Tsubota A, Arase Y, Ren F, Tanaka H, Ikeda K, Kumada H
Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan.
J Med Virol. 2001 Oct;65(2):257-65. doi: 10.1002/jmv.2028.
To identify the influence of hepatitis B virus (HBV) genotype on development of hepatocellular carcinoma (HCC) and clinical outcome in chronic HBV infection, 26 consecutive cirrhotic patients infected with HBV subtype adw were investigated prospectively. HBV serology was undertaken using subtype-specific antibodies against hepatitis B surface antigens. The HBV genotype was determined by sequencing directly the polymerase chain reaction products of the HBV S gene. When HCC occurred, patients underwent transcatheter arterial embolization therapy. If tumor necrosis was incomplete, additional embolization therapy was carried out after a 3- to 4-month interval. At a median follow-up of 14.1 years (range 2.2 to 31.7), HCC occurred in 9 (35%) of 26 patients. Nineteen patients were infected with genotype B and 7 with genotype C. Four of the 19 genotype B patients (21%) and 5 of the 7 genotype C patients (71%) developed HCC (P = 0.058). Patient age (<45 years or 45 < or = ) at diagnosis of cirrhosis was the only significant independent factor influencing liver carcinogenesis by multiple logistic regression analysis and Cox's regression analysis (P = 0.0069 and 0.029, respectively). When analysis was limited to the age of 45 years or more at the last visit, genotype was the only contributory factor to HCC development by univariate analysis (P = 0.038). Whereas genotype B patients responded well to embolization therapy and had no recurrence of HCC for a prolonged period of time, genotype C patients showed poor responses and died of hepatic failure due to rapid HCC progression despite embolization therapy. The cumulative incidence of survival was significantly higher in the genotype B group (P = 0.0049). The HBV genotype correlated with the development of HCC, response to embolization therapy, and recurrence of HCC. Determination of HBV genotype may be useful in predicting outcomes in HBV subtype adw-related cirrhosis.
为确定乙型肝炎病毒（HBV）基因型对慢性HBV感染患者肝细胞癌（HCC）发生及临床结局的影响，我们对26例连续的感染HBV adw亚型的肝硬化患者进行了前瞻性研究。采用针对乙型肝炎表面抗原的亚型特异性抗体进行HBV血清学检测。通过直接对HBV S基因的聚合酶链反应产物进行测序来确定HBV基因型。当发生HCC时，患者接受经导管动脉栓塞治疗。如果肿瘤坏死不完全，则在3至4个月的间隔后进行额外的栓塞治疗。中位随访14.1年（范围2.2至31.7年），26例患者中有9例（35%）发生了HCC。19例患者感染B基因型，7例感染C基因型。19例B基因型患者中有4例（21%）发生HCC，7例C基因型患者中有5例（71%）发生HCC（P = 0.058）。通过多因素逻辑回归分析和Cox回归分析，诊断肝硬化时的患者年龄（<45岁或45岁及以上）是影响肝癌发生的唯一显著独立因素（分别为P = 0.0069和0.029）。当分析仅限于最后一次就诊时年龄在45岁及以上的患者时，单因素分析显示基因型是HCC发生的唯一促成因素（P = 0.038）。B基因型患者对栓塞治疗反应良好，且HCC长时间无复发，而C基因型患者反应较差，尽管接受了栓塞治疗，但由于HCC快速进展死于肝衰竭。B基因型组的累积生存率显著更高（P = 0.0049）。HBV基因型与HCC的发生、栓塞治疗反应及HCC复发相关。确定HBV基因型可能有助于预测HBV adw亚型相关肝硬化的结局。
