| Study | Design | Location | Setting | Time period | Total no. of subjects | No. of HCC cases | Variables adjusted fora | Study qualityb | 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 | | | |
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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.
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