Table 1.

HRs^a for HCC incidence associated with statin use and total cholesterol (TC) in main cohort participants (n = 400,318)

			Multivariable-adjusted (except TC)		Multivariable-adjusted (including TC) (main analysis)		Analysis when only those who initiated statins within 1 year after baseline were considered as users
TC or statin use characteristics	No. of participants	HCC cases	p-value	HR (95% CI)	p-value	HR (95% CI)	HCC cases	p-value	HR (95% CI)
1 mmol/L (39 mg/dL) increase in TCb	400,318	1686			<0.001	0.54 (0.51–0.58)
Statin use within 6 months after baselinec
No use	389,052	1657		1.00 (Reference)		1.00 (Reference)
Use	11,266	29	0.005	0.59 (0.41–0.85)	0.427	1.16 (0.80–1.69)
≤91 cDDDs	9350	24	0.007	0.57 (0.38–0.86)	0.597	1.12 (0.74–1.68)
>91 cDDDs	1916	5	0.395	0.68 (0.28–1.64)	0.402	1.46 (0.60–3.52)
No use	389,052	1657		1.00 (Reference)		1.00 (Reference)
<40 cDDDs (<50th percentile)	4812d	17	0.266	0.76 (0.47–1.23)	0.144	1.43 (0.88–2.32)
≥40 cDDDs (≥50th percentile)	6454d	12	0.006	0.45 (0.25–0.79)	0.769	0.92 (0.52–1.63)
Per 60 cDDD increase	400,318	1686	0.020	0.64 (0.44–0.93)	0.633	1.08 (0.78–1.49)
1 mmol/L (39 mg/dL) increase in TCe	400,318	1686			<0.001	0.55 (0.52–0.59)	1686	<0.001	0.55 (0.52–0.58)
Statin use within 2 years after baselinec
No use	366,896	1620		1.00 (Reference)		1.00 (Reference)	1642		1.00 (Reference)
Use	33,422	66	<0.001	0.44 (0.34–0.57)	0.004	0.69 (0.54–0.89)	44	0.669	0.94 (0.69–1.27)
≤182 cDDDs	25,288	51	<0.001	0.46 (0.34–0.60)	0.016	0.71 (0.53–0.94)	31	0.839	1.04 (0.72–1.49)
183–365 cDDDs	5741	8	<0.001	0.30 (0.15–0.61)	0.042	0.48 (0.24–0.97)	7	0.195	0.61 (0.29–1.29)
>365 cDDDs	2393	7	0.228	0.63 (0.30–1.33)	0.819	1.09 (0.52–2.30)	6	0.903	1.05 (0.47–2.35)
No use	366,896	1620		1.00 (Reference)		1.00 (Reference)	1642		1.00 (Reference)
<30 cDDDs (1st quartile)	7850	23	0.042	0.65 (0.43–0.99)	0.954	0.99 (0.65–1.49)	14	0.205	1.41 (0.83–2.39)
30–79 cDDDs (2nd quartile)	8626	12	<0.001	0.32 (0.18–0.57)	0.015	0.49 (0.28–0.87)	6	0.291	0.65 (0.29–1.45)
80–179 cDDDs (3rd quartile)	8322	15	<0.001	0.40 (0.24–0.66)	0.092	0.64 (0.39–1.07)	10	0.947	0.98 (0.52–1.83)
≥180 cDDDs (4th quartile)	8558	16	<0.001	0.40 (0.25–0.66)	0.100	0.66 (0.40–1.08)	14	0.394	0.79 (0.47–1.35)
Per 60 cDDD increase	400,318	1686	<0.001	0.80 (0.73–0.88)	0.055	0.92 (0.84–1.00)	1686	0.403	0.96 (0.89–1.05)
No use	366,896	1620		1.00 (Reference)		1.00 (Reference)
Statin initiation≤182 days after baseline	11,266	29	0.002	0.56 (0.39–0.81)	0.563	1.12 (0.77–1.62)
Statin initiation 183–365 days after baseline	7085	15	0.002	0.45 (0.27–0.76)	0.125	0.67 (0.40–1.12)
Statin initiation 366–730 days after baseline	15,071	22	<0.001	0.34 (0.22–0.52)	<0.001	0.47 (0.31–0.72)

To convert cholesterol from mg/dL to mmol/L, multiply by 0.02586

cDDDs cumulative DDDs; CI confidence interval; DDD defined daily dose; HCC hepatocellular carcinoma; HR hazard ratio

^aHRs were calculated by Cox models stratified by age (baseline age, years: 40–44, 45–54, 55–64, 65–74, ≥75), after adjustment for age at baseline, sex, pre-existing diabetes, smoking status, alcohol use, physical activity, hepatitis B virus infection, hepatitis C virus infection, liver cirrhosis, body mass index, alanine aminotransferase levels, and total cholesterol (when applicable)

^bStatin use within 6 months after baseline was adjusted for in the multivariable analysis

^cThe first 6 months of follow-up were excluded

^dBecause 833 users were prescribed exactly 40 cDDDs, during 6 months after baseline health examination, the number of participants were different between two groups

^eStatin use within 2 years after baseline was adjusted for in the multivariable analysis