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Summary: Background: Tenofovir amibufenamide (TMF) can provide more efficient delivery than tenofovir disoproxil fumarate (TDF). Aim: To compare the efficacy and safety of TMF and TDF for 48 weeks in patients with chronic hepatitis B (CHB). Methods: We performed a randomised, double‐blind, non‐inferiority study at 49 sites in China. Patients with CHB were assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo. The primary efficacy endpoint was the proportion of patients with hepatitis B virus (HBV) DNA less than 20 IU/mL at week 48. We also assessed safety, particularly bone, renal and metabolic abnormalities. Results: We randomised 1002 eligible patients. The baseline characteristics were well balanced between groups. After a median 48 weeks of treatment, the non‐inferiority criterion was met in all analysis sets. In the HBeAg‐positive population, 50.2% of patients receiving TMF and 53.7% receiving TDF achieved HBV DNA less than 20 IU/mL. In the HBeAg‐negative population, 88.9% and 87.8%, respectively, achieved HBV DNA less than 20 IU/mL in the TMF and TDF groups. Patients receiving TMF had significantly less decrease in bone mineral density at both hip (P < 0.001) and spine (P < 0.001), and a smaller increase in serum creatinine at week 48 (P < 0.05). Other safety results were similar between groups. Conclusion: TMF was non‐inferior to TDF in terms of anti‐HBV efficacy and showed better bone and renal safety. (NCT03903796). [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the association between MDR1 gene polymorphisms and hepatocellular carcinoma (HCC) risk. Genomic DNA of 1431 subjects was extracted from peripheral blood and genotyping was performed using the created restriction site-polymerase chain reaction (CRS-PCR). We found that the c.1465C > T single nucleotide polymorphisms (SNP) increased HCC risk in all genetic models ( p < 0.05) and the allele-T of c.1465C > T may contribute to the risk of HCC. No significantly increased HCC risk was detected in c.159G > T SNP. Our data indicated that the genetic variants of MDR1 gene may be a valuable molecular marker for HCC. [ABSTRACT FROM AUTHOR]

Background and Aims: Tenofovir amibufenamide (TMF) is a novel phosphoramidated prodrug of tenofovir with noninferior efficacy and better bone and renal safety to tenofovir disoproxil fumarate (TDF) in 48 weeks of treatment. Here, we update 96-week comparison results., Methods: Patients with chronic hepatitis B were assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks. The virological suppression was defined as HBV DNA levels <20 IU/mL at week 96. Safety was evaluated thoroughly with focusing on bone, renal, and metabolic parameters., Results: Virological suppression rates at week 96 were similar between TMF and TDF group in both HBeAg-positive and HBeAg-negative populations. Noninferior efficacy was maintained in the pooled population, while it was first achieved in patients with HBV DNA ≥7 or 8 log10 IU/mL at baseline. Non-indexed estimated glomerular filtration rate for renal safety assessment was adopted, while a smaller decline of which was seen in the TMF group than in the TDF group ( p =0.01). For bone mineral density, patients receiving TMF displayed significantly lower reduction levels in the densities of spine, hip, and femur neck at week 96 than those receiving TDF. In addition, the lipid parameters were stable after week 48 in all groups while weight change still showed the opposite trend., Conclusions: TMF maintained similar efficacy at week 96 compared with TDF with continued superior bone and renal safety profiles (NCT03903796)., Competing Interests: ZL has served as a speaker for Bristol Myers Squibb (BMS), Gilead Sciences, and Hansoh Pharma. QJ has served as a speaker for Abbott, Amoytop Biotech, Chiatai Tianqing, Gilead, and has received research funding from Kawin Technology, Chiatai Tianqing, Hansoh Pharma, Johnson and Johnson (J&J), BMS, HEC Pharmaceutical, TaiGen Biotechnology, Gilead Science. JN has served as a speaker for and has received research funding from HEC Pharmaceutical, Xintong Pharmacy, Hansoh Pharma, Qilu Pharmaceutical, Kelun Industry, Roche, J&J, GlaxoSmithKline (GSK), Assembly, Gilead, Brii Biosciences, Huahui Health, Zhimeng Biopharma, Hengrui Medicine, Aligos, Hepu Pharmaceutical, Ascletis Pharma, Sanhome, Ginkgo pharma, Changzhou Yinsheng pharma. JH has received consulting fee from AbbVie, Arbutus, BMS, Gilead Sciences, J&J, Roche and received grants from BMS and J&J. QW, CP, WJ, CL, and CS are employees of Hansoh Pharmaceuticals Co., Ltd. JN has has been an associate editor of Journal of Clinical and Translational Hepatology since 2013, and JH has has been an executive associate editor of Journal of Clinical and Translational Hepatology since 2021. The other authors have no conflict of interests related to this publication., (© 2023 Authors.)

Objective: The base excision repair (BER) pathway and nucleotide excision repair (NER) pathway play important roles in the repair of benzene-induced genetic damage, and the effects of polymorphisms in these pathways on genetic damage and global DNA methylation are of great interest., Methods: Ten single nucleotide polymorphisms (SNPs) in the BER (XRCC1: rs25489, rs25487; APE1: rs1130409) and NER pathways (XPA: rs1800975; XPC: rs2228000, rs2228002; XPD: rs13181, rs1799793; XPG: rs17655; ERCC1: rs3212986) were analyzed by a Kompetitive allele-specific PCR (KASP) assay to find associations with cytokinesis-block micronucleus (MN) frequency and global DNA methylation in 294 shoe factory workers and 102 control participants., Results: Workers who possessed the following genotypes were associated with high MN frequency: rs25487 AA (FR (95% CI): 1.50 (1.16,1.9), p = 0.002, reference GG); rs1130409 GG (FR (95% CI): 1.28 (1.05,1.55), p = 0.010, reference TT); rs17655 GC (FR (95% CI): 1.18 (1.02,1.38), p = 0.038, reference GG); and rs3212986 TT (FR (95% CI): 1.55 (1.31,1.83), p < 0.001, reference GG). Workers with four and three mutant alleles showed 3.72-fold (OR (95% CI): 3.72 (1.34, 10.03), p = 0.009) and 2.48-fold (OR (95% CI): 2.48 (1.27, 4.88), p = 0.008) increased risk of genetic damage compared with workers with no or one mutant allele, and a dose-response relationship was found by the trend test (p = 0.006). The rs1130409 variant allele (GG+GT) was associated with low global DNA methylation (β=-0.20, 95% CI: -0.42, 0.03, p = 0.045)., Conclusion: In benzene-exposed workers, BER and NER pathway polymorphism haplotypes are associated with different levels of chromosome damage and had little effect on global DNA methylation., (Copyright © 2019. Published by Elsevier B.V.)