Radioembolization of hepatocellular carcinoma activates liver regeneration, induces inflammation and endothelial stress and activates coagulation.
OBJECTIVE
Radioembolization may rarely induce liver disease resulting in a syndrome that is similar to veno-occlusive disease complicating bone marrow transplantation where inflammation, endothelial cell activation and thrombosis are likely involved. We hypothesized that similar mechanisms could be implicated in radioembolization-induced liver disease (REILD). Moreover, lobar radioembolization may induce hypertrophy of the non-treated hemiliver most probably by inducing liver regeneration.


METHODS
In patients with hepatocellular carcinoma, we prospectively studied serum levels of markers of liver regeneration, oxidative stress, pro-inflammatory pathways, endothelial activation and coagulation parameters over 2 months after radioembolization.


RESULTS
Although REILD did not occur among 14 treated patients, a decrease in effective liver blood flow was observed. Radioembolization was followed by a persistent increase in pro-inflammatory (interleukin 6 and 8) and oxidative stress (malondyaldehide) markers, an induction of endothelial injury markers (vW factor and PAI-1) and an activation of the coagulation cascade (factor VIII, PAI-1, D-Dimer) as well as a significant increase in factors related to liver regeneration (FGF-19 and HGF).


CONCLUSIONS
Radioembolization activates liver regeneration, produces oxidative stress, activates inflammatory cytokines and induces endothelial injury with partial activation of the coagulation cascade. These findings may have implications in the pathogenesis, prevention and therapy of REILD and in the development of new therapies to enhance hypertrophy with a surgical perspective.
Liver Unit, Clinica Universidad de Navarra, Pamplona, Spain.
Nerea
N
Fernandez-Ros
Mercedes
M
Iñarrairaegui
Jose A
JA
Paramo
Carmen
C
Berasain
Matias A
MA
Avila
Ana
A
Chopitea
Nerea
N
Varo
Pablo
P
Sarobe
Jose I
JI
Bilbao
Ines
I
Dominguez
Delia
D
D'Avola
J Ignacio
JI
Herrero
Jorge
J
Quiroga
Bruno
B
Sangro
D000368:Aged; D015415:Biomarkers / Q000097:blood*; D001777:Blood Coagulation; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000532:radiotherapy*; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood; D004621:Embolization, Therapeutic / Q000379:methods*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008099:Liver / Q000098:blood supply / Q000473:pathology; D008113:Liver Neoplasms / Q000097:blood / Q000532:radiotherapy*; D008115:Liver Regeneration; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D018384:Oxidative Stress; D012039:Regional Blood Flow
D015415:Biomarkers; D016207:Cytokines
endothelial injury; inflammation; liver hypertrophy; liver regeneration; liver tumours; radioembolization-induced liver disease