''Minimizing tacrolimus' ' strategy and long-term survival after liver transplantation

AIM: To investigate the effect of the ‘‘minimizing tacrolimus' ' strategy on long-term survival of patients after liver transplantation(LT).METHODS: We conducted a retrospective study of 319 patients who received LT between January 2009 and December 2011 at the First Affiliated Hospital of Zhejiang University School of Medicine. Following elimination of ineligible patients, 235 patients were included in the study. The relationship between early tacrolimus(TAC)exposure and survival period was analyzed by Kaplan Meier curves. Adverse effects related to TAC were eval-uated by the χ2 test. Routine monitoring of blood TAC concentration(TC) was performed using the PRO-TracTM Ⅱ Tacrolimus Elisa Kit(Diasorin, United States). RESULTS: Of 235 subjects enrolled in the study, 124(52.8%) experienced adverse effects due to TAC. When evaluating mean TC, the survival time of patients with a mean TC < 5 ng/mL was significantly shorter than that in the other groups(911.3 ± 131.6 d vs 1381.1 ± 66.1 d, 911.3 ± 131.6 d vs 1327.3 ± 47.8 d, 911.3 ± 131.6 d vs 1343.2 ± 83.1 d, P < 0.05), while the survival times of patients with a mean TC of 5-7, 7-10 and 10-15 ng/mL were comparable. Adverse effects due to TAC in all four groups were not significantly different. When comparing the standard deviation(SD) of TC among the groups, the survival time of patients with a SD of 2-4 was significantly longer than that in the other groups(1388.8 ± 45.4 d vs 1029.6 ± 131.3 d, 1388.8 ± 45.4 d vs 1274.9 ± 57.0 d, P < 0.05), while in patients with a SD < 2 and SD > 4, the survival time was not statistically different. Adverse effects experienced in all three groups were not statistically different. In Cox regression analysis, male patients and those with a primary diagnosis of benign disease, mean TC > 5 ng/mL and TC SD 2-4 had better outcomes.CONCLUSION: The early ‘‘minimizing tacrolimus' ' strategy with a mean TC of 5-10 ng/mL and SD of 2-4 was beneficial in terms of long-term survival after LT.

Role of [18F] fludeoxyglucose positron emission tomography in the selection of liver transplantation candidates in patients with hepatocellular carcinoma

BACKGROUND： The Milan criteria are widely accepted among many centers. However, patients with hepatocellular carcinoma beyond the Milan criteria might still benefit from liver transplantation （LT） when tumor itself is not aggressive. [18F] fluorodeoxyglucose positron emission tomography/computed tomography imaging could provide useful information of tumor behaviors, which is helpful to predict the prognosis for many tumors. METHOD： In order to determine its role in candidate selection for LT, we therefore retrospectively analyzed 103 recipients with preoperative positron emission tomography （PET） findings. RESULTS： Positive PET findings （PET＋） were significantly associated with tumor nodule numbers （P=0.013）, tumor grade （P=0.025）, macro- （P=0.002） and micro-vascular invasion （P=0.002）, as well as the Milan criteria （P=0.018）. PET＋ patients had significantly increased risk of tumor recurrence post-LT compared to PET negative （PET-） patients （P=0.007）. The 1-, 3-, and 5-year overall survival rate of PET- patients were 96.0%, 87.2% and 76.2%, compared to 74.7%, 55.4% and 49.9% in PET＋ patients, respectively （P〈0.05）. The 1-, 3-, and 5-year recurrence-free survival rate of PET- patients were 91.8%,81.9% and 76.0%, compared to 70.1%, 39.3% and 21.9% in PET＋ patients, respectively （P〈0.05）. Recipients within the Milan criteria showed comparable 1-, 3-, and 5-year survival rates in comparison with those beyond the Milan criteria with a PET- findings （1-, 3-, and 5-year overall survival rates, 97.5%, 83.3%, and 83.3% vs 90.0%, 80.0%, and 66.7%, P= 0.123; 1-, 3-, and 5-year recurrence-free survival rates, 95.1%, 73.1%, and 73.1% vs 90.0%, 78.8%, and 65.6%, P=0.148）. CONCLUSIONS： Certain patients with hepatocellular carcinoma and negative PET findings, who have exceeded the Milan criteria, are also eligible candidates for LT. Preoperative PET/CT imaging is an important marker, which should be incorporated in extended candidate selection criteria for LT.

Anti-virus prophylaxis withdrawal may be feasible in liver transplant recipients whose serum HBeAg and HBV DNA are negative

Anti-virus prophylactic therapy may be not nec- essary for the prevention of hepatitis B virus （HBV） recur- rence after HBV-related liver transplantation （LT）. However, studies on completely stopping the hepatitis B immune globu- lin （HBIG） and nucleos（t）ide analogs （NUC） after LT are few. The aim of the current study was to evaluate the safety of anti- virus prophylaxis withdrawal in liver recipients whose serum hepatitis B e antigen （HBeAg） and HBV DNA are negative. We analyzed 190 patients undergone LT for HBV-related liver dis- ease from 2006 to 2012 and found that 10 patients completely stopped the HBIG and NUC due to poor compliance. These patients were liver biopsied and checked monthly with serum HBV markers, HBV DNA and liver function. Among the 10 patients, 9 did not show the signs of HBV recurrence after a mean follow-up of 51.6 months （range 20-73） after with- drawal of the HBIG and NUC. The average time from LT to the withdrawal of the anti-virus drug was 23.8 （13-42） months; one patient showed hepatitis B surface antigen-positive and detectable HBV DNA after stopping anti-virus drugs and this patient was successfully treated with entecavir. Our data sug- gested that complete withdrawal of anti-virus prophylaxis was safe and feasible for patients whose serum HBeAg and HBV DNA were negative at the time of LT.

Lower tacrolimus trough levels in the late period after living donorliver transplantation contribute to improvements in long-term clinicaloutcomes

Background： Previous studies have emphasized the need to reduce tacrolimus （TAC） trough levels in theearly post-liver transplantation （LT） period. However, whether late-period TAC trough levels influence the long-term outcomes of liver recipients is not clear.