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Although liver transplantation (LT) lengthens the survival time of patients with hepatocellular carcinoma (HCC), LT patients exhibit a high recurrence rate; particularly those that had advanced HCC associated with the tumor biological characteristics and long‑term application of immunosuppressants. A consensus on optimal prophylaxis and treatment for recurrent HCC following LT does not currently exist. The present study retrospectively analyzed data from 36 non‑University of California at San Francisco criteria‑eligible patients with advanced HCC who underwent LT, and then treated them with sirolimus (SRL)‑based therapy with thymalfasin and huaier granules (SRL+, n=18), or with tacrolimus‑based therapy (controls; n=18). The SRL+ group had significantly longer recurrence times (P=0.008) and survival times (P<0.0001) (OS, 1‑year: 100%, 3‑year: 94.4%, 5‑year: 77.8%; DFS, 1‑year: 88.9%, 3‑year: 55.6%, 5‑year: 50.0%). Furthermore, compared with pre‑LT values and the control group, the SRL+ group had significantly lower serum α‑fetoprotein (AFP) levels (both P<0.0001) and percentage of Forkhead box P3 (FoxP3)+ Treg lymphocytes (P<0.001) during the first year. In the SRL+ group, FoxP3+/cluster of differentiation (CD)8+ Treg lymphocyte percentages decreased significantly following LT (P<0.001); however, CD8+/CD3+ T‑cells significantly increased (P<0.001). Levels of serum AFP and FoxP3+ Treg cells increased when tumors relapsed, and decreased to near‑normal when relapse foci were cured or stabilized. SRL+ therapy may decrease AFP and Treg levels, while increasing CD8+ T cells, indicating an associated mechanism among them. In conclusion, SRL+ therapy appears to be safe and effective in preventing HCC recurrence following LT with no significant adverse events, and warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: Histone deacetylases (HDACs) have been reported to be poor prognostic indicators in patients with cancer. However, no data are available for the role of single nucleotide polymorphism (SNP) of class I HDAC in hepato-cellular carcinoma (HCC). Therefore, we investigated the association of class I HDAC isoforms genomic polymorphisms with risk of HCC and tumor recurrence following liver transplantation (LT). Methods: One hundred and ninety-six Chinese subjects consisting of 97 HCC patients and 99 controls were enrolled in this study. Nine polymorphisms of the HDAC1, HDAC2, and HDAC3 gene (rs2530223, rs1741981, rs2547547, rs13204445, rs6568819, rs10499080, rs11741808, rs2475631, rs11391) were examined using Applied Biosystems SNaP-Shot and TaqMan technology. Results: We found no significant difference in genotype frequencies between the HCC cases and controls. In terms of tumor recurrence following LT, patients carrying the T allele of HDAC1 SNP rs1741981 showed a favorable outcome for recurrence free survival when compared with patients homozygous for CC. In addition, the same significant trend was observed in HDAC3 SNP rs2547547. Kaplan-Meier analysis showed that the combination of the T variant allele (CT+TT) of HDAC1 SNP rs1741981 and the homozygous TT variant allele of HDAC3 SNP rs2547547 was the most favorable prognostic factor. The risk for postoperative tumor recurrence was about 2.2-fold lower for patients with this genotype combination compared with carriers of the HDAC1 SNP rs1741981 CC and HDAC3 SNP rs2547547 CT genotype combination (hazard ratio: 2.235, p=0.003). Conclusions: Our data suggest that combined analysis of HDAC1 SNP rs1741981 and HDAC3 SNP rs2547547 may be a potential genetic marker for HCC recurrence in LT patients. Clin Chem Lab Med 2010;48:1785-91. [ABSTRACT FROM AUTHOR]

Background: Vascular endothelial growth factor (VEGF), an important regulator of angiogenesis and vascular permeability, is involved in various steps of many malignancies. Gene polymorphisms within the gene encoding VEGF have been shown to be independently associated with an adverse outcome in various malignancies including hepatocellular carcinoma (HCC) with resection. However, no data are available for HCC treated with liver transplantation (LT). Therefore, we investigated association of VEGF genomic polymorphisms with risk for developing HCC and tumor recurrence after LT. Methods: Seven polymorphisms in the VEGF gene (rs699947, rs1570360, rs2010963, rs3024997, rs3025010, rs3025035, rs3025039) were examined in 93 HCC patients treated with LT and 99 controls using Applied Biosystems SNaP-Shot and TaqMan technology. Cox proportional hazard model was used to estimate the hazard ratios associated with polymorphisms. Results: The association between rs3025035 and recurrence was significant (p =0.003). However, no other SNP in VEGF was associated with recurrence. Interestingly, we found that patients with rs3025035 CT heterozygous was independently associated with a shortened recurrence-free survival (odds ratio: 3.3; 95% confidence interval: 1.8–6.0; p <0.001). Conclusions: Our data suggest that polymorphism rs3025035 in the VEGF gene may be a potential genetic marker for HCC recurrence in LT patients. [Copyright &y& Elsevier]

MicroRNA‑424 (miR‑424) has previously been described as a biomarker of poor prognosis in patients with hepatocellular carcinoma (HCC). In the present study, the clinical significance of miR‑424 expression in predicting the rate of tumor recurrence in patients with HCC following liver transplantation (LT) was evaluated. miR‑424 expression in HCC samples from 121 patients undergoing LT was examined, and the associations between clinical parameters and patient tumor recurrence were evaluated. The miR‑424 expression level in cancer tissues was low compared with that in adjacent noncancerous tissues. Multivariate analyses revealed that low miR‑424 expression was an independent prognostic factor for tumor recurrence in patients with HCC following liver transplantation. Patients who no longer met the Milan criteria and had decreased miR‑424 expression levels exhibited earlier tumor recurrence following LT. In addition, the upregulation of miR‑424 expression significantly reduced the migration, invasion and proliferation of HCC cells. Similarly, the downregulation of miR‑424 in HCC cells significantly promoted the migration, invasion and proliferation of HCC cells. [ABSTRACT FROM AUTHOR]

Background: Early recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is associated with poor surgical outcomes. This study aims to construct a preoperative model to predict individual risk of post-LT HCC recurrence.Methods: Data of 748 adult patients who underwent deceased donor LT for HCC between January 2015, and February 2019 were collected retrospectively from the China Liver Transplant Registry database and randomly divided into training (n = 486) and validation(n = 262) cohorts. A multivariate analysis was performed and the five-eight model was developed.Results: A total of 748 patients were included in the study; of them, 96% had hepatitis B virus (HBV) and 84% had cirrhosis. Pre-LT serum alpha-fetoprotein (AFP), tumor number and largest tumor diameter were incorporated to construct the 5-8 model which can stratify patients accurately according to their risk of recurrence into three prognostic subgroups; low-(0-5 points), medium-(6-8 points) and high-risk (> 8 points) with 2-year post-LT recurrence rate of (5,20 and 51%,p <  0.001) respectively. The 5-8 model was better than Milan, Hangzhou, and AFP-model for prediction of HCC early recurrence. These findings were confirmed by the results of the validation cohort.Conclusions: The 5-8 model is a simple validated and accurate tool for preoperative stratification of early recurrence of HCC after LT. [ABSTRACT FROM AUTHOR]