Octreotide prevents liver failure through upregulating 5′‐methylthioadenosine in extended hepatectomized rats

Du, Zhenggui; Zhou, Yongjie; Lu, Xufeng; Li, Lei; Lu, Changli; Li, Li; Li, Bo; Bu, Hong; Yang, Jiayin; Shi, Yujun

doi:10.1111/liv.12863

Cited by 21 publications

(19 citation statements)

References 39 publications

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“…Octreotide has been shown in the rat 90% hepa tectomy model to reduce mortality from 63% to 33% 22 . Interestingly, although octreotide had this beneficial effect on mortality, it actually reduced early hepatocyte prolifer ation.…”

Section: Key Pointsmentioning

confidence: 99%

Liver regeneration — mechanisms and models to clinical application

Forbes

Newsome

2016

Nat Rev Gastroenterol Hepatol

322

296

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Although the normal liver has a fantastic regenerative capacity, following acute injury or resection this regener ative ability becomes overwhelmed in two important scenarios: in the setting of severe acute liver injury or when there is severe chronic liver injury with aberrant liver architecture and marked liver fibrosis 1,2 . These scenarios are clinically relevant and often result in serious morbidity and mortality 3 . While there have been decades of excellent and clinically informative research into understanding the signals that control regener ation of the normal liver 4 , the mechanisms at play when the abnor mal liver attempts regeneration are less well described 5 . Understanding how regeneration fails or is impaired in the severely damaged liver is an important goal. Lessons learned from relevant animal models might have impor tance in the clinical setting and aid the develop ment of new therapies to either promote regener ation or prevent complications that arise during the period of liver regeneration.A clinical scenario in which an improved understand ing of regeneration of the compromised liver would be of benefit includes liver transplantation, here the increas ingly common use of partial liver grafts such as split livers and living donor transplants relies upon regener ation of the donor graft to reach the correct liver mass 6 .Failure of regeneration in these settings results in poor or delayed graft function, prolonged intensive care stays, occasionally a requirement for retransplantation or, ulti mately, even death of the recipient 7,8 . By understanding the pathological mechanisms driving these adverse con ditions it is hoped that the period of regeneration can be more predictable and the associated clinical complications ultimately preventable. The ability to predict or improve liver regeneration when the liver is compromised -for example, in the setting of cirrhosis when surgical resection of hepatocellular cancer (HCC) is commonly performed, or following the resection of colorectal hepatic metastasis, when the liver has received prior chemotherapy -would enable clinicians to optimize cancer resection approaches. Furthermore, by understanding the mechanisms under lying normal liver regeneration and aberrant liver regener ation in chronic liver injury it is hoped that we will be able to promote 'healthy regeneration' or remodel ling in chronic liver disease. Such a scenario in which this approach could be applied includes liver cirrhosis. Here, the initial insult (such as viral hepatitis or autoimmune hepatitis) can sometimes be directly treated, but the liver tissue is left severely damaged and still susceptible to the clinical consequences of liver failure, portal hypertension and an increased risk of HCC 9 .Abstract | Liver regeneration has been studied for many decades and the mechanisms underlying regeneration of the normal liver following resection or moderate damage are well described. A large number of factors extrinsic (such as bile acids and circulating growth factors) and intrinsi...

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Section: Key Pointsmentioning

confidence: 99%

Liver regeneration — mechanisms and models to clinical application

Forbes

Newsome

2016

Nat Rev Gastroenterol Hepatol

322

296

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“…In 2016, Mohkam et al [44] demonstrated the preventive effect of somatostatin by decreasing portal vein flow in a porcine model of SFSS [44]. Similar results were demonstrated in 90% of hepatectomized murine models using octreotide infusion [45]. Treatment of SFSS by somatostatin and propranolol has also been clinically tested and resulted in a favorable outcome [46].…”

Section: Reducing the Amount Of Parenchyma Harvested In The Donormentioning

confidence: 89%

Morbidity and Mortality of Hepatic Right Lobe Living Donors: Systematic Review and Perspectives

Brige

Hery

Chopinet

et al. 2018

JGLD

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Background & Aims: The main restriction in the development of adult-adult Living Donor Liver Transplantation (LDLT) is the risk of morbidity and mortality for donors, which raises ethical questions. The objectives of this study are to review published studies dealing with morbidity and mortality in LDLT and to identify the proposed management and strategies for preventing donor mortality and morbidity in LDLT.Methods: The Medline database was searched from 2000 to 2017 using the MeSH terms “liver transplantation” and “morbidity” or “mortality” in combination with keywords “living donor liver transplantation”.Results: Among the 382 articles obtained, 43 articles were relevant for morbidity, 15 for mortality and 6 for both morbidity and mortality. Twenty-three papers reported donor deaths. The major cause of death was sepsis (30%). Morbidity ranged from 10% to 78.3% depending on the studies.Conclusions: The living donors’ morbidity and mortality is high, currently representing the main restriction in the development of LDLT. Some promising techniques, such as the donor portal vein flow modulation could lead to the further development of LDLT.

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“…Pigs undergoing 70% and 90% extreme hepatectomy receiving somatostatin had a protective decreased portal vein flow and normalization of the hepatic venous pressure gradient. Other murine studies using octreotide infusion in rats undergoing extreme hepatectomy (90% of hepatic mass) have demonstrated a protective effect through upregulation of methylthioadenosine, thus improving hepatic histology and reducing inflammatory cytokines . Pharmacological modulation strategies evaluated in randomized controlled trials in human models of SFSS are still lacking, limiting its use in clinical practice.…”

Section: Applied Strategies To Prevent/treat Sfssmentioning

confidence: 99%

Small‐for‐size syndrome in live donor liver transplantation—Pathways of injury and therapeutic strategies

Goldaracena

Echeverri

Selzner

2017

Clinical Transplantation

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Due to the severe organ shortage and the increasing gap between the supply and demand for donor grafts, live donor liver transplantation (LDLT) has become an accepted and alternative technique for the expansion of the donor pool. However, donor safety and good recipient outcomes must be balanced regarding risk stratification and decision-making within this patient population. Small-for-size syndrome (SFSS) is one of the complications encountered after LDLT, thus increasing the burden of optimizing donor graft selection and effective treatments during its occurrence. A graft-to-recipient weight ratio (GRWR) <0.8 predisposes the graft to SFSS. However, other factors may induce this complication even without a graft-to-patient size mismatch. Several strategies to prevent this complication include portal vein flow and liver outflow modulation, as well as pharmacological treatment. Also, as an entity with a multifactorial etiology, outcomes vary between right-lobe, left-lobe, and posterior-lobe donation among series encountered in the literature. In this review, we analyze the pathophysiology and classification of this complication, the state-of-the-art on management of SFSS, and the outcomes regarding the best treatment strategy on this patient population.

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Octreotide prevents liver failure through upregulating 5′‐methylthioadenosine in extended hepatectomized rats

Abstract: Octreotide exclusively regulates the methionine cycle reaction and augments the MTA level in hepatocytes. MTA prominently protects hepatocytes against shear stress injury and reduces the secondary inflammation, thereby protecting rats from PLF.

Cited by 21 publications

References 39 publications

Liver regeneration — mechanisms and models to clinical application

Liver regeneration — mechanisms and models to clinical application

Morbidity and Mortality of Hepatic Right Lobe Living Donors: Systematic Review and Perspectives

Small‐for‐size syndrome in live donor liver transplantation—Pathways of injury and therapeutic strategies

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