Angiopoietin-2 as a predictor of fibrosis regression in chronic hepatitis C virus patients after direct-acting antiviral drugs

Abstract
Background
HCV infection is a major health concern. Disease progression to fibrosis, cirrhosis, and HCC is aided by the persistence of inflammatory reactions and cellular damage. Moreover, angiogenesis was found to have a substantial pathogenic role in disease progression. Serum Angiopoietin-2 appears to be correlated with liver stiffness in chronic HCV and its elevation is linked to disease progression from chronic hepatitis to cirrhosis. The aim of this study was to evaluate the role of serum Angiopoietin-2 in the prediction of regression of fibrosis in chronic HCV patients receiving direct-acting antiviral agents. Forty Egyptian chronic HCV patients for whom direct-acting antiviral agent (DAA) therapy was planned were included. All patients underwent assessment twice, at baseline and at SVR12, for standard laboratory tests, measurement of fibrosis using FibroScan, FIB-4 and APRI scores, and Angiopoietin-2 level.

Results
Statistically significantly higher levels of baseline Ang-2 were detected with the progression of fibrosis stages with a p-value of <0.001. The best cutoff value of baseline Ang-2 in discrimination of liver cirrhosis (F4) from F0-F3 was > 630 pg/ml with 85.71% sensitivity and 84.85% specificity. A statistically significant decline of Ang-2 (from 464.3±237.2 pg/ml to 401.3±277.1 pg/ml) was noted after the achievement of SVR12 with a p-value < 0.001. Regression of liver fibrosis in this study is defined as a decrease of more than or equal to one stage in liver fibrosis. Lower baseline fibrosis stages and other non-invasive scoring systems (FIB-4 and APRI scores) were associated with regression of fibrosis following successful DAAs treatment. However, higher baseline Ang-2 levels were significantly associated with non-regression of fibrosis, and at a cutoff of >680 pg/ml, it might predict non-regression of fibrosis after successful eradication of HCV with DAAs with 93.33% sensitivity and 70% specificity.

Conclusions
Angiopoietin-2 can be a useful predictor of fibrosis regression in chronic HCV patients receiving direct-acting antiviral agents. Elevated baseline Angiopoietin-2 and advanced fibrosis stages may predict non-regression of liver fibrosis.