The role of bile duct reactive change in the pathogenesis of liver fibrosis due to hepatitis C

The question addressed here is: does the bile duct reactive component of hepatitis C disease progress during the progression of the disease to cirrhosis? The question is important because if the answer to the question is yes, then an important correllary question is: does the bile duct reactive component contribute to the fibrotic change which leads to cirrhosis? The first question is addressed in the present study of a series of liver biopsies taken at the four stages of liver fibrosis in patients with hepatitis C. Sixty-four patients with hepatitis who had been biopsied for staging purposes were reviewed retrospectively. The liver biopsies were routinely stained with antibodies for liver cells, bile duct cells, activated stellate cells and cells in S phase of the cell cycle and histochemical stains for collagen and basement membrane. Selective biopsies were stained for stem cells and oval cells. There was a progressive increase in metaplastic bile ductules but the increase did not reach a significant level until stages III and IV of fibrosis. There was a positive correlation between the number of ductules formed and the stage of liver fibrosis. The incidence of proliferating metaplastic ductules was low and did not change significantly during the progression of the stage of the fibrosis. Stains for oval cells and stem cells were negative. It is concluded that the answer to the question posed is: bile ductule reaction does increase during the development of cirrhosis caused by hepatitis C but the increase is due to bile ductular metaplasia, not due to proliferation.