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. 2023 Mar;68(3):1060-1070.
doi: 10.1007/s10620-022-07565-x. Epub 2022 Jun 27.

Clinical Course and Outcomes of Patients with Nonalcoholic Fatty Liver Disease-Related Hepatocellular Cancer (NAFLD-HCC)

Jinna Chu #  1 , George Cholankeril #  2   3 , Xian Yu  4 , Abbas Rana  2 , Yamini Natarajan  3   4 , Hashem B El-Serag  3   4 , Jennifer Kramer  4 , Fasiha Kanwal  5   6
Affiliations

Clinical Course and Outcomes of Patients with Nonalcoholic Fatty Liver Disease-Related Hepatocellular Cancer (NAFLD-HCC)

Jinna Chu et al. Dig Dis Sci. 2023 Mar.

Abstract

Background & aims: Among etiologies for hepatocellular (HCC), nonalcoholic fatty liver disease (NAFLD) carries a high risk of competing non-cancer mortality. The effect of cancer and non-cancer factors on risk of death after NAFLD-HCC diagnosis remains unclear. We aimed to evaluate the role of non-cancer mortality with NAFLD-HCC.

Methods: Using a retrospective cohort of patients with NAFLD diagnosed at 130 facilities in the Veterans Administration, we identified patients with incident HCC diagnosed between January 1, 2005 and June 30, 2018. We determined cause of death as HCC-related, non-HCC liver-related, and non-liver-related after HCC diagnosis. We used Cox proportional hazards regression models to evaluate the effect of clinical factors on cause-specific mortality after NAFLD-HCC diagnosis.

Results: We identified 776 patients with incident HCC. Mean age at HCC diagnosis was 70.1 year, 22.2% had Barcelona Clinic Liver Cancer (BCLC) stage 0-A, and 67.0% had more than one comorbidity. 1- and 3-year mortality rates were 47.0% and 69.6%, respectively. Most deaths (72.2% at 3 years) were attributable to HCC. In HCC patients who received curative treatment, non-cancer mortality accounted for 40% of all deaths between 3 and 5 years after treatment. Poor performance status (ECOG 3/4, HR 5.03, 95% CI: 2.59-9.77) and older age (65-75, HR 1.94, 95% CI: 1.06-3.54) were strongly associated with non-cancer mortality.

Conclusion: Although most patients with NAFLD-HCC die of HCC, non-cancer mortality represents a clinically meaningful competing event for patients receiving curative treatment, underscoring the importance of assessing and managing risk factors of non-cancer morbidity and mortality.

Trial and registration: N/A.

Keywords: Cause-specific mortality; Disparities; Fatty liver disease; Liver cancer.

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Conflict of interest statement

Conflict of Interest

The authors have no other relevant financial disclosures or conflicts of interest pertinent to this subject matter.

Figures

Figure 1.
Figure 1.
Cumulative mortality risk for NAFLD-related HCC after diagnosis.
Figure 2.
Figure 2.
Cumulative mortality risk for NAFLD-related HCC stratified within subgroups. A. All NAFLD-related HCC patients who underwent curative treatment (n= 121). B. NAFLD-related HCC limited to patients under the age of 75 who underwent curative treatment (n=106). C. NAFLD-related HCC limited to patients 75 years or older who underwent curative treatment (n=15). D. NAFLD-related HCC limited to patients with CIRCOM 0 who underwent curative treatment (n=52). E. NAFLD-related HCC limited to patients with CIRCOM 1 or higher who underwent curative treatment (n=69). F. NAFLD-related HCC limited to patients who underwent palliative treatments (n=234).
Figure 2.
Figure 2.
Cumulative mortality risk for NAFLD-related HCC stratified within subgroups. A. All NAFLD-related HCC patients who underwent curative treatment (n= 121). B. NAFLD-related HCC limited to patients under the age of 75 who underwent curative treatment (n=106). C. NAFLD-related HCC limited to patients 75 years or older who underwent curative treatment (n=15). D. NAFLD-related HCC limited to patients with CIRCOM 0 who underwent curative treatment (n=52). E. NAFLD-related HCC limited to patients with CIRCOM 1 or higher who underwent curative treatment (n=69). F. NAFLD-related HCC limited to patients who underwent palliative treatments (n=234).
Figure 2.
Figure 2.
Cumulative mortality risk for NAFLD-related HCC stratified within subgroups. A. All NAFLD-related HCC patients who underwent curative treatment (n= 121). B. NAFLD-related HCC limited to patients under the age of 75 who underwent curative treatment (n=106). C. NAFLD-related HCC limited to patients 75 years or older who underwent curative treatment (n=15). D. NAFLD-related HCC limited to patients with CIRCOM 0 who underwent curative treatment (n=52). E. NAFLD-related HCC limited to patients with CIRCOM 1 or higher who underwent curative treatment (n=69). F. NAFLD-related HCC limited to patients who underwent palliative treatments (n=234).
Figure 2.
Figure 2.
Cumulative mortality risk for NAFLD-related HCC stratified within subgroups. A. All NAFLD-related HCC patients who underwent curative treatment (n= 121). B. NAFLD-related HCC limited to patients under the age of 75 who underwent curative treatment (n=106). C. NAFLD-related HCC limited to patients 75 years or older who underwent curative treatment (n=15). D. NAFLD-related HCC limited to patients with CIRCOM 0 who underwent curative treatment (n=52). E. NAFLD-related HCC limited to patients with CIRCOM 1 or higher who underwent curative treatment (n=69). F. NAFLD-related HCC limited to patients who underwent palliative treatments (n=234).
Figure 2.
Figure 2.
Cumulative mortality risk for NAFLD-related HCC stratified within subgroups. A. All NAFLD-related HCC patients who underwent curative treatment (n= 121). B. NAFLD-related HCC limited to patients under the age of 75 who underwent curative treatment (n=106). C. NAFLD-related HCC limited to patients 75 years or older who underwent curative treatment (n=15). D. NAFLD-related HCC limited to patients with CIRCOM 0 who underwent curative treatment (n=52). E. NAFLD-related HCC limited to patients with CIRCOM 1 or higher who underwent curative treatment (n=69). F. NAFLD-related HCC limited to patients who underwent palliative treatments (n=234).
Figure 2.
Figure 2.
Cumulative mortality risk for NAFLD-related HCC stratified within subgroups. A. All NAFLD-related HCC patients who underwent curative treatment (n= 121). B. NAFLD-related HCC limited to patients under the age of 75 who underwent curative treatment (n=106). C. NAFLD-related HCC limited to patients 75 years or older who underwent curative treatment (n=15). D. NAFLD-related HCC limited to patients with CIRCOM 0 who underwent curative treatment (n=52). E. NAFLD-related HCC limited to patients with CIRCOM 1 or higher who underwent curative treatment (n=69). F. NAFLD-related HCC limited to patients who underwent palliative treatments (n=234).
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