Abstract：
OBJECTIVE: Progression to hepatocellular carcinoma (HCC) is restricted by viral suppression in chronic hepatitis B (CHB); however, some patients still progress despite antiviral therapy. Presence of single nucleotide polymorphisms (SNPs) such as PNPLA3 rs738409 and TM6SF2 rs58542926 are associated with the development and progression of steatotic liver disease to HCC, whereas a splice variant in HSD17B13 rs72613567:TA has been shown to be protective. We investigated the role of these SNPs in the development or prognosis of HCC in pure CHB etiology, in the absence of hepatic steatosis, remains unknown.
METHODS: We analysed PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 SNPs in a prospectively recruited cohort (n=323) consisting of healthy controls, CHB and CHB-HCC patients without hepatic steatosis. SNPs were determined by PCR analysis and associations for the alleles and genotypes were investigated using adjusted-logistic regression analyses. The overall survival (OS) data were collected from CHB-HCC patients for survival analysis.
RESULTS: The genotype and allelic distribution of PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 were similar between healthy controls, CHB, and CHB-HCC groups. No genotype, allele or haplotype analysis was found to be associated with increased risk for CHB-HCC. Survival analysis revealed no genotype or allele to be associated with OS in patients with CHB-HCC.
CONCLUSIONS: We could not demonstrate any association of PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 with the development or prognosis of CHB-HCC, supporting the initial hypothesis that they should be considered specific hotspots for liver diseases characterized with hepatic steatosis.
METHODS: We analysed PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 SNPs in a prospectively recruited cohort (n=323) consisting of healthy controls, CHB and CHB-HCC patients without hepatic steatosis. SNPs were determined by PCR analysis and associations for the alleles and genotypes were investigated using adjusted-logistic regression analyses. The overall survival (OS) data were collected from CHB-HCC patients for survival analysis.
RESULTS: The genotype and allelic distribution of PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 were similar between healthy controls, CHB, and CHB-HCC groups. No genotype, allele or haplotype analysis was found to be associated with increased risk for CHB-HCC. Survival analysis revealed no genotype or allele to be associated with OS in patients with CHB-HCC.
CONCLUSIONS: We could not demonstrate any association of PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 with the development or prognosis of CHB-HCC, supporting the initial hypothesis that they should be considered specific hotspots for liver diseases characterized with hepatic steatosis.
摘要：
目的：慢性乙型肝炎（CHB）的病毒抑制限制了肝细胞癌（HCC）的进展；然而，一些患者尽管接受了抗病毒治疗，但仍有进展。单核苷酸多态性（SNPs）的存在，如PNPLA3rs738409和TM6SF2rs58542926与脂肪肝病的发展和进展为HCC相关。而HSD17B13rs72613567：TA中的剪接变体已被证明具有保护性。我们调查了这些SNP在肝癌的发展或预后在纯CHB病因的作用，在没有肝脏脂肪变性的情况下，仍然未知。
方法：我们分析了由健康对照组成的前瞻性招募队列（n=323）中的PNPLA3rs738409、TM6SF2rs58542926和HSD17B13rs72613567SNP，CHB和CHB-HCC患者无肝脂肪变性。通过PCR分析确定SNP，并使用调整逻辑回归分析研究等位基因和基因型的关联。从CHB-HCC患者收集总生存（OS）数据进行生存分析。
结果：PNPLA3rs738409，TM6SF2rs58542926和HSD17B13rs72613567的基因型和等位基因分布在健康对照组之间相似，CHB,和CHB-HCC组。没有基因型，等位基因或单倍型分析被发现与CHB-HCC风险增加相关。生存分析显示，在CHB-HCC患者中，没有基因型或等位基因与OS相关。
结论：我们无法证明PNPLA3rs738409，TM6SF2rs58542926和HSD17B13rs72613567与CHB-HCC的发展或预后的任何关联，支持最初的假设，即它们应被视为以肝脏脂肪变性为特征的肝脏疾病的特定热点。
方法：我们分析了由健康对照组成的前瞻性招募队列（n=323）中的PNPLA3rs738409、TM6SF2rs58542926和HSD17B13rs72613567SNP，CHB和CHB-HCC患者无肝脂肪变性。通过PCR分析确定SNP，并使用调整逻辑回归分析研究等位基因和基因型的关联。从CHB-HCC患者收集总生存（OS）数据进行生存分析。
结果：PNPLA3rs738409，TM6SF2rs58542926和HSD17B13rs72613567的基因型和等位基因分布在健康对照组之间相似，CHB,和CHB-HCC组。没有基因型，等位基因或单倍型分析被发现与CHB-HCC风险增加相关。生存分析显示，在CHB-HCC患者中，没有基因型或等位基因与OS相关。
结论：我们无法证明PNPLA3rs738409，TM6SF2rs58542926和HSD17B13rs72613567与CHB-HCC的发展或预后的任何关联，支持最初的假设，即它们应被视为以肝脏脂肪变性为特征的肝脏疾病的特定热点。
