Preoperative Alfa-Fetoprotein and Fibrinogen Predict Hepatocellular Carcinoma Recurrence After Liver Transplantation Regardless of the Milan Criteria: Model Development with External Validation.

BACKGROUND/AIMS: Patient selection is critically important in improving the outcomes of liver transplantation for hepatocellular carcinoma. The aim of the current study was to identify biochemical measures that could affect patient prognosis after liver transplantation. METHODS: A total of 119 patients receiving liver transplantation for hepatocellular carcinoma were used to construct a model for predicting recurrence. The results were validated using an independent sample of 109 patients from independent hospitals. All subjects in both cohorts met the Hangzhou criteria. RESULTS: Analysis of the discovery cohort revealed an association of recurrence with preoperative fibrinogen and AFP levels. A mathematical model was developed for predicting probability of recurrence within 5 years: Y = logit(P) = -4.595 + 0.824 ×fibrinogen concentration (g/L) + 0.641 × AFP score (1 for AFP<=20ng/ml, 2 for 20 400ng/ml). At a cutoff score of -0.85, the area under the curve (AUC) was 0.819 in predicting recurrence (vs. 0.655 when using the Milan criteria). In the validation cohort, this model had reasonable performance in predicting 5-year overall survival (68.8% vs. 28.1% in using the -0.85 cutoff, p< 0.001) and disease-free survival (65.7% vs. 25.9%, p< 0.001). The sensitivity and specificity were 77.0% and 62.5%, respectively. The AUC of this newly developed model was similar to that with the Milan criteria (0.698 vs. 0.678). Surprisingly, the DFS in patients with score <= -0.85 under this model but not meeting the Milan criteria was similar to that in patients meeting the Milan criteria (53.8% vs. 60.0%, p=0.380). CONCLUSIONS: Preoperative AFP and fibrinogen are useful in predicting recurrence of hepatocellular carcinoma after liver transplantation.

Therapeutic potentials of umbilical cord-derived mesenchymal stromal cells for ischemic-type biliary lesions following liver transplantation.

BACKGROUND AIMS: Ischemic-type biliary lesions are severe, graft-threatening complications after orthotopic liver transplantation, and a novel and efficient therapeutic strategy is urgently needed. Due to the immunosuppressive and regenerative properties, mesenchymal stromal cells (MSCs) could be an interesting candidate. METHODS: We initiated safety and efficacy of human umbilical cord-derived MSC (UC-MSC) transfusions for patients with ischemic-type biliary lesions after liver transplantation. From January 2013 to June 2014, 12 ischemic-type biliary lesions patients were recruited as the MSCs group in this phase I, prospective, single-center clinical study. Patients in this group received six doses of UC-MSCs (about 1.0 × 106 MSCs per kilogram body weight through peripheral intravenous infusion). The traditional therapeutic protocol was applied during October 2003 to December 2012 in 70 ischemic-type biliary lesions patients who were treated as the control group. Liver function tests, the need for interventional therapies and graft survival rate were chosen to evaluate the therapeutic efficacy of MSC treatment. Adverse events were closely monitored up to 2 years after MSC transfusions. RESULTS: No significant MSC-related adverse events were observed during the trial. Compared with baseline, the levels of total bilirubin, γ-glutamyl transferase and alkaline phosphatase were decreased after UC-MSC treatment at week 20 and week 48. Interventional therapies were performed in 64.3% (45/70) of patients in the control group and 33.3% (4/12) of patients in the MSCs groups. MSC therapy significantly decreased the need for interventional therapies (P = 0.046). The 1- and 2-year graft survival rates were higher in the MSCs group (100% and 83.3%, respectively) than in the control group (72.9% and 68.6%, respectively). CONCLUSIONS: The UC-MSC transfusions are clinically safe and short-term favorable, which may become a novel treatment for patients with ischemic-type biliary lesions after liver transplantation.

miR-630 overexpression in hepatocellular carcinoma tissues is positively correlated with alpha-fetoprotein.

BACKGROUND: MicroRNA-630 (miR-630) has been shown to be involved in various human malignancies. However, its role in hepatocellular carcinoma (HCC) remains unknown. MATERIAL AND METHODS: TaqMan qRT-PCR assay was performed to detect the expression of miR-630 in 42 pairs of HCC tissues and corresponding noncancerous hepatocellular tissues, and its correlations with clinicopathologic features and serum alpha-fetoprotein (AFP) level of patients were analyzed. RESULTS: The present study found that miR-630 expression was significantly increased in HCC tissues and cells compared with their normal counterparts. miR-630 expression level did not significantly chang at stage I but was markedly increased at advanced TNM stage (stage II~III). In addition, the increased expression of miR-630 in tissues of HCC appeared in patients who exhibited elevated serum levels of AFP (>25 ng/ml), but not in those with normal AFP levels (≤25 ng/ml). The miR-630 expression in carcinoma tissues revealed a positive correlation with the levels of serum alpha-fetoprotein (AFP; R2=0.768). CONCLUSIONS: These results suggest that miR-630 is associated with tumor progression of hepatocellular carcinoma and may be a potential prognosis indicator.

A three-factor preoperative scoring model predicts risk of recurrence after liver resection or transplantation in hepatocellular carcinoma patients with preserved liver function.

BACKGROUND: No staging systems of hepatocellular carcinoma (HCC) are tailored for assessing recurrence risk. We sought to establish a recurrence risk scoring system to predict recurrence of HCC patients receiving surgical curative treatment (liver resection or transplantation). METHODS: We retrospectively studied 286 HCC patients with preserved liver function receiving liver resection (n=184) or transplantation (n=102). Independent risk factors were identified to construct the recurrence risk scoring model. The recurrence free survival and discriminatory ability of the model were analyzed. RESULTS: Total tumor volume, HBsAg status, plasma fibrinogen level were included as independent prognostic factors for recurrence-free survival and used for constructing a 3-factor recurrence risk scoring model. The scoring model was as follows: 0.758 x HBsAg status (negative: 0; positive: 1) + 0.387 x plasma fibrinogen level (≤ 3.24 g/L: 0; >3.24 g/L: 1) + 0.633 x total tumor volume (≤ 107.5 cm3: 0; > 107.5 cm3: 1). The cut-off value was set to 1.02, and we defined the patients with the score ≤ 1.02 as a low risk group and those with the score > 1.02 as a high risk group. The 3-year recurrence-free survival rate was significantly higher in the low risk group compared with that in the high risk group (67.9% vs 41.3%, P < 0.001). In the subgroup analysis, liver transplantation patients had a better 3-year recurrence-free survival rate than the liver resection patients in the low risk group (80.0% vs 64.0%, P < 0.01). Additionally for patients underwent liver transplantation, we compared the recurrence risk model with the Milan criteria in the prediction of recurrence, and the 3-year recurrence survival rates were similar (80.0% vs 79.3%, P = 0.906). CONCLUSION: Our recurrence risk scoring model is effective in categorizing recurrence risks and in predicting recurrence-free survival of HCC before potential surgical curative treatment.

Downregulation of miR-610 promotes proliferation and tumorigenicity and activates Wnt/ß-catenin signaling in human hepatocellular carcinoma.

BACKGROUND: Wnt/ß-catenin signaling pathway plays important roles in human cancer progression. Better understanding the mechanism underlying regulation of Wnt/ß-catenin signaling pathway might provide novel therapeutic targets for cancer treatment. METHODS: miR-610 expression levels in hepatocellular carcinoma (HCC) cell lines, HCC tissues and 76 archived HCC specimens were determined using real-time PCR. Cell viability was measured by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. The level of DNA synthesis was determined by BrdU incorporation assay. Flow cytometry analysis was used to analyze cell cycle progression. The cells proliferation and tumorigenesis were determined by colony formation and anchorage-independent growth assays in vitro, and by xenograft tumors in vivo. Luciferase assay and micro-ribonucleoprotein complex immunoprecipitation assay were used to confirm the association of the targeted mRNAs with miR-610. RESULTS: miR-610 was downregulated in human HCC cells and tissues, and correlated with HCC progression and patient survival. Inhibition of miR-610 promoted, but overexpression of miR-610 reduced, HCC cell proliferation and tumorigenicity both in vitro and in vivo. Furthermore, we found that inhibiting miR-610 activated, but overexpressing miR-610 decreased, the Wnt/ß-catenin activity through directly suppressing lipoprotein receptor-related protein 6 (LRP6) and transducin ß-like protein 1 (TBL1X). The in vitro analysis was consistent with the inverse correlation detected between miR-610 levels with expression of LRP6 and TBL1X in a cohort of human HCC samples. CONCLUSIONS: Our results indicate that miR-610 downregulation plays essential roles in HCC progression and reduced miR-610 is correlated with Wnt/ß-catenin signaling pathway.

Long-term results of liver transplantation for over 60 years old patients with hepatitis B virus-related end-stage liver disease.

BACKGROUND: Hepatitis B virus (HBV)-related end-stage liver disease is the leading indication for liver transplantation in China, but long-term results of liver transplantation in patients aged over 60 years are not clear. The present study was to reveal the natural history of liver recipients with hepatitis B older than 60 years. METHODS: The recipients who had received liver transplantation between December 2003 and December 2005 were divided into two groups: those equal or older than 60 years (older group, n=60) and those younger than 60 years (younger group, n=305). Risk factors for poor long-term outcome in patients aged over 60 years were also analyzed. RESULTS: Except for age and preexisting chronic disease (P<0.05), no significant differences were observed in perioperative characteristics between the two groups. There was also no significant difference in HBV and hepatocellular carcinoma recurrence (P>0.05). The actuarial 1-, 3-, 5- and 8-year survival rates were 81.6%, 71.6%, 66.7% and 63.3% respectively for the older group vs 84.9%, 77.7%, 70.8% and 65.6% for the younger group (P>0.05). Multivariate analyses showed that pre-liver transplant renal insufficiency was a risk factor for poor outcome in the older group (odds ratio=3.615, P=0.014). CONCLUSIONS: Liver transplantation is safe and feasible for patients with HBV-related end-stage liver disease aged over 60 years. Older patients with renal insufficiency should undergo transplantation earlier than younger patients.

[Preoperative neutrophil-lymphocyte ratio as a prognostic predictor after liver transplantation for hepatocellular carcinoma].

OBJECTIVE: To analyze the negative impact of preoperative neutrophil-lymphocyte ratio (NLR) on the tumor recurrence of hepatocellular carcinoma (HCC) after orthotopic liver transplantation. METHODS: The clinical data of HBV (hepatitis B virus)-associated HCC patients undergoing liver transplantation were retrospectively analyzed. Their clinical and pathological risk factors for tumor-free survival were evaluated by univariate analysis. The analysis of Cox multiple regression was performed to determine the parameters of predicting the HCC recurrence. NLR ≥ 2.5 was considered to be elevated. RESULTS: A total of 76 patients were identified. Among them, 37 had an elevated NLR. The 1, 3 and 5-year tumor-free survival rates were 69.2%, 52.7% and 50.9% respectively. The disease-free survival for patients with high NLR was significantly worse than that for those with normal NLR (1, 3, and 5 year survivals at 56.3%, 37.6% and 37.6% vs 81.1%, 66.9% and 63.3% respectively; P = 0.011). Univariate analysis of factors revealed that tumor size > 5 cm, tumor number > 3, vascular invasion, serum α-fetoprotein level ≥ 400 µg/L and NLR ≥ 2.5 were preoperative predictors of disease-free survival. Cox regression analysis showed that the presence of vascular invasion, tumor number > 3 and NLR ≥ 2.5 were independent prognostic factors of worse disease-free survival. CONCLUSION: An elevated NLR significantly increases the risk for tumor recurrence in HCC patients undergoing liver transplantation.

[The relationship between hepatocellular carcinoma recurrence and hepatitis B virus recurrence after liver transplantation].

OBJECTIVE: To investigate the relationship between hepatocellular carcinoma (HCC) recurrence and hepatitis B virus (HBV) recurrence. METHODS: The clinical data of 340 patients underwent liver transplantation due to HBV related end-stage liver disease and received long-term follow up in our hospital from Jan 2004 to Dec 2008 were retrospectively analyzed. All patients received nucleoside analogues therapy formally before entering into the waiting list and nucleoside analogues combined low-dose HBIG therapy during and after transplantation. Patients were regularly followed up at the outpatient, monitoring the HBV recurrence and survival. Multivariate Cox regression analysis was used to evaluate the risk factors for hepatitis recurrence. RESULTS: 33 patients suffered from HBV recurrence post transplantation. The 1-, 3- and 5- year recurrence rates were 7.0%, 10% and 13% respectively. The median HBV recurrence time was 5 months (1-21 months). COX regression analysis revealed that risk factors for HBV recurrence were HCC (HR = 2.98; 95% CI 1.08-8.25; P < 0.05) and pre-transplantation HBV-DNA load over 5 log10 copies/ml (HR = 3.99; 95% CI 1.85-8.62; P < 0.01). Further stratified analysis showed that patients who suffered from carcinoma recurrence had a higher incidence of HBV recurrence than those who did not, which were 27.9% and 8.7% (HR = 4.58;95% CI 1.88-11.12; P < 0.01) respectively. 12 patients suffered from both HCC and HBV recurrence. Spearman correlation analysis demonstrated a strong correlation between HBV and HCC recurrence times (r = 0.583, P < 0.05). CONCLUSIONS: Post transplantation HCC recurrence is a risk factor for HBV recurrence.

[Effect of artificial liver support system on the survival rate of high risk patients after liver transplantation].

OBJECTIVE: To observe the effect of artificial liver support system (ALSS) after liver transplantation on the survival rate of severe hepatitis patients. METHODS: Patients with severe hepatitis with model for end stage liver disease (MELD) score above 35 were divided into two groups according to whether pre-transplantation ALSS was instituted (n=23) or not (n=41). Evaluation was performed on the day when the patient entered into the waiting list and 1 day pre-transplantation. Survival rates and survival curves were estimated with Kaplan-Meier method. Log-Rank test for trends was used when comparing curves. RESULTS: There was no significant difference between two groups when comparing the parameters including prothrombin time, fibrinogen, total bilirubin, blood ammonia, creatinine, MELD score on the day of entering into the waiting list (all P>0.05). After the therapy of ALSS, the parameters of ALSS group were significantly improved comparing to those of the control group (all P<0.01). MELD score of ALSS group on the day pre-transplant was decreased significantly comparing to that on the day entering into the waiting list (37.6+/-2.0 vs. 41.4+/-2.2, P<0.01), with the difference in MELD score (DeltaMELD) of -3.8. MELD score of control group on the day entering into the waiting list and 1 day pre-transplant was 40.6+/-1.7 and 41.0+/-1.6 respectively, with DeltaMELD of +0.4 ( P>0.05). The blood loss and operation time in ALSS group was significantly less than the control group [(4 070.0+/-688.1) ml vs. (4 905.9+/-1 142.1) ml, (9.4+/-1.1) hours vs. (10.5+/-1.0) hours, P<0.05 and P<0.01). Thirty days and 1 year survival rate of ALSS group was 91% and 82%, and that of control group was 76% and 59% respectively (P=0.044). CONCLUSION: ALSS can improve the survival rate of patients with severe hepatitis undergoing liver transplantation through ameliorating physiological status, lessening blood loss during operation and operation time.

[Risk factors predicting late mortality after liver transplantation for benign end-stage liver disease].

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

[Immunization with dendritic cells infected with mTERT adenovirus vector effectively elicits immunity against mouse H22 hepatoma in vivo].

OBJECTIVE: To investigate the effects of dendritic cells (DCs) infected with adenovirus vector encoding mTERT on induction of mTERT antigen specific immunity against H22 hepatoma in vivo. METHODS: Forty Bal B/c mice were subcutaneously immunized with Ad-mTERT infected DC. Cytotoxicity of mTERT specific CTL was determined by 51Cr release assay. IL-2 and IFN-gamma were tested by ELISA. IFN-gamma ELISPOT assays were performed for measuring antigen specific IFN-gamma production by T cells. Tumor size and survival of the immunized mice were recorded and evaluated whether preexisting hepatoma metastases could be supressed after immunization with mTERT-expressing DCs. RESULTS: The lytic activity of CTL, IL-2 (871.25 pg/ml), IFN-gamma (169.15 ng/ml) and IFN-gamma secreting cells (378/10(6) spleen cells) elicited by the Ad-mTERT infected DCs were much stronger and higher than that by Ad-GFP group (131.6 pg/ml, 15.4 ng/ml, 36/10(6) spleen cells, P<0.05), DC group (71.3 pg/ml, 10.5 ng/ml, 21/10(6) spleen cells, P<0.05), PBS group (65.8 pg/ml, 7.4 ng/ml, 18/10(6) spleen cells, P<0.05). In prophylaxis and treatment experiment the Ad-mTERT/DCs immunized mice lived significantly longer than other groups, demonstrating that primary DCs were genetically modified to express the mTERT antigen and could suppress the tumor growth. CONCLUSION: Adenovirus vector mediated mTERT infected DCs can effectively induce mTERT antigen specific antitumor activity, and can induce protective and therapeutic antitumor immunity.

[Significance of lipopolysaccharides, toll-like receptor and inducible nitric oxide synthase in hepatopulmonary syndrome].

OBJECTIVE: To investigate the role of lipopolysaccharides (LPS), toll-like receptor 2 (TLR2) and inducible nitric oxide synthase (iNOS) in the development of hepatopulmonary syndrome (HPS). METHODS: Seventy-one patients were divided into 3 groups: end-stage liver disease with HPS (HPS group, n = 31), end-stage liver disease without HPS (non-HPS group, n = 30) and healthy volunteers (n = 10). Blood was collected at pre-OLT and Days 3, 7, 14, 21 and 28 post-OLT to detect the plasma LPS level, TLR2mRNA and iNOSmRNA in peripheral blood monocytes. RESULTS: The LPS, TLR2mRNA and iNOSmRNA at pre-OLT in HPS group were 4.31 +/- 3.267 ng/L, 336,594.10 +/- 366,901.14 and 63,982.24 +/- 74,127.47 copies/microg RNA respectively; 1.62 +/- 1.34 ng/L, 336,321.53 +/- 222,317.17 and 44,169.9 +/- 24,993.00 copies/microg RNA respectively in non-HPS group and 0.94 +/- .69 ng/L, 10,338.28 +/- 3,814.64 and 19,168.49 +/- 2,417.35 copies/microg RNA in normal control group. LPS, TLR2mRNA and iNOSmRNA at pre-OLT in HPS group were higher than those in non-HPS group without significance (P > 0.05), but significantly higher than those in control group (P < 0.05). The TLR2mRNA decreased in all end-stage liver disease patients at post-OLT with the improvement of liver function and oxygenation. CONCLUSION: The dysfunction of intestinal barrier and intestinal endotoxemia may be the important mechanisms of HPS through the elevation of LPS level and the expressions of TLR2mRNA and iNOSmRNA.

[Risk factors predicting the prognosis of orthotopic liver transplantation in hepatopulmonary syndrome].

OBJECTIVE: To observe the effect of orthotopic liver transplantation (OLT) on hepatopulmonary syndrome (HPS) and investigate risk factors predicting the prognosis of OLT. METHODS: Twenty-six cases of HPS and 30 cases of non-HPS were analyzed treated from April 2004 to January 2006. Survival rates after OLT were compared and risk factors predicting the prognosis of OLT in HPS were researched by univariant and COX analysis. RESULTS: The 28 days survival rate in HPS after OLT was 76.9% (20/26), half a year survival rate and one year survival rate were both 61.5% (16/26). Whereas the one year survival rate of patients without HPS was 100%(P < 0.05). By univariant analysis, shunt of (99)Tc(m)-labeled macro-aggregated albumin in lungs, PaO2 and PaO2/FiO2 in room air before operation were relative to the prognosis of peri-operative period and half a year outcome after OLT in HPS (P < 0.05). Shunt of (99)Tc(m)-labeled macro-aggregated albumin in lungs (OR = 1.182, P = 0.001), and mechanical ventilation time (OR = 1.003, P = 0.053) after OLT were independent risk factors predicting the prognosis of OLT in HPS by COX analysis. Shunt of (99)Tc(m)-labeled macro-aggregated albumin in lungs > or = 28.4%, or PaO2 < or = 56 mm Hg (1 mm Hg = 0.133 kPa) before OLT predicted the poor outcome of OLT in HPS. The sensitivity were 83.3% and 85.0% respectively, and the specificity were 95.0% and 83.3% respectively. CONCLUSIONS: OLT is an effective treatment for HPS.Shunt of (99)Tc(m)-labeled macro-aggregated albumin in lungs before OLT and mechanical ventilation time after OLT were independent risk factors for the prognosis of OLT in HPS.

Hepatic artery complications after orthotopic liver transplantation: interventional treatment or retransplantation?

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Long-term survival after liver transplantation for benign end-stage liver disease in adults].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

[Retransplantation for hepatic artery complications after orthotopic liver transplantation].

OBJECTIVE: To evaluate the efficacy and timing of re-transplantation for hepatic artery complications after orthotopic liver transplantation. METHODS: Between December 2003 and December 2006, the clinical data of 13 patients diagnosed as hepatic artery complications after liver transplantation were retrospectively analyzed. RESULTS: There were no significant difference in duration of operation and anhepatic phase between the initial transplantation and the second transplantation (P = 0.291, P = 0.312). However, intra-operative blood loss [(3.1 +/- 1.1) L vs. (1.5 +/- 0.9) L, P = 0.005] and intensive care unit stays [(4.3 +/- 1.8) d vs. (3.2 +/- 2.5) d, P = 0.015] were significantly increased in the re-transplant patients. No perioperative mortality occurred. The postoperative mortality of liver re-transplantation was 38.5% (5/13) including acute renal failure in two patients, severe infection in two and heart infarction in one. The other 8 patients were followed from 6 months to 51 months, with a median survival time of 22.5 months. CONCLUSIONS: Liver re-transplantation is the only viable option for patients with irreversible graft dysfunction secondary to hepatic artery complications after liver transplantation. Proper indication and optimum time of re-transplantation, reasonable individual immunosuppression regime and effective perioperative care program contribute to the increase of the survival rate of the patients performed liver re-transplantation.

Prophylaxis of hepatitis B recurrence in post-liver transplantation patients with lamivudine-resistant YMDD mutant.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: ADV combined with intramuscular HBIG can effectively prevent patients with pre-transplantation YMDD mutant from HBV recurrence after LT.

[The impact of itraconazole versus fluconazole on the prevention of postoperative invasive fungal infections after orthotopic liver transplantation].

OBJECTIVE: To compare the efficiency and safety of itraconazole oral solution with those of fluconazole to prevent invasive fungal infections (IFI) in postoperative patients receiving orthotopic liver transplantation (OLT). METHODS: In a randomized, controlled, open trial, 60 patients receiving OLT were randomized into itraconazole treatment group (n = 30) and fluconazole treatment group (n = 30). The patients in itraconazole treatment group were given itraconazole oral solution in a dose of 20 ml once a day for 15 days and the patients in the fluconazole treatment group were given fluconazole in a dose of 150 mg once a day also for 15 days. The incidences of fungal infections after liver transplantation and the resistance to drugs were recorded. RESULTS: There were three patients in the itraconazole treatment group getting IFI; the infection rate was 10.0%. One patient had confirmed diagnosis and two other patients were diagnosed clinically. In the fluconazole treatment group there were 10 patients getting IFI, the infection rate was 33.3%. Two patients had confirmed diagnosis, six patients were diagnosed clinically and the remaining two were diagnosed tentatively. There was a significant difference between the two groups (P < 0.05). CONCLUSION: Compared with fluconazole, itraconazole oral solution is more effective in the treatment of invasive fungal infections in postoperative patients receiving OLT.

[ABO-incompatible liver transplantation for liver failure].

OBJECTIVE: To evaluate the efficacy of ABO-incompatible orthotopic liver transplantation (OLT) in treatment of liver failure. METHODS: The clinical data of 66 cases of OLT, including 21 cases of ABO-incompatible OLT, for liver failure were retrospectively analyzed. RESULTS: The 3-month, and 1-, 2-, and 3-year survival rates of the ABO-identical group were 84.2%, 77.4%, 67.6%, and 60.1%, respectively, while those of the ABO-incompatible group were 75.6%, 64.0%, 58.2%, and 58.2%, respectively. The mean survival time of the ABO-identical group was (806.0+/-70.0) d, not significantly different from that of the ABO-incompatible group (720.3+/-118.5 d, P=0.417). The acute rejection rate of the ABO-identical group was 8.9%, not significantly different from that of ABO-incompatible group (9.0%, P=0.253). The biliary tract complication rate and infection rate of the ABO-incompatible group were 76.2% and 28.6% respectively, both significantly higher than those of the ABO-identical group (48.9% and 8.9% respectively, P=0.037 and P=0.038). The major causes of death in the ABO-incompatible group were serious infection (5/21) and renal failure (4/21). CONCLUSION: ABO-incompatible OLT is an acceptable option to cure liver failure in emergency. Intensive perioperative supervision is essential to improve the effect of ABO-incompatible OLT.