Division of Internal Medicine, Athens University Medical School, Athens, Greece.
J Hepatol. 2011 Jul;55(1):61-8. doi: 10.1016/j.jhep.2010.10.027. Epub 2010 Dec 5.
BACKGROUND & AIMS: Translation of HBsAg depends on transcription of the appropriate mRNAs from cccDNA, but its relation to other hepatitis B virus (HBV) replication parameters is not known, inasmuch as integrated sequences of HBV-DNA may also contribute to its serum levels, especially in HBeAg-negative chronic hepatitis B (CHB) patients.
We investigated HBsAg serum levels, its hepatocellular expression, and their relationship to HBV replicative- and host-response parameters before treatment in 54 HBeAg-negative CHB patients and in 15 of them after 40.1±33.3months of virological response on oral antiviral (NUC) therapy also. Liver cccDNA and HBV-DNA quantitation, HBsAg- and HBcAg-immunostaining were performed in the same needle biopsy material, while serum HBsAg and HBV-DNA levels were measured in samples drawn on the day of liver biopsy.
In untreated patients, serum HBsAg correlated positively with HBsAg-positive hepatocytes/mm(2) (p=0.003) and weakly with serum HBV-DNA, but not with cccDNA, liver HBV-DNA, HBcAg-positive hepatocytes/mm(2), or ALT. cccDNA correlated significantly with liver HBV-DNA (p<0.00001), ALT (p=0.001), and serum HBV-DNA levels (p=0.012) but not with liver HBsAg or HBcAg. Antiviral therapy decreased serum HBsAg levels by 79.6% (p=0.012) and liver HBV-DNA by 84.4% (p=0.026) in paired comparisons and, as expected, significantly decreased serum HBV-DNA and ALT levels, but not cccDNA.
In untreated HBeAg-negative CHB, serum HBsAg levels reflect liver HBsAg, but not cccDNA or liver HBV-DNA, suggesting that they are not solely dependent on the replicative cycle of HBV. Effective NUC therapy for 3.34 years significantly lowers serum HBsAg and liver HBV-DNA, but not cccDNA.
HBsAg 的翻译取决于 cccDNA 中适当 mRNA 的转录，但尚不清楚其与其他乙型肝炎病毒 (HBV) 复制参数的关系，因为 HBV-DNA 的整合序列也可能影响其血清水平，尤其是在 HBeAg 阴性慢性乙型肝炎 (CHB) 患者中。
我们在 54 例 HBeAg 阴性 CHB 患者和其中 15 例接受抗病毒 (NUC) 治疗 40.1±33.3 个月后，检测了治疗前患者的 HBsAg 血清水平、肝细胞表达及其与 HBV 复制和宿主反应参数的关系。采用相同的肝组织活检材料进行肝 cccDNA 和 HBV-DNA 定量、HBsAg 和 HBcAg 免疫组化染色，同时检测肝活检当天血清 HBsAg 和 HBV-DNA 水平。
在未经治疗的患者中，血清 HBsAg 与 HBsAg 阳性肝细胞/mm²（p=0.003）呈正相关，与血清 HBV-DNA 呈弱相关，但与 cccDNA、肝 HBV-DNA、HBcAg 阳性肝细胞/mm²或 ALT 无关。cccDNA 与肝 HBV-DNA（p<0.00001）、ALT（p=0.001）和血清 HBV-DNA 水平（p=0.012）显著相关，但与肝 HBsAg 或 HBcAg 无关。抗病毒治疗后血清 HBsAg 水平降低 79.6%（p=0.012），肝 HBV-DNA 水平降低 84.4%（p=0.026），与预期一致，显著降低了血清 HBV-DNA 和 ALT 水平，但 cccDNA 水平没有降低。
在未经治疗的 HBeAg 阴性 CHB 中，血清 HBsAg 水平反映了肝 HBsAg，而不是 cccDNA 或肝 HBV-DNA，提示其不仅依赖于 HBV 的复制周期。经过 3.34 年有效的 NUC 治疗，血清 HBsAg 和肝 HBV-DNA 显著降低，但 cccDNA 没有降低。
