A Long-term Follow-up Study on Risk Factors for Hepatocellular Carcinoma among Japanese Patients with Liver Cirrhosis

To identify virological parameters (serostatus of hepatitis B surface antigen [HBsAg] and antibodies to hepatitis C virus [anti-HCV], HCV genotypes and HCV-RNA titer) and other clinico-biological and lifestyle variables that may influence or predict the development of hepatocellular carcinoma (HCC) in cirrhosis, we followed 100 cirrhotic patients without HCC, who visited Kyushu University Hospital between 1985 and 1987, until the end of 1995 (follow-up rate: 98%; average follow-up period: 5.3 years). After elimination of 4 patients who developed HCC or were censored within the initial 6 months, 37 (39%) out of 96 patients developed HCC during follow-up. As compared with HBsAg(+) patients, anti-HCV(+) HBsAg(–) patients demonstrated significantly elevated HCC risk (adjusted hazard ratio [HR]=5.85, 95% confidence interval [CI] 1.65–20.67). Genotype 1 HCV infection was not associated with increased risk compared with genotype 2 (HR = 0.64, 95% CI 0.21–1.99). For genotype 1 HCV infection, patients with HCV-RNA levels <1 Meq/ml tended to present lower risk than patients with ≥1 Meq/ml ( P = 0.03). Male sex, advanced Child's class, lower serum albumin, and higher serum aminotransferase and α-fetoprotein were also found to be strong predictors. Overall, drinking and smoking habits were not associated with significantly elevated risk. Among virological parameters, anti-HCV positivity and, possibly high HCV-RNA titer, were predictive of HCC occurrence in cirrhosis in our clinical setting.     

原发性肝癌患者血清中庚型肝炎病毒基因的检测

用逆转录－聚合酶链反应法（ＰＴ－ＰＣＲ）检测了６７例原发性肝癌（ＰＬＣ）患者血清中的庚型肝炎病毒（ＨＧＶ）ＲＮＡ，以ＰＣＲ－双脱氧末端终止法分析了ＰＣＲ产物的核苷酸序列。结果显示，ＨＧＶＲＮＡ的检出率为１９．４％（１３／６７），其在ＨＢｓＡｇ阳性组和ＨＢｓＡｇ／抗ＨＣＶ阴性组中的阳性率分别是１２．２％（６／４９）和５０％（７／１４）；５’非编码区（５’－ＮＣＲ）扩增片段的核苷酸序列与美国株ＧＢＶ－Ｃ的同源性为９１．７％，提示在我国ＰＬＣ患者中存在ＨＧＶ感染。     

EB病毒感染与子宫颈癌

 为探讨EB病毒与宫颈癌的关系，本文采用PCR法对40例宫颈癌的EB病毒感染情况进行了检测，发现其中29例有EB病毒感染（72．5％）。首次在国内报道了宫颈癌与EB病毒感染有关。     

In Vitro Effects of Retinoids on the Proliferation and Differentiation Features of Epstein-Barr Virus-Immortalized B Lymphocytes

Retinoids have been shown to be effective in the chemoprevention and treatment of certain human malignancies. In this review, we will summarize our recent results concerning the effects of retinoids on the proliferation and differentiation of Epstein-Barr virus (EBV)-immortalized lymphoblastoid B-cell lines (LCLs), an in vitro model of EBV-related lymphoproliferative disorders arising in immunosuppressed hosts. Retinoids proved to be powerful inhibitors of the proliferation of EBV-infected LCLs in vitro, with 13-cis-retinoic acid (RA), all-trans-RA, and 9-cis-RA being the most effective compounds. Of note, retinoid-induced growth arrest in vitro appears irreversible at drug concentrations (10-^-6 mol/L) which may be reached in man after oral systemic therapy. The antiproliferative activity exerted by retinoids on LCLs is a generalized phenomenon usually associated with a progressive accumulation in G₀/G₁ phases of treated cells. The strong upregulation of p27^Kipl invariably observed in cells exposed to retinoids may contribute to the decreased number of cycling cells, probably by inhibiting the transition from the G₁ to S phase. Moreover, we obtained evidence indicating that the antiproliferative effects of retinoids are not dependent on the induction of terminal differentiation of EBV-immortalized B lymphocytes. In fact, the modifications induced by retinoids relative to LCL morphology, phenotype (downregulation of CD19, HLA-DR, and s-Ig, and upregulation of CD38 and c-Ig), and IgM production were highly variable among the lines tested and often only slightly relevant. Finally, the antiproliferative activity exerted by retinoids on LCLs is not mediated by a direct modulation of viral latent antigens, since EBNA-2 and LMP-1 downregulation was a late event detected only in some cell lines. These results indicate that retinoids may be useful in the medical treatment of EBV-related lymphoproliferative disorders of immunosuppressed patients, particularly in the earlier phases of these diseases.     

Successful treatment with lamivudine for fulminant reactivated hepatitis B infection following intensive therapy for high-grade non-Hodgkin's lymphoma

Chronic carriers of Hepatitis B virus (HBV) infection, who are treated for malignant lymphoma, are at high risk of mortality from reactivated HBV infection. We report a case of a 29-year-old male chronic HBV carrier who developed fulminant reactivated HBV infection following intensive chemotherapy for stage IV^B large cell B-cell non-Hodgkin's lymphoma associated with extensive central nervous system and bone marrow involvement. Prior to chemotherapy the patient had normal liver function tests and was negative for HBV DNA by semi-quantitative PCR assay. Fulminant HBV reactivation was confirmed following clinical deterioration, massive rises in hepatic transaminases (peak alanine aminotransferase = 2,850 U/l), liver biopsy and rising levels of serum HBV DNA. Following treatment with lamivudine 150 mg bd for 18 weeks dramatic and sustained recovery ensued. Symptoms and liver function tests improved within days and HBV DNA became negative within 12 weeks. Our patient later died from relapsed lymphoma but without evidence of reactivated HBV infection. We advise that lamivudine should be considered during intensive chemotherapy treatment of chronic carriers of HBV.     

EB病毒VCA-IgA抗体水平与鼻咽癌病人远期疗效关系

目的：分析ＥＢ病毒血清学ＶＣＡ－ＩｇＡ抗体与鼻咽癌病人远期疗效关系，为临床治疗提供参考依据。方法：１９８５年本院病理确诊的５２２例鼻咽癌病人，按治疗前、后ＶＣＡ－ＩｇＡ抗体滴度分为三组：低滴度组（１：５～１：２０）、中滴度组（１：４０～１：８０）和高滴度组（１：１６０以上），随访１０年，比较生存率的异同。结果：治疗前鼻咽癌病人高滴度组１０年生存率低于低滴度组（Ｐ＜０．０５），但和中滴度组差别无显著性（Ｐ＞０．０５）。治疗后三组病人１０年生存率比较，高、中滴度二组差别无显著性（Ｐ＞０．０５），但低于低滴度组。结论：ＥＢ病毒ＶＣＡ－ＩｇＡ抗体水平可以作为估计预后的重要参考依据，与远期疗效有密切关系。     

青年人与老年人原发性肝癌的临床分析

为提高青年人和老年人原发性肝癌临床诊断和防治水平，作者比较５５例青年人与７８例老年人原发性肝癌的临床病理特征，结果显示：血清ＨＢｓＡｇ阳性者青年组高于老年组；合并肝硬化者老年组较高；两组肿瘤类型和临床ＴＮＭ分期等亦有差异。两组原发性肝癌患者在某些临床特征方面存在差异。     

THE INTRACELLULAR FORM OF EPSTEIN-BARR VIRUS GENOME IN NASOPHARYNGEAL CARCINOMA

ＴＨＥＩＮＴＲＡＣＥＬＬＵＬＡＲＦＯＲＭＯＦＥＰＳＴＥＩＮＢＡＲＲＶＩＲＵＳＧＥＮＯＭＥＩＮＮＡＳＯＰＨＡＲＹＮＧＥＡＬＣＡＲＣＩＮＯＭＡＷａｎｇＨｕｉｍｉｎ１汪慧民ＣｈｅｎＪｕｎ１陈军ＺｅｎｇＭｕｓｈｅｎｇ１曾木圣ＬｉＭａｎｚｈｉ１李满枝Ｊｉａ...     

利用分子生物学方法检测鼻咽癌颈部转移性淋巴结中EB病毒基因研究(二)

目的利用分子生物学方法聚合酶链反应技术（ＰＣＲ）和Ｓｏｕｔｈｅｒｎ印迹杂交（ＳＢＨ）为隐性鼻咽癌和原发灶不明的颈部转移癌提供诊断和鉴别诊断的参考依据。材料与方法利用ＰＣＲ基因扩增技术和Ｓｏｕｔｈｅｒｎ印迹杂交检测经针吸活检取材或活检取材的２０例鼻咽癌（ＮａｓｏｐｈａｒｙｎｇｅａｌＣａｒｃｉｎｏｍａ，ＮＰＣ）（实验组）３３份标本和２６例非鼻咽癌（对照组）２７份标本中ＥＢ病毒（Ｅｐｓｔｅｉｎ－Ｂａｒｒｖｉｒｕｓ，ＥＢＶ）。结果在ＮＰＣ组中ＥＢＶ基因检测，１７／２０例是阳性，１８份针吸活检取材标本中１３／１８呈阳性；对照组中仅３／２０例ＥＢＶ检测呈阳性，其中２例为霍奇金病，１例鼻咽腺样增殖体。结论ＥＢ病毒基因检测结果再次显示本研究能准确地为隐性鼻咽癌提供诊断和鉴别诊断的参考依据，而且针吸活检取材较石腊切片取材更省时，痛苦小而经济。应强调的是分析ＥＢＶ检测结果应与病理，临床检查相结合     

输血传播病毒在不同人群中的感染状况及致病性分析

目的探讨TTV在不同人群中的感染状况及其致病性。方法对454例人员,采用微板核酸杂交ELISA法检测TTV;血清酶测定ALT、AST和TBILI。结果454例标本中TTV阳性检出率为5.95%(27/454)。其中在肝病组检出率为3.92%(6/153),分别为肝硬化7.69%(1/13),肝癌0%(0/16),重症慢性乙肝0%(0/22),急性黄疸型乙肝11.11%(1/9),未分型急性黄疸型肝炎0%(0/2),乙肝病毒携带者4.40%(4/91)。在非肝病组检出率为6.89%(21/301),分别为新生儿高胆红素血症0%(0/25),恶性肿瘤9.76%(4/41),献血员11.0%(11/100),体检人员4.44%(6/135)。献血员和体检人员与各种疾病患者的感染率无明显差异(P>0.05);TTV感染者与未感染者的肝功能状况无明显差异(P>0.05);在肝炎患者中,感染TTV者和未感染TTV者的肝功能状况无明显差异(P>0.05)。结论在一般人群和献血员中TTV感染呈“无症状”的“携带状态”,在多种疾病患者中TTV感染无明显加重病情的作用。