Combination of branched-chain amino acid and angiotensin‑converting enzyme inhibitor improves liver fibrosis progression in patients with cirrhosis

Yoshiji, Hitoshi; Noguchi, Ryuichi; Ikenaka, Yasuhide; Kaji, Kosuke; Aihara, Yosuke; Douhara, Akitoshi; Yamao, Junichi; Toyohara, Masahisa; Mitoro, Akira; Sawai, Masayoshi; Yoshida, Motoyuki; Morioka, Chie; Fujimoto, Masao; Uemura, Mamoru; Fukui, Hiroshi

doi:10.3892/mmr.2011.676

Cited by 7 publications

(10 citation statements)

References 38 publications

(43 reference statements)

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“…A 48-month follow-up revealed that single treatment with ACEI did not exert inhibitory effects on hepatic fibrosis. 31 In a hepatitis C long-term treatment against cirrhosis trial, continuous ACEIs/ARBs use for 3.5 years did not retard the progression of hepatic fibrosis. 32 Several randomized controlled trials (RCTs) investigated the role of ACEI/ARBs in liver fibrosis with conflicting findings.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic effect of renin angiotensin system inhibitors on liver fibrosis

Zhu

et al. 2016

Renin-Angiotensin-Aldosterone System

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Background and objective:Currently, there is no effective therapy available for liver fibrosis. This study aims to evaluate the efficacy of renin angiotensin system inhibitors on liver fibrosis.Method:Full-text randomized controlled trials in patients with liver fibrosis were identified and included in the meta-analysis. The primary outcome measure was the histological fibrosis score of the liver. Secondary outcome measures included fibrosis area of the liver, serological levels of fibrosis markers, adverse events, and withdrawals.Results:From 6973 non-duplicated entries by systematic search, four randomized controlled trials with 210 patients were identified. The renin angiotensin system inhibitors therapy resulted in a marginally significant reduction in liver fibrosis score (MD = -0.30; 95% CI: -0.62–0.02, p = 0.05) and a significant reduction in liver fibrosis area (MD = -2.36%; 95% CI: -4.22%–-0.50%, p = 0.01) as compared with control. The therapy was well tolerated and there was no significant difference in withdrawals between treatment and control groups (RD = 0.00; 95% CI: -0.06–0.06, p = 0.97).Conclusions:Renin angiotensin system inhibitor therapy results in a reduction in liver fibrosis score and liver fibrosis area in patients with hepatic fibrosis with good safety profile. However, randomized controlled trials of high-quality will clarify the effectiveness of renin angiotensin system inhibitors on liver fibrosis.

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Section: Introductionmentioning

confidence: 99%

Therapeutic effect of renin angiotensin system inhibitors on liver fibrosis

Zhu

et al. 2016

Renin-Angiotensin-Aldosterone System

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“…The precise biological mechanisms underlying the protective effects of ACEIs or ARBs against cancer development is that the angiotensin I–VII levels increase during the inhibition of the ACE–angiotensin II–angiotensin II type 1 receptor (AT1R) axis, resulting in the activation of the Mas receptor and subsequent inhibition of cell proliferation and angiogenesis [ 27 , 28 ]. Moreover, ACEIs or ARBs have been reported to reduce liver fibrosis in human studies [ 29 , 30 ]. Further studies are warranted to determine whether these positive scientific findings can be used to extrapolate the efficacy of ACEIs or ARBs into clinical practice and translate this rationale into effective health intervention for high-risk populations [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

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

Lee

et al. 2018

BMC Cancer

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BackgroundResearch has revealed that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) may prevent cancers such as hepatocellular carcinoma (HCC). The comparative chemopreventive effects of ACEIs and ARBs in high-risk populations with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection have yet to be investigated.MethodsFrom 2005 to 2014, high-risk HBV and HCV cohorts of hypertensive patients without HCC history were recruited from three linked national databases of Taiwan, and were classified into two groups based on the ACEI or ARB exposure within the initial six months after initiating antiviral agent. Intergroup differences in clinical characteristics and duration of drug exposure within study period were evaluated. HCC-free survival was compared using the log-rank test. Multivariate Cox regression including time-dependent variables for the use of ACEIs or ARBs and other medications was applied to adjust for confounders.ResultsAmong the 7724 patients with HBV and 7873 with HCV, 46.3% and 42.5%, respectively, had an initial exposure to ACEIs or ARBs. The median durations of exposure were 36.4 and 38.9 months for the HBV and HCV cohorts, respectively. The median durations of ACEI or ARB use during study period between initial exposure and nonexposure groups were 41.8 vs. 18.3 months and 46.4 vs. 22.7 months for the HBV and HCV cohorts, respectively. No significant difference was observed in HCC risk within 7 years between the initial exposure and non-exposure groups. After adjustment for comorbidities, namely liver cirrhosis, diabetes mellitus (DM), and hyperlipidemia, and medications, namely aspirin, metformin, and statins, the hazard ratios (HRs) for ACEI or ARB exposure for HCC risk were 0.97 (95% confidence interval [CI]: 0.81–1.16) and 0.96 (0.80–1.16) in the HBV and HCV cohorts, respectively. In the HCV cohort, the increased HCC risk was associated with ACEI or ARB use in patients without cirrhosis, DM, and hyperlipidemia (HR: 4.53, 95% CI: 1.46–14.1).ConclusionCompared with other significant risk and protective factors for HCC, ACEI or ARB use in the HBV and HCV cohorts was not associated with adequate protective effectiveness under standard dosages and may not be completely safe.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4292-y) contains supplementary material, which is available to authorized users.

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“…However, it may be difficult to really suppress the cumulative development of HCC with either single agent in clinical practice. Actually, we have shown that the combination treatment with ACE‐I and branched‐chain amino acids (BCAA), which are used for improvement of nutrition in patients with liver cirrhosis, exerted a marked inhibitory effect on rat hepatocarcinogenesis, whereas single treatment with ACE‐I or BCAA alone did not exert any inhibitory effect in clinical practice both in the cumulative recurrence of HCC and liver fibrosis development . Only the combination treatment with ACE‐I and BCAA induced a significant inhibition in clinical practice.…”

Section: Discussionmentioning

confidence: 99%