Statin use and risk of liver cancer: A meta-analysis of 7 studies involving more than 4.7 million patients

Table 1 Baseline characteristics and results of multivariate analysis in included studies

Ref.	Country	Study time/mean follow-up years	Total participants	Liver cancer cases	AdjustedRR(95%CI)	Confounding adjustment1
Case-control studies (n = 3)
El-Serag et al[37]	United State	1997-2002	6515	1303	0.74 (0.64-0.87)	12, 22, 3-5, 62, 7, 9, 10, 17-19
Chiu et al[17]	Taiwan	2005-2008	2332	312	0.62 (0.45-0.83)	1, 2, 32, 42, 5-10
Leung et al[38]	Taiwan	2000-2008	34205	6841	0.44 (0.28-0.72)	12, 22, 6, 8, 9,
Cohort studies (n = 4)
Friis et al[39]	Denmark	3.3 (exposure)	334754	171	1.16 (0.46-2.90)	1, 2, 9, 15, 16
		5.1 (control)
Friedman et al[40]	United State	4.91	4222660	32	0.47 (0.34-0.64)	15
Marelli et al[41]	United State	4.7 (exposure)	91714	105	0.88 (0.60-1.28)	12, 22, 152, 172, 202, 212
		4.6 (control)
Tsan et al[18]	Taiwan	328196	33413	1021	0.47 (0.36-0.61)	1-14
		(person-years)

¹1: Age; 2: Sex; 3: HBV infection; 4: HCV infection; 5: Alcohol liver disease; 6: Diabetes mellitus; 7: Liver cirrhosis; 8: Other lipid-lowering drugs; 9:Nonsteroidal anti-inflammatory drugs/aspirin; 10: Angiotensin-converting enzyme inhibitors; 11: Number of hospitalization; 12: anti-HBV treatment; 13: Income; 14: Level of urbanization; 15: Calendar period; 16: Hormone replacement therapy; 17: Race; 18: Anti-HCV treatment; 19: Propensity to use statins; 20: Body mass index; 21: Smoking.

²Variables which had been indicated were controlled by matching, and others were controlled by multivariate analyses. RR: Relative risk; HBV: Hepatitis B virus; HCV: Hepatitis C virus.

Table 2 Subgroup analyses of included studies

Subgroup	No. of studies	Fixed-effects model			Random-effects model			Heterogeneity
		RR	95%CI	P value	RR	95%CI	P value	Q	P	I2(%)
Type of design of studies
Case-control	3	0.69	0.60-0.79	< 0.001	0.63	0.49-0.82	< 0.001	4.75	0.093	57.9
Cohort	4	0.56	0.47-0.66	< 0.001	0.62	0.43-0.89	0.01	10.74	0.013	72.1
Country or area
Asian	3	0.51	0.43-0.62	< 0.001	0.51	0.42-0.63	< 0.001	2.30	0.317	13.0
Euro- American	4	0.71	0.62-0.80	< 0.001	0.71	0.52-0.95	0.023	9.14	0.028	67.2
Confounding adjustment
Adequately1	3	0.65	0.58-0.74	< 0.001	0.61	0.46-0.81	0.001	8.64	0.013	76.8
Inadequately	4	0.59	0.48-0.73	< 0.001	0.63	0.41-0.95	0.028	9.82	0.020	69.4
Study population
General population	5	0.60	0.50-0.71	< 0.001	0.62	0.46-0.83	0.001	9.89	0.042	59.5
Restricted to specified patients2	2	0.66	0.58-0.75	< 0.001	0.60	0.38-0.93	0.023	8.50	0.004	88.2

¹The confounding factors would be regarded as been controlled adequately when these 5 factors had been controlled, including age, sex, HBV infection, HCV infection and alcohol liver disease;

²The study population of two studies was restricted to specified patients, including patients with diabetes mellitus (Ref. 37) and those with HBV infection (Ref. 18). RR: Relative risk; HBV: Hepatitis B virus; HCV: Hepatitis C virus.