Ultrasonographic hemodynamics for prediction of poor liver regeneration induced by severe portal vein stenosis in rats

BACKGROUND: Insufficient portal vein blood flow, such as portal vein stenosis (PVS), plays a significant influence on liver regeneration. Early prediction of poor liver regeneration induced by severe PVS is critical. Ultrasound serves as a first-line imaging technique in diagnosing PVS based on the changes of portal vein hemodynamics. However, there is still no consensus on the criteria for evaluating the degree of PVS. Moreover, which degree of PVS can induce poor liver regeneration still is unclear. Therefore, it is essential to determine the stenosis degree that leads to significantly poor liver regeneration and to evaluate the value of ultrasonographic hemodynamics for predicting poor liver regeneration induced by severe PVS. METHODS: Rats were randomly subjected to sham operation rats group (SOR), PH group (group A), and PVS groups with mild, moderate, or severe stenosis flowing PH (groups B-D). PH group was set up a model of 70% hepatectomy, and PVS groups were produced by different degrees of partial portal vein ligation following PH. In the SOR group and PH group, the portal vein diameter (PVD) and portal vein velocity (PVV) were measured by Ultrasound at preoperative and postoperative 1, 3, 7, and 14 d. In PVS groups, PVD and PVV at the stenotic (PVD(s), PVV(s)) and pre-stenotic (PVD(pre), PVV(pre)) sites were also detected on 1, 3, 7, and 14 d after surgery, calculating the diameter stenosis ratio (DSR) and accelerating blood flow velocity ratio (AVR). Rats were sacrificed at 1, 3, 7, and 14 d post-surgery, and the expression of proliferating cell nuclear antigen (PCNA) and the liver regeneration rate (LRR) at 14 d were evaluated. The PVV(s), DSR, and AVR in the different groups were analyzed combined with the status of liver regeneration, and receiver operating characteristic (ROC) analysis was also applied to assess the value of PVV(s), DSR, and AVR in diagnosing severe PVS and the resulting poor liver regeneration. RESULTS: Seventy-two rat models of different degrees of PVS were successfully set up following 70% PH. The stenosis ratios (SRs) of each PVS group were 45.16%±3.44%, 59.21%±3.83%, and 69.56%±2.16%, respectively. Poor liver regeneration appeared to be significant when PVS was greater than 65% (group D), of which the LRR at 14 d was significantly lower compared to PH group (group A) and PVS groups with SR ≤50% (group B) and SR >50–65% (group C), respectively (all P<0.05). Meanwhile, PCNA expression of group D was significantly lower compared to group C at 1 d and groups A-C at 3 d (all P<0.05). Differences were also detected at 3 d between groups A and B and groups A and C (both P<0.05). Among PVS groups, PVV(s) accelerated dramatically, with significant differences demonstrated between group D and groups B and C at 1 d, as well as group B and groups C and D at 3 d (all P<0.05). At 1, 3, and 7 d, DSR of groups C and D were significantly higher than that of group A (all P<0.05). At 1 and 3 d, AVR of group D was significantly higher than that of groups B and C (all P<0.05). ROC analysis showed the AUC of PVV(s) at 1 d in diagnosing severe PVS was 0.84, while at 3 d, it was unable to differentiate from mild-moderate or severe PVS by PVV(s) (P>0.05 vs. AUC =0.50). At 1 and 3 d, the AUC of DSR and AVR in diagnosing severe PVS were all greater than 0.80, comparatively much better in AVR (AUC >0.95). The best cut-off points of AVR at 1 and 3 d were 6.91 and 5.36, with the sensitivity and specificity respectively 100%, 91.67% at 1 d, and 100%, 83.33% at 3 d. CONCLUSIONS: Poor liver regeneration could be significantly induced when PVS was greater than 65%. Ultrasound can well prove the changes of portal vein hemodynamics in different degrees of PVS in rats. The parameters PVV(s) could be regarded as a valid index for diagnosing PVS but were not applicable for evaluating the stenosis degree. Comparatively, the parameters DSR and AVR, especially AVR, proved to be useful for differentiating severe PVS (>65%) in the early postoperative period, predicting the resulting poor liver regeneration.