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.

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.

Association of phenotypic transformation of circulating tumor cells and early recurrence in patients with hepatocellular carcinoma following liver transplantation.

BACKGROUND: CTCs play a critical role in the diagnosis and prognosis of liver cancer. However, there are few studies on whether different types of CTCs can predict the prognosis in patients with HCC following LT. METHODS: Retrospective data including CTCs detected by the CanPatrolTM platform combined with RNA-ISH were collected and analyzed on 56 patients from December 2016 to December 2019 at the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China. RESULTS: During the study period, fifty-six patients (51 males, 5 females) were included with an mean age of 52 ± 9 years. The 1-, 2- and 3-year recurrence rates of postoperative interstitial CTC-positive and CTC-negative groups were 21.7% vs 10.8%, 37.5% vs 10.8% and 55.5% vs 10.8%, confirming a statistically significant difference between the 2 groups (p = 0.044). The 1-, 2- and 3-year recurrence rates of the increasing interstitial CTCs group were 25.2%, 36.9% and 66.9%, while 12.6%, 24.4% and 24.4% in the decreasing and unchanged group, indicating a significant difference (p = 0.038). CONCLUSION: CanPatrolTM platform presents a superior analytical sensitivity, and may be used as a dynamic monitoring tool for CTCs. And interstitial CTCs which are more aggressive and metastatic caused by EMT can be regarded as a predictor of post-transplant tumor recurrence after LT for HCC.

[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.

[Clinical analysis between "early" versus "late" liver retransplantation].

OBJECTIVE: To compare early and late orthotopic liver retransplantation (re-OLT) for patients with poor graft function after primary transplantation at our center and sum up our clinical experience in re-OLT. METHODS: The clinical data of 36 re-OLTs from January 2004 to July 2009 were analyzed retrospectively, consisting of the first group with 17 cases of early re-OLT and the second group with 19 cases of late re-OLT. The average ages were (45 ± 13) years and (48 ± 10) years, and the time intervals were (49 ± 54) days and (514 ± 342) days in early re-OLT group and late re-OLT group, respectively. RESULTS: Biliary tract complications were the main indications for early re-OLT and late re-OLT. Other common indications were vascular complications in early re-OLT and recurrence of primary diseases in late re-OLT. No significant differences were found between the groups with regard to the volume of bleeding during operation, cold ischemia time, operative duration and perioperative mortality except the MELD score. Outcome was fatal for 8 patients in early re-OLT and 10 patients in late re-OLT. Three deaths were due to severe sepsis-related disease, 3 deaths due to multiple organ failure in early re-OLT and 4 deaths due to severe sepsis-related disease, 3 deaths due to recurrence of HCC in late re-OLT. One and 2-year actuarial survival rates after re-OLT were 52.9% and 41.2%, respectively, for patients in early re-OLT, and 63.2% and 52.6%, respectively, for patients in late re-OLT. No significant differences were found regarding survival rates between the two groups (P > 0.05). CONCLUSIONS: The similar clinical results can be achieved in early and late re-OLT. Proper indications and optimal operation timing, experienced surgical procedures and effective perioperative anti-infection strategy contribute to the improvement of the overall survival rate of the patients after re-OLT.

Contrast-enhanced ultrasonography to evaluate risk factors for short-term and long-term outcomes after liver transplantation: A pilot prospective study.

PURPOSE: To evaluate whether Doppler ultrasonography (DUS) and contrast-enhanced ultrasonography (CEUS) can identify liver donation after brain death (DBD) and cardiac death (DCD) with the risk of developing short-term primary graft dysfunction (PGD) or arterial and biliary complications within 1 year. MATERIALS AND METHODS: Consecutive DBD and DCD donors who underwent DUS/CEUS examinations before surgical procurement from February 2016 to June 2018 at our institution were included. The US and CEUS images of each donor liver were analysed, and the parameters were recorded. RESULTS: The mean time for US examination was 32 min (range, 20-59 min), and all donors tolerated the examination well. In terms of short-term outcomes, among the 52 eligible donor livers, 20 (38.5 %) of their recipients developed PGD. The multivariable analysis showed that decreased enhancement of donor livers on CEUS (OR = 15.976, 95 % CI: 1.652-154.628, P = 0.017) and high recipient model for end-stage liver disease (MELD) scores (OR = 1.050, 95 % CI: 1.004-1.099, P = 0.034) before liver transplantation (LT) were independent factors of PGD. In contrast, for long-term complications, among the 48 eligible donor livers, 16 (33.3 %) developed arterial or biliary complications within 1 year. The multivariable analysis did not show any independent factors of arterial or biliary complications within 1 year. CONCLUSIONS: A decrease in enhancement on CEUS is an independent risk factor for poor short-term outcomes of LT. CEUS may be promising for predicting post-LT outcomes of critically ill donors effectively and safely by evaluating the haemodynamic changes in DBD and DCD donor livers.

Doppler ultrasonography and contrast-enhanced ultrasonography to evaluate liver allograft discard: A pilot prospective study.

BACKGROUND: Broad hemodynamic changes, is believed to have a profoundly damaging effect on donor livers after brain death (DBD) or cardiac death (DCD). It remains unclear whether Doppler ultrasonography (DUS) and contrast-enhanced ultrasonography (CEUS), the imaging modalities to evaluate perfusion, could provide more information of liver discarded. OBJECTIVE: To evaluate the ability of DUS and CEUS to predict the risk of DBD or DCD liver discarded. METHODS: The consecutive DBD or DCD donors with DUS/CEUS examinations before surgical procurement from February 2016 to June 2018 at our institution were included. The US and CEUS images of each donor liver were analyzed and the parameters were recorded. RESULTS: Among the 67 eligible donor livers, 15 (22.4%) were discarded and 52 (77.6%) were used. The discarded livers showed prolonged SAT of hepatic artery (0.08s vs 0.06s, OR = 2.169, P = 0.008) on DUS, less cases with homogeneous enhancement (40.0% vs 73.1%, OR = 0.243, P = 0.028) on CEUS, more cases with decreased enhancement (53.3% vs 19.2%, OR = 4.800, P = 0.009), and less difference of the peak time between portal vein and liver parenchymal (0.5s vs 6.7s, OR = 0.917, P = 0.034). The multivariable analysis showed that donor liver with prolonged SAT of hepatic artery (OR = 7.304, 95% CI: 1.195-44.655, P = 0.031) and decreased enhancement (OR = 2.588, 95% CI: 1.234-5.426, P = 0.012) were independent factors of liver discarded. CONCLUSIONS: DUS/CEUS could be applied as a promising predictive tool to screen high-risk liver donors. The prolonged SAT of hepatic artery on DUS and the decrease of liver donor in enhancement on CEUS, indicating hemodynamic changes in DBD and DCD donor livers, were risk factors of liver discarded.

CEUS detection of biliary ischaemia during the first 4 weeks after liver transplantation predicts non-anastomotic biliary stricture.

BACKGROUND: Biliary ischaemia is an important factor in the pathogenesis of non-anastomotic biliary stricture (NAS) after liver transplantation (LT). Contrast-enhanced ultrasound (CEUS) can be used to detect biliary ischaemia, but no study has examined the utility of CEUS in predicting NAS. OBJECTIVE: To evaluate whether repeated CEUS as a non-invasive method of biliary ischaemia can identify NAS. METHODS: Consecutive LT patients who underwent CEUS examinations at 1-4 weeks after LT from September 2012 to December 2015 at our institution were included. The CEUS images and clinical data were analysed. RESULTS: Among 116 eligible LT patients, 39 (33.6%) were diagnosed with NAS within 1 year after LT. The patients with NAS had a significantly higher CEUS score at weeks 2-4 (all P < 0.05) and a higher slope of CEUS score progression (0.480 vs -0.044, P < 0.001). The accuracy of CEUS in identifying NAS improved over time after LT, reaching its maximum at week 4, with a sensitivity of 66.7%, a specificity of 87.9%, a positive predictive value (PPV) of 75.9%, a negative predictive value (NPV) of 82.3%, and an accuracy of 80.2%in the full cohort when a CEUS score≥3 was used as the cut-off. Multivariate analysis identified gamma-glutamyl transpeptidase (GGT), alanine transaminase (ALT) and the CEUS score at week 4 as independent predictors of NAS. In the task of identifying NAS, an NAS score combining the above 3 variables at week 4 showed areas under the receiver operating characteristic curve of 0.88 (95%CI, 0.78-0.99) in the estimation group (n = 60) and 0.82 (95%CI, 0.69-0.96) in the validation group (n = 56). An NAS score cut-off of 0.396 identified 87.2%of NAS cases in the estimation group, with a PPV of 93.3%; and 75.0%of NAS cases in the validation group, with a PPV of 58.8%. CONCLUSIONS: CEUS examination during the first 4 weeks is useful in assessing the risk of NAS within 1 year after LT. In particular, an NAS score combining the CEUS score, GGT level, and ALT level at week 4 can be used to accurately predict the risk of NAS in LT patients.

[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.

[Multimodality interventional treatments for biliary complications after orthotopic liver transplantation: a preliminary study].

OBJECTIVE: To describe the technique, efficacy, and safety of multimodality interventional treatments for biliary complications after orthotopic liver transplantation (OLT). The core of multimodality interventional treatments is percutaneous transhepatic biliary drainage (PTBD). METHODS: From January 2006 to May 2008, seventy-two patients with biliary complications afte OLT were closed in our study. On the basis of the cholangiographic appearance, patients were classified into 4 groups: anastomotic biliary strictures (n = 19), hilar biliary strictures (n = 16), multifocal/diffuse biliary strictures (n = 31), and anastomotic biliary fistulae (n = 6). All patients were treated in our hospital, including PTBD only in 6 patients, PTBD combined with balloon dilation in 50 patients, balloon dilation and plastic stent implantation in 10 patients, balloon dilation and metallic stent implantation in 6 patients. Their data were analyzed retrospectively, including serum hemobilirubin, cholangiographic appearance and complications. RESULTS: PTBD were successful in all cases. The clinical symptoms improved or eliminated were observed in 66 cases, the effective rate was 91.7% (66/72). Among 72 patients, 26 patients were free of drainage tube, 8 patients underwent second PTBD for the obstruction of biliary stents, and 38 patients maintained drainage tube for long-term. In 66 patients with biliary obstruction, the direct bilirubin was (145 +/- 106) micromol/L before treatments and 76 micromol/L +/- 59 micromol/L one month after PTBD (t = 3.78, P < 0.001). The rate of biliary tract infection was 14.3% and 43.8% respectively with the tip of drainage tube placed in biliary duct and in duodenum. There was a significantly statistical difference between these two items (chi(2) = 4.886, P = 0.027). CONCLUSION: PTBD combined with balloon dilation and biliary stent implantation is a effective therapeutic modality for biliary complications after OLT, which can improve patients' clinical symptoms, elevate patients' quality of life. The tip of drainage tube being placed in biliary duct can decrease the rate of biliary tract infection significantly.

[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.

[Model for end-stage liver disease-sodium predicts prognosis in patients with chronic severe hepatitis B].

OBJECTIVES: To study the practical use of the serum sodium incorporated model for end-stage liver disease (MELD-Na) on clinic and to assess its validity by the concordance-statistic in predicting the prognosis of the patients with chronic severe hepatitis B. METHODS: Adult patients with a diagnosis of chronic severe hepatitis B between January 2007 and December 2007 in a single center were analyzed. The serum sodium, MELD, MELD-Na, and Delta MELD-Na (Delta MELD=MELD score at 14 days after medical treatment-MELD score at admission) scores of 426 patients with chronic severe hepatitis B were calculated. The 3-month mortality in patients was measured, and the validity of the models was determined by means of the concordance-statistic. RESULTS: The area under the receiver-operating characteristic curves of Na, MELD and MELD-Na for the occurrence of death in 3 month were 0.718, 0.875 and 0.922. The 3-month mortality of the MELD-Na scores group <25, 25-30, >30-35, >35- <40 and > or = 40 were 2.0%, 5.4%, 35.4%, 53.8% and 86.9% respectively. There was a significant difference of 3-month mortality between the five groups (P<0.05). The 3-month mortality of Delta MELD-Na> 0 group was 65.9%, and the Delta MELD-Na < or = 0 group was 15.8%. There was a significant difference of 3-month mortality between the two groups (P<0.05). CONCLUSIONS: MELD-Na score is a valid model to predict 3-month mortality in patients with chronic severe hepatitis B. Delta MELD-Na is clinically useful parameters for predicting the therapeutic effect of chronic severe hepatitis B.

Early liver retransplantation versus late liver retransplantation: analysis of a single-center experience.

BACKGROUND: Orthotopic liver retransplantation (re-OLT) is the only effective therapy for irreversible failure of a liver graft. Early and late graft failure gives way to two different clinical conditions that should be discussed separately. This study was designed to compare early and late re-OLT for patients with poor graft function after primary transplantation at our center and sum up our clinical experience in re-OLT. METHODS: The clinical data of 31 re-OLTs at our center from January 2004 to February 2007 were analyzed retrospectively, consisting of the first group with 14 cases of early re-OLT and the second group with 17 cases of late re-OLT. RESULTS: Biliary tract complications were the main indications for early re-OLT (57.1%) and late re-OLT (52.9%). Other common indications were vascular complications in early re-OLT and recurrence of primary diseases in late re-OLT. No significant differences were found between the groups with regard to the volume of bleeding during operation, cold ischemia time, operative duration, and perioperative mortality; except for the model of end-stage liver disease (MELD) score. Outcome was fatal for 7 patients in early re-OLT and 9 patients in late re-OLT. Two deaths were due to multiple organ failure with 3 deaths due to severe sepsis-related disease in early re-OLT, and 4 deaths were due to severe sepsis-related disease with 3 deaths due to recurrence of hepatocellular carcinoma (HCC) in late re-OLT. One and 2-year actuarial survival rates after re-OLT were 55.2% and 36.9%, respectively, for patients in early re-OLT, and 65.1% and 52% respectively, for patients in late re-OLT. No significant differences were found regarding survival rates between the two groups. CONCLUSIONS: Similar clinical results can be achieved in early and late re-OLT. Proper indications and optimal operation timing, adequate preoperative preparation, experienced surgical procedures, and effective perioperative anti-infection strategy contribute to the improvement of overall survival rates of patients after re-OLT.

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.

Tardus parvus waveforms in Doppler ultrasonography for hepatic artery stenosis after liver transplantation: can a new cut-off value guide the next step?

PURPOSE: Considering the high false-positive diagnosis of the tardus parvus waveform (TPW) in Doppler ultrasonography (DUS) for hepatic artery stenosis (HAS) after liver transplantation (LT), this study aimed to determine clinical features and new cut-off values to help guide treatment. MATERIALS AND METHODS: This retrospective study was approved by an Institutional Review Board. A total of 171 LT recipients were included and underwent DUS and either computed tomography angiography or digital subtraction angiography with an interval < 4 weeks at least 1 month post-LT. The DUS of 69 patients exhibited TPW [defined as resistive index (RI) < 0.5 and systolic acceleration time (SAT) > 0.08 s]. A multilevel likelihood ratio (LR) analysis was used to explore new cut-off values for DUS. In addition, abnormal liver function was considered additional evidence (defined as any liver enzyme > 3-fold of the upper limit of normal level or 2-fold increased). The results were stratified into three categories, category 1 (subjects with traditional TPW), category 2 (subjects with traditional TPW and abnormal liver function), and category 3 (subjects with traditional TPW and abnormal liver function, or with new cut-off values), and the diagnostic performance of each category was analyzed. RESULTS: The LR analysis revealed new cut-off values of RI < 0.4 (LR = 10.58) or SAT > 0.12 s (LR = 16.46). The false-positive rates for categories 2 and 3 were significantly lower (7.6% vs. 18.1%, P = 0.038; 1.9% vs. 18.1%, P < 0.001, respectively) than those for category 1, while the sensitivity for category 2 was significantly lower (41.8% vs. 74.6%, P < 0.001; 41.8% vs. 61.2%, P = 0.038, respectively) than that for categories 1 and 3. CONCLUSION: Using either (1) RI < 0.4 or SAT > 0.12 s, or (2) traditional TPW (RI < 0.5 and SAT > 0.08 s) in the presence of abnormal liver functions as the DUS criteria for HAS will significantly decrease the false-positive rate compared to traditional TPW without a significant increase in the false-negative rate.