Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China.
Hepatology. 2011 Sep 2;54(3):829-36. doi: 10.1002/hep.24551. Epub 2011 Jul 21.
We aimed to investigate the incidence of occult hepatitis B infection (OBI) in patients with "cryptogenic" hepatocellular carcinoma (HCC) and to study the HBV replicative activity in these patients. Tumorous and adjacent nontumorous liver tissues were obtained from 33 cryptogenic HCC patients and 28 HCC patients with identifiable causes (13 with chronic hepatitis B [CHB], six with chronic hepatitis C, and nine alcohol-related). OBI was identified by nested polymerase chain reaction (PCR). Intrahepatic HBV DNA, covalently closed circular DNA (cccDNA), and pregenomic RNA (pgRNA) were quantified by real-time PCR and reverse-transcription PCR (RT-PCR), respectively. OBI was identified in 24 (73%) cryptogenic HCC patients, one (17%) HCC patient with HCV, and five (56%) patients with alcohol-related HCC. In HCC patients with OBI, HBV DNA were detected in ≥2 HBV genomic regions more often in nontumorous tissues than in tumorous tissues (90% versus 57%, respectively; P = 0.007). Cryptogenic HCC patients with OBI had lower intrahepatic total HBV DNA levels than HCC patients with CHB (median: 0.010 versus 3.19 copies/cell, respectively; P < 0.0001). Only six (26%) cryptogenic HCC patients with OBI had detectable cccDNA (median: <0.0002 copies/cell), which was significantly lower than that of the CHB patients (median: 0.005 copies/cell; P < 0.0001). HBV pgRNA were detectable in 12 (52%) cryptogenic HCC patients with OBI (median: 0.0001 copies/cell), which was significantly lower than that of the CHB patients (median: 2.90 copies/cell; P < 0.001).
73% of patients with apparently unidentifiable causes for HCC were HBV-related. The detection rate was higher in nontumorous tissues than tumorous tissues. The low intrahepatic HBV DNA and pgRNA levels indicated that persistent viral replication and possibly HBV integration are the likely causes of HCC in OBI patients.
研究隐匿性乙型肝炎病毒（HBV）感染（OBI）在不明原因肝细胞癌（HCC）患者中的发生率，并研究这些患者的 HBV 复制活性。从 33 例隐匿性 HCC 患者和 28 例有明确病因的 HCC 患者（慢性乙型肝炎[CHB]患者 13 例、慢性丙型肝炎患者 6 例、酒精性肝炎患者 9 例）的肿瘤和非肿瘤组织中获得标本。采用巢式聚合酶链反应（PCR）检测 OBI。采用实时 PCR 和逆转录 PCR（RT-PCR）分别定量检测肝内 HBV DNA、共价闭合环状 DNA（cccDNA）和前基因组 RNA（pgRNA）。采用巢式 PCR 检测 OBI。在 33 例隐匿性 HCC 患者中，24 例（73%）患者检测到 OBI，1 例（17%）丙型肝炎患者和 5 例（56%）酒精性肝炎患者检测到 OBI。在 OBI 的 HCC 患者中，HBV DNA 在非肿瘤组织中比肿瘤组织中更常检测到≥2 个 HBV 基因组区域（90%比 57%；P = 0.007）。与 CHB 患者相比，隐匿性 HCC 患者的 OBI 患者的肝内总 HBV DNA 水平较低（中位数：0.010 比 3.19 拷贝/细胞，分别；P < 0.0001）。仅 6 例（26%）隐匿性 HCC 患者 OBI 患者可检测到 cccDNA（中位数：<0.0002 拷贝/细胞），明显低于 CHB 患者（中位数：0.005 拷贝/细胞；P < 0.0001）。12 例（52%）隐匿性 HCC 患者 OBI 患者可检测到 HBV pgRNA（中位数：0.0001 拷贝/细胞），明显低于 CHB 患者（中位数：2.90 拷贝/细胞；P < 0.001）。结论：73%的 HCC 患者病因不明与 HBV 相关。在非肿瘤组织中的检出率高于肿瘤组织。肝内低水平的 HBV DNA 和 pgRNA 表明持续性病毒复制和可能的 HBV 整合是 OBI 患者发生 HCC 的可能原因。
