BACKGROUND:Human leucocyte antigen (HLA)-DR plays a crucial role in the immune response against hepatitis B virus (HBV). We aimed to investigate the associations of HLA-DR single nucleotide polymorphisms (SNPs) with the generation of hepatocellular carcinoma (HCC)-related HBV mutations. The effects of HLA-DR SNPs and their interactions with HBV mutations on HCC risks were also determined.METHODS:Five HLA-DR SNPs (rs3135363, rs9268644, rs35445101, rs24755213, and rs984778) were genotyped in 792 healthy controls, 586 chronic hepatitis B (CHB) patients, 536 liver cirrhosis (LC) patients, and 1500 HCC patients using quantitative PCR. Sanger sequencing was used to identify the HBV mutations. Logistic regression model was performed to evaluate the association of HLA-DR SNPs with HCC risk and the frequencies of HCC-related HBV mutations.RESULTS:The variant genotypes at rs3135363, rs9268644, rs35445101, rs24755213, and rs984778 were associated with decreased HCC risks. In genotype C HBV-infected subjects, variant genotypes of these SNPs were associated with decreased frequencies of HCC-related HBV mutations such as C1653T, T1674C/G, G1719T, T1753A/C, A1762T/G1764A, A1846T, G1896A, G1899A, and preS deletion. AG genotype at rs3135363, CA genotype at rs9268644, and AG genotype at rs24755213 reduced the generation of T1753A/C and G1896A in genotype B HBV-infected subjects, respectively. In addition, the interactions of rs3135363, rs9268644, rs24755213 with C1653T, T1753A/C, A1846T, and G1896A decreased the risks of HCC.CONCLUSIONS:HLA-DR genetic polymorphisms might predispose the host to immunoselection of HCC-related HBV mutations and affect the HCC risks possibly through interacting with HBV mutations.

Background: Recurrence is a major obstacle to improve the prognosis of hepatocellular carcinoma (HCC) patients. Transcatheter arterial chemoembolization (TACE) has been routinely used as an adjuvant therapy in treating HCC, but efficacy of TACE in preventing the recurrence of HCC remains unsatisfactory. This study aimed to compare the efficacy of a traditional herbal medicine (THM) therapy and TACE in preventing tumor recurrence and improving survival in postsurgical patients with HCC. Materials and methods: A total of 1506 HCC patients were enrolled from January 2008 to June 2017, including 262 patients who received THM therapy and 1244 patients who were treated with TACE. All patients were followed up until the occurrence of outcome event or June 30th, 2019. The recurrence-free survival (RFS) and overall survival (OS) were calculated by the Kaplan-Meier method, and the differences of RFS and OS between THM group and TACE group were analyzed by the log-rank test. Factors affecting the RFS or OS among these patients were assessed by the Cox proportional hazard regression model. A nomogram was built with the factors based on the Cox regression analysis to predict the prognosis. Results: The 1-, 3-, and 5-year RFS were 91.0%, 68.3%, and 49.7%, respectively, in the THM group and 79.4%, 38.6%, and 19.3%, respectively, in the TACE group. The RFS in the THM group was significantly higher than that of the TACE group (P = 6.2 x 10 (-11)). The 1-, 3-, and 5-year OS were significantly improved in the THM group as compared to those in the TACE group (94.3%, 65.2%, and 41.4% vs. 82.7%, 46.0%, and 25.4%, P = 2.2 x 10 (-11)). Multivariate analysis revealed that serum AFP level >= 400 ng/mL, HBV DNA load >= 500 copies/mL, TNM stage III-IV, tumor diameter >= 5 cm, presence of MVI, and multiple tumor nodules were independent risk factors for RFS, while complete tumor encapsulation and THM therapy were protective factors for RFS and OS. The nomogram demonstrated good accuracy in predicting RFS and OS, with the adjusted C-index of 0.748 and 0.796, respectively. Conclusion: The efficacy of THM therapy was superior to that of TACE in preventing recurrence and improving survival for HCC patients after hepatectomy.