Trauma is the most common cause of death in young adults and it is the third most common cause of death at all ages with liver being the most commonly blunt injured abdominal organ. In the present study we will analyze the role of HMGB1, NALP3, IL-1beta, IL-6, TNF-alpha and serum electrolytes in predicting the severity of blunt liver trauma according to the Injury Severity Score (ISS), and the American Association for the Surgery of Trauma for liver Trauma (AAST) and the potential prognostic value for morbidity, mortality and length of stay. Our study will be conducted at the Policlinico Umberto I and San Giovanni-Addolorata. All consecutive patients emergently admitted in the next 12 months for blunt liver trauma will be selected after the exclusion of patients who eventually will die in the emergency room before any type of treatment. We estimate to include at least 50 patients. Demographics, cause and mechanism of injury, hematochemical tests, HMBG1, NALP3, IL-1, IL-6 and TNF-a plasma levels at admittance and thereafter every 8 hours for the next 48 hours, serum electrolytes (Na+, Cl-, K+) values, associated injuries and computed tomography (CT) scan findings at admission will be evaluated.The patients will undergo three different types of treatment: 1-non-operative management, 2-interventional radiologic treatment, 3-operative management (peri-hepatic packing, hepatotomy and selective vascular suture or ligation and anatomical or nonanatomical hepatic resection). All patients who will undergo to an open surgical treatment will be harvested a segment of the damaged and not vital liver 2x2 cm for further biologic analysis. Three different levels of biological analyses will be performed to evaluate the influence and prognostic values of the cytokines, HMBG1and NALP3: 1-plasma level concentration with ELISA technique; 2-Western blot and RT-PCR from the hepatic cell to quantitatively calculated the RNA expression.
Several biochemical markers are associated with trauma severity and mortality but their role in predicting the outcome after blunt trauma is uncertain.
Differences in cytokines profiles and plasma level of K+ between patients affected with different degrees of blunt liver trauma may predict trauma severity. Two physiologic responses to liver trauma may be proposed; the direct hepatocytes damage, and the organ ischemia due to hypotension at various degree after the traumatic event, which determine hypothalamic activation of the sympathetic autonomous nerve system triggering norepinephrine secretion from presynaptic nerve terminals and catecholamine discharge from the adrenal medulla.
HMGB1, a typical alarmin rapidly release from cell after damage, is a marker of liver injury and its plasma level increase may be dependent from the severity of the injury. HMGB1 is passively released by necrotic/damaged cells or actively secreted by immunocompetent cells and It is well known that HMGB1 is a late mediator of lethal systemic inflammation and has a prolonged therapeutic as compared to the early inflammatory cytokines. We do not want to study the role of HMGB1 during follow-up but the elevation of HMGB1 in plasma may help as reliable biomarker to provide early and sensitive detection of liver injury at first presentation to a hospital. Although no studies regarding the release of proinflammatory cytokines in blunt liver trauma have been published, it is known that TNF release is fast after trauma and it is correlated with trauma severity.
The activation of proinflammatory cytokines through a proteolytic cleavage pathway is mediated by the activation of caspase and a direct link between HMGB1, K+ efflux, IL-1 and NALP3, the latter binded with apoptosis-associated speck-like protein and pro-capspase-1 creating the inflammosoma.
K+ serum level elevation after blunt liver trauma may be correlated with the severity of trauma. After liver trauma, in fact, K+ serum level rapidly decreases and hypo-K+ is usually observed. This finding is attributed neither to a decrease intake nor to an abnormal K+ depletion, but to an enhanced K+ uptake into the intracellular hepatic compartment due to adrenergic stimulation. Beal et al. reported that the epinephrine levels on admission are high in patients with hypo-K+. Epinephrine induces hypo-K+ because K+ normally shifts into the cells responding to epinephrine. Epinephrine levels decreased toward the normal level simultaneously with the recovery of hypo-K+ after 24¿36 hours. In liver parenchyma, the epinephrine stimulation, activates ß2-adrenergic receptors, leading to an increased cellular K+ uptake from the hepatocytes through a direct or an indirect mechanism. Meriggi et al. demonstrated the utility of K+ level at admission after blunt liver trauma in a small series of 11 patients. They concluded that, after blunt liver injury, K+ must be carefully monitored to establish an appropriate treatment and avoid complications. Recently, Ookuma et al. demonstrated the role of hypo-K+ in predicting outcomes in a series of 520 patients with head trauma. Patients presenting with hypo-K+ on admission had a severe head trauma requiring life-saving craniotomy and an increased trend toward in-hospital mortality.
Trauma severity may proportionally influence the amount of adrenergic/epinephrine stimulation affecting correspondingly the serum K+ concentration, which may be used as prognostic parameter of outcome.
If our hypotheses will result correct the AAST classification for liver trauma may have a minor role in predicting postoperative survival. Therefore, monitoring patients affected with blunt liver injury with a panel of plasma biomarkers might be predictive of survival and postoperative complication because these markers may reflect a local inflammatory status reflecting the generalized inflammatory profile of the injuries patients.