Therapeutic effect of renin angiotensin system inhibitors on liver fibrosis

Abstract

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.

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

“…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 ].…”

Captopril mitigates splenomegaly and myelofibrosis in the Gata1low murine model of myelofibrosis

“…Thus, we hypothesized that inhibition of fibrotic signalling pathways would result in a reduction in bone marrow abnormalities of MF, possibly mitigating the disease. ACE and Ang II are believed to play a causative role in fibrosis of a number of tissues, and captopril and other ACE inhibitors or angiotensin receptor blockers (ARBs) were demonstrated to reduce fibrotic remodelling in a number of rodent models of fibrosis in tissues including kidney, lung, skin, liver and heart . In many of these studies, prevention of fibrosis by ACE inhibitors or ARBs was accompanied by reduced levels of myofibroblasts, attenuated collagen production, decreased inflammation and the preservation of normal tissue function and structure.…”

Role of the renin-angiotensin system in hepatic fibrosis and portal hypertension

“…The antifibrotic effects of RAS antagonists, including ACEis, ARBs, and AAs, have been evaluated in several clinical studies [ 82 , 86 - 94 ]. The benefits of candesartan, an ARB, in patients with compensated alcoholic liver fibrosis were first reported as part of a well-established open-label randomized controlled trial (RCT) [ 82 ].…”