Impact of hepatic immunoreactivity of angiotensin-converting enzyme 2 on liver fibrosis due to non-alcoholic steatohepatitis.

Background: We aimed to evaluate the hepatic immunoreactivity of angiotensin-converting enzyme 2 (ACE2) in non-alcoholic steatohepatitis (NASH) patients, elucidate its association with the clinicopathological characteristics and also determine its role in fibrosis progression.

Methods: The consecutive biopsy proven NASH patients were subdivided into two groups according to their fibrosis score. Fibrotic stages<3 in mild fibrosis group and fibrotic stages ≥ 3 in advanced fibrosis depending on the presence of bridging fibrosis. Liver biopsy specimens were immunohistochemically stained for ACE2 immunoreactivity. Demographics and clinical properties were compared between the groups. Univariate and multivariate analysis were also performed to evaluate the independent predicting factors for the presence of advanced liver fibrosis caused by NASH.

Results: One hundred and eight patients were enrolled in the study. Out of this, ninety-four patients representing 87% were classified as mild fibrosis group, whilst fourteen representing 13% were in advanced fibrosis group. We compared high hepatic immunoreactivity of ACE2 between mild and advanced fibrosis groups and found a statistically significant difference 65.9% vs 28.5%, respectively and P=0.008. Hepatic ACE2 immunoreactivity was inversely correlated with the fibrosis score (r: -0.337; P<0.001). The significant variables in the univariate analysis were then evaluated in multivariate logistic regression analysis and hepatic ACE2 immunoreactivity was an independent predicting factor of liver fibrosis [odds ratio (OR): 0.194; 95% confidence interval (CI): 0.082-0.897, P=0.036].

Conclusion: Hepatic immunoreactivity of ACE2 was inversely correlated with the liver fibrosis among biopsy proven NASH patients and it was also an independent predicting factor of advanced fibrosis.