Comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in chemoprevention of hepatocellular carcinoma: a nationwide high-risk cohort study

Ho, Cheng‐Maw; Lee, Chih Hsin; Lee, Ming Chia; Zhang, Jun Fu; Wang, Jann‐Yuan; Hu, Rey‐Heng; Lee, Po‐Huang

doi:10.1186/s12885-018-4292-y

Cited by 25 publications

(30 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is interesting, however, to note that the HCC risk among participants receiving anti-hypertensive agents was 1.94fold higher than that among those not receiving such agents (95% CI = 1.45-2.6, p < 0.001; Table 2). Although our present findings cannot explain this conflict, Ho et al [24] found that the use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers was associated with higher HCC occurrence in patient subgroups consisting of patients with no cirrhosis, no DM, and no hyperlipidemia. This issue requires further study in the future.…”

Section: Discussioncontrasting

confidence: 82%

Aspirin decreases hepatocellular carcinoma risk in hepatitis C virus carriers: a nationwide cohort study

et al. 2020

View full text Add to dashboard Cite

Background: Aspirin has been found to lower the occurrence rates of some cancers through the inhibition of the cyclooxygenase enzyme. For example, there is a well-known association between aspirin use and the occurrence of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV) carriers. However, the association, if any, between aspirin use and HCC in hepatitis C virus (HCV) carriers is unknown. Therefore, this study compared the occurrence rates of HCC in HCV carriers treated with or without aspirin. Methods: The participants in this retrospective cohort study consisted of people newly diagnosed with HCV in Taiwan from 2000 to 2012. Those who were treated with aspirin were defined as the control group, whereas those not treated with aspirin were defined as the comparison cohort. We used a 1:1 propensity score matching by age, sex, comorbidities, drugs, diagnosis year, and index year with covariate assessment. Results: Our study sample consisted of 2980 aspirin-treated HCV carriers and 7771 non-aspirin-treated HCV carriers. After propensity score matching, each cohort consisted of 1911 HCV carriers. The adjusted hazard ratio (aHR) of HCC incidence in the aspirin users (aHR = 0.56, 95% CI = 0.43-0.72, p < 0.001) was significantly lower than that in the non-aspirin users. A Kaplan-Meier analysis showed that among the HCV carriers, the aspirin users had a lower cumulative incidence rate of HCC over the first 10 years of aspirin treatment (p < 0.0001). Conclusions: The HCC incidence rate was lower in the aspirin-using HCV carriers than in the non-aspirin-using HCV carriers, indicating that the effects of aspirin might occur through inhibition of the cyclooxygenase enzyme pathway. Moreover, protection from HCC was provided by less than a year of aspirin treatment, while treatment with aspirin for 1 to 2 years exhibited the greatest protective effect. We therefore encourage aspirin treatment to prevent HCC in HCV carriers.

show abstract

Section: Discussioncontrasting

confidence: 82%

Aspirin decreases hepatocellular carcinoma risk in hepatitis C virus carriers: a nationwide cohort study

et al. 2020

View full text Add to dashboard Cite

show abstract

“…It is interesting, however, to note that the HCC risk among participants receiving anti-hypertensive agents was 1.94-fold higher than that among those not receiving such agents (95% CI = 1.45-2.6, p < 0.001; Table 2). Although our present findings cannot explain this conflict, Ho et al [24] found that the use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers was associated with higher HCC occurrence in patient subgroups consisting of patients with no cirrhosis, no DM, and no hyperlipidemia. This issue requires further study in the future.…”

Section: Discussioncontrasting

confidence: 82%

Aspirin Decreases Hepatocellular Carcinoma Risk in Hepatitis C Virus Carriers: A Nationwide Cohort Study

Liao

Hsu

Wang

et al. 2019

Preprint

View full text Add to dashboard Cite

Background Aspirin has been found to lower the occurrence rates of some cancers through the inhibition of the cyclooxygenase enzyme. For example, there is a well-known association between aspirin use and the occurrence of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV) carriers. However, the association, if any, between aspirin use and HCC in hepatitis C virus (HCV) carriers is unknown. Therefore, this study compared the occurrence rates of HCC in HCV carriers treated with or without aspirin. Methods The participants in this retrospective cohort study consisted of people newly diagnosed with HCV in Taiwan from 2000 to 2012. Those who were treated with aspirin were defined as the control group, whereas those not treated with aspirin were defined as the comparison cohort. We used a 1:1 propensity score matching by age, sex, comorbidities, drugs, diagnosis year, and index year with covariate assessment. Results Our study sample consisted of 2980 aspirin-treated HCV carriers and 7771 non-aspirin-treated HCV carriers. After propensity score matching, each cohort consisted of 1911 HCV carriers. The adjusted hazard ratio (aHR) of HCC incidence in the aspirin users (aHR=0.56, 95% CI=0.43-0.72, p < 0.001 ) was significantly lower than that in the non-aspirin users. A Kaplan-Meier analysis showed that among the HCV carriers, the aspirin users had a lower cumulative incidence rate of HCC over the first 10 years of aspirin treatment ( p < 0.0001 ). Conclusions The HCC incidence rate was lower in the aspirin-using HCV carriers than in the non- aspirin-using HCV carriers, indicating that the effects of aspirin might occur through inhibition of the cyclooxygenase enzyme pathway. Moreover, protection from HCC was provided by less than a year of aspirin treatment, while treatment with aspirin for 1 to 2 years exhibited the greatest protective effect. We therefore encourage aspirin treatment to prevent HCC in HCV carriers.

show abstract

“…Six more recent retrospective observational studies evaluated the effect of ACE-Is or ARBs on overall survival (OS) and/or time to recurrence in patients who underwent different HCC treatments (Table 1). Ho et al[16] evaluated the effect of ACE-I or ARB exposure within the first six months after initiating antiviral agents in a high-risk HBV and HCV large cohorts of patients and did not find any protective effect of these drugs on HCC development adjusted for potential confounders. Surprisingly, in HCV patients without cirrhosis, diabetes, and hyperlipidemia, they found an increased HCC risk associated with ACE-I or ARB use in (HR = 4.53, 95%CI: 1.46-14.1).…”

Section: Resultsmentioning

confidence: 99%

“…The more recent human studies are all observational retrospective cohort or case-control studies[7,16-21]. All these studies evaluated the effect of ACEIs and/or ARBs on overall survival.…”

Section: Discussionmentioning

confidence: 99%

Systematic review: Renin-angiotensin system inhibitors in chemoprevention of hepatocellular carcinoma

Barone¹,

Viggiani²,

Losurdo³

et al. 2019

WJG

View full text Add to dashboard Cite

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.

show abstract

Comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in chemoprevention of hepatocellular carcinoma: a nationwide high-risk cohort study

Cited by 25 publications

References 50 publications

Aspirin decreases hepatocellular carcinoma risk in hepatitis C virus carriers: a nationwide cohort study

Aspirin decreases hepatocellular carcinoma risk in hepatitis C virus carriers: a nationwide cohort study

Aspirin Decreases Hepatocellular Carcinoma Risk in Hepatitis C Virus Carriers: A Nationwide Cohort Study

Systematic review: Renin-angiotensin system inhibitors in chemoprevention of hepatocellular carcinoma

Contact Info

Product

Resources

About