对拉米夫定耐药的慢性乙型肝炎病人治疗研究现状

核苷类似物拉米夫定于1998年在我国上市，为乙型肝炎的抗病毒治疗带来了新的希望。然而持续的拉米夫定治疗会使病人产生耐药从而导致严重后果。本文对这部分病人的抗病毒治疗进展进行综述。     

急性重症肝炎患者发生肝性脑病危险因素多元Logistic回归研究

目的探索急性重症肝炎患者发生肝性脑病的危险因素，以便进行早期干预。方法收集血浆凝血酶原时间（PT）延长，活动度〈40％的急性重症肝炎患者69例，对69例患者的年龄、性别和基础疾病等临床背景资料和总胆红素、直接胆红素、谷草转氨酶（AST）、谷丙转氨酶（ALT）、血浆白蛋白、胆碱脂酶、血浆凝血酶原时间（PT）、白细胞计数（WBC）、血小板计数（Plt）等实验室检查数据进行单因素分析和多元Logistic回归分析。结果单因素分析和多元Logistic回归分析均提示年龄、血胆红素水平和血浆凝血酶原时间在肝性脑病组和非肝性脑病组之间有统计学差异。结论约30％的急性重症肝炎患者发展成为肝性脑病。高龄、血浆凝血酶原时间延长、活动度下降、高血浆总胆红素等是急性重症肝炎患者发展成为肝性脑病的潜在危险因素。     

Synthesis of a new carrier for immunization: polytuftsin

Sequential poly(Arg-Thr-Lys-Pro) consisting mainly of the repeat of tuftsin Thr-Lys-Pro-Arg was synthesized by condensing the p-nitrophenyl ester of Arg(HCI)-Thr-Lys-(2-CI-Z)-Pro in the presence of HOBt . Two haptenic sequences of the Pre-S region of hepatitis B virus antigen (10–26 and 39–55) were prepared by solid phase and coupled to polytuftsin via glutaraldehyde. The peptides, either free or coupled to polytuftsin, were administrated to mice and the antisera were assayed by ELISA . Coupling the peptides to the polypeptide significantly improved the anti-peptide antibody titer in Freund complete adjuvant or in NaCI 0.9%. Cross-reaction between antibodies induced by the peptides and the native protein was also improved. Polytuftsin alone is very poorly immunogenic.     

Hepatitis B virus genetic diversity and its impact on diagnostic assays

Summary.  Hepatitis B virus (HBV) circulates in blood as closely related, but genetically diverse molecules called quasispecies. During replication, HBV production may approach 10¹¹ molecules/day, although during peak activity this rate may increase 100–1000 times. Generally, DNA polymerases have excellent fidelity in reading DNA templates because they are associated with an exonuclease which removes incorrectly added nucleotides. However, the HBV-DNA polymerase lacks fidelity and proofreading function partly because exonuclease activity is either absent or deficient. Thus, the HBV genome and especially the envelope gene, is mutated with unusually high frequency. These mutations can affect more than one open reading frame because of overlapping genes. The S gene contains an exposed major hydrophilic region (residues 110–155), which encompasses the 'a' determinant that is important for inducing immunity. Nucleotide substitutions in this region are common and result in reduced binding or failure to detect hepatitis B surface antigen (HBsAg) in diagnostic assays. Adaptive immunity also depends on the recognition of HBsAg by specific antibody and variants pose a threat if they interfere with binding to antibody. Finally, genomic hypervariability allows HBV to escape selection pressures imposed by antiviral therapies, vaccines and the host immune system, and is responsible for creating genotypes, subgenotypes and subtypes.     

肝病治疗仪治疗高原慢性乙型肝炎患者的临床观察

目的观察WGLY-801型电脑肝病治疗仪对慢性乙型肝炎的治疗效果。方法随机选取慢性乙型肝炎患者144例,分为治疗组66例,在常规治疗基础上加用肝病治疗仪;对照组78例,采用常规治疗,观察两组治疗效果。治疗三疗程共45天(每疗程15天),观察临床症状、肝功能的动态变化,并对最终效果进行评价。结果经治疗后,两组患者临床症状、肝功能较前均有好转,但治疗组起效快,疗程明显缩短,疗效好,差异有明显统计学意义(p<0.05)。结论肝病治疗仪,操作简单,疗效确切,值得进一步推广应用。     

A case of acute hepatitis E associated with multidrug hypersensitivity and cytomegalovirus reactivation

A 65-year-old Japanese man was hospitalized because of acute hepatitis and severe cholestasis due to hepatitis E virus (HEV) infection combined with a drug reaction to a cold preparation. He died of disseminated intravascular coagulation and severe intestinal bleeding due to systemic cytomegalovirus reactivation following the development of severe eruptions with marked eosinophilia due to drug hypersensitivity to taurine and ursodeoxycholate preparations. The close interaction between viral infection or reactivation and drug hypersensitivity was considered as a pathophysiology in this case, which emphasizes the need for further study of the immunological mechanism of the interaction.     

The comparative evaluation of cellular localization of viral antigens with microscopic changes in the ileum of cattle infected with bovine viral diarrhea

The correlation between microscopic changes with cellular localization of viral antigens was studied in the ileum of 16 cases infected with bovine viral diarrhea virus (BVDV). Microscopic lesions in the ileum included multifocal erosive and ulcerative ileitis, severe congestion and hemorrhage, crypt dilation and mucus engorgement, epithelial debris and leukocytes, lymphoid depletion of Peyer’s patches, herniation of mucosal epithelium into depleted Peyer’s patches, and fibrinoid vasculitis of submucosal vessels. BVDV antigen was detected by immunohistochemistry in macrophages, dendritic cells, smooth muscle cells, endothelial cells, epithelial cells of crypts, and mucosal epithelium, together with other mononuclear cells including lymphocytes, plasma cells, fibroblasts, and intramural ganglial cells. No consistent correlation between the presence of BVDV antigen and vascular lesions in the ileum was identified. The intensity and distribution of the immunoperoxidase stain in the ileum was graded as highly positive (18.7%), moderately positive (56.3%), and mildly positive (25%). In conclusion, the pattern and density of distribution and localization of BVDV antigen in the ileum was not consistently correlated with the severity of microscopic lesions.     

C4d in Acute Rejection After Liver Transplantation—A Valuable Tool in Differential Diagnosis to Hepatitis C Recurrence

Hepatitis C is the most common indication for liver transplantation. Recurrence of HCV is universal leading to graft failure in up to 40% of all patients. The differentiation between acute rejection and recurrent hepatitis C is crucial as rejection treatments are likely to aggravate HCV recurrence. Histological examination of liver biopsy remains the gold standard for diagnosis of acute rejection but has failed in the past to distinguish between acute rejection and recurrent hepatitis C. We have recently reported that C4d as a marker of the activated complement cascade is detectable in hepatic specimen in acute rejection after liver transplantation. In this study, we investigate whether C4d may serve as a specific marker for differential diagnosis in hepatitis C reinfection cases. Immunohistochemical analysis of 97 patients was performed. A total of 67.7% of patients with acute cellular rejection displayed C4d-positive staining in liver biopsy whereas 11.8% of patients with hepatitis C reinfection tested positive for C4d. In the control group, 6.9% showed C4d positivity. For the first time we were able to clearly demonstrate that humoral components, represented by C4d deposition, play a role in acute cellular rejection after LTX. Consequently C4d may be helpful to distinguish between acute rejection and reinfection after LTX for HCV.     

载氧血红蛋白纯化工艺研究

目的改善心脑血管缺氧载氧药物是一种创新药物。由于它半径比红细胞小400~1 000倍,易于通过毛细血管,给缺血组织及时供氧,迅速缓解或纠正缺氧状态,达到治疗抢救目的。血红蛋白的纯化工艺是载氧药物研制的重要工艺步骤。方法本研究建立了一套通过热敏法分离纯化人脐带血血红蛋白的工艺以及较为完善的纯化血红蛋白质量检测指标。结果与现有的纯化方式相比,热敏法操作简便,仪器设备造价低廉,纯化与病毒灭活同时进行,得到的纯化产品损失少,纯度高,各项理化指标达到国际水平。结论本工艺适用于规模制备纯化血红蛋白,为进一步研制治疗心脑血管缺氧载氧药物创造了有利条件。     

江门市区实施乙型肝炎免疫策略16年的效果评价

目的：对江门市区1986年1月1日起全面实施的乙型肝炎(乙肝)免疫策略进行效果评价。方法：运用血清流行病学调查和疫情资料对比分析，比较实施“免疫策略”前后江门市区0～15岁人群乙肝发病率和感染率变化情况和乙肝表面抗体(抗-HBs)增长情况。结果：实施“免疫策略”后16年，0～15人群的乙肝发病率由1985年的367．39／10万，降至2001年的21．10／10万，下降94．26％；HBsAg阳性率由1985年的9．17％降至2002年的0．6％，下降93．46％；乙肝病毒总感染率由1985年的35．82％降至2002年的1．20％，下降96．65％；抗-HBs阳性率由1985年的24．64％上升到2002年的93．00％，上升2．77倍。结论：江门市区现行乙肝免疫策略效果显，能有效预防和控制地区性大面积的乙肝流行与传播。经过一代人的努力，能彻底改变人口乙肝高发病率和HBV高感染率及高携带率的状况。