Prediction of progressive liver fibrosis in hepatitis C infection by serum and tissue levels of transforming growth factor‐β

Abstract

Although many patients with chronic viral hepatitis C infection suffer from progressive liver disease, the rate of fibrosis progression is highly variable and some patients do not show any measurable progression. However, our ability to predict which patients progress is very limited. Since transforming growth factor-beta (TGF-beta) is a key mediator of liver fibrogenesis, we assessed the predictive role of TGF-beta for fibrogenesis in chronic hepatitis C. We studied 39 patients with chronic hepatitis C in whom two liver biopsies were taken at least 12 months apart, and who did not receive therapy during this period. TGF-beta was measured by bioassay and by ELISA in serum samples taken at the time of the first biopsies, and TGF-beta was determined semiquantitatively by immunostaining of liver biopsy sections. Fibrosis was scored blinded in the biopsy samples by two pathologists independently. There was a close correlation between TGF-beta serum levels and the rate of fibrosis progression. Patients with no progression of fibrosis had significantly lower (59 ng/mL +/- 22) TGF-beta serum levels than patients with progressive disease (115 ng/mL +/- 20), and a TGF-beta level below 75 ng/mL was predictive for stable disease. Immunohistology for TGF-beta in biopsy samples was also predictive for progressive liver disease with fibrosis progression found in those patients displaying staining of hepatocytes and sinusoidal cells. No such correlation was found with other markers such as procollagen III peptide, viral load or transaminase levels. These results further support the role of TGF-beta in liver fibrogenesis, and offer an opportunity to predict clinical disease progression, which may help in selecting patients who are in need of therapeutic interventions.

Diagnosis and Quantitation of Fibrosis

“…115 A small study of 38 patients with chronic HCV found a close correlation between TGF-␤ levels and the rate of fibrosis progression. 116 Tumor necrosis factor (TNF)-␣ has been associated with liver injury in patients with alcoholic liver disease. 117 Platelet derived growth factor is up-regulated following liver injury, 118 and levels may correlate with the degree of liver injury.…”

Review article: chronic hepatitis C – natural history and cofactors

“…15 Other studies have linked polymorphisms in the genes of transforming growth factors-b. 16 and angiotensin II 17 to a more progressive type of chronic hepatitis C.…”

Diagnosing Fibrosis in Hepatitis C: Is the Pendulum Swinging From Biopsy to Blood Tests?

“…14,15 Advances in our understanding of the hepatic ECM has led to many potential markers being identified, but none have sufficient merit for clinical use as solitary markers. [16][17][18][19][20] A large multicenter European study combining multiple markers that measure ECM production and breakdown has shown promise in the diagnostic staging of liver disease, and further longitudinal studies from this cohort are awaited. 21 So, are surrogate markers of liver fibrosis ready for clinical primetime?…”