RESUMO
AIM: To investigate the efficacy of angiotensin II receptor antagonist on hepatic stellate cells (HSCs) activation in the patients with non-alcoholic steatohepatitis (NASH). METHODS: Seven patients with NASH were prescribed losartan, a selective angiotensin II type 1 receptor antagonist (50 mg/d) for 48 wk. Liver biopsies were performed both at the entry and end of the study in all patients. Quiescent and activated HSCs were identified by double immunostaining using anti-p75 and -smooth muscle actin antibodies, and the number of each phenotype was counted. Similarly, the liver specimens obtained from the eight patients with non-alcoholic fatty liver (NAFL) were also examined as controls. RESULTS: In NASH hepatic tissues, activated HSCs were dominantly distributed as compared with those in NAFL. The 48-wk losartan treatment induced a remarkable decrease in activated HSCs and a mild increase in quiescent phenotypes. CONCLUSION: Our data suggest the crucial involvement of HSCs in anti-fibrotic effect of angiotensin II receptor antagonist on patients with NASH.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Fígado Gorduroso/tratamento farmacológico , Cirrose Hepática/prevenção & controle , Fígado/efeitos dos fármacos , Losartan/farmacologia , Adulto , Idoso , Fígado Gorduroso/patologia , Feminino , Humanos , Fígado/citologia , Losartan/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Transformador beta/sangue , Fator de Crescimento Transformador beta1RESUMO
The therapeutic efficacy of angiotensin II receptor antagonist, losartan, was studied in patients with nonalcoholic steatohepatitis (NASH). Seven patients with both NASH and hypertension were treated with losartan (50 mg/d) for 48 weeks. Treatment with losartan resulted in a significant decrease in blood markers of hepatic fibrosis, plasma TGF-beta1 and serum ferritin concentration concurrently with an improvement in serum aminotransferase levels. Histological assessment showed improvement of hepatic necroinflammation in five patients, reduction of hepatic fibrosis in four patients, and disappearance of iron deposition in two patients. No side effect of treatment was noted at any time during the study. In conclusion, the present data raise the possibility that an angiotensin II receptor antagonist may be therapeutically efficacious for NASH.
