Liver transplantation for severe hepatic trauma:Experience from a single center

Liver transplantation has been reported in the literature as an extreme intervention in cases of severe and complicated hepatic trauma.The main indications for liver transplant in such cases were uncontrollable bleeding and postoperative hepatic insufficiency.We here describe four cases of orthotopic liver transplantation after penetrating or blunt liver trauma.The indications were liver failure,extended liver necrosis,liver gangrene and multiple episodes of gastrointestinal bleeding related to portal hypertension,respectively.One patient died due to postoperative cerebral edema.The other three patients recovered well and remain on immunosuppression.Liver transplantation should be considered as a saving procedure in severe hepatic trauma,when all other treatment modalities fail.

Effects of Wy14643 on hepatic ischemia reperfusion injury in rats

AIM: To investigate the effects and possible mechanisms of Wy14643 on hepatic ischemia-reperfusion (I/R) injury in rats.METHODS: Thirty male Sprague-Dawley rats weighing 220-280 g were randomly divided into five experimental groups: sham group (G1, n = 6): a sham operation was performed (except for liver I/R); I/R-untreated group (G2, n = 6): rats underwent liver ischemia for 90 min followed by reperfusion for 4 h; and I/R + Wy14643 groups (G3, G4, G5; n = 6): after the same surgical procedure as in group 2, animals were pretreated with Wy14643 at the dose of 1, 5 and 10 mg/kg 1 h before ischemia, respectively. Hepatic ischemia-reperfusion (I/R) was induced by clamping blood supply to the left lateral and median lobes of the liver for 90 min, and atraumatic clamp was removed for 4 h reperfusion. Blood samples and liver tissues were obtained at the end of reperfusion to assess serum and hepatic tissue homogenate aminotransferase (ALT), aspartate aminotransferase (AST), myeloperoxidase (MPO), serum interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α), as well as activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) in the hepatic tissue homogenate. RESULTS: Hepatic I/R induced a significant increase in the serum levels of ALT, AST, TNF-α, IL-1β and MPO, as well as the levels of ALT, AST and MDA in the liver tissue homogenate, which were reduced bypretreatment with Wy14643 at the dose of 1, 5 and 10 mg/kg, respectively. The activity of SOD in the liver tissue homogenate was decreased after hepatic I/R, which was enhanced by Wy14643 pretreatment. In addition, serum and liver tissue homogenate ALT and AST in the Wy14643 10 mg/kg group were lower than in the Wy14643 1 mg/kg and 5 mg/kg groups, respectively.CONCLUSION: Wy14643 pretreatment exerts significant protection against hepatic I/R injury in rats. The protective effects are possibly associated with enhancement of anti-oxidant and inhibition inflammation response.

Epigenetics of proteasome inhibition in the liver of rats fed ethanol chronically

AIM： TO examine the effects of ethanol-induced proteasome inhibition, and the effects of proteasome inhibition in the regulation of epigenetic mechanisms.METHODS： Rats were fed ethanol for 1 mo using the Tsukamoto-French model and were compared to rats given the proteasome inhibitor PS-341 （Bortezomib, Velcade^TM） by intraperitoneal injection. Microarray analysis and real time PCR were performed and proteasome activity assays and Western blot analysis were performed using isolated nuclei.RESULTS： Chronic ethanol feeding caused a significant inhibition of the ubiquitin proteasome pathway in the nucleus, which led to changes in the turnover of transcriptional factors, histone-modifying enzymes, and, therefore, affected epigenetic mechanisms. Chronic ethanol feeding was related to an increase in histone acetylation, and it is hypothesized that the proteasome proteolytic activity regulated histone modifications by controlling the stability of histone modifying enzymes, and, therefore, regulated the chromatin structure, allowing easy access to chromatin by RNA polymerase, and, thus, proper gene expression. Proteasome inhibition by PS-341 increased histone acetylation similar to chronic ethanol feeding. In addition, proteasome inhibition caused dramatic changes in hepatic remethylation reactions as there was a significant decrease in the enzymes responsible for the regeneration of S-adenosylmethionine, and, in particular, a significant decrease in the betaine-homocysteine methyltransferase enzyme. This suggested that hypomethylation was associated with proteasome inhibition, as indicated by the decrease in histone methylation.CONCLUSION： The role of proteasome inhibition in regulating epigenetic mechanisms, and its link to liver injury in alcoholic liver disease, is thus a promising approach to study liver injury due to chronic ethanol consumption.

Association between TRAIL expression on peripheral blood lymphocytes and liver damage in chronic hepatitis B

AIM:To explore a novel mechanism for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), upregulation of CD4+ and CD8+T lymphocytes participating in the patho-physiological process of chronic hepatitis B (CHB). METHODS: The levels of serum soluble TRAIL (sTRAIL), serum IFN-γ and membrane-bound TRAIL expression on peripheral leucocytes from 58 CHB patients were examined by ELISA and flow cytometry respectively. The levels of TRAIL were compared with the baseline levels of 17 healthy controls, and correlation analysis was performed between ALT, TBIL, PT, morphological change in hepatic tissues, and serum IFN-γ. RESULTS: The results showed that TRAIL levels on membranes of CD4+, CD8+ T cells in CHB patients were much higher than those in healthy controls (P<0.001), and were correlated with serum TBIL (r=0.354, P= 0.008 for CD4+ and r= 0.522, P= 0.000 for CD8+, respectively), ALT (r= 0.393, P= 0.003 for CD8+), PT (r = 0.385, P = 0.004 for CD8+) and serum IFN-y level (r = 0.302, P= 0.011 for CD4+ and r= 0.307, P= 0.009 for CD8+). On the contrary to membrane-bound TRAIL expression, serum level of sTRAIL was not correlated with that of TBIL and PT, though it was higher than that of the normal population and was positively correlated with serum HBeAg expression (r= 0.695, P = 0.001). CONCLUSION: The expression level of TRAIL on the membrane of lymphocytes was upregulated and associated with the liver injury in CHB patients. These findings suggest that upregulation of TRAIL expression may be induced by virus antigen and inflammatory cytokine IFN-γ.

Pre-existing cirrhosis is associated with increased mortality of traumatic patients: Analysis of cases from a trauma center in East China

AIM:To determine the impact of cirrhosis on trauma patients and define the factors predicting death.METHODS:The data on patients admitted to the trauma center from January 2000-2005 were studied retrospectively.The clinical variables were recorded and compared to identify the factors differentiating cirrhotic trauma survivors from non survivors.Child's classification criteria were derived from the reviewed charts of cirrhotic trauma patients to evaluate their predictive value in cirrhotic trauma.Trauma registry was also used to generate a trauma control group by matching for age,sex,abbreviated injury score(AIS)over the same period of time.The outcome variables compared were mortality rate,time of ICU and hospital stay.Results were expressed as mean ± SD.These data were analyzed by SPSS.11.0 statistical software.Univariate analysis was performed to identify significant medical factors for survivor and non survivors subjected to chi-square test.Fisher's exact test and Student's t test were performed to determine the statistical difference between cirrhotic and control groups.P < 0.05 was considered statistically significant.RESULTS:Poor prognosis of traum patients was associated with one or more of the following findings:ascitcs,hyperbilirubinemia(more than 2 mg/dL),hypoalbuminemia(less than 3.5 mg/dL),and prolonged prothrombin time(more than 12.5 seconds).Although Child's classification was used to predict the outcome in cirrhotic patients undergoing portacaval shunt procedures,no significant difference was found in mortality rate as a function of Child's classification.CONCLUSION:Cirrhosis is associated with a highermortality,a longer time of ICU and hospital stay of trauma patients.It seems that treatment of trauma patients with pre-existing severe liver disease is a challenge to surgeons.

Inhibitory effects of grape procyanidins on free radical-induced cell damage in rat hepatocytes in vitro

AIM： To study the protective effect of grape procyanidins on oxidative injury induced by ethanol and carbon tetrachloride in rat hepatocytes. METHODS： Normal rat hepatocytes as well as cells damaged by ethanol or carbon tetrachloride were incubated with different doses of grape procyanidins for 24 h. Cell proliferation, apoptosis and TNFα mRNA expression were subsequently determined using MTT assay, cell death ELISA and in situ hybridization. RESULTS： Proliferative levels of the control cells from ethanol and CCh injury groups significantly decreased while apoptosis and TNFα mRNA expression significantly increased compared to the normal control and grape procyanidins co-treatment groups （0.455 ± 0.051 vs 0.318 ±0.045, P 〈 0.05）. In comparison with the normal control, 50 and 100 mg/L grape procyanidins significantly stimulated cell growth, with a better effect observed with 100 mg/L grape procyanidins. CONCLUSION： Grape procyanidins inhibit the hepatocyte damage induced by ethanol and carbon tetrachloride, and stimulate normal hepatocyte proliferation.

Intrahepatic natural killer T cell populations are increased in human hepatic steatosis

AIM: To determine if natural killer T cell (NKT) populations are affected in nonalcoholic fatty liver disease (NAFLD). METHODS: Patients undergoing bariatric surgery underwent liver biopsy and blood sampling during surgery. The biopsy was assessed for steatosis and immunocyte infiltration. Intrahepatic lymphocytes (IHLs) were isolated from the remainder of the liver biopsy, and peripheral blood mononuclear cells (PBMCs) were isolated from the blood. Expression of surface proteins on both IHLs and PBMCs were quantified using flow cytometry. RESULTS: Twenty-seven subjects participated in thisstudy. Subjects with moderate or severe steatosis had a higher percentage of intrahepatic CD3+/CD56+ NKT cells (38.6%) than did patients with mild steatosis (24.1%, P = 0.05) or those without steatosis (21.5%, P = 0.03). Patients with moderate to severe steatosis also had a higher percentage of NKT cells in the blood (12.3%) as compared to patients with mild steatosis (2.5% P = 0.02) and those without steatosis (5.1%, P = 0.05). CONCLUSION: NKT cells are significantly increased in the liver and blood of patients with moderate to severe steatosis and support the role of NKT cells in NAFLD.

Accuracy of the AAST organ injury scale for CT evaluation of traumatic liver and spleen injuries

Objective： Detection of abdominal in- jury is a very important component in trauma management, so a precise assessment of liver and spleen injuries includ- ing their severity degree is necessary. There is a good case to believe that in emergency situations the radiologists＇ performance may profit from a systematic approach using established scoring systems. Score systems as the organ injury scale （OIS） drawn up by the American Association for the Surgery of Trauma are a valuable guidance for objec- tive trauma assessment. Aim of this study was to evaluate retrospectively whether a structured approach using the OIS may help improve trauma assessment. Methods： Fifty-three patients, 38 male and 15 female who underwent CT and laparotomy after abdominal trauma were included in this study. The laparotomy was performed by experienced surgeons with a minimum experience of 6 years. While the original CT reports were written by differ- ent radiologists with a minimum experience of 3 years, and then a radiologist with experience of 4 years reviewed the same original CT pictures, resulting in the structured report. Both the original and structured CT results on liver and spleen injuries were transferred into OIS grades. Finally, the initial and structured CT results were compared with theintraoperative findings gathered from the surgery report. Results： Regarding the original CT report we found a mean divergence of 0.68±0.8 （r=-0.45） to the OIS finding in the surgery report for liver injuries （0.69±1.17 for spleen injuries; r=-0.69）. In comparison with the structured approach, where we detected a divergence of 0.8±0.68; r=-0.63 （0.47±0.77 for spleen injuries; r=0.91）, there was no significant difference. However we detected a lower rate of over-diag- nosis in structured approaches. Conclusion： Our study shows that a structured ap- proach to triage abdominal trauma using an imaging check- list does not lead to a significantly higher detection rate, but a nonsignificant trend to reduce the rate of over- diagnoses, thus being more precise in grading the severity grade. Concerning the bias by retrospective study design, further prospective investigations are needed to evaluate the impact of trauma scores on the workflow in emergency department procedure as structured reporting systems are a valuable guidance in other radiological disciplines.

Severe hepatic trauma: surgical strategies

To probe into effective surgical procedures and improve the outcome of treatment for patients with severe hepatic injury. Methods: A retrospective study involving 113 patients with seve re hepatic trauma (AAST grade IV and V) during the past 12 years was carried out . Ninety eight patients underwent surgical treatment. Surgical interventions in cluding hepatectomy or direct control of bleeding vessels by finger fracture tec hnique with Pringle maneuver, selective ligation of hepatic artery, retrohepatic caval repair with total hepatic vascular occlusion, and perihepatic packing wer e mainly used. Results: In the 98 patients treated operatively, the survival r ate was 69.4 % (68/98). Among 40 patients with juxtahepatic venous injury (JH VI), 15 were cured with the maximum blood transfusion of 12 000 ml. Eight ca ses of Grade IV injury treated nonoperatively were cured. The percentage of fail ure of nonoperative management was 42.9 % (6/14). The overall mortality rate was 32.7 % (37/113), and 57% of the deaths were due to exsanguination. Conclusions: Reasonable surgical procedures based on classifica tion of hepatic injuries can increase the survival rate of severe liver trauma. Accurate perihepatic packing is effective in dealing with JHVI.

Treatment strategy for hepatic trauma

Liver is one of the organs with the highest injury rate, and in recent decades, the guidelines for the treatment of liver trauma have changed considerably. Now, there is a growing consensus that the most important step is diagnosis and depending upon the degree of severity, non-operative therapy is the main treatment method for hepatic trauma if conditions permit. For serious hepatic trauma patients such as those with hemodynamic instability, they should be operated upon as soon as possible. Regardless of the surgical options, doctors should control damage to patients and try to prevent complications. New therapies such as hepatic artery embolization and liver transplantation have been more and more used for the treatment of serious heoatic damage in clinics.

Treatment of 209 cases of liver injury

Objective: To summarize the experience of the treatment of traumatic hepatorrhexis. Methods: The clinical data of 209 cases of liver trauma treated in the three affiliated hospitals of the Third Military Medical University from 1989 to 1999 were retrospectively analyzed. Among the 209 patients, 108 ( 51.7 %) had Grade III or more severe liver injury. Operative treatment was performed in 186 cases and preservative treatment in 23. Results: In the operated group, 169 patients were cured. The complications occurred in 18 patients and 17 of them died. In the non operated group, the complications occurred in 22 patients and only 1 of them died. Conclusions: Severe injury and delayed treatment are two major factors leading to death from liver injuries. Surgical intervention is still the principal measure to treat traumatic hepatorrhexis. The indications for non operative treatment should be carefully selected.

Increased incidence of adrenal gland injury in blunt ab- dominal trauma： a computed tomography-based study from Pakistan

Objective： To determine the frequency of adrenal injuries in patients presenting with blunt abdomi- nal trauma by computed tomography （CT）. Methods： During a 6 month period from January 1, 2011 to June 30, 2011, 82 emergency CT examinations were performed in the setting of major abdominal trauma and ret- rospectively reviewed for adrenal gland injuries. Results： A total of 7 patients were identified as having adrenal gland injuries （6 males and 1 female）. Two patients had isolated adrenal gland injuries. In the other 5 patients with nonisolated injuries, injuries to the liver （1 case）, spleen （1 case）, retroperitoneum （2 cases） and mesentery （4 cases） were identified. Overall 24 cases with liver injuries （29 %）, 11cases with splenic injuries （13%）, 54 cases with mesenteric injuries （65%）, 14 cases （17%） with retroperitoneal injuries and 9 cases with renal injuries were identified. Conclusion： Adrenal gland injury is identified in 7 patients （11.7%） out of a total of 82 patients who underwent CT after major abdominal trauma. Most of these cases were nonisolated injuries. Our experience indicates that adrenal injury resulting from trauma is more common than suggested by other reports. The rise in incidence of adrenal injuries could be attributed to the mode of injury.

Comparison of fondaparinux sodium and low molecular weight heparin in the treatment of hypercoagulability secondary to traumatic infection

Purpose： To compare the effects and side-effects of fondaparinux sodium and low molecular weight heparin in patients with hypercoagulability accompanied with traumatic infection. Methods： Thirty-six patients with post-traumatic infections in our hospital intensive care center were diagnosed with hypercoagulability from February 2012 to February 2013. These patients were randomly divided into 2 groups. In group F （18 patients）, the patients were treated with fondaparinux sodium, 2.5 rag, 1/d for 11 d. In group L （18 patients）, the patients were treated with low molecular weight heparin, 4100 U, 1/12 h for 11 d. The incidence of deep vein thrombosis, bleeding events and multiple organ dysfunction syndrome （MODS） and mortality of two groups after anticoagulation therapy were analyzed. Fibrinogen, D-dimer level and activity of antithrombin Ⅲ were measured by the coagulation analyzer. Results： The incidence of deep vein thrombosis, MODS incidence and mortality were not significantly different between the two groups. The rate of bleeding evens in group F was lower than group L （p 〈 0.05）. Antithrombin Ⅲ got an upward trend after anticoagulant therapy, in which it was higher in group F than in group L on the 5th d and llth d （p 〈 0.05）. Fibrinogen levels were gradually increased, and there was no significant difference between two groups （p 〉 0.05）. D-dimer was significantly decreased after anticoagulant therapy for 5 d （p 〈 0.01 ）, and there were significant differences between two groups on the 5th d and 7th d （p 〈 0.05）. It showed no significant difference on the llth d （p 〉 0.05）. Conclusion： Fondaparinux sodium and low molecular weight heparin can effectively improve coagulopathy in patients with traumatic infection. Compared with low molecular weight heparin, fondaparinux sodium may reduce the risk of bleeding events in patients with hypercoagulability accompanied by traumatic infection.