Triggered Liver Regeneration: From Experimental Model to Clinical Implications

2015 ◽  
Vol 54 (3-4) ◽  
pp. 148-161 ◽  
Author(s):  
Attila Szijártó ◽  
András Fülöp
Keyword(s):  
Liver Resection ◽  
Surgical Technique ◽  
Liver Regeneration ◽  
Molecular Mechanisms ◽  
Liver Tumors ◽  
Therapeutic Option ◽  
Liver Volume ◽  
Postoperative Liver Failure ◽  
Remnant Liver ◽  
Comprehensive Overview

Background: Major liver resection is the only therapeutic option for patients with malignant liver tumors. However, extended hepatectomy often leads to postoperative liver failure, mainly due to insufficient amounts of the remnant liver. Recently, selective portal vein occlusion (PVO) has been introduced to increase the remnant liver volume. This novel surgical technique initiated a progressive development in liver surgery, resulting in a significant increment in potential candidates for curative liver resection. Summary: The theoretical basis for this great advancement is formed by an understanding of the mechanisms of PVO-induced liver regeneration, mainly obtained from animal studies. The aim of this review is to give a comprehensive overview of the relevant animal models of PVO and to discuss the main characteristics of triggered liver regeneration, including the induced hemodynamic, morphological and functional alterations as well as the underlying molecular mechanisms, which might be of interest in both the laboratory and the clinic. Key Messages: Although basic research revealed the main characteristics of PVO-triggered liver regeneration within the last decades, several important issues regarding the regenerative process remain uncertain. To answer these open questions, additional well-designed animal experiments are needed in the future, which allow further refinement of this surgical technique.

Relationship between platelet count and hepatic failure and residual liver regeneration after hemihepatectomy in patients with hepatitis B-related primary hepatocellular carcinoma

2019 ◽  
Author(s):  
Chuhui Ye ◽  
Banghao Xu ◽  
Kaiyi Lu ◽  
Tingting Lu ◽  
Ling Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Resection ◽  
Hepatitis B ◽  
Liver Failure ◽  
Liver Regeneration ◽  
Liver Volume ◽  
Primary Hepatocellular Carcinoma ◽  
Postoperative Liver Failure ◽  
Regeneration Rate ◽  
Significant Difference

Abstract Objective A retrospective analysis of the influences of platelet (PLT) counts on liver failure and liver regeneration in patients with primary hepatocellular carcinoma (HCC) provides a treatment strategy for clinical prevention and treatment of postoperative liver failure and residual liver regeneration. Method The clinical data of 111 patients with a background of hepatitis B virus infection and who underwent (expanded) half liver resection at the First Affiliated Hospital of Guangxi Medical University from June 2012 to June 2017 were collected and statistically analyzed. Results　On the basis of the International Study Group of Liver Surgery liver failure-grading standards and Dino–Clavien postoperative complication criteria, the incidence of grade B and above liver failure was 55%, and complication II level and above was 47.5% in the PLT decline group after semihepatectomy. The incidence rates in the normal group were 26.8% and 23.9%. A statistically significant difference was determined in the two groups (P1=0.003, P2 = 0.011). The average volumes of liver hyperplasia (residual liver volume (RLV)80.4 days − RLV) in the PLT decline and normal groups were 132.09 ± 61.89 cm3 and 190.89 ± 91.98c cm3, respectively; the average rates of hyperplasia ((RLV80.4days−RLV)/RLV) were 16.59%± 7.36% and 24.78% ± 10.82%. The difference between the two groups was statistically significant (PProliferation = 0.001, PProliferation rate = 0.001). Univariable and multivariable logistic regression analyses of postoperative liver failure grade and proliferation rate in patients who underwent semihepatectomy suggested that the decrease in postoperative PLT count (PLT < 125 × 109/L) might be an independent risk factor of severe posthepatectomy liver failure (PHLF) (PHLF-B or above) and residual liver regeneration rate for patients with primary HCC after half liver resection. No death occurred. Conclusions A correlation existed between PLT count and postoperative PHLF or liver regeneration. Monitoring PLT counts after liver resection may help us predict the suffering from PHLF-B or above and severe postoperative complications.

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

2018 ◽  
Vol 102 (9-10) ◽  
pp. 431-439 ◽  
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.

LINC00265 maintains hepatocyte proliferation during liver regeneration by targeting miRNA-28-5p

2021 ◽  
Vol 85 (3) ◽  
pp. 528-536
Author(s):  
Sheng Yu ◽  
Zhonglin Cui ◽  
Jie Zhou ◽  
Kai Wang ◽  
Qingping Li ◽  
...  
Keyword(s):  
Liver Resection ◽  
Liver Regeneration ◽  
Therapeutic Option ◽  
Weight Ratio ◽  
Hepatocyte Proliferation ◽  
Phase Cell ◽  
Luciferase Reporter ◽  
Hepatocyte Regeneration ◽  
M Phase ◽  
Reporter Assays

ABSTRACT Long noncoding RNAs have been implicated in many biological processes, but their roles in liver regeneration still need to be illustrated. Therefore, we aimed to investigate the role of LINC00265 as a pivotal regulator of hepatocyte proliferation during liver regeneration. It was found that LINC00265 is significantly upregulated in rat liver tissues at various time points after 2/3 liver resection. LINC00265 knockdown inhibited hepatocyte proliferation, induced cell apoptosis and led to G2/M phase cell cycle arrestment. In rats subjected to surgery, LINC00265 knockdown decreased liver/body weight ratio, attenuated improvement from liver damage and reduced Ki67 and PCNA expression. Luciferase reporter assays confirmed that miR-28-5p was a direct target of LINC00265, and inhibition of miR-28-5p abolished the effect of LINC00265 knockdown. In summary, LINC00265 might maintain hepatocyte proliferation by targeting miR-28-5p during liver regeneration and should be considered as a promising therapeutic option for hepatocyte regeneration after liver resection.

Preoperative Alanine Aminotransferase and Remnant Liver Volume Predict Liver Regeneration After Live Donor Hepatectomy

2019 ◽  
Vol 24 (8) ◽  
pp. 1818-1826
Author(s):  
Nihar Mohapatra ◽  
Piyush Kumar Sinha ◽  
Shridhar Vasantrao Sasturkar ◽  
Yashwant Patidar ◽  
Viniyendra Pamecha
Keyword(s):  
Liver Regeneration ◽  
Alanine Aminotransferase ◽  
Liver Volume ◽  
Remnant Liver ◽  
Live Donor ◽  
Donor Hepatectomy ◽  
Remnant Liver Volume

scholarly journals Notch Inhibition Promotes Differentiation of Liver Progenitor Cells into Hepatocytes via sox9b Repression in Zebrafish

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jacquelyn O. Russell ◽  
Sungjin Ko ◽  
Satdarshan P. Monga ◽  
Donghun Shin
Keyword(s):  
Liver Disease ◽  
Liver Regeneration ◽  
Notch Signaling ◽  
Chronic Liver Disease ◽  
Progenitor Cells ◽  
Molecular Mechanisms ◽  
Therapeutic Option ◽  
Chronic Liver ◽  
Hepatocyte Proliferation ◽  
Hepatocyte Differentiation

Liver regeneration after most forms of injury is mediated through the proliferation of hepatocytes. However, when hepatocyte proliferation is impaired, such as during chronic liver disease, liver progenitor cells (LPCs) arising from the biliary epithelial cell (BEC) compartment can give rise to hepatocytes to mediate hepatic repair. Promotion of LPC-to-hepatocyte differentiation in patients with chronic liver disease could serve as a potentially new therapeutic option, but first requires the identification of the molecular mechanisms driving this process. Notch signaling has been identified as an important signaling pathway promoting the BEC fate during development and has also been implicated in regulating LPC differentiation during regeneration. SRY-related HMG box transcription factor 9 (Sox9) is a direct target of Notch signaling in the liver, and Sox9 has also been shown to promote the BEC fate during development. We have recently shown in a zebrafish model of LPC-driven liver regeneration that inhibition of Hdac1 activity through MS-275 treatment enhances sox9b expression in LPCs and impairs LPC-to-hepatocyte differentiation. Therefore, we hypothesized that inhibition of Notch signaling would promote LPC-to-hepatocyte differentiation by repressing sox9b expression in zebrafish. We ablated the hepatocytes of Tg(fabp10a:CFP-NTR) larvae and blocked Notch activation during liver regeneration through treatment with γ-secretase inhibitor LY411575 and demonstrated enhanced induction of Hnf4a in LPCs. Alternatively, enhancing Notch signaling via Notch3 intracellular domain (N3ICD) overexpression impaired Hnf4a induction. Hepatocyte ablation in sox9b heterozygous mutant embryos enhanced Hnf4a induction, while BEC-specific Sox9b overexpression impaired LPC-to-hepatocyte differentiation. Our results establish the Notch-Sox9b signaling axis as inhibitory to LPC-to-hepatocyte differentiation in a well-established in vivo LPC-driven liver regeneration model.

scholarly journals A Protective Effect of Sivelestat From Ischemia/Reperfusion Injury in a Porcine Hepatectomy Model

2018 ◽  
Vol 103 (3-4) ◽  
pp. 191-198 ◽  
Author(s):  
Mitsugi Shimoda ◽  
Yoshimi Iwasaki ◽  
Shuji Suzuki
Keyword(s):  
Liver Regeneration ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Liver Volume ◽  
Therapeutic Drug ◽  
Control Group ◽  
Tunel Staining ◽  
Remnant Liver ◽  
Elastase Inhibitor ◽  
Sivelestat Sodium Hydrate

Summary of background data: Sivelestat sodium hydrate (Sive), a neutrophil elastase inhibitor, has been approved as a worldwide therapeutic drug for acute lung injury associated with systemic inflammatory response syndrome. Yet how Sive influences hepatic ischemic reperfusion (I/R) injury and liver regeneration has not been clarified. Objective: We investigated the effect of Sive against hepatic I/R injury and liver regeneration using porcine hepatectomy model, and found that Sive contributes significantly in increasing the liver volume. Methods: We induced 1-hour ischemia by occluding the vessels and the bile duct of the right and median lobes. About 40% left hepatectomy was performed after reperfusion. A total of 6 animals received Sive (10 mg/kg/h) intravenously and 6 control animals received physiologic saline (10 mg/kg/h) from commencement of laparotomy. Remnant liver volume, hemodynamics, and liver function test were compared between the groups. Expressions of TRL4 mRNA in hepatic tissues were examined using RT-PCR. Apoptosis and cell proliferation were demonstrated by TUNEL staining. Results: AST, LDH, and LA levels at 5 minutes after reperfusion were significantly lower in Sive group than in the control group. Sive significantly increased the liver volume, yet did not have any effect for liver regeneration. Conclusion: Sive is considered to reduce hepatic injury in the early phase of I/R injury.

scholarly journals Does acid-base equilibrium correlate with remnant liver volume during stepwise liver resection?

2017 ◽  
Vol 313 (4) ◽  
pp. G313-G319 ◽  
Author(s):  
Mohammad Golriz ◽  
Sepehr Abbasi ◽  
Parham Fathi ◽  
Ali Majlesara ◽  
Thorsten Brenner ◽  
...  
Keyword(s):  
Liver Resection ◽  
Hepatic Artery ◽  
Base Excess ◽  
Jugular Vein ◽  
Liver Volume ◽  
Remnant Liver ◽  
Extended Hepatectomy ◽  
Acid Base ◽  
Jugular Veins ◽  
Small For Size

Small for size and flow syndrome (SFSF) is one of the most challenging complications following extended hepatectomy (EH). After EH, hepatic artery flow decreases and portal vein flow increases per 100 g of remnant liver volume (RLV). This causes hypoxia followed by metabolic acidosis. A correlation between acidosis and posthepatectomy liver failure has been postulated but not studied systematically in a large animal model or clinical setting. In our study, we performed stepwise liver resections on nine pigs to defined SFSF limits as follows: step 1: segment II/III resection, step 2: segment IV resection, step 3: segment V/VIII resection (RLV: 75, 50, and 25%, respectively). Blood gas values were measured before and after each step using four catheters inserted into the carotid artery, internal jugular vein, hepatic artery, and portal vein. The pH, [Formula: see text], and base excess (BE) decreased, but [Formula: see text] values increased after 75% resection in the portal and jugular veins. EH correlated with reduced BE in the hepatic artery. Pco2 values increased after 75% resection in the jugular vein. In contrast, arterial Po2 increased after every resection, whereas the venous Po2 decreased slightly. There were differences in venous [Formula: see text], BE in the hepatic artery, and Pco2 in the jugular vein after 75% liver resection. Because 75% resection is the limit for SFSF, these noninvasive blood evaluations may be used to predict SFSF. Further studies with long-term follow-up are required to validate this correlation. NEW & NOTEWORTHY This is the first study to evaluate acid-base parameters in major central and hepatic vessels during stepwise liver resection. The pH, [Formula: see text], and base excess (BE) decreased, but [Formula: see text] values increased after 75% resection in the portal and jugular veins. Extended hepatectomy correlated with reduced BE in the hepatic artery. Because 75% resection is the limit for small for size and flow syndrome (SFSF), postresection blood gas evaluations may be used to predict SFSF.

scholarly journals The Application of Selective Hepatic Inflow Vascular Occlusion with Anterior Approach in Liver Resection: Effectiveness in Managing Major Complications and Long-Term Survival

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Khai Viet Ninh ◽  
Nghia Quang Nguyen ◽  
Son Hong Trinh ◽  
Anh Gia Pham ◽  
Thi-Ngoc-Ha Doan
Keyword(s):  
Liver Resection ◽  
Blood Loss ◽  
Anterior Approach ◽  
Liver Volume ◽  
Operation Time ◽  
Vascular Occlusion ◽  
Remnant Liver ◽  
Term Survival ◽  
Average Hospital ◽  
Hepatic Pedicle

Background. Hepatectomy is always a challenge to surgeons and requires an appropriate approach for specific tumors to achieve effective complication management. Selective hepatic pedicle clamping is more considerable strategy when comparing with total hepatic pedicle clamping in the balance between reducing blood loss and transfusion with causing the hepatic parenchyma damages (two main complications affecting liver resection result). Objectives. In this study, we aim to describe the application of selective hepatic inflow vascular occlusion (SHIVO) and anatomical anterior approach in liver resection and evaluate the results, focusing on intraoperative and postoperative complications. Methods. We enrolled 72 patients who underwent liver resection with SHIVO at Viet Duc University Hospital in 4-year period (2011-2014) and then followed up all of them until June 2020 (in 52.6 ± 33 months; range, 2-105 months) or up to the time of death. All the patients were diagnosed with primary or secondary liver cancer, and their future remnant liver volume measured on 64-slice CT scan (dm3) to body   weight   kg > 0.8 % (for right hepatectomy). Perioperative parameters were collected and analyzed. Results. The average operation time was 196.2 ± 62.2 minutes, and blood loss was 261.4 ± 202.9  ml; total blood transfusion proportion during and after surgery was 16.7%. Complications accounted for 44.5% of patients in which pleural effusion was the most common one (41.7%). There were no liver failure and biliary fistula after surgery. No deaths were recorded during 30 days postoperatively. Average hospital stay was 11.4 ± 3.7 days. Blood transfusions during the operation and major liver resection were the factors significantly affecting the percentage of complications after liver surgery in our study. In the last follow-up evaluation, 44 patients were dead and 28 patients were alive, in which 7 with recurrence and 21 without recurrence. The overall survival rate was 38.9%. Conclusion. SHIVO in anatomical liver resection is a safe and feasible approach to help resect precisely targeted tumors and manage several complications in liver resection.

Does acid-base equilibrium correlate with remnant liver volume during stepwise liver resection?

2018 ◽  
Vol 56 (01) ◽  
pp. E2-E89
Author(s):  
S Abbasi ◽  
M Golriz ◽  
P Fathi ◽  
A Majlesara ◽  
T Brenner ◽  
...  
Keyword(s):  
Liver Resection ◽  
Liver Volume ◽  
Remnant Liver ◽  
Acid Base ◽  
Base Equilibrium ◽  
Remnant Liver Volume ◽  
Acid Base Equilibrium
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