Division of Clinical and Molecular Hepatology, University Hospital of Messina, Italy.
J Hepatol. 2013 Jan;58(1):190-3. doi: 10.1016/j.jhep.2012.09.005. Epub 2012 Sep 16.
Co-existence of multiple causes of liver injury increases the risk of hepatocellular carcinoma (HCC) development. HCC usually develops in patients with cirrhosis although it may also occur in individuals with no or mild liver disease, in particular in cases with hepatitis B virus (HBV) infection. Here we report the case of a 43year-old man with HFE-haemochromatosis, seronegative for hepatitis B and C infections, who developed HCC in the absence of severe liver damage. Both tumoural and non-tumoural liver DNA extracts were tested by nested-PCR and primers specific for four different HBV genomic regions in order to evaluate the presence of occult HBV infection. Only X gene sequences were detected in tumour (but not in non-tumour) DNA extracts. HBV-Alu PCR showed a HBV integration involving a 5'-deleted X gene with an intact enhancer-II/basal-core promoter region. The viral-host junction sequencing revealed that this integrant was located upstream of the partitioning-defective-6-homolog-gamma gene (PARD6G) and real time-PCR quantification demonstrated that PARD6G was overexpressed in tumour compared to non-tumour liver tissues. In conclusion, the combination of HFE-haemochromatosis and occult HBV infection in this patient might have led to a sequel of cellular events that determined the development of HCC even in the absence of cirrhosis.
多种原因导致的肝损伤会增加肝细胞癌（HCC）发展的风险。尽管 HCC 通常发生在肝硬化患者中，但也可能发生在无或轻度肝病的个体中，特别是在乙型肝炎病毒（HBV）感染的情况下。在此，我们报告了一例 43 岁的 HFE 血色病患者，其乙型肝炎和丙型肝炎感染均呈血清阴性，但在无严重肝损伤的情况下发生了 HCC。通过巢式 PCR 和针对四个不同 HBV 基因组区域的引物对肿瘤和非肿瘤肝 DNA 提取物进行了检测，以评估隐匿性 HBV 感染的存在。仅在肿瘤（而非非肿瘤）DNA 提取物中检测到 X 基因序列。HBV-Alu PCR 显示 HBV 整合涉及 5'缺失的 X 基因，具有完整的增强子-II/基本核心启动子区域。病毒-宿主连接测序显示，这种整合体位于分割缺陷 6-同源-γ 基因（PARD6G）的上游，实时 PCR 定量显示，与非肿瘤肝组织相比，PARD6G 在肿瘤中过度表达。总之，在该患者中，HFE 血色病和隐匿性 HBV 感染的结合可能导致了一系列细胞事件的发生，即使在没有肝硬化的情况下，也导致了 HCC 的发展。
