Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jul 3;7(7):e00183.
doi: 10.1097/HC9.0000000000000183. eCollection 2023 Jul 1.

Incidence of hepatocellular carcinoma in nonalcoholic fatty liver disease without cirrhosis or advanced liver fibrosis

Jaideep Behari  1   2   3 , Amir Gougol  1 , Renwei Wang  2 , Hung N Luu  2   4 , Pedram Paragomi  2   4 , Yi-Chuan Yu  2   4 , Michele Molinari  5 , Kapil Chopra  1 , Shahid M Malik  1 , David Geller  3   5 , Jian-Min Yuan  2   3   4
Affiliations

Incidence of hepatocellular carcinoma in nonalcoholic fatty liver disease without cirrhosis or advanced liver fibrosis

Jaideep Behari et al. Hepatol Commun. .

Abstract

Background: HCC can develop in the absence of cirrhosis in patients with NAFLD. We aimed to estimate the incidence of HCC in patients with NAFLD with and without cirrhosis or advanced liver fibrosis.

Methods: We performed a cohort study to determine the incidence of HCC in patients with NAFLD identified by the International Classification of Diseases 9/10 codes in the electronic health records of a US health care system between 2004 and 2018. The incidence of HCC was stratified by the presence or absence of cirrhosis and by the Fibrosis-4 index (FIB-4) at the time of HCC diagnosis.

Results: Of 47,165 patients with NAFLD aged 40-89 years, 981 (2.1%) developed HCC (mean follow-up 3.4 y). Among patients with HCC, 842 (85.8%) had cirrhosis, while 139 (14.2%) did not. Of the 139 patients with HCC without cirrhosis-related diagnostic codes, 26 (2.7%) had FIB-4 >2.67 (advanced fibrosis likely), whereas 43 (4.4%) had FIB-4 < 1.30 (excluding advanced fibrosis). The annual incidence of HCC in patients with NAFLD with and without cirrhosis was 23.6 and 1.1 per 1000 person-years, respectively. Among patients without cirrhosis, the annual incidence of HCC was 2.8 per 1000 person-years with FIB-4 >2.67 and 0.7 per 1000 person-years with FIB-4 <1.30. Patients with NAFLD and cirrhosis were 31.8 times (95% CI, 23.3-43.4) more likely to develop HCC than those without cirrhosis and FIB-4 <1.30, after adjustment for age and sex.

Conclusions: Patients with NAFLD without cirrhosis nor advanced fibrosis have a low incidence of HCC.

PubMed Disclaimer

Conflict of interest statement

Jaideep Behari has received research grant funding from Gilead, Pfizer, AstraZeneca, and Endra Life Sciences. His institution has research contracts with Intercept, Pfizer, Galectin, Exact Sciences, Inventiva, Enanta, Shire, Gilead, Allergan, Celgene, Galmed, Rhythm, and Genentech. The remaining authors have no conflicts to report.

Figures

FIGURE 1
FIGURE 1
Flow diagram of the patient cohort used in the analysis. Abbreviation: FIB-4, Fibrosis-4 index.
See this image and copyright information in PMC

References

    1. Huang DQ, El-Serag HB, Loomba R. Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2021;18:223–38. - PMC - PubMed
    1. Younossi ZM, Otgonsuren M, Henry L, Venkatesan C, Mishra A, Erario M, et al. . Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009. Hepatology. 2015;62:1723–30. - PubMed
    1. Younossi Z, Stepanova M, Ong JP, Jacobson IM, Bugianesi E, Duseja A, et al. . Nonalcoholic steatohepatitis is the fastest growing cause of hepatocellular carcinoma in liver transplant candidates. Clin Gastroenterol Hepatol. 2019;17:748–55.e743. - PubMed
    1. Kanwal F, Kramer JR, Li L, Dai J, Natarajan Y, Yu X, et al. . Effect of metabolic traits on the risk of cirrhosis and hepatocellular cancer in nonalcoholic fatty liver disease. Hepatology. 2020;71:808–19. - PubMed
    1. Ascha MS, Hanouneh IA, Lopez R, Tamimi TA, Feldstein AF, Zein NN. The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology. 2010;51:1972–8. - PubMed

Publication types

MeSH terms