ang Y

Contrast‐enhanced ultrasound for the evaluation of hepatic artery stenosis after liver transplantation: potential role in changing the clinical algorithm

Hepatic artery stenosis (HAS) is a common complication in liver transplant patients. Conventional angiography remains the gold standard for diagnosis. Recently, contrast‐enhanced ultrasound (CEUS) has begun providing real‐time angiographic‐like images of vessels and allowing the accurate diagnosis of arterial diseases such as hepatic artery thrombosis. The purpose of this study was to evaluate the efficacy of CEUS in depicting HAS after liver transplantation. Forty‐seven liver transplant recipients underwent CEUS examinations with the intravenous injection of microbubble contrast agents. The reference standard was conventional angiography for 15 patients and computed tomographic angiography for 32 patients. The presence, degree, location, and type of HAS were evaluated. For the detection of HAS by CEUS, the following was found: an accuracy of 91.5% (43/47), a sensitivity of 92.3% (36/39), a specificity of 87.5% (7/8), a positive predictive value of 97.3% (36/37), and a negative predictive value of 70% (7/10). CEUS corrected false‐positive findings on color Doppler ultrasound in 7 of 47 cases (14.9%). The accuracy of CEUS in identifying the location and type of HAS was 92.3% (36/39) and 84.6% (33/39), respectively. CEUS is a useful noninvasive technique for the detection of HAS in liver transplant patients because it provides comprehensive information, including the presence, location, degree, and type. A positive CEUS finding suggests angiography as the next step rather than a computed tomography scan and may thereby alter the clinical imaging algorithm. Liver Transpl 16:729‐735, 2010.

The Role of Liver Transplantation for Intrahepatic Cholangiocarcinoma: A Single-Center Experience

Background/Aim: Intrahepatic cholangiocarcinoma (ICC) is not a widely accepted indication for liver transplantation (LT). The present study describes our institutional experience with patients who underwent transplantation for ICC. Methods: A retrospective analysis was performed on 11 consecutive patients with ICC who underwent LT between October 2003 and November 2008 at our institution. Results: At a median patient follow-up interval of 10 months (2–56), the median survival time was 9 months (2.5–53). The perioperative mortality and the recurrence rate were 0 and 45.5%, respectively. Five patients are currently alive 10, 12, 41, 51 and 53 months after LT, respectively. One patient died 3 months after LT as a result of bile leak and toxic shock, and 5 patients died of tumor recurrences at 2.5, 8, 8, 9 and 10 months post-LT, respectively. The 1-, 2-, 3- and 4-year disease-free survival rates and overall survival rates of all the patients were 51.9, 51.9, 51.9 and 51.9%, and 50.5, 50.5, 50.5 and 50.5%, respectively. Conclusion: With better and strict patient selection, the prognosis of LT for ICC could be improved. ICC patients with lymph node involvement, vascular or bile duct invasion are contraindicated for LT.

Alleviation of ischemia-reperfusion injury in rat liver transplantation by induction of small interference RNA targeting Fas

BackgroundCellular apoptosis plays an important role in ischemia-reperfusion (I/R) injury during organ transplantation. Synthetic small interference RNA (siRNA) targeting apoptotic receptor Fas has proven effective to protect mice against hepatitis and renal I/R injury. The objective of this study is to investigate the silencing impact of Fas siRNA to alleviate I/R injury in rat liver transplantation.Materials and methodsRat hepatocytes (BRL cells) were transfected with three pairs of synthesized Fas siRNA; cells untreated and treated with GFP siRNA were taken as blank and siRNA control. The most effective Fas siRNA was chosen for in vivo experiments. Syngeneic orthotopic liver transplantation was performed in Fas siRNA group, siRNA control group, and blank control group of Sprague–Dawley rats. There were 25 pairs of rats in each group. siRNA transfection of donor rats was done with hydrodynamic injection method 48xa0h before liver procurement. Blood and liver samples were collected for evaluation of serum ALT levels, Fas protein and mRNA expression, and apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, 1, 3, 6, 12, and 24xa0h after liver transplantation.ResultsFas siRNA2, which inhibited Fas gene expression much more than other siRNAs, was chosen for in vivo experiment. The serum ALT levels of Fas siRNA group were much less than those of blank and siRNA control groups 1, 3, 6, 12, and 24xa0h after blood reperfusion, indicating diminishing ischemia-reperfusion injury. Donor livers in Fas siRNA group had substantially less cell apoptosis. The expression of Fas mRNA and protein was reduced dramatically in the Fas siRNA group compared with the other two groups.ConclusionFas-mediated apoptosis play an important role in I/R injury of rat liver transplantation. Silencing Fas by hydrodynamic injection of siRNA holds therapeutic promise to limit I/R injury.

A Single-Center Experience of Retransplantation for Liver Transplant Recipients With a Failing Graft

With the accumulation of orthotopic liver transplantation (OLT) recipients, an increased number of patients with graft failure need retransplantation (re-OLT). This study was undertaken to examine our clinical experience of re-OLT for patients with poor graft function after primary transplantation at a single center. We analyzed retrospectively, the clinical data of 32 re-OLTs in 31 patients at our center from January 2004 to February 2007, including indications and causes of death, timing of retransplantation, and surgical techniques. The indications included bile leak (2 cases), biliary stricture (16 cases), recurrence of hepatocellular carcinoma (HCC) (5 cases), hepatic artery stenosis (4 cases), hepatic artery thrombosis (HAT) (2 cases), and hepatitis B recurrence (3 cases). The rate of re-OLT was 4.29%. All patients underwent modified piggyback liver transplantations with cadaveric allografts. No intraoperative mortality and acute rejection occurred. Overall, 17 of 31 patients (54.8%) died after re-OLT with survival times ranging from 2 weeks to 28 months. Another 14 patients were cured with survival times of 4 to 32 months. The perioperative mortality rate of patients who underwent re-OLT between 8 and 30 days after their initial transplantation was highest (66.7%). The most common cause of death after re-OLT was sepsis (47.1%), multiple-organ failure (17.6%), and recurrence of HCC (17.6%), whereas the majority of deaths posttransplantation were sepsis-related (54%) within 1 year. Re-OLT is the only therapeutic option for a failing liver graft. Proper indications and optimal operative time, advanced surgical procedures, reasonable individual immunosuppression regimens, and effective perioperative anti-infection treatments contribute to the improved survival of patients after re-OLT.

Single-center experience of therapeutic management of hepatic artery stenosis after orthotopic liver transplantation. Report of 20 cases.

Background/Aims: Hepatic artery stenosis (HAS) is a potentially life-threatening complication of liver transplantation because the associated mortality and morbidity rates are high. Surgical reconstruction was recommended as first choice of treatment and interventional radiologic techniques have been introduced recently. However, the mid- or long-term outcomes of HAS were unclear. The purpose of this study was to evaluate the efficacy of interventional therapy and clinical outcomes of HAS following liver transplantation. Methods: A retrospective analysis was performed for 20 cases of HAS documented by angiography from October 2003 to August 2007 at the authors’ institution. All patients underwent transluminal interventional therapy including percutaneous transluminal angioplasty and endovascular stent placement. The technical results, hepatic artery patency and clinical outcome were reviewed. Results: All patients were treated with interventional management. Technical and immediate success was 100%. Of 8 patients with early HAS (within 1 month of transplantation), 1 underwent retransplantation due to deterioration of liver function. One died of acute liver failure waiting for retransplantation. Of 12 patients with late HAS (after 1 month of liver transplantation), 1 died of severe sepsis 38 days after transplantation. Five patients underwent late retransplantation due to ischemic-type biliary strictures or recurrent attacks of cholangitis. One of these patients died 11 days after retransplantation. The median follow-up of all 20 patients was 14.4 months after liver transplantation. The Kaplan-Meier curve of patency showed that cumulated primary patency of hepatic artery interventional treatment at 3, 6 and 12 months was 94, 87 and 79%, respectively. Two patients died of causes unrelated to HAS. Three patients developed recurrent HAS and were successfully treated with second interventional therapy. Eight patients (40%) developed ischemic-type biliary strictures and 7 underwent endoscopic treatment or percutaneous transhepatic cholangiodrainage. Graft function in 5 patients improved. The Kaplan-Meier curve of survival showed that the 1- and 2-year cumulated survival rates of early and late HAS were 87.5 and 43.8% and 81.5 and 61.1%, respectively. There was no significant difference in 1- and 2-year survival rates between early and late HAS (log-rank test, p = 0.928). Conclusion: Interventional therapy is an effective treatment for both early and late HAS with excellent short- and mid-term outcomes, while without irreversible graft dysfunction resulted from HAS. However, the patients have a high incidence of ischemic-type biliary lesions.

Quantitative diffusion tensor deterministic and probabilistic fiber tractography in relapsing–remitting multiple sclerosis

PURPOSEnOur aim was to study the quantitative fiber tractography variations and patterns in patients with relapsing-remitting multiple sclerosis (RRMS) and to assess the correlation between quantitative fiber tractography and Expanded Disability Status Scale (EDSS).nnnMATERIAL AND METHODSnTwenty-eight patients with RRMS and 28 age-matched healthy volunteers underwent a diffusion tensor MR imaging study. Quantitative deterministic and probabilistic fiber tractography were generated in all subjects. And mean numbers of tracked lines and fiber density were counted. Paired-samples t tests were used to compare tracked lines and fiber density in RRMS patients with those in controls. Bivariate linear regression model was used to determine the relationship between quantitative fiber tractography and EDSS in RRMS.nnnRESULTSnBoth deterministic and probabilistic tractographys tracked lines and fiber density in RRMS patients were less than those in controls (P<.001). Both deterministic and probabilistic tractographys tracked lines and fiber density were found negative correlations with EDSS in RRMS (P<.001). The fiber tract disruptions and reductions in RRMS were directly visualized on fiber tractography.nnnCONCLUSIONnChanges of white matter tracts can be detected by quantitative diffusion tensor fiber tractography, and correlate with clinical impairment in RRMS.

Acute leukemia, a rare but fatal complication after liver transplantation

Little information is available about the risk factors and means to improve the survival rate of acute leukemia in a rare but often fatal complication after liver transplantation (LT). We report the development of AML-M2 in one of the 764 patients who underwent liver transplantation at our center, and review the literature on similar cases. The patient, a 42-year-old man who developed acute leukemia 38 months after liver transplantation, was successfully treated with chemotherapy and has subsequently been in remission. With appropriate adjustment of immunosuppressive agents, he was able to safely benefit from chemotherapy. Only 16 patients with acute leukemia after liver transplantation have been reported, and the mortality rate is extraordinarily high (52.94%, 9/17). More cases of acute leukemia will emerge as the rate of survival after liver transplantation increases. The patients chromosomal mutation profile, the choice of immunosuppressive agent, and infection by hepatitis virus may be the risk factors for the development of acute leukemia after LT. Our experience suggests that clinicians should adjust the immunosuppressive agents according to the immunosuppressive state of the patient and explore the option of reducing or stopping the medication as long as liver function remains stable. These measures could help reduce the high mortality rate among these patients.

Liver transplantation for end-stage alcoholic liver disease: a single-center experience from mainland China

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.

Elevated Blood Eosinophil Count Is a Valuable Biomarker for Predicting Late Acute Cellular Rejection After Liver Transplantation

BACKGROUNDnRecent studies have indicated the value of increased blood eosinophil counts for the diagnosis of acute cellular rejection (ACR) after orthotopic liver transplantation (OLT). However, the relationship between eosinophil count and late ACR at more than 6 months after OLT is still unclear.nnnMETHODSnWe sought to retrospectively analyzed the ACR predictive value of eosinophil counts. In the day before or the day of biopsy among 40 biopsies performed on 37 patients beyond 6 months after OLT.nnnRESULTSnRelative eosinophil count was significantly higher in the ACR (n = 24) than the non-ACR cohort, albeit with no significant difference in absolute eosinophil count. Receiver operating characteristic (ROC) analysis showed an absolute eosinophil count of 0.145 × 10(9)/L and a relative eosinophil count of 2.3% to show the highest Youden index with area under the ROC curves of 0.746 and 0.813, respectively. When absolute eosinophil count ≥ 0.145 × 10(9)/L or relative eosinophil count ≥ 2.3% was defined to be elevated, the sensitivity and specificity to predict ACR were 45.8% and 87.5%, and 75% and 87.5%, respectively. When the absolute eosinophil count ≥ 0.285 × 10(9)/L or relative eosinophil count ≥ 3% was defined as elevated, the sensitivity and specificity were 25% and 100%, and 50% and 100%, respectively. All patients with an absolute eosinophil count ≥ 0.285 × 10(9)/L showed a relative eosinophil count ≥ 3%.nnnCONCLUSIONSnElevated blood eosinophil count was a valuable biomarker to predict late ACR after OLT.

Effects of gene transfer CTLA4Ig and anti-CD40L monoclonal antibody on islet xenograft rejection in mice.

Blockade of a costimulatory pathway by adenovirus-mediated cytotoxic T lymphocyte associated antigen 4 immunoglobulin (CTLA4-Ig) gene transfer and anti-CD40L mAb(MR1) have been reported to enhance graft survival in several experimental transplantation models. In this study, we investigated the effects of gene transfer of CTLA4Ig and MR1 on islet xenograft rejection in mice. Recombinant adenovirus AdCTLA4Ig was constructed to express CTLA4Ig. Islet grafts from adult male DA rats transferred with AdCTLA4Ig were transplanted to streptozocin-induced diabetic Balb/c mice. The diabetic mice were treated with MR1 after transplantation. We evaluated the islet xenograft mean survival time as well as changes in interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha) levels in transplanted mice. The mean survival of islet xenografts in the MR1 treatment group was 34.9 +/- 5.62 days, in the AdCTLA4Ig treatment group it was 56.5 +/- 10.64 days, and in the AdCTLA4Ig plus MR1 treatment group it was 112.9 +/- 19.26 days, all significantly prolonged compared with an untreated group (8.1 +/- 0.83 days). Within 1 week after transplantation the levels of IL-2 and TNF-alpha showed sharp increases in the untreated group, being significantly higher than those observed prior to transplantation. In conclusion, using both AdCTLA4Ig and MR1 can improve the islet xenograft survival. The beneficial effects of the combined use of the 2 reagents were superior to either 1 alone, possibly related to down-regulated expression of Th1 cell-related cytokines.