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Sheung Tat Fan

Publications and source records attributed to Sheung Tat Fan.

At least 55 records · Page 3Linked to original sources
PubMed2006

Molecular adsorbent recirculating system treatment for patients with liver failure: the Hong Kong experience.

BACKGROUND: The molecular adsorbent recirculating system (MARS) is an extracorporeal liver dialysis system that allows selective removal of bilirubin and other albumin-bound toxins. We reported here our experience with the use of this technique for management of liver failure at Queen Mary Hospital, Hong Kong. METHODS: From December 2002 to 2004, a total of 74 MARS sessions were performed on 22 patients. The cause of liver failure included acute liver failure (n = 2), acute on chronic liver failure (n = 12), posthepatectomy liver failure (n = 4), and posttransplantation allograft failure (n = 4). RESULTS: MARS treatment showed significant reduction in total bilirubin level, serum ammonia level and blood urea, and nitrogen (P < 0.001 for all three parameters). Five patients (22.7%) were able to bridge to transplantation and one patient (4.5%) made a spontaneous recovery. The 30-day mortality rate was 72.7%. CONCLUSIONS: Our results indicated that MARS can effectively improve serum biochemistry and is suitable for temporarily supporting patients with liver failure where transplantation is not immediately available. There is, however, no clear evidence showing that MARS can increase survival, improve the chance of transplantation or assist liver regeneration. Future studies in the form of randomized-controlled trials are crucial to characterize the true potential of this treatment.

Adult↗
PubMed2006

High doses of tyrosine kinase inhibitor PTK787 enhance the efficacy of ischemic hypoxia for the treatment of hepatocellular carcinoma: dual effects on cancer cell and angiogenesis.

The present study aimed to investigate the therapeutic efficacy of combining vascular endothelial growth factor (VEGF) receptor blockade using tyrosine kinase inhibitor PTK787 with hypoxia for the treatment of hepatocellular carcinoma (HCC). The in vivo effects of the treatments were determined in a rat orthotopic HCC model, in which hypoxia was generated by hepatic artery ligation (HAL). Compared with HAL alone, PTK787 combined with HAL significantly prolonged the animal survival, reduced the tumor size, induced more tumor tissue necrosis and apoptosis, and down-regulated the expression of von Willebrand factor. The mechanism was explored in vitro using murine HCC and endothelial cell lines, respectively. PTK787 combined with hypoxia decreased the expression of VEGF and VEGF receptors in both cell lines and suppressed the cell viability by induction of cell cycle arrest and promotion of apoptosis. Up-regulation of cleaved form caspase-9 and down-regulation of Bcl-2 and cyclin D1 were detected with the combined treatment. Hypoxia sensitized endothelial cells to the inhibitory effect of PTK787 on forming tubular-like structure. The motility of tumor cells was inhibited by hypoxia and the combined approach, with down-regulation of Rac1, Rho, and phosphorylated Akt expression. However, in the endothelial cells, the combined treatment inhibited the hypoxia-enhanced cell motility, with suppressed Rac1, Rho, and phosphorylated Akt expression. In conclusion, PTK787 combined with hypoxia achieved a better therapeutic efficacy than hypoxia alone through enhancing hypoxia-induced antitumor cell effect and preventing the activation of angiogenic process.

Angiogenesis Inhibitors↗
PubMed2006

Preoperative plasma transcript AA454543 level is an independent prognostic factor for hepatocellular carcinoma after partial hepatectomy.

BACKGROUND: We have previously reported that tissue expression levels of transcript AA454543 in hepatocellular carcinoma (HCC) are significantly higher than those of normal livers, livers with cirrhosis, and livers with hepatitis. In addition, a higher level of transcript AA454543 in tumor tissues is associated with poor prognosis. We aim to examine whether quantitative measurement of preoperative plasma transcript AA454543 can provide similar prognostic information. PATIENTS AND METHODS: Blood samples were obtained from 84 HCC patients before surgery. Real-time quantitative reverse transcription-polymerase chain reaction, using TaqMan system, was employed to measure plasma transcript AA454543 and alpha-fetoprotein (AFP) RNA levels. We assessed their prediction power in prognosis using univariate and multivariate analyses. RESULTS: High plasma transcript AA454543 RNA levels were associated with poor overall survival (log-rank test, P < .01). Patients with different plasma AFP RNA levels revealed no difference in overall survival (log-rank test, P = .88). By multivariate Cox regression analysis, plasma transcript AA454543 RNA level (hazard ratio = 4.8, P < .01) and tumor stage (hazard ratio = 1.7, P < .01) were determined to be independent risk factors for the prediction of overall survival. CONCLUSION: Preoperative plasma transcript AA454543 RNA level can provide prognostic information for HCC patients receiving curative partial hepatectomy.

Adult↗
PubMed2006

GEP associates with wild-type p53 in hepatocellular carcinoma.

Granulin-epithelin precursor (GEP) is a novel growth factor whose up-regulation we previously reported in 72% of hepatocellular carcinoma (HCC). GEP expression has been reported to be associated with p53 protein accumulation in a breast cancer study, though the p53 mutation status was not revealed. We aim to investigate whether p53 protein and mutation status correlates with GEP expression in HCC. The statistical comparison of p53 and GEP data revealed an overall positive association between the two protein expression patterns (P<0.001). Upon detailed analysis, the association of p53 and GEP protein expression was found to be highly significant only in HCCs with wild-type p53 (P=0.001); there was no association in HCCs with p53 mutation (P=0.669). The GEP levels in the HepG2 hepatoma cell line with a wild-type p53 background were modulated by transfection experiments. Overexpression of the GEP protein resulted in an increased p53 protein level and suppression of the GEP protein resulted in a decreased p53 protein level in HepG2 cells. In summary, we demonstrated that p53 wild-type protein nuclei accumulation is associated with GEP protein expression in human HCC specimens, and GEP modulates p53 wild-type protein levels in vitro.

Carcinoma, Hepatocellular↗
PubMed2006

Significance of the serum brain-derived neurotrophic factor and platelets in hepatocellular carcinoma.

The present study investigated the significance of the serum brain-derived neurotrophic factor (BDNF) and platelets in relation to the clinicopathological features of hepatocellular carcinoma (HCC) patients. Localization of the BDNF expression in human HCC tissues was performed by immunohistochemistry. The measurement of soluble BDNF in the serum was performed by enzyme-linked immunosorbent assay. BDNF was expressed in the cytoplasm of the tumor cells. A positive correlation between the tissue and serum levels of BDNF was identified in the HCC patients. The serum levels of BDNF were positively correlated with the platelet counts in the HCC patients. A higher level of serum BDNF was significantly correlated with a tumor size >5 cm, poorly differentiated HCC, the presence of microsatellite tumor nodules, and the absence of cirrhosis in the non-tumorous tissues. A higher level of the serum BDNF/platelet ratio was associated with a poorer disease-free survival after hepatic resection. This study suggested that the tumor cell was a source of serum BDNF in HCC. A higher serum BDNF level was associated with a more advanced tumor status in the HCC patients. The interaction between serum BDNF and platelets might play an important role in HCC tumor progression.

Blood Platelets↗
PubMed2005

FTY720: a promising agent for treatment of metastatic hepatocellular carcinoma.

PURPOSE: Recurrence after resection and metastasis are common in hepatocellular carcinoma and are associated with poor prognosis. Therefore, effective treatment is urgently needed for improvement of patients' survival. Previously, we reported that FTY720 has an antimetastatic effect on hepatocellular carcinoma cell line through down-regulation of Rac signaling pathway. This study aims to investigate the in vivo antimetastatic potential of FTY720 in an orthotopic nude mice model using metastatic human hepatocellular carcinoma cell lines MHCC-97L (lower metastatic potential) and MHCC-97H (higher metastatic potential). EXPERIMENTAL DESIGN: The nude mice bearing liver tumors were randomized into a treatment group and a control group, each with 12 mice. FTY720 was administered at a dosage of 5 or 10 mg/kg via i.p. injection after 7 days of tumor inoculation. Thirty-five days later, the mice were sacrificed for record of intrahepatic and pulmonary metastases. RESULTS: After 35 days of FTY720 treatment at the dosages of 5 and 10 mg/kg, all 12 mice in the treatment group were alive and well. FTY720 at the dosages of 5 and 10 mg/kg significantly suppressed the tumor volume and intrahepatic and pulmonary metastases in the metastatic nude mice model. FTY720 suppressed intrahepatic and pulmonary metastases by inhibition of Rac expression, which at least in part down-regulated the vascular endothelial growth factor expression and CD34 staining in a dose-dependent manner. CONCLUSION: FTY720 is a promising novel therapeutic drug for treatment of hepatocellular carcinoma metastasis.

Animals↗
PubMed2005

Allograft inflammatory factor-1 (AIF-1) is crucial for the survival and pro-inflammatory activity of macrophages.

Our previous studies revealed that macrophages played an important role in linking injury, inflammatory and immune response in small-for-size liver transplantation. However, the molecular basis that promoted macrophage activation was not clear. In the present study, we explored the potential role of allograft inflammatory factor-1 (AIF-1) in mediating the survival and pro-inflammatory activity of macrophages in a macrophage cell line. First, the expression of AIF-1 was investigated with the stimulation of pro-inflammatory cytokines and anti-inflammatory treatment. Second, the level of inducible nitric oxide synthase (iNOS) and the survival and migration activity of macrophages were determined with the alterations of AIF-1 expression. Finally, a potential molecule that regulated AIF-1 expression was identified by the proteomic approach. The macrophage cell line expressed a certain level of endogenous AIF-1, which could be enhanced by pro-inflammatory cytokines IL-1beta or tumor necrosis factor-alpha and suppressed by anti-inflammatory drug sodium salicylate. AIF-1 augmentation induced by AIF-1/PCDNA3.1(+) transfection enhanced the levels of iNOS and monocyte chemoattractant protein-1, and promoted the cell migration. On the other hand, suppression of AIF-1 expression by AIF-1/short interference RNA (siRNA) inhibited iNOS production, induced macrophage cell apoptosis and blocked the cell migration. Using two-dimensional electrophoresis, a disintegrin and metalloproteinase domain 3 (ADAM3) was identified after AIF-1/siRNA transfection. Transfection of ADAM3/PCDNA3.1(+) up-regulated the expression of AIF-1 and iNOS, whereas suppression of ADAM3 expression down-regulated AIF-1 and iNOS expression. In conclusion, AIF-1 played an important role in the survival and pro-inflammatory activity of macrophages, and ADAM3 might be an upstream molecule that regulated AIF-1 expression.

Animals↗
PubMed2005

Both antiangiogenesis- and angiogenesis-independent effects are responsible for hepatocellular carcinoma growth arrest by tyrosine kinase inhibitor PTK787/ZK222584.

Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis of hepatocellular carcinoma. Inhibition of VEGF receptors could theoretically reduce angiogenesis and tumor growth in hepatocellular carcinoma, but this remains to be proven with an experimental study. This study examined the angiogenesis-dependent and angiogenesis-independent activities of PTK787/ZK222584 (PTK787), a tyrosine kinase inhibitor of VEGF receptors, in nude mice bearing human hepatocellular carcinoma xenografts. The in vitro effects of PTK787 on proliferation, apoptosis, and cell cycle distribution in human hepatocellular carcinoma cell lines were also studied. Oral administration of PTK787 resulted in a significant reduction in tumor volume and microvessel formation of hepatocellular carcinoma xenografts in nude mice. PTK787 inhibited tumor cell proliferation in a dose-dependent manner and also induced tumor cells to undergo apoptosis both in vivo and in vitro. The proapoptotic response was associated with down-regulation of Bcl-2 and Bcl-x(L) expression and induction of cleavage of caspase-3. In addition, PTK787 induced growth arrest in hepatocellular carcinoma cells, which was associated with G1 arrest and partial G2-M block. This effect correlated with an increase in p21(WAF1/ CIP1) (p21) and p27KIP1 (p27) protein expression. In conclusion, this study showed that PTK787 is a potent inhibitor of tumor growth in hepatocellular carcinoma by both antiangiogenic effect and direct effects on tumor cell proliferation and apoptosis. Our data suggest that blockage of VEGF receptors may provide an effective therapeutic approach for human hepatocellular carcinoma.

Angiogenesis Inhibitors↗
PubMed2005

Is hepatic resection for large or multinodular hepatocellular carcinoma justified? Results from a multi-institutional database.

BACKGROUND: The role of surgical resection in patients with large or multinodular hepatocellular carcinoma (HCC) remains unclear. This study evaluated the long-term outcome of patients with hepatic resection for large (>5 cm in diameter) or multinodular (more than three nodules) HCC by using a multi-institutional database. METHODS: The perioperative and long-term outcomes of 404 patients with small HCC (<5 cm in diameter; group 1) were compared with those of 380 patients with large or multinodular HCC (group 2). The prognostic factors in the latter group were analyzed. RESULTS: The postoperative complication rate (27% vs. 23%; P = .16) and hospital mortality rate (2.4% vs. 2.7%; P = .82) were similar between groups. The overall survival rates were significantly higher in group 1 than group 2 (1 year, 88% vs. 74%; 3 years, 76% vs. 50%; 5 years, 58% vs. 39%; P < .001). Among patients in group 2, five independent prognostic factors were identified to be associated with a worse overall survival: namely, symptomatic disease, presence of cirrhosis, multinodular tumor, microvascular tumor invasion, and positive histological margin. CONCLUSIONS: Hepatic resection can be safely performed in patients with large or multinodular HCC, with an overall 5-year survival rate of 39%. Symptomatic disease, the presence of cirrhosis, a multinodular tumor, microvascular invasion, and a positive histological margin are independently associated with a less favorable survival outcome.

Aged↗
PubMed2005

Porcine liver: morphologic characteristics and cell viability at experimental radiofrequency ablation with internally cooled electrodes.

PURPOSE: To evaluate morphologic characteristics and cell viability of radiofrequency ablation zones in porcine liver. MATERIALS AND METHODS: Approval of the study protocol was obtained from the Ethics Committee on Use of Live Animals for Teaching and Research at University of Hong Kong. Internally cooled electrodes were used to produce 120 ablated zones ex vivo and 60 ablated zones in vivo with single electrodes (1-, 2-, and 3-cm exposed lengths) or clustered electrodes (1.0-, 2.0-, and 2.5-cm exposed lengths) at 4, 8, 12, and 16 minutes of ablation (ex vivo) and 8 and 12 minutes of ablation (in vivo). Morphologic measurements of each ablated zone were performed. Cell viability in each ablated zone was assessed qualitatively with histochemical staining and quantitatively with measurement of intracellular adenosine 5'-triphosphate (ATP) concentration. RESULTS: Exposed length of electrode (coefficient = 0.79, standard error = 0.04, P < .001), duration of ablation (coefficient = 0.14, standard error = 0.01, P < .001), and clustered electrode design (coefficient = 1.21, standard error = 0.05, P < .001) were independent factors that affected minimal transverse diameter and volume of ablated zone in ex vivo study. Similar morphologic characteristics existed among ablated zones in in vivo study. Mean distance of ablation beyond the electrode tip remained constant (ex vivo, 1.0 cm +/- 0.08 [standard deviation]; in vivo, 0.5 cm +/- 0.05) regardless of different ablation conditions. Histochemical staining revealed no viable hepatocytes from center to margins of white zone in each ablated area. Mean intracellular ATP concentration in margins of white zone (9.5 x 10(-12) mol/microg DNA +/- 1.43) was lower than that in red zone (4088 x 10(-12) mol/microg DNA +/- 65.97, P < .001) and in adjacent normal liver (4528 x 10(-12) mol/microg DNA +/- 52.74, P < .001). CONCLUSION: Distance of ablation beyond the tip of the electrode remained constant (ex vivo, 1.0 cm; in vivo, 0.5 cm) with different conditions of ablation. Complete and uniform cellular destruction was achieved in the white zone of ablated area.

Adenosine Triphosphate↗
PubMed2005

Alternative mRNA splicing of liver intestine-cadherin in hepatocellular carcinoma.

PURPOSE: To identify alternative splicing of the liver intestine-cadherin (LI-cadherin) gene in hepatocellular carcinoma (HCC) and correlate its aberrant expression with clinical outcomes. EXPERIMENTAL DESIGN: Reverse transcription-PCR (RT-PCR) and quantitative real-time RT-PCR were used to examine alternative mRNA splicing and mRNA level of LI-cadherin in 50 paired tumor-peritumor tissues of 50 HCC and 8 normal liver specimens. The minigene exon-trapping strategy was employed to investigate the splicing mechanism introduced by nucleotide polymorphisms. Association of LI-cadherin splicing with tumor venous infiltration, first-year tumor recurrence, and overall survival after partial hepatectomy were determined. RESULTS: Alternative mRNA splicing of LI-cadherin was identified in half of the HCC specimens. Sequencing analysis indicated the loss of exon 7 in the spliced LI-cadherin gene. LI-cadherin mRNA was up-regulated from 2.58-fold to 800-fold in over 80% of HCC samples when compared with normal liver by quantitative PCR. Furthermore, nucleotide polymorphisms were identified in putative branch point at IVS6 + 35 (intron 6) as well as in coding sequence 651 (exon 6) in HCC tissues, which may affect alternative mRNA splicing. Clinically, those patients who harbored the alternative splicing of LI-cadherin were strongly associated with shorter overall survival time (P < 0.01) as well as higher incidences of tumor recurrences and venous infiltration (both P < 0.05) after hepatectomy. CONCLUSIONS: Over-expression of LI-cadherin was frequently detected in liver cancer patients. Aberrant alternative splicing of LI-cadherin was detected in 50% of HCC specimens and its clinical significance hinted at early tumor recurrence and poor overall survival of HCC patients.

Alternative Splicing↗
PubMed2005

Claudin-10 expression level is associated with recurrence of primary hepatocellular carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) patients with the same clinicopathologic features can have remarkably different disease outcomes after curative hepatectomy. To address this issue, we evaluated the cDNA microarray gene expression profiles of HCCs and identified claudin-10 expression level was associated with disease recurrence. The aim of the current study is to validate the microarray data by an alternative research method applicable for routine practice. EXPERIMENTAL DESIGN: Quantitative reverse transcription-PCR (RT-PCR) was used to validate the microarray data on claudin-10 expression level. The assay was repeated on a separate HCC sample set to consolidate the prognostic significance of claudin-10. RESULTS: Claudin-10 expression level by quantitative RT-PCR and by microarray measurement showed a high concordance (r = 0.602, P < 0.001). Quantitative RT-PCR was repeated on a separate HCC sample set and the association of claudin-10 expression with recurrence was again confirmed (hazard ratio, 1.2; 95% confidence interval, 1.0-1.4; P = 0.011). By multivariable Cox regression analysis, claudin-10 expression and pathologic tumor-node-metastasis stage were independent factors for prediction of disease recurrence. CONCLUSION: Claudin-10 expression of HCC can be used as a molecular marker for disease recurrence after curative hepatectomy.

Carcinoma, Hepatocellular↗
PubMed2005

Identification of brain-derived neurotrophic factor as a novel functional protein in hepatocellular carcinoma.

This study aims to identify a novel molecule that may contribute to hepatocarcinogenesis in a rat orthotopic hepatocellular carcinoma model. The hepatocellular carcinoma model was generated by injection of tumor cells into the left lobe of the liver. Proteomic approaches, including ProteinChip and two-dimensional electrophoresis, were used to identify proteins from serially collected rat serum samples. By both ProteinChip and two-dimensional electrophoresis techniques, the level of a 27-kDa protein was found to be augmented in serum samples during tumor development, decreased after left lobectomy, and reincreased at the time of tumor recurrence. The protein was identified to be brain-derived neurotrophic factor (BDNF). By using specific primers and monoclonal antibody, the expression pattern of BDNF was confirmed in tumor tissue but not in the adjacent nontumorous liver tissue. In addition, the truncated isoform of BDNF receptor-tyrosine protein kinase receptor B was only found in tumor tissue. An in vitro study showed that exogenous BDNF could induce tumor cell proliferation predominantly in relatively small numbers of inoculated cells. Administration of BDNF to tumor cell lines induced significantly increased expression of heat shock protein 90 (Hsp90) and cyclin D1, and blocking the activity of Hsp90 could reverse the up-regulation of cyclin D1 induced by BDNF. The present study revealed that BDNF and its receptor were uniquely expressed in tumor tissue and cell lines of hepatocellular carcimona but not in nontumorous liver tissue and normal cell line. BDNF could stimulate tumor cell proliferation in a Hsp90-dependent manner.

Animals↗
PubMed2005

Variation in the use of laparoscopic cholecystectomy for acute cholecystitis: a population-based study.

HYPOTHESIS: There is wide variation in the use of laparoscopic cholecystectomy (LC) for acute cholecystitis among all public hospitals in Hong Kong. The objective of this study was to determine the factors responsible for the use of LC for acute cholecystitis in a stable population. DESIGN: A retrospective survey on 2353 patients with pathologically proven acute cholecystitis treated with cholecystectomy in Hong Kong from 1998 to 2002. SETTING: All public hospitals in Hong Kong. RESULTS: The rate of using LC for acute cholecystitis increased by 30.4% from 1998 to 2002. We observed a wide variation in the use of LC for acute cholecystitis ranging from 3.7% to 92.9% (P<.001). There was no correlation between the number of cholecystectomies performed and the percentage of LCs performed in each hospital (P = .39). Logistic regression analysis showed that the hospital, year of operation, and age of the patients were independent variables for LC. CONCLUSIONS: A wide variation in the use of LC for acute cholecystitis was observed among the public hospitals in Hong Kong. Young female patients from selected hospitals recently are more likely to be treated with LC.

Aged↗
PubMed2005

Safety of donor right hepatectomy without abdominal drainage: a prospective evaluation in 100 consecutive liver donors.

Although the role of routine abdominal drainage after liver resection for tumors has been questioned, abdominal drainage after donor right hepatectomy for live donor liver transplantation (LDLT) has been a routine practice in most transplant centers. The present study aimed to evaluate the safety of the procedure without abdominal drainage. A prospective study was performed on 100 consecutive liver donors who underwent right hepatectomy for LDLT from July 2000 to September 2003. Biliary anatomy was carefully studied with intraoperative cholangiography using fluoroscopy. The middle hepatic vein was included in the graft in all except 1 patient. Parenchymal transection was performed using an ultrasonic dissector. The right hepatic duct was transected at the hilum and the stump was closed with 6-O polydioxanone continuous suture. Absence of bile leakage was confirmed with methylene blue solution instilled through the cystic duct stump. The abdomen was closed after careful hemostasis without drainage in all donors. The median age of the donors was 36 years (range 18-56 years). Median operative blood loss and operating time were 350 mL (range 42-1,400 mL) and 7.5 hours (range 5.2-10.7 hours), respectively. None of the donors required any blood or blood product transfusion. There was no operative mortality. The median postoperative hospital stay was 8 days (range 5-30 days). Postoperative morbidity occurred in 19 patients (19%), most of which were minor complications. No donor experienced bile leakage, intraabdominal bleeding, or collection. None required surgical, radiologic, or endoscopic intervention for postoperative complications, except for 1 donor who developed late biliary stricture that required endoscopic dilatation. All donors were well with a median follow-up of 32 months (range 11-50 months). In conclusion, with detailed study of the biliary anatomy and meticulous surgical technique, donor right hepatectomy can be safely performed without abdominal drainage. Abdominal drainage is not a mandatory procedure after donor hepatectomy in LDLT.

Abdomen↗
PubMed2005

MARS treatment for a patient presenting with acquired hepatic glutamine synthetase deficiency after orthotopic liver transplantation.

We report a 48-year-old man presenting with refractory hyperammonemia after orthotopic liver transplantation. On investigation he was found to have acquired hepatic glutamine synthetase deficiency, a rare condition that occurs after organ transplantations. The patient was started on continuous venovenous hemofiltration treatment, but the hyperammonemia did not respond. The patient was then subjected to molecular adsorption recirculation system (MARS) therapy and the ammonia level gradually improved with successive treatments. In conclusion, the response was unlikely due to the hemofiltration component of MARS alone but more probably due to the removal of putative albumin-bound toxin by the adsorption circuit that had ameliorated the internal milieu of the graft and reversed the enzyme deficiency.

Bilirubin↗
PubMed2005

Liver transplantation for chronic hepatitis B with lamivudine-resistant YMDD mutant using add-on adefovir dipivoxil plus lamivudine.

Lamivudine treatment in patients with chronic hepatitis B virus (HBV) infection may improve clinical state and suppress viral replication before liver transplantation. Emergence of lamivudine-resistant YMDD mutant is common. We report the results of liver transplantation in 16 patients with pretransplantation YMDD mutants after receiving lamivudine treatment for a median of 738 days (range, 400-1799 days). Adefovir dipivoxil (10 mg daily) was added on to lamivudine for a median of 20 days (range, 8-271 days) before (n = 11) or at (n = 5) liver transplantation, and the combination was continued indefinitely thereafter. Eight patients received additional intravenous hepatitis B immune globulin (HBIG) for a median of 24 months. Fifteen patients with known pre-adefovir HBV DNA levels had a median titer of 14,200 x 10(3) copies/mL (2 x 10(3) to 4,690,000 x 10(3) copies/mL), and 14 had HBV DNA >10(5) copies/mL. All but 1 patient remained positive for HBV DNA (by quantitative polymerase chain reaction [qPCR]) at the time of liver transplantation, and the titer was greater than10(5) copies/mL in 8 patients. The median follow-up after liver transplantation was 21.1 (range, 4.4-68.9) months. One patient (6%) died of an unrelated cause 12.2 months after transplantation, and 15 patients (94%) were alive with the original graft. All patients cleared HBV DNA and had no detectable HBV DNA by qPCR at the latest follow-up. Fourteen patients had cleared hepatitis B surface antigen (HBsAg), but 2 patients who received only adefovir dipivoxil and lamivudine without HBIG remained HBsAg positive after 7.7 and 9.5 months. Serum HBV DNA, however, was negative, and there was no biochemical or histological evidence of recurrence. Adefovir dipivoxil was well tolerated with no significant renal toxicity. In conclusion, a combination of add-on adefovir dipivoxil plus lamivudine therapy provides effective prophylaxis in patients with pretransplantation YMDD mutant that may be actively replicating. The cost effectiveness of additional passive immunoprophylaxis remains to be defined.

Adenine↗