Spanu D, Pretta A, Lai E, Persano M, Donisi C, Mariani S, Dubois M, Migliari M, Saba G, Ziranu P, Pusceddu V, Puzzoni M, Astara G, Scartozzi M. Hepatocellular carcinoma and microbiota: Implications for clinical management and treatment. World J Hepatol 2022; 14(7): 1319-1332 [PMID: 36158925 DOI: 10.4254/wjh.v14.i7.1319]
Corresponding Author of This Article
Mario Scartozzi, MD, Chairman, Full Professor, Medical Oncology Unit, University Hospital and University of Cagliari, SS 554 km 4500 Bivio per Sestu, Monserrato 09042, Cagliari, Italy. marioscartozzi@gmail.com
Research Domain of This Article
Oncology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Hepatol. Jul 27, 2022; 14(7): 1319-1332 Published online Jul 27, 2022. doi: 10.4254/wjh.v14.i7.1319
Hepatocellular carcinoma and microbiota: Implications for clinical management and treatment
Dario Spanu, Andrea Pretta, Eleonora Lai, Mara Persano, Clelia Donisi, Stefano Mariani, Marco Dubois, Marco Migliari, Giorgio Saba, Pina Ziranu, Valeria Pusceddu, Marco Puzzoni, Giorgio Astara, Mario Scartozzi
Dario Spanu, Andrea Pretta, Eleonora Lai, Mara Persano, Clelia Donisi, Stefano Mariani, Marco Dubois, Marco Migliari, Giorgio Saba, Pina Ziranu, Valeria Pusceddu, Marco Puzzoni, Giorgio Astara, Mario Scartozzi, Medical Oncology Unit, University Hospital and University of Cagliari, Monserrato 09042, Cagliari, Italy
Author contributions: Spanu D, Pretta A, Lai E, Persano M, Donisi C, Mariani S, Dubois M, Migliari M, Saba G, Ziranu P, Pusceddu V, Puzzoni M, Astara G, Scartozzi M wrote and edited the manuscript; All authors meet conditions 1, 2 and 3.
Conflict-of-interest statement: Eleonora Lai has received advisory board and consultant fees from AstraZeneca and MSD. Mario Scartozzi has received consultant, advisory board and speakers’ bureau fees from Amgen, Sanofi, MSD, EISAI, Merck, Bayer.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mario Scartozzi, MD, Chairman, Full Professor, Medical Oncology Unit, University Hospital and University of Cagliari, SS 554 km 4500 Bivio per Sestu, Monserrato 09042, Cagliari, Italy. marioscartozzi@gmail.com
Received: January 31, 2022 Peer-review started: January 31, 2022 First decision: March 25, 2022 Revised: April 11, 2022 Accepted: July 11, 2022 Article in press: July 11, 2022 Published online: July 27, 2022 Processing time: 177 Days and 0.3 Hours
Abstract
Gut microbiota plays an essential role in host homeostasis. It is involved in several physiological processes such as nutrients digestion and absorption, maintenance of intestinal epithelial barrier integrity and immune system self-tolerance. Especially the gut microbiota is assumed to play a crucial role in many gastrointestinal, pancreatic and liver disorders. Its role in hepatic carcinogenesis is also gaining increasing interest, especially regarding the development of therapeutic strategies. Different studies are highlighting a link between some bacterial strains and liver disease, including hepatocellular carcinoma (HCC). Indeed, HCC represents an interesting field of research in this perspective, due to the gut-liver axis, to the implication of microbiota in the immune system and to the increasing number of immunotherapy agents investigated in this tumour. Thus, the assessment of the role of microbiota in influencing clinical outcome for patients treated with these drugs is becoming of increasing importance. Our review aims to give an overview on the relationship between microbiota and HCC development/progression and treatment. We focus on potential implications on the available treatment strategies and those under study in the various stages of disease. We highlight the pathogenic mechanisms and investigate the underlying molecular pathways involved. Moreover, we investigate the potential prognostic and/or predictive role of microbiota for target therapies, immune checkpoint inhibitors and loco-regional treatment. Finally, given the limitation of current treatments, we analyze the gut microbiota-mediated therapies and its potential options for HCC treatment focusing on fecal microbiota transplantation.
Core Tip: The gut-liver axis plays an important role in the pathogenesis of liver diseases, including hepatocellular carcinoma (HCC). Growing evidence has supported the role of the gut microbiota in the development of HCC and as a prognostic and predictive factor. Thus, manipulation of the gut microbiota might represent a novel way to treat or prevent HCC.
