Systemic cytokine response to hepatic resections under total vascular exclusion

Badia, Josep M.; Ayton, Lynne C.; Evans, Thomas J.; Carpenter, Adam; Nawfal, G.; Kinderman, Hannah; Zografos, Georges; Üemoto, Shinji; Cohen, Jonathan; Habib, Nagy

doi:10.1080/110241598750004625

Cited by 36 publications

(24 citation statements)

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“…3,22,23 Therefore, treatments to minimize the cytokine response may play a potentially relevant role in reducing perioperative morbidity. 12,13,24,25 The aim of the present study was to investigate the effects of preoperative steroids administration in patients undergoing hepatic resection.…”

Section: Discussionmentioning

confidence: 99%

Impact of preoperative steroids administration on ischemia-reperfusion injury and systemic responses in liver surgery: A prospective randomized study

et al. 2006

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Hepatic injury secondary to warm ischemia-reperfusion (I/R) injury and alterations in haemostatic parameters are often unavoidable events after major hepatic resection. The release of inflammatory mediator is believed to play a significant role in the genesis of these events. It has been suggested that preoperative steroid administration may reduce I/R injury and improve several aspects of the surgical stress response. The aim of this prospective randomized study was to investigate the clinical benefits on I/R injury and systemic responses of preoperatively administered corticosteroids. Seventy-six patients undergoing liver resection were randomized either to a steroid group or to a control group. Patients in the steroid group received preoperatively 500 mg of methylprednisolone. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, coagulation parameters, and inflammatory mediators, interleukin 6 and tumor necrosis factor alpha were compared between the 2 groups. Length of stay, and type and number of complications were recorded as well. Postoperative serum levels of ALT, AST, total bilirubin, and inflammatory cytokines were significantly lower in the steroid than in the control group at postoperative days 1 and 2. Changes in hemostatic parameters were also significantly attenuated in the steroid group. In conclusion, the incidence of postoperative complications in the steroid group tended to be significantly lower than the control group. It is of clinical interest that preoperative steroids administration before major surgery may reduce I/R injury, maintain coagulant/anticoagulant homeostasis, and reduce postoperative complications by modulating the inflammatory response. The human body reacts to surgical stimuli through various systemic responses including the endocrine, metabolic, coagulation, and immune systems. However, extended damage may result in an exaggerated systemic response with an overwhelming activation of immune cells and the release of various mediators of stress. [1][2][3] The systemic reaction to the operation is considered to be equivalent to the systemic inflammation response syndrome, mainly caused by cytokine networks. 4,5 Raised levels of inflammatory cytokines have been related to higher postoperative mortality and morbidity rates. 2,3,6 Therefore, increased attention has evolved toward modulating potentially deleterious inflammatory response to the operation.The anti-inflammatory and immune modulating effects of steroids have been known for decades and have found extensive therapeutic use in a wide range of diseases in which inflammatory responses play major role. 7,8 Several trials have investigated the benefits of administering corticosteroids as a modulator of cytokine response in patients undergoing elective cardiothoracic or gastrointestinal surgery, as well as in cases of septic shock, suggesting that several aspects of the surgical stress responses, organ dysfunction, and postAbbreviations: POD, postoperative day; ALT, alanine aminotr...

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Section: Discussionmentioning

confidence: 99%

Impact of preoperative steroids administration on ischemia-reperfusion injury and systemic responses in liver surgery: A prospective randomized study

et al. 2006

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“…The elevation of the IL-6 concentration after hepatectomy is an important component of the early signaling pathways in liver regeneration, and IL-6 activates the acute phase of protein synthesis by hepatocytes as a part of the overall inflammatory response. 67 The plasma IL-6 concentration increases after hepatectomy from 6 h, with a peak by 24 h. 68 IL-6 binds to the receptor on hepatocytes, which leads to phosphorylation of STAT3 monomers. The relationship between platelets and LSECs is well documented in ischemia/reperfusion models.…”

Section: 54mentioning

confidence: 99%

Novel functions of platelets in the liver

Kurokawa

Zheng

Ohkohchi

2016

J of Gastro and Hepatol

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Platelets contain not only proteins needed for hemostasis but also many growth factors that are required for organ development, tissue regeneration, and repair. Thrombocytopenia, which is frequently observed in patients with chronic liver disease (CLD) and cirrhosis, is due to various causes, such as decreased thrombopoietin production and accelerated platelet destruction caused by hypersplenism; however, the relationship between thrombocytopenia and hepatic pathogenesis and the role of platelets in CLD are poorly understood. Thus, in this paper, the experimental evidence for platelets improving liver fibrosis and accelerating liver regeneration is summarized and addressed based on studies conducted in our laboratory and current progress reports from other investigators. Platelets improve liver fibrosis by inactivating hepatic stellate cells to decrease collagen production. The level of intracellular cAMP is increased by adenosine through its receptors on hepatic stellate cells, thereby resulting in inactivation of these cells. Adenosine is produced by degradation of adenine nucleotides, which are stored in abundance within the dense granules of platelets. The regenerative effect of platelets in the liver consists of three mechanisms: a direct effect on hepatocytes, a cooperative effect with liver sinusoidal endothelial cells, and a collaborative effect with Kupffer cells. Based on these experiments, a clinical trial suggested that the increase in platelets induced by platelet transfusion improved liver function in patients with CLD in a clinical setting.We highlight the current knowledge concerning the role of platelets in CLD and expect to open a novel avenue for application of these clinical therapies to treat liver disease.

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“…IL-6 produced by LSECs and Kupffer cells is one of the important components of early signaling pathways in liver regeneration, and it activates the acute phase of protein synthesis by hepatocytes as part of the overall inflammatory response (Gauldie et al, 1992;Michalopoulos & DeFrances, 1997). After hepatectomy, plasma IL-6 concentration is reported to increase from 6 hours to a peak by 24 hours (Rai et al, 1996;Badia et al, 1998). IL-6 binds to its receptor on hepatocytes, which subsequently leads to phosphorylation of STAT3 monomers (Fausto et al, 2006).…”

Section: The Effect With Liver Sinusoidal Endothelial Cellsmentioning

confidence: 99%