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Vaccine therapies for chronic hepatitis B: can we go further?

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《医学前沿（英文）》 2014年 第8卷 第1期   页码 17-23 doi: 10.1007/s11684-014-0313-7

摘要：

Chronic hepatitis B is a major health burden worldwide. In addition to the recent progress in antiviral treatment, therapeutic vaccination is a promising new strategy for the control of chronic hepatitis B. On the basis of the major specific and non-specific immune dysregulations and defects in chronic hepatitis B patients, this paper presents the peptide and protein-based, DNA-based, cell-based, and antigen-antibody-based therapeutic vaccines, which have undergone clinical trials. The advantages, disadvantages, and future perspectives for these therapeutic vaccines are discussed.

关键词： chronic hepatitis B     therapeutic     antigen-antibody complexes     DNA     vaccine    

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Chronic hepatitis B virus infection: epidemiology, prevention, and treatment in China

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《医学前沿（英文）》 2014年 第8卷 第2期   页码 135-144 doi: 10.1007/s11684-014-0331-5

摘要：

Chronic hepatitis B is a major health problem in China. The universal vaccination program since 1992 has changed the epidemiology of hepatitis B virus infection in China from highly to moderately endemic. The most prevalent hepatitis B virus strains in China are genotypes B and C, whereas those in western provinces are genotypes D and C/D hybrid. Chronic hepatitis B poses a heavy burden to the society in China. Different treatment strategies have been explored to improve patient outcomes in a cost-effective manner. However, antiviral drugs with a low genetic barrier to resistance are still extensively used because of the generally low income and limited resources in China. Individualized antiviral therapy is closely associated with translational medicine, which utilizes information from studies on genomics, immune biomarkers, and fibrosis. The results of these studies are crucial in further improving treatment outcomes.

关键词： chronic hepatitis B     epidemiology     prevention     treatment    

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Correlation between viral load and liver cirrhosis in chronic hepatitis B patients

Lili LIU MM , Jiyao WANG MD , Weimin SHE MM ,

《医学前沿（英文）》 2009年 第3卷 第3期   页码 271-276 doi: 10.1007/s11684-009-0054-1

摘要： The aim of this paper is to investigate the relationship between hepatitis B virus (HBV) DNA levels during the course and the progression to cirrhosis with chronic hepatitis B. A total of 239 chronic hepatitis B patients confirmed by liver biopsy between 2001 and 2007 were followed up for a median of 28 months. Compared with the patients without cirrhosis, the patients progressed to cirrhosis were older and with higher HBV-DNA levels at end point. However, there was no significant difference in cirrhosis progression between different HBV-DNA groups at baseline ( = 0.531). Kaplan-Meier analysis showed higher HBV-DNA level at endpoint had increasing risk of cirrhosis ( = 0.019). The results of Cox model indicated that HBV-DNA levels at endpoint, stage of fibrosis, negative hepatitis B e antigen, and γ-glutamyl transpeptidase at baseline were independent risk factors of cirrhosis. The relative risk ratios were 1.898, 1.918, 8.976, and 1.006, respectively. Progression to cirrhosis in chronic hepatitis B patients is correlated with HBV-DNA levels during follow-up.

关键词： hepatitis B     chronic     viral load     liver cirrhosis    

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Clinical characteristics and risk factors of COVID-19 patients with chronic hepatitis B: a multi-center

《医学前沿（英文）》 2022年 第16卷 第1期   页码 111-125 doi: 10.1007/s11684-021-0854-5

摘要： The coronavirus disease 2019 (COVID-19) has spread globally. Although mixed liver impairment has been reported in COVID-19 patients, the association of liver injury caused by specific subtype especially chronic hepatitis B (CHB) with COVID-19 has not been elucidated. In this multi-center, retrospective, and observational cohort study, 109 CHB and 327 non-CHB patients with COVID-19 were propensity score matched at an approximate ratio of 3:1 on the basis of age, sex, and comorbidities. Demographic characteristics, laboratory examinations, disease severity, and clinical outcomes were compared. Furthermore, univariable and multivariable logistic and Cox regression models were used to explore the risk factors for disease severity and mortality, respectively. A higher proportion of CHB patients (30 of 109 (27.52%)) developed into severe status than non-CHB patients (17 of 327 (5.20%)). In addition to previously reported liver impairment markers, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin, we identified several novel risk factors including elevated lactate dehydrogenase (≥245 U/L, hazard ratio (HR) = 8.639, 95% confidence interval (CI) = 2.528–29.523; P <0.001) and coagulation-related biomarker D-dimer (≥0.5 μg/mL, HR= 4.321, 95% CI= 1.443–12.939; P = 0.009) and decreased albumin (<35 g/L, HR= 0.131, 95% CI= 0.048–0.361; P <0.001) and albumin/globulin ratio (<1.5, HR= 0.123, 95% CI= 0.017–0.918; P = 0.041). In conclusion, COVID-19 patients with CHB were more likely to develop into severe illness and die. The risk factors that we identified may be helpful for early clinical surveillance of critical progression.

关键词： COVID-19     chronic hepatitis B     liver injury     coagulation dysfunction    

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New perspective on the natural course of chronic HBV infection

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《医学前沿（英文）》 2014年 第8卷 第2期   页码 129-134 doi: 10.1007/s11684-014-0339-x

摘要：

Chronic hepatitis B virus (HBV) infection is a significant threat to public health and an enormous burden on society. Mechanisms responsible for chronic HBV infection remain poorly understood. A better understanding of the natural course of chronic HBV infection may shed new light on the mechanisms underlying this disease and help in designing new antiviral strategies. Natural course of chronic HBV infection is conventionally viewed as an uninterrupted process that is usually marked by HBV e antigen (HBeAg) seroconversion or characterized by different phases associated with assumed host responses to HBV infection. However, none of these descriptions captures or highlights the core events that determine the natural course of chronic HBV infection. In this review, we briefly present the current knowledge on this subject and explain the significance and implication of events that occur during infection. A pre-core mutant becomes predominant in the viral population following elimination of the wild-type virus in duck hepatitis B virus-chronically infected animals. The coupled events in which first there is viral clearance that clears wild-type virus and then there is the reinfection of wild-type virus cleared livers with mutant virus are highly relevant to understanding of the natural course of chronic HBV infection under both treated and untreated conditions. In our new perspective, a general natural course of chronic HBV infection comprises cycles of viral clearance and reinfection, and such cycles prolong the chronic HBV infection course. Reviewing published data on the natural course of chronic HBV infection can reduce the possibility of missing important points in the initial data interpretation.

关键词： hepatitis B virus     chronic HBV infection     natural course     hepatitis B     seroconversion    

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Comprehensive treatment of acute-on-chronic liver failure in a patient with hepatitis B: a case report

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《医学前沿（英文）》 2014年 第8卷 第2期   页码 250-253 doi: 10.1007/s11684-014-0333-3

摘要：

The clinical data of a patient with acute-on-chronic liver failure were analyzed retrospectively. The patient has suffered from hepatitis B for 30 years. His liver function deteriorated, yielding Child-Pugh grade C and reaching a model for end-stage liver disease score of 33 points within a short period; this condition was complicated with highly active variceal bleeding and coagulation system failure (PT > 100 s). The patient also presented hepatocellular carcinoma. Comprehensive treatments included effective inhibition of hepatitis B virus replication and intensive care support. Piggyback orthotopic liver transplantation was performed as the final treatment. The patient recovered uneventfully and was discharged after surgery.

关键词： acute-on-chronic liver failure     submassive necrosis     viral hepatitis B     esophageal variceal bleeding     liver transplantation    

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Potential use of serum HBV RNA in antiviral therapy for chronic hepatitis B in the era of nucleos(t)ide

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《医学前沿（英文）》 2017年 第11卷 第4期   页码 502-508 doi: 10.1007/s11684-017-0590-z

摘要：

Although the efficacy of nucleos(t)ide analogue (NA) has been confirmed for treatment of chronic hepatitis B, long-term therapy has been recommended due to the high frequency of off-therapy viral DNA rebound and disease relapse. In this review, the RNA virion-like particles of hepatitis B virus (HBV) are integrated into the life cycle of HBV replication, and the potential significance of serum HBV RNA is systematically described. The production of HBV RNA virion-like particles should not be blocked by NA; in this regard, serum HBV RNA is found to be a suitable surrogate marker for the activity of intrahepatic covalently closed circular DNA (cccDNA), particularly among patients receiving NA therapy. Therefore, the concept of virological response is redefined as persistent loss of serum HBV DNA and HBV RNA. In contrast to hepatitis B surface antigen (HBsAg) that can originate from either the cccDNA or the integrated HBV DNA fragment, serum HBV RNA, with pregenomic RNA origination, can only be transcribed from cccDNA. Therefore, the loss of serum HBV RNA would likely be a promising predicator for safe drug discontinuation. The clinical status of consistent loss of serum HBV RNA accompanied with low serum HBsAg levels might be implicated as a “para-functional cure,” a status nearly close to the functional cure of chronic hepatitis B, to distinguish the “functional cure” characterized as serum HBsAg loss with or without anti-HBs seroconversion.

关键词： chronic hepatitis B     serum HBV RNA     nucleos(t)ide analogs     virological response     para-functional cure    

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Current hepatitis B treatment guidelines and future research directions

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《医学前沿（英文）》 2014年 第8卷 第2期   页码 145-157 doi: 10.1007/s11684-014-0335-1

摘要：

Hepatitis B virus (HBV) infection causes a tremendous clinical burden across the world with more than half a million people dying annually from HBV related disease. Significant advances have been made in HBV treatment in the past decade and several guidelines have been published by professional societies and expert panels. Although these recommendations have been valuable to help optimize HBV treatment, there is discordance in treatment criteria and many patients infected with HBV may fall outside of these recommendations. This paper systematically reviews the natural history of the disease and compares and contrasts the recommendations for initiation of treatment from the various societies. There is also discussion of special groups that require particular consideration and some of the open research questions and future research directions within the field.

关键词： chronic hepatitis B     HBV treatment guidelines     APASL guidelines     EASL guidelines     AASLD guidelines    

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Advances in newly developing therapy for chronic hepatitis C virus infection

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《医学前沿（英文）》 2014年 第8卷 第2期   页码 166-174 doi: 10.1007/s11684-014-0334-2

摘要：

Chronic hepatitis C virus (HCV) infection afflicts a reported 170 million people worldwide and is often complicated by cirrhosis and hepatocellular carcinoma. Morbidity and mortality are decreased with the successful treatment of chronic HCV infection. Increased understanding of the HCV has allowed further development of new direct-acting antiviral (DAA) agents against the HCV and has also allowed the development of IFN-free oral treatment regimens. In late 2013 the first nucleotide polymerase inhibitor regimen with RBV alone for genotypes 2/3 and in combination with a 12-week regimen of PEG-IFN+RBV for genotypes 1, 4 was approved for use in the US. A number of promising new DAA regimens which are IFN-free are in phase 3 development and the first will likely be approved for use in the US in 2014. The currently approved regimens are discussed in detail and currently available data on future regimens are reviewed herein.

关键词： direct-acting antiviral (DAA)     nucleotide polymerase inhibitors     protease inhibitors    

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MicroRNAs and hepatitis viruses

Gang LI MD , Xiaojia XIONG MM ,

《医学前沿（英文）》 2009年 第3卷 第3期   页码 265-270 doi: 10.1007/s11684-009-0055-0

摘要： MicroRNAs (miRNAs) are a class of small RNA molecules. They play a pivotal role in diverse domains such as infection, tumorigenesis, and immune reaction. As key regulators of most genes’ expression, they react at posttranscriptional level. It is increasingly clear that miRNAs are necessary for physiological and pathological processes. In the past few years, investigators gradually brought the concept of miRNA into studies of viral infection, including hepatitis viruses. The hepatitis B and C viruses are common causes of liver disease worldwide. It is very difficult to cure chronic hepatitis due to drug resistance during antivirus therapy. Elucidating the mechanisms of virus-host interactions in hepatitis B and C is very important in diagnosis, prognosis, and therapy. This article reviews the current knowledge of viral hepatitis (B and C type) at the level of miRNA and tries to outline areas of potential studies.

关键词： microRNA     hepatitis B virus     hepatitis C virus    

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Current advances in the elimination of hepatitis B in China by 2030

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《医学前沿（英文）》 2017年 第11卷 第4期   页码 490-501 doi: 10.1007/s11684-017-0598-4

摘要：

With its 78 million chronic carriers, hepatitis B virus (HBV) infection is still one of the leading public health challenges in China. Over the last two decades, China has made great progress on the prevention of HBV transmission through national vaccination programs. Zero transmission from mother to infant has been proposed as the current goal. Available anti-HBV therapy is efficacious in suppressing HBV replication; however, it fails to completely cure patients with chronic hepatitis B and even requires lifelong treatment. To reduce the costs and improve the efficacy, several trials have been recently conducted in China to optimize the current anti-HBV managements. Novel biomarkers were identified to predict treatment outcomes, and new promising treatment strategies were developed. Reports also indicate that coinfections of HBV with other hepatotropic viruses and human immunodeficiency virus are common in China and cause severe liver diseases, which should be recognized early and treated properly. Work is still needed to eliminate hepatitis B in China by 2030.

关键词： HBV     CHB     biomarker     functional cure     coinfection    

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血清N-聚糖生物标志物诊断ALT水平正常慢性乙型肝炎患者显著肝纤维化和肝硬化的临床意义 Article

王林, 刘艺琪, 顾启馨, 张驰, 徐蕾, 王蕾, 陈翠英, 刘学恩, 赵鸿, 庄辉

《工程（英文）》 2023年 第26卷 第7期   页码 151-158 doi: 10.1016/j.eng.2023.03.008

摘要： 在诊断肝硬化（≥F5）时，血清N-聚糖RF-B模型的AUROC为0.97，与肝组织活检的符合率为88.94%。血清N-聚糖模型（RF-A和RF-B）的诊断效能优于肝硬度值测量（liver stiffness measurement, LSM）、基于4因子的纤维化指数（fibrosis index

关键词： 肝纤维化     慢性乙型肝炎     血清N-聚糖     N-聚糖模型     丙氨酸转移酶    

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Association of novel mutations and heplotypes in the preS region of hepatitis B virus with hepatocellular

Jia-Xin XIE, Jian-Hua YIN, Qi ZHANG, Rui PU, Wen-Ying LU, Hong-Wei ZHANG, Guang-Wen CAO, Jun ZHAO, Hong-Yang WANG,

《医学前沿（英文）》 2010年 第4卷 第4期   页码 419-429 doi: 10.1007/s11684-010-0160-0

摘要： The association of viral mutations and haplotypic carriages with mutations in the preS region of hepatitis B virus (HBV) genotypes B and C with hepatocellular carcinoma (HCC) is of great significance for the prediction of this malignancy, but it remains obscure. We analyzed the preS sequences of HBV genotypes B and C from 1172 HBV-infected subjects including 231 patients with HCC. As compared with the HBV-infected subjects without HCC, C2875T, G2946C, A3054C, C3060A, T3066C, C3116T, A3120C, G3191A, A1C, C7A, C10A, A31C, C76T, G105C, and G147C in both genotypes were significantly associated with increased risks of HCC. C2875A, G2950A, G2951A, A3054T, C3060T, T3066A, T3069G, A3120T, and G3191C were significantly associated with increased risks of HCC in genotype C, whereas these mutations were inversely associated with HCC in genotype B. Multivariate regression analyses showed that C76A/T was a novel factor independently associated with an increased risk of HCC, as compared with those without HCC. The frequencies of haplotypes 2964A-3116T-preS2 start codon wild-type-7C, 2964C-3116T-7A-76C, and 2964A-3116T-7C-76A/T were significantly higher in the patients with HCC (<0.001), whereas a haplotypic carriage with a single mutation and another three wild-types were inversely associated with HCC. Conclusively, the association of HBV mutations in the preS region with HCC depends on HBV genotype and haplotypic carriage with two or more mutations that are each associated with an increased risk of HCC independently.

关键词： hepatitis B virus     hepatocellular carcinoma     mutation     genotype     haplotype    

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Association of miRNA-122-binding site polymorphism at the interleukin-1 α gene and its interaction with hepatitisB virus mutations with hepatocellular carcinoma risk

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《医学前沿（英文）》 2014年 第8卷 第2期   页码 217-226 doi: 10.1007/s11684-014-0326-2

摘要：

This study was designed to investigate the contribution of miRNA-122-binding site polymorphism at the IL-1A gene and its multiplicative interactions with hepatitis B virus (HBV) mutations in the risk of hepatocellular carcinoma (HCC). A total of 1021 healthy controls, 302 HBV surface antigen (HBsAg) seroclearance subjects, and 2011 HBsAg-positive subjects (including 1021 HCC patients) were enrolled in this study. Quantitative PCR was used to genotype rs3783553. HBV mutations were determined by direct sequencing. Multivariate logistic regression analyses were performed to test the associations of rs3783553, mutations, and their interactions with the risk of HCC. No significant association was found between rs3783553 and the risk of HCC among healthy controls, HBsAg seroclearance subjects, HBsAg-positive subjects without HCC, and all controls. Additionally, rs3783553 was not significantly associated with chronic HBV infection, liver cirrhosis, HBV e antigen seroconversion, abnormal alanine aminotransferase, and high viral load (>104 copies/ml). However, the TTCA insertion allele of rs3783553 was significantly associated with an increased frequency of HBV C7A mutation compared with homozygous TTCA deletion carriers [(del/ins+ ins/ins) vs. del/del, adjusted odds ratio (OR)=1.48, 95% confidence interval (CI)=1.09-2.02, P=0.013]. Multiplicative interaction of rs3783553 with HBV preS deletion significantly reduced the risk of HCC in males, with an adjusted OR of 0.64 (95% CI=0.42-0.98; P=0.041) after age and HBV genotype were adjusted. Although rs3783553 did not significantly affect genetic susceptibility to HBV-related HCC, its variant allele may predispose the host to selecting HBV C7A mutation during evolution and significantly reduce the risk of HCC caused by HBV preS deletion. This study provides an insight into the complex host-virus interaction in HBV-induced hepatocarcinogenesis and is helpful in determining HBsAg-positive subjects who are likely to develop HCC.

关键词： hepatocellular carcinoma (HCC)     interaction     miRNA-122-binding site     IL-1A     rs3783553     hepatitis B virus (HBV) mutations    

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Dysregulation of β-catenin by hepatitis B virus X protein in HBV-infected human hepatocellular carcinomas

Lei CHEN, Liang HU, Liang LI, Yuan LIU, Qian-Qian TU, Yan-Xin CHANG, He-Xin YAN, Meng-Chao WU, Hong-Yang WANG,

《医学前沿（英文）》 2010年 第4卷 第4期   页码 399-411 doi: 10.1007/s11684-010-0170-y

摘要： β-catenin is a key molecule involved in both cell-cell adhesion and Wnt signaling pathway. In our study, we found that, in the development of hepatocellular carcinoma (HCC), β-catenin was correlated with hepatitis B virus (HBV) X gene encoded protein, which is essential for HBV infectivity and is a potential cofactor in viral carcinogenesis. The expression levels of wild-type β-catenin and E-cadherin were decreased in HepG2 cells expressing hepatitis B virus X protein (HBx), accompanied by destabilization of adherens junction. Reverse transcriptase PCR (RT-PCR), Northern and Western blot showed that reduction of wild-type β-catenin expression involved degradation of the protein. However, RNA interference (RNAi) and luciferase assay indicated that HBx enhanced β-catenin mediated signaling in HepG2 cells. In addition, immunohistochemical and Western blot analysis of β-catenin revealed that a decrease in the β-catenin protein level was found in 58.3% of HBV-related HCCs 19.2% of non-HBV-related tumors. Our data suggest that the expression of HBx contributed to the development of HCC, in part, by repressing the wild-type β-catenin expression and enforcing β-catenin-dependent signaling pathway, thus inducing cellular changes leading to acquisition of metastatic and/or proliferation properties.

关键词： hepatocellular carcinoma     hepatitis B virus X protein     β     -catenin     cell adhesion     E-cadherin     transcriptional activation    

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标题 作者 时间 类型 操作

Vaccine therapies for chronic hepatitis B: can we go further?

null

期刊论文

Chronic hepatitis B virus infection: epidemiology, prevention, and treatment in China

null

期刊论文

Correlation between viral load and liver cirrhosis in chronic hepatitis B patients

Lili LIU MM , Jiyao WANG MD , Weimin SHE MM ,

期刊论文

Clinical characteristics and risk factors of COVID-19 patients with chronic hepatitis B: a multi-center

期刊论文

New perspective on the natural course of chronic HBV infection

null

期刊论文

Comprehensive treatment of acute-on-chronic liver failure in a patient with hepatitis B: a case report

null

期刊论文

Potential use of serum HBV RNA in antiviral therapy for chronic hepatitis B in the era of nucleos(t)ide

null

期刊论文

Current hepatitis B treatment guidelines and future research directions

null

期刊论文

Advances in newly developing therapy for chronic hepatitis C virus infection

null

期刊论文

MicroRNAs and hepatitis viruses

Gang LI MD , Xiaojia XIONG MM ,

期刊论文

Current advances in the elimination of hepatitis B in China by 2030

null

期刊论文

血清N-聚糖生物标志物诊断ALT水平正常慢性乙型肝炎患者显著肝纤维化和肝硬化的临床意义

王林, 刘艺琪, 顾启馨, 张驰, 徐蕾, 王蕾, 陈翠英, 刘学恩, 赵鸿, 庄辉

期刊论文

Association of novel mutations and heplotypes in the preS region of hepatitis B virus with hepatocellular

Jia-Xin XIE, Jian-Hua YIN, Qi ZHANG, Rui PU, Wen-Ying LU, Hong-Wei ZHANG, Guang-Wen CAO, Jun ZHAO, Hong-Yang WANG,

期刊论文

Association of miRNA-122-binding site polymorphism at the interleukin-1 α gene and its interaction with hepatitisB virus mutations with hepatocellular carcinoma risk

null

期刊论文

Dysregulation of β-catenin by hepatitis B virus X protein in HBV-infected human hepatocellular carcinomas

Lei CHEN, Liang HU, Liang LI, Yuan LIU, Qian-Qian TU, Yan-Xin CHANG, He-Xin YAN, Meng-Chao WU, Hong-Yang WANG,

期刊论文