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The slow progression of hepatic fibrosis in intrahepatic cholestasis as compared with extrahepatic biliary atresia.

It has been shown that the progression of hepatic fibrosis in intrahepatic cholestasis (IHC) is not so prominent as in extrahepatic biliary atresia (EHBA), and that the biosynthetic activity of collagen increases along with the fibrotic disease process. We conducted immunohistochemical and ultrastructural studies on the distribution of collagen types III and IV and of alpha-actinin in the smooth musculature in liver specimens obtained from 4 patients with IHC and 14 patients with EHBA in liver transplantation from living related donors (LRLT). A recently developed sandwich enzyme immunoassay (EIA) was used to determine serum concentrations of type IV collagen, laminin and prolyl 4-hydroxylase (PH) in the patients before and after LRLT. Pathological study showed that the excessive deposition of type IV collagen in the perisinusoidal walls resulted in a clearly developed basal membrane beneath the sinusoidal endothelial cells, so-called sinusoidal capillarization. In the fibrous septa of IHC, fibrogenesis was apparently lower than in EHBA, since collagen deposition and myofibroblast proliferation were not so prominent compared to EHBA. Serum type IV collagen, laminin and PH increased in IHC, although not so markedly as in EHBA, and returned to normal within 5 weeks after successful LRLT. In conclusion, it is suggested that an increased level of serum type IV collagen reflects the de novo synthesis of basal membrane components, and that the determination of their serum levels by EIA can be utilized for the differentiation of the specific fibrogenic activity in each disease, and for monitoring patients before and after liver transplantation.