Application Of Hepatic Lobe Hyperplasia Techniques In The Treatment Of Advanced Hepatic Alveolar Echinococcosis

Objective: Hepatic lobe hyperplasia techniques refers to the application including portal vein embolization(PVE),two-stage hepatectomy(TSH),to promote the hyperplasia of the healthy liver volume of patients with end-stage hepatic diseases who are unable to tolerate surgery due to insufficient future liver remnant volume(FLRV),and so as to meet the requirements of surgery.Therefore,this current study aimed to(1)evaluate the safety and efficacy of FLRV induced by selective PVE and TSH in patients with end-stage hepatic alveolar echinococcosis(AE),and further describe indications of these above techniques.(2)When FLRV met to the surgical standards,most end-stage AE patients received ex vivo liver resection and auto-transplantation(ELRA)for radical surgery according to the AE lesions characteristics,and evaluating regeneration status of the transplanted liver was extremely significant in clinical settings.Thus,this current study also aimed to explore the trend of changes in transplanted liver volume and functions in hepatic AE patients after ELRA,and to explore correlation between liver regeneration status and serum levels of mi R-1-3p and mi R-133b-3p in hepatic AE patients.Methods:(1): Clinical data of 15 patients with end-stage hepatic AE who received PVE due to insufficient FLRV were retrospectively analyzed,and 3D Slicer software was used to describe 3D mapping of liver volume before PVE and after PVE.Lesion volume(LV),total liver volume(TLV)and FLRV were measured before and after PVE.Moreover,ratio of FLRV to TLV(FLRV/TLV),liver volume growth rate,interval time and monthly liver volume growth rate were calculated,and changes in FLRV before and after PVE were evaluated.Liver function indexes,including total bilirubin(TBil),albumin(Alb),alanine aminotransferase(ALT),aspartate aminotransferase(AST)and γ-glutamyl transpeptide(γ-GGT),were collected before and after PVE to evaluate effects of PVE on the alterations in patients’ liver functions.Meanwhile,all patients receiving PVE were followed up to evaluate safety and effectiveness of this technique in end-stage hepatic AE patients.(2)A retrospective analysis was performed on four patients with end-stage hepatic AE who received TSH due to insufficient FLRV.3DSlicer software was used to conduct three-dimensional liver mapping before and after the first stage of TSH,and LV,TLV and FLRV before and after TSH were determined.FLRV/TLV,monthly liver volume growth rate and interval time were also calculated.Changes in FLRV were evaluated in these patients receiving TSH before and after first stage surgery.Liver function indexes,including TBil,Alb,ALT,AST,γ-GGT,before and after TSH were collected to evaluate effects of TSH on the alterations in patients’ liver functions.Meanwhile,all patients receiving TSH were followed up to evaluate safety and efficacy of this technique in end-stage hepatic AE patients.(3)Relevant clinical data of 21 patients with end-stage liver AE who were treated with ELRA were collected.LV,liver functions and liver regeneration index were measured,and plasma levels of mi R-1-3p and mi R-133b-3p were detected through quantitative real time polymerase chain reaction(q RT-PCR)to analyze their dynamic changes in hepatic AE patients before and after RLRA.Based on the expression data of mi R-1-3p and mi R-133b-3p target genes related to liver regeneration in mi RDB(mirdb.org),changes in liver regeneration index and micro RNA levels were comprehensively analyzed to explore clinical significance of mi R-1-3p and mi R-133b-3p as biomarkers of liver regeneration in hepatic AE patients after ERLA.Results:(1)Among the 15 patients who received PVE,and there were no significant differences in TBil,Alb,ALT,AST and γ-GGT before and after PVE in the patients(P>0.05).There were also no significant differences in TLV and LV before and after PVE(P>0.05).However,FLRV increased significantly after PVE(P<0.05),and FLRV/TLV were greater than 30% in all these patients.During the follow-up,one patient was lost to follow-up,The follow-up period was 4.10(IQR2.61-4.64)months in the other14 patients,and the median monthly growth rate of FLRV was 4.49%(IQR 3.55 to 7.06).During the waiting period after PVE,there were no Clavien-Dindo Ⅲa or above complications in these 14 patients,and there was also no obvious progression of hepatic AE lesions.Ultimately,two patients could not receive further surgical treatment due to economic reasons,and the remaining 12 patients received radical surgery to remove AE lesions,The median interval time from PVE to AE pre-resection was 3.95(IQR 2.56-4.44)months.(2)Among the four patients receiving TSH,ALT,AST and γ-GGT showed a decreased trend after the first stage surgery compared with those before the first stage surgery.The median FLRV after the first stage surgery was greater than that before the first stage surgery,and the median interval time between the two stages of surgery was7.53 months(IQR 3.52-10.30).The median monthly growth rate of FLRV was 3.34%(IQR 2.17-4.61).In the first stage,there were no Clavien-Dindo Ⅲa or above complications,and there was no obvious progression of hepatic AE lesions.(3)The liver volume and liver regeneration index showed an obvious rapid hyperplasia period and a plateau period after ELRA in hepatic AE patients.AE patients showed an obvious rapid hyperplasia period and a plateau period after ELRA.whose differences were statistically significant(P<0.05).Meanwhile,liver function of these patients decreased after surgery and then returned to the normal level.The changes of liver regeneration index were correlated with the changes of liver function.Expression level of mi R-133b-3p in hepatic AE patients before ELRA,at the early postoperative period and at the late long postoperative period showed a pattern of significant decline,significant increase and return to the normal level,the trend was similar to that of liver regeneration.Conclusions:(1)PVE and TSH are safe and feasible techniques to promote hepatic hyperplasia in patients with end-stage hepatic AE and insufficient FLRV;(2)At the molecular level,the dynamic changes of mi R-133b-3p were in the same direction as the liver regeneration index.The results preliminarily indicate that mi R-133b-3p may be used as a biomarker of liver regeneration in patients with liver AE after ELRA surgery,which has certain clinical significance.