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. 2023 Mar;21(3):670-680.e18.
doi: 10.1016/j.cgh.2022.03.010. Epub 2022 Mar 17.

Clinical Characteristics and Outcomes of Nonalcoholic Fatty Liver Disease-Associated Hepatocellular Carcinoma in the United States

Mohammad A Karim  1 , Amit G Singal  2 , Hye Chung Kum  3 , Yi-Te Lee  4 , Sulki Park  3 , Nicole E Rich  2 , Mazen Noureddin  5 , Ju Dong Yang  6
Affiliations

Clinical Characteristics and Outcomes of Nonalcoholic Fatty Liver Disease-Associated Hepatocellular Carcinoma in the United States

Mohammad A Karim et al. Clin Gastroenterol Hepatol. 2023 Mar.

Abstract

Background & aims: The extent to which nonalcoholic fatty liver disease (NAFLD) contributes to hepatocellular carcinoma (HCC) prevalence in contemporary practices and whether there are any etiologic differences in surveillance receipt, tumor stage, and overall survival (OS) remain unclear. We aimed to estimate the burden of NAFLD-related HCC and magnitude of associations with surveillance receipt, clinical presentation, and outcomes in a contemporary HCC cohort.

Methods: In a cohort of HCC patients from the Surveillance, Epidemiology and End Results-Medicare database between 2011 and 2015, we used multivariable logistic regression to identify factors associated with surveillance receipt, early-stage tumor detection, and curative treatment. Cox regression was used to identify factors associated with OS.

Results: Among 5098 HCC patients, NAFLD was the leading etiology, accounting for 1813 cases (35.6%). Compared with those with hepatitis C-related HCC, NAFLD was associated with lower HCC surveillance receipt (adjusted odds ratio, 0.22; 95% confidence interval [CI], 0.17-0.28), lower early-stage HCC detection (adjusted odds ratio, 0.49; 95% CI, 0.40-0.60), and modestly worse OS (adjusted hazard ratio, 1.20; 95% CI, 1.09-1.32). NAFLD subgroup analysis showed that early-stage HCC, absence of ascites/hepatic encephalopathy, surveillance, and curative treatment receipt were associated with improved OS. NAFLD patients with coexisting liver disease were more likely to have surveillance, early-stage detection, curative treatment, and improved OS than NAFLD patients without coexisting liver diseases.

Conclusions: NAFLD is the leading etiology of HCC among Medicare beneficiaries. Compared with other etiologies, NAFLD was associated with lower HCC surveillance receipt, early-stage detection, and modestly poorer survival. Multifaceted interventions for improving surveillance uptake are needed to improve prognosis of patients with NAFLD-related HCC.

Keywords: Liver Cancer; NAFLD; NASH; Surveillance.

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Conflict of interest statement

Conflict of interest:

Dr. Yang provides a consulting service for Exact Sciences and Gilead Sciences and Eisai.

Dr. Singal has been on advisory boards and served as a consultant for Wako Diagnostics, Glycotest, Exact Sciences, Roche, Genentech, Bayer, Eisai, BMS, Exelixis, AstraZeneca, and TARGET RWE.

Dr Rich as served as consultant for AstraZeneca.

Dr. Noureddin has been on the advisory board for 89BIO, Gilead, Intercept, Pfizer, Novo Nordisk, Blade, EchoSens, Fractyl, Terns, Siemens and Roche diagnostic; MN has received research support from Allergan, BMS, Gilead, Galmed, Galectin, Genfit, Conatus, Enanta, Madrigal, Novartis, Pfizer, Shire, Viking and Zydus; Dr. Noureddin is a minor shareholder or has stocks in Anaetos, Rivus Pharma and Viking.

Figures

Figure 1.
Figure 1.. HCC surveillance receipt by etiology
(A) All HCC patients. (B) HCC patients with cirrhosis. A low proportion of individuals with NAFLD-associated HCC had surveillance. ALD, alcoholic liver disease; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; NAFLD, nonalcoholic fatty liver disease.
Figure 2.
Figure 2.. Overall survival, stratified by HCC etiology.
Patients with NAFLD had the shortest median overall survival among subgroups with different etiologies. ALD, alcoholic liver disease; HBV, hepatitis B virus; HCV, hepatitis C virus; NAFLD, nonalcoholic fatty liver disease.
See this image and copyright information in PMC

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