Angiotensin Blockade Does Not Affect Fibrosis Progression in Recurrent Hepatitis C After Liver Transplantation

Guillaud, Olivier; Gurram, Krishna C.; Puglia, Marco; Lilly, Les; Adeyi, Oyedele; Renner, Eberhard L.; Selzner, Nazia

doi:10.1016/j.transproceed.2013.01.067

Cited by 9 publications

(18 citation statements)

References 34 publications

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“…Angiotensin-converting enzyme inhibitors, which have been shown to exert antifibrotic properties in rodent models of liver fibrosis 32 have no significant effects in humans. [33][34][35] Interestingly, LOS had no effects in our hands, thus confirming the marked relevance of this model.…”

Section: Discussionsupporting

confidence: 80%

Development of an in vitro model to test antifibrotic drugs on primary human liver myofibroblasts

Aoudjehane¹,

Boëlle²,

Bisch³

et al. 2016

Laboratory Investigation

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We have developed a culture model to assess antifibrotic drugs using normal human liver myofibroblasts (HLMFs) obtained from 31 subjects. Activation was evaluated in terms of α-smooth muscle actin (α-SMA) and collagen 1 (Coll1) expression using RT-PCR, and proliferation as the uptake of 5-ethynil-2′-deoxyuridine. Under analysis of variance, between-subject differences accounted for 70% of all variability and inter-experiment differences for 30%. The sensitivity of the model was determined by quantifying the effects in terms of relative expression, which were 0.74 ± 0.03 for cyclosporine A (CsA) and 2.4 ± 0.10 for transforming growth factor-beta (TGF-β) (Po0.0001 vs no treatment) for α-SMA expression. Inter-subject variations in α-SMA and Coll1 expression enabled the classification of subjects as potentially low or high fibrosers. Finally, we observed that pirfenidone (which has beneficial effects in vivo) significantly reduced the expressions of α-SMA and Coll1, whereas the angiotensin-converting enzyme inhibitor losartan (which has no effect in vivo) had no significant effect. Our model may thus detect the antifibrotic properties of drugs. Antifibrotic drugs with promising clinical relevance could possibly be selected using a bank of HLMFs from high fibrosers.

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Section: Discussionsupporting

confidence: 80%

Development of an in vitro model to test antifibrotic drugs on primary human liver myofibroblasts

Aoudjehane¹,

Boëlle²,

Bisch³

et al. 2016

Laboratory Investigation

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“…Abstracts and full texts were obtained for articles to determine eligibility for inclusion. Fifteen papers were included in this rev iew [27][28][29][30][31][32][37][38][39][40][41][42][43][44][45] (Table 1) and four RCTs 30,40,43,44 (Table 2) were identified and included in the meta-analysis (Figure 1). The reasons for excluding the 11 studies from meta-analysis are listed in Table 3.…”

Section: Searchmentioning

confidence: 99%

“…Yoshiji H, 2012 31 The treated group was given both IFN and perindopril while the controlled group treated nothing. Guillaud O, 2013 45 Not RCT. The results were demonstrated by change of median fibrosis score which could not be calculated with other studies in the meta-analysis.…”

Section: First Author Yearmentioning

confidence: 99%

Therapeutic effect of renin angiotensin system inhibitors on liver fibrosis

Zhu

et al. 2016

J Renin Angiotensin Aldosterone Syst

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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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“…Some isolated data suggested that angiotensin blockade inhibits fibrosis progression in recurrent HCV post-liver transplantation ( 28 ). Results of our research showed elevated values of serum activity of ACE in group of respondents with chronic hepatitis C relative to control group of respondents who did not have manifestations of liver disease.…”

Section: Discussionmentioning

confidence: 99%

Effect of Antiviral Therapy on Serum Activity of Angiotensin Converting Enzyme in Patients with Chronic Hepatitis C

Husić-Selimović¹,

Sofić²,

Huskić³

et al. 2016

Med Arh

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Introduction:Renin-angiotenzin system (RAS) is frequently activated in patients with chronic liver disease. Angiotenzin - II (AT-II), produced by angiotenzin converting enzyme (ACE), has many physiological effects, including an important role in liver fibrogenesis. Combined antiviral therapy with PEG-IFN and ribavirin besides its antiviral effect also leads to a reduction in liver parenchyma fibrosis.Aim of the study:Determining the value of ACE in serum of patients with chronic hepatitis C before and after combined antiviral therapy, as well as the value of ACE activities in sera of the control group.Materials and methods:We studied 50 patients treated at Gastroenterohepatology Department, in the time-period of four years. Value of ACE in serum was determined by Olympus AU 400 device, with application of kit “Infinity TN ACE Liquid Stable Reagent”. HCV RNA levels in sera were measured by real time PCR. HCV RNA test was performed with modular analysis of AMPLICOR and COBAS AMPLICOR HCV MONITOR test v2.0, which has proved infection and was used for quantification of the viruses and monitoring of the patients’ response to therapy. Liver histology was evaluated in accordance with the level of necroinflammation activity and stage of fibrosis.Results:Serum activities of ACE in chronic hepatitis C patients is statistically higher than the values in the control group (p=0.02). Antiviral therapy in chronic hepatitis C patients statistically decreases serum activities of ACE (p= 0.02) and indirectly affects fibrogenesis of the liver parenchyma. Correlation between ACE and ALT activity after the therapy was proved (0.3934).Conclusion:Our findings suggest that the activity of ACE in serum is a good indirect parameter of the liver damage, and could be used as an indirect prognostic factor of the level of liver parenchyma damage. Serum activity of ACE can be used as a parameter for non-invasive assessment of intensity of liver damage.

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Angiotensin Blockade Does Not Affect Fibrosis Progression in Recurrent Hepatitis C After Liver Transplantation

Cited by 9 publications

References 34 publications

Development of an in vitro model to test antifibrotic drugs on primary human liver myofibroblasts

Development of an in vitro model to test antifibrotic drugs on primary human liver myofibroblasts

Therapeutic effect of renin angiotensin system inhibitors on liver fibrosis

Effect of Antiviral Therapy on Serum Activity of Angiotensin Converting Enzyme in Patients with Chronic Hepatitis C

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