgical treatment were consecutively enrolled in the study. Among the LPA receptors in HCC, higher LPA2 mRNA levels correlated with poorer differentiation, and higher LPA6 mRNA levels correlated with microvascular invasion, which suggested a higher malignant potential of HCC with increased LPA2 and LPA6 expression. In patients with primary HCC, neither LPA2 nor LPA6 mRNA levels were associated with recurrence. However, when serum ATX levels were combined for analysis as a surrogate for plasma LPA levels, the cumulative intra-hepatic recurrence rate was higher in patients in whom both serum ATX levels and LPA2 or LPA6 mRNA levels were higher than the median. However, the mRNA level of phosphatidic acid-selective phospholipase A1?, another LPA-generating enzyme, in HCC patients was not associated with pathological findings or recurrence, even in combination with the expression of LPA receptors. Higher LPA2 mRNA levels were associated with poorer differentiation, and higher LPA6 levels were associated with microvascular invasion in HCC; both became a risk factor for recurrence after surgical treatment when combined with increased serum ATX levels. ATX and LPA receptors merit consideration as therapeutic targets of HCC.
| S-EPMC5008774 | biostudies-literature