时空变异轮廓洞察其例HBV将开发HCC

StephenW

Temporal mutation profile discerns which patients with HBV will develop HCC

Sung F-Y, et al. Hepatology. 2016;doi:10.1002/hep.28654.
July 25, 2016

  
Researchers from Taiwan developed a temporal mutation profile that discerned which patients with hepatitis B virus are more likely to develop hepatocellular carcinoma within 5 years, according to recent findings published in Hepatology.


“Here, we show a set of 10 HBV-[single nucleotide polymorphisms (SNPs)] associated with a statistically increased risk for HCC, each with a greater than 1.8-fold OR value after taking into account HBV genotype,” Ming-Whei Yu, PhD, professor of epidemiology and preventive medicine at National Taiwan University College of Public Health, and colleagues wrote. “Our whole viral genome analysis highlights the importance of progressive accumulation of a set of HBV mutations for hepatitis B progression to HCC in addition to well-established predictors such as HBV genotype and viral load.”

Previous studies associated viral load, genotype and certain mutations with progression from chronic HBV to HCC, the researchers wrote. However, those studies only used a small number of sequences whereas Yu and colleagues scanned the entire HBV genome.

In a cohort of patients with HBV, the researchers assessed blood obtained no more than 20 years prior to diagnosis from 117 patients who developed HCC and 118 patients who did not. Using logistic regression based on five periods to diagnosis, the researchers examined the relationship between each SNP and HCC development, while adjusting for HBV genotype.

They found 31 SNPs significantly associated with time to diagnosis, 24 of which could be analyzed with full-length data from the cohort. The 10 best SNP candidates had ORs ranging between 1.89 and 8.68 (P ≤ .0304) and were further confirmed using 163 HBV sequences from nine Asian regions that were assessed after HCC diagnosis.

The prevalence and mutation score of these SNPs increased as time moved closer to HCC diagnosis. When compared with a score of 0, the OR for a score of 1 was 2.17, for a score of 2 it was 4.21, for a score of 3 it was 8.15 and for a score of 4 it was 9.15. This mutation score outperformed HBV-DNA levels, viral genotype and other risk factors while showing increasing accuracy over time when the time to diagnosis was less than 4.5 years (area under the curve = 0.83-0.89; sensitivity = 72.7-94.1%; specificity = 58.3-70.5%).

The most noteworthy finding — according to the researchers — was that mutations continuously increased up until the clinical onset of HCC and that a mutation score would help predict short-term risk for HCC.

“The mutation score may be useful for both monitoring hepatitis B progression and early detection of HCC,” Yu and colleagues wrote. “A further study using deep sequencing to determine the importance of quantifying mutants for mutation tracking is warranted.” – by Will Offit

Disclosure: The researchers report no relevant financial disclosures.

StephenW

时空变异轮廓洞察其例HBV将开发HCC

成的F-Y，等人。肝病。 2016年：10.1002 / hep.28654。
2016年7月25日

  
来自台湾的研究人员开发出一种时空变异配置文件辨别哪些患者乙肝病毒更可能在5年内发展肝细胞癌，根据发表在肝病的最新发现。


“在这里，我们展示了一组与HCC，每一个大于1.8倍或值有统计学风险增加10 HBV- [单核苷酸多态性（SNPs）考虑HBV基因型后，”明玉Whei ，博士，公共卫生台大医学院流行病学和预防医学教授及其同事写道。 “我们的整个病毒基因组分析突出的一组的HBV突变乙肝进展为肝细胞癌除了成熟的预测，如HBV基因型和病毒载量的逐步积累的重要性”。

以往的研究相关的病毒载量，基因型，并与慢性乙肝肝癌进程某些突变，研究人员写道。然而，这些研究只使用了少量的序列，而宇和他的同事扫描的整个HBV基因组。

在例HBV队列，研究者评估血液117例谁开发HCC和谁没有118例患者没有获得超过20年诊断前。使用基于五个时期Logistic回归分析，研究人员检测了每个SNP与HCC发展之间的关系，同时调整了HBV基因型。

他们发现与时间显著关联到诊断31个SNP，其中24可以与从队列全长数据进行分析。最好的10个SNP的候选人有OR值范围（≤0.0304 P）1.89 8.68之间，并使用163 HBV序列从被确诊肝癌后评价九个亚洲地区进行了进一步证实。

这些SNP的流行和变异分数随时间移近肝癌诊断。当得分为0相比，或为1分是2.17，为2分是4.21，对于3分是8.15和4的得分是9.15。这种突变分数跑赢HBV-DNA水平，病毒基因型和其他风险因素，同时表现出越来越大的精度随时间到时诊断为小于4.5岁（下曲线= 0.83-0.89区域;灵敏度= 72.7-94.1％;特异性= 58.3-70.5％）。

最值得注意的发现 - 根据研究人员 - 是突变的不断加大，直至临床发作肝癌和突变比分将有助于预测肝癌的短期风险。

“突变比分可能是肝癌的两个监测乙肝进展和早期发现有用的，”玉和同事写道。 “通过深度测序，确定量化突变跟踪突变体的重要性，进一步的研究是必要的。” - 威尔Offit

披露：研究人员报告没有相关财务披露。