TG Simon et al. Hepatology 2021; 74: 2410-2423. Open Access. Cancer Risk in Patients With Biopsy-Confirmed Nonalcoholic Fatty Liver Disease: A Population-Based Cohort Study
Key findings from this retrospective study with median of 14 yrs f/u (1966-2016, n=8892):
- HCC incidence rates increased monotonically across categories of simple steatosis, nonfibrotic NASH, noncirrhotic fibrosis, and cirrhosis (0.8 per 1,000 PYs, 1.2 per 1,000 PYs, 2.3 per 1,000 PYs, and 6.2 per 1,000 PYs, respectively; Ptrend < 0.01) and were further amplified by diabetes (1.2 per 1,000 PYs, 2.9 per 1,000 PYs, 7.2 per 1,000 PYs, and 15.7 per 1,000 PYs, respectively
- “Compared with controls, patients with NAFLD had a17-fold higher rate of developing HCC and a 20-year absolute excess risk of 2.1%.”
- The 20-year absolute excess risk of patients with noncirrhotic NAFLD fibrosis (4.6%) or cirrhosis (11.4%) developing HCC was comparable to that of all EHSO [extrahepatic solid organ] cancers combined (4.7% -11.4%).
- The risk of extrahepatic solid organ cancers was increased 12% compared to general population


G Chonlakeril et al. Hepatology 2021; 74: 2336-2338 Associated Editorial. NAFLD and HCC: Time to Bridge the Gap
- In this analysis, the authors note the annual incidence rate of HCC for cirrhosis in NAFLD was 0.62% which is below rate of 1.5% in which “HCC surveillance may be cost-effective;” however, the rate was 1.52% in those with cirrhosis and diabetes.
- The authors note that the 9-fold higher risk for HCC in those with simple steatosis compared to matched population could be related to ascertainment bias (at least in part) as not all patients with steatosis undergo a liver biopsy; in addition, misclassification of liver biopsies is possible.
My take: Lots of increased risk with fatty liver disease, especially increased HCC/cancers and increased cardiovascular disease.
Related blog posts:
- NAFLD Guidance from American Association for the Study of Liver Diseases
- Trends in Liver Diseases: Autoimmune Liver Diseases and Fatty Liver (2021)
- Increasing Incidence of Hepatocellular Carcinoma in the U.S. (2017)
- Bad Fatty Liver Disease Can Get Worse Quickly
- Liver Shorts April 2019 Obesity/NAFLD and alcoholic liver disease are driving an increase in HCC and liver cancer mortality