Transjugular intrahepatic portosystemic shunt: effect of bile leak on smooth muscle cell proliferation

To evaluate the effect of bile on smooth muscle cell (SMC) proliferation in vitro and in vivo in a porcine transjugular intrahepatic portosystemic shunt (TIPS) model.

In vitro, SMCs explanted from porcine thoracic aorta were cultured with standard techniques. After initial pilot studies, they were subcultured in one of three groups: 1% porcine serum plus 1% bile, 10% porcine serum plus 1% bile, and 10% porcine serum. Cells were harvested at 3, 10, or 14 days, and DNA, protein, and disintegrations per minute (an indicator of proliferation) were measured. In vivo, TIPS creation was successful in 45 swine. All pigs were euthanized at 10-16 days. The proliferative response within the stent was histologically quantified and correlated for evidence of bile leak.

In pilot studies, 2.5%-10.0% bile solutions caused 100% SMC mortality by 3 days. In the presence of 1% bile (with or without porcine serum), both DNA and protein production decreased significantly compared with that in porcine serum alone (P < .05). In vivo, 13 of 45 specimens (29%) showed bile leak at gross or microscopic examination. SMC proliferation was less overall in animals with versus those without bile leak (difference not significant).

These data suggest that the proliferative response in a TIPS is not primarily due to bile leak. Bile leak may promote thrombosis, but it appears to inhibit myointimal proliferation.