Abstract | BACKGROUND: 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.
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Authors | Michele Barone, Maria Teresa Viggiani, Giuseppe Losurdo, Mariabeatrice Principi, Alfredo Di Leo |
Journal | World journal of gastroenterology
(World J Gastroenterol)
Vol. 25
Issue 20
Pg. 2524-2538
(May 28 2019)
ISSN: 2219-2840 [Electronic] United States |
PMID | 31171895
(Publication Type: Journal Article, Systematic Review)
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Chemical References |
- Angiotensin Receptor Antagonists
- Angiotensin-Converting Enzyme Inhibitors
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Topics |
- Angiotensin Receptor Antagonists
(pharmacology, therapeutic use)
- Angiotensin-Converting Enzyme Inhibitors
(pharmacology, therapeutic use)
- Animals
- Carcinoma, Hepatocellular
(blood supply, mortality, therapy)
- Chemotherapy, Adjuvant
(methods)
- Disease Models, Animal
- Drug Therapy, Combination
(methods)
- Hepatectomy
- Humans
- Liver
(blood supply, drug effects, surgery)
- Liver Neoplasms
(blood supply, mortality, therapy)
- Neoplasm Recurrence, Local
(epidemiology, prevention & control)
- Neovascularization, Pathologic
(prevention & control)
- Observational Studies as Topic
- Randomized Controlled Trials as Topic
- Renin-Angiotensin System
(drug effects)
- Treatment Outcome
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