OBJECTIVE: To introduce the immune response of CD4~+ T helper lymphocytes (Th) and their cytokines following liver transplantation. DATA SOURCE: A computer-based online search was conducted in Medline from January 1970 to December 2008, Wanfang Database from January 1998 to December 2008, and China Hospital Knowledge Database from January 1998 to December 2008 with the key words of "liver transplantation, rejection, immune Tolerance, T helper lymphocytes, Th1 cells, Th2 cells" in both Chinese and English. DATA SELECTION: Articles about immune response of Th and their cytokines following liver transplantation were included, but reviews and duplicated studies were excluded. MAIN OUTCOME MEASURES: A total of 36 relative articles about immune response of Th and their cytokines following liver transplantation (n=3), immune effect of Th and cytokines on liver transplantation (n=22), and relationship among Th, cytokines, and transplantation immunity (n=11) were included. RESULTS: T helper lymphocyte was of importance to regulate the immune response, with function of supporting body fluid and cellular immune. Th and their cytokines played a very important role in immune tolerance following liver transplantation. The ration of Th1/Th2 was correlated with the immune response following liver transplantation. The increased Th1 secretion might induce rejection of liver tissue. When the ration turned to Th2, the immune tolerance easily occurred. CONCLUSION: Up to now, the theory of relationship between Th1/Th2 ration and transplantation immunity is not used for clinical application. Therefore, how to determine the immune state of organism by detecting and regulating cytokines, adjust Th1/Th2 ration, and induce specific immunologic tolerance of host become hot topics in the future.

Objective To investigate the clinicopathological characteristics of HBV recurrence after liver transplantation. Methods The retrospective analysis of the clinicopathological changes was performed on 17 patients who had HBV recurrence after liver transplantation in our medical department. Results HBV recurrence happened from 4 to 48 months. Twelve of them which were identified to be YMDD mutation switched to entecavir or added adefovir. Three of them receiving chemotherapy when liver cancer recurred switched to entecavir. Two of them with withdrawal of lamivudine were given lamivudine continuously. Liver function returned to the normal level and HBVDNA was ＜ 102 U/ml after anti-hepatitis B virus. The histological changes in the transplanted livers included hepatocellular degeneration, necrosis and apoptosis, portal infiltrations and fibrosis.With time after recurrence, it was easier to see hepatitis B virus replication in liver cells, incidence of acute rejection, increases of liver fibrosis and the formation of fibrous septa, even pseudolobule.Conclusion In native HBV infection livers, fibrosis occurs more early and develops rapidly. The number of virus is closely related to liver necrosis and inflammation. Early discovery and change to quick and effective treatment of anti-hepatitis B virus in time can improve greatly the prognosis of the patients.

BACKGROUND:Prolonged therapy with lamivudine has been associated with tyrosine-methionine-aspartate-aspartate mutation, which results in hepatitis B recurrence. Recently, antiviral agents, such as entecavir, have high efficacy and low resistance rate in hepatitis B-related liver disease. However, the researches on the effect of entecavir in preventing hepatitis B recurrence after liver transplantation are rare. OBJECTIVE:To investigate the effect of entecavir combined with low-dose hepatitis B immunoglobulin in preventing hepatitis B recurrence after liver transplantation. METHODS:The fol ow-up data of 253 patients who had liver transplantation for hepatitis B virus related liver disease were retrospectively analyzed. Al patients received nucleoside analogues therapy formal y before liver transplantation. The effects of entecavir+hepatitis B immunoglobulin and lamivudine+hepatitis B immunoglobulin were compared in al the patients and the patents with hepatitis B recurrence risk factors (positive preoperative HBeAg, DNA-positive hepatitis B virus, hepatoma and tyrosine-methionine-aspartate-aspartate mutation). RESULTS AND CONCLUSION:A total of 253 patients received hepatitis B virus-related liver transplantation, and 29 patients died. There were 202 patients in lamivudine group in which 26 patients were dead and 16 patients had hepatitis B virus recurrence, and the recurrence rate was 7.92%(16/202). However, entecavir group had 51 patients without hepatitis B virus recurrence in which three patients were dead. There were significant differences in the mortality rate and recurrence rate between two groups. Compared with the lamivudine+hepatitis B immunoglobulin, entecavir+hepatitis B immunoglobulin could effectively reduce the recurrence rate of the patients with hepatitis B virus-related risk factors. Hepatitis B immunoglobulin was terminated and nucleoside analogues were modulated when recurrence appeared. Al patients hepatitis B virus DNA were control ed less than 500 IU/mL and liver function returned to normal level. Log-rank test showed that there was no significant difference in the long-term survival rate after timely treatment of hepatitis B virus recurrence. With the prevention of nucleoside analogues combined with hepatitis B immunoglobulin therapy, timely treatment of hepatitis B recurrence has little influence on the prognosis. Entecavir combined with hepatitis B immunoglobulin can effectively prevent the hepatitis B recurrence. For the patients with hepatitis B virus-related risk factors, entecavir combined with hepatitis B immunoglobulin can better reduce the recurrence rate of hepatitis B than lamivudine+hepatitis B immunoglobulin after liver transplantation.

Mammalian reproduction is closely related to their metabolic status. The hypothalamus-pituitary-gonad axis ( HPG axis) is regulated by various metabolic factors. Glucagon-like peptide-1 ( GLP-1) is one of various metabolic factors that not only affect glycemic and metabolic control, but also with many other effects, including affecting HPA axis. The function of GLP-1 is related to the location of glucagon-like peptide-1 receptor ( GLP-1R) distribution. It has been confirmed that GLP-1R is widely distributed in HPG axis. The effects of GLP-1 and GLP-1R agonists on the HPG axis have also attracted much attention. The positive effects of GLP-1 and GLP-1R agonists on the HPG axis indicated it could be the new target for the new treatment for gonadal diseases. The role of GLP-1 and GLP-1R agonists in the central nervous system is reviewed.

ObjectiveTo investigate the risk factors for tumor recurrence and death after liver transplantation in patients with hepatocellular carcinoma (HCC) and their survival. MethodsThe patients with HCC who underwent liver transplantation in The Fifth Medical Center of Chinese PLA General Hospital from January 2005 to February 2019 were enrolled, and according to the presence or absence of HCC recurrence after liver transplantation, they were divided into recurrence group and non-recurrence group. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate Cox proportional-hazards regression model analyses were used to determine the risk factors for HCC recurrence and death after liver transplantation. The Kaplan-Meier method was used for survival analysis, and the receiver operating characteristic (ROC) curve was used to investigate the predictive value of death-related risk factors after liver transplantation. ResultsA total of 391 HCC patients who underwent liver transplantation were enrolled, with a median follow-up time of 2 years, among whom 78(19.95%) experienced HCC recurrence. Preoperative alpha-fetoprotein (AFP) level＞200 ng/ml (recurrence: hazard ratio ［HR］=252, 95% confidence interval ［CI］: 1.58-4.03, P＜0.001; death: HR=2.99, 95%CI: 1.59-5.62, P＜0.001］, total tumor diameter (recurrence: HR=1.20, 95%CI: 1.12-1.28, P＜0.001; death: HR=1.10, 95%CI: 1.02-1.17, P=0.002), and vascular invasion (recurrence: HR=1.15, 95%CI: 1.04-1.26, P=0.016; death: HR=1.10, 95%CI: 1.03-1.18, P=0.004) were independent risk factors for tumor recurrence and death after liver transplantation. The 1-, 5-, and 10-year overall survival rates after liver transplantation were 94.8%, 84.2%, and 83.5%, respectively, and the 1-, 5-, and 10-year disease-free survival rates were 840%, 75.1%, and 75.1%, respectively. AFP, involvement of major blood vessels, body mass index, and total tumor diameter had a certain value in predicting the death of HCC patients with recurrence, with an area under the ROC curve of 0.789 (95% CI: 0.719-0858). ConclusionTumor biological features before transplantation are the key factors for tumor recurrence after transplantation.

Objective:To investigate the clinical efficacy of neoadjuvant chemo-hormonal therapy(NCHT)followed by radical prostatectomy(RP) plus extended pelvic lymphadenectomy for very-high-risk locally advanced prostate cancer.Methods:The data of 327 cases of very-high-risk locally advanced prostate cancer treated in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, The Second Hospital of Tianjin Medical University, and The Third Affiliated Hospital of Sun Yat-sen University from December 2014 to July 2019 were retrospectively analyzed. Patients were divided into two groups according to treatment regimens: the RP group (direct RP + extended pelvic lymphadenectomy 4-6 weeks after the biopsy of prostate) and the NCHT group (4-6 cycles of NCHT prior to RP). There were 171 cases in RP group and 156 cases in NCHT group, respectively. In the RP group, the median age was 67 (ranging 44-83)years. The median PSA at diagnosis was 27.24 (ranging 4.55-207.00) ng/ml. Patients’numbers of clinical T 2, T 3a, T 3b, T 4 stage were 13, 85, 57, 16, respectively, and clinical N 1, N 0 stage were 33 and 138, respectively. Patients’numbers of ISUP grade groups of 1, 2, 3, 4, 5 were 5, 35, 41, 51, 39, respectively. In the NCHT group, The median age was 67 years, ranging 46-78 years. The median PSA at diagnosis was 72.09(ranging 4.08-722.95)ng/ml. Patients’ numbers of clinical T 2, T 3a, T 3b, T 4 stage were 11, 47, 58, 40, respectively, and clinical N 1, N 0stage were 76 and 80, respectively. Patients’numbers of ISUP grade groups of 1, 2, 3, 4, 5 were 1, 11, 33, 43, 68, respectively. At baseline, the NCHT group showed higher PSA, higher ISUP grade, and more advanced clinical stage at diagnosis( P<0.05). The PSA, pathological down-staging rate, and positive surgical margin rate as well as the biochemical recurrence free survival(bRFS)were compared between the two groups. Results:After radical prostatectomy, compared with the RP group, the NCHT group had a higher proportion of patients achieving PSA<0.2 ng/ml at 6-week postoperative follow-up ( P<0.001), a higher pathologic tumor stage down-staging rate ( P<0.001), a higher ISUP down-grading rate ( P<0.001), and a lower positive surgical margins rate ( P<0.001). In addition, 10.9% of the NCHT group achieved pT 0 or minimal residual disease in postoperative pathology exams. Eighty-three patients (48.5%) in the RP group and 125 patients (80.1%) in the NCHT group achieved undetectable PSA after surgery and entered further analysis for bRFS, which showed NCHT group had significantly longer bRFS (19.46 months vs. 6.35 months). NCHT significantly reduced the risk for biochemical recurrence in locally advanced prostate cancer patients( HR=0.278, 95% CI 0.198-0.390, P<0.001). Such a reduce in risk for biochemical recurrence was seen in all subgroups( P<0.001). Conclusions:NCHT might improve surgical outcomes as well as bRFS in very-high-risk locally advanced prostate cancer patients.

Objective:To study the impact of simultaneous ligation of splenic artery on prognosis of patients with severe hypersplenism in liver transplantation.Methods:A retrospective analysis was performed on the clinical data of 206 patients who underwent liver transplantation in the Fifth Medical Center of PLA General Hospital from December 2016 to February 2019. There were 180 males and 26 females, aged (51.0±9.0) years old. Fifty-one patients underwent splenic artery ligation during liver transplantation and they were enrolled into the observation group, and 155 patients without splenic artery ligation were enrolled into the control group. The changes in white blood cells (WBC), platelets, alanine aminotransferase, total bilirubin and serum creatinine as well as the incidence of postoperative complications were compared between the two groups.Results:The platelet count of the observation group was significantly lower than those of the control group before operation and on days 1, 3, 7, 30 and 90 after operation, (all P<0.05). The WBC counts in the observation group were significantly lower than those in the control group before operation and on days 1 and 3 after operation (all P<0.05). However, there were no significant differences in the WBC counts between the two groups on days 5, 7, 30 and 90 after operation (all P>0.05). There were also no significant differences in alanine aminotransferase and total bilirubin indexes between the two groups after surgery (all P>0.05), but the serum creatinine levels in the observation group were significantly lower than those in the control group on days 3, 5, 7 and 30 after surgery (all P<0.05). There were no significant differences in the rates of infection, severe acute rejection, biliary tract complications, arterial/portal thrombosis and mental complications between the two groups (all P>0.05). The rate of renal replacement therapy for acute kidney injury in the observation group (9.8%, 5/55) was significantly higher than that in the control group (1.3%, 2/155) ( P<0.05). Conclusion:Ligation of splenic artery during liver transplantation was safe and it had a significant advantage in the early postoperative recovery of WBC count and creatinine without increasing the incidence of complications in patients with severe hypersplenism.

Objective:To study the risk factors and treatment of portal vein thrombosis (PVT) in patients after liver transplantation.Methods:The clinical data of 290 recipients who underwent liver transplantation at the Department of Hepatology, the Fifth Medical Center of PLA General Hospital from July 2015 to April 2019 were retrospectively analyzed. There were 245 males and 45 females, with a median age of 51(44, 56) years old. The liver transplantation recipients were divided into two groups according to whether PVT occurred or not after operation: the PVT group ( n=16) and the non-PVT group ( n=274). Gender, age and other clinical data of the recipients were compared between the two groups. Outpatient and inpatient follow-up were performed. The risk factors of postoperative PVT were analysed in the liver transplantation recipients. Results:The median follow-up of these 290 liver transplant recipients was 59(42, 73) months, and 16 patients were confirmed to have PVT after operation, with an incidence of 5.5%(16/290). Multivariate logistic regression analysis showed that preoperative PVT ( OR=12.773, 95% CI: 3.887-41.973) was an independent risk factor for PVT after liver transplantation. For the 16 patients with postoperative PVT, 10 were treated with portal vein intervention, and the remaining 6 patients were treated with oral aspirin or rivaroxaban anticoagulation due to mild symptoms. The 3-year survival rate of the PVT group was 93.8% (15/16), while that of the non-PVT group was 90.1% (247/274). There was no significant difference in the 3-year survival rates between the two groups (χ 2<0.01, P=0.969). Conclusions:Preoperative PVT in recipients was an independent risk factor for PVT after liver transplantation. For patients with postoperative PVT, appropriate treatment resulted in good results without affecting the long-term prognosis of these patients.

Objective:To evaluate the ability of 68Ga-Pentixafor (nuclide ligand imaging agents for chemokine receptor 4) PET/CT to differentiate between aldosterone-producing adenoma (APA) and adrenal nonfunctional adenoma (NFA), and to assess how well this imaging method correlates with clinical features and postoperative outcomes. Methods:This was a cross-sectional study involving 73 APA and 12 NFA patients who received 68Ga-Pentixafor PET/CT imaging at Peking Union Medical College Hospital from August 2018 to October 2021. The receiver operating characteristic (ROC) curve was used to evaluate the differential value of visual analysis and the maximum standard uptake value (SUV max) of the focus on APA and NFA. The related factors of SUV max, and its predictive effect on postoperative outcomes were analyzed using Pearson or Spearman analysis and χ2 text. Results:68Ga-Pentixafor PET/CT imaging was positive in 64 APA patients (sensitivity=87.7%) and negative in all 12 NFA patients (specificity=100%). The area under the ROC curve with SUV max differentiating APA and NFA was 0.932 ( P<0.001). When the SUV max cut-off point was 6.23, the sensitivity was 80.8% and the specificity was 100%. The SUV max correlated positively with lesion size ( r=0.598) and aldosterone/renin activity ratio ( r=0.313) and correlated negatively with potassium level ( r=-0.286), renin activity ( r=-0.240) and age of diagnosis ( r=-0.273) (all P<0.05). Of the patients who underwent adrenalectomy and received more than 6 months of post-surgical follow-up, the clinical complete remission rate was higher for 68Ga-Pentixafor PET/CT imaging-positive patients than imaging-negative patients (24/39 vs. 0/4, P=0.031). Conclusions:68Ga-Pentixafor PET/CT is effective at differentiating between APA and NFA. The SUV max of 68Ga-Pentixafor PET/CT correlates with age at onset, lesion size, and the severity of clinical manifestations, and is able to predict postoperative outcomes.

Familial hyperaldosteronism type Ⅲ(FH-Ⅲ) is extremely rare, and there are no reported cases in China. Herein, we reported two cases with FH Ⅲ, both of which presented with severe hypertension and hypokalemia in their early childhood. One patient had significantly enlarged adrenal glands and developed clinical manifestations of Cushing′s syndrome at the age of 20. Complete relief of symptoms was achieved after bilateral adrenalectomy. The other case had normal adrenal imaging, and with spironolactone treatment, blood pressure and potassium levels were well-controlled. Both cases had germline mutation of KCNJ5 gene which were c. 433G>C(p.Glu145Gln) and c. 452G>A(p.Gly151Glu), respectively.