High HBV Viral Load Predicts Liver Fibrosis and Cancer

StephenW

http://hivandhepatitis.com/hepatitis-b/hepatitis-b-topics/hbv-disease-progression/3203-high-hbv-viral-load-predicts-liver-fibrosis-and-cancer
High HBV Viral Load Predicts Liver Fibrosis and Cancer

Category: HBV Disease Progression                                                                Published on Tuesday, 30 August 2011 00:00                                                      Written by Liz Highleyman               
                                                                                                

© Russell Kightley

                                       
               
               
High hepatitis B virus (HBV) DNA levels were associated with worse liver fibrosis, hepatitis reactivation, and development of hepatocellular carcinoma (HCC) in hepatitis B "e" antigen (HBeAg) negative patients in 2 recent studies described in the July 2011 Journal of Viral Hepatitis.
Over years or decades, chronic hepatitis B can cause severe liver disease including cirrhosis and hepatocellular carcinoma. But the factors that lead to advanced disease progression in some patients but not others are not fully understood.
Liver Fibrosis
In the first study, Faisal Sanai from King Abdulaziz Medical City in Riyadh, Saudi Arabia, and colleagues compared occurrence of moderate-to-severe fibrosis (Metavir stage F2 or higher) and predictive factors among chronic hepatitis B patients with HBV DNA viral load above or below 2000 or 20,000 IU/mL.
        The researchers performed prospective liver biopsies on 203 HBeAg negative patients. Most (86%) had HBV genotype D. Participants were categorized into 4 groups:

• Group 1 (n = 55): HBV DNA > 20,000 IU/mL and persistently elevated (> 40 U/L) alanine aminotransferase (ALT);
• Group 2 (n = 34): HBV DNA > 20,000 IU/mL and persistently normal ALT;
• Group 3 (n = 40): HBV DNA < 20,000 IU/mL and persistently elevated ALT;
• Group 4 (n = 74): HBV DNA < 20,000 IU/mL and persistently normal ALT.
  

They later re-analyzed all groups using a lower viral load cut-off of 2000 IU/mL.
        Results

• Stage F2 or higher fibrosis was detected in 72.7% of patients in Group 1, 52.9% in Group 2, 57.5% in Group 3, and 18.9% in Group 4.
• There were no significant differences when using an HBV DNA cut-off of 20,000 vs 2000 IU/mL, although there was a trend toward less fibrosis in Group 2.
• In a multivariate analysis, being in Group 4 -- that is, having viral load < 20,000 and normal ALT -- and milder necroinflammatory grade (A0-A1) were independent predictors of lower fibrosis risk (odds ratio 0.03 and 0.14, respectively).
• The specificity, positive predictive value, and negative predictive value of persistently elevated AL for detection of stage F2 or higher fibrosis were 80%, 69%, and 65%, respectively, using the 2000 IU/mL viral load cut-off.
• Values were 86%, 73%, and 63%, respectively, using the 20,000 IU/mL cut-off.
• Sensitivity improved marginally using the lower viral load cut-off (51% vs 42%, respectively).
  

"Significant fibrosis is prevalent in a large proportion of HBeAg negative patients with high viremia and persistently normal ALT," the study authors concluded. "Lower HBV DNA cut-offs could be adopted with marginal gains in fibrosis detection and without loss of diagnostic accuracy."

Hepatitis Reactivation and Liver Cancer
In the second study, Takahide Nakazawa from Kitasato University in Sagamihara, Japan, and colleagues looked at the time course and predictive factors for hepatitis reactivation and development of liver cancer, and their association with HBV DNA level, among 104 HBeAg negative patients with persistently normal ALT.
Results

• During an average follow-up period of about 6 years, 5 participants (4.8%) developed liver cancer and 14 (13.5%) experienced hepatitis reactivation.
• At 5 years the cumulative rates of liver cancer and hepatitis reactivation were 2.4% and 13.7%, respectively.
• At 10 years the corresponding rates were 9.9% and 15.5%, respectively.
• In a univariate analysis, HBV DNA viral load > 5 log copies/mL was the only predictor of liver cancer.
• In a multivariate analysis, HBV DNA > 5 log copies/mL and ALT between 20 and 40 IU/L were independent predictors of hepatitis reactivation.
• Because there was no independent association between ALT level and development of liver cancer, the researchers proposed that HBV DNA level was an "essential predictor."
• Baseline HBV DNA level was related to future levels, and was not subject to wide fluctuations.
  

"Our results showed that an HBV DNA level of > 5 log copies/mL predicts subsequent hepatocarcinogenesis and hepatitis reactivation in HBeAg negative carriers with persistently normal ALT," the researchers concluded. "As the baseline HBV DNA level reflects the future level, appropriate clinical management according to the viral level is expected to decrease future risk."
Investigator affiliations:
Sanai study: Department of Hepatobiliary Sciences, King Abdulaziz Medical City, Riyadh; Division of Gastroenterology, Department of Medicine, King Faisal Specialist Hospital & Research Center, Riyadh; Gastroenterology Department, Riyadh Military Hospital, Riyadh; Division of Gastroenterology, Department of Medicine, King Fahad General Hospital, Jeddah; Department of Molecular Virology, Research Center, King Faisal Specialist Hospital & Research Center, Riyadh; Department of Medicine, King Abdulaziz Medical City, Al-Ahsa; Division of Gastroenterology, Department of Medicine, King Khalid University Hospital, King Saud University, Riyadh; Clinical Research Center, King Abdullah International Medical Research Center, National Guard Health Affairs, Riyadh; Liver Disease Research Center, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Nakazawa study: Department of Gastroenterology, Kitasato University East Hospital, Sagamihara; Nakazawa Medical Clinic, Sagamihara; Department of Clinical Laboratory, Kitasato University East Hospital, Sagamihara, Japan.
8/30/11
References
FM Sanai, A Helmy, KI Bzeizi, et al. Discriminant value of serum HBV DNA levels as predictors of liver fibrosis in chronic hepatitis B. Journal of Viral Hepatitis 18(7):e217-25 (abstract). July 2011.
T Nakazawa, A Shibuya, A Takeuchi, et al. Viral level is an indicator of long-term outcome of hepatitis B virus e antigen-negative carriers with persistently normal serum alanine aminotransferase levels. Journal of Viral Hepatitis 18(7):e191-199 (abstract). July 2011.

StephenW

谷歌翻译
不是100％准确，请只作为参考使用。

乙型肝炎病毒（HBV）DNA水平与糟糕的肝纤维化，肝炎活化，肝癌（HCC）的发展在乙肝的“e”抗原e抗原（HBeAg）在最近的研究2阴性的患者在2011年7月杂志介绍病毒性肝炎。

在几年或几十年，慢性B型肝炎可以导致严重的肝病，包括肝硬化和肝癌。但导致先进，部分患者病情恶化的因素，但不是别人是不充分的理解。

肝纤维化

在第一项研究中，费萨尔三爱，沙特阿拉伯在利雅得的阿卜杜勒阿齐兹国王医学城，和他的同事相比发生中度至重度纤维化（METAVIR阶段F2或更高）和慢性乙型肝炎患者中HBV - DNA病毒载量高于预测因素或低于2000年或20,000国际单位/毫升。

研究者进行准203 HBeAg阴性患者肝活检。大多数（86％）HBV基因型D.参加者分为4组分类：

    第1组（N = 55）：HBV - DNA> 20,000 IU / mL和持续升高（> 40 U / L）丙氨酸转氨酶（ALT）;
    第2组（N = 34）：HBV - DNA> 20,000 IU / mL和持续ALT正常;
    第3组（N = 40）：HBV - DNA <20000 IU / mL和坚持ALT升高;
    第4组（N = 74）：HBV - DNA <20000 IU / mL和持续ALT正常。

后来，他们重新分析所有群体使用2000 IU / mL的低病毒载量切断。

结果

    期
F2或更高纤维化检测在72.7％的患者在第1组，2组为52.9％，57.5％在第3组，并在第4组的18.9％。
    有没有显著差异时，使用的乙肝病毒DNA切断20000 VS 2000 IU /毫升，虽然有一个趋势走向少在第2组的纤维化。
    在多变量分析中，在第4组 - 就是病毒载量<20000和ALT正常 - ，和温和的坏死性炎症级（A0 - A1）的低纤维化的风险（比值比分别为0.03和0.14，）的独立预测因素。
    特异性，阳性预测值，阴性预测值持续升高的AL阶段F2或更高纤维化检测分别为80％，69％和65％，分别使用截止2000年IU / mL的病毒载量。
    值分别为86％，73％和63％，分别使用20,000个国际单位/毫升切断。
    灵敏度提高轻微使用的病毒载量较低（分别为51％比42％）切断。

“显着肝纤维化是在一个大的比例高血症和持续ALT正常的HBeAg的阴性的患者中普遍存在，”该研究的作者得出结论。下HBV DNA的切割取舍，可以采用与纤维化的检测和诊断准确性的损失没有边际收益。“

肝炎恢复和肝癌

在第二项研究中中，从日本，在相模原市，北里大学和他的同事Takahide泽看着时间的推移和预测因素激活型肝炎和肝癌的发展，及其与HBV DNA水平的关系，其中104 e抗原阴性的患者持续正常ALT键。

结果

    在一个平均随访6年左右的时间，5人（4.8％），肝癌和14例（13.5％），经验丰富的肝炎激活。
    肝癌和肝炎活化的累积率分别为5年，分别为2.4％和13.7％。
    在10年的相应变动率分别为9.9％和15.5％。
    在单因素分析显示，HBV - DNA病毒载量> 5日志拷贝/ mL的是肝癌的唯一预测。
    在多变量分析中，HBV DNA> 5日志拷贝/ mL和20至40 IU / L，ALT肝炎活化的独立预测因素。
    因为没有独立协会之间的ALT水平和肝癌的发展，研究人员提出，HBV DNA水平是一个“必要的预测。”
    基线HBV DNA水平与未来的水平，并没有受到大幅波动。

“我们的研究结果表明，> 5日志拷贝/ ml的HBV DNA水平预测，在随后的肝癌和肝炎活化持续ALT正常的HBeAg的负面运营商，研究人员得出结论。” “作为基线HBV DNA水平，反映未来水平，适当的临床管理，根据病毒的水平，预计将减少未来的风险。”