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Lipophilic Statins and Risk of Hepatocellular
Carcinoma and Mortality: A Prospective,
Nationwide Population with Chronic Viral
Hepatitis
Tracey G Simon, Massachusetts General Hospital, Ann-Sofi
Duberg, Orebro University Hospital, Soo Aleman, Department
of Infectious Diseases, Karolinska University Hospital,
Hannes Hagström, Center for Digestive Diseases, Division of
Hepatology, Karolinska Institutet, Raymond T. Chung, Liver
Center and Gastrointestinal Division, Massachusetts General
Hospital and Harvard Medical School and Jonas F Ludvigsson,
Medical Epidemiology and Biostatistics, Karolinska Institutet
Background: In the U.S. and Europe, the incidence of
hepatocellular carcinoma (HCC) has tripled over the past
thirty years, and rates of HCC mortality are rising more
rapidly than for any other cancer. A body of epidemiological
evidence now suggests that for patients with chronic
hepatitis B virus (HBV) or hepatitis C virus (HCV), statins
may improve clinical outcomes and reduce HCC risk. Recent
experimental data further suggests that lipophilic statins (i.e.
atorvastatin, simvastatin, fluvastatin and lovastatin) may
prevent hepatocarcinogenesis more potently than hydrophilic
statins (i.e. pravastatin, rosuvastatin). However, in humans,
prospective data regarding the optimal statin type and
dose for effective HCC prevention are limited. Methods:
We conducted a nationwide, propensity score-matched
cohort study of 16,668 patients with confirmed chronic HBV
(n=3,906) or HCV (n=12,762) living in Sweden between
2005-2015, using prospectively-collected and updated data
from validated, nationwide Swedish Registers. Using the
Prescribed Drug Register, we defined lipophilic statin use or
hydrophilic statin use as a filled prescription for ≥30 cumulative
defined daily doses (cDDD) of the relevant statin type, and
data were updated monthly over the study follow-up. All HCC
cases and deaths were confirmed. Using Cox proportional
hazard modeling with time-varying exposures and covariates,
we estimated multivariable-adjusted subdistribution hazard
ratios (aHRs) for HCC and all-cause mortality, accounting
for competing risks. Results: Over a median follow-up of
96 months, we identified 606 cases of incident HCC and
1,664 deaths. Significantly lower HCC risk was observed
with lipophilic statin use, compared to non-use (aHR 0.56,
95% CI 0.33-0.80; number-needed-to-treat=23). This benefit
appeared dose-related: compared to non-users, the aHRs for
HCC were 0.78 (95% CI 0.51-1.09) for 30-299 cDDD, 0.57
(95% CI 0.50-0.65) for 300-599 cDDD, and 0.48 (95% CI 0.34-
0.62) for ≥600 cDDD (Ptrend among users <0.0001). Lipophilic statin
use was also associated with significantly lower risk of death
(aHR 0.73, 95%CI 0.72-0.75), in a dose-dependent manner
(Ptrend among users<0.0001). In contrast, hydrophilic statin use was
not associated with HCC risk reduction (aHR 1.01, 95%CI
0.81-1.88), or with a dose-dependent reduction in mortality
(Ptrend among users=0.52). Similarly, no significant association was
found with incident HCC risk, when non-statin lipid-lowering
medication users and non-users were compared (aHR 1.06,
95% CI 0.86-1.29). Conclusion: In this nationwide population
with chronic viral hepatitis, use of lipophilic but not hydrophilic
statins was associated with dose-dependent reductions in
risk for incident HCC and all-cause mortality. Our findings
support the potential incorporation of lipophilic statins into
HCC primary prevention strategies.作者: StephenW 时间: 2018-10-7 18:46