Dataset Information

Association between statin use and the prognosis of hepatocellular carcinoma after resection: a nationwide cohort study.

ABSTRACT:

Background

The majority of patients with hepatocellular carcinoma (HCC) following hepatic resection experience tumor recurrence. Statin use is associated with a reduced risk of HCC development; however, the association between statin use and the prognosis of HCC after resection remains unclear. We aimed to investigate the effect of statin use on the prognosis after hepatic resection among patients with HCC.

Methods

A nationwide cohort study was performed with data from the National Health Insurance Service Database in Korea. Among 65,101 HCC patients who underwent hepatic resection between January 2002 and December 2017, we included 21,470 patients. For validation, a hospital-based cohort of 3366 patients with very early or early-stage HCC who received curative-intent hepatic resection between January 2010 and December 2018 was analyzed. Recurrence-free survival (RFS) and overall survival (OS) was compared between statin users and non-users.

Findings

Among the nationwide cohort of 21,470 patients, 2399 (11.2%) used statins and 19,071 (88.8%) did not. Among the hospital cohort of 3366 patients, 363 (10.8%) used statins and 3003 (89.2%) did not. In the propensity score-matched nationwide cohort, statin users had better RFS (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.56-0.64; P < 0.001) and OS (HR, 0.49; 95% CI, 0.45-0.53; P < 0.001), with a duration-response relationship. In the propensity score-matched validation hospital cohort, statin treatment was significantly associated with better RFS (HR, 0.73; 95% CI, 0.59-0.90; P = 0.003) and OS (HR, 0.48; 95% CI, 0.32-0.72; P < 0.001). The beneficial effects of statins were more prominent in non-cirrhotics, tumors sized ≥3 cm, tumors with microscopic vascular invasion, or early HCC recurrence (<2 years after resection).

Interpretation

Statin use was associated with a better prognosis in a population-based cohort of patients with HCC after hepatic resection, which was further validated in a large hospital-based cohort.

Funding

Asan Institute for Life Sciences and Corporate Relations; Korean Association for the Study of the Liver.

SUBMITTER: Jeon D

PROVIDER: S-EPMC10641481 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association between statin use and the prognosis of hepatocellular carcinoma after resection: a nationwide cohort study.

Jeon Dongsub D Cha Hye Ryeong HR Chung Sung Won SW Choi Jonggi J Lee Danbi D Shim Ju Hyun JH Kim Kang Mo KM Lim Young-Suk YS Lee Han Chu HC Lee Seung Won SW Choi Won-Mook WM

EClinicalMedicine 20231101

<h4>Background</h4>The majority of patients with hepatocellular carcinoma (HCC) following hepatic resection experience tumor recurrence. Statin use is associated with a reduced risk of HCC development; however, the association between statin use and the prognosis of HCC after resection remains unclear. We aimed to investigate the effect of statin use on the prognosis after hepatic resection among patients with HCC.<h4>Methods</h4>A nationwide cohort study was performed with data from the Nationa ...[more]

PMID: 37965429

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Project description:ObjectiveTo investigate the association between recent statin exposure and risk of severe COVID-19 infection and all-cause mortality in patients with COVID-19 in Denmark.Design and settingObservational cohort study using data from Danish nationwide registries.ParticipantsPatients diagnosed with COVID-19 from 22 February 2020 to 17 May 2020 were followed from date of diagnosis until outcome of interest, death or 17 May 2020.InterventionsUse of statins, defined as a redeemed drug prescription in the 6 months prior to COVID-19 diagnosis.Primary and secondary outcome measuresAll-cause mortality, severe COVID-19 infection and the composite.ResultsThe study population comprised 4842 patients with COVID-19 (median age 54 years (25th-75th percentile, 40-72), 47.1% men), of whom 843 (17.4%) redeemed a prescription of statins. Patients with statin exposure were more often men and had a greater prevalence of comorbidities. The median follow-up was 44 days. After adjustment for age, sex, ethnicity, socioeconomic status and comorbidities, statin exposure was not associated with a significantly different risk of mortality (HR 0.96 (95% CI 0.78 to 1.18); 30-day standardised absolute risk (SAR), 9.8% (8.7% to 11.0%) vs 9.5% (8.2% to 10.8%); SAR difference, -0.4% (-1.9% to 1.2%)), severe COVID-19 infection (HR 1.16 (95% CI 0.95 to 1.41); 30-day SAR, 13.0% (11.8% to 14.2%) vs 14.9% (12.8% to 17.1%); SAR difference, 1.9% (-0.7% to 4.5%)), and the composite outcome of all-cause mortality or severe COVID-19 infection (HR 1.05 (95% CI 0.89 to 1.23); 30-day SAR, 17.6% (16.4% to 18.8%) vs 18.2% (16.4% to 20.1%); SAR difference, 0.6% (-1.6% to 2.9%)). The results were consistent across subgroups of age, sex and presumed indication for statin therapy. Among patients with statin exposure, there was no difference between statin drug or treatment intensity with respect to outcomes.ConclusionsRecent statin exposure in patients with COVID-19 infection was not associated with an increased or decreased risk of all-cause mortality or severe infection.

Project description:ImportanceGiven the burden of chronic liver disease on the health care system, more information on the hepatoprotective association of statins in the general population is needed.ObjectiveTo examine whether regular statin use is associated with a reduction in liver disease, particularly hepatocellular carcinoma (HCC) and liver-related deaths, in the general population.Design, setting, and participantsThis cohort study used data from the UK Biobank (UKB) (individuals aged 37-73 years) collected from baseline (2006-2010) to the end of follow-up in May 2021, from the TriNetX cohort (individuals aged 18-90 years) enrolled from baseline (2011-2020) until end of follow-up in September 2022, and from the Penn Medicine Biobank (PMBB) (individuals aged 18-102 years) with ongoing enrollment starting in 2013 to the end of follow-up in December 2020. Individuals were matched using propensity score matching according to the following criteria: age, sex, body mass index, ethnicity, diabetes with or without insulin or biguanide use, hypertension, ischemic heart disease, dyslipidemia, aspirin use, and number of medications taken (UKB only). Data analysis was performed from April 2021 to April 2023.ExposureRegular statin use.Main outcomes and measuresPrimary outcomes were liver disease and HCC development as well as liver-associated death.ResultsA total of 1 785 491 individuals were evaluated after matching (aged 55 to 61 years on average, up to 56% men, and up to 49% women). A total of 581 cases of liver-associated death, 472 cases of incident HCC, and 98 497 new liver diseases were registered during the follow-up period. Individuals were aged 55-61 years on average, with a slightly higher proportion of men (up to 56%). In UKB individuals (n = 205 057) without previously diagnosed liver disease, statin users (n = 56 109) had a 15% lower hazard ratio (HR) for the association of developing a new liver disease (HR, 0.85; 95% CI, 0.78-0.92; P < .001). In addition, statin users demonstrated a 28% lower HR for the association with liver-related death (HR, 0.72; 95% CI, 0.59-0.88; P = .001) and a 42% lower HR for the development of HCC (HR, 0.58; 95% CI, 0.35-0.96; P = .04). In TriNetX individuals (n = 1 568 794), the HR for the association of HCC was reduced even further for statin users (HR, 0.26; 95% CI, 0.22-0.31; P = .003). The hepatoprotective association of statins was time and dose dependent, with a significant association in PMBB individuals (n = 11 640) for incident liver diseases after 1 year of statin use (HR, 0.76; 95% CI, 0.59-0.98; P = .03). Taking statins was particularly beneficial in men, individuals with diabetes, and individuals with a high Fibrosis-4 index at baseline. Carriers of the heterozygous minor allele of PNPLA3 rs738409 benefited from statin use and had a 69% lower HR for the association with HCC (UKB HR, 0.31; 95% CI, 0.11-0.85; P = .02).Conclusions and relevanceThis cohort study indicates substantial preventive associations of statins against liver disease, with an association with duration and dose of intake.

Project description:ImportanceProspective data on the risk of hepatocellular carcinoma (HCC) according to dose and duration of aspirin therapy are limited.ObjectiveTo examine the potential benefits of aspirin use for primary HCC prevention at a range of doses and durations of use within 2 prospective, nationwide populations.Design, setting, and participantsPooled analysis of 2 prospective US cohort studies: the Nurses' Health Study and the Health Professionals Follow-up Study. Data were accessed from November 1, 2017, through March 7, 2018. A total of 133 371 health care professionals who reported data on aspirin use, frequency, dosage, and duration of use biennially since 1980 in women and 1986 in men were included. Individuals with a cancer diagnosis at baseline (except nonmelanoma skin cancer) were excluded.Main outcomes and measuresCox proportional hazards regression models were used to calculate multivariable adjusted hazard ratios (HRs) and 95% CIs for HCC.ResultsOf the 133 371 participants, 87 507 were women and 45 864 were men; in 1996, the median time of follow-up, the mean (SD) age was 62 (8) years for women and 64 (8) years for men. Over more than 26 years of follow-up encompassing 4 232 188 person-years, 108 incident HCC cases (65 women, 43 men) were documented. Compared with nonregular use, regular aspirin use (≥2 standard-dose [325-mg] tablets per week) was associated with reduced HCC risk (adjusted HR, 0.51; 95% CI, 0.34-0.77). This benefit appeared to be dose related: compared with nonuse, the multivariable-adjusted HR for HCC was 0.87 (95% CI, 0.51-1.48) for up to 1.5 standard-dose tablets per week, 0.51 (95% CI, 0.30-0.86) for more than 1.5 to 5 tablets per week, and 0.49 (95% CI, 0.28-0.96) for more than 5 tablets per week (P for trend = .006). Significantly lower HCC risk was observed with increasing duration (P for trend = .03); this decrease was apparent with use of 1.5 or more standard-dose aspirin tablets per week for 5 or more years (adjusted HR, 0.41; 95% CI, 0.21-0.77). In contrast, use of nonaspirin nonsteroidal anti-inflammatory drugs was not significantly associated with HCC risk (adjusted HR, 1.09; 95% CI, 0.78-1.51).Conclusions and relevanceThis study suggests that regular, long-term aspirin use is associated with a dose-dependent reduction in HCC risk, which is apparent after 5 or more years of use. Similar associations were not found with nonaspirin NSAIDs. Further research appears to be needed to clarify whether aspirin use represents a feasible strategy for primary prevention against HCC.

Dataset Information

Association between statin use and the prognosis of hepatocellular carcinoma after resection: a nationwide cohort study.

Background

Methods

Findings

Interpretation

Funding

Publications

Association between statin use and the prognosis of hepatocellular carcinoma after resection: a nationwide cohort study.

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