[326] CHRONIC LIVER INJURY IS ASSOCIATED WITH THE UPREGULATION OF THE ACE2-ANGIOTENSIN-(1-7)-Mas AXIS IN THE RAT

Herath, Chandana B; Lubel, JS; Warner, Fiona J.; Jia, Zhuangzhuang; Dean, Rachael; Lew, Rebecca A.; Smith, Ian; Burrell, LM; Angus, PW

doi:10.1016/s0168-8278(07)61924-2

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“…Herath et al [63] examined the expression of these novel components of RAS and the production of Ang-1-7 in the bile duct ligated rats and observed that hepatic ACE2 gene and activity, plasma Ang-1-7 and Mas receptor expression increased after bile duct ligation. Moreover, perfusion experiments confirmed that bile-duct ligated livers produced increased Ang-1-7 from Ang-Ⅱ and this was augmented by ACE inhibition, leading to the conclusion that the RAS activation in chronic liver injury is associated with upregulation of ACE2, Mas and hepatic conversion of Ang-Ⅱ to Ang-1-7.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin-receptor blockers as therapy for mild-to-moderate hypertension-associated non-alcoholic steatohepatitis

Georgescu¹,

Ionescu²,

Niculescu³

et al. 2009

WJG

159

127

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AIM:To evaluate insulin resistance, cytolysis and nonalcoholic steatohepatitis (NASH) score (NAS) using the Kleiner and Brunt criteria in 54 patients with NASH and mild-to-moderate hypertension, treated with telmisartan vs valsartan for 20 mo. METHODS:All patients met the NCEP-ATP Ⅲ criteria for metabolic syndrome. Histology confirmed steatohepatitis, defined as a NAS greater than five up to 3 wk prior inclusion, using the current criteria. Patients with viral hepatitis, chronic alcohol intake, drug abuse or other significant immune or metabolic hepatic pathology were excluded. Subjects were randomly assigned either to the valsartan (V) group (standard dose 80 mg o.d., n = 26), or to the telmisartan (T) group (standard dose 20 mg o.d., n = 28). Treatment had to be taken daily at the same hour with no concomitant medication or alcohol consumption allowed. Neither the patient nor the medical staff was aware of treatment group allocation. Paired liver biopsies obtained at inclusion (visit 1) and end of treatment (EOT) were assessed by a single blinded pathologist, not aware of patient or treatment group. Blood pressure, BMI, ALT, AST, HOMA-IR, plasma triglycerides (TG) and total cholesterol (TC) were evaluated at inclusion and every 4 mo until EOT (visit 6). RESULTS:At EOT we noticed a significant decrease in ALT levels vs inclusion in all patients and this decrease did not differ significantly in group T vs group V. HOMA-IR significantly decreased at EOT vs inclusion in all patients but in group T, the mean HOMA-IR decrease per month was higher than in group V. NAS significantly diminished at EOT in all patients with a higher decrease in group T vs group V. CONCLUSION:Angiotensin receptor blockers seem to be efficient in hypertension-associated NASH. Telmisartan showed a higher efficacy regarding insulin resistance and histology, perhaps because of its specific PPAR-gamma ligand effect.

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Section: Discussionmentioning

confidence: 99%