Min-Qiang Lu

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.

Clinical study on prevention of HBV re‐infection by entecavir after liver transplantation

Cai C‐j, Lu M‐q, Chen Y‐h, Zhao H, Li M‐r, Chen G‐h. Clinical study on prevention of HBV re‐infection by entecavir after liver transplantation. 
Clin Transplant 2011 DOI: 10.1111/j.1399‐0012.2011.01448.x. 
© 2011 John Wiley & Sons A/S.

Enhanced antitumor efficacy of a novel fiber chimeric oncolytic adenovirus expressing p53 on hepatocellular carcinoma

Oncolytic adenoviruses may offer a new treatment option and improve the prognosis for patients with hepatocellular carcinoma (HCC). However, the antitumor efficacy of oncolytic adenoviruses on HCC cells is compromised due to low expression of the adenovirus serotype 5 (Ad5) receptor on the target cells. In this study we showed that all HCC cell lines and clinical samples expressed high level of CD46, the receptor for Adenovirus 35 (Ad35) and constructed new fiber chimeric oncolytic adenoviruses with or without a p53 gene expression cassette, SG635-p53 and SG635, respectively. These variants were derived from the previously described Ad5 vectors SG600-p53 and SG600 by replacing the Ad5 fiber with a chimeric Ad5/35 fiber. It was found that the 5/35 fiber chimeric adenovirus vector (Ad5/35-EGFP) demonstrated significantly improved transduction in all tested HCC cell lines compared with the Ad5 vector (Ad5-EGFP). The new fiber chimeric oncolytic adenoviruses produced more progeny viruses in HCC cells than did the Ad5-based viruses but replicated weakly in normal fibroblast BJ cells. In addition, SG635-p53 mediated a higher level of transgenic expression than SG600-p53 in Hep3B and Huh7 cells and showed a markedly enhanced antitumor effect on HCC cells in vitro compared with SG635 or SG600-p53 without causing significant cytotoxicity to normal cells. Antitumor activity of SG635-p53 was shown in Hep3B subcutaneous xenograft tumor models following intratumoral injection, resulting in significant inhibition of tumor growth and prolonged survival of animals. Our data suggest that SG635-p53, as a fiber chimeric oncolytic adenovirus in combination with p53 expression, may serve as a novel, promising and safe anticancer agent for the treatment of HCC.

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.

Evaluating Biliary Anatomy and Variations in Living Liver Donors by a New Technique: Three-Dimensional Contrast-Enhanced Ultrasonic Cholangiography

Accurate assessment of the biliary anatomy is important for the safety of liver donors in living donor liver transplantation (LDLT). We evaluated the biliary anatomy and variations of 12 living liver donors with 3-D contrast-enhanced ultrasonic cholangiography (3-D CEUSC) by injecting microbubble contrast agents into the common hepatic ducts intraoperatively. Two radiologists assessed the diagnostically adequate, delineation of biliary branch orders, visibility scores (grades 0 to 3) and anatomical patterns of the intrahepatic biliary tree by consensus. The results were compared with findings on intraoperative cholangiography (IOC) and surgery. 3-D CEUSC successfully demonstrated the spatial structure of the intrahepatic biliary tree in all 12 donors. The maximum branching order of intrahepatic bile ducts displayed on 3-D CEUSC was the fifth order in the right lobe and fourth order in the left lobe of the liver, respectively. The visibility scores of the first-order (3.00 +/- 0.00) and second-order (2.67 +/- 0.69) branches were significantly (p < 0.001) higher than that of the third-order (1.98 +/- 1.13) branches, whereas visibility scores of the second-order (2.88 +/- 0.34) and third-order (2.44 +/- 1.01) branches in the right lobe were significantly (p = 0.040 and p < 0.001, respectively) higher than those in the left lobe (2.46 +/- 0.88 and 1.33 +/- 0.99). The 3-D CEUSC images of the 12 donors were diagnostically adequate for evaluating the biliary anatomy. Normal biliary pattern in nine donors and biliary variations in three donors were confirmed by both IOC and surgical findings. 3-D CEUSC may be a potential alternative to IOC in the evaluation of biliary anatomical variation before graft harvesting in LDLT.

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.