Impact of hepatic vein deprivation on liver regeneration and function after major hepatectomy

Abstract Background The capacity of the liver to restore its architecture and function assures good prognoses of patients who suffer serious hepatic injury or cancer resection. In our study, we found that the P53/miR-34a/SIRT1 positive feedback loop has a remarkable negative regulatory effect, which is related to the termination of liver regeneration. Here, we described how P53/miR-34a/SIRT1 positive feedback loop controls liver regeneration and its possible relationship with liver cancer.Method We performed partial hepatectomy (PH) in mice transfected with adenovirus (Ade) overexpressing P53 and adenovirus-associated virus (AAV) knock-downing miR-34a. LR was analyzed by liver weight/body weight, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and cell proliferation, and the related cellular signals were investigated. Bile acid (BA) levels during LR were analyzed by metabolomics of bile acids. Results We found that the P53/miR-34a/SIRT1 positive feedback loop was activated in the late phase of LR. Overexpression of P53 terminated LR early and enhanced P53/miR-34a/SIRT1 positive feedback loop expression and its proapoptotic effect. Mice from the Ade-P53 group showed smaller livers and higher levels of serum ALT and AST than control mice. While knock-down of miR-34a abolished P53/miR-34a/SIRT1 positive feedback loop during LR. Mice from anti-miR-34a group showed larger livers and lower levels of PCNA-positive cells than control mice. T-β-MCA increased gradually during LR and peaked at 7 days after PH. T-β-MCA inhibited cell proliferation and promoted cell apoptosis via facilitating the P53/miR-34a/SIRT1 positive feedback loop during LR by suppressing FXR/SHP. Conclusion The P53/miR-34a/SIRT1 positive feedback loop plays an important role in the termination of LR. Our findings shed light on the molecular and metabolic mechanisms of LR termination and provide a potential therapeutic alternative for treating P53-wild-type HCC patients.

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In search of a pathogenesis for impaired liver regeneration after major hepatectomy with extrahepatic bile duct resection: The plot thickens!

Hepatology Research ◽

10.1111/hepr.13414 ◽

2019 ◽

Vol 49 (10) ◽

pp. 1091-1093 ◽

Cited By ~ 1

Author(s):

Riccardo Pravisani ◽

Umberto Baccarani ◽

Susumu Eguchi

Keyword(s):

Bile Duct ◽

Liver Regeneration ◽

Major Hepatectomy ◽

Extrahepatic Bile Duct ◽

Bile Duct Resection ◽

Extrahepatic Bile Duct Resection ◽

Impaired Liver

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Sarcopenia affects liver regeneration and postoperative course after a major hepatectomy. A prospective study on 125 patients using HIDA scintigraphy

HPB ◽

10.1016/j.hpb.2019.10.387 ◽

2019 ◽

Vol 21 ◽

pp. S643

Author(s):

M. Fulbert ◽

M. El Amrani ◽

C. Baillet ◽

A.C. Deshorgue ◽

K. Lecolle ◽

...

Keyword(s):

Prospective Study ◽

Liver Regeneration ◽

Major Hepatectomy ◽

Postoperative Course ◽

A Prospective Study

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Preoperative Chemotherapy on Functional Liver Regeneration for Colorectal Liver Metastases Assessed With 99mTc-GSA SPECT/CT Imaging

International Surgery ◽

10.9738/intsurg-d-16-00209.1 ◽

2018 ◽

Vol 102 (9-10) ◽

pp. 431-439 ◽

Cited By ~ 1

Author(s):

Toru Beppu ◽

Hiromitsu Hayashi ◽

Morikatsu Yoshida ◽

Hidetoshi Nitta ◽

Katsunori Imai ◽

...

Keyword(s):

Liver Resection ◽

Liver Metastases ◽

Liver Regeneration ◽

Preoperative Chemotherapy ◽

Colorectal Liver Metastases ◽

Major Hepatectomy ◽

Liver Volume ◽

Control Group ◽

Remnant Liver ◽

Resection Rate

Objective: To investigate the functional liver regeneration after chemotherapy and liver resection for colorectal liver metastases (CRLM). Background/Purpose: Preoperative chemotherapy followed by liver resection for CRLM has been increasing; however, its negative impact on liver regeneration remains unknown. Methods: From January 2009 to December 2013, we enrolled 40 selected patients who underwent major hepatectomy without viral hepatitis and severe liver fibrosis. CRLM patients with preoperative chemotherapy (CT-CRLM group, n = 12) and patients without preoperative chemotherapy (control group, n = 28) were evaluated. Liver volume (LV) and functional liver volume (FLV) was assessed using Tc-99m–labeled galactosyl human serum albumin (99mTc-GSA) scintigraphy, single-photon emission computed tomography (SPECT), CT-fused images. Preoperative, future remnant liver, and post 1-month values were compared. Results: Median course of preoperative chemotherapy was 8 (range: 6–16). Preoperative background factors were almost identical including resection rate and functional resection rate. In the CT-CRLM group and in the control group, the percentage increases in LV were 39.3% ± 29.0% and 23.2% ± 23.5% (P = 0.037), and FLV were 79.4% ± 43.1% and 57.0% ± 33.4% (P = 0.417), respectively; absolute differences in LV were 216.2 ± 155.7 cm3 and 148.7 ± 134.7 cm3 (P = 0.086) and FLV were 19.4% ± 8.5%/m2 and 17.4% ± 7.9%/m2 (P = 0.235), respectively. We found no obvious tendency for negative influence on liver functional regeneration by the preoperative regimens for CRLM. Conclusions: Several courses of preoperative chemotherapy may not affect functional liver regeneration for CRLM patients after major hepatectomy.

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