Heterogeneous inflammatory changes in liver graft recipients with normal biochemistry.
BACKGROUND
Patients with established liver grafts may receive excessive immune suppression. Liver biopsies were analyzed in those with normal liver biochemistry to identify parameters that might identify such cases.


METHODS
Patients with established grafts (>3 years from engraftment) and normal liver biochemistry (normal alanine transaminase, alkaline phosphatase, and bilirubin) were invited to undergo liver biopsy. Liver tissue was assessed by routine histopathology, a modified Ishak score, and immunohistochemistry for lymphocyte and cell-cycle markers. Circulating and intrahepatic lymphocytes were subjected to flow cytometry. Data were subjected to principal component analysis.


RESULTS
Two hundred twenty-five (40%) patients under regular review had an established graft with normal liver biochemistry; liver tissue was obtained in 55. Liver histology was normal in eight cases (14.5%). The most common abnormalities were mild nonspecific hepatitis in 25 (45.4%) and disease recurrence in 14 (25.4%). Principal component analysis identified a cluster of variables that accounted for a significant degree of variation within the dataset. These were lobular inflammation, portal inflammation, interface hepatitis, and fibrosis.


CONCLUSIONS
Inflammation persisted in established grafted livers in most patients with normal liver biochemistry. Systematic histological and lymphocyte phenotype analysis generated an index that distinguished patient groups. Those with least inflammation and the lowest alanine transaminase may have a reduced requirement for immune suppression.
Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
William
W
Gelson
Matthew
M
Hoare
Esther
E
Unitt
Christopher
C
Palmer
Paul
P
Gibbs
Nicholas
N
Coleman
Susan
S
Davies
Graeme J M
GJ
Alexander
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D006505:Hepatitis / Q000097:blood / Q000209:etiology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D018836:Inflammation Mediators / Q000378:metabolism; D008103:Liver Cirrhosis / Q000097:blood / Q000209:etiology* / Q000473:pathology; D016031:Liver Transplantation / Q000009:adverse effects*; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D025341:Principal Component Analysis; D012720:Severity of Illness Index; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D015415:Biomarkers; D018797:Cell Cycle Proteins; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D001663:Bilirubin