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AIM To determine whether diabetes mellitus (DM) affects prognosis/recurrence after liver transplantation (LT) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS A retrospective study was conducted between January 2000 and August 2013 on 1631 patients with HBV-related HCC who underwent LT with antiviral prophylaxis. Patient data were obtained from the China Liver Transplant Registry (https://www.cltr.org/). To compare the outcomes and tumor recurrence in the HBV-related HCC patients with or without DM, statistical analyses were conducted using χ2 tests, Mann-Whitney tests, the Kaplan-Meier method, log-rank tests and multivariate step-wise Cox regression analysis. RESULTS Univariate analysis of 1631 patients who underwent LT found overall 1-, 3- and 5-year survival rates of 79%, 73% and 71% respectively in the DM patients, and 84%, 78% and 76% in the non-DM patients respectively. Overall survival rate differences after LT between the two groups were significant (P = 0.041), but recurrence-free survival rates were not (P = 0.096). By stratified analysis, the overall survival rates in DM patients for age > 50 years (P = 0.002), the presence of vascular invasion (P = 0.096), tumors ≤ 3 cm (P = 0.047), two to three tumor nodules (P = 0.007), Child-Pugh grade B (P = 0.018), and pre-LT alanine aminotransferase levels between 40 and 80 IU/L (P = 0.017) were significantly lower than in non-DM patients. Additionally, serum α-fetoprotein level > 2000 ng/mL (P = 0.052) was associated with a significant survival difference trend between DM and non-DM patients. Multivariate analysis showed that the presence of DM (P < 0.001, HR = 1.591; 95%CI: 1.239-2.041) was an independent predictor associated with poor survival after LT. CONCLUSION HBV-related HCC patients with DM have decreased long-term overall survival and poor LT outcomes. Prevention strategies for HCC patients with DM are recommended.

BACKGROUND/AIMS Liver transplant recipients include patients who present with almost all kinds of end-stage liver disease. Studying the relationship between gallstones and end-stage liver disease among liver transplant recipients is becoming important. MATERIALS AND METHODS Multiple logistic regression analysis was applied to assess 1640 liver transplant recipients. Multiple factors were involved in the analysis, including age, sex, total bilirubin and total cholesterol levels, Child score, hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, alcoholic cirrhosis, and hepatocellular carcinoma (HCC). RESULTS Age and Child score are independent risk factors for the development of gallstone disease (GD). The average age of the recipients in the GD group was 49.22±9.96 years, which was significantly higher than that in the GD-free group (48.23±9.79 years). The Child score of the recipients in the GD group was 9.21±2.47, which was significantly lower than that of the recipients in the GD-free group, which was 8.79±2.48 (t=3.23, p

Donor shortage is the biggest obstacle in organ transplantation. Living donor liver transplantation (LDLT) has been considered as a valuable approach to shortening waiting time. The objectives of this study were to investigate the feasibility of utilizing donors older than 50 years in LDLT and to evaluate the graft function and recipient survival.All LDLT cases (n=159) were divided into the older (donor age≥50 years, n=10) and younger (donor age50 years, n=149) donor groups. Donor graft and recipient condition pre-, intra- and post-operation were compared between the two groups. In particular, graft functions and recipient survivals were analyzed.The median donor age was 58.5 (52.5-60.0) years in the older donor group and 25.0 (23.0-32.0) in the younger donor group. There was no significant difference in cold ischemic time, anhepatic phase and operation time between the older and younger donor groups (P0.05). However, the volume of red blood cell transfused in operation was greater in the older donor group than in the younger donor group (1900 vs 1200 mL, P=0.023). The 1-, 3- and 5-year graft survival rates were 90%, 80% and 80% for the older donor group, and 92%, 87% and 87% for the younger donor group, respectively (P=0.459). The 1-, 3- and 5-year survival rates were 100%, 90% and 90% for recipients with older grafts, and 93%, 87% and 87% for those with younger grafts, respectively (P=0.811).It is safe for a LDLT recipient to receive liver from donors older than 50 years, and there is no significant adverse effect on graft function and long-term patients' survival.

To improve the technique of suprahepatic vena cava (SHVC) reconstruction in rat OLT, novel magnetic rings were designed and manufactured to facilitate reconstruction of SHVC and shorten the anhepatic time. One-hundred and twenty adult male Wistar rats were randomly divided into two groups: rings group (n = 30), using magnetic rings for SHVC reconstruction; suture group (n = 30), 7/0 prolene suture was used for SHVC running anastomosis as control. Cuff techniques were used for portal vein and infrahepatic vena cava reconstruction as Kamada and Calne described. The bile duct was reconnected with a stent. The hepatic re-arterialization was omitted. In the rings group, the SHVC reconstruction took 0.91 ± 0.24 (mean ± SD) min; the anhepatic phase and the recipient operation time were 5.63 ± 0.65 min and 36.02 ± 8.02 min, respectively. In suture group, the anastomotic time of SHVC was 10.40 ± 2.11 min; the anhepatic phase and the recipient operation time were 17.76 ± 2.51 and 49.38 ± 12.06 min, respectively, and there was statistically significant difference between the two groups. The ALT levels reached peak at 24 h post-OLT (186.2 ± 32.5 IU/l) and restored to normal level at 96 h gradually. In the rings group, 29 of 30 rats survived at day 7 and 28 of 30 rats survived at day 30. In contrast, only 25 of 30 recipients in suture group remained alive at day 7 and 22 of 30 remained alive at day 30 (P < 0.05). Better anastomotic healing was founded in rings group by pathology and scanning electron microscope. The magnetic rings technique provides a novel, simple method for SHVC reconstruction of OLT in rat. It significantly shortens anhepatic phase, while the success rate of the operation is satisfactory.

Use of livers infected with Clonorchis sinensis as donor organs for transplantation is controversial because of the potential associated risks. The low availability of donor livers at Tianjin First Center Hospital since 2003 prompted us to undertake cadaveric liver transplantation in 14 patients using donor livers infected with C. sinensis. None of the donors had been diagnosed with liver fluke infection before organ procurement, and in none of them was there laboratory evidence of abnormal liver function. After livers had been harvested and preserved, dead liver flukes were found in the bile of each donor; subsequent pathological examination of the flukes confirmed the diagnosis of clonorchiasis. Conventional orthotopic liver transplantation, with insertion of a T- tube, was undertaken in all 14 patients. Praziquantel, 25 mg/kg three times daily for two days, was administrated to the recipients starting on postoperative day 2. Results of tests of liver function improved rapidly after the operation in all of the patients. The median duration of follow-up was 31 months. The 1- and 3-year survival rates of the grafts were 85.7% and 78.6%, respectively. Postoperative biliary complications occurred in 2 patients (14.3%). No ova were detected in the bile or feces of any of the patients postoperatively. These findings suggest that livers infested with C. sinensis can be used as donor organs for liver transplantation. Further studies are required to establish definitive criteria for determining whether such donor organs may be used in a liver transplantation program.

AIM: To investigate the incidence of de novo hepatitis B virus (HBV) infection after pediatric living donor liver transplantation (LDLT) and to analyze the risk factors associated with this de novo HBV infection. METHODS: The clinical and laboratory data of children who underwent LDLT from June 2010 to September 2012 in First Center Hospital in Tianjin, China, were retrospectively included in the study. Intrahepatic HBV DNA in donors and recipients was quantified by real-time polymerase chain reaction using DNA extracted from formalin-fixed, paraffin-embedded tissues. RESULTS: Between June 2010 to September 2012, 32 consecutive pediatric patients underwent LDLT in our institute. Thirty LDLT patients (13 girls and 17 boys) were followed up for a median of 15 mo, of whom 53.3% (16/30) were hepatitis B core antibody (HBcAb) positive and 36.7% (11/30) were hepatitis B surface antibody (HBsAb)/HBcAb positive before transplantation. Sixteen of the children received HBcAb-positive allografts, and 43.7% (7/16) of the grafts were found to be intrahepatic HBV DNA positive. De novo HBV infection developed in 16.1% (5/30) of the children within a median of 11 mo after transplantation. All five of the HBV-infected children had received HBcAb-positive allografts, four of which were intrahepatic HBV DNA positive. Two of the children developed de novo HBV infection despite the preoperative presence of both HBsAb and HBcAb CONCLUSION: In pediatric recipients, positive intrahepatic HBV DNA in allografts could be a risk factor for de novo HBV infection from HBcAb-positive allografts. HBsAb/HBcAb positivity in pediatric LDLT patients before transplantation exhibited only weak effectiveness in protecting them against de novo HBV infection from HBcAb-positive allografts.

To provide a basis for improved prevention and treatment of hepatitis B virus (HBV) re-infection after liver transplantation, variations in the S and P genes of HBV under immunosuppression in vitro and their association with patient prognosis were investigated. For the in vitro study, HepG2.2.15 hepatocellular carcinoma cells stably producing HBV particles were treated with the immunosuppressants methylprednisolone (MP) and tacrolimus (FK506) at doses found to be non-toxic by the methylthiazolyl tetrazolium (MTT) cell viability assay. MP dose-dependently inhibited HBV DNA expression in HepG2.2.15 cells, while FK506 did not, as determined by quantitative real-time PCR (qRT-PCR). By gene sequencing, both MP and FK506 were found to cause variations in HBV S, P, and S/P overlapping regions. MP- but not FK506-induced mutations were common in the glucocorticoid response element of the P region, while both immunosuppressants caused mutations outside the nucleoside analogue resistance sites. For the in vivo study, 14 patients with HBV-related end-stage liver disease re-infected after liver transplantation, and 20 cases without HBV re-infection as controls, were studied. Seventy-five percent of re-infected recipients showed multi-loci amino acid mutations at different sites besides lamivudine (LAM)-resistant loci in the P region, including in the glucocorticoid response element. Fifty percent of re-infected recipients had mutations in the "a" determinant region and flanking sequences. Re-infection was associated with negative serum hepatitis B immunoglobulin (HBIG), as measured by a microparticle capture enzyme immunoassay. Nucleotide mutations in the S region caused missense or synonymous mutations, which caused synonymous mutations in the overlapping P region. These results showed that effects of immunosuppressants on HBV genes in vitro were different from those in clinical recipients. Positive HBV DNA and gene mutations pre-transplantation were factors affecting re-infection post-transplantation. Multiple mutations found in the P and S genes suggest that the formation of quasispecies contributes to HBV re-infection after liver transplantation.

BACKGROUND Although liver transplantation has become a standard therapy for end-stage liver diseases, the experience of pediatric liver transplantation is limited in China. In this article we report our experience in pediatric liver transplantation, and summarize its characters in their indications, surgical techniques, and postoperative managements. METHODS Thirty-one children (< or = 18 years old) underwent liver transplantation in our centers. The mean age at transplantation was 12.4 years old (ranged from 5 months to 18 years) with 7 children being less than 4 years of age at transplantation. The most common diagnosis of patients who underwent liver transplantation were biliary atresia, Wilson's disease, primary biliary cirrhosis, glycogen storage disease, hepatoblastoma, urea cycle defects, fulminant hepatic failure, etc. The surgical procedures included 12 standard (without venovenous bypass), 6 pigyback, 6 reduced-size, 3 split, 3 living donor liver transplantation, and 1 Domino liver transplantation. The triple-drug (FK506, steroid, and mycophenolate mofetil) immunosuppressive regimen was used in most of patients. Patients were followed up for a mean of 21.8 months. RESULTS Five of the 31 patients died during perioperative time; mortality rate was 16.1%. The reasons of death were infections, primary non-function, heart failure, and hypovolemic shock. Postoperative complications in 10 patients included biliary leakage, acute rejection, abdominal infection, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and pulmonary infection. Overall patient cumulative survival rate at 1-, 3-, and 5-year was 78.1%, 62.6%, 62.6%, respectively. CONCLUSIONS The most common indications of pediatric liver transplantation were congenital end-stage liver diseases. According to patients' age and body weight, standard, piggyback, reduced-size, split, or living donor liver transplantation should be performed. Pediatric liver transplantation especially requires higher surgical skills. The early postoperative management is the key to success. Postoperative bile leak was common, but most patients underwent liver transplantation had a better prognosis.

Ischemic-type biliary lesions (ITBLs) play an extremely important role in influencing the long-term survival and quality of life of recipients after orthotopic liver transplantation (OLT). Some patients can be cured by interventional therapies, however others lose their grafts at last and receive liver retransplantation (re-OLT). The aim of this study was to analyze the data of 66 patients who had received re-OLT at our center because of ITBL and to discuss the treatment of ITBL after OLT.We retrospectively analyzed 66 re-OLT cases due to ITBL from September 2001 to February 2007 at our center. The Kaplan-Meier method and the Cox-Mantel test were used to identify factors associated with mortality for univariate analysis and multivariate analysis, respectively.Fifty-five of 66 ITBL cases underwent interventional therapies before re-OLT. The actuarial survival at 1 month and 1 year for these patients was 83% and 74%, respectively. Prognostic factors for mortality in univariate analysis were model of end-stage liver disease score (MELD)16.5 (Chi(2)=5.856, P=0.016), cold ischemia time8 hours (Chi(2)=6.539, P=0.011), infections (Chi(2)=5.550, P=0.018) and complications (Chi(2)=12.168, P=0.002) after re-OLT. In the multivariate analysis (Cox regression), the risk factors independently associated with mortality were MELD score16.5 (RR: 3.140; P=0.035), cold ischemia time8.2 hours (RR: 0.192; P=0.016) and complications (RR: 3.896, P=0.003).The incidence of ITBL in China is higher than in other countries. Based on our experience, MELD score, cold ischemia time and complications after re-OLT are risk factors independently associated with mortality in retransplanted ITBL patients.

Because the orthotopic liver transplantation (OLT) was performed widely in recent 5 years throughout China, the proportion of recipients whose graft function deteriorated to be retransplantation candidates increased gradually. This study was undertaken to analyze clinical experience of orthotopic liver retransplantation (re-OLT) at our center.The medical records of 80 patients who had undergone liver retransplantation at our center from January 1999 to July 2005 were analyzed retrospectively, including indications and timing of retransplantation, surgical techniques, and the causes of death.The commonest cause leading to hepatic graft loss and subsequent retransplantation was biliary complications in 36 patients (45%). The patients underwent retransplantation more than 30 days after their primary transplant recovered better than those who underwent retransplantation within 8-30 days after primary transplantation (perioperative mortality 19.6% versus 70%). Sepsis (12 of 22 patients, 54.5%) and multiple organ failure (4 of 22 patients, 18.2%) were leading causes of re-OLT recipient deaths.Proper indications and optimal operative time, surgical procedures, perioperative monitoring and appropriate postoperative treatment contribute to the improvement of the survival rate of patients after liver retransplantation.

Background Liver transplantation is a treatment option for combined hepatocellular and cholangiocellular carcinoma (cHCC-CC) but its prognostic significance remains unclear. The present study aimed to evaluate the therapeutic effects of liver transplantation on cHCC-CC and analyze the clinicopathological factors affecting prognosis. Methods Retrospective analysis of the clinicopathological data of a case series of 21 patients with cHCC-CC who underwent orthotopic liver transplantation from April 2000 to April 2011 was performed. Cumulative survival rate and tumor-free survival rate were calculated using the Kaplan-Meier method followed by the log-rank test. Results The operative survival rate of the 21 patients was 100%; the 30 day mortality was 4.8% (1/21) and 90-day mortality was 9.5% (2/21); 1-, 2-, 3-, and 5-year overall cumulative survival rates were 64%, 47%, 39%, and 39%, respectively; and the corresponding cumulative tumor-free survival rates were 64%, 37%, 30%, and 30%, respectively. Cumulative tumor diameter, lymph node metastasis, macroscopic portal vein tumor thrombus, and mixed states according to Allen typing were identified as the primary influencing factors of poor prognosis (all P