Increased Levels of Endoglin are Associated with Liver Fibrosis in Hepatitis C Patients

Endoglin is a transforming growth factor (TGF)-beta1 co-receptor that has been linked with fibrosis of the kidneys and skin, since over-expression of this protein has been observed in biopsy samples from patients with glomerulosclerosis and scleroderma.

Spanish researchers conducted a study to examine whether levels of endoglin might also be elevated in chronic hepatitis C patients with liver fibrosis.

The study included 52 HCV positive patients, five HCV negative patients, and 27 healthy control subjects. Western blot and immunohistochemistry assays were used to quantify the expression levels of endoglin and TGF-beta1 in liver biopsy samples. Serum concentrations of endoglin and hyaluronic acid (a component of the extracellular matrix material that proliferates in fibrosis) were determined by ELISA assays.

Results

In patients with advanced fibrosis, intrahepatic expression of endoglin and TGF-beta1 were significantly higher compared to patients with early fibrosis (mean 3-fold and 5.8-fold higher, respectively).

Patients with advanced fibrosis also had higher endoglin and TGF-beta1 levels compared to subjects with normal livers (i.e., without fibrosis) (mean 3.9-fold and 12-fold higher, respectively).

Activated hepatic stellate cells, as well as portal and septal myofibroblasts (cells that produce extracellular matrix material) were observed to express endoglin.

Serum levels of endoglin were significantly higher in patients with advanced fibrosis than in those with early fibrosis (55.5 vs 47.5 ng/mL; P < 0.001).

There was a positive correlation between endoglin and serum hyaluronic acid concentrations (r = 0.57; P = 0.01).

Conclusion

In conclusion, the authors wrote, "Increased intrahepatic endoglin and TGF-beta1 expression is significantly associated with progressive hepatic fibrosis in chronic HCV infection. Circulating endoglin levels are elevated in HCV patients showing a significant correlation with histological and serum markers of hepatic fibrosis."

Further understanding of endoglin and its role in fibrosis may in the future contribute to the development of anti-fibrotic therapies for patients with chronic hepatitis C.

9/12/06

Reference
M Clemente, O Nunez, R Lorente, and others. Increased intrahepatic and circulating levels of endoglin, a TGF-beta1 co-receptor, in patients with chronic hepatitis C virus infection: relationship to histological and serum markers of hepatic fibrosis. Journal of Viral Hepatitis 13(9): 625-632. September 2006.