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Review
. 2021 Aug;6(4):100185.
doi: 10.1016/j.esmoop.2021.100185. Epub 2021 Jun 15.

Cancer and hepatic steatosis

R Paternostro  1 , W Sieghart  1 , M Trauner  1 , M Pinter  2
Affiliations
Review

Cancer and hepatic steatosis

R Paternostro et al. ESMO Open. 2021 Aug.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent and increasing liver disease, which encompasses a variety of liver diseases of different severity. NAFLD can lead to liver cirrhosis with all its complications as well as hepatocellular carcinoma (HCC). Steatosis of the liver is not only related to obesity and other metabolic risk factors, but can also be caused by several drugs, including certain cytotoxic chemotherapeutic agents. In patients undergoing liver surgery, hepatic steatosis is associated with an increased risk of post-operative morbidity and mortality. This review paper summarizes implications of hepatic steatosis on the management of patients with cancer. Specifically, we discuss the epidemiological trends, pathophysiological mechanisms, and management of NAFLD, and its role as a leading cause of liver cancer. We elaborate on factors promoting immunosuppression in patients with NAFLD-related HCC and how this may affect the efficacy of immunotherapy. We also summarize the mechanisms and clinical course of chemotherapy-induced acute steatohepatitis (CASH) and its implications on cancer treatment, especially in patients undergoing liver resection.

Keywords: cancer; chemotherapy-induced steatohepatitis; hepatic steatosis; hepatocellular carcinoma; non-alcoholic fatty liver disease.

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Conflict of interest statement

Disclosure MT received speaker fees from Bristol-Myers Squibb (BMS), Falk Foundation, Gilead, Intercept, and Merck Sharp & Dohme (MSD); advisory board fees from Albireo, Boehringer Ingelheim, BiomX, Falk Pharma GmbH, Genfitt, Gilead, Intercept, Janssen, MSD, Novartis, Phenex, Regulus and Shire; travel grants from AbbVie, Falk, Gilead, and Intercept; and research grants from Albireo, CymaBay, Falk, Gilead, Intercept, MSD, and Takeda. He is also co-inventor of patents on the medical use of norUDCA filed by the Medical University of Graz. MP is an investigator for Bayer, BMS, Lilly, and Roche; he received speaker honoraria from Bayer, BMS, Eisai, Lilly, and MSD; he is a consultant for Bayer, BMS, Ipsen, Eisai, Lilly, MSD, and Roche; he received travel support from Bayer and BMS. All other authors have declared no conflicts of interest.

Figures

Figure 1
Figure 1
Surveillance algorithm for hepatocellular carcinoma in patients with non-alcoholic fatty liver disease. BCLC, Barcelona Clinic Liver Cancer; CT, computed tomography scan; FIB-4, Fibrosis-4; HCC, hepatocellular carcinoma; MRE, magnetic resonance elastography; MRI, magnetic resonance imaging; NAFLD, non-alcoholic fatty liver disease; VCTE, vibration controlled transient elastography.
Figure 2
Figure 2
Factors promoting immunosuppression in patients with non-alcoholic fatty liver disease. NAFLD impacts the liver immune microenvironment. While the number of CD4+ T cells with antitumor functions is reduced, CD8+ T cells, NKT cells, and macrophages with tumor-promoting properties expand in NAFLD. Gut dysbiosis in NAFLD-related hepatocellular carcinoma promotes peripheral immunosuppression, characterized by reduced numbers of CD8+ T cells and antigen-presenting cells and expansion of regulatory T cells. Obesity is a risk factor for NAFLD and thus frequently present in patients with NAFLD. Obesity impairs the function of CD8+ T cells and enhances the immunosuppressive potency of tumor-infiltrating MDSCs. APCs, antigen-presenting cells; HCC, hepatocellular carcinoma; MDSCs, myeloid-derived suppressor cells; NAFLD, non-alcoholic fatty liver disease; NKT cells, natural killer T cells; Tregs, regulatory T cells.
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