Fibrous obliterative lesions of veins contribute to progressive fibrosis in chronic liver allograft rejection

Fibrosis in liver allografts undergoing chronic rejection (CR) is variable and poorly understood. The temporal and spatial relationships of venous, ar terial, and biliary lesions were studied to clarify their potential contrib utions to graft fibrosis. The severity, prevalence, and morphology of intim al lesions of vessels were analyzed and compared with the fibrosis stage. T hree groups were found; group 1 (n = 5) with no hepatic vein (HV) lesions, group 2 (n = 5) with HV lesions only, and group 3 with lesions of both HV a nd portal veins (PV), The earliest lesion to develop, in 71% of grafts, was concentric intimal thickening of small HV, This was significantly more sev ere and frequent in grafts from group 3. With increasing frequency and seve rity of small HV sclerosis, fibrosis developed in medium/large veins. The m orphology of larger vessel lesions suggested organized thrombus. Centrilobu lar fibrosis was significantly more severe in group 3 and developed unpredi ctably and sometimes rapidly. Conversely, portal fibrosis scores were signi ficantly higher in grafts with ductular proliferation and did not correlate with venous lesions. This suggests that in CR, venoocclusive-like lesions develop commonly in terminal hepatic venules, probably caused by immune-med iated damage. In only a proportion, with increased frequency and severity o f the lesions, stasis and thrombosis in portal and larger veins occur and c ould result in loss of hepatic and portal venous outflow, which leads to is chemia and fibrosis. The stage of fibrosis did not correlate with foam-cell arteriopathy, A second pathway of portal fibrosis occurs in patients with longstanding biliary proliferation.