**1. Introduction**

Hepatocellular carcinoma (HCC) is the second most common cancer-related cause of death worldwide, and, both domestically and internationally, incidence rates are rising. HCC is globally caused by two conditions: alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) [1,2]. Every year, approximately 750,000 novel instances of liver cancer are recorded worldwide. According to population-based interventions, the liver cancer proliferation rate continues to be close to death, meaning that the majority of patients who develop HCC die from it. According to data, the five-year survival rates in the United States have increased slightly to approximately 26%. This expansion is thought to be a result of better surveillance in high-risk patients who can be identified (those who have hepatitis B and C viruses), as well as clinical intervention (resection or transplant) for patients with early-stage disease [3].

Guidelines have been published by a number of organizations, including the National Comprehensive Cancer Network (NCCN), the European Association for the Study of the Liver (EASL), and the American Association for the Study of Liver Disease (AASLD), to normalize the approaches to judgment and treatment [4–6]. The earlier that HCC is detected and treated, the better the prognosis, as is true for the majority of disease processes. The observation of patients who are known to be at a high risk provides the best opportunity for an early diagnosis. Both people who have cirrhosis from any cause and hepatitis B carriers fall under this category [5]. According to the 2012 NCCN guidelines, high-risk patients should receive liver ultrasonography and AFP screenings every six to twelve months. A hepatic nodule larger than 1 cm accompanied by an increasing AFP should be evaluated.

**Citation:** Ganesan, R.; Yoon, S.J.; Suk, K.T. Microbiome and Metabolomics in Liver Cancer: Scientific Technology. *Int. J. Mol. Sci.* **2023**, *24*, 537. https:// doi.org/10.3390/ijms24010537

Academic Editor: Maria Teresa Mascellino

Received: 28 September 2022 Revised: 12 December 2022 Accepted: 19 December 2022 Published: 28 December 2022

**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

Over the past ten years, the criteria for the diagnosis of HCC have changed. The AASLD, NCCN, and EASL working groups have developed imaging criteria that effectively predict malignancy so as to reduce the necessity for a percutaneous biopsy and its accompanying risks in patients with underlying liver conditions (tract seeding, hemorrhage, etc.) [4,6]. On contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) images, early arterial enhancement and venous phase washout, which are related to the fact that these hypervascular lesions are primarily supplied by branches of the hepatic artery, are imaging markers of HCC. In the context of chronic liver disease, HCC refers to tumors larger than 1 cm in size that have certain imaging characteristics on triple-phase CT or contrast-enhanced MRI.

*Escherichia, Pseudomonas, Lactobacillus* and other gut bacteria are crucial to the 'gut origin of sepsis' theory. The dominant signs of the gut microbial imbalance are significant increases in gram-negative bacteria such as *Escherichia coli* and the *Atopobium cluster,* which includes the genera *Atopobium, Coriobacterium, Collinsella,* and *Eggerthella,* as well as significant decreases in *Bifidobacterium, Enterococcus,* and *Lactobacillus* species [7]. Moreover, it was discovered that *Fusobacterium nucleatum* was prevalent and abundant in patients with cancer [8].

The previous recommendations required typical enhancement on both imaging modalities (CT and MRI) for lesions between 1 cm and 2 cm to define HCC. Although the imaging standards have changed, only lesions larger than 2 cm and exhibiting typical enhancement qualify as Model for End-Stage Liver Disease (MELD) exemption points for liver transplantation. To more accurately characterize lesions that do not fulfill these criteria on standard arterial and venous phase imaging alone, some facilities have utilized MRI with new contrast agents, such as gadoxetic acid. On T1-weighted (hepatocyte phase) imaging, lesions that could be HCC are darker than the surrounding liver [9]. Despite indications of a better diagnosis accuracy, gadoxetic acid-enhanced MR imaging has not yet altered the paradigm used to determine therapy eligibility. Thus, despite an increased imaging specificity, gadoxetic acid-enhanced MR imaging has not yet altered the diagnostic pattern used to establish clinical prevention [10].
