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Review
. 2023 Mar 10:10:413-428.
doi: 10.2147/JHC.S347959. eCollection 2023.

Perspectives on the Underlying Etiology of HCC and Its Effects on Treatment Outcomes

Takanori Ito  1 , Mindie H Nguyen  2   3
Affiliations
Review

Perspectives on the Underlying Etiology of HCC and Its Effects on Treatment Outcomes

Takanori Ito et al. J Hepatocell Carcinoma. .

Abstract

Hepatocellular carcinoma (HCC) continues to be a serious medical problem with poor prognosis worldwide. The distribution of the major etiologies of HCC is changing due to the progress of anti-viral treatments, including hepatitis B virus (HBV) suppression by nucleoside/nucleotide analogues (NAs) and increased sustained virologic response (SVR) rates by direct-acting antivirals (DAAs) for hepatitis C virus (HCV), as well as the rising trend of nonviral liver disease. Although viral hepatitis remains the most common cause of HCC, non-alcoholic liver disease (NAFLD) with metabolic syndrome and alcohol-associated liver disease (ALD) are increasing. Effective and well-tolerated NAs treatment can slow the disease progression of chronic HBV infection to cirrhosis, end-stage liver disease, and reduce HCC risk. Treatment with NAs is also associated with significant improvement in the long-term survival of patients with HBV infection who already have HCC. DAAs have achieved viral elimination in almost all patients with HCV without significant adverse events, even in patients with decompensated liver cirrhosis and HCC. Similarly, DAA therapy can reduce disease progression, liver and non-liver complications, and improve the long-term survival of patients with chronic HCV infection with or without HCC. Meanwhile, NAFLD is a rapidly increasing cause of HCC along with the epidemics of obesity and type 2 diabetes globally. NAFLD-related HCC can occur in patients without cirrhosis and is known to have a lower survival rate than viral hepatitis-related HCC. Since there is currently no specific pharmacotherapy effective for NAFLD, lifestyle modification and prevention of complications are important to improve prognosis. Additionally, ALD is the second fastest-growing cause of HCC-related deaths, especially with an accelerated trend since the COVID-19 pandemic. This review provides an overview of the epidemiologic trends in the etiologies of HCC, and the progress of treatments for each etiology and the impact on outcome in the patients with HCC.

Keywords: alcohol-associated liver disease; etiology; hepatitis B; hepatitis C; hepatocellular carcinoma; non-alcoholic fatty liver disease.

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Conflict of interest statement

MHN received Research support from Pfizer, Enanta, CurveBio, Delfi Biotech, Innogen, Astra Zeneca, Gilead, Exact Sciences, Vir Biotech, Helio Health, National Cancer Institute, Glycotest, and B.K. Kee Foundation; also Consulting and/or Advisory Board for Intercept, Exact Science, Gilead, GSK, Eli Lilly, Laboratory of Advanced Medicine, and Janssen outside the submitted work. TI received speaker’s fees from Chugai Pharmaceutical Co., Ltd outside the submitted work. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
The etiology of Liver cancer diagnosed as new cases based on GLOBOCAN 2020.Reproduced from GLOBOCAN 2020. Available from: https://gco.iarc.fr/. East Asia includes China, Japan, Republic of Korea, Democratic People’s Republic of Korea, and Mongolia. North America includes USA and Canada. Western Europe includes Austria, Belgium, France, Germany, Luxembourg, Switzerland, and Netherlands.
Figure 2
Figure 2
Sustained virologic response (SVR) rate with interferon-free direct-acting antivirals (DAAs) in hepatitis C patients with or without cirrhosis / HCC.
Figure 3
Figure 3
Risk factors and prevention for HCC development in patients with NAFLD.
See this image and copyright information in PMC

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No external funding to disclose.