Supplementary table 1. Characteristics of all included studies regarding the association between statin use and risk of HCC.
References Study design Country Sample Size
Gender (male%)
Mean Age (SD)
Virus infection
Adjusted variables Results
Friis et al.
(2005) [1]
Cohort Denmark 347005 50.1 NR NR Age, sex, calendar period, use of NSAID, HRT and cardiovascular drugs
RR: 1.16 (0.46-2.90)
Friedman et al.
(2008) [2]
Cohort USA 361859 53.2 NR NR NR RR:
Male: 0.49 (0.34-0.70) Female: 0.40 (0.21-0.75) El-Serag et
al. (2009)
[3]
Cohort USA 6515 98.7 72 NR Alcoholism, alcoholic
liver disease, cirrhosis, HCV or HBV infection, race, HCV treatment, propensity to use statins,
ASA/NSAID, ACE
inhibitors
RR: 0.74 (0.64-0.87)
Chiu et al.
(2010) [4]
Case-control China, Taiwan
2332 68.9 65.9-
66.1
NR Matching variables, hospitalizations, diabetes, HBV or HCV infection, cirrhosis, alcoholic liver
OR: 0.62 (0.45-0.83)
disease, use of other lipid- lowering drugs.
Leung et al. (2012)
[5]
Case-control China, Taiwan
34205 47.2 58.3 (12.1)
NR Age, sex, Charlson score, other lipid-lowering agents use
OR: 0.44 (0.28-0.72)
Tsan et al.
(2012) [6]
Cohort China, Taiwan
33413 58.2 NR HBV Age, sex, income,
urbanization, diabetes, liver cirrhosis
RR: 0.47 (0.36-0.61)
Tsan et al.
(2013) [7]
Cohort China, Taiwan
260864 49.2 40-62 HCV Age, sex, urbanization, income, liver cirrhosis, diabetes
RR: 0.66 (0.59-0.74)
Lai et al.
(2013) [8]
Case-control China, Taiwan
17400 72.6 62.2- 62.7
NR Age, sex, diabetes mellitus, cirrhosis, alcoholic liver damage, non-alcoholic fatty liver disease, hepatitis B or C infection, treatments for Hepatitis B or C, thiazolidinediones
OR: 0.72 (0.59-0.88)
Björkhem- Bergman
Case-control Sweden 23964 52.0 NR NR Age, sex, diabetes, education, treatment with
OR: 0.88 (0.81-0.96)
et al.
(2014) [9]
cortisone, acetylsalicylic acid, NSAID and chemotherapy, liver disease
McGlynn et al.
(2014) [10]
Case-control USA 562 74.4 NR NR Race, HCV, alcohol-
related conditions, diabetes, chronic obstructive pulmonary disease, hypertension
OR: 0.32 (0.15-0.67)
Butt et al.
(2015) [11]
Cohort USA 7248 95.6 52-53 HCV NR RR: 0.51 (0.34-0.76)
Chen et al.
(2015) [12]
Case-control China, Taiwan
1700 77.9 62.4-
62.6
NR Age, sex, ALD, HBV, NAFLD, metformin, cirrhosis duration
OR: 0.37 (0.27-0.49)
Chen et al.
(2015) [13]
Cohort China, Taiwan
71824 57.2 NR HBV Baseline propensity score RR: 0.34 (0.27-0.42)
Fu et al.
(2015) [14]
Cohort China, Taiwan
4179 58.5 49.1-
49.2
HBV Age, sex, new onset diabetes, cirrhosis, hyperlipidaemia, CHB treatment, DM treatment, obesity
RR: 0.53 (0.28-0.99)
Hsiang et al. (2015)
[15]
Cohort China, Hong Kong
53513 26.4 NR HBV Age, sex, comorbidities, diabetes, laboratory parameters, medications
RR: 0.68 (0.48-0.97)
Huang et al. (2015)
[16]
Cohort China, Taiwan
2187 44.9 58.1-
58.3
HCV Age, sex, new onset diabetes, cirrhosis, hyperlipidaemia, CHC treatment, DM treatment, obesity
RR: 1.12 (0.48-2.61)
McGlynn et al.
(2015) [17]
Case-control UK 5835 71.6 NR NR BMI, smoking, alcohol-
related disorders, hepatitis B virus or hepatitis C virus, diabetes, paracetamol use, rare metabolic disorders, aspirin, and antidiabetics
OR: 0.55 (0.45-0.69)
Simon et al. (2016)
[18]
Cohort USA 9135 95.7 52.5-
53.5
HCV Age, sex, race, smoking, alcohol, caffeine intake, BMI, Diabetes, baseline FIB-4 score, Metformin and ACE inhibitor use,
RR: 0.51 (0.36-0.72)
other lipid-lowering agent use, non-steroidal anti- inflammatory medication use, prior completed HCV treatment, attainment of sustained virologic response (SVR), daily caffeine intake
Tsai et al.
(2017) [19]
Cohort China, Taiwan
546 73.4 57.7
(11.1)
HBV Age, sex, BMI, diabetes, hypertension, baseline HBV-DNA, Child-Pugh class
RR: 2.42 (1.17-5.01)
Kim et al.
(2017) [20]
Case-control South Korea
1374 81.4 40-80 NR chronic viral hepatitis, cirrhosis, alcoholic liver disease, previous cancer, medicine use, history of chronic obstructive pulmonary disease, Charlson comorbidity score, household income level, residential area
OR: 0.36 (0.22-0.60)
Kim et al.
(2018) [21]
Case-control South Korea
9852 83.6 61.8
(9.2)
NR Diabetes mellitus, liver cirrhosis, Charlson comorbidity index, BMI, alcohol related disorders, smoking, aspirin and antidiabetic medications use, household income level, residential area
OR: 0.44 (0.33-0.58)
Lee et al.
(2017) [22]
Cohort China, Taiwan
18080 52.6 NR NR Age, gender, ALT
elevation, hypertension, hypercholesterolemia, diabetes mellitus, gout, metformin use, aspirin use
RR: 0.29 (0.12-0.68)
German et al. (2020)
[23]
Case-control USA 102 64.7 64.3-
65.2
NR Age, sex, metformin use, aspirin use, angiotensin- converting enzyme inhibitor/angiotensin II receptor antagonist use
OR: 0.20 (0.07-0.60)
Simon et al. (2019)
[24]
Cohort Sweden 16668 NR NR NR NR RR:
lipophilic statin: 0.56 (0.41-0.79)
hydrophilic statin: 0.95 (0.86-1.08)
Goh et al.
(2019) [25]
Cohort South
Korea
7713 66.2 47-50 HBV Age, sex, cirrhosis, diabetes, hypertension,
serum alanine
aminotransferase,
cholesterol, HBV DNA level, antiviral treatment, antiplatelet therapy
RR: 0.36 (0.19-0.68)
Tran et al.
(2020) [26]
Case-control UK 2537 67.1 50-80 NR Age, sex, practice,
obesity, comorbidities in exposure period, other medication use in exposure period
OR: 0.61 (0.43-0.87)
Tran et al.
(2020) [26]
Cohort UK 471851 46.1 50-80 NR Age, sex, deprivation,
BMI, alcohol, smoking, comorbidities at baseline, other medication use at baseline
RR: 0.48 (0.24-0.94)
Abbreviations: CIs, confidence intervals; NR, not reported; ORs, odds ratios; RR, relative risks; SD, standard deviation; USA, united states.
Supplementary table 2. Characteristics of all included studies.
References Study design Country Sample Size (Statin User:
Nonuser)
Gender (male%)
Mean Age (SD)
Adjusted variables Results
Kim et al, (2019) [27]
Case-control study
South Korea
13063 (980:12083)
51.0% 52.1(9.0) Age, sex, BMI, ALT,
GGT, total
cholesterol, fasting blood glucose, hypertension, family history of liver disease, smoking status, alcohol consumption
Liver cancer mortality: 0.17 (0.04-0.70)
Thrift et al, (2019) [28]
Case-control study
USA 15422
(2293:13129)
99.2% 63.3 Age, sex, race, BMI, alcohol abuse, smoking, HCV/HBV infection, cirrhosis, NAFLD, stage, MELD score, APRI, ascites, hepatic encephalopathy,
Cancer specific mortality: 0.85 (0.77-0.93) All-cause mortality: 0.89 (0.83-0.95)
varices, Deyo comorbidity score, treatment, ECOG performance status, pre-diagnosis statin use, post-diagnosis aspirin/NSAID use Jeon et al,
(2016) [29]
Case-control study
USA 1036 (363:673)
64.3% NR Age, sex, race, income, grade, tumor size and stage, resection, radiofrequency ablation, TACE, cardiovascular disease prior, cirrhosis, obesity, diabetes,
hypertension, dyslipidemia, hepatitis B and C
All-cause mortality: 0.98 (0.80-1.20)
Shao et al, (2015) [30]
Cohort study China, Taiwan
20200
(1988:18212)
80.2% 59.84 Age, sex,
nucleoside/nucleotide analogs, interferons, aspirin, metformin, cirrhosis, liver failure, hypertension, diabetes
All-cause mortality:
Cancer specific mortality:
HBV: Non- HBV:
HBV: Non- HBV:
Stage 1 0.73 (0.54- 0.98)
0.77 (0.64- 0.93)
0.46 (0.25- 0.86)
0.64 (0.45- 0.92) Stage 2 0.72
(0.52- 0.99)
0.77 (0.62- 0.95)
0.38 (0.19- 0.78)
0.70 (0.48- 1.03) Stage 3 0.83
(0.71- 0.97)
0.91 (0.82- 1.01)
1.08 (0.82- 1.44)
0.80 (0.67- 0.96) Stage 4 1.04
(0.82- 1.32)
0.95 (0.83- 1.08)
1.29 (0.86- 1.93)
0.93 (0.76- 1.15) Wu et al,
(2016) [31]
Case-control study
China, Taiwan
18892 (934:17958)
70.4% 64.3 Age, stage, gender, nucleoside/nucleotide analogues,
interferons, aspirin,
All-cause mortality:
HBV: 0.45 (0.30-0.67) Non-HBV: 0.59 (0.48-0.73) Cancer specific mortality:
metformin, cirrhosis, liver failure, hypertension,
diabetes, chronic obstructive
pulmonary disease, acute coronary syndrome, cerebral vascular disease
HBV: 0.16 (0.05-0.49) Non-HBV: 0.70 (0.50-0.98)
Nishio et al, (2018) [32]
Case-control study
Japan 643 (43:600) 78.2% NR Sex, age, body mass index, daily ethanol intake, prevalence of diabetes,
dyslipidemia,
hypertension, Child- Pugh classification,
serum alpha-
fetoprotein, tumor size, tumor number, tumor differentiation,
presence of
All-cause mortality:
0.62 (0.30-1.27)
microvascular
invasion, liver cirrhosis
Kawaguchi et al, (2017) [33]
Case-control study
Japan 734 (31:703) 77.2% NR Age, sex, hepatitis B and C, fibrosis, ALT, AFP, DCP, surgical margin, tumor size, tumor differentiation, vascular invasion
All-cause mortality:
0.44 (0.11-1.15)
Abbreviations: CIs, confidence intervals; NR, not reported; ORs, odds ratios; RR, relative risks; SD, standard deviation; USA, united states.
