A Meta-Analysis of Statin Use and Risk of Hepatocellular Carcinoma

Table 1

Characteristics and quality of included studies assessing the risk of HCC with statin use.

Study	Design	Location	Setting	Time period	Total no. of subjects	No. of HCC cases	Variables adjusted for^a	Study quality^b
								Selection	Comparability	Outcome/exposure
Observational studies
Karl et al. (2019)	Cohort	Swedish	Population based	1998–2012	2,440,620	2742	1, 2, 7, 9, 12, 13, 18, 21
Friis et al. (2005)	Cohort	Danish	Population based	1989–2002	348262	171	1, 2, 9, 25
Tsan et al. (2013)	Cohort	Taiwan	Population based	1999–2010	260864	27883	1, 2, 5, 7, 11
Butt et al. (2015)	Cohort	United States	Population based	2002–2013	7248	141	16
Simon et al. (2016)	Cohort	United States	Population based	2001–2014	9,135	233	1, 2, 4, 6, 7, 8, 9,10, 12, 13, 16, 22, 26
Kim et al. (2017)	Case-control	Korea	Population based	2002–2013	9,852	1642	5, 6, 7, 9, 11, 12, 13, 20
Yi et al. (2019)	Cohort	Korea	Population based	2004–2007	400,318	1686	1, 2, 3,4, 5, 6, 7, 12, 13, 21, 28
Goh et al. (2019)	Cohort	Korea	Population based	2008–2012	7,713	702	1, 2, 3, 5, 7, 9, 18, 21, 22
El-Serag et al. (2009)	Case-control	United States	Population based	1997–2002	6,515	1303	3, 4, 5, 6, 8, 9, 10
McGlynn et al. (2015)	Case-control	UK	Population based	1988–2011	5,835	1195	3, 4, 6, 7, 9, 12, 13, 31
Tran et al. (2019)^#	Case-control	UK	Population based	2000–2011	2,537	434	1, 2, 6, 9, 13, 14, 23
Tran et al. (2019)	Cohort	UK	Population based	2006–2010	471,851	182	1, 2, 6, 9, 13, 14, 23
Marelli et al. (2011)	Cohort	United States	Population based	1990–2009	91,714	105	1, 2, 8, 12, 13, 14
Friedman et al. (2008)	Cohort	United States	Population based	1994–2003	361,859	42	14		/
Hsiang (2015)	Cohort	Hong Kong	Population based	2000–2012	53,513	6883	1, 2, 5, 7, 14
Mohanty (2016)	Cohort	United States	Population based	1996–2009	40,512	173	1, 2,7, 8, 12, 19, 24
Björkhem-Bergman (2014)	Case-control	Swedish	Population based	2006–2010	23,964	3994	1, 2, 3, 4, 6, 7, 9, 21, 17
Friedman (2016)	Case-control	United States	Population based	1996–2014	145,727	2,877	3, 4, 6, 9, 12, 14, 17
McGlynn (2014)	Case-control	United States	Population based	1999–2010	562	94	4, 6, 8, 14, 17
German et al. (2020)	Case-control	United States	Population based	2002–2016	102	34	1, 2, 9
Galli et al. (2014)	Cohort	Italy	Population based	1991–2012	5357	19	NR
Kumar et al. (2013)	Cohort	United States	Population based	1988–2011	243	29	7, 14, 17, 24
McGlynn et al. (2016)	Case-control	UK	Population based	1988–2011	1657	339	3, 4, 6, 7, 12, 13, 31
Kim et al. (2016)	Case-control	Korea	Population based	2002–2013	1374	229	3, 4, 5, 6, 9, 11, 20, 34, 35
Kim et al. (2019)	Cohort	Korea	Population based	2002–2003	13063	193	1, 2, 6, 12, 13, 18, 32, 33
Kaplan et al. (2019)	Cohort	United States	Population based	2008–2016	74,984	2420	3, 4, 6, 7, 8, 12, 13, 18, 20, 32, 36, 37
Simon et al. (2019)	Cohort	Swedish	Population based	2005–2013	16 668	1012	NR
RCTs
Matsushita et al. (2010)	RCT	Japan	Individual patient data analysis of trials	2010	13,724	12	NR
CTT (2012)	RCT	Europe, Australia, North America	Individual patient data analysis of trials	2012	134,537	68	NR
Sato et al. (2006)	RCT	Japan	Secondary analysis of RCT	1991–1995	263	1	1, 2, 13

N/A, not applicable. ^a1, age; 2, sex; 3, HBV; 4, HCV; 5, cirrhosis; 6, alcoholic liver disease/alcohol use; 7, diabetes mellitus; 8, race; 9, other medications (aspirin/nonsteroidal anti-inflammatory medications, angiotensin-converting enzyme inhibitors, metformin, antidiabetic medications, PPIs, H2RAs, antihypertension medications, paracetamol, insulin, thiazolidinedione, and sulfonylurea); 10, other lipid-lowering agents; 11, socioeconomic status; 12, body mass index; 13, smoking; 14, comorbidities; 15, calendar year; 16, FIB-4 score; 17, other liver disease etiology; 18, hypertension; 19, dyslipidemia/hyperlipidemia/hypercholesterolemia; 20, CCI index; 21, complete biochemical tests; 21, education level; 22, antiviral therapy/attainment of SVR; 23, obesity; 24, MELD score; 25, hormone replacement therapy; 26, caffeine intake; 27, the presence of nonhemorrhagic varices; 28, physical activity; 29, follow-up duration; 30, gout; 31, rare metabolic disorders; 32, biochemical indicators; 33, family history of liver disease; 34, previous cancer; 35, pulmonary disease; 36, history of substance abuse; 37, center characteristics. ^bStudy quality assessment of observational studies was performed using the Newcastle–Ottawa scale; each asterisk represents if an individual criterion within the subsection was fulfilled.