Beyond the Liver: A Comprehensive Review of Strategies to Prevent Hepatocellular Carcinoma

Abstract

Background/objectives: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, primarily developing in the context of chronic liver disease. Traditional prevention has focused on liver-specific interventions like antiviral therapies and surveillance. However, extrahepatic factors also significantly contribute to HCC risk. This review explores comprehensive strategies for HCC prevention, including both hepatic and extrahepatic factors.

Methods: An extensive literature search of peer-reviewed articles up to October 2024 was conducted, focusing on studies addressing HCC prevention strategies. Studies that focused on both hepatic and extrahepatic factors were included. Data were extracted and synthesized to provide an overview of current prevention strategies and their effectiveness in reducing HCC incidence.

Results: Hepatitis B vaccination and antiviral treatments for hepatitis B and C significantly reduce HCC incidence. Lifestyle modifications-such as reducing alcohol consumption, maintaining a healthy weight through diet and exercise, and smoking cessation-are crucial in lowering HCC risk. Environmental measures to limit exposure to aflatoxins and other hazards also contribute to prevention. Regular surveillance of high-risk groups enables early detection and improves survival rates. Emerging strategies like immunotherapy and gene therapy show potential for further reducing HCC risk.

Conclusions: A comprehensive approach combining medical interventions, lifestyle changes, and environmental controls is essential for effectively decreasing HCC incidence globally. Implementing these combined measures could significantly reduce the global burden of HCC.

Keywords: hepatocellular carcinoma (HCC); liver cancer; prevention; surveillance.

Figure 1

Summary of the mechanisms of action of SGLT2 inhibitors and GLP-1 analogs for HCC prevention. AMPK—5′-adenosine monophosphate-activated protein kinase; cAMP—cyclic adenosine monophosphate; GLP-1—glucagon-like peptide-1; HCC—hepatocellular carcinoma; IFN-γ—interferon gamma; JNK—c-Jun N-terminal kinase; MASLD—metabolic dysfunction-associated steatotic liver disease; PKA—protein kinase A; PLC—phospholipase C; SGLT2i—sodium-glucose cotransporter 2 inhibitor; TGF-β1—transforming growth factor beta 1.

Figure 2

Summary of overall strategies for HCC prevention. HBV—hepatitis B virus; HCV—hepatitis C virus; HCC—hepatocellular carcinoma; IFN—interferon; DAA—direct-acting antiviral; GLP-1—glucagon-like peptide-1; SGLT2—sodium-glucose cotransporter 2; ACE—angiotensin-converting enzyme; ARB—angiotensin II receptor blocker; AFP—alpha-fetoprotein; DCP—des-gamma-carboxy prothrombin; REACH-B—risk estimation for hepatocellular carcinoma in chronic hepatitis B; PAGE-B—platelet, age, gender-HBV score; aMAP—age, male gender, albumin-bilirubin score, and platelet count; GALAD—gender, age, AFP, AFP-L3, and DCP; GAAD—Gender, Age, AFP, and AFP-L3.