Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, University Hospital of Pisa, Pisa, Italy.
Department of Economics and Management, University of Pisa, Pisa, Italy.
Liver Int. 2017 Nov;37(11):1622-1631. doi: 10.1111/liv.13416. Epub 2017 Apr 18.
BACKGROUND & AIMS: The difference between the long-term outcome of low-viraemic (HBV-DNA≤20 000-IU/mL, LV-AC) and inactive HBsAg carriers (HBV-DNA≤2000-IU/mL, IC) remains to be defined. We studied prospectively 153 HBeAg-negative HBsAg-carriers with baseline HBV-DNA≤20 000-IU/mL and normal transaminases.
IC, LV-AC or chronic hepatitis B (CHB) (HBV-DNA persistently ≤2000-IU/mL, ≤20 000-IU/mL or >20 000-IU/mL respectively) were diagnosed after 1-year, 3-monthly monitoring. Thereafter IC and LV-AC were followed-up for additional 57.2 (8.5-158.3) months. HBV-DNA, HBsAg, HBV"core-related"Antigen (HBcrAg) and total-anti-HBc were quantified at baseline.
After the 1st year diagnostic follow-up CHB [higher HBV-DNA (P=.005), total-anti-HBc (P=.012), ALT (P=.007) and liver-stiffness (P=.021)] was identified in 20 (13.1%) carriers; baseline HBsAg≤1000IU/HBV-DNA≤2000IU/mL excluded the presence of CHB (NPV-100%). Thereafter, during the long-term follow-up none of 87 IC reactivated, 19 (21.8%) cleared HBsAg [older-age (P=.004), lower HBsAg (P<.001), higher yearly HBsAg decline (P<.001)]. Twenty-five of 46 (54.3%) LV-AC remained stable, 20 (43.5%) became IC and 1 (2.2%) developed CHB. The best single-point CHB and IC diagnostic-accuracies were total-anti-HBc (84.2%, NPV-98.2%) and HBV-DNA/total-anti-HBc/HBcrAg combination (89.5%, 93%-sensitivity, 84.8%-specificity) respectively.
Viraemia persistently ≤20 000-IU/mL predicts a benign clinical outcome: it was associated with transition to IC in 43% of LV-AC and to Occult HBV Infection in 20% of IC within 5-years. Nevertheless, 13.1% of individuals with low viraemia at presentation develops CHB within 1 year: 1-year HBV-DNA monitoring resulted the most accurate diagnostic approach that can be limited to at least a half of cases by the single point HBV-DNA/HBsAg quantification. The IC-diagnostic-accuracy combining HBV-DNA/total-anti-HBc/HBcrAg needs to be confirmed in further studies.
低病毒载量（HBV-DNA≤20000IU/mL，LV-AC）和非活动 HBsAg 携带者（HBV-DNA≤2000IU/mL，IC）的长期结局之间的差异仍有待确定。我们前瞻性研究了 153 例基线 HBV-DNA≤20000IU/mL 且肝功能正常的 HBeAg 阴性 HBsAg 携带者。
在 1 年、3 个月的监测后，分别诊断为 IC、LV-AC 或慢性乙型肝炎（CHB）（HBV-DNA 持续≤2000IU/mL、≤20000IU/mL 或>20000IU/mL）。此后，对 IC 和 LV-AC 进行了额外的 57.2（8.5-158.3）个月的随访。在基线时定量检测 HBV-DNA、HBsAg、HBV“核心相关”抗原（HBcrAg）和总抗-HBc。
在第 1 年的诊断随访后，20 例（13.1%）携带者中发现了 CHB[更高的 HBV-DNA（P=.005）、总抗-HBc（P=.012）、ALT（P=.007）和肝硬度（P=.021）]；基线 HBsAg≤1000IU/ml，HBV-DNA≤2000IU/ml 排除了 CHB 的存在（NPV-100%）。此后，在长期随访中，87 例 IC 中无一例再次激活，19 例（21.8%）清除了 HBsAg[年龄较大（P=.004）、HBsAg 较低（P<.001）、HBsAg 每年下降幅度较大（P<.001）]。46 例 LV-AC 中有 25 例保持稳定，20 例（43.5%）转为 IC，1 例（2.2%）发展为 CHB。HBV-DNA/总抗-HBc/HBcrAg 组合是诊断 CHB 和 IC 的最佳单项指标，其准确性分别为 84.2%（NPV-98.2%）和 89.5%（敏感性 93%，特异性 84.8%）。
病毒血症持续≤20000IU/ml 预示着良好的临床结局：它与 LV-AC 中 43%的患者向 IC 转化和 IC 中 20%的患者向隐匿性 HBV 感染转化有关。然而，在发病时病毒载量较低的 13.1%的个体在 1 年内发展为 CHB：1 年 HBV-DNA 监测是最准确的诊断方法，通过单点 HBV-DNA/ HBsAg 定量检测，至少可以将一半的病例进行限制。HBV-DNA/总抗-HBc/HBcrAg 联合的 IC 诊断准确性需要在进一步的研究中得到证实。
