Research Article
Statin and the risk of hepatocellular carcinoma and death in a hospital-based hepatitis B-infected population: A propensity score landmark analysis- John Chen Hsiang1,
- Grace Lai-Hung Wong1, 2, 3,
- Yee-Kit Tse1, 2,
- Vincent Wai-Sun Wong1, 2, 3,
- Terry Cheuk-Fung Yip4,
- Henry Lik-Yuen Chan1, 2, 3, ,
- 1 Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
- 2 Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- 3 State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
- 4 Department of Statistics, The Chinese University of Hong Kong, Hong Kong, China
Received 23 March 2015, Revised 17 June 2015, Accepted 9 July 2015, Available online 21 July 2015
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doi:10.1016/j.jhep.2015.07.009Get rights and content
Background & AimsThe use of statin in hepatocellular carcinoma (HCC) and death prevention is still uncertain among hepatitis B infected (HBV) patients. This study aimed to examine the effect of statin on HCC and death in a HBV population. MethodsWe conducted a hospital-based population study of HBV patients, using the Hospital Authority database in Hong Kong. We defined statin use by landmark analysis to abrogate “immortal time bias” and propensity score (PS) weighting to minimize baseline confounders and “indication bias”. Multiple imputations for missing data were performed. The weighted Cox regression analyses was performed for the risk of HCC (adjusting for competing mortality) and death. ResultsA total of 73,499 patients with a crude HCC incidence of 1.75 per 100 patient-years were entered into the 2-year landmark analysis. After landmark analysis and PS weighting of baseline covariates, statin users had a 32% risk reduction in HCC (weighted sub-hazard ratio (SHR) 0.68; 95% CI 0.48–0.97) compared to non-users. There was no decreased risk of death in statin users (weighted HR 0.92; 0.76–1.11, p = 0.386). In subgroup analysis, concurrent statin and nucleos(t)ide analogue (NA) use was associated with 59% risk reduction in HCC (weighted SHR 0.41; 0.19–0.89, p = 0.023) compared to NA use alone. ConclusionIn this HBV cohort adjusted for confounders and biases, statin use is associated with reduced HCC risk by 32%. Additive HCC chemopreventive effect was seen with the concomitant use of NA and statin. Further prospective studies are warranted to investigate the potential use of statin in NA users.
Graphical abstract
Abbreviations- HBV, hepatitis B virus;
- HCC, hepatocellular carcinoma;
- NA, nucleos(t)ide analogue;
- HMG-CoA, 3-hydroxy-3-methylglutaryl CoA;
- DDD, daily defined doses;
- HR, hazard ratio;
- CI, confidence interval;
- HA, Hospital Authority;
- HCV, hepatitis C virus;
- HIV, human immunodeficiency virus;
- ALT, alanine aminotransferase;
- DM, type 2 diabetes mellitus;
- SD, standard deviation;
- IQR, interquartile range;
- PS, propensity score;
- ATE, average treatment effect
Keywords- Hepatitis B;
- Statin;
- Hepatocellular carcinoma;
- Death;
- Albumin;
- Alanine aminotransferase;
- Landmark analysis;
- Nucleos(t)ide analogue
Corresponding author. Address: Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong, China. Tel.: +852 2632 3942; fax: +852 2637 3852.
Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier Ireland Ltd. All rights reserved. |
发表于 2015-12-4 18:30
