Efficacy and safety of sirolimus early conversion protocol in liver transplant patients with hepatocellular carcinoma: A single-arm, multicenter, prospective study.

Mammalian target of rapamycin (mTOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant (LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival (RFS) in hepatocellular carcinoma (HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specific for the first 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefits for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data. Trial register: Trial registered at http://www.chictr.org.cn: ChiCTR2100042869.

Role of selected criteria and preventive chemotherapy in tumor recurrence after liver transplantation.

BACKGROUND: Long-term survival after liver transplantation (LT) for hepatocellular carcinoma (HCC) patients remains poor because of tumor recurrence. To improve the prognosis of HCC patients after LT, we aimed to identify different transplantation criteria and risk factors related to tumor recurrence and evaluate the effect of preventive chemotherapy in a single center. METHODS: In total, data on 20 variables and the survival of 199 patients with primary HCC who underwent LT between 2005 and 2015 were included for analysis. The patients were divided into the following three groups: Group 1, within the Milan and Hangzhou criteria (n = 51); Group 2, beyond the Milan but within the Hangzhou criteria (n = 36); and Group 3, beyond the Milan and Hangzhou criteria (n = 112). Survival probabilities for the three groups were calculated using multivariate Cox regression analysis. The association between preventive therapy and HCC-recurrence after LT was analyzed by multiple logistic regression analysis. RESULTS: Child-Pugh stage C and hepatitis B virus (HBV) infection were independent risk factors for patients with tumor recurrence who did not meet the Milan criteria. The overall survival rates of the 199 patients showed statistically significant differences among the three groups (P < 0.001). Moreover, no significant difference was noted in the survival rate between Group 1 and Group 2 (P > 0.05). Multivariate logistic regression analysis showed that postoperative prophylactic chemotherapy reduced the risk of tumor recurrence in patients who did not meet the Hangzhou and Milan criteria (OR = 0.478; 95% CI: 0.308-0.741; P = 0.001). CONCLUSIONS: Child-Pugh classification and HBV infection were the independent risk factors of tumor recurrence in HCC patients with LT. The Hangzhou criteria were effective and analogous compared with the Milan criteria. Preventive chemotherapy significantly reduced the risk of recurrence and prolonged the survival time for HCC patients beyond the Milan and Hangzhou criteria after LT.

Recombinant IL-33 prolongs leflunomide-mediated graft survival by reducing IFN-γ and expanding CD4(+)Foxp3(+) T cells in concordant heart transplantation.

Interleukin (IL)-33 is a novel IL-1 family member, and its administration has been associated with promotion of T helper type-2 (Th2) cell activity and cytokines, particularly IL-4 and IL-5 in vivo. Recently, IL-33 was shown to increase CD4(+)Foxp3(+) regulatory T cells (Tregs) and to suppress levels of the Th1-type cytokine IFN-γ in allogeneic heart transplantation in mice. Therefore, we hypothesized that IL-33 and leflunomide (Lef) could prolong graft survival in the concordant mouse-to-rat heart transplantation model. In this model, xenografts undergo acute humoral xenograft rejection (AHXR) typically on day 3 or cell-mediated rejection approximately on day 7 if AHXR is inhibited by Lef treatment. Recipients were treated with Lef (n=6), IL-33 (n=6), IL-33 combined with Lef (n=6), or left untreated (n=6) for survival studies. Heart grafts were monitored until they stopped beating. Mouse heterotopic grafts were performed, and recipients were sacrificed on days 2 and 7 for histological and flow cytometric analyses. The combination of IL-33 and Lef significantly prolonged the grafts from 17.3±2.3 to 2.8±0.4 days, compared to untreated controls. IL-33 administration with Lef, while facilitating Th2-associated cytokines (IL-4 on day 2 but not day 7), also decreased IFN-γ on day 2 and day 7, compared with Lef treatment only. Furthermore, IL-33 with Lef administration caused an expansion of suppressive CD4(+)Foxp3(+) Tregs in rats. The IL-33 and Lef combination therapy resulted in significantly prolonged graft survival, associated with markedly decreased Th1 cells and increased IL-10 levels. In addition, the combination therapy significantly decreased the percentage of CD-45(+) B cells on days 2 and 7, compared with monotherapy. These findings reveal a new immunoregulatory property of IL-33. Specifically, it facilitates regulatory cells, particularly functional CD4(+)Foxp3(+) Tregs that underlie IL-33-mediated cardiac xenograft survival. Moreover, it can decrease Th1 cells and cytokine expression of Th1 T cells in xenograft recipients, for example IFN-γ.

Prognostic Factors of Liver Transplantation for Hepatocellular Carcinoma: A Surveillance, Epidemiology, and End Results (SEER) Database Analysis.

OBJECTIVE: We aimed to identify new, more accurate risk factors of liver transplantation for liver cancer through using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Using the SEER database, we identified patients that had undergone surgical resection for non-metastatic hepatocellular carcinoma (HCC) and subsequent liver transplantation between 2010 and 2017. Overall survival (OS) was estimated using Kaplan-Meier plotter. Cox proportional hazards regression modelling was used to identify factors independently associated with recurrent disease [presented as adjusted hazard ratios (HR) with 95% CIs]. RESULTS: Totally, 1530 eligible patients were included in the analysis. There were significant differences in ethnicity (P=0.04), cancer stage (P<0.001), vascular invasion (P<0.001) and gall bladder involvement (P<0.001) between the groups that survived, died due to cancer, or died due to other causes. In the Cox regression model, there were no significant differences in OS at 5 years with different operative strategies (autotransplantation versus allotransplantation), nor at survival at 1 year with neoadjuvant radiotherapy. However, neoadjuvant radiotherapy did appear to improve survival at both 3 years (HR: 0.540, 95% CI: 0.326-0.896, P=0.017) and 5 years (HR: 0.338, 95% CI: 0.153-0.747, P=0.007) from diagnosis. CONCLUSION: This study demonstrated differences in patient characteristics between prognostic groups after liver resection and transplantation for HCC. These criteria can be used to inform patient selection and consent in this setting. Preoperative radiotherapy may improve long-term survival post-transplantation.

Sirolimus in combination with low-dose extended-release tacrolimus in kidney transplant recipients.

Introduction: Many challenges remain for long-term survival of renal allografts. Once-daily sirolimus (SRL) combined with low-dose extended-release tacrolimus (LER-TAC) may improve medication adherence and reduce the potential nephrotoxicity of calcineurin inhibitors (CNI) compared with standard immunosuppression regimens, thus potentially improving long-term graft survival. Methods: This retrospective, observational, single-center, propensity score matching (PSM) study compared conversion to SRL combined with low-dose ER-TAC and mycophenolic acid (MPA) combined with standard-dose TAC in kidney transplant recipients. After PSM, there were 56 patients in each group. Efficacy, safety, and medication adherence were evaluated over 12 months. Results: There was no significant difference between the two groups in terms of graft and recipient survival and incidence of biopsy-proven acute rejection (p = 1.000), and none of the recipients developed dnDSA after conversion. The mean eGFR improved in SRL + LER-TAC group after conversion compared to before conversion (51.12 ± 20.1 ml/min/1.73 m2 vs. 56.97 ± 19.23 ml/min/1.73 m2, p < 0.05). The medication adherence at 12 months after conversion was superior to before conversion (p = 0.002). Discussion: Our findings suggest that an immunosuppressive regimen of SRL combined with low-dose ER-TAC is no less effective and safe than standard immunosuppressive regimens for renal transplant recipients and may improve graft renal function and medication adherence.

Values of Donor Serum Lipids and Calcium in Predicting Graft Function after Kidney Transplantation: A Retrospective Study.

OBJECTIVE: Delayed graft function (DGF) and early graft loss of renal grafts are determined by the quality of the kidneys from the deceased donor. As "non-traditional" risk factors, serum biomarkers of donors, such as lipids and electrolytes, have drawn increasing attention due to their effects on the postoperative outcomes of renal grafts. This study aimed to examine the value of these serum biomarkers for prediction of renal graft function. METHODS: The present study consecutively collected 306 patients who underwent their first single kidney transplantation (KT) from adult deceased donors in our center from January 1, 2018 to December 31, 2019. The correlation between postoperative outcomes [DGF and abnormal serum creatinine (SCr) after 6 and 12 months] and risk factors of donors, including gender, age, body mass index (BMI), past histories, serum lipid biomarkers [cholesterol, triglyceride, high-density lipoprotein (HDL) and low-density lipoprotein (DL)], and serum electrolytes (calcium and sodium) were analyzed and evaluated. RESULTS: (1) Donor age and pre-existing hypertension were significantly correlated with the incidence rate of DGF and high SCr level (≥2 mg/dL) at 6 and 12 months after KT (P<0.05); (2) The donor's BMI was significantly correlated with the incidence rate of DGF after KT (P<0.05); (3) For serum lipids, merely the low level of serum HDL of the donor was correlated with the reduced incidence rate of high SCr level at 12 months after KT [P<0.05, OR (95% CI): 0.425 (0.202-0.97)]; (4) The serum calcium of the donor was associated with the reduced incidence rate of high SCr level at 6 and 12 months after KT [P<0.05, OR (95% CI): 0.184 (0.045-0.747) and P<0.05, OR (95% CI): 0.114 (0.014-0.948), respectively]. CONCLUSION: The serum HDL and calcium of the donor may serve as predictive factors for the postoperative outcomes of renal grafts after KT, in addition to the donor's age, BMI and pre-existing hypertension.

[Jinghuaweikang capsules combined with triple therapy in the treatment of Helicobacter pylori associated gastritis and duodenal ulcer and analysis of antibiotic resistance: a multicenter, randomized, controlled, clinical study].

OBJECTIVE: To explore the efficacy of Jinghuaweikang capsules plus triple therapy (LACJ) in treatment of Helicobacter pylori (H. pylori) associated gastritis or duodenal ulcer, compare it with bismuth-containing quadruple therapy (LACB) and standard triple therapy (LAC) and analyze the antibiotic sensitivity of gastric mucosal H. pylori strains from the failed patients. METHODS: A total of 565 patients with H. pylori infection were recruited from 11 hospitals from January 2010 to June 2011. There were 336 males and 229 females. They underwent gastroendoscopy examination due to upper gastrointestinal symptoms and had never received H. pylori eradication therapies. Duodenal ulcer patients were divided randomly into LACJ therapy group, LACB therapy group and LAC therapy group while gastritis patients LACJ therapy group and LACB therapy group. Group LAC received lansoprazole 30 mg + amoxicillin 1000 mg + clarithromycin 500 mg, twice a day, for 7 d (d1-7). Group LACJ: LAC therapy plus Jinghuaweikang, 3 capsules, twice a day, for 7 d (d1-7) then Jinghuaweikang, 3 capsules, twice a day, for 14 d (d8-21). Group LACB: LAC plus bismuth potassium citrate 220 mg, twice a day, for 7 d (d1-7) and then bismuth potassium citrate 220 mg, twice a day, for 14 d (d8-21). All duodenal ulcer patients received lansoprazole (30 mg, once a day) for 14 days after the first 7-day of treatment (d 8-21). At least 28 days after the end of treatment, all patients underwent (13)C urea breath test. Gastric mucosa was collected under endoscopy from the failed patients. The detection technique of gene chip was employed to detect antibiotics resistant gene from mucosa. RESULTS: The eradication rates of duodenal ulcer patients in groups LACJ, LACB and LAC were as follows: per-protocol (PP), 80.2% (77/96), 89.9% (89/99) and 72.2% (70/97) (P = 0.007), intention-to-treat (ITT), 78.6% (77/98), 88.1% (89/101) and 70.0% (70/100) (P = 0.007). No statistical differences existed between groups LACJ and LACB or LAC (all P > 0.05). But there were statistical differences between groups LACB and LAC (both P = 0.002). The eradication rates of PP and ITT of chronic gastritis patients in groups LACJ and LACB were as follows: 75.8% (97/128), 74.6% (97/130) vs 83.8% (109/130), 80.1% (109/136) (both P > 0.05). The symptomatic improvements of abdominal pain, burning and acid reflux of duodenal ulcer patients in group LACJ were higher than those in groups LACB and LAC. There were statistical differences between groups LACJ and LAC (all P < 0.05). The symptomatic improvements of bloating and belching for chronic gastritis patients in group LACJ were higher than those of group LACB. But no significant difference existed between two groups (all P > 0.05). Sixty samples of gastric mucosa were collected from the failed patients. The detection rates of antibiotic-resistant gene to clarithromycin and amoxicillin were 60.0% (36/36) and 18.3% (11/60) respectively. CONCLUSIONS: The efficacy of LACJ for the treatment of H. pylori infection patients is similar to LACB and superior to LAC. And the symptomatic improvement of patients is better than the other two regimens. The main cause of treatment failure is antibiotic resistance of H. pylori strains.

Infective Artery Rupture of Renal Allografts: A Single-Center Retrospective Study in China.

OBJECTIVE: This study investigated the composition of pathogenic microorganisms, clinical features, and therapeutic strategies of infective artery rupture of renal allografts in recipients receiving deceased donor (DD) kidneys. METHODS: We retrospectively studied the clinical data of the DD kidney transplant recipients with donor-associated infection at Tongji Hospital, Wuhan, China from January 1, 2015 to December 31, 2018, related recipients and corresponding donors. We collected the entire results of pathogenic microorganisms cultured from these related ruptured kidneys and then analyzed their distribution and differences. RESULTS: A total of 1440 kidney transplants from DD were performed in our center. The total incidence of infective artery rupture in kidney transplants was about 0.76% (11/1440), and the annual incidence ranged from 0.25% to 1.03%. The microbial culture results revealed that 11 recipients suffered from infective artery rupture and 3 recipients who accepted the kidney from same donor had the donor-associated pathogens, including 9 fungal strains (28.1%) and 23 bacterial strains (71.9%). There were 4 recipients infected with multi-drug-resistant Staphylococcus and Klebsiella pneumoniae from the above 11 recipients, of which, 10 recipients underwent graft loss, and one died of septic shock. The microbial cultures of the remaining 3 recipients who received appropriate anti-infective regimens turned negative eventually, and the patients were discharged successfully without significant complications. CONCLUSION: Renal recipients with infections derived from DDs were at high risk of artery rupture, graft loss, or even death. Appropriate anti-infective treatment is essential to reduce the incidence of artery rupture and mortality.

[Histopathologic analysis of 1500 renal allograft biopsies].

OBJECTIVE: To summarize the histopathological features of posttransplant complications for renal allografts and evaluate the biopsy values. METHODS: Between January 1997 and May 2010, a total of 1712 percutaneous renal allograft biopsies were performed in 1500 kidney transplants and diagnostic procedures for staining, classification and staging had been performed according to the Banff 1997 and 2005 Schema. RESULTS: There were 213 (14.2%) cases of acute T cell-mediated rejection post transplantation in 1500 kidney transplants. Meanwhile there were 36 (2.4%) cases of acute antibody-mediated rejection. Chronic T cell-mediated rejection and chronic antibody-mediated rejection were 251 (16.7%) cases and 45 (3.0%) cases, respectively. Acute CNI-nephrotoxicity and chronic CNI-nephrotoxicity were 106 (7.1%)cases and 251 (16.7%) cases, respectively. Relapsed or new nephropathy were 6 (0.4%) cases. Chronic CNI-nephrotoxicity is the most common cause of allograft dysfunction in the long survival recipients. CONCLUSION: Percutaneous renal allograft biopsy is valuable for the diagnosis of various posttransplantation complications.

[Histopathological study of 268 hepatic allograft biopsies].

OBJECTIVE: To observe the histopathological features of posttransplant complications for hepatic allografts and evaluate their biopsy values. METHODS: From January 1999 to May 2011, a total of 268 percutaneous hepatic allograft biopsies were conducted in 207 recipients and the diagnostic procedures for staining, classification and staging performed according to the Banff schema and Chinese Schema on hepatic allograft rejection. RESULTS: Among them, there were ischemia/reperfusion injury (n = 26, 9.7%), acute T cell-mediated rejection (n = 83, 31.0%), acute antibody-mediated rejection (n = 12, 4.5%), chronic posttransplantation rejection (n = 31, 11.6%), immunosuppressive-induced liver injury (n = 70, 26.1%) and recurrent diseases (n = 18, 6.7%). Acute T cell-mediated rejection and drug-induced liver injury were two most common causes of allograft dysfunctions. CONCLUSION: Percutaneous hepatic allograft biopsy is valuable for the diagnosis and evaluation of various posttransplantation complications.

An improved purification approach with high cell viability and low cell loss for cryopreserved hepatocytes.

A modified purification procedure is described for effectively eliminating dead cells after hepatocyte cryopreservation. Isolated hepatocytes from six pig tissue samples were cryopreserved in liquid nitrogen for 2 weeks. After thawing, we developed a pre-incubation step prior to gradient centrifugation. The hepatocytes were subsequent cultured in suspension overnight (12-16 h), and then dead cells were eliminated by Ficoll 400 purification. The results showed that a high viability (mean of 96%) of cells was obtained, with a low viable cell loss in number (2-5%), by using this modified method.

[Inducing of epithelial mesenchymal transition of HK-2 cells by connective tissue growth factor in vitro].

OBJECTIVE: To investigate the role of connective tissue growth factor (CTGF) in epithelial mesenchymal transition of HK-2 cells in vitro. METHODS: HK-2 cells were randomly divided into two groups: (1) control group including cells cultured in DMEM medium supplemented with 10% fetal bovine serum only; and (2) experimental group including cells cultured in DMEM medium supplemented with 10% fetal bovine serum and recombinant CTGF at a final concentration of 5 microg/L. The cells were collected at 72 h time points. Direct immunofluorescence staining and immunohistochemistry were used to evaluate the E-cadherin, Vimentin, alpha-SMA and ERK2 in cells. Western-blotting was used to detect the E-cadherin, Vimentin and ERK2 protein expression. Boyden Chamber was used to detect the migration of tubular endothelium at 1 d, 3 d and 5 d. RESULTS: There were less E-cadherin but more Vimentin expressed in cells of the experimental group. The presence of alpha-SMA was detected at 48 h with peak at 72 h in the cells of the experimental group. On the first day, the cellular migration in the two groups showed no difference. However, after 3 days, the transformed cells migrated surpassed the control group with peak at the 5th day [(45.0+/-1.1):(14.0+/-1.2), P<0.05)]. CONCLUSION: Connective tissue growth factor induces mesenchymal transformation of HK-2 cells, in which the ERK2 signaling pathway may play an important role.

[Ideas and methods for treatment of gastrointestinal diseases by integrated Chinese and Western medicine].

The fundamental mechanism of gastrointestinal diseases is the imbalance between the attack factor and the protective factor of stomach mucous membrane. It can not outbreak if the protective factor is stronger than the attack factor; otherwise, it will. Attack and protective function inside the stomach are mediated by various factors. These related factors interaction constitutes a complicated network system. This kind of outbreak theories of imbalance in Western medicine is same as that, "The sense of right saves inside, the evil can't do" and "Evil is competing with right, all diseases occur", in Chinese medicine. So, it is the key which points to futher study the interaction between gastrointestinal attack factors and protective factors by traditional Chinese medicine, thus improving the clinical effect.

Resistance to anti-xenogeneic response by combining alpha-Gal silencing with HO-1 upregulation.

BACKGROUND: A major barrier to clinical xenotransplantation is preformed xenoreactive natural antibodies (XNA) found in higher primates which react to Galalpha(1,3)Gal (alpha-Gal) epitopes found on lower species. Accommodation of organs to xenogeneic recipients involves upregulation of cytoprotective genes and resistance to complement dependent cytotoxicity (CDC). METHODS: To develop methods of increasing these organ-protective effects, we established an in vitro CDC model utilizing human serum as the source of XNA and porcine endothelial cells (pEC) as targets. RESULTS: Using this system we demonstrated that downregulation of alpha-Gal epitopes by siRNA silencing of alpha1,3-galactosyltransferase (alpha-GT) led to marginal protection from CDC while alpha-Gal silencing combined with Griffonia simplicifolia isolectin B4 (GS-IB4), a lectin that specifically binds to alpha-Gal epitopes, led to complete protection. Interestingly, alpha-Gal silencing and GS-IB4 mediated effects were not associated with inhibition of XNA binding to cells, but with significant decreased E-selectin expression and cytoprotective gene HO-1 upregulation. PI3K inhibitor LY294002 could block the elevation of HO-1 protein expression and reverse the protective effect of alpha-Gal silencing and GS-IB4 against CDC. CONCLUSION: These data support the use of combination approaches targeting independent accommodation mechanisms to synergistically enhance donor organ survival in a xenogeneic setting.

Updated Genetic Testing of Primary Hyperoxaluria Type 1 in a Chinese Population: Results from a Single Center Study and a Systematic Review.

Primary hyperoxaluria type 1 (PH1) is a rare but devastating autosomal recessive inherited disease caused by mutations in gene AGXT. Pathogenic mutations of AGXT were mostly reported in Caucasian but infrequently in Asian, especially in Chinese. To update the genotypes of PH1 in the Chinese population, we collected and identified 7 Chinese probands with PH1 from 2013 to 2017 in our center, five of whom had delayed diagnosis and failed in kidney transplantation. Samples of peripheral blood DNA from the 7 patients and their family members were collected and sequencing analysis was performed to test the mutations of gene AGXT. Western blotting and enzyme activity analysis were conducted to evaluate the function of the mutations. Furthermore, a systematic review from 1998 to 2017 was performed to observe the genetic characteristics between Chinese and Caucasian. The results showed that a total of 12 mutations were identified in the 7 pedigrees. To the best of our knowledge, 2 novel variants of AGXT, p.Gly41Trp and p.Leu33Met, were first reported. Bioinformatics and functional analysis showed that only 7 mutations led to a reduced expression of alanine-glyoxylate amino transferase (AGT) at a protein level. The systematic review revealed significant population heterogeneity in PH1. In conclusion, new genetic subtypes and genetic characteristics of PH1 are updated in the Chinese population. Furthermore, a genotype-phenotype correlation is found in PH1.

Early steroid withdrawal after liver transplantation for hepatocellular carcinoma.

AIM: To evaluate the impact of early steroid withdrawal on the incidence of rejection, tumor recurrence and complications after liver transplantation for advanced-stage hepatocellular carcinoma. METHODS: Fifty-four patients underwent liver transplantation for advanced-stage hepatocellular carcinoma from April 2003 to June 2005. These cases were divided into a steroid-withdrawal group (group A, n = 28) and a steroid-maintenance group (group B, n = 26). In group A, steroid was withdrawn 3 mo after transplantation. In group B, steroid was continuously used postoperatively. The incidence of rejection, 6-mo and 1-year recurrence rate of carcinoma, 1-year survival rate, mean serum tacrolimus trough level, and liver and kidney function were compared between the two groups. RESULTS: In the two groups, no statistical difference was observed in the incidence of rejection (14.3 vs 11.5%, P > 0.05), mean serum tacrolimus trough levels (6.9 +/- 1.4 vs 7.1 +/- 1.1 microg/L, P > 0.05), liver and kidney function after 6 mo [alanine aminotransferase (ALT): 533 +/- 183 vs 617 +/- 217 nka/L, P > 0.05; creatinine: 66 +/- 18 vs 71 +/- 19 micromol/L, P > 0.05], 6-mo recurrence rate of carcinoma (25.0 vs 42.3%, P > 0.05), and 1-year survival rate (64.2 vs 46.1%, P > 0.05). The 1-year tumor recurrence rate (39.2 vs 69.2%, P < 0.05), serum cholesterol level (3.9 +/- 1.8 vs 5.9 +/- 2.6 mmol/L, P < 0.01) and fasting blood sugar (5.1 +/- 2.1 vs 8.9 +/- 3.6 mmol/L, P < 0.01) were significantly different. These were lower in the steroid-withdrawal group than in the steroid-maintenance group. CONCLUSION: Early steroid withdrawal was safe after liver transplantation in patients with advanced-stage hepatocellular carcinoma. When steroids were withdrawn 3 mo post-operation, the incidence of rejection did not increase, and there was no demand to maintain tacrolimus at a high level. In contrast, the tumor recurrence rate and the potential of adverse effects decreased significantly. This may have led to an increase in long-term survival rate.

Impact of early biliary complications in liver transplantation in the presence or absence of a T-tube: a Chinese transplant centre experience.

BACKGROUND: Biliary complications continue to be an important determinant of the recipient's survival rate after orthotopic liver transplantation (OLT). The objective of this study was to evaluate the incidence of early biliary complications in OLT in the presence or absence of a T-tube. METHODS: This retrospective study, based on inpatient data, focused on the relationship between T-tube placement and early biliary complications of 84 patients after OLT, from November 2002 to June 2005. Patients were divided into two groups based on whether or not a T-tube was used following bile duct reconstruction: T-tube group (group I, n = 33); non-T-tube group (group II, n = 51). RESULTS: 45.2% of OLT recipients had a malignant neoplasm. There were no significant differences in the demographic characteristics or operation data between the two groups. Overall, early biliary tract complications developed in 19.0% (16/84) of patients. The rate of early biliary complications was 30.3% (10/33) and 11.8% (6/51) in groups I II, respectively (p = 0.035). Biliary complications which were directly caused by T-tube placement occurred in 12.1% (4/33) of patients in group I. Overall, the percentage of malignant neoplasms, chronic viral cirrhosis, fulminant liver failure and other primary disease recipients with early biliary complications were 6.2%, 37.5%, 43.8% and 12.5%, respectively. CONCLUSION: This study suggests that the use of a T-tube in Chinese patients undergoing OLT causes a higher incidence of early biliary complications. Most of the early biliary complications occurred in chronic viral cirrhosis and fulminant liver failure recipients.

Recombinant anti-HBsAg Fab blocks hepatitis B virus infection after orthotopic liver transplantation.

BACKGROUND: Recurrence of hepatitis B virus (HBV) after orthotopic liver transplantation is very common in the absence of adequate prophylaxis and is often associated with poor prognosis because of the development of cirrhosis, fibrosing cholestatic hepatitis, or fulminant hepatitis. Therefore it is important to study the prevention of HBV reinfection after liver transplantation. METHODS: Recombinant Fab (rFab) was constructed to evaluate gene therapy for post-transplantation HBV reinfection. Hepatocytes were divided into three groups: HBV-infection, rFab-blocked HBV-infection, and control. The inhibition of HBsAg adsorption test, the micro-cytotoxicity assay, and the blockade test of HBV infection were carried out. The HBsAg adsorption rate, the hepatocyte death rate and the HBV infection rate were statistically analyzed. RESULTS: The HBsAg adsorption rate blocked by rFab in the HBsAg adsorption test was 0.3%. The hepatocyte death rate was 98.8% induced by rFab in the micro-cytotoxicity assay, 1.3% in the rFab-blocked HBV-infected group and 77% in the HBV-infected group in the blockade test of HBV. CONCLUSIONS: We found that rFab effectively blocked HBV infection in human hepatocytes. This provides an attractive alternative for hepatitis B prophylaxis.

[Technology and application of simultaneous pancreas-kidney transplantation with modified enteric drainage].

OBJECTIVE: To report the modified technique and the short-term results of simultaneous pancreas-kidney transplantation (SPK) with the enteric drainage (ED) of exocrine secretions. METHODS: From June 2000 to August 2006, thirty-eight patients with diabetes complicated with uremia underwent SPK. The pancreas graft was placed intraperitoneally with exocrine secretions drained into the proximal jejunum without Roux-en-Y procedure. The mean cold ischemic times of pancreas and kidney were (10 +/- 2.0) h and (7 +/- 2.0) h, respectively. Quadruple immunosuppressive therapy with antilymphocyte globulin or anti-CD25 monoclonal antibody, tacrolimus, mycophenolate mofetil and steroids was adopted except one patient. RESULTS: The 6-month survival rates of patients and grafts were both 97.4% after transplantation. All patients achieved insulin-free euglycemia at (7 +/- 6.9) d postoperative except one. For preoperative patients, mean fasting insulin and C-peptide values were (9 +/- 8.1) mU/L and (6 +/- 4.5) mU/L. After operation, fasting insulin and C-peptide values of patients were (12 +/- 5.8) mU/L and (6 +/- 4.7) mU/L, respectively, which peaked to an insulin level of (57 +/- 43.0) mU/L and a C-peptide level of (11 +/- 6.8) mU/L with stimulation. There were eight cases of delayed renal graft function. All other patients achieved immediate renal graft function. No graft losses occurred due to leakage or intra-abdominal infection. The most common surgical complications were wound infection (n = 12), enteric anastomostic hemorrhage (n = 5) and perirenal hemorrhage (n = 2). Three patients (7.9%) had been reoperated for the reasons of intra-abdominal hemorrhage and perirenal hemorrhage. CONCLUSIONS: SPK is an effective treatment option for selected patients with diabetes mellitus and approaching end-stage renal disease. Enteric exocrine drainage by direct side-to-side anastomosis (without Roux-en-Y) seems to be a simple and reliable technique.