Liver Cancer Predictors in Chronic Hepatitis B Identified

StephenW

Liver Cancer Predictors in Chronic Hepatitis B Identified                By: MARY ANN MOON,  Oncology Report Digital Network

In patients with chronic hepatitis B who are negative for hepatitis B e antigen and have low viral loads, serum levels of hepatitis B surface antigen can be used to predict risk for hepatocellular carcinoma (HCC), Dr. Tai-Chung Tseng and colleagues reported in the May issue of Gastroenterology.

In such patients, high levels of hepatitis B surface antigen (HBsAg) indicate higher risk for liver cancer, regardless of low hepatitis B DNA levels, said Dr. Tseng of the Buddhist Tzu Chi General Hospital Taipei, and associates.

HBV DNA levels are considered the major driver of disease progression in patients with chronic hepatitis B, and those with low viral loads are usually considered to be at low risk for developing HCC. However, even these patients still carry some risk for the malignancy, with an estimated annual incidence of 0.06%.

"Therefore, identification of factors predictive of HCC other than viral load in these ‘low-risk’ patients remains [imperative]," the investigators wrote (Gastroenterology 2012 Feb. 13 [doi:10.1053/j.gastro.2012.02.007]).

"Recently, HBsAg quantification has become increasingly recognized as a marker for evaluating viral replication and possible host immune control over HBV infection. A lower HBsAg level is associated with ... a lower risk of hepatitis activity," they noted.

So Dr. Tseng and colleagues assessed a large cohort of treatment-naive patients who had chronic HBV infection with genotypes B or C, but no cirrhosis. The study subjects and had been enrolled in a study of HBsAg loss in 1985-1995, and study enrollment later was extended until 2000.

The study population comprised 2,688 HBV carriers aged 28 and older at baseline who underwent frequent liver function tests, serum sampling, and abdominal ultrasonography for HCC surveillance. Approximately 61% of them were men.

The average duration of follow-up was 14.7 years (range, 2.5 to 25.8 years). A total of 191 patients developed HCC during that time, with an overall incidence of 4.8 cases per 1,000 person-years.

The average interval between baseline and development of HCC was 11 years (range, 2.5 to 24.5 years).

As expected, HBeAg positivity, higher levels of HBV DNA, and higher levels of alanine aminotransferase all were associated with a higher rate of HCC. Other factors known to raise the risk of HCC did so in this study, including older age, male gender, and infection with genotype C.

HBsAg level also was found to correlate with HCC risk, in a dose-response manner. However, it was not as strong as the other predictors in the study population as a whole or in the subgroup of patients who were HBeAg positive.

But the researchers were particularly interested in patients who were HBeAg-negative and had low viral loads, and thus were lacking the two risk factors that best predicted HCC risk.

In a univariate analysis, the hazard ratio (HR) for developing HCC was 5.4 in such patients who had a high (1,000 IU/mL or greater) HBsAg level, compared with those who had an HBsAg level lower than 1,000 IU/mL.

Further multivariate analysis showed that a high HBsAg level remained an independent risk factor for HCC, with an HR of 13.7.

"These data suggest that HBsAg level may complement HBV DNA level in predicting HCC development," especially in patients with low viral loads, Dr. Tseng and colleagues said.

They proposed that patients with low viral loads but high HBsAg levels "may harbor more hepatocytes with HBV integration than those who have a low HbsAg level. Therefore, the higher risk of HCC ... may be attributed to the increased genomic instability as a result of integrated viral sequences, which play an important role in hepatocarcinogenesis."

In this study population, the subgroup of patients who had both a low HBV DNA level and a low HBsAg level showed a cumulative incidence of HCC of only 0.2%, which is similar to the level reported in control subjects in previous studies. Thus, a low HbsAg level accompanied by a low HBV DNA level appears to reflect adequate host immune control against HBV infection and can be used to identify patients at low risk for developing HCC.

Clinicians "urgently require a good indictor to stop nucleotide analogue therapy in HBeAg-negative patients. If an HbsAg level of less than 1000 IU/mL could be reliably used to define low-risk or inactive HBV carriers, we may adopt this cutoff level as the intermediate treatment goal," assuming that the results of this study are confirmed in future research, the authors wrote.

This study was supported by the Buddhist Tzu-Chi General Hospital Taipei Branch, the National Taiwan University Hospital, the Department of Health, and the National Science Council. Dr. Tseng’s associates reported ties to Abbott, Bayer, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, and Roche.

StephenW

慢性肝炎乙鉴定肝癌预测
玛丽安月亮，肿瘤报告数字网络：

在谁是乙型肝炎e抗原阴性和低病毒载量的慢性乙型肝炎患者，乙肝表面抗原的血清可以用来预测肝细胞癌（HCC），大涌曾博士和同事报告的风险五月消化科。

在这类患者中，乙型肝炎表面抗原（HBsAg）的高水平表明肝癌的风险较高，不管低乙肝DNA水平，说博士曾在佛教慈济综合医院台北，及联营公司。

被认为是HBV DNA水平与慢性乙型肝炎患者病情恶化的主要驱动力，病毒载量低者通常被认为是低风险的发展肝癌。然而，即使这些患者仍携带一些恶性肿瘤的风险，估计每年的发病率0.06％。

“因此，预测肝癌在这些”低风险“的患者病毒载量的其他因素的识别仍然势在必行，”研究者写道（胃肠病学2012年2月13日[DOI：10.1053/j.gastro.2012.02.007]） 。

“最近，HBsAg的定量已成为越来越认识到，作为评估病毒复制和可能的主机了乙肝病毒感染的免疫控制的标记。HBsAg水平较低与风险较低的肝炎活动，”他们指出。

因此，曾博士和他的同事评估了治疗过的病人有B或C基因型慢性乙肝病毒感染的大型队列，但没有肝硬化。研究对象，并已参加了HBsAg的亏损在1985-1995年的研究，并研究招生后来被延长至2000年。

研究人口由2,688乙肝基线时的年龄28及以上的运营商进行了频繁的肝功能试验，血清采样，以及腹部超音波肝癌监视。其中约61％为男性。

平均随访时间为14.7岁（范围2.5至25.8岁）。共有191例患者在这段时间的肝癌，每1000人 - 年4.8例，总发病率。

肝癌的基线和发展之间的平均间隔为11岁（范围2.5至24.5岁）。

正如所料，HBeAg阳性，HBV DNA的更高层次，更高水平和谷丙转氨酶所有率较高的肝癌相关。这样做在这项研究中已知提高肝癌的风险等因素，包括年龄，男性，感染C型

HBsAg水平也被发现在剂量 - 反应的方式，与肝癌的风险关联。然而，它并不如在研究人口作为一个整体或HBeAg阳性的患者群中的其他预测强。

但研究人员在HBeAg阴性和低病毒载量，从而缺乏，最好的预测肝癌风险的两个危险因素的患者特别感兴趣。

在单因素分析，发展肝癌的风险比（HR）为5.4（1,000 IU /毫升或更大）在这类病人有高HBsAg水平相比，与那些HBsAg水平低于1,000 IU / mL的。

进一步多因素分析显示，高HBsAg水平仍然是一个肝癌的独立危险因素，与HR的13.7。

“这些数据表明，HBsAg水平可以补充HBV DNA水平预测肝癌发展，”尤其是在低病毒载量的患者，曾博士和他的同事说。

他们建议，患者病毒载量低，但HBsAg水平高“可能含有更多的肝细胞与HBV的整合比那些有HBsAg水平低，因此，肝癌的风险较高......可归结为结果增加基因组不稳定综合病毒序列，从而起到在肝癌发生的重要作用。“

在本研究人群中，有低HBV DNA水平和HBsAg水平低的患者群显示了肝癌的累积发生率只有0.2％，这是在控制科目在以往的研究报告的水平相似。因此，HBsAg水平低，低HBV DNA水平的陪同下，似乎反映了足够的宿主对乙肝病毒感染的免疫控制，可用于识别低风险的发展肝癌的患者。

医生“，迫切需要一个很好的指示剂停止核苷酸类似物治疗的HBeAg阴性患者，如果低于1000 IU / mL的HBsAg水平可以可靠地用来定义低风险或无效的乙肝病毒携带者，我们可能采取这一截止水平中间处理的目标，“作者写道，假设在未来的研究证实，这项研究的结果。

这项研究是由佛教慈济综合医院台北分院，台大医院，卫生署，国科会的支持。曾博士的联营公司，雅培，拜耳，施贵宝公司，Gilead Sciences公司，葛兰素史克，默沙东，诺华，罗氏的关系。