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Incidence of hepatocellular carcinoma in nonalcoholic fatty liver disease without cirrhosis or advanced liver fibrosis
Open accessAbstract
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.
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“the HCC incidence in individuals without cirrhosis is very low, ranging from 0.08 to 0.63 per 1,000 PY. 240 -244”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [243]
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“In another retrospective cohort study, the annual incidence of HCC was 2.8 per 1,000 PY with FIB-4 > 2.67 and 0.7 per 1,000 PY with FIB-4 < 1.30. 243”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [243]
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Cites
Younossi, Z. M., Koenig, A. B., Abdelatif, D., Fazel, Y., Henry, L., & Wymer, M. (2016) · Hepatology · doi:10.1002/hep.28431 · Cited by 10,781
Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data
Quan, H., Sundararajan, V., Halfon, P., Fong, A., Burnand, B., Luthi, J.-C., Saunders, L. D., Beck, C. A., Feasby, T. E., & Ghali, W. A. (2005) · Medical Care · doi:10.1097/01.mlr.0000182534.19832.83 · Cited by 10,669
Sterling, R. K., Lissen, E., Clumeck, N., Sola, R., Correa, M. C., Montaner, J., S. Sulkowski, M., Torriani, F. J., Dieterich, D. T., Thomas, D. L., et al. (2006) · Hepatology · doi:10.1002/hep.21178 · Cited by 5,021 · cited 1×
“[16] The FIB-4 was calculated as follows [(age[years] × AST [U/L])/(platelet [109/L] ×√ALT [U/L])].[17] The AST/√ALT ratio was previously shown as a marker of fibrosis in patients with NAFLD,[18] and the ALBI score was a discriminatory factor in the liver function and prognosis in patients with HCC.”
MethodMarrero, J. A., Kulik, L., Sirlin, C. B., Zhu, A. X., Finn, R. S., Abecassis, M. M., Roberts, L. R., & Heimbach, J. K. (2018) · Hepatology · doi:10.1002/hep.29913 · Cited by 4,597
MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease
Eslam, M., Sanyal, A. J., George, J., Sanyal, A., Neuschwander-Tetri, B., Tiribelli, C., Kleiner, D. E., Brunt, E., Bugianesi, E., Yki-Järvinen, H., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.11.312 · Cited by 3,286
Expanding consensus in portal hypertension
de Franchis, R. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.05.022 · Cited by 3,078
Johnson, P. J., Berhane, S., Kagebayashi, C., Satomura, S., Teng, M. J., Reeves, H. L., O’Beirne, J. P., Fox, R., Skowrońska, A., Palmer, D. H., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.57.9151 · Cited by 2,865
Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention
Huang, D. Q., El-Serag, H. B., & Loomba, R. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-00381-6 · Cited by 1,855
Comparison of Noninvasive Markers of Fibrosis in Patients With Nonalcoholic Fatty Liver Disease
Shah, A. G., Lydecker, A. D., Murray, K. F., Tetri, B., Contos, M. J., & Sanyal, A. J. (2009) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2009.05.033 · Cited by 1,561
Ascha, M. S., Hanouneh, I. A., Lopez, R., Tamimi, T. A.-R., Feldstein, A. F., & Zein, N. N. (2010) · Hepatology · doi:10.1002/hep.23527 · Cited by 1,296
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Tacke, F., Horn, P., Wai-Sun Wong, V., Ratziu, V., Bugianesi, E., Francque, S., Zelber-Sagi, S., Valenti, L., Roden, M., Schick, F., et al. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.04.031 · Cited by 2,210
Epidemiology of metabolic dysfunction-associated steatotic liver disease
Younossi, Z. M., Kalligeros, M., & Henry, L. (2025) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2024.0431 · Cited by 960
Metadata
- Authors
- Behari, J., Gougol, A., Wang, R., Luu, H. N., Paragomi, P., Yu, Y.-C., Molinari, M., Chopra, K., Malik, S. M., Geller, D., & Yuan, J.-M.
- Affiliations
- University of Pittsburgh (US)
- UPMC Hillman Cancer Center (US)
- Corresponding author
- Behari, Jaideep
- Yu, Yi-Chuan
- Yuan, Jian-Min
- ORCID
- Venue
- Hepatology Communications
- Published
- 2023-07
- Volume
- 7
- Issue
- 7
- ISSN
- 2471-254X (ISSN-L)
- PMC
- PMC10319365
- OpenAlex
- W4382919370
- Cited by
- 35
- References
- 34
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 13
- FWCI
- 5.92
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Hepatology Communications (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (UH3TR003289)
- National Institute on Alcohol Abuse and Alcoholism (U01AA026264, U01AA026978)
- National Cancer Institute (T32CA186873, R01CA255809)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- hepatocellular carcinoma, non-alcoholic fatty liver disease, liver cirrhosis, liver fibrosis, FIB-4, cancer incidence, advanced fibrosis
- MeSH terms
- Carcinoma, Hepatocellular, Humans, Liver Cirrhosis, Liver Neoplasms, Retrospective Studies, Risk Factors, Cohort Studies, Incidence, Non-alcoholic Fatty Liver Disease
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- Behari, J., Gougol, A., Wang, R., Luu, H. N., Paragomi, P., Yu, Y.-C., Molinari, M., Chopra, K., Malik, S. M., Geller, D., & Yuan, J.-M. (2023). Incidence of hepatocellular carcinoma in nonalcoholic fatty liver disease without cirrhosis or advanced liver fibrosis. Hepatology Communications. https://doi.org/10.1097/hc9.0000000000000183
