Published online Nov 18, 2017. doi: 10.4254/wjh.v9.i32.1227
Peer-review started: August 7, 2017
First decision: September 13, 2017
Revised: October 9, 2017
Accepted: October 30, 2017
Article in press: October 30, 2017
Published online: November 18, 2017
Processing time: 101 Days and 0 Hours
To clarify the histological changes associated with liver atrophy after percutaneous transhepatic portal embolization (PTPE) in pigs and humans.
As a preliminary study, we performed pathological examinations of liver specimens from five pigs that had undergone PTPE in a time-dependent model of liver atrophy. In specimens from embolized lobes (EMB) and nonembolized lobes (controls), we measured the portal vein to central vein distance (PV-CV), the area and number of hepatocytes per lobule, and apoptotic activity using the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Immunohistochemical reactivities were evaluated for light chain 3 (LC3) and lysosomal-associated membrane protein 2 (LAMP2) as autophagy markers and for glutamine synthetase and cytochrome P450 2E1 (CYP2E1) as metabolic zonation markers. Samples from ten human livers taken 20-36 d after PTPE were similarly examined.
PV-CVs and lobule areas did not differ between EMB and controls at day 0, but were lower in EMB than in controls at weeks 2, 4, and 6 (P ≤ 0.001). Hepatocyte numbers were not significantly reduced in EMB at day 0 and week 2 but were reduced at weeks 4 and 6 (P ≤ 0.05). Apoptotic activity was higher in EMB than in controls at day 0 and week 4. LC3 and LAMP2 staining peaked in EMB at week 2, with no significant difference between EMB and controls at weeks 4 and 6. Glutamine synthetase and CYP2E1 zonation in EMB at weeks 2, 4, and 6 were narrower than those in controls. Human results were consistent with those of porcine specimens.
The mechanism of liver atrophy after PTPE has two histological phases: Hepatocellular atrophy is likely caused by autophagy in the first 2 wk and apoptosis thereafter.
Core tip: Liver atrophy after percutaneous transhepatic portal embolization (PTPE) in time-independent human studies is associated with hepatocyte shrinkage and apoptosis. In this preliminary study, we performed pathological examinations of liver specimens from five pigs that had undergone PTPE in a time-dependent model of liver atrophy. Two distinct phases of liver atrophy were identified: A hepatocellular atrophic phase, which may relate to autophagy, and an apoptotic phase. Despite liver atrophy appearing to be mostly resolved 2 wk after embolization, the period after PTPE could beneficially be extended to 4 wk to ensure contralateral hypertrophy and to allow the completion of liver atrophy.