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Objective:To investigate the safety and efficacy of combining programmed death-1 (PD-1) with tyrosine kinase inhibitors (TKIs) in patients with advanced hepatocellular carcinoma (HCC) before liver transplantation(LT).Methods:The data of six males with a mean ± s. d. age of (57.5±4.3) years who were treated with PD-1 inhibitors combined with TKIs for advanced HCC before LT at Beijing You'an Hospital, Capital Medical University and the First Medical Center of Chinese PLA General Hospital were retrospectively analysed. The tumor stagings, the use of PD-1 inhibitors and TKIs with their discontinuation in pre-LT/post-LT liver function recovery durations, incidences of complication. The tumor recurrence and disease-free survival rates were determined on follow-up of these patients at outpatients clinics.Results:For the 6 patients included in this study, four patients were classified by the Barcelona Clinic Liver Cancer Staging (BCLC) as C and the China Liver Cancer Staging (CNLC) as Ⅲa, and two patients were classified by the BCLC staging as B and the CNLC asⅡb. The mean cycle of PD-1 inhibitor used was 5.5 (1-20), and the mean duration of PD-1 inhibitor discontinuation was 19.5 (12-45) days pre-LT. All patients who were treated with PD-1 inhibitors combined with TKIs reached the liver transplantation standard, and all successfully underwent orthotopic liver transplantation. The liver function recovered well without any serious complications post-LT. All the patients survived without developing any acute rejection or other complications. The follow-up time ranged from 8.2 to 27.3 months, with a median of 11.9 months. No patients had died, and 2 patients developed tumor recurrence. The median (range) tumor-free survival time was 10.9 (2.9-27.3) months.Conclusion:Patients with advanced HCC could benefit from combined PD-1 inhibitors with TKIs therapy pre-LT. There were no increased incidences of acute rejection and other complications post-LT.
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Objective:To investigate the risk factors for short-term mortality and long-term survival after liver transplantation in patients with hepatitis B related acute-on-chronic liver failure.Methods:Forty patients with hepatitis B related acute-on-chronic liver failure performing liver transplantation were prospectively collected from August 2018 to July 2021 in Beijing YouAn Hospital of Capital Medical University. The mean age was (44.5±8.79) years, there were 36 males and 4 females. The basic data, including liver and kidney function, blood routine, coagulation function, lactic acid, infection indexes as well as MELD score, MELD-Na score, CLIF-C ACLFs score, CLIF OFs score, CLIF grade within 48 hours before liver transplantation were counted. The post-LT mortality within 90 days and long-term survival were observed for these patients who were divided into survival group ( n=34) and death group ( n=6) according to the survival in 3 months after liver transplantation. The measurement data conforming to the normal distribution were expressed by mean ± standard deviation ( ± s), and the comparison was performed by t-test between groups; The skewness data were expressed by M ( Q1, Q3), and the rank sum test was used for inter-group comparison. The counting data were tested by Chi square test or Fisher exact probability method. The risk factors of short-term mortality and long-term survival were analyzed through univariate and multivariate analysis as well as survival analysis. The sensitivity, specificity and cut off value were calculated by ROC curve. The patients were divided into ≥ 48.5 scores group ( n=10) and < 48.5 scores group ( n=30) by CLIF-C ACLFs score 48.5 as cut-off value. Kaplan Meier was used for survival analysis and comparison. Results:The total bilirubin (TBIL), creatinine (CR), platelet count, international normalized ratio (INR), lactic acid and neutrophil/lymphocyte ratio (NLR) within 48 hours before liver transplantation were 24.30 (13.45, 33.95) mg/dL, 0.68 (0.53, 1.11) mg/dL and 56 (39, 82)×10 9/L, 3.12(2.33, 4.46), 2.14(1.59, 4.14) mmol/L, 4.06(2.12, 9.13) for all forty patients, respectively. The mean MELD, MELD Na, CLIF OFs, CLIF-C ACLFs and AARC scores within 48 hours before transplantation were (32.1±6.3), (33.2±5.3), (11.2±2.6), (43.8±8.8) and (10.6±2.4) scores, respectively. 65% of patients were complicated with hepatic encephalopathy, 17 patients with controllable systemic infection, 10 patients with renal function injury, 2 patients with variceal bleeding and 6 patients underwent ventilator-assisted ventilation (endotracheal intubation). All 40 patients underwent emergency orthotopic liver transplantation. The incidence of postoperative complications was 47.5%, the most common was post-LT infection (27.5%), followed by renal insufficiency (17.5%). There were significant differences in neutrophil lymphocyte ratio (NLR), lactic acid, MELD score, MELD Na score, CLIF-C ACLFs score, CLIF OFs score, CLIF grades, hepatic encephalopathy, infection and renal injury between survival group and death group ( P<0.05). Univariate logistic regression analysis showed that NLR, MELD Na score, CLIF-C ACLFs score and CLIF OFs score were the risk factors for short-term mortality after liver transplantation ( P<0.05). Multivariate logistic regression analysis showed that CLIF-C ACLFs score was an independent risk factor for 3-month mortality after liver transplantation. ROC curve showed that the area under the curve of CLIF-C ACLFs score was 0.895 (95% CI: 0.779-1.000, P=0.002), and the diagnostic sensitivity and specificity were the highest, 83.3% and 85.3% respectively when cut off value was 48.5. Meanwhile, there was significant difference in long-term survival between the patients with CLIF-C ACLFs score ≥ 48.5 and < 48.5 ( P=0.001). Conclusions:NLR, MELD Na score, CLIF-C ACLFs score and CLIF OFs score within 48 hours before liver transplantation are the risk factors for short-term mortality after liver transplantation, however CLIF-C ACLFs score is an independent risk factor for three-months mortality and long-term survival in patients with hepatitis B related acute-on-chronic liver failure after liver transplantation.
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Objective:To study the impact and the mechanism of splenectomy combined with pericardial devascularization on cirrhotic livers.Methods:Serum samples and clinical data were collected preoperatively and postoperatively from 54 patients with cirrhosis who underwent splenectomy combined with pericardial devascularization from May 2013 to Oct 2014 at Beijing You’an Hospital, Capital Medical University. Changes in hepatic arterial and portal venous blood flow, liver function and fibroscan results were analyzed. The levels of nitric oxide (NO), endothelin-1 (ET-1), interleukin-6 (IL-6), hepatocyte growth factor (HGF), transforming growth factor-β1 (TGF-β1) and matrix metalloproteinase 1 (MMP1) were measured.Results:There were 31 males and 23 females, aged(45.48±10.21)years. Free portal vein pressure decreased significantly from (37.0±7.1) cmH 2O (1 cmH 2O=0.098 kPa) to (26.1±5.7) cmH 2O after surgery ( P<0.05). Significant increases in postoperative lumen diameter (4.0±1.0) mm vs (3.1±0.7) mm were observed, accompanied by increase in peak flow velocity and blood flow of the hepatic artery. Significant deductions in lumen diameter (11.9±2.0) mm vs (13.1±1.9) mm, accompanied by reduction of peak flow velocity and blood flow of the portal vein were observed following surgery (all P<0.05). The NO level was significantly elevated immediately after splenectomy and was subsequently remained at high levels. The ET-1 level decreased 2 days after surgery and became fluctuated at low levels. The IL-6 and HGF levels increased significantly 2 days after surgery and decreased gradually after 7 days and 1 month, respectively. The TGF-β1 and the MMP1 levels increased after surgery. The endotoxin level decreased significantly after surgery (all P<0.05). Conclusion:Splenectomy combined with pericardial devascularization induced hepatic blood flow restoration, hepatocyte regeneration and reversal of fibrosis in cirrhotic livers. Splenectomy has a protective effect on cirrhotic liver when combined with pericardial devascularization.
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Objective To evaluate the role of live webcast as a new medium in the propaganda and education of liver transplant recipients. Methods According to the contents of live webcast propaganda and education meeting for liver transplant recipients, relevant data of the live webcast meeting were counted and analyzed, including baseline data of participants, participation pattern, viewing frequency and duration, etc. The characteristics between live webcast and traditional propaganda and education meetings were compared. Results By the end of the live webcast meeting, 273 participants were registered, including 2 oversea participants and 271 from China. These domestic participants were from 26 provinces, autonomous regions and municipalities in China. The total number of views was 1 526. Participants attended the meeting by clicking direct link (n=243), WeChat group access (n=22), WeChat chat access (n=7) and Dingding App access (n=1). The viewing duration was (68± 5) min. Compared with the traditional method, the number and places of registers of the live webcast propaganda and education meeting were increased. The questioning methods and filling out follow-up information were more convenient. Participants could attend the meeting free from charge anywhere, and saved more time. The live webcast propaganda and education meeting was not affected by the COVID-19 pandemic, and data statistical method was optimized. Conclusions Live webcast as a new medium, has a wide range of advantages, which provides a novel form of propaganda and education for the recipients after liver transplantation. It is of significance to improve the long-term survival rate and to enhance the quality of life of recipients after liver transplantation.
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Objective To investigate the role of cytokines combined with CLIF consortium organ failure score (CLIF-COFs) for predicting the occurrence of acute respiratory distress syndrome (ARDS) in for post-liver transplant for hepatitis B-related acute-on-chronic liver failure (HB-ACLF) patients.Methods From Jul.2014 to Oct.2017,there were 37 cases of HB-ACLF undergoing liver transplantation in Beijing YouAn Hospital,Capital Medical University.According to whether the patients happened ARDS or not,37 cases were divided into ARDS group (n =9) and non-ARDS group (n =28).All patients' plasma was prospectively collected immediately before liver transplantation and on the I st,3rd,5th,7th day post-liver transplantation.The serum levels of twenty-seven cytokines were determined by 200 LUMINEX liquid chip technology.Cytokines,CLIF-COFs,clinical and biochemical indexes were analyzed with logistic regression and the receiver operating characteristic (ROC) to confirm the correlation with ARDS post liver transplantation.Results There were significant differences between HB-ACLF patients between ARDS group and non-ARDS group in age and pre-transplant infection (P ＜ 0.05).The CLIF-COFs was higher in ARDS non-without than that in non-ARDS group (P =0.019).The serum levels of vascular endothelial growth factor and platelet-derived growth factor bb were lower but IL-6 was higher post transplantation in ARDS group.The COX analysis indicated that CLIF-COFs and post liver transplantation PDGF-BB were predictors of post-LT ARDS.The area under the receiver operating characteristic (AUROC) curves was 0.728 and 0.175,respectively.The area under the curve of the discriminatory power of CLIF-COFs combined with PDGF-BB was 0.913,and the maximum Youden index is 0.786.Conclusion CLIF-COFs combines with PDGF-BB can predict the occurrence of ARDS post-liver transplantation in HB-ACLF patients.
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Objective To study the impact of splenectomy and esophagogastric devascularization on the nutritional status of patients with cirrhosis and portal hypertension.Methods Sixty consecutive patients with cirrhosis and portal hypertension who underwent splenectomy and esophagogastric devascularization at the Beijing YouAn Hospital from April 5,2015 to January 23,2017 were included in this study.The body mass index (BMI),albumin (Alb),prealbumin (PA) and lymphocyte counts were prospectively collected at the end of 1-week,1-month,3-month,6-month and 1-year after surgery.The postoperative results were compared with the preoperative results in these patients.Results The BMI results obtained at 1-week and 1-month after surgery were significantly lower than the preoperative level [(22.14 ± 3.08)kg/m2 vs.(22.85 ± 3.14) kg/m2,(21.72 ± 3.05) kg/m2 vs.(22.86 ± 3.16) kg/m2,P ＜ 0.05].The BMI result at the end of 1-year after surgery was significantly elevated when compared with the preoperative level [(23.24 ± 3.64) kg/m2 vs.(22.68 ± 3.47) kg/m2,P ＜ 0.05].The ALB levels at 1-month and 3-month after surgery were significantly higher than the preoperative level [(39.87 ± 4.22)g/L vs.(35.35 ±5.15) g/L,(39.35 ± 4.75) g/L vs.(34.82 ± 5.50) g/L,P ＜ 0.05].The PA obtained at 1-week after surgery was significantly lower than the preoperative levels [(79.59 26.52)mg/L vs.(121.77 ±39.96)mg/L,P ＜ 0.05].The lymphocyte counts at all the points after surgery were significantly higher than the preoperative level (P ＜ 0.05).Conclusion Short term and long term nutritional status improved in patients with cirrhosis and portal hypertension after splenectomy and esophagogastric devascularization.
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Objective To investigate the role of cytokines combined with CLIF Consortium organ failure score (CLIF-COFs) in determining the prognosis of liver transplant in hepatitis B-related acute-on-chronic liver failure (HB-ACLF) patients.Methods Thirty-seven cases of HB-ACLF patients undergoing liver transplantation were divided into HB-ACLF patients with complications group (n =15) and those without complications (n =22).Plasma were prospectively collected immediately before LT and on the 1st,3rd,5th,7th day after LT in HB-ACLF patients.The serum levels of twenty-seven cytokines were determined by 200 LUMINEX liquid chip technology.Cytokines and CLIF-COFs were analyzed with logistic regression and the receiver operating characteristic to confirm the correlation with the total complications post-LT.Results The serum levels of post-transplant G-CSF and MCP-1 in HB-ACLF patients with complications were higher than those of without complications (P ＜ 0.05).The COX analysis indicated that MCP-1 and CLIF-COFs were predictors of post-LT complications [A UC:0.821,95％ CI:0.668-0.974;AUC:0.738,95％ CI:0.578-0.898].The discriminatory power of MCP-combined with CLIF-COFs [AUC:0.839,95％ CI:0.703-0.975] was better than that of either.Conclusions MCP-1 combined with CLIF organ failure score can better predict the short-term outcomes of liver transplantation in HB-ACLF patients.
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<p><b>OBJECTIVE</b>To investigate the levels of hepatitis B virus (HBV) total DNA and covalently closed circular (ccc) DNA in liver transplant recipients due to HBV-associated liver diseases and detemaine their clinical significance.</p><p><b>METHODS</b>Sixty patients undergoing liver transplantation (LT) due to HBV-associated liver diseases were enrolled for the study. Levels of HBV total and ccc DNA in plasma, liver and PBMCs were measured by RT-PCR.</p><p><b>RESULTS</b>The ratio of male:female participants was 48:12. The mean age was 52.98+/-9.40 years old, and the median duration post-LT was 72 (25-128) months. 59 of the patients had no detectable HBV DNA in plasma.Four patients had detectable levels of total HBV DNA in PBMCs, but no detectable ccc DNA. Five patients had detectable levels of total HBV DNA in liver, and two of those also had detectable levels of ccc DNA. One patients who had detectable HBV DNA in PBMCs suffered HBV recurrence.</p><p><b>CONCLUSION</b>The liver transplant recipients with detectable levels of HBV total and ccc DNA in PBMCs and liver should be considered high risk for HBV recurrence following LT.</p>
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Female , Humans , Male , Middle Aged , DNA, Circular , DNA, Viral , Hepatitis B , Hepatitis B virus , Liver Transplantation , RecurrenceABSTRACT
Objective To evaluate the influence of hepatitis B surface antigen positive or antihepatitis B core positive donors on HBV allograft re-infection or de novo hepatitis B and recipients and grafts survival after liver transplantation.Methods Between June 2004 and December 2011,510 liver transplants were performed at our department while 387 patients were followed up.Among them,9 patients received hepatitis B surface antigen positive grafts,50 patients received anti-hepatitis B core positive grafts,and 328 patients received HBV marks negative grafts.The rate of HBV allograft reinfection or de novo hepatitis B and accumulative recipients as well as grafts survival were compared.Results All recipients with hepatitis B surface antigen positive donors remained hepatitis B surface antigen carriers after operation.HBV allograft re-infection occurred in one recipient of anti-hepatitis B core positive donor group. Five recipients with HBV marks negative donors appeared hepatitis B surface antigen positive,including two cases of Lamivudine resistance leading to HBV allograft reinfection and three cases of de novo hepatitis B from non-related diseases. The 1-,3-,5-year accumulative survival rate in anti-hepatitis B core positive grafts group,hepatitis B surface antigen positive grafts group and HBV marks negative grafts group was 100％,86％,43％; 87％,79％,57％; and 87％,80％,79％,respectively (Log-rank =1.287,P =0.525).And the 1-,3-,5-year accumulative grafts survival rate in these three groups was 100％,86％,43％; 85％,77％,56％;and 86％,79％,77％,respectively (Log rank=1.288,P =0.525).During the follow-up period,no graft loss or death was found to be related to the HBV allograft re-infection or de novo hepatitis B.Conclusion Liver grafts from anti-hepatitis B core positive donors do not increase the risk of graft loss or recipient death due to HBV allograft re-infection or de novo hepatitis B under effective antiviral therapy.Hepatitis B surface antigen positive donors are feasible to save lives or prolong life in emergency situation.