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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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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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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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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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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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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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Direct acting antiviral-induced dynamic reduction of serum

Tung Huynh, Ke-Qin Hu

《医学前沿（英文）》 2019年 第13卷 第6期   页码 658-666 doi: 10.1007/s11684-019-0707-7

摘要： Direct acting antiviral (DAA) treatments may reduce the elevated α fetoprotein (AFP), but data on how these treatments affect elevated AFP in patients with chronic hepatitis C (CHC) remain insufficient. In the present study, the frequency of baseline AFP elevations and their related factors, AFP dynamics during and after DAA treatment, and factors associated with AFP reduction was assessed. This retrospective study included 141 patients with CHC without hepatocellular carcinoma who received DAA and achieved sustained virological response. The details are as follows: mean post-treatment follow-up was 99 weeks (12–213); mean age, 57.8 years old; 52%, males; 79%, genotype (GT) 1; and 47%, cirrhosis. Pre-treatment AFP elevation (>5.5 ng/mL) was seen in 48.2% patients. On multivariate analysis, baseline AFP>5.5 was associated with the presence of cirrhosis ( =0.001), co-existing non-alcoholic steatohepatitis (NASH) ( = 0.035), and GT 1 ( = 0.029). AFP normalization was seen in 28.2% patients at treatment week 2, in 52% at the end of treatment, and in 73.4% at the end of follow-up. Post-treatment week 24 AFP normalization was associated with the absence of cirrhosis ( = 0.003), Child–Pugh score<6 ( = 0.015), and baseline AFP<10 ( = 0.015). AFP elevation is common in patients with CHC and independently associated with NASH, cirrhosis, and GT 1. DAA treatment resulted in AFP normalization as early as treatment week 2. Post-treatment week 24 AFP normalization is independently associated with the absence of cirrhosis, Child–Pugh score<6, and baseline AFP<10.

关键词： chronic hepatitis C     α fetoprotein     direct acting antiviral treatment     cirrhosis    

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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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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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NKT cells in liver diseases

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《医学前沿（英文）》 2018年 第12卷 第3期   页码 249-261 doi: 10.1007/s11684-018-0622-3

摘要：

Natural killer T cells are innate-like and tissue-resident lymphocytes, which recognize lipid antigens and are enriched in the liver. Natural killer T cells play important roles in infections, tumors, autoimmune diseases, and metabolic diseases. In this study, we summarize recent findings on biology of natural killer T cells and their roles in hepatitis B virus and hepatitis C virus infection, autoimmune liver diseases, alcoholic liver disease, nonalcoholic fatty liver disease, and hepatocellular carcinoma. Controversial results from previous studies are discussed, and indicate the dynamic alteration in the role of natural killer T cells during the progression of liver diseases, which might be caused by changes in natural killer T subsets, factors skewing cytokine responses, and intercellular crosstalk between natural killer T cells and CD1d-expressing cells or bystander cells.

关键词： natural killer T cells     hepatitis B virus and hepatitis C virus infection     autoimmune liver diseases     alcoholic liver disease     nonalcoholic fatty liver disease     hepatocellular carcinoma    

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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：

本研究目的是探讨血清N-聚糖模型在285例丙氨酸转移酶（alanine aminotransferase, ALT）水平正常（＜40 U·L–1）的慢性乙型肝炎（慢性乙肝）患者中诊断显著肝纤维化和肝硬化的临床意义。入组患者均进行肝组织活检，并使用Ishak评分系统评估患者肝组织纤维化程度。应用基于DNA测序仪的荧光糖电泳技术检测患者血清N-聚糖图谱，每例患者的血清样本中共鉴定出9个N-聚糖峰。利用机器学习算法，即随机森林（random forest, RF）构建更理想的血清N-聚糖模型，以诊断显著肝纤维化（≥ F3）和肝硬化（≥ F5），并比较血清N-聚糖模型和其他纤维化标志物的诊断效能。肝组织活检结果显示，有显著肝纤维化和肝硬化患者分别占63.86%（182/285）和16.49%（47/285），有显著炎症患者为4.91%（14/285）。血清N-聚糖RF-A模型具有很好的诊断显著肝纤维化（≥ F3）的效能，其受试者工作特征曲线下面积（area under receiver operating characteristic curve, AUROC）为0.94，与肝活检的符合率为90.45% 。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 based on the four factors, FIB-4）和天冬氨酸转氨酶与血小板比率指数（aspartate aminotransferase-to-platelet ratio index, APRI）。在ALT水平正常的慢性乙肝患者中，血清N-聚糖模型可作为诊断显著肝纤维化或肝硬化的潜在生物标志物。

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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Effect of renal function and hemodialysis on the serum tumor markers in patients with chronic kidney

YU Xiaofang, XU Xialian, YE Zhibin

《医学前沿（英文）》 2007年 第1卷 第3期   页码 308-311 doi: 10.1007/s11684-007-0059-6

摘要： In patients with chronic renal failure, whether they have had hemodialysis or not, the specificity of some of the serum tumor markers for the diagnosis of the corresponding tumors is decreased while others remain as valuable as they are in patients with normal kidney function. The detection of tumor markers is extensively used for the diagnosis of corresponding tumors. It has been recently shown that some tumor markers are higher in patients with chronic kidney disease (CKD) than in the normal population. The effects of renal function and hemodialysis were examined on serum levels of some of the tumor markers including CEA, CA, CA, AFP, CA, CA, CYFRA, NSE, SCC-Ag, PSA, and fPSA. The 232 non-dialysis patients with CKD and 37 chronic uremic patients treated with maintenance hemodialysis were enrolled in this study. The 232 non-dialysis patients were divided into three groups according to their Ccr. In group 1, Ccr was ≤25 mL/min. In group 2, Ccr was between 25 and 50 mL/min. In group 3, Ccr was ≥50 mL/min. The male patients were also divided into three groups to compare the serum levels of PSA and fPSA among the three groups. Nine tumor markers in 37 uremic patients were tested. For comparison, 37 non-dialysis patients with similar Ccr of the same age and gender served as controls. There existed significant differences in serum levels of CEA, CA, CYFRA, NSE, and SCC-Ag among different Ccr groups and the markers bore a negative correlation with Ccr. There were no significant differences among the three groups in the serum concentrations of CA, AFP, CA, CA, PSA and fPSA. The serum levels of CA and NSE were significantly higher (199, CYFRA, NSE, CA and SCC-Ag for the diagnosis of the corresponding tumors was decreased while serum AFP, CA, CA, PSA and fPSA were as valuable as they were in patients with normal kidney function. Hemodialysis further increased the serum level of CA and NSE.

关键词： CKD     non-dialysis     valuable     detection     chronic    

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Acupuncture is ineffective for chronic low back pain? A critical analysis and rethinking

Xuqiang Wei, Baoyan Liu

《医学前沿（英文）》 2021年 第15卷 第5期   页码 767-775 doi: 10.1007/s11684-020-0785-6

摘要： Acupuncture is a promising treatment for relieving pain and improving lower back function in clinical practice. However, evidence from randomized clinical trials (RCTs) remains controversial. Most RCTs conclude that acupuncture procedures for chronic low back pain (CLBP) had no significant difference in efficacy and belonged to placebo. We carefully reviewed and analyzed the methodology and implementation of sham acupuncture in RCTs. Controversial evidence of acupuncture for CLBP is only a microcosm of the evaluation methodological limitation of acupuncture. Inappropriate selection of sham acupuncture controls, rigorous RCT research models, and incorrect interpretation of results may contribute to negative evidence. Evaluating and disregarding the holistic efficacy of acupuncture with an explanatory RCT model based on evaluation drugs may be unwise. Moreover, sham acupuncture is often proven to be non-inert, unreasonable, and with low fidelity. Pitfalls of the explanatory RCT model and sham acupuncture design should be avoided. Establishing a new evaluation system that is in line with the clinical characteristics of acupuncture and obtaining high-quality evidence are difficult but promising tasks.

关键词： chronic low back pain     sham acupuncture     acupuncture     methodology     therapeutic evaluation    

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标题 作者 时间 类型 操作

Advances in newly developing therapy for chronic hepatitis C virus infection

null

期刊论文

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

New perspective on the natural course of chronic HBV infection

null

期刊论文

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

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

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

null

期刊论文

Direct acting antiviral-induced dynamic reduction of serum

Tung Huynh, Ke-Qin Hu

期刊论文

Current hepatitis B treatment guidelines and future research directions

null

期刊论文

MicroRNAs and hepatitis viruses

Gang LI MD , Xiaojia XIONG MM ,

期刊论文

NKT cells in liver diseases

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

Effect of renal function and hemodialysis on the serum tumor markers in patients with chronic kidney

YU Xiaofang, XU Xialian, YE Zhibin

期刊论文

Acupuncture is ineffective for chronic low back pain? A critical analysis and rethinking

Xuqiang Wei, Baoyan Liu

期刊论文