Table 1.
Incidence, Trend, and Risk Factors for HCC in NAFLD
| Study Author Year | Study Type | Population | Study Duration or Follow-Up in Years | Cumulative Incidence | Risk Factors and Other Findings |
|---|---|---|---|---|---|
| Cho et al, 2011180 | Retrospective cohort | 329 patients with non-B non-C, non-alcohol, or specific cause-related HCC | 2001–2010 | NR | Increased proportion of NAFLD related HCC increased from 3.8% to 12.2% |
| Dyson et al, 2014128 | Retrospective cohort | 632 patients with HCC | 2000–2010 | NR | The proportion of NAFLD HCC 21.5% (136/632) in 2010. 10 fold increase in NAFLD HCC over 10 years |
| Wong et al, 201446 | Retrospective cohort | UNOS registry; 61,868 adults with LT including 10,061 with HCC | 2002–2012 | NR | Increase in % of NASH related HCC 8.3% in 2002 versus 10.3% in 2007 versus 13.5% in 2012 |
| Younossi et al, 2015127 | Retrospective cohort | SEER registries, 4929 HCC cases 14,937 controls | 2004–2009 | NR | The proportion of NAFLDHCC: 14.1%; 9% annual increase of NAFLDHCC; |
| Park et al, 201545 | Retrospective cohort | BRIDGE, 14 countries, 18,031 HCC patients | 2005–2012 | NR | The proportion of NASHHCC: North America 12%, Europe 10%, China 5%, South Korea 6%, Japan 2% |
| Beste et al, 2015181 | Retrospective cohort | 129,998 cirrhosis, 21,326 HCC | 2001–2013 | NR | Incidence of NAFLDHCC increased from 2.63 to 5.14 per 100, 000 |
| Younossi et al, 201947 | Retrospective cohort | 158,347 adult LT candidates 26,121 HCC | 2002–2017 | NR | The proportion of NASH in HCC increased 7.7-fold from 2.1% to 16.2% |
| Hashimoto et al, 2009182 | Prospective Cohort | 137 NASH with advanced fibrosis | 1990–2007 | 5-year cumulative incidence of HCC was 7.6% | RF: Older age, AST level AST, low grade of histological activity, and advanced fibrosis stage. 5-year survival rate was 82.8% |
| Yatsuji et al, 2009183 | Prospective cohort | 68 patients with cirrhotic NASH 69 patients with HCV Cirrhosis |
1990–2006 | 5-year HCC rate was 11.3% for NASH | the 5-year survival rates were 75.2% |
| Ascha et al, 201053 | Prospective cohort | 195 NASH cirrhosis 315 HCV cirrhosis |
2003–2007 3.2 yrs. follow up | 2.6% yearly CI | 12.8% of NASH cirrhosis developed HCC RF: Older age and alcohol consumption |
| Kawamura et al, 201285 | Retrospective cohort | 6508 patients with NAFLD | 1997–2010 Median follow-up Yrs. | Cumulative rates of NAFLDHCC were 0.02% (year 4), 0.19% (year 8), 0.51% (year 12) | RF: AST level ≥40, platelet count ≤150, age ≥ 60 years and diabetes at baseline. |
| Amarapurkar et al 2013184 | Retrospective cohort | 585 patients with liver cirrhosis NASH-related cirrhosis 7%, cryptogenic cirrhosis 17.8% |
Cumulative follow-up 6.8 + 1.2 years | The annual rate of cirrhotic NASHHCC: 0.46% | The annual rate of cryptogenic cirrhosis HCC: 0.6% |
| Kodama et al, 2013185 | Retrospective cohort | 72 patients with NASH cirrhosis and 85 with ALD cirrhosis | 1990–2010 | 5 yrs. CI 10.5% in NASH-cirrhosis |
RF: older age, higher γ-GTP level, and higher Child-Pugh score |
| Younossi et al, 201614 | Meta-analysis | 86 studies with population of 8,515,431 | 1989–2015 | NAFLD-HCC incidence 0.44 per 1000 person-years | The global prevalence of NAFLD: 25.24% |
| Vilar-Gomez et al, 201835 | Retrospective cohort | 458 NAFLD patients, bridging fibrosis/ compensated cirrhosis | 1995–2016 mean follow-up time of 5.5 years | 1 yr CI. 0.2 F3 1.8 CPT A5 4.7 CPT A6 |
RF: Older age, male sex, diabetes, current smoking, (All cohort) Moderate alcohol consumption, current smoking (Cirrhosis cohort) 10 years accumulated NAFLDHCC rate: 9% |
| Marot et al, 2016186 | Retrospective cohort | 752 patients with cirrhosis (78 NAFLD, 145 HCV, 529 ALD) | 1995–2014 | Annual risks of NAFLDHCC: 3.1% | 10-year cumulative incidence rate: 23.7% |
| Bhala et al, 2011187 | Prospective/Retrospective cohort | 247 NAFLD patients (118 F3, 129 F4) | mean follow up of 7.1 yrs. | 2.4% of NAFLD patients developed HCC | No risk factors identified |
| Lee et al 201779 | Retrospective cohort | 18,080 noncirrhotic NAFLD | 6.3 years | 1 year (0.18) 5 years (1.03) 10 years (2.73) |
RF: Older age High ALT |
| Fuji et al 202256 | Retrospective cohort | 1398 patient with biopsy-confirmed NAFLD | Median follow-up period 4.6 years 8874 person-years | HCC incidence 4.17/1000 person-years (95% CI 3.02–5.75). | Liver-specific mortality 2.34/1000 person-years overall mortality 5.34/1000 person-years |
| Pinyopornpanish et al 202184 | Retrospective cohort | 392,800 adult patients with NAFLD. 367,690 non-cirrhotic NAFLD 25,110 cirrhotic NAFLD |
Median follow up 5 years 2015 to 2020 | HCC in non-cirrhotic NAFLD 4.6/10,000 persons HCC in cirrhotic NAFLD 374.4/10,000 persons |
RF for HCC in non-cirrhotic NAFLD Age > 65 DM ever had elevated ALT Male gender Smoking |
| Alexander et al 2019154 | Matched-cohort study | 136,703 patients with NAFLD/NASH | Median follow up of 3.3 years | Incidence of NAFLD-HCC 0.3 per 1000 person-years, | Hazard ratio for HCC among NAFLD patients was 3.51 DM at baseline strongest independent predictor of HCC |
| Kanwal et al 201854 | Retrospective cohort | 296,707 NAFLD patients with matched controls | 2004–2015 Mean follow up of 9 years | 0.21/1000 PY | 490 NAFLD patients developed HCC during a mean follow up of 9 years HR for HCC among NAFLD patients: 7.62 RF: Cirrhosis, Older Hispanics |
| Sanyal et al, 2006188 | Prospective cohort | 152 NASH cirrhosis | 10 years | 10 patients developed HCC over 10 years | No risk factors identified |
Abbreviations: NR, Not reported; RF, Risk factors.