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Systematic review: Renin-angiotensin system inhibitors in chemoprevention of hepatocellular carcinoma
BACKGROUND: Neoangiogenesis is one of the key pathogenetic mechanisms in hepatocellular carcinoma (HCC). Modulation of the renin-angiotensin system (RAS) by angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) seems to be a possible adjuvant therapy for HCC, due...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Baishideng Publishing Group Inc
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543242/ https://www.ncbi.nlm.nih.gov/pubmed/31171895 http://dx.doi.org/10.3748/wjg.v25.i20.2524 |
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author | Barone, Michele Viggiani, Maria Teresa Losurdo, Giuseppe Principi, Mariabeatrice Leo, Alfredo Di |
author_facet | Barone, Michele Viggiani, Maria Teresa Losurdo, Giuseppe Principi, Mariabeatrice Leo, Alfredo Di |
author_sort | Barone, Michele |
collection | PubMed |
description | BACKGROUND: Neoangiogenesis is one of the key pathogenetic mechanisms in hepatocellular carcinoma (HCC). Modulation of the renin-angiotensin system (RAS) by angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) seems to be a possible adjuvant therapy for HCC, due to the anti-angiogenic and anti-fibrogenic activity of these drugs. AIM: To elucidate the role of ARBs and ACE-Is in HCC. METHODS: We performed an electronic search of the literature using the most accessed online databases (PubMed, Cochrane library, Scopus and Web of Science), entering the query terms "angiotensin-converting enzyme inhibitors" OR "ACE inhibitors" OR "ACE-I" AND "hepatocarcinoma*" OR "hepatocellular carcinoma; moreover "angiotensin II type 1 receptor blockers" OR "ARBs" AND "hepatocarcinoma*" OR "hepatocellular carcinoma". Eligibility criteria were: (1) prospective or retrospective clinical studies; (2) epidemiological studies; and (3) experimental studies conducted in vivo or in vitro. Abstracts, conference papers, and reviews were excluded a priori. We limited our literature search to articles published in English, in peer-reviewed journals. RESULTS: Thirty-one studies were selected. Three interventional studies showed that ACE-Is had a significant protective effect on HCC recurrence only when used in combination with vitamin K or branched chain aminoacids, without a significant increase in overall survival. Of six retrospective observational studies, mainly focused on overall survival, only one demonstrated a prolonged survival in the ACE-Is group, whereas the two that also evaluated tumor recurrence showed conflicting results. All experimental studies displayed beneficial effects of RAS inhibitors on hepatocarcinogenesis. Numerous experimental studies, conducted either on animals and cell cultures, demonstrated the anti-angiogenetic and antifibrotic effect of ACE-Is and ARBs, thanks to the suppression of some cytokines such as vascular endothelial growth factor, hypoxia-inducible factor-1a, transforming growth factor-beta and tumor necrosis factor alpha. All or parts of these mechanisms were demonstrated in rodents developing fewer HCC and preneoplastic lesions after receiving such drugs. CONCLUSION: In humans, RAS inhibitors - alone or in combination - significantly suppressed the cumulative HCC recurrence, without prolonging patient survival, but some limitations intrinsic to these studies prompt further investigations. |
format | Online Article Text |
id | pubmed-6543242 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Baishideng Publishing Group Inc |
record_format | MEDLINE/PubMed |
spelling | pubmed-65432422019-06-06 Systematic review: Renin-angiotensin system inhibitors in chemoprevention of hepatocellular carcinoma Barone, Michele Viggiani, Maria Teresa Losurdo, Giuseppe Principi, Mariabeatrice Leo, Alfredo Di World J Gastroenterol Systematic Reviews BACKGROUND: Neoangiogenesis is one of the key pathogenetic mechanisms in hepatocellular carcinoma (HCC). Modulation of the renin-angiotensin system (RAS) by angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) seems to be a possible adjuvant therapy for HCC, due to the anti-angiogenic and anti-fibrogenic activity of these drugs. AIM: To elucidate the role of ARBs and ACE-Is in HCC. METHODS: We performed an electronic search of the literature using the most accessed online databases (PubMed, Cochrane library, Scopus and Web of Science), entering the query terms "angiotensin-converting enzyme inhibitors" OR "ACE inhibitors" OR "ACE-I" AND "hepatocarcinoma*" OR "hepatocellular carcinoma; moreover "angiotensin II type 1 receptor blockers" OR "ARBs" AND "hepatocarcinoma*" OR "hepatocellular carcinoma". Eligibility criteria were: (1) prospective or retrospective clinical studies; (2) epidemiological studies; and (3) experimental studies conducted in vivo or in vitro. Abstracts, conference papers, and reviews were excluded a priori. We limited our literature search to articles published in English, in peer-reviewed journals. RESULTS: Thirty-one studies were selected. Three interventional studies showed that ACE-Is had a significant protective effect on HCC recurrence only when used in combination with vitamin K or branched chain aminoacids, without a significant increase in overall survival. Of six retrospective observational studies, mainly focused on overall survival, only one demonstrated a prolonged survival in the ACE-Is group, whereas the two that also evaluated tumor recurrence showed conflicting results. All experimental studies displayed beneficial effects of RAS inhibitors on hepatocarcinogenesis. Numerous experimental studies, conducted either on animals and cell cultures, demonstrated the anti-angiogenetic and antifibrotic effect of ACE-Is and ARBs, thanks to the suppression of some cytokines such as vascular endothelial growth factor, hypoxia-inducible factor-1a, transforming growth factor-beta and tumor necrosis factor alpha. All or parts of these mechanisms were demonstrated in rodents developing fewer HCC and preneoplastic lesions after receiving such drugs. CONCLUSION: In humans, RAS inhibitors - alone or in combination - significantly suppressed the cumulative HCC recurrence, without prolonging patient survival, but some limitations intrinsic to these studies prompt further investigations. Baishideng Publishing Group Inc 2019-05-28 2019-05-28 /pmc/articles/PMC6543242/ /pubmed/31171895 http://dx.doi.org/10.3748/wjg.v25.i20.2524 Text en ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ 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. |
spellingShingle | Systematic Reviews Barone, Michele Viggiani, Maria Teresa Losurdo, Giuseppe Principi, Mariabeatrice Leo, Alfredo Di Systematic review: Renin-angiotensin system inhibitors in chemoprevention of hepatocellular carcinoma |
title | Systematic review: Renin-angiotensin system inhibitors in chemoprevention of hepatocellular carcinoma |
title_full | Systematic review: Renin-angiotensin system inhibitors in chemoprevention of hepatocellular carcinoma |
title_fullStr | Systematic review: Renin-angiotensin system inhibitors in chemoprevention of hepatocellular carcinoma |
title_full_unstemmed | Systematic review: Renin-angiotensin system inhibitors in chemoprevention of hepatocellular carcinoma |
title_short | Systematic review: Renin-angiotensin system inhibitors in chemoprevention of hepatocellular carcinoma |
title_sort | systematic review: renin-angiotensin system inhibitors in chemoprevention of hepatocellular carcinoma |
topic | Systematic Reviews |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543242/ https://www.ncbi.nlm.nih.gov/pubmed/31171895 http://dx.doi.org/10.3748/wjg.v25.i20.2524 |
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