Caffeine in Hepatocellular Carcinoma: Cellular Assays, Animal Experiments, and Epidemiological Investigation

Abstract

The use of caffeine in treating various liver diseases has made substantial progress in the past decade owing to advances in science, technology, and medicine. However, whether caffeine has a preventive effect on hepatocellular carcinoma (HCC) and its mechanism are still worth further investigation. In this review, we summarize and analyze the efficacy and safety of caffeine in the prevention of HCC. We conducted a review of articles published in PubMed and Web of Science in the past 2 decades until December 6, 2023, which were searched for using the terms “Caffeine” and “Hepatocellular Carcinoma.” Studies have found that coffee intake is negatively correlated with HCC risk, especially caffeinated coffee. Recent studies have found that caffeine has beneficial effects on liver health, decreasing levels of enzymes responsible for liver damaging and slowing the progression of hepatic fibrosis and cirrhosis. Caffeine also acts against liver fibrosis through adenosine receptors (ARs), which promote tissue remodeling by inducing fibrin and collagen production. Additionally, new studies have found that moderate consumption of caffeinated beverages can decrease various the levels of various collagens in patients with chronic hepatitis C. Furthermore, polyphenolic compounds in coffee can improve fat homeostasis, reduce oxidative stress, and prevent liver steatosis and fibrosis. Moreover, many in vitro studies have shown that caffeine can protect liver cells and inhibit the activation and proliferation of hepatic stellate cells. Taken together, we describe the benefits of caffeine for liver health and highlight its potential values as a drug to prevent various hepatic diseases. As a protective agent of liver inflammation, non-selective AR inhibitor caffeine can inhibit the growth of HCC cells by inhibiting adenosine and AR binding to initiate immune response, providing a basis for the future development of caffeine as an adjuvant drug against HCC.

Keywords:

• coffee
• caffeine
• hepatocellular carcinoma
• adenosine
• adenosine receptor

Data Sharing Statement

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Acknowledgments

We thank LetPub for its linguistic assistance during the preparation of this manuscript.

Author Contributions

All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors have no conflicts of interest in this work.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China (Grant 82003849), the National Natural Science Foundation of China (Grant 81970518), Hefei Municipal Natural Science Foundation (Grant 2021012), the Special Doctoral Fund of Hefei Hospital Affiliated to Anhui Medical University (the 2nd People’s Hospital of Hefei) (Grant 2020BSZX04), the Key Scientific Research Foundation of the Education Department of the Province Anhui (Grant 2023AH052595), and the Scientific Research Projects of Health Commission of Anhui Province in 2023 (Grant AHWJ2023BAc20099).