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Gu J.,Nanjing Medical University | Gu J.,Jiangsu Provinces Key Medical Center for Hepatobiliary Disease | Gu J.,Nanjing University | Wu X.,Nanjing Medical University | And 10 more authors.
Hepatology International

To evaluate the efficacy and safety of early steroid withdrawal or steroid avoidance in the tacrolimus (Tac)-based immunosuppressive regimen for liver transplant recipients. According to the requirements of the Cochrane systematic review, a thorough literature search was performed in the PubMed/MEDLINE and Cochrane electronic databases between 1995 and 2011 using the key words "liver transplantation," "Tac," and "steroid free" or "steroid withdrawal," restricting articles to the English language. Data were processed for a meta-analysis by Stata 12 software. Altogether 17 prospective randomized controlled trials containing 1,980 transplanted patients were included in this study. The overall pooled RR estimates of 1-, 2-, 3-, and 5-year patient and graft survival rates were 0.985, 0.998, 0.995, and 1.100 (95 % CI 0.925-1.048, 0.934-1.067, 0.894-1.107, and 0.968-1.250, respectively), as well as 0.998, 0.993, 0.945, and 1.053, respectively (95 % CI 0.928-1.072, 0.902-1.092, 0.833-1.072, and 0.849-1.307, respectively). The other pooled RR estimates of acute rejection and chronic rejection rates for all enrolled studies were 1.077 and 0.311 (95 % CI 0.864-1.343 and 0.003-37.207). As for secondary predictors, the pooled RR estimates such as HCV recurrence, HCC recurrence, diabetes, hypertension, kidney dysfunction, bacterial infection, and CMV were 1.101, 1.403, 1.836, 1.607, 0.842, 1.096, and 2.280, respectively (95 % CI 0.964-1.257, 0.422-4.688, 1.294-2.606, 0.926-1.228, 0.693-1.022, 0.783-1.533, and 1.500-3.465, respectively). There were no differences between the steroid group and steroid-free group for all clinical observational indices except for the incidence of diabetes (p = 0.001) and CMV infection (p < 0.001). In summary, our study indicate that rapid discontinuation of steroid in the Tac-based immunosuppressive regimen may not lead to an increased risk of morbidity and rejection rate. © 2014 The Author(s). Source

Shi X.-L.,Jiangsu Provinces Key Medical Center for Hepatobiliary Disease | Shi X.-L.,Nanjing Medical University | Gu J.-Y.,Jiangsu Provinces Key Medical Center for Hepatobiliary Disease | Gu J.-Y.,Nanjing Medical University | And 6 more authors.
World Journal of Gastroenterology

AIM: To evaluate tracking of magnetically labeled mesenchymal stem cells (MSCs) after intraportal transplantation. METHODS: Mononuclear cells were isolated from bone marrow aspirates of pigs by density gradient centrifugation, cultured and expanded, after which, they were incubated with super paramagnetic iron oxide (SPIO). Prussian blue staining was performed to highlight intracellular iron. To establish swine models of acute liver injury, 0.5 g/kg D-galactosamine was administrated to 10 pigs, six of which were injected via their portal veins with SPIO-labeled MSCs, while the remaining four were injected with unlabeled cells. Magnetic resonance imaging (MRI) was performed with a clinical 1.5T MR scanner immediately before transplantation and 6 h, 3 d, 7 d and 14 d after transplantation. Prussian blue staining was again performed with the tissue slices at the endpoint. RESULTS: Prussian blue staining of SPIO-labeled MSCs had a labeling efficiency of almost 100%. Signal intensity loss in the liver by SPIO labeling on the FFE (T2*WI) sequence persisted until 14 d after transplantation. Histological analysis by Prussian blue staining confirmed homing of labeled MSCs in the liver after 14 d; primarily distributed in hepatic sinusoids and liver parenchyma. CONCLUSION: MSCs were successfully labeled with SPIO in vitro. MRI can monitor magnetically labeled MSCs transplanted into the liver. © 2010 Baishideng. Source

Zhu W.,Nanjing University | Zhu W.,Nanjing Medical University | Shi X.-L.,Nanjing Medical University | Shi X.-L.,Jiangsu Provinces Key Medical Center for Hepatobiliary Disease | And 6 more authors.
Hepatobiliary and Pancreatic Diseases International

BACKGROUND: Adipose-derived stem cells (ADSCs) are particularly attractive in future clinical applications of stem cell-based therapy for acute-on-chronic liver failure (ACLF). This study was undertaken to evaluate the therapeutic potential of ADSCs on ACLF. METHODS: ADSCs isolated from porcine fat tissue were expanded and labeled with BrdU. Rabbit models of ACLF were created by administration of D-Gal following CCl4-induced cirrhosis. One day after administration of D-Gal, rabbits of the ACLF/ADSCs group (n=15) were received ADSCs transplantation, while those in the ACLF/saline group (n=15) were treated with the same volume of saline. Biochemical parameters and histomorphological scoring were evaluated; the distribution and characteristics of transplanted ADSCs as well as the pathology of the liver were examined. RESULTS: ADSCs transplantation improved the survival rate and the liver function of rabbits with ACLF. Biochemical parameters of the ACLF/ADSCs group were improved compared with those of the ACLF/saline group, and histomorphological scoring of the ACLF/ADSCs group was significantly lower than that of the ACLF/saline group. ADSCs were identified in the periportal region of the liver after cell transplantation. CONCLUSION: Xenogenic ADSCs have therapeutic efficacy in the ACLF rabbit model. © 2013, Hepatobiliary Pancreat Dis Int. Source

Ren H.,Nanjing Medical University | Ren H.,Jiangsu Provinces Key Medical Center for Hepatobiliary Disease | Shi X.,Nanjing Medical University | Shi X.,Jiangsu Provinces Key Medical Center for Hepatobiliary Disease | And 9 more authors.
Liver International

Aim: Hepatic tissue engineering is considered as a possible alternative to liver transplantation for end-stage liver disease. Several methods of decellularization of xenogeneic liver are available to produce three-dimensional organ scaffolds for engineering liver tissues. However, rare studies have examined and compared the effectiveness of different methods on the structure and composition of intact decellularized liver extracellular matrix. Methods: Two decellularization methods were adopted herein. Their effects on collagen, elastin, glycosaminoglycans (GAGs), hepatocyte growth factor (HGF) content and influence to the function of hepatocytes cultured in scaffolds were examined and compared. Results: The complete tissue decellularization was successfully achieved after treatment with sodium dodecyl sulphate (SDS) and Triton X-100. The total absence of nuclear structures and removal of viable cells were confirmed by haematoxylin-eosin staining and scanning electron microscopy. Collagen was preserved after both treatments. However, the elastin content decreased to about 20% and 60%, the GAGs content decreased to about 10% and 50% and the HGF content decreased to about 20% and 60% of the native liver level after SDS and Triton X-100 treatment respectively. The Triton X-100-treated scaffolds were much superior than SDS-treated scaffolds in supporting liver-specific function, including albumin secretion (P = 0.001), urea synthesis (P = 0.002), ammonia elimination (P = 0.007) and mRNA expression levels of drug metabolism enzymes. Conclusion: This study suggested that liver extracellular matrix scaffolds constructed using perfusion of Triton X-100 as described herein might provide a more effective and ideal material for the usage in tissue engineering and regenerative medicine approaches. © 2012 John Wiley & Sons A/S. Source

Gu J.,Nanjing Medical University | Gu J.,Jiangsu Provinces Key Medical Center for Hepatobiliary Disease | Bai J.,Nanjing Medical University | Shi X.,Nanjing Medical University | And 15 more authors.
International Journal of Cancer

The aim of our study was to evaluate the efficacy and safety of liver transplantation in patients with cholangiocarcinoma. According to the requirements of Cochrane systematic review, a thorough literature search was performed in PubMed/Medline, Embase and Cochrane electronic databases between 1995 and 2009 in terms of the key words "liver transplantation" and "cholangiocarcinoma," "cholangiocellular carcinoma" or "bile duct cancer," with restricted articles for the English language. Data were processed for a meta-analysis by Stata 10 software. Altogether 14 clinical trials containing 605 transplanted patients of bile duct cancers were finally enrolled in our study. The overall 1-, 3- and 5-year pooled survival rates were 0.73 [95% confidence interval (CI) = 0.65-0.80], 0.42 (95% CI = 0.33-0.51) and 0.39 (95% CI = 0.28-0.51), respectively. Of note, preoperative adjuvant therapies [orthotopic liver transplantation (OLT)-PAT group] rendered the transplanted individuals with comparably favorable outcomes with 1-, 3- and 5-year pooled survival rates of 0.83 (95% CI = 0.57-0.98), 0.57 (95% CI = 0.18-0.92) and 0.65 (95% CI = 0.40-0.87). In addition, the overall pooled incidence of complications was 0.62 (95% CI = 0.44-0.78), among which that of OLT-PAT group (0.58; 95% CI = 0.20-0.92) was relatively acceptable compared to those of liver transplantation alone (0.61; 95% CI = 0.33-0.85) and liver transplantation with extended bile duct resection (0.78; 95% CI = 0.55-0.94). In comparison to curative resection of cholangiocarcinoma with the 5-year survival rate reported from 20 to 40%, the role of liver transplantation alone is so limited. In the future, attention will be focused on liver transplantation following neoadjuvant radiochemotherapy, which requires a well-designed, prospective randomized controlled study. © 2011 UICC. Source

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