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, arterial, and biliary lesions were studied to clarify their potential contributions to graft fibrosis. The severity, prevalence, and morphology of intimal lesions of vessels were analyzed and compared with the fibrosis stage. Three 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 and portal veins (PV). The earliest lesion to develop, in 71% of grafts, was concentric intimal thickening of small HV. This was significantly more severe and frequent in grafts from group 3. With increasing frequency and severity of small HV sclerosis, fibrosis developed in medium/large veins. The morphology of larger vessel lesions suggested organized thrombus. Centrilobular fibrosis was significantly more severe in group 3 and developed unpredictably and sometimes rapidly. Conversely, portal fibrosis scores were significantly higher in grafts with ductular proliferation and did not correlate with venous lesions. This suggests that in CR, veno-occlusive-like lesions develop commonly in terminal hepatic venules, probably caused by immune-mediated damage. In only a proportion, with increased frequency and severity of the lesions, stasis and thrombosis in portal and larger veins occur and could result in loss of hepatic and portal venous outflow, which leads to ischemia 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.
Nakazawa
Y
Y
Department of Pathology, Princess Alexandra Hospital, Brisbane, Australia.
Jonsson
J R
JR
Walker
N I
NI
Kerlin
P
P
Steadman
C
C
Lynch
S V
SV
Strong
R W
RW
Clouston
A D
AD
D000293:Adolescent; D000328:Adult; D001158:Arteries / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D018450:Disease Progression; D005260:Female; D005355:Fibrosis; D005487:Foam Cells / Q000473:pathology; D006084:Graft Rejection / Q000150:complications* / Q000473:pathology*; D006503:Hepatic Veins / Q000473:pathology*; D006801:Humans; D007223:Infant; D008099:Liver / Q000098:blood supply / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011169:Portal Vein / Q000473:pathology*; D012598:Sclerosis; D014652:Vascular Diseases / Q000150:complications* / Q000473:pathology*; D014657:Vasculitis / Q000150:complications / Q000473:pathology