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

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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.

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Abbreviations

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

BCLC:

Barcelona clinic liver cancer

BMI:

Body mass index

CCR:

Central cancer registry

CDW:

Corporate data warehouse

ECOG:

Eastern cooperative oncology group

 FIB-4:

Fibrosis-4

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

HCV:

Hepatitis C virus

ICD:

International classification of diseases

MDR:

Mortality data repository

NAFLD:

Nonalcoholic fatty liver disease

VA:

Veterans administration

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Acknowledgments

J.C, G.C., X.Y., J.K., F.K. equally contributed to this paper with conception and design of the study, literature review and analysis, statistical analysis and interpretation of the data, drafting and critical revision and editing, and approval of the final version, assisted in the statistical analysis and interpretation of the data. All authors (J.C., G.C., X.Y., A.R., Y.N., H.E., J.K., F.K.) assisted in manuscript preparation and critical appraisal of the manuscript.

Funding

This material is based on work supported by a Cancer Prevention & Research Institute of Texas grant (RP150587). This work is also supported by the National Cancer Institute’s (NCI) U01 CA230997 and P30DK056338.

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    Authors and Affiliations

    1. Department of Medicine, Baylor College of Medicine, Houston, TX, USA

      Jinna Chu

    2. Liver Center, Division of Abdominal Transplantation, Michael E DeBakey Department of General Surgery, Baylor College of Medicine, Houston, TX, USA

      George Cholankeril & Abbas Rana

    3. Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, 2002 Holcombe Boulevard (152), Houston, TX, USA

      George Cholankeril, Yamini Natarajan, Hashem B. El-Serag & Fasiha Kanwal

    4. Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA

      Xian Yu, Yamini Natarajan, Hashem B. El-Serag, Jennifer Kramer & Fasiha Kanwal

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    Chu, J., Cholankeril, G., Yu, X. et al. Clinical Course and Outcomes of Patients with Nonalcoholic Fatty Liver Disease-Related Hepatocellular Cancer (NAFLD-HCC) . Dig Dis Sci 68, 1060–1070 (2023). https://doi.org/10.1007/s10620-022-07565-x

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