Prediction of progressive liver fibrosis in hepatitis C infection by serumand tissue levels of transforming growth factor-beta

Although many patients with chronic viral hepatitis C infection suffer from progressive liver disease, the rate of fibrosis progression is highly vari able and some patients do not show any measurable progression. However, our ability to predict which patients progress is very limited. Since transfor ming growth factor-beta (TGF-beta) is a key mediator of liver fibrogenesis, we assessed the predictive role of TGF-beta for fibrogenesis in chronic he patitis C. We studied 39 patients with chronic hepatitis C in whom two live r biopsies were taken at least 12 months apart, and who did not receive the rapy 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 det ermined semiquantitatively by immunostaining of liver biopsy sections. Fibr osis was scored blinded in the biopsy samples by two pathologists independe ntly. There was a close correlation between TGF-beta serum levels and the r ate of fibrosis progression. Patients with no progression of fibrosis had s ignificantly lower (59 ng/mL +/- 22) TGF-beta serum levels than patients wi th 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 biop sy 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 f urther support the role of TGF-beta in liver fibrogenesis, and offer an opp ortunity to predict clinical disease progression, which may help in selecti ng patients who are in need of therapeutic interventions.