乙型肝炎病毒丹氏颗粒抗原在慢性乙型肝炎病毒检测中应用的研究

目的分析乙肝病毒五项检测方法和乙肝病毒丹氏颗粒抗原检测试剂在检测慢性乙型肝炎感染中的一致性,探讨丹氏颗粒抗原检测试剂在检测慢性乙肝感染的经济性和可靠性。方法ELISA方法检测134例慢性乙肝患者的血清标志物和丹氏颗粒抗原,荧光定量PCR方法检测HBV DNA。比较各组丹氏颗粒抗原水平及HBVDNA定量水平和乙肝五项的相互关系。结果慢性乙肝患者HBsAg、HBeAg、HBcAb阳性组、HBsAg、HBcAb阳性组、HBsAg、HBeAb、HBcAb阳性组和HBsAb、HBeAb、HBcAb阳性组丹氏颗粒抗原阳性率分别为100.0(、100.0(、94.3(和0。结论丹氏颗粒抗原试剂在检测慢性乙肝感染中与乙肝五项指标及HBV DNA定量之间具有一致性。丹氏颗粒抗原是一个能较好的反应乙肝病毒复制的指标,对乙肝的诊断、预后及抗病毒疗效观察有较好的实用价值。     

Long-term clinical impact of occult hepatitis B virus infection in chronic hepatitis B patients

BACKGROUND/AIMS: Long-term clinical outcomes of occult hepatitis B virus (HBV) infection were studied. METHODS: Fifteen chronic hepatitis B patients were monitored for a median of 4.4 years (range 0.9-15.3) after hepatitis B surface antigen (HBsAg) seroclearance. Serum HBV DNA was measured by real-time detection polymerase chain reaction. Thirteen patients underwent liver biopsies at the end of follow-up and liver histology was evaluated by Ishak score. Liver HBV DNA was also measured for 12 patients. RESULTS: At the end of follow-up, HBV viremia was absent in 13 (87%) patients, and antibody titers to hepatitis B core antigen showed an inverse correlation with time from HBsAg seroclearance (r=-0.554; P=0.0040). However, all patients retained liver HBV DNA and tested positive for the covalently closed circular HBV DNA replicative intermediate. The hepatic HBV DNA loads had no relation to liver histology. Paired biopsies from 11 patients disclosed that each necroinflammatory score significantly improved after HBsAg seroclearance. Amelioration of liver fibrosis was also evident in eight (73%) patients (P=0.0391 by signed rank test). CONCLUSIONS: A long-standing but strongly suppressed HBV infection may confer histological amelioration after HBsAg seroclearance.     

Principles in the management of chronic hepatitis B viral infection.

Recently licensed and promising new experimental agents should have a profound impact on the treatment of patients with chronic hepatitis B virus (HBV) infection. However, certain management principles should remain unaltered. Recognizing the need for more urgent treatment in some individuals, being able to identify which patients require treatment and those who are most likely to respond to treatment, and selecting the optimal timing for treatment are clinical decisions that must continue to be addressed regardless of the antiviral agent 'of the month'. This review outlines general principles and provides a generic, timeless approach to the management of patients with chronic HBV infection.     

The management of chronic hepatitis B infection

Chronic hepatitis B infection is frequently diagnosed within the genitourinary clinic setting with sexual transmission the commonest route of acquisition in the United Kingdom. Only 3--5% of adults who contract acute hepatitis B will progress to chronic infection, and these individuals can be identified by the presence of hepatitis B surface antigen (HBsAg) in the bloodstream 6 months after infection. Individuals at highest risk of long-term complications such as cirrhosis and hepatocellular carcinoma, carry HBeAg and have high levels of circulating hepatitis B virus (HBV) deoxyribonucleic acid (DNA). Therapy should be targeted towards this group of patients. Two forms of therapy are now licensed for use in chronic hepatitis B infection: interferon-alpha and lamivudine. Seroconversion occurs in 30--40% of patients treated with interferon and treatment is often limited by toxicity. Lamivudine is well tolerated with seroconversion rates of 15--20% at one year, rising with increasing duration of therapy. Long-term monotherapy is limited however by the development of resistance mutations and combination nucleoside therapy is likely to become the treatment of choice in the future. Patients with chronic hepatitis B should be counselled regarding transmission, partner vaccination and alcohol intake and co-infection with other hepatitis viruses should be excluded.     

Effects of prednisolone/azathioprine in chronic hepatitis B viral infection.

Changes in markers of hepatitis B viral replication and standard liver function tests were studied in 30 patients with HBsAg positive chronic liver disease starting or stopping prednisolone/azathioprine therapy, and compared with those occurring in 15 patients who did not receive therapy. On stopping prednisolone/azathioprine, 10 out of 11 HBeAg positive patients and one out of three patients negative for HBeAg and anti-HBe, lost HBV-DNA polymerase activity (p less than 0.01), five lost HBeAg, three developed anti-HBe and HBsAg concentration decreased (p less than 0.01). Only one out of seven untreated HBeAg positive patients lost HBeAg and there were no significant changes in DNA polymerase activity. In the anti-HBe positive patients, 14 starting therapy and eight untreated, there were no significant changes in the markers of viral replication - although two patients developed DNA polymerase activity on high maintenance doses of prednisolone - but a significant decrease (p less than 0.05) in aspartate transaminase in the treated group. It is concluded that the cessation of prednisolone/azathioprine therapy in HBeAg positive patients will result in a reduction in viral replication. In anti-HBe positive patients such therapy may be beneficial.     

慢性乙型肝炎病毒感染孕妇及其婴幼儿随访管理研究*

目的 探讨针对慢性乙型肝炎病毒感染孕妇及其婴幼儿进行规范、科学、合理的随访管理模式。方法 2012年9月~2017年9月我科门诊或住院的乙型肝炎病毒感染孕妇1103例及其婴幼儿456名,成立乙型肝炎母婴传播阻断随访管理专家团队,开设乙型肝炎母婴传播阻断指导专家门诊,通过发放自制的乙型肝炎防治知识认知调查表和健康知识需求调查表进行调查。结果 32.28%孕妇可以接受母乳喂养,44.33%孕妇认为可以考虑自然分娩,多数人认为采取刨宫产可以减少乙型肝炎病毒母婴传播;41.89%孕妇认为孕期使用抗病毒药物是安全的,但也有担心抗病毒药物会对婴儿远期的生长发育产生不良影响;在1103例孕妇中,干预前对乙型肝炎知识和母婴传播阻断知识知晓率分别为59.11%和47.69%,依从性为77.61%,经采取一系列的干预措施,分别被提高到83.86%、79.69%和93.20%（P<0.05）,满意度为89.66%;在456名全程参与乙型肝炎母婴传播阻断随访管理的婴幼儿中,2例（0.44%）婴儿在6月时血清HBsAg阳性,提示母婴传播阻断成功率为99.56%（454/456）。结论 建立规范、科学、合理、人文和全程全面的随访管理体系,可以提高乙型肝炎母婴传播阻断成功率,以努力实现乙型肝炎病毒母婴“零”传播。     

Prevention of hepatocellular carcinoma in chronic viral hepatitis B and C infection

Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality worldwide,with the majority of cases associated with persistent infection from hepatitis B virus(HBV)or hepatitis C virus(HCV).Natural history studies have identified risk factors associated with HCC development among chronic HBV and HCV infection.High-risk infected individuals can now be identified by the usage of risk predictive scores.Vaccination plays a central role in the prevention of HBV-related HCC.Treatment of chronic HBV infection,especially by nucleoside analogue therapy,could also reduce the risk of HBV-related HCC.Concerning HCV infection,besides the advocation of universal precautions to reduce the rate of infection,pegylated interferon and ribavirin could also reduce the risk of HCV-related HCC among those achieving a sustained virologic response.Recently there has been mounting evidence on the role of chemopreventive agents in reducing HBV-and HCV-related HCC.The continued advances in the understanding of the molecular pathogenesis of HCC would hold promise in preventing this highly lethal cancer.     

HLA-A, B, C and DR antigens in chronic hepatitis B viral infection

To study the role of genetic factors in hepatitis B virus (HBV)-related liver diseases, HLA typing with 47 specificities of HLA-A, B, C and DR loci using Terasaki's 2-stage microlymphocytotoxicity method was performed in 253 normal subjects and 305 patients with various HBV-related liver diseases, including 95 healthy carries of HBV, 30 with chronic persistent hepatitis (CPH), 74 with chronic active hepatitis (CAH), 51 with liver cirrhosis and 55 with hepatocellular carcinoma (HCC). The frequency of HLA-B17 was significantly higher in patients with HCC than in healthy carriers (27.3% vs 4.2%, Pc less than 0.01). A similar situation was noted for HLA-DR3 in a comparison of patients with CAH and healthy carriers (37% vs 10%, Pc less than 0.05). Comparisons among various groups involving other specificities were statistically nonsignificant. It is concluded that genetic predisposition to the development of CAH, as well as HCC is present in HBsAg carriers, and further clarification of underlying mechanisms is needed.     

Anti-pre-S responses and viral clearance in chronic hepatitis B virus infection.

Serial sera were collected prospectively during the clinical course of 13 HBsAg carriers with chronic liver disease and analyzed for ALT levels, pre-S1 and pre-S2 antigens and corresponding antibodies and other serological hepatitis B virus markers. In five patients, anti-pre-S1 and anti-pre-S2 antibodies became detectable in multiple serum samples, whereas in eight patients anti-pre-S was never detected or only appeared transiently during the follow-up. The first pattern was associated with normalization of ALT levels and undetectable pre-S antigens and viral DNA by the polymerase chain reaction assay at final follow-up. HBsAg clearance occurred in two of the five patients. The second pattern was one of persistence of HBsAg and pre-S antigens, associated with the presence of serum HBV DNA detectable by spot hybridization or polymerase chain reaction regardless of clinical outcome. These findings demonstrate the occurrence of anti-pre-S antibodies in chronic hepatitis B virus-induced liver disease and associate anti-pre-S appearance with the clearance of hepatitis B virus from serum.     

The pancreatic lesions in chronic viral hepatitis B]

Sings of pancreas damage among 206 patients with chronic hepatitis B (CHB) appears in 45.1%: hyperamylasemia--in 18.9% patients, ultrasonography (USG) sings of pancreatic disorders--in 44.2%. Some parallelism was revealed between increasing of frequency and degree of pancreas damage and rising of CHB activity and viremia intensity. Pancreas USG can early revealed the symptoms of pancreas damage. Among all USG pancreas parameters in CHB changes of pancreas sound thickness appears more frequency, pancreas contours, sizes and structure changed more rarely.     

Hepatocellular carcinoma in noncirrhotic young adult patients with chronic hepatitis B viral infection

Background The aims of this study were to define the clinical characteristics of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in young adult patients without cirrhosis and to evaluate the efficacy of interferon (IFN) therapy on HCC recurrence.Methods Of 187 patients with HBV-related HCC treated at our hospital, 4 had no liver cirrhosis and were less than 30 years of age (10, 22, 23, and 26 years).Results At the time of diagnosis of HCC, all cases had antibody to hepatitis B e antigen (anti-HBe) and histological staging of nontumorous liver was F0 or F1, i.e., low-grade hepatitis. The mothers of all 4 young adult patients with HCC had HBV-related liver disease. Three cases developed recurrence of HCC. In these patients, long-term intermittent IFN therapy after reresection of HCC resulted in long-term survival without recurrence for more than 3 years of follow-up.Conclusions (1) Young adult patients with HCC are positive for anti-HBe, lack cirrhosis, and the route of infection seems to be mother-to-infant transmission. Transplacental transmission of HBV and HBV DNA integration into the cellular genomic DNA during fetal life is a possible explanation of HBV-related hepatocarcinogenesis in young adults; and (2) long-term IFN therapy seems to be useful for prevention of tumor recurrence after radical operation for HBV-related HCC.     

Permanent HBsAg clearance in chronic hepatitis B viral infection following acute delta superinfection

Three patients are described with chronic hepatitis B virus infection for three to six years before hepatitis delta virus superinfection occurred. Liver biopsy performed in two patients prior to their delta illness revealed chronic persistent hepatitis and chronic active hepatitis, respectively. Within one to seven months of the acute delta event, all three patients lost their circulating hepatitis B surface antigen. Subsequently, delta antibody also cleared. Clinical well-being and normal transaminases were documented over 10-44 months of follow-up. Although most cases of delta infection in chronic hepatitis B result in severe or progressive disease, a small number of patients may develop clearance of the HBsAg with clearance of both B and delta infections.     

慢性乙型肝炎病毒感染的疾病进展:病毒持续复制的作用

目前全球大约有3.5亿人感染乙型肝炎病毒(HBV),绝大多数感染者在中国.据估计,大约有1.12亿中国人慢性感染HBV[1],约占全世界感染者的33%.     

厦门市乙型肝炎病毒亚基因型分布的初步研究

目的探讨厦门地区乙型肝炎患者血清乙型肝炎病毒（HBV）基因型的分布情况。方法应用混合性型特异性引物聚合酶链反应法结合琼脂糖电泳，根据PCR产物片段大小直接判定HBV基因型；应用PCR扩增全S基因序列-DNA测序-生物信息学分析方法确定部分样本的亚基因型，并探讨前前S区编码的流行情况。结果在217例可以通过混合性型特异性引物聚合酶链反应法确定基因型的感染者中，B型83例（38．2％）、C型71例（32．7％），B／C混合型63例（29．0％）。HBeAg阳性患者中感染B基因型占50％，B／C型混合感染占22％；抗-HBe阳性患者中B／C型混合感染36％，B型38％；在慢性乙型肝炎患者中，以B基因型多见（46％），在肝硬化和肝癌患者中，以C（41％和42％）或B／C混合基因型（38％和33％）感染为主；20例患者血清经过DNA测序-生物信息学分析方法确定了亚基因型，其中B2亚型2例，C2亚型18例，其中混合性型特异性引物聚合酶链反应判断为B型的4例经过测序分析为C2亚型。B2亚型不编码前前S区，18例C2亚型均编码前前S区。结论本研究提示厦门地区乙型肝炎患者群的HBV基因型B、C型的感染率大致相同，亚基因型分析提示C2亚基因型占90％，可能是B／C基因型重组的结果。C2亚基因型病毒株均编码前前S区，提示前前S区的编码可能具有亚基因型特异性。     

Current treatment and future directions in the management of chronic hepatitis B viral infection

The World Health Organization places hepatitis B virus (HBV) in the top 10 causes of death worldwide. It is estimated that there are over 400 million carriers of HBV as well. At least 20% to 30% of hepatitis B surface antigen (HBsAg) carriers will die of complications of chronic liver disease, including cirrhosis and liver cancer. The serious consequences of end-stage liver disease and liver cancer occur in 30% of chronic carriers and confront patients and physicians throughout the world. Vaccination is the major form of treatment (prevention) that may eventually eliminate HBV worldwide. This article discusses the currently available treatments as well as evolving treatments for chronic HBV infection.