[Show abstract][Hide abstract] ABSTRACT: Ischemic-type biliary lesions (ITBLs) are a major cause of graft loss and mortality after orthotopic liver transplantation (OLT). Impaired blood supply to the bile ducts may cause focal or extensive damage, resulting in intra- or extrahepatic bile duct strictures or dilatations that can be detected by ultrasonography, computed tomography, magnetic resonance cholangiopancreatography, and cholangiography. However, the radiographic changes occur at an advanced stage, after the optimal period for therapeutic intervention. Endoscopic retrograde cholangio-pancreatography (ERCP) and percutaneous transhepatic cholangiodrainage (PTCD) are the gold standard methods of detecting ITBLs, but these procedures cannot be used for continuous monitoring. Traditional methods of follow-up and diagnosis result in delayed diagnosis and treatment of ITBLs. Our center has used the early diagnosis and intervention model (EDIM) for the diagnosis and treatment of ITBLs since February 2008. This model mainly involves preventive medication to protect the epithelial cellular membrane of the bile ducts, regular testing of liver function, and weekly monitor of contrast-enhanced ultrasonography (CEUS) to detect ischemic changes to the bile ducts. If the liver enzyme levels become abnormal or CEUS shows low or no enhancement of the wall of the hilar bile duct during the arterial phase, early ERCP and PTCD are performed to confirm the diagnosis and to maintain biliary drainage. Compared with patients treated by the traditional model used prior to February 2008, patients in the EDIM group had a lower incidence of biliary tract infection (28.6% vs. 48.6%, P = 0.04), longer survival time of liver grafts (24±9.6 months vs. 17±12.3 months, P = 0.02), and better outcomes after treatment of ITBLs.
PLoS ONE 01/2014; 9(9):e105795. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Primary graft dysfunction or nonfunction after liver transplantation, which is usually caused by ischemia/reperfusion injury (IRI), is a serious clinical problem. Although bone marrow mesenchymal stem cells (MSCs) have shown great potential in cell therapy for IRI in several organs, the mechanism(s) by which MSCs offer protection is unclear. METHODS: In the present study, we injected MSCs systemically via the tail vein in the rat model of 70% hepatic IRI and measured the biochemical and pathologic alterations to evaluate the therapeutic effect of MSC transplantation. Concurrently, H(2)O(2) was used in vitro to mimic oxidative injury and to induce apoptosis in the human normal liver cell line LO2 to evaluate the protective effects of mesenchymal stem cell conditioned medium (MSC-CM) on LO2 cells. RESULTS: The systemic infusion of MSCs led to a significant prevention of liver enzyme release and an improvement in the histology of the acutely injured liver. In vitro assays demonstrated that MSC-CM promoted hepatocyte proliferation and had a direct inhibitory effect on hepatocyte apoptosis induced by H(2)O(2). In addition, we demonstrated that the prevention of MEK/ERK pathway activation played a pivotal role in the protection. CONCLUSIONS: These data suggest that MSC may represent a potential therapeutic strategy to alleviate hepatic ischemia/reperfusion injuries after liver transplantation via inactivation of the MEK/ERK signaling pathway.
Journal of Surgical Research 05/2012; · 2.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There are increasing numbers of patients who survive more than one year after liver transplantation. Many studies have focused on the early mortality of these patients. However, the factors affecting long-term survival are not fully understood. This study aims to evaluate prognostic factors predicting long-term survival and to explore measures for improving the survival outcomes of patients who underwent liver transplantation for benign end-stage liver diseases.
The causes of late death after liver transplantation and potential prognostic factors were retrospectively analyzed for 221 consecutive patients who underwent liver transplantation from October 2003 to June 2008. Twenty-seven variables were assessed using the Kaplan-Meier method, and those variables found to be univariately significant at P < 0.10 were entered into a backward step-down Cox proportional hazard regression analysis to identify the independent prognostic factors influencing the recipients' long-term survival.
Twenty-eight recipients died one year after liver transplantation. The major causes of late mortality were infectious complications, biliary complications, and Hepatitis B virus recurrence/reinfection. After Cox analysis, the five remaining co-variables were: age, ABO blood group, cold ischemia time, post-infection region, and biliary complications.
The major causes of late mortality were infection, biliary complications and Hepatitis B virus recurrence/reinfection. Five variables (Age, ABO blood group, cold ischemia time, infection, and biliary complications) had significant impacts on patient survival.
Chinese medical journal 12/2011; 124(24):4229-35. · 0.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To study the effects of cluster of differentiation 40 ligand immunoglobulin (CD40LIg) gene-modified bone marrow mesenchymal stem cells (MSCs) on liver graft rejection in rats.
The orthotopic liver transplantation models were established with DA rats as the donors and Lewis rats as the recipient. MSCs infected with the recombinant adenoviruses containing CD40LIg gene were infused into the liver graft after transplantation. The liver function, survival of the recipient rats and the morphological changes of the liver grafts were observed after the transplantation. The serum levels of the cytokines interferon-γ (INF-γ) and interleukin-2 (IL-2) in the recipient rats were quantified by ELISA.
The survival of the recipient rats receiving transplantation of genetically modified MSCs (group D) was significantly prolonged compared with that of the control group (group A), MSCs group (group B) and gene transfection group (group C); the survival of groups B and C were significantly longer than that of group A (F=7.615, P<0.05). The level of serum alanine aminotransferase, total bilirubin, IL-2 and INF-γ were significantly higher in group A than in the other 3 groups (F=8.738, P<0.05). HE staining of the liver grafts showed severe acute rejection in group A, mild acute graft rejection in groups B and group C, but no rejection in group D.
CD40LIg gene-modified MSCs can prolong the survival of the recipient rats and suppress graft rejection following liver transplantation.
Nan fang yi ke da xue xue bao = Journal of Southern Medical University 11/2011; 31(11):1903-6.
[Show abstract][Hide abstract] ABSTRACT: To find out the risk factors predicting long-term survival, and to explore the measures for further improving the survival outcome of whom underwent liver transplantation (LT) for benign end-stage liver disease.
The common causes of late death after LT and risk factors were retrospectively analyzed in 221 consecutive patients, who underwent LT from October 2003 to June 2007 and survived more than one year. Twenty-six potential risk factors were assessed by the Kaplan-Meier method, and those variables found to be univariately significant at P < 0.10 were entered into a backward step down Cox proportional hazard regression analysis to screen the independent risk factors influencing the recipient's long-term survival.
There were 28 recipients died one year later after LT during the follow-up period. The major causes of late mortality were related to infectious complications 5.0% (11/221), biliary complications 3.6% (8/221) and HBV recurrence/reinfection 1.4% (3/221). After Cox proportional hazard regression analysis, 5 covariables finally retained in the formula were: age (RR = 2.325, P = 0.009), ABO blood group (RR = 2.206, P = 0.015), cold ischemia time (RR = 3.001, P = 0.000), post-infection region (RR = 1.665, P = 0.007) and biliary complications (RR = 2.655, P = 0.004).
Age (≥ 60 years), ABO blood group (incompatible), cold ischemia time (> 12 h), infectious complications (lung infection) and biliary complications (diffuse biliary stricture) significantly impact patient's survival time.
Zhonghua wai ke za zhi [Chinese journal of surgery] 07/2010; 48(14):1083-7.
[Show abstract][Hide abstract] ABSTRACT: There has been a gradual increase in the number of patients with end-stage alcoholic liver disease (ALD) undergoing liver transplantation (LT) in mainland China. However, few studies have focused on the post-transplant outcomes of this population. The aim of this study was to evaluate the efficacy of LT in patients with ALD, mainly focusing on survival rates, complications, and alcohol recidivism. The results were retrospectively analyzed from 20 patients, who underwent LT for ALD from December 2003 to September 2007 at Liver Transplant Center of Third Affiliated Hospital of Sun Yat-sen University. The 1-, 2-, and 3-year survival rates of the ALD group and non-ALD group were 90.0, 80.0, 80.0% and 90.3, 84.7, 79.8%, respectively. There was no significant difference in 1-, 2-, and 3-year survival rates between these two groups (P=.909). No significant difference was observed in complications such as pulmonary infection (50.0 vs. 31.9%, P=.137), biliary complications (15.0 vs. 27.4%, P=.297), hepatic arterial complications (10.0 vs. 6.9%, P=.641), and rejection (15.0 vs. 8.1%, P=.394) after LT between the ALD group and non-ALD group. There was only one person who resumed mild, intermittent drinking after LT. End-stage ALD is a good indication for LT, with similar results in non-ALD patients. The major cause of death in ALD patients after LT was infectious complications. More attention is needed for the prophylaxis of infectious complications after LT.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the long-term survival rates of the adults with benign end-stage liver disease (BELD) after liver transplantation (LT) and the causes of death.
The common causes of late death (after more than 1 year) after LT were retrospectively analyzed in 203 consecutive patients with BELD who underwent LT from Oct. 2003 to May.2006.
The 1, 2 and 3-year survival rates were 88.7%, 85.5%, and 81.2% respectively. The 2-year and 3-year survival rates of the patients with HBV-related liver disease were 88.4% and 84.5% respectively, not significantly different from those of patients with non-HBV-related liver disease (75.6% and 64.0% respectively, P = 0.144). 165 recipients survived for more than 1 year and 21 recipients died during the period between 12 and 48 months after LT with a mean of (22.7 +/- 6.6) months. The common causes of late death included related to infectious complications (4.8%, 8/165), biliary tract complications (3.6%, 6/165), HBV re-infection (1.8%, 3/165), chronic rejection (1.2%, 2/165), renal functional lesion (0.6%, 1/165), and hepatic arterial complication (0.6%1/165).
Satisfactory long-term survival can be achieved in most adult recipients with BELD after LT and the major causes that influence the long-term survival are infectious complications, biliary tract complications, and HBV re-infection. Prevention of these complications, rational use of immunosuppressant, and regular follow-up are essential to improve long-term survival.
[Show abstract][Hide abstract] ABSTRACT: The main therapeutic treatments for hepatic artery complications after orthotopic liver transplantation (OLT) include thrombolysis, percutaneous transluminal angioplasty, stent placement, and liver retransplantation. The prognosis of hepatic artery complications after OLT is not only related to the type, extent, and timing but also closely associated with the selection and timing of the therapeutic methods. However, there is no consensus of opinion regarding the treatment of these complications. The aim of this study was to determine optimal treatment for hepatic artery complications after OLT.
The clinical data of 25 patients diagnosed with hepatic artery thrombosis (HAT) and hepatic artery stenosis (HAS) between October 2003 and March 2007 were retrospectively reviewed. Treatments included liver retransplantation and interventions which contain thrombolysis, percutaneous transluminal angioplasty and stent placement.
Among five patients with HAT, 3 were treated with thrombolysis. One recovered, one died after thrombolysis and another one died of multi-organ failure after retransplantation because of recurrent HAT. The remaining 2 patients underwent successful retransplantation and have survived after that. Among 12 patients presented with HAS within 1 month postoperatively, 2 patients underwent retransplantation due to irreversible liver failure and another 10 patients were treated with interventions. The liver function failed to improve in 3 patients and retransplantations were performed in 4 patients after stent placement because of ischemic cholangitis. Among 6 patients undergoing liver retransplantations, two died of intracranial hemorrhage and infection respectively. Eight patients presented with HAS after 1 month postoperatively, 5 patients were treated with interventional management and recovered after stent placement. Among another 3 patients presented with HAS, 2 patients' liver function was stable and one patient received late liver retransplantation due to ischemic bile duct lesion.
Individualized therapeutic regimens should be adopted in treating hepatic artery complications after OLT, according to postoperative periods, types and whether ischemic bile duct lesion exists or not. Liver retransplantation is the best treatment for patients with hepatic artery thrombosis. Interventional treatments of late HAS without irreversible liver failure or bile duct ischemia are appropriate, whereas retransplantation is recommended for early HAS.
Chinese medical journal 11/2008; 121(20):1997-2000. · 0.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The most frequently used therapy for post-transplantation recurrence of hepatitis B virus (HBV) infection is lamivudine, but this drug is associated with a high resistance rate due to YMDD mutant. In preliminary reports, adefovir dipivoxil (ADV) has been shown to have activity against lamivudine-resistant strains of HBV. However, clinical experience in treatment of HBV infection after liver transplantation (LT) is still not entirely clear. This study was aimed to evaluate the prophylactic efficacy of ADV plus hepatitis B immunoglobulin (HBIG) in patients with YMDD mutant before LT.
From March 2004 to March 2006, 16 patients with chronic hepatitis B had lamivudine-resistant YMDD mutants detected prior to liver transplantation and received treatment with ADV plus additional intramuscular HBIG after LT as prophylaxis against graft reinfection. Tests for liver function, serum HBsAg, anti-HBs (HBIG), HBeAg, anti-HBc, anti-HBe, HBV-DNA, and creatinine were assessed pre- or post-liver transplantation.
The median follow-up of these patients post-liver transplantation was 19.4 months. Fifteen patients survived and one patient died of recurrence of hepatocellular carcinoma (HCC). There was significant difference (10.98% vs. 2.26%, P < 0.05) in YMDD mutant rate between the patients with HBV-DNA over 10(6) copies/ml and those with HBV-DNA less than 10(6) copies/ml. Fifteen patients (93.8%) had undetectable HBV-DNA at 4 weeks and 1 (6.3%) at 6 months after LT. No hepatitis B recurrence was detected by persistent testing of HBsAg, HBeAg, and HBV-DNA and no increase of serum creatinine level associated with ADV was observed in any of the patients.
ADV combined with intramuscular HBIG can effectively prevent patients with pre-transplantation YMDD mutant from HBV recurrence after LT.
Chinese medical journal 08/2007; 120(16):1400-3. · 0.90 Impact Factor