Laboratory of Molecular Virology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ, Brazil.
Hepatol Res. 2008 Dec;38(12):1194-203. doi: 10.1111/j.1872-034X.2008.00392.x. Epub 2008 Jun 24.
To determine the prevalence of occult hepatitis B virus (HBV) infection in a group of human immunodeficiency virus (HIV)-infected Brazilian patients and to investigate its association with biochemical, virological and molecular features.
Sera from 43 patients positive for HBV core antibody and negative for HBV surface antigen (HBsAg) were tested for HBV DNA positivity by semi-nested PCR. HBV loads were assessed by real-time PCR. S gene was cloned and sequenced for HBV isolates from 3 patients. HBsAg expression of these cases was performed in HuH7 cells.
HBV DNA was found in 6/43 (14%) samples, all except one associated with low viral loads. Occult HBV infection was further correlated with anti-hepatitis C virus (anti-HCV) antibodies positivity, but not with alanine aminotransferase (ALT) elevated levels. S gene sequences derived from three patients were determined. Two of them displayed mutations that may explain HBsAg negativity. In the first one, a stop codon mutation was found at position 216 in the C-terminal end of HBsAg. In the second patient, E164D and I195M substitutions in HBsAg, associated with lamivudine-resistance mutations in the polymerase were identified. As expected, all clones showing those mutations displayed undetectable or very low levels of HBsAg.
Occult HBV infection was frequent in HIV-infected patients, was not associated with ALT elevation but significantly correlated with HCV seropositivity. The low viremia and the detection of HBsAg mutants confirm that multifactorial mechanisms are involved in occult HBV infection. HBV molecular monitoring should be employed for an adequate management of HBV/HIV co-infected patients.
确定一组感染人类免疫缺陷病毒（HIV）的巴西患者中隐匿性乙型肝炎病毒（HBV）感染的流行情况，并研究其与生化、病毒学和分子特征的关系。
对 43 例 HBV 核心抗体阳性且 HBV 表面抗原（HBsAg）阴性的患者血清进行半巢式 PCR 检测 HBV DNA 阳性。通过实时 PCR 评估 HBV 载量。对 3 例患者的 HBV 分离株进行 S 基因克隆和测序。对这些病例进行 HuH7 细胞的 HBsAg 表达。
在 6/43（14%）样本中发现 HBV DNA，除一个样本外，均与低病毒载量相关。隐匿性 HBV 感染与抗丙型肝炎病毒（抗-HCV）抗体阳性进一步相关，但与丙氨酸氨基转移酶（ALT）升高水平无关。从 3 例患者中确定了 S 基因序列。其中 2 例显示突变可能导致 HBsAg 阴性。在第一个病例中，在 HBsAg 的 C 末端位置 216 发现终止密码子突变。在第二个患者中，发现 HBsAg 中的 E164D 和 I195M 取代，与聚合酶中的拉米夫定耐药突变相关。如预期的那样，所有显示这些突变的克隆均显示无法检测或极低水平的 HBsAg。
在 HIV 感染患者中，隐匿性 HBV 感染很常见，与 ALT 升高无关，但与 HCV 血清阳性显著相关。低病毒血症和 HBsAg 突变体的检测证实，多种因素参与隐匿性 HBV 感染。应进行 HBV 分子监测，以对 HBV/HIV 合并感染患者进行适当管理。
