Objective To investigate the value of cytokines in bile combined with clinical indices in predicting the degree of liver injury after liver transplantation. MethodsA total of 16 patients undergoing liver transplantation who were hospitalized in Center of Organ Transplantation, The Affiliated Hospital of Qingdao University, from January to December 2018 were enrolled, and according to the level of alanine aminotransferase (ALT) on day 1 after surgery, the patients were divided into mild liver injury (ALT ＜500 U/L) group with 10 patients and severe liver injury (ALT ＞500 U/L) group with 6 patients. Bile samples were collected on days 1, 3, 5, and 7 after surgery, and MILLIPLEX assay was used to measure the levels of 17 cytokines. R software was used to perform principal component analysis (PCA) of bile cytokines and clinical indices and gene ontology (GO) enrichment analysis of bile cytokines. The two-independent-samples t-test was used for comparison of normally distributed continuous data between two groups; The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. A Spearman correlation analysis was performed to evaluate the correlation between clinical indices and bile cytokines. ROC curve analysis was used to evaluate the predictive value of cytokines in bile and clinical indices for liver injury after liver transplantation. ResultsCompared with the mild liver injury group, the severe liver injury group had significantly higher expression levels of bile Fractalkine (Z=-2.828, P=0.003), soluble CD40 ligand (sCD40L) (Z=-2.850, P=0.008), interleukin-4 (Z=-2.398, P=0.017), CXCL10 (Z=-2.475, P=0.023), and macrophage inflammatory protein-1α (Z=-1844, P=0.043). The correlation analysis showed that on day 1 after liver transplantation, aspartate aminotransferase, ALT, and lactate dehydrogenase were positively correlated with the levels of several cytokines in bile (all P＜0.05). The area under the ROC curve of Fractalkine, sCD40L and AST were 0.933 (0.812-1.000), 0.833 (0.589-1.000) and 0.917 (0.779-1.000), respectively, suggesting that AST and Fractalkine and sCD40L in bile on the first day after liver transplantation have significant predictive value for liver injury. The results of PCA showed that bile cytokines combined with clinical indices on day 1 after liver transplantation could better distinguish the patients with mild liver injury from those with severe liver injury. GO analysis showed that bile cytokines were associated with positive feedback regulation of external stimulus, cell chemotaxis, receptor ligand activity, cytokine activity, and cytokine-cytokine receptor interaction. ConclusionFractalkine and sCD40L in bile can predict the degree of liver injury after liver transplantation.

Objective:To determine the prevalence of Helicobacter pylori (Hp) infection in orthotopic liver transplantation (LT) recipients, and to study the efficacy and safety of Hp eradication therapy.Methods:13C-urea breath test was carried out between July 2018 and October 2019. There were 104 males and 26 females with an average age of 52.1 year for these LT recipients who were regularly followed-up in the Organ Transplant Center, the Affiliated Hospital of Qingdao University. Propensity scoring was used to match age and gender in a ratio of 1∶3. A healthy group of individuals consisting of 299 males and 91 females, with an average age of 51.8 years, were selected as the control group also in a ratio of 1∶3. All patients underwent 13C-urea breath test to evaluate Hp infection and results of quadruple therapy. Results:The prevalence of Hp infection among the LT recipients was 18.5%(24/130) which was significantly lower than the control group 36.4% (142/390) (χ 2=14.400, P<0.001). Among the recipients who received LT and 13C-urea breath test for less than 1 year, 1-3 years and more than 3 years, the prevalences of Hp infection were 14.3% (6/42), 17.8%(8/45) and 23.3%(10/43), respectively. Although the prevalence of Hp showed a gradually increasing trend, no correlation between Hp infection and duration from LT was observed (χ 2=1.321, P=0.517). Seventeen Hp positive recipients underwent Hp eradication therapy. The success rate of Hp eradication was 100.0%(17/17). Immunosuppressant concentration was monitored regularly in 10 patients. During Hp eradication, the blood concentration of immunosuppressant increased from 1.7 to 3.6 times, and the drug dosage was reduced to one half to one third of what it was before Hp eradication. Seven of these 17 recipients suffered from adverse effects caused by increased levels of blood concentration of immunosuppressants, including headache, hypertension, insomnia and irritability. Normal liver and kidney functions were observed during eradication. Conclusion:In this study, the prevalence of Hp infection among liver transplant recipients was 18.5%. The success rate of Hp eradication was 100% using bismuth-containing quadruple therapy. The dosage of immunosuppressant required to be monitored, and if necessary, adjusted during eradication to reduce adverse side effects.

Objective ::To investigate the role of trehalose in hepatic ischemia-reperfusion injury and its underlying mechanisms.Methods:C57BL/6J mice were randomly divided into no-ischemia group, ischemia-reperfusion group, trehalose-treated group and normal saline control group. After ischemia for 90 minutes, reperfusion immediately or 6h, blood and liver tissues were collected, and serum was separated. The liver function parameters of ALT, AST, the inflammatory factors of TNF-α, IL-1β and IL-2, and the pathological changes of liver were detected to study the role of trehalose during hepatic ischemia-reperfusion injury. Hypoxia-reoxygenation cell model was established by AML12 mouse hepatocyte line, and divided into experimental group and control group. The experimental group was divided into low dose group and high dose group according to the concentration of trehalose administrated. And the control group had no use of trehalose. The level of apoptosis was measured to study the effect of trehalose on apoptosis induced by hepatic ischemia-reperfusion injury with flow cytometry. Western blot was utilized for detecting the levels of Caspase-3, Cleaved Caspase-3 and Bcl-2 protein to understand the molecular mechanisms of trehalose in apoptosis during hepatic ischemia-reperfusion injury.Results:In vivo animal experiments showed that liver function and such inflammatory factors as ALT, AST, TNF-α, IL-1β and IL-2 increased in ischemia-reperfusion group after hepatic ischemia-reperfusion ( P<0.05), and liver tissue became necrotic. After a treatment of trehalose, the levels of ALT, AST, TNF-α, IL-1β and IL-2 were lower than those of normalsaline control group and the area of liver tissue necrosis also decreased ( P<0.05). In vitro cell experiments showed that the apoptosis level of hepatocytes in the experimental group decreased compared with the control group.And the level of activated pro-apoptotic protein Cleaved Caspase-3 decreased, the level of anti-apoptotic protein Bcl-2 increased. Conclusions:Trehalose has protective effects on hepatic ischemia-reperfusion injury in vivo and in vitro. The mechanism may be involved in inhibiting inflammation induced by hepatic ischemia-reperfusion injury, suppressing the activation of Caspase-3 and promoting the expression of Bcl-2, thus played a protective role by extenuation of hepatocyteapoptosis.

Objective:To investigate the application value of triangular modal construed for planning approach of laparoscopic local resection of liver tumors located in superior part of central liver lobe.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 10 patients who underwent local laparoscopic resection of liver tumors located in superior part of central liver lobe at the Affiliated Hospital of Qingdao University from January to June 2020 were collected. There were 6 males and 4 females, aged from 41 to 63 years, with a median age of 54 years. Preoperative triangular model was constructed for all patients to plan approach of laparoscopic local resection of liver tumors located in superior part of central liver lobe. Observation indicators: (1) preoperative general situations of patients; (2) surgical situations; (3) follow-up. Follow-up was conducted by outpatient examination or telephone interview to detect tumor recurrence and survival of patients up to February 2021. Measurement data with normal distribution were expressed as Mean± SD. Count data were expressed was absolute numbers. Results:(1) Preoperative general situations of patients: hepatocellular carcinoma was found in 7 cases, inthahepatic cholangiocarcinoma was found in 2 cases and ovarian cancer with liver metastasis was found in 1 case. Three cases had tumors located in S4a segment, 2 cases had tumors located in ventral subsegment of S8 segment, 2 cases had tumors located in dorsal subsegment of S8 segment, and 3 cases had tumors across the ventral segment of S4a+S8. The diameter of tumors was (3.4±1.0)cm. (2) Surgical situation: all the 10 patients underwent R 0 resection successfully, with no intraoperative blood transfusion or conversion to open surgery. The operation time of 10 patients was (149±59)minutes, the volume of intraoperative blood loss was (294±163)mL, the minimum surgical margin of specimen was (1.1±0.2)cm. The alanine aminotransferase was (324±151)U/L on the postoperative first day, the aspartic aminotransferase was (401±113)U/L on the postoperative first day, and the duration of postoperative hospital stay was (9±4)days. No bile leakage, hemorr-hage, reoperation or other complications occurred in all patients. (3) Follow-up: 10 patients were followed up for 7?13 months, with a median follow-up time of 11 months. All patients had no margin recurrence or distant metastasis. Conclusion:It is safe and feasible to construct triangular modal for planning approach of local laparoscopic resection of liver tumors located in superior part of central liver lobe.

Objective:To explore the value of FibroScan in liver grafts from brain-dead donors (DBD) prior to liver transplantation (LT).Methods:Liver grafts from 52 DBD were examined using ultrasound and FibroScan before LT. The causes of death were cerebral hemorrhage ( n=25), brain trauma ( n=21) and ischemic-hypoxic cerebropathy ( n=6). Blood samples were tested before LT and a biopsy was performed pre- or intra-operation for determining pathology. The diagnostic accuracy of FibroScan results was compared with that of pathological examinations. The latter is a gold standard for evaluating liver grafts. The eligible donors were grouped by stage of liver fibrosis (F0-F4) and steatosis (S0-S3) based upon Kleiner's scoring system of nonalcoholic fatty liver disease. Results:The value of liver stiffness (LS) significantly rose in group F1 as compared with group F0 (8.74±1.32) kPa and (5.93±1.64) kPa respectively ( P<0.01). The value of LS had a significantly positive correlation with liver graft fibrosis stage ( r=0.73, P<0.01). The area under receiver operating characteristic curve (AUROC) was 0.93 for F1 stage fibrosis ( P<0.01). Significant differences existed in controlled attenuation parameter (CAP) among groups S0, S1 and S2 (173.30±38.36), (230.29±23.27) and (250.00±57.01) dB/m respectively ( F=12.41, P<0.01). CAP was correlated with liver graft steatosis stage ( r=0.64, P<0.01). And AUROC for S1/S2 stage steatosis in liver grafts was 0.89 ( P=0.002) and 0.83 ( P=0.007) respectively. Conclusions:With a high diagnostic accuracy, FibroScan quantifies fibrosis and steatosis in liver grafts from DBD and provides further imaging evidence for assessing liver grafts.

Objective:To summarize the experience of diagnosing and treating de novo gastric cancer after liver transplantation(LT).Methods:The clinical data were analyzed for 3 LT patients with de novo gastric cancer during follow-ups.Results:The mean diagnostic age was 57(47~67)years, mean time interval between LT and diagnosis of de novo gastric cancer 82(40~122)months and mean follow-up time 23(4~42)months. After surgical resections, 2 survived and another died of recurrence.Conclusions:LT recipients are recommended for regular screening of de novo malignancies. Regular endoscopic screening of gastric tumors contributes to early detection, diagnosis and treatment. It may improve long-term survival outcomes in LT recipients.

Objective To investigate the incidence of de novo malignant tumors of the digestive system after liver transplantation (LT) in China. Methods Relevant literature review was performed from Wanfang data, China National Knowledge Infrastructure (CNKI) and Chongqing VIP. The retrieval time started from the establishment of each database to May 9, 2019. The Chinese search terms were liver transplantation+ postoperative/de novo+ malignant tumor/cancer. The age distribution, sex composition, time of diagnosis, involved organs, treatment and clinical prognosis of recipients with de novo malignant tumors of the digestive system after LT in China were retrospectively analyzed. Results After literature screening, 16 articles were eventually selected including 47 cases of de novo malignant tumors of the digestive system after LT. A majority of them were male recipients. The age of the recipients was 51 (23-65) years old, most of them were middle age (45-59 years old). The average time of diagnosis of de novo malignant tumors of the digestive system after operation was 43 (2-156) months, with the highest number of cases within postoperative 1-3 years. Colon and stomach were the most common tumor sites. Surgery combined with radiotherapy and chemotherapy remained the main treatment option. However, the overall clinical prognosis of patients with de novo malignant tumors of the digestive system after LT was poor with a mortality rate of 51%. Conclusions In China, colon cancer and gastric cancer are the main de novo malignant tumors of the digestive system after LT. The overall clinical prognosis of patients with de novo malignant tumors of the digestive system is poor. Sufficient attention should be paid to postoperative monitoring and prevention.

Objective To explore the functions of extracorporeal membrane oxygenation (ECMO ) with continuous renal replacement therapy (CRRT ) for potential organ donors with cardiopulmonary failure after brain death and boost the coefficient of utilization of livers .Methods Analysis was conducted for clinical data of 5 donors with cardiopulmonary failure after brain death and their corresponding recipients from July 2015 to May 2017 .Five donors received the treatments of ECMO and CRRT .The relevant data included changes of blood pressure ,dosage of vasoactive agents , liver function ,renal function and urine volume of those treated donors .Also liver functions of liver recipients were observed .Then the clinical data of 18 normal DBD and their liver recipients were compared .Results After ECMO/CRRT ,donor blood pressures rose and the doses of vasoactive agents decreased .Meanwhile urine volume also increased .Finally 4/5 livers could be transplanted . And 10 kidneys were transplanted successfully .There was no significant inter-group difference of liver function .Conclusions The applications of ECMO and CRRT improve liver function of donors with cardiopulmonary failure after brain death and boost the rates of organ donation and utilization .

Objective To evaluate the efficacy of in-situ split liver transplantation (ISSLT) in children.Methods From June 2015 to August 2018,10 liver grafts from DBD were split in-situ.All the donors were male,and the median age of the donors was 28.5 year old (18-48 year).One left half graft and 9 left lateral lobe grafts (including 2 reduced size grafts) were transplanted to 10 pediatric recipients.Four grafts were transplanted in our center,and the rest 6 grafts were shared to other two transplant center.The primary diseases of the recipients included biliary atresia (8/10),hepatic sinus obstruction syndrome (1/10) and Alagille syndrome (1/10).The median age of the recipients was 10 month (7 month-11 year),and the mean body weight was 9.8 ± 6.6 kg (5-28 kg).Results All liver grafts were split in-situ.The mean split time of liver grafts was 88.5 ± 18.9 min.The mean weight of split grafts was 336.7-± 85.4 g.All recipients were subjected to piggyback liver transplantation.Operation time was 542.5 ± 112.1 min.Anhepatic time was 52.0 ±-13.5 min.GRWR was (3.98 ±0.96)％.GRWR of two cases was more than 5％,so segment Ⅲ was partially reduced.During the follow-up period,9 cases were alive and 1 case died due to multiple organ failure 1 day after liver transplantation.Conclusions ISSLT can enlarge the graft pool for children and achieve good results.