HBV-RNA,Quantitative HBsAg,Levels of HBV in Peripheral Lymphocytes and HBV Mutation Profiles in Chronic Hepatitis B

A comprehensive characterization of chronic HBV (CHB) patients is required to guide therapeutic decisions. The cumulative impact of classical and novel biomarkers on the clinical categorization of these patients has not been rigorously assessed. We determined plasma HBV-RNA and HBsAg levels, HBV in peripheral lymphocytes (PBMCs) and HBV mutation profiles in CHB patients. Patient demographics (n = 139) and classical HBV biomarkers were determined during a clinical routine. HBV-RNA in plasma and HBV-DNA in PBMCs were determined by RT-PCR. HBsAg levels were determined using Architect. In samples with HBV-DNA viral load >1000 IU/mL, genotype mutations in precore (PC), basal core promoter (BCP), HBsAg and Pol regions were determined by sequencing. Most patients (n = 126) were HBeAg-negative (HBeAgNeg) with significantly lower levels of HBV-RNA, HBV-DNA and HBsAg compared to HBeAg-positive (HBeAgPos) patients (p < 0.05). HBV genotype D prevailed (61/68), and >95% had BCP/PC mutations. Escape mutations were identified in 22.6% (13/63). HBeAgNeg patients with low levels of HBsAg (log IU ≤ 3) were older and were characterized by undetectable plasma HBV-DNA and undetectable HBV-RNA but not undetectable HBV-DNA in PBMCs compared to those with high HBsAg levels. In >50% of the studied HBeAgNeg patients (66/126), the quantitation of HBsAg and HBV-RNA may impact clinical decisions. In conclusion, the combined assessment of classical and novel serum biomarkers, especially in HBeAgNeg patients, which is the largest group of CHB patients in many regions, may assist in clinical decisions. Prospective studies are required to determine the real-time additive clinical advantage of these biomarkers.     

母婴间乙型肝炎与丙型肝炎双重感染的研究

从流行病角度，利用分子生物学技术及免疫学方法，对２１０例产妇血清及新生儿 脐带血清，应用聚合酶链反应（ＰＣＲ）、反转录聚合酶链反应（ＲＴ－ＰＣＲ），检测乙型肝炎病毒（ＨＢＶ） 及丙型肝炎病毒（ＨＣＶ）标志物，其结果为：ＨＢｓＡｇ阳性产妇的新生儿阳性率为６５．５％，ＨＢｅＡｇ阳 性产妇的新生儿阳性率为８１．８％，抗－ＨＣＶ阳性产妇的新生儿阳性率为７５．０％，ＨＢＶ－ＤＮＡ及 ＨＣＶ－ＲＮＡ双重阳性产妇的新生儿阳性率为１００．０％，说明母婴间存在乙型肝炎（ＨＢ）、丙型肝炎 （ＨＣ）及双重感染，其垂直传播可发生于宫内及围产期，是婴幼儿患病毒性肝炎的主要感染途径。 由于乙型肝炎及丙型肝炎的临床表现无特异性，不能从临床症状和体征中得以诊断，所以建立敏 感、特异的实验检测方法，为临床提供早期诊断依据，建立围产期保健制度，分娩过程中对婴儿加 强保护，阻断传播途径，是目前可行的有效措施。控制和降低病毒性肝炎的母婴间传播，有利优生 优育，提高人口素质的基本国策。”     

Viral and immune factors associated with successful treatment withdrawal in HBeAg-negative chronic hepatitis B patients

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Drug Discovery Study Aimed at a Functional Cure for HBV

Hepatitis B virus (HBV) causes acute and, most importantly, chronic hepatitis B worldwide. Antiviral treatments have been developed to reduce viral loads but few patients with chronic hepatitis B (CHB) achieve a functional cure. The development of new therapeutic agents is desirable. Recently, many novel agents have been developed, including drugs targeting HBV-DNA and HBV-RNA. This review provides an overview of the developmental status of these drugs, especially direct acting antiviral agents (DAAs). Serological biomarkers of HBV infection are essential for predicting the clinical course of CHB. It is also important to determine the amount and activity of covalently closed circular DNA (cccDNA) in the nuclei of infected hepatocytes. Hepatitis B core-associated antigen (HBcrAg) is a new HBV marker that has an important role in reflecting cccDNA in CHB, because it is associated with hepatic cccDNA, as well as serum HBV DNA. The highly sensitive HBcrAg (iTACT-HBcrAg) assay could be a very sensitive HBV activation marker and an alternative to HBV DNA testing for monitoring reactivation. Many of the drugs currently in clinical trials have shown efficacy in reducing hepatitis B surface antigen (HBsAg) levels. Combination therapies with DAAs and boost immune response are also under development; finding the best combinations will be important for therapeutic development.