原发性肝癌与HBV DNA的关系分析

目的：探讨原发性肝癌（PHCC）与患者血清乙肝病毒（HBV）的关系。方法：对286例PHCC患者进行HBV DNA检测。结果：在286例肝癌患者中，HBV DNA阳性率为62．59％，其中85．47％的感染者血清HBV DNA水平≤10^6。结论：乙肝病毒感染仍是肝癌的主要发病因素，而且这类患者的血清HBV DNA水平大多较低。     

乙型肝炎病毒e抗体检测在原发性肝癌中的临床意义

本文报告119例PHC和非肝脏恶性肿瘤和肝良性占位变82例血清HBV感染结果。表明在PH-C和其他疾病的HBV感染标志的阳性率分别是:e抗体60.5％和24.4％,HBsAg63.0％和17.1％,抗HBc为78.2％和24.4％,抗HBs 5％和14.6％,HBeAg11.8％和8.5％,HBV总暴露率91.6％和32.9％,其中e抗体,抗HBc,HBV总暴露率PHC组显著地高于对照组。抗HBs则相反。资料表明e抗体阳性率随病情的进展,肿块的增大而增高。提示e抗体的存在与癌细胞的增殖,肝细胞的癌变有关。它作为HBV感染标志之一应予重视。     

肝细胞癌与肝炎后肝硬化中多种肿瘤标志物的比较

目的探讨多种肿瘤标志物在肝细胞癌和肝炎后肝硬化中的表达情况。方法采用多种肿瘤标志物蛋白芯片检测系统测定85例肝细胞癌患者和92例肝炎后肝硬化患者血清中肿瘤标志物（CA199、CEA、CA242、FER、AFP、CA125、CA153）的水平,并比较各指标在两组间的差异情况。结果 7项肿瘤指标在肝细胞癌和肝炎后肝硬化中都有不同程度的阳性表达,且CA242和AFP在两组肝病间的比较有明显的统计学意义。结论多种肿瘤标志物的联合检测对肝细胞癌的诊断有较高的临床参考价值,适合于无明显症状的门诊患者的筛查和肿瘤高危人群的普查。     

Elevation of Serum MAGE-4 Protein Levels and Prediction of Hepatocellular Carcinogenesis in Patients with Liver Cirrhosis

Early detection of hepatocellular carcinoma (HCC) is clinically important because advanced HCC limits treatment modalities for the cancer. We have previously reported that serum levels of MAGE-4 protein are strongly associated with the development of HCC. The present study was designed to determine whether elevated serum MAGE-4 protein levels can predict hepatocellular carcinogenesis in patients with liver cirrhosis before clinical diagnosis. Among 62 cirrhotic patients, 28 patients were diagnosed with HCC during the follow-up period. The levels of MAGE-4 protein and a-fetoprotein (AFP) were significantly elevated in cirrhotic patients with HCC. Univariate and multivariate analyses suggest that elevated serum MAGE-4 protein is more significant than AFP. Importantly, retrospective analysis of prefrozen sera of cirrhotic patients revealed a transient or continuous elevation of serum MAGE-4 protein levels in 14 of 28 cirrhotic patients with HCC (50%) before clinical diagnosis. In contrast, elevated serum MAGE-4 protein levels were observed in 3 of 33 cirrhotic patients without HCC (9%), and in 2 of 34 hepatitic patients (6%). These results indicate that elevated serum MAGE-4 protein levels can be a predictive marker of hepatocellular carcinogenesis in cirrhotic patients, thereby enabling us to treat patients at an earlier stage.     

Spontaneous clearance of high-titer serum HBV DNA and risk of hepatocellular carcinoma in a Chinese population

Chronic hepatitis B virus (HBV) carriers with high-titer viremia (>10(5) virions/ml) are at increased risk for hepatocellular carcinoma (HCC). The aim of this study was to determine the relationship between clearance of high-titer viremia and subsequent risk of HCC. The study population was a prospective cohort of 114 adults from Haimen City, China, all HBV DNA(+) at study entry and followed for 797.8 person-years in total. During follow-up, 54 (47.4%) subjects spontaneously cleared high-titer viremia at least once. Of these, 27 were considered to have undergone stable seroconversion, 16 were considered unstable (12 reversions to HBV DNA positivity and 4 multiple clearances), and 11 did not have sufficient follow-up to determine stability. Of the 114 persons, 26 (22.8%) died during follow-up, 21 (18.4%) from HCC. Using Cox proportional hazards models, the RR of HCC death associated with seroconversion was 2.8 (95% CI = 1.1-7.4), controlling for age, sex, family HCC history, history of acute hepatitis, alcohol use and cigarette smoking. In conclusion, fluctuations of high-titer viremia may indicate increased hepatocellular damage and at least short-term increases in HCC risk. Long-term longitudinal studies are needed to clarify this relationship and its potential usefulness as a prognostic marker in chronic HBV infection.     

肝动脉化疗栓塞对原发性肝癌患者HBV DNA水平的影响

背景与目的：化疗可抑制恶性肿瘤患者的免疫功能,导致合并乙型肝炎病毒（hepatitis B virus,HBV）感染的肿瘤患者出现HBV激活,严重影响了患者的预后。本研究旨存了解肝癌患者肝动脉化疗栓塞（trans catheter arterial ehemoembolization,TACE）前后乙型肝炎病毒脱氧核糖核酸（HBVDNA）含量的变化及其影响凶素。方法：回顾性分析2004年12月至2008年7月期间,162例肝癌患者TACE治疗前后HBVDNA的变化．并分析HBVDNA变化与AFP的关系。结果：治疗后HBVDNA阳性率较治疗前显著降低『55．6％VS．71．6％,P〈0．01]。治疗前HBVDNA≥ 1×10^5／L者更易出现HBVDNA水平的下降（OR=2．7,P〈0．01）;治疗后AFP的下降与HBVDNA下降有关联（OR=2．6,P〈O．05）。结论：TACE能降低HBV相关的肝癌患者体内的HBVDNA水平,特别是治疗前HBVDNA≥ 1×10^5／L者及治疗后AFP降低者。     

ABO血型与PHC患者HBV感染标记相关性研究

研究伴ＨＢＶ感染的ＰＨＣ４４５例乙型肝炎抗原抗体与ＡＢＯ血型的关系，结果表明：１．伴ＨＢＶ感染的ＰＨＣＡ型血者显著高于对照组（Ｐ＜０．０１）。２．ＰＨＣ患者中ＨＢｓＡｇ、抗－ＨＢｃ的阳性率均以Ａ型血显著高于对照组（Ｐ＜０．０５）。３．ＰＨＣ患者中ＨＢｓＡｇ与抗－ＨＢｃ均阳性模式Ａ型血者显著多于对照组，而Ｂ型血者显著少（Ｐ＜０．０５）；抗－ＨＢｅ与抗ＨＢｃ均阳性的ＰＨＣ中，亦为Ａ型血者显著多（Ｐ＜０．０５）。提示有ＨＢＶ感染的Ａ型血者罹患ＰＨＣ的倾向性最高；而有ＨＢＶＭ、ＨＢｓＡｇ、抗－ＨＢｃ的Ａ型血者则为ＰＨＣ的易感人群，其中以ＨＢｓＡｇ和抗－ＨＢｃ同时阳性或抗－ＨＢｅ和抗－ＨＢｃ同时阳性的感染模式更易发生ＰＨＣ；也提示ＰＨＣ、ＨＢＶ、Ａ型血三者之间存在某种密切的、复杂的联系，对ＰＨＣ的发生有协同作用。对上述人群应密切关注，定期复查，以期早诊早治。     

Changes in Inflammatory Markers Predict the Prognosis of Resected Hepatocellular Carcinoma with Child–Pugh A

(1) Background: The reasons for changes in the inflammatory markers of patients with surgically resected hepatocellular carcinoma are unclear. We aimed to investigate the association of an inflammatory status with the prognosis of patients with hepatocellular carcinoma, who underwent surgical resection. (2) Methods: We retrospectively enrolled 91 patients with Child A hepatocellular carcinoma, who had received surgical resection, to explore the influence of preoperative inflammatory markers and postoperative changes on the prognosis. (3) Results: The platelet-to-lymphocyte ratio (PLR) and its alteration were independent prognostic factors. Patients with a low PLR had a significantly better recurrence-free survival (RFS) than those with a high PLR (1-year RFS of 88.5% versus 50.0%; 3-year RFS of 62.1% versus 25.0%, p = 0.038). The patients with a low PLR showed a significantly better overall survival (OS) than those with a high PLR (1-year OS of 98.9% versus 75.0%; 3-year OS of 78.2% versus 25.0%, p = 0.005). The patients whose PLR had increased at 6 months after operation showed a worse OS than patients whose PLR had decreased (1-year OS of 96.3% versus 98.4%; 3-year OS of 63.0% versus 79.7%, p = 0.048). However, neither the neutrophil-to-lymphocyte ratio nor Onodera’s prognostic nutritional index had any prognostic significance. (4) Conclusions: The PLR and its alteration are significant prognostic factors for the RFS and OS of patients with Child A hepatocellular carcinoma who had received curative surgery.     

HBV激活Notch1信号通路上调GP73的表达

目的:探索HBV上调GP73表达的相关机制.方法:通过real-time PCR和Western blot检测HepG2和整合HBV的HepG2.2.15细胞中Notch1及其下游分子Hes1的表达.分别转染Notch1过表达载体和干扰载体,观察Notch1对GP73表达的影响.免疫组织化学法检测GP73、Notch1在肝癌组织中的表达,分析两者的相关性.结果:HBV可引起Notch1的表达升高;Notch1可引起GP73的表达升高,两者在肝癌组织中呈正相关.结论:HBV可通过激活Notch1通路上调GP73的表达,这可能是GP73在肝癌组织中表达升高的原因之一.     

Detection of MAGE-4 Protein in the Sera of Patients with Hepatitis-C Virus-associated Hepatocellular Carcinoma and Liver Cirrhosis

The aim of this study was to determine whether MAGE-4 protein is detectable in sera of patients with hepatocellular carcinoma and other liver diseases. An enzyme-linked immunosorbent assay was employed for detection of MAGE-4 protein in sera of liver disease patients, healthy men and women (control I) and those undergoing prostatic cancer screening (control II). MAGE-4 protein levels in sera of patients with hepatitis C virus-associated HCC (HCC-C) ( n =45, mean=2.160 ng/ml) and HCV-associated cirrhosis (LC-C) ( n = 55, 1.072 ng/ml) were significantly higher ( P < 0.0001) than those of control I (0.327 ng/ml) or control II (0.394 ng/ml). MAGE-4 protein was positive in 21/45 (46.7%) HCC-C patients and 18/55 (32.7%) LC-C patients (cut-off, mean plus 2 SD in healthy controls) but in 0/12 (0%) hepatitis B virus-associated HCC (HCC-B) patients, 3/49 (6.1%) hepatitis B virus-associated LC (LC-B) patients, 4/47 (8.5%) alcoholic liver disease patients, and 1/49 (2.0%) controls. Serum MAGE-4 protein level may be useful as a marker for identification of LC-C patients suffering from HCC that is undetectable by presently available methods.