OBJECTIVE: To report the experience with liver transplantation at the Queen Mary Hospital from 1991 to 2000. DESIGN: Retrospective study. SETTING: Liver transplant centre of a University teaching hospital, Hong Kong. PATIENTS: One hundred and forty-eight patients (127 adults and 21 children) who underwent a total of 155 liver transplants using 75 cadaver grafts (full-size, 67; reduced-size, 5; split, 3) and 80 living donor grafts (left lateral segment, 15; left lobe, 6; right lobe, 59) from October 1991 to December 2000 were reviewed. MAIN OUTCOME MEASURES: Graft and patient survival rate. RESULTS: The most common disease indications for liver transplantation were chronic hepatitis B-related liver disease (n=74) in adults and biliary atresia (n=14) in children. Eighteen patients had hepatocellular carcinoma. Forty-eight (31%) liver transplants (three ABO-incompatible) were performed in high-urgency situations for patients requiring intensive care. The proportion of living donor liver transplants was 47.7% in adults and 73.9% in children. The overall 1-year and 5-year patient survival rates were 82% and 77%, respectively. The survival of high-risk recipients, such as those with fulminant hepatic failure (80%), chronic hepatitis B (81%), or hepatocellular carcinoma (94%), was not inferior to that of other patients. CONCLUSION: Over the last decade, the promotion of (cadaver) organ donation through public education coupled with innovative techniques in living donor liver transplantation have enabled a liver transplantation programme to be established in Hong Kong with gratifying results.

C. M. Lo;上达 范;C. L. Liu;B. H. Yong;C. L. Lai;G. K. Lau;W. I. Wei;P. K. Tam;N. S. Tsoi;I. O. Ng;K. Young;J. K. Chan;W. K. Tso;K. Y. Yuen;J. Wong

Hong Kong Medical Journal

2002-8

上达 范

2011-1-1

Living-donor liver transplantation has provided a solution to the severe lack of cadaveric grafts for the replacement of livers afflicted with end-stage cirrhosis, fulminant disease, or inborn errors of metabolism. The pioneering experience in Japan in the early 1990s helped open wide the avenues of a new branch of science that is technically demanding and whose benefits are clearly dramatic. The need for alternative sources of liver grafts was common to the entire Asian region and, fortunately, the option of obtaining partial liver grafts from live donors had already become tenable. By the second half of the past decade, living-donor liver transplant programs had been successfully established in Hong Kong, Taiwan, and Korea. More than 1,500 cases have been performed over a 12-year period. This report describes the cumulative experience in living-donor liver transplantation in Asia on the basis of data from five major liver transplant centers.

Chao Long Chen;上达 范;Sung Gyu Lee;Masatoshi Makuuchi;Koichi Tanaka

Transplantation

2003-2-15

Patients in high-urgency situations for liver transplantation have a high mortality rate while on the waiting list for cadaveric grafts. In countries where cadaveric organ donation is scarce, the use of living-donor liver transplantation (LDLT) provides the only chance of survival for both pediatric and adult patients. It results in a satisfactory overall survival, from approximately 60% to 75% in pediatric patients and from 70% to 90% in adult patients. Patients who had early LDLT were shown to have a better survival outcome than those who waited for cadaveric organ donation, because a timely graft was available to them before they deteriorated further to multiple organ failure. Patients who were in high-urgency situations for liver transplantation and opted for LDLT were also shown to have significantly better survival outcomes than those who did not opt for this procedure. Although left lobe liver graft can be used successfully in adult-to-adult LDLT in high-urgency situations, there is a trend toward a more frequent use of the larger mass provided by the right lobe of the liver. Adequate venous drainage of the anterior segment of the right lobe liver graft is also considered essential for the favorable outcome of the recipients. Although donor morbidity has been reported to be low in LDLT and no donor death has been reported from Asian transplant centers, standardized definitions of morbidity and better methods for observing and measuring outcomes are necessary to understand and to potentially reduce morbidity.

Chi Leung Liu;上达 范;Chung Mau Lo;John Wong

Transplantation

2003-2-15

Inclusion of the middle hepatic vein in a right lobe graft from a living-donor may improve venous drainage and avoid graft dysfunction, but reconstruction of the middle hepatic vein is technically difficult. We developed a hepatic venoplasty technique, which was applied in eight consecutive right lobe liver transplantations. The right and middle hepatic veins of the graft were joined together to form a triangular cuff for a single anastomosis to the recipient's inferior vena cava. Hepatic venoplasty was successful in all cases, and no interposition graft was required. Venovenous bypass was not used. All grafts showed immediate function, and no hepatic venous outflow obstruction was observed. There was no reoperation and the graft survival rate was 100%. This hepatic venoplasty technique can be applied systemically as a standard one in right lobe liver graft with the middle hepatic vein to simplify the recipient hepatectomy and to obviate venous outflow obstruction.

Chung Mau Lo;上达 范;Chi Leung Liu;John Wong

Transplantation

2003-2-15

p53-p21/WAF1 cell cycle pathway plays an important role in growth control, and the inappropriate deregulation of this pathway has been implicated in carcinogenesis. Although the role of p53 in hepatocellular carcinoma (HCC) has been suggested, its exact molecular mechanism in relation to its down-stream gene p21/WAF1 remains unclear. To investigate the relationship between the expression of p53 and p21/WAF1 and the possible roles of the 2 proteins in HCC, we examined the intracellular expression of p53, p21/WAF1 and PCNA immunohistochemically, together with apoptosis by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay in 35 clinical tissue specimens. The correlation between the clinicopathologic parameters and the intracellular gene expression were analyzed. The results showed that p53 over-expression is a reliable marker for mutational modulation of p53 function. p53 was negatively correlated with p21/WAF1 in hepatitis B virus-related HCC (p=0.024, r=-0.432). Patients with a high p53 expression had a significantly higher Edmondson grading (12/21 vs 13/14, p=0.024) and larger tumor size (10 vs 6 cm, p=0.029). Patients with higher p53 expression had shorter disease-free survival (4 vs 19 months, p=0.0131) and overall survival (11 vs 42 months, p=0.0031). Intracellular expression of p21/WAF1 was positively correlated to proliferating cell nuclear antigen (p=0.001, r=0.776) and apoptosis (p=0.003, r=0.639). Our findings suggest that disruption of p53-p21/WAF1 cell cycle pathways contributes to tumor progression and worse clinical outcome of HCC.

Terence Kin Wah Lee;Kwan Man;Ronnie Tung Ping Poon;Chung Mau Lo;Irene Oi Lin Ng;上达 范

Oncology Reports

2004-7

Background. Recombinant adeno-associated virus vector (rAAV) is a promising vehicle for gene delivery, but few reports have documented its application in solid organ transplantation. In a rat orthotopic liver transplantation model, we investigated the efficacy of rAAV-mediated human cytotoxic T-lymphocyte-associated antigen 4 and immunoglobulin G (hCTLA4Ig) gene transfer to induce long-term allograft survival. Methods. Dark Agouti and Lewis rats were used as donors and recipients, respectively, in six experimental groups: (a) syngeneic control, (b) no treatment, (c) rAAV-green fluorescent protein, (d) rAAV-hCTLA4Ig, (e) low-dose FK506 for 7 days, and (f) rAAV-hCTLA4Ig and low-dose FK506 for 7 days. Results. The liver allografts were rejected within 10 days when no treatment was given or rAAV-green fluorescent protein was delivered. rAAV-hCTLA4Ig transduction slightly prolonged the survival time to 11 days. Long-term survival was achieved using the combined treatment of rAAV-hCTLA4Ig and low-dose FK506, whereas grafts were rejected on day 33 in the low-dose FK506 group. A sustained hCTLA4 level in plasma was detected in the combined treatment group from day 5 to day 180. On postoperative day 5, combined treatment significantly decreased the interleukin-2 and interferon-γ protein levels in the grafts and the number of infiltrating B, T, CD25⁺, CD4⁺, CD8⁺, and NK cells. Conclusion. This study shows that rAAV-hCTLA4Ig gene transfer combined with low-dose FK506 can achieve long-term liver allograft survival.

Zhenfan Yang;Xiaobing Wu;Tung Yu Tsui;云德 侯;John M. Luk;上达 范

Transplantation

2003-2-15

The necessity of providing venous drainage for the right anterior sector of a right-lobe graft in adult-to-adult right-lobe live-donor liver transplantation has been controversial. Inclusion of the middle hepatic vein in the right-lobe graft to ensure better early graft function is also under debate. This report summarizes the views of five Asian centers on the necessity of providing venous drainage to the right anterior sector in a right-lobe graft as presented at the Asian Living Donor Transplantation Symposium 2002. All five centers recognize the importance of adequate drainage of the right anterior sector, but they adopt different approaches in including the middle hepatic vein in the graft. Tokyo University uses an occlusion test of the right hepatic artery and middle hepatic vein to define whether the right anterior sector is dusky or regurgitation of blood flow is present in the right anterior portal vein before the decision is made for middle hepatic vein reconstruction. The Asan Medical Center uses hydrostatically dilated saphenous venous graft to anastomose prominent segment V and VIII hepatic vein branches to the inferior vena cava. The University of Hong Kong Medical Centre includes the middle hepatic vein in every graft and anastomoses it to the recipient's middle or left hepatic vein. Kyoto University uses venous jump graft for anastomosing prominent middle hepatic vein branches to the inferior vena cava for recipients receiving a small-for-size graft or graft with dominant middle hepatic vein drainage. The Chang Gung Memorial Hospital adopts a flexible approach in inclusion of the middle hepatic vein in the graft depending on the donor size and the hepatic venous configuration of the right-lobe graft. In summary, the criteria for inclusion and reconstruction of the middle hepatic vein vary. Further analysis is needed to confirm the importance of adequate drainage of the right anterior sector in right-lobe live-donor liver transplantation.

上达 范;Vanessa H. De Villa;Tetsuya Kiuchi;Sung Gyu Lee;Masatoshi Makuuchi

Transplantation

2003-2-15

Chronic hepatitis B virus (HBV) infection is the leading cause of end-stage liver disease in Asia. The results of liver transplantation in these patients have significantly improved to a level comparable to those of other recipients as a result of the rapid evolution in the strategies of prevention and treatment of recurrent hepatitis B over the past decade. Hepatitis B immune globulin (HBIG) and lamivudine, either alone or in combination, are effective in preventing reinfection, but the most cost-effective dosing regimen with optimum efficacy without the prohibitive cost remains to be determined, an issue that is particularly relevant to liver transplant centers with serious financial constraints in Asia. The idea of active immunization is attractive, but the results have been conflicting to date. The newer nucleoside analogs appear most promising, and a combination of two or more antiviral agents is likely to represent the future strategy of choice in the prophylaxis and treatment of recurrent hepatitis B after liver transplantation.

Chung Mau Lo;上达 范;Chi Leung Liu;Ching Lung Lai;John Wong

Transplantation

2003-2-15

Hepatocellular carcinoma is characterized by hypervascularity and a propensity for vascular invasion. Detailed analysis of complementary DNA (cDNA) microarray global gene expression data and further validation on a smaller independent sample set by reverse transcription-polymerase chain reaction established the presence of two endothelial gene clusters in hepatocellular carcinoma. Cluster I, consists of 20 cDNA clones, representing 15 unique genes. Cluster II consists of nine unique genes. The expression of the cluster I genes appeared to be significantly upregulated in hepatocellular carcinoma compared with normal liver, cirrhotic liver, or nontumor liver tissues adjacent to the hepatocellular carcinoma. The pattern of gene expression of cluster I genes correlated positively with the 'proliferation gene cluster' and 'stromal cells cluster 2'. Expression of cluster II genes, in contrast, was not significantly different between hepatocellular carcinoma and non-neoplastic liver tissues. Studies conducted to localize the protein products of these genes by immunohistochemical staining of tissue arrays with up to 350 cores of tissues, and by in situ hybridization led to the discovery of novel sinusoidal endothelial cell markers in hepatocellular carcinoma: podocalyxin-like and regulator of G protein signaling-5. Our results underscore fundamental differences not only between neoplastic vs non-neoplastic liver cells but also between the hepatic sinusoidal endothelium of hepatocellular carcinoma and normal liver.

Xin Chen;John Higgins;Siu Tim Cheung;Rui Li;Veronica Mason;Kelli Montgomery;上达 范;Matt Van De Rijn;Samuel So

Modern Pathology

2004-10