Evolution of Proinfl ammatory Cytokines in Hepatocellular Carcinoma Patients Undergoing Orthotopic Liver Transplantation

Hepatocellular carcinoma (HCC) is one of the most common tumors in the world, with a global incidence of 500,000 new cases per year and 82% of the cases (and deaths) occurring in developing countries (with 55% in China)[1,2]. HCC is up to 4 times more common in men than in women with 60%-90% of these tumors developing from liver cirrhosis[3]. In China, approximately 200,000 people die from HCC every year. Liver transplantation, which allows both resection of the entire, potentially tumor-bearing, liver and elimination of the cirrhosis, holds great theoretical appeal in treating this disease. However, ischemia, reperfusion injury, and antigen-independent events, are unavoidable consequences of liver transplantation, and these events are also implicated in a variety of non-transplant conditions, including liver resection and hypovolemia in the liver, which may partially determine the outcome of transplant and non-transplant clinical settings. The ischemia and reperfusion injury cause up to 10% of primary graft nonfunctioning, and can lead to a higher incidence of both acute and chronic rejection, and are also main risks for developing complications and mortality in liver transplantation patients[4-7]. Whilst the mechanisms of injury are complex, it has been reported that primary graft nonfunctioning is strongly associated with the involvement of the impaired sinusoidal endothelial and activated Kupffer cells[8,9]. The potential mediators involved in ischemia and reperfusion injury are numerous. They include proinfl ammatory cytokines such as tumor necrosis factor alpha (TNFa); interleukin (IL) 1β; and IL-6. These mediators are produced in large amounts by macrophages. The macrophages that produce them are Kupffer cells and endothelial cells. They are released rapidly by various stimuli. Recent studies have highlighted a relationship between the perioperative serum levels of proinflammatory cytokines and the clinical outcomes after liver transplantation[10,11]. These levels directly affect endothelial cells (ECs) and hepatocyte damage and hepatic sequestration of polymorphological neutrophils (PMNs), forming the crucial step in full-scaled ischemia and reperfusion injury[12,13]. In this study, researchers examined the evolutions of serum proinfl ammatory cytokines (TNFa and IL-6) in patients with hepatocellular carcinoma (