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.

[Reproduction after liver transplantation: a report of 13 cases from a single Chinese center].

OBJECTIVE: To explore the recipient's reproduction after liver transplantation (LT) and assess the outcomes of their offspring. METHODS: We retrospectively analyzed the reproduction status of 13 post-LT patients among 336 post-LT recipients during a follow-up period. Physical and intellectual status of their offspring were evaluated by developmental index and Denever developmental screening test. RESULTS: A total of 16 children were mothered or fathered by 13 LT patients. Two female patients mothered a boy and a girl. Ten male patients fathered 6 male and 8 female children while another male fathered a child at 28 gestational weeks. Eleven patients fathered the first gestation 21 mon (medium) since LT, and fathered 15 pregnancies. Twelve of 14 deliveries had a mean gestation age of (38.2 ± 1.8) weeks, with a mean birth weight of (3.1 ± 0.5) kg. Among 12 newborns, 3 were premature and 2 of a low birth weight. Two female patients delivered 2 babies with a gestation age of 37.3 and 40.4 weeks, a birth weight of 2.7 and 3.4 kg, and anoxia neonatorum in one case. No deformity was found. Thirteen of 16 children had almost normal developmental indices and ten had almost normal Denever developmental screening. CONCLUSION: Post-LT patients of reproductive age are able to reproduce offspring. The short-term development of their offspring is relatively normal.

[Alterations of immune status in liver transplant patients with sepsis].

OBJECTIVE: To explore the alterations of immune status in liver transplant recipients with sepsis so as to provide rationales for the adjustments of immunosuppressive agents. METHODS: A total of 47 cases complicated with sepsis after abdominal operations from January 2009 to December 2010 were divided into 4 groups according to the type of operations and the stage of sepsis: A. sepsis after transplantation (TS, n = 11), B. severe sepsis after transplantation (TSS, n = 10), C. sepsis without transplantation (NTS, n = 15) and D. severe sepsis without transplantation (NTSS, n = 11). Ten healthy volunteers were selected as the control group. Blood samples were collected from these patients to measure the immunological parameters associated with T lymphocyte. RESULTS: The APACHII and SOFA score of TSS group and NTSS group were both higher than TS group and NTS group respectively (all P < 0.01). In addition, SOFA score in TSS group was significantly higher than that in NTSS group (17.0 ± 4.5 vs 12.1 ± 2.8, P < 0.01). The percentages of T cell in 4 groups were all significantly lower than healthy volunteers (all P < 0.01). The CD4/CD8 ratio was slightly lower in the TSS group than those in the control group and the other three groups (P = 0.095). As compared with the control group, the IFN-γ/IL-4 ratios were significant lower in the TSS and NTSS groups (0.039 ± 0.012, 0.047 ± 0.018 vs 0.062 ± 0.006) while the level of IL-10 was higher ((32.6 ± 7.5), (25.9 ± 4.3) vs (8.2 ± 1.4) ng/L, all P < 0.05). And the difference was more significant in the TSS group. As compared with the healther, the percentage of CD4(+)CD25(+)Foxp3(+)Treg was lower in NTS group (2.21% ± 0.96% vs 4.06% ± 0.52%, P < 0.01), and significantly higher in NTSS group (8.02% ± 3.57% vs 4.06% ± 0.52%, P = 0.003). No significant difference existed in the percentage of Treg between the TS and control groups (P = 0.398). And it was significantly higher that in the TSS group (5.16% ± 0.99% vs 4.06% ± 0.52%, P = 0.006). But the magnitude of increase level was not so great as that in the NTSS group. The changes of Foxp3 mRNA demonstrated the similar trend as the percentage of Treg. CONCLUSIONS: The immune states of transplant recipients with sepsis are comparable with healthy persons during sepsis. It may subsequently develop into serious immunosuppression. Immunosuppressant should be withdrawn in severe sepsis stage so as to reconstitute the immune system.

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

PURPOSE: This aims to evaluate the effects of lamivudine (LAM) and entecavir (ETV) in preventing hepatitis B virus (HBV) re-infection after liver transplantation (LT). METHODS: A retrospective matched case-control method was used in this study. From June 2005 to May 2007, the patients who received LAM (100 mg qd) or ETV (0.5 mg qd) were chosen. The LAM and ETV groups were matched using a 3:1 ratio based on the factors, such as age, gender, LAM or ETV antiviral duration, primary disease, and HBV DNA levels at the initiation of antiviral therapy. Data on serum HBV markers, HBV DNA, and cumulative recurrence were collected. RESULTS: Two hundred and fifty-two patients were enrolled. The average duration of follow-up was 38.5 and 41.2 months (LAM and ETV groups) (p>0.05). Duration of pre-operative antiviral therapy was 30.3 and 25.8 d (LAM and ETV groups) (p>0.05). The HBV DNA level decreased from 3.89×10(6) to 5.31×10(5) copies/mL before LT in the LAM group, and decreased from 8.74×10(6) to 5.49×10(4) copies/mL in the ETV group (p<0.05). Eighteen patients in LAM group developed HBV re-infection and 0 in ETV group. CONCLUSION: ETV is superior to LAM for preventing HBV re-infection following LT.

Rapamycin combined with donor immature dendritic cells promotes liver allograft survival in association with CD4(+) CD25(+) Foxp3(+) regulatory T cell expansion.

AIM: To determine whether donor immature dendritic cells (imDCs) combined with a short postoperative course of rapamycin (Rapa) has the ability to expand the CD4(+) CD25(+) Foxp3(+) regulatory T (Treg) cells and prolong liver allograft survival. METHODS: Orthotopic liver transplantation (OLT) was performed from Lewis rats to Brown Norway recipients. Three days before transplantation, animals were injected intravenously with 2 × 10(6) donor bone marrow-derived imDCs. Recipient rats (the combined treated group) also received Rapa for 7 d after liver transplantation. Additional groups received either imDCs alone, Rapa alone, or saline alone. Every six recipients from each group were killed at 14 days, 28 days after OLT. The changes of CD4(+) CD25(+) Foxp3(+) Treg cells in peripheral blood and spleen, histological changes of liver grafts, and serum cytokine levels were investigated. The other six recipients were left in each group to observe the animal survival. RESULTS: Donor imDCs followed by a short postoperative course of Rapa induced long-term allograft survival. The percentage of CD4(+) CD25(+) Foxp3(+) Treg cells in CD4(+) T cells in the combination treatment group were significantly higher compared with the acute rejection group. Moreover, within the CD4(+) CD25(+) T cell population the combination treatment recipients maintained a higher incidence of Foxp3(+) T cells compared with the other groups. Despite the lower serum levels of interleukin (IL)-2, IL-12, and interferon-γ in the combined treated group, the cytokine levels in the combined treated group at 7 days after OLT was nearly twice that at 3 days after OLT but decreased significantly compared with the other groups at 28 days after OLT. Serum IL-10 level in the combined treated group was higher than the other groups. CONCLUSIONS: A single imDC infusion followed by a short postoperative course of Rapa prolongs liver allograft survival and enhances the expansion of Treg cells. This optimal protocol may be a promising administration protocol for the peritransplant tolerance induction.

A scoring model based on neutrophil to lymphocyte ratio predicts recurrence of HBV-associated hepatocellular carcinoma after liver transplantation.

BACKGROUND: Neutrophil to lymphocyte ratio (NLR) has been proposed to predict prognosis of hepatocellular carcinoma (HCC). However, the cut-off values are empirical. We determined the optimal cut-off value to predict HCC recurrence after liver transplantation (LT) and further established a scoring model based on NLR. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the outcome of 101 HBV-associated HCC patients undergoing LT. Preoperative risk factors for tumor recurrence were evaluated by univariate analysis. By using ROC analysis, NLR≥3 was considered elevated. The disease-free survival (DFS) and overall survival (OS) for patients with high NLR was significantly worse than that for patients with normal NLR (the 5-year DFS and OS of 28.5% and 19.5% vs. 64.9% and 61.8%, respectively; P<0.001). Univariate analysis revealed that tumor size >5 cm, tumor number >3, macrovascular invasion, AFP≥400 µg/L, NLR≥3, and HBV-DNA level >5 log10 copies/mL were preoperative predictors of DFS. Cox regression analysis showed macrovascular invasion, tumor number, and high NLR were independent prognostic factors. We then established a preoperative prognostic score based on multivariate analysis. Each factor was given a score of 1. Area under the ROC curve of the score was 0.781. All nine patients with score 3 developed recurrence within 6 months after LT. Of 71 patients without vascular invasion, three patients with both tumor number >3 and NLR≥3 developed recurrence within 14 months after LT while the 5-year DFS and OS for patients with a score of 0 or 1 were 68.1% and 62.8%, respectively. CONCLUSIONS/SIGNIFICANCE: Preoperative elevated NLR significantly increases the risk of recurrence in patients underwent LT for HCC. Patients with both NLR≥3 and tumor number >3 are not a good indication for LT. Our score model may aid in the selection of patients that would most benefit from transplantation 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.

High hepatitis B virus DNA level in serum before liver transplantation increases the risk of hepatocellular carcinoma recurrence.

AIM: To analyze the relationship between hepatitis B virus (HBV) and hepatocellular carcinoma (HCC) recurrence in orthotopic liver transplantation (OLT) patients. METHODS: 340 HBV patients with OLT were included in the study; among them were 148 patients with HBV-associated HCC. RESULTS: HCC recurrence rates at 1, 3 and 5 years were 21, 29, and 46%, respectively. Exceeding Milan criteria (hazard ratio, HR = 12.35; 95% confidence interval, CI, 2.80-54.49; p = 0.001), HBV DNA level >5 log(10) copies/ml before transplant (HR = 2.45; 95% CI 1.10-5.45; p = 0.03) and HBV recurrence (HR = 2.27; 95% CI 1.10-4.75; p = 0.03) were significant independent predictors of HCC recurrence. HBV DNA >5 log(10) copies/ml before transplant (HR = 8.65; 95% CI 3.40-21.98; p < 0.001) and concomitance with HCC (HR = 2.79; 95% CI 1.33-5.87; p = 0.007) were predictors of HBV recurrence. Further stratified analysis showed that HBV recurrence was more prevalent in the HCC recurrence group (HR = 4.58; 95% CI 1.88-11.12; p = 0.001). CONCLUSIONS: There is a close relationship between HBV and HCC recurrence after transplant. High HBV DNA levels before transplant are associated with HCC recurrence after transplant.

[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.

[Application of somatostatin combined with oral vancomycin in the treatment of intestinal obstruction after liver transplantation].

OBJECTIVE: To investigate the effect of somatostatin combined with oral vancomycin in the treatment of intestinal obstruction after liver transplantation. METHODS: Fifty-eight cases of intestinal obstruction after liver transplantation from Jan. 2005 to Dec. 2006 were divided into two groups: Group A (from Jan. 2005 to Dec. 2005) received traditional treatment, including fasting,gastrointestinal decompression, maintaining electrolyte and acid-base balance, enteral and parenteral nutrition support and antibiotics; Group B (from Jan. 2006 to Dec. 2006) received somatostatin combined oral vancomycin in addition to the above mentioned traditional treatment. RESULTS: Fifty-eight cases out of 441 patients (13%) suffered from intestinal obstruction after liver transplantation. Group B had a better outcome as compared with Group A, including a quick recovery of flatus and stool, [(7.1+/-2.0) d and (8.4+/-2.4) d vs (9.1+/-3.0) d and (10.8+/-3.4) d] (P<0.05), less amount of gastric drainage [(298+/-58) ml/d vs (485+/-106) ml/d](P<0.05). The rate of intestinal flora imbalance in Group B was 55%, which was significantly less than the 77% in Group A(P<0.05). CONCLUSION: The application of somatostatin combined with oral vancomycin can improve the symptoms of intestinal obstruction after liver transplantation and decrease the rate of intestinal flora imbalance.

[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.

[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.

[The distribution and pathogen of bacteria infection in patients after liver transplantation].

OBJECTIVE: To find out the epidemiology of bacteria infection after orthotopic liver transplantation (OLT). METHOD: Postoperative bacteria infection of 451 OLT cases were retrospectively analyzed. RESULT: Bacteria infection were detected in 239 OLT cases, and the infection rate was 52.9%. Sum up to 304 bacilli lines were separated from all above cases. Among them, the detectable Gram-positive bacilli (G(+)) accounted for 59.9% (182/304), while Gram-negative bacilli (G(-)) accounted for 40.2% (122/304). The impressionable organ were respiratory tract and bile duct, which occupying 81.5% (248/304) and 15.1% (46/304) among all infective cases respectively. The main infected strain were G(+) bacteria in respiratory tract, account for 65.3%; while G(-) bacteria were mainly in bile duct, account for 60.9%. There was significant difference between each other (P = 0.018). CONCLUSIONS: The bacteria infection rate was high after OLT, and the main infected strain was the G(+) bacteria. Most fo them were the opportunistic pathogenic bacteria and the antibiotic multi-resistant bacteria. The bacteria category was significantly related to the infected tissue, according to which we could adopt corresponding antibacterial approach.