Objectives To assess the performance of theMilan,ShanghaiFudan andHangzhou criteria based on a preoperative evaluation in patients undergoing liver transplantation (LT) for hepatitisB-related hepatocellular carcinoma (HCC).Methods Using a prospectively collected database, the data of consecutive patients with hepatitisB-relatedHCC undergoingLT at the Department of Liver Surgery of Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University fromJanuary 2005 to December 2009 were reviewed. Overall survival and tumor recurrence rates of patients fulfilling theMilan,ShanghaiFudan andHangzhou criteria were compared using log-rank test.Results Altogether 148 patients were enrolled in the study, among whom 88 fulfilled theMilan criteria and 24 and 39 were beyondMilan but within theShanghaiFudan orHangzhou criteria, respectively. After a median follow-up of 44 months, survival rates did not differ among the three groups (P=0.8780). Recurrence rates were significantly higher for newly eligible patients by theShanghaiFudan orHangzhou criteria compared with those within theMilan criteria.Conclusions TheMilan criteria should be used as the preferred criteria for the selection of hepatitisB-relatedHCC for LT. Considering the high tumor recurrence rates and donor scarcity, a moderate expansion of the Milan criteria must be performed cautiously until high-quality clinical trials are conducted.

To assess the performance of the Milan, Shanghai Fudan and Hangzhou criteria based on a preoperative evaluation in patients undergoing liver transplantation (LT) for hepatitis B-related hepatocellular carcinoma (HCC). Using a prospectively collected database, the data of consecutive patients with hepatitis B-related HCC undergoing LT at the Department of Liver Surgery of Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University from January 2005 to December 2009 were reviewed. Overall survival and tumor recurrence rates of patients fulfilling the Milan, Shanghai Fudan and Hangzhou criteria were compared using log–rank test. Altogether 148 patients were enrolled in the study, among whom 88 fulfilled the Milan criteria and 24 and 39 were beyond Milan but within the Shanghai Fudan or Hangzhou criteria, respectively. After a median follow-up of 44 months, survival rates did not differ among the three groups ( P  = 0.8780). Recurrence rates were significantly higher for newly eligible patients by the Shanghai Fudan or Hangzhou criteria compared with those within the Milan criteria. The Milan criteria should be used as the preferred criteria for the selection of hepatitis B-related HCC for LT. Considering the high tumor recurrence rates and donor scarcity, a moderate expansion of the Milan criteria must be performed cautiously until high-quality clinical trials are conducted.

OBJECTIVE: The aim of this study was to analyze the incidence and risk factors of de novo hepatitis B virus (HBV) infection from hepatitis B core antibody (anti-HBc)-positive donors in pediatric living donor liver transplantation (LDLT).METHODS: We retrospectively analyzed 46 recipients without pre-liver transplantation (LT) HBV infection evidence who underwent LDLT from October 2006 to May 2011 in our center. HBV markers, including hepatitis B surface antigen (HBsAg) and antibody (anti-HBs), anti-HBc, hepatitis B e antigen (HBeAg) and antibody (anti-HBe) were determined in both donors and recipients before LT and in recipients after LT. HBV DNA titer was measured if the recipients were strongly suspected of de novo HBV infection.RESULTS: Without prophylaxis, de novo HBV infection occurred in 11 of 46 recipients (23.9%) 6-36 months after LT. All 11 patients received grafts from anti-HBc-positive donors. The donors' baseline status and the characteristics of recipients at the time of transplantation were not associated with the acquisition of de novo hepatitis B infection. The overall 2-year survival rate of patients from anti-HBc-positive donors was 84.2%. Two de novo HBV-infected patients who had YMDD mutation were given adefovir combined with lamivudine, and their liver function gradually improved during the follow-up period.CONCLUSIONS: Anti-HBc-positive donors can significantly increase the incidence of de novo HBV infection in HBsAg-negative recipients. Administration with adefovir in patients who are resistant to lamivudine seems to be an effective and safe way for de novo HBV infection.

The aim of this study was to analyze the incidence and risk factors of de novo hepatitis B virus (HBV) infection from hepatitis B core antibody (anti-HBc)-positive donors in pediatric living donor liver transplantation (LDLT). We retrospectively analyzed 46 recipients without pre-liver transplantation (LT) HBV infection evidence who underwent LDLT from October 2006 to May 2011 in our center. HBV markers, including hepatitis B surface antigen (HBsAg) and antibody (anti-HBs), anti-HBc, hepatitis B e antigen (HBeAg) and antibody (anti-HBe) were determined in both donors and recipients before LT and in recipients after LT. HBV DNA titer was measured if the recipients were strongly suspected of de novo HBV infection. Without prophylaxis, de novo HBV infection occurred in 11 of 46 recipients (23.9%) 6–36 months after LT. All 11 patients received grafts from anti-HBc-positive donors. The donors' baseline status and the characteristics of recipients at the time of transplantation were not associated with the acquisition of de novo hepatitis B infection. The overall 2-year survival rate of patients from anti-HBc-positive donors was 84.2%. Two de novo  HBV-infected patients who had YMDD mutation were given adefovir combined with lamivudine, and their liver function gradually improved during the follow-up period. Anti-HBc-positive donors can significantly increase the incidence of de novo  HBV infection in HBsAg-negative recipients. Administration with adefovir in patients who are resistant to lamivudine seems to be an effective and safe way for de novo HBV infection.

Objective To discuss the impact of a immunosuppressive protocol using tacrolimus combined with mycophenolate without steroid on glycometabolism after liver tansplantation (LT).Methods 295 adult liver transplant recipients were under investigation and divided into two groups,to receive immunosuppression therapy using tacrolimus and mycophenolate with (n =142) or without steroid (n =153).The fasting blood-glucose level,rate of hyperglycemia,infection and metabolic complications were followed up at 1st,2nd,4th,8th,12th,16th,20th and 24th week after LT.Results There were no significant differences between two groups in gender,age.body weight and FBG level before LT.In both groups,the FBG levels were significantly elevated immediately and reached the peak at 1st week after LT,then gradually decreased over time post-LT.The FBG level and rate of hypcrglycemia were significantly lower in steroid-free group than in steroid group in each observation time point with the differences being significant (P＜0.05) at 4th week post-LT.The overall rate of hyperglycemia was 52.9％ in steroid free group and 76.8％ in steroid group with the difference being significant between the two groups (P＜0.05) and a risk ratio of 2.94 (steroid-free group versus steroid group).The rate of acute rejection was slightly higher in steroid-free group (8.50 ％ ) than in steroid group (7.75％ ) (P ＞ 0.05 ).Also the incidence of intention badness,infection and hypercholesterinemia was significantly lower in steroid group than in steroid-free group.Conclusion The immunosuppressive protocol without steroids is safe and effective of reducing the risk of hyperglycemia and metabolic complications after LT.

Objective: We examined the value of two potential novel urinary biomarkers, neutrophil gelatinase-associated lipocalin (NGAL) and L-type fatty acid binding protein (L-FABP), in diagnosing acute kidney injury (AKI) in liver transplant recipients.Methods: NGAL and L-FABP in urinary sample from Twenty-five patients before surgery and at 2, 4, 6, 12, 24, 48, 72 and 120 h after the anhepatic phase were tested. Standard statistics were used along with receiver-operating characteristic (ROC) analysis to evaluate the diagnostic value of selected markers.Results: Urinary NGAL was only slightly elevated at 2 h in the non-AKI group while rose and stayed high from 2-6 h in the AKI group. However, urinary L-FABP rose transiently in both groups 2-120 h following surgery. The level of urinary NGAL presented differences at 2-6 h (p < 0.05) and urinary L-FABP at 4 h (p < 0.05) between AKI and non-AKI groups. ROC analysis showed that area under the curves (AUCs) of NGAL were 0.766, 0.773, and 0.773 at 2, 4 and 6 h respectively while 0.760 of L-FABP at 4 h.Conclusion: Urinary NGAL rather than L-FABP appeared to be a sensitive and specific marker of AKI in liver transplant recipients.

Objective To investigate the value of urinary neutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid-binding proteins (L-FABP) in early diagnosis of acute kidney injury (AKI) after liver transplantation. Methods During 2007-2008, 25 liver transplant recipients were recruited. Blood and urinary samples were collected before operation and at 2, 4, 6,12, 24, 48, 72, 120 h after portal vein opening, and used to determine serum creatinine (Scr), as well as urinary NGAL and L-FABP, which were normalized to urinary creatinine. According to the Acute Kidney Injury Network (AKIN) criteria of AKI, all the patients were divided into AKI and non-AKI groups. Standard statistics were used along with ROC analysis to evaluate the diagnose value of selected markers. Results There were no significant differences in clinical parameters between non-AKI (n=14) and AKI (n=11) groups. Both groups had a transient rise in Scr 2-12 hours after surgery, but the rise lasted longer in AKI patients (2-24 hours). While urinary L-FABP rose transiently in both groups 2-120 hours following surgery, urinary NGAL was only slightly elevated at 2 h in the non-AKI group, but rose and stayed high from 2 to 6 h in the AKI group.ROC analysis revealed that NGAL (cut-off 43.02, 26.97 and 17.19 ng/mgCr, AUC 0.766, 0.773 and 0.773 at 2, 4 and 6 h, respectively) was better than L-FABP (cut-off 3451.75 ng/mgCr, AUC 0.760 at 4 h). Conclusion Urinary NGAL appears to be a sensitive and specific marker of AKI in liver transplant recipients, but these data need to be validated in larger prospective studies.

Objective To determine the incidence,risk factor and outcome of acute kidney injury (AKI) after living donor liver transplantation (LDLT).Methods Clinical data of adult patients undergone LDLT first were retrospectively analyzed.Acute Kidney Injury Net (AKIN) criteria was applied to define and classify the postoperative AKI.Logistic regression analysis was used to determine the risk factor of AKI.Kaplan-Meier survival curve was used to investigate the association between AKI stage and survival rate.Results Of 220 patients during the period of investigation,94 patients received LDLT.Of these 94 patients,56 patients presented AKI.The incidence of AKI after LDLT was 59.6%,and the percentages of stage Ⅰ,stage Ⅱ and stage Ⅲ AKI were 31.9%,12.8% and 14.9% respectively.Two patients with AKI (3.6%) needed the renal replacement therapy(RRT).One year survival rate of AKI patients was much lower than that of non-AKI patients (65.0% vs 96.7%,P＜0.05).Multivariate Logistic regression analysis showed that preoperative acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score (OR=5.126),the change of mean artery pressure (△MAP) during anhepatic phase (OR =5.564) and colloid transfusion in operation (OR =1.650) were independent risk factors for stage Ⅰ AKI.Preoperative prothrombin international normalized ratio (INR) (OR=4.940),preoperative proteinuria (OR=3.385)and RBC transfusion during operation (OR=1.752) were independent risk factors for stage Ⅱ-Ⅲ AKI.Conclusions Incidence of AKI after LDLT is quite high and the prognosis is poor.Paying close attention to the potential risk factors of AKI may be beneficial to the prognosis of patients.

Objective To investigate the efficacy, safety and pharmacokinetics of a once- daily extended release formulation of tacrolimus (MR4) in liver transplant recipients.Methods In an open- label study, stable liver transplant recipients (n=26) were randomly divided into MR4 or tacrolimus (TAC) group. MR4 group were converted from twice- a- day TAC to once- daily MR4 on a 1∶1 (mg:mg) basis for their total daily dose in the morning and were maintained for 3 months post- conversion, using the same therapeutic monitoring and patient care techniques employed with TAC. During the experimental period, patients’ vital signs, adverse events, liver biochemistry, blood glucose and lipid, and tacrolimus trough concentration were under evaluation. All statistics were carried out by SAS 8.0 software.Results The efficacy and safety profile of MR4 was consistent with that previously reported for TAC. MR4 group had a tendency to have less flu or upper respiratory tract infection and the incidence of adverse events and side effects was comparable in both groups. Based on pharmacokinetic profiles obtained on study day 1 (TAC) and day 86 (MR4), steady state exposure (AUC_0- 24) was equivalent between MR4 and TAC; the mean MR4/TAC ratio was 96.4%; MR4 obtained extended release pharmacy characteristics.Conclusions These results support that the safety profile of MR4 was consistent with that previously reported for TAC. Liver transplant recipients can be converted from twice- a- day TAC to once- daily MR4 with neither special efficacy nor safety concerns. Compliance in transplant recipients might be improved with MR4- based regimens owing to its less frequent dosing.

OBJECTIVE:Although hepatitis B recurrence after liver transplantation has been reduced to 0%-10% since the application of the combination therapy of hepatitis B immunoglobulin (HBIG) and lamivudine, the viral mutation resistance of lamivudine is still an obstacle to the outcome of liver transplantation. Here we evaluate the role of entecavir in preventing hepatitis B recurrence after liver transplantation.METHODS:Patients who received a liver transplantation for hepatitis B virus (HBV)-related end-stage liver disease in our center from March 2006 to December 2008 were enrolled in this study. All patients received entecavir (0.5 mg orally, daily) or lamivudine (100 mg orally, daily) together with a long-term low dosage of HBIG to prevent hepatitis B recurrence after transplantation. Serum viral markers (HBsAg, anti-HBs, HBeAg, anti-HBc and anti-HBe) and HBV-DNA level were determined.RESULTS:Thirty patients receiving entecavir and 90 patients receiving lamivudine were matched with the same age and sex in both groups. No reinfection of hepatitis B was detected in the entecavir group. The hepatitis B surface antigen of patients in the entecavir group became negative within one week and no patient had any adverse effect relating to entecavir. There was no difference in the cumulative survival rate between the entecavir group and the lamivudine group (P > 0.05).CONCLUSION:This study shows that entecavir combined with low dosages of HBIG is effective and safe in preventing hepatitis B recurrence after liver transplantation, but its long-term effect is still under investigation and a large-sample study will be carried out in the future.

Objective To evaluate the value of model for end-stage liver disease(MELD) score in predicting acute kidney injury(AKI) and its prognosis in patients receiving liver transplantation.Methods A total of 193 patients who received single donor orthotopic liver transplantation(OLT) in Renji transplantation center,Shanghai Jiaotong University School of Medicine from 2004 to 2006,were enrolled in this study.The MELD scores and other peri-operation data were collected.Post-OLT AKI was diagnosed by using AKIN criteria,and the outcomes of AKI patients were observed 28 days and 1 year later.The diagnostic and prognostic accuracy of MELD in prediction of AKI were analyzed by using receiver operating characteristic(ROC) curve.Results One hundred and sixteen(60.1%) patients developed post-OLT AKI in our group,with the incidences of AKI stage 1,2 and 3 being 50.0%,21.6%,and 28.5%,respectively.The AKI incidence was higher in patients with MELD score≥16.87 than that in patients with MELD score<16.87(71.6% vs.51.8%,P<0.05).The MELD score in patients with AKI was higher than those without AKI(19.53±12.08 vs.12.86±9.71,P<0.05).The area under curve(AUC) of pre-operation MELD scores in predicting incidence of AKI was 0.671;the AUC values in predicting AKI stage 1,2 and 3 were 0.469,0.575 and 0.775,respectively.When the cutoff of MELD was 18.50,the sensitivity and specificity in predicting AKI stage 3 were 72.7% and 71.2%,respectively.In AKI patients,post-OLT mortalities at 28 days and 1 year after operation were 15.5% and 25.9%,respectively.The MELD score of patients who died within 28 days after operation was significantly higher than that in the survived patients(30.99±11.0 vs.15.42±10.74,P<0.05).The MELD scores of patients who survived for one year after operation were significantly higher than that in the survived patients(23.22±14.08 vs.15.65±10.78,P<0.05).The AUC values of MELD scores in predicting the 28 days and 1 year mortality were 0.842 and 0.651,respectively.Conclusion Patients with AKI post-OLT have higher pre-OLT MELD scores.The pre-OLT MELD score is a sensitive predictor for predicting AKI stage 3 and early mortality after liver transplantation.The value of the MELD scores in predicting long-term prognosis needs to be further investigated.

OBJECTIVE:  Although hepatitis B recurrence after liver transplantation has been reduced to 0%–10% since the application of the combination therapy of hepatitis B immunoglobulin (HBIG) and lamivudine, the viral mutation resistance of lamivudine is still an obstacle to the outcome of liver transplantation. Here we evaluate the role of entecavir in preventing hepatitis B recurrence after liver transplantation. Patients who received a liver transplantation for hepatitis B virus (HBV)-related end-stage liver disease in our center from March 2006 to December 2008 were enrolled in this study. All patients received entecavir (0.5 mg orally, daily) or lamivudine (100 mg orally, daily) together with a long-term low dosage of HBIG to prevent hepatitis B recurrence after transplantation. Serum viral markers (HBsAg, anti-HBs, HBeAg, anti-HBc and anti-HBe) and HBV-DNA level were determined. RESULTS:  Thirty patients receiving entecavir and 90 patients receiving lamivudine were matched with the same age and sex in both groups. No reinfection of hepatitis B was detected in the entecavir group. The hepatitis B surface antigen of patients in the entecavir group became negative within one week and no patient had any adverse effect relating to entecavir. There was no difference in the cumulative survival rate between the entecavir group and the lamivudine group ( P > 0.05). CONCLUSION:  This study shows that entecavir combined with low dosages of HBIG is effective and safe in preventing hepatitis B recurrence after liver transplantation, but its long-term effect is still under investigation and a large-sample study will be carried out in the future.

OBJECTIVE:To investigate the prognosis after orthotopic liver transplantation (OLT), and to elucidate the risk factors of poor prognosis in these patients. METHODS:Adult recipients of OLT in Renji Hospital of Shanghai Jiaotong University were retrospectively analyzed. Data in pre-, intra- and post-OLT periods of these patients were collected. Acute kidney injury net (AKIN) criteria were used to analyze the post-OLT acute kidney injury (AKI). By following up all the patients for over a year, Kaplan-Meier survival analysis was used to evaluate the prognosis within 28 days and 1 year. Cox regression analysis was performed to evaluate risk factors of patient death, especially the influence of AKI on patient prognosis. RESULTS:There were 193 patients enrolled, the average age was (48.07+/-10.02) years old. The ratio of male to female was 4:1. One hundred and sixteen patients (60.1%) were found to have AKI after OLT. Twenty-eight-day mortality of post-OLT AKI patients was higher than that without AKI patients [15.5%(18/116) vs. 0, P<0.05], 1 year survival rate of post-OLT AKI patients was lower than that without AKI patients [(70.7% (82/116) vs. 90.9 (70/77), P<0.05). Kaplan-Meier survival analysis showed the survival rate of non-AKI (77 patients), AKI stage 1, 2 and 3 patients (58, 25 and 33 patients respectively) post-OLT were 90.9%, 81.0%, 84.0% and 42.4%, respectively. All the non-survivors were discovered to have AKI within 28 days post-OLT. Cox regression analysis showed pre-OLT hypertension [hazard ratio (HR)=4.398, 95% confidence interval (CI)ú 1.535-12.604, P=0.006], post-OLT AKI (HR=12.100, 95%CI: 1.565-93.540, P=0.017), infection (HR=4.709, 95%CI: 1.813-12.226, P=0.001) and acute physiology and chronic health evaluation II (APACHE II) score > or =10 (HR=3.627, 95%CI: 1.244-10.573, P=0.018) were risk factors of 1 year death. CONCLUSION:AKI is an independent risk factor of poor prognosis after liver transplantation. Prevention of AKI may improve the survival rate of OLT patients.

Objective To investigate the incidence of acute kidney injury (AKI) post-orthotopic liver transplant (OLT) and its association with prognosis. Methods Data of 28 patients received single OLT in our hospital from 2004 to 2006 were retrospectively analyzed. The incidence of AKI was investigated by new acute kidney injury network (AKIN) criteria. The follow-up was over one year. The prognosis of AKI patients at day 28 and 1 year was evaluated by Kaplan-Meier survival analysis. The association between AKI and prognosis was examined. Results A total of 193 patients were enrolled. The average age was (48.07±10.02) years old. The ratio of male to female was 4:1. One hundred and sixteen (60.1%) patients of post-OLT AKI were found, whose AKI stage 1, 2 and 3 were 50.0%, 21.6% and 28.4% respectively. Ten (8.6%) patients required renal replacement therapy (RRT) after OLT. In AKI post-OLT patients, day 28 and 1 year mortality were significantly higher than those in non-AKI patients (15.5% vs 0, 25.9% vs 3.9%, respectively, both P<0.05). Kaplan-Meier survival analysis showed the 1-year survival rates of AKI stage 1, 2, 3 post-OLT and non-AKl were 84.0%, 81.0%, 42.4% and 90.9%, respectively. The 1-year survival rate of non-AKI was significantly higher than that of AKI stage 1, 2, 3. The 1-year survival rate of AKI stage 3 was significantly lower than that of stage 1 and 2. There was no significant difference between AKI stage 1 and 2. Sct at 1 year post-OLT was significantly higher than that of baseline [(88.35±37.15) vs (73.70±33.88) μmol/L, P<0.05). The change of Scr value at 1 year compared to baseline in AKI patients was similar to non-AKI patients. However such change in AKI stage 2 and 3 was higher than that in stage 1. Conclusions The incidence of AKI post-OLT is quite high and associated to the poor prognosis in short and long periods. Renal function may decrease gradually which is associated to the AKI stage pest-OLTI.

Objective To understand the pre-operative nutritional situation in liver transplantation patients and explore its correlation with post-operative infections. Methods The medical histories, physical examinations, and laboratory test results of 81 patients who underwent liver transplantation were collected and analyzed and their nutrition statuses were assessed before operations. After the operations, there infection events were recorded and the correlation between pre-operative nutritional situation and post-operative infections were analyzed. Results Body mass index showed the malnutrition rate was 44.9% in these patients before operation, while the malnutrition rate was 69.1% by subjective global assessment (SGA), 80.2% by measuring the amount of serum albumin (ALB), and 96.1% by measuring the amount of pre-albumin. Single variable analysis showed malnutrition status (P0.01) and ascitic fluid status (P﹤0.001) were the independent risk factors of infections, while multiple variable analysis showed malnutrition grading by SGA (OR=10.057; 95% CI: 2.810-35.997) and malnutrition by measuring ALB (OR=0.324; 95%CI: 0.112-0.938) were correlated with post-operative infections. Conclusions Liver transplantation patients have severe malnutrition beforeoperation, which may influence post-operative infections·A comprehensive pre-operational nutritional assess-ment, especially SGA, is required·