Background
The association between hepatitis B virus (HBV) mutations and hepatocarcinogenesis remains controversial because of conflicting data in the literature. We conducted a meta-analysis of case–control and cohort studies to examine HBV PreS, enhancer II (EnhII), basal core promoter (BCP), and precore mutations in relation to the risk of hepatocellular carcinoma (HCC).

Associations Between Hepatitis B Virus Mutations and the Risk of Hepatocellular Carcinoma: A Meta-Analysis

https://www.journal-of-hepatology.eu/article/S0168-8278(16)00063-5/pdf

Overview of hepatitis B viral replication and genetic variability

A high rate of chronic hepatitis B virus (HBV) infection in China is mainly caused by perinatal or early childhood transmission. Administration of universal HBV vaccination in infants has led to a dramatic decrease in HBV epidemiology, with hepatitis B surface antigen (HBsAg) prevalence declining from 9.75% in 1992 to 7.18% in 2006. The major HBV genotypes are B and C, with B being more prevalent in the southern part and C more prevalent in the northern part of China. A national survey carried out in 1992 showed that the hepatitis C virus (HCV) infection rate was 3.20% in general population in China. After implementation of mandatory HCV screening for blood transfusion and other precautions to prevent blood-borne disease since 1993, the new cases of HCV infection associated with blood or blood product has become very rare. Although the anti-HCV prevalence would be much higher in high-risk groups, a survey carried in 2006 showed that the anti-HCV prevalence rate was only 0.43% in general population. This sharp decline in HCV infection rate was mainly due to stringent administration and monitoring of blood donors and blood products, but may also be related to the remarkably improved specificity of anti-HCV test. The predominant HCV genotype in China is genotype 1b (60–70%), and the host interleukin-28b rs12979860 CC genotype is very frequent in Chinese population (over 80%).

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jgh.12220

Update on epidemiology of hepatitis B and C in China.

Hepatitis B virus (HBV) infection has shown an intermediate or high endemicity level in low-income countries over the last five decades. In recent years, however, the incidence of acute hepatitis B and the prevalence of hepatitis B surface antigen chronic carriers have decreased in several countries because of the HBV universal vaccination programs started in the nineties. Some countries, however, are still unable to implement these programs, particularly in their hyperendemic rural areas. The diffusion of HBV infection is still wide in several low-income countries where the prevention, management and treatment of HBV infection are a heavy burden for the governments and healthcare authorities. Of note, the information on the HBV epidemiology is scanty in numerous eastern European and Latin-American countries. The studies on molecular epidemiology performed in some countries provide an important contribution for a more comprehensive knowledge of HBV epidemiology, and phylogenetic studies provide information on the impact of recent and older migratory flows.

Hepatitis B virus burden in developing countries.

Geographical and genetic diversity of the human hepatitis B virus.

Hepatitis B virus (HBV) genotypes/subgenotypes in China: Mutations in core promoter and precore/core and their clinical implications

Objective Angiotensin-converting enzyme 2 (ACE-2) has been identified as a functional receptor of severe acute respiratory syndrome coronavirus (SARS-CoV), so its gene was cloned and eukaryotic expressed for further insight into mechanisms in SARS-CoV entry and pathogenesis, as well as development of a safe and reliable neutralization assay for SARS-CoV. Methods Total RNA was extracted from right atrial tissue of a patient with right heart failure resected during a valvular replacement surgery by Trizol one-step method, and the full-length ACE-2 encoding gene was acquired by RT-nested-PCR. The ACE-2 encoding gene was then cloned into pcDNA4/HisMax-TOPO eukaryotic expression vector to construct the recombinant plasmid pcDNA4/ ACE-2, which was then transfected into 293 T cell and ACE-2 eukaryotic transient expression was detected by Western Blot. Syncytia inhibition assay was established to detect SARS-CoV neutralizing antibody, and compared parallelly with SARS pseudovirus neutralization assay. Results The recombinant plasmid pcDNA4/ ACE-2 could express ACE-2 protein in eukaryotic cells and induce cell-cell fusion between S protein- and ACE2-expressing cells. This cell-cell fusion assay could be used to detect SARS-CoV neutralizing antibody. Conclusion SARS-CoV receptor ACE-2 gene was successfully cloned and eukaryotic expressed, and used to establish syncytia inhibition assay for SARS-CoV neutralizing antibody assay.

[Cloning of ACE-2 gene encoding the functional receptor for the SARS coronavirus and its expression in eukaryotic cells].

Objective To clone and express nucleocapsid (N) protein of the severe acute respiratory syndrome (SARS)-associated coronavirus, and to evaluate its antigenicity and application value in the development of serological diagnostic test for SARS. Methods SARS-associated coronavirus N protein gene was amplified from its genomic RNA by reverse transcript nested polymerase chain reaction (RT-nested-PCR) and cloned into pBAD/Thio-TOPO prokaryotic expression vector. The recombinant N fusion protein was expressed and purified, and its antigenicity and specificity was analyzed by Western Blot, to establish the recombinant N protein-based ELISA for detection of IgG antibodies to SARS-associated coronavirus, and SARS-associated coronavirus lysates-based ELISA was compared parallelly. Results The recombinant expression vector produced high level of the N fusion protein after induction, and that protein was purified successfully by affinity chromatography and displayed higher antigenicity and specificity as compared with whole virus lysates. Conclusion The recombinant SARS-associated coronavirus N protein possessed better antigenicity and specificity and could be employed to establish a new, sensitive, and specific ELISA for SARS diagnosis.

[Molecular cloning and expression of the severe acute respiratory syndrome-associated coronavirus nucleocapsid protein and its clinical application].

OBJECTIVE: To study into the genetic polymorphism of DC-SIGN and DC-SIGNR's exon 4 in Chinese hepatitis C patients and its relationship with HCV infection susceptibility. METHODS: Patients with hepatitis C (n=300, group A) and healthy subjects (n=520, group B) were genotyped and analysed for the repeat sequence of polymorphism of DC-SIGN and DC-SIGNR's exon 4 using PCR and DNA sequencing. RESULTS: The distribution of genotypes and alleles in DC-SIGN's exon 4 in the two groups did not differ significantly (P > 0.05). The difference of allele frequency in DC-SIGNR's exon 4 between the two groups was also not significant (P > 0.05). However, 9/5 genotype distribution frequency of DC-SIGNR's exon 4 in patients with hepatitis C was significantly higher than that in the healthy subjects (P < 0.05). CONCLUSION: There is no significant correlation between the genetic polymorphism of DC-SIGN's exon 4 and HCV infection susceptibility. 9/5 genotype distribution frequency of DC-SIGNR's exon 4 in patients with hepatitis C is significantly higher and may be associated with HCV infection susceptibility.

[Genetic polymorphism of dendritic cell-specific ICAM-3 grabbing nonintegrin and DC-SIGNR's exon 4 in Chinese hepatitis C patients].

Objective To investigate the association of genetic polymorphism of dendritic cellspecific ICAM-grabbing nonintegrin(DC-SIGNR)and hepatitis C infection.Methods Patients with hepatitis C(n=268)were genotyped and analysed for the repeat sequences polymorphism of DC-SIGNR using PCR and DNA sequencing.HCV virus load and HCV RNA genotypes were analyzed.Inter-group comparison was analyzed using LSD method.Results No significant correlation was found between DC-SIGNR genotypes/alleles and HCV RNA genotypes in patients.HCV-infected patients with 7-repeat(medium)alleles had lower HCV RNA levels compared to patients with 9-repeat(onger)alleles(P=0.036).HCV-infected patients with 7/7 genotype had lower HCV RNA levels compared to patients with 9/7 genotype(P=0.025).These findings suggest that optimal attachment of hepatitis C virions to DC-SIGNR may be associated with longer alleles.Conclusion The fact that DC-SIGNR polymorphism might affect HCV loads suppons the concept that DC-SIGNR contributes to HCV replication efficacy.There is no significant correlation between the genetic polymorphism of DC-SIGNR and HCV-RNA genotypes.

Key words: 
Hepatitis C:Hepatitis C virus; Genotype; Dendritic cell-specific ICAM-3 grabbing nonintegrin related

Jian Lu

Papers

Hepatitis B virus (HBV) genotypes/subgenotypes in China: Mutations in core promoter and precore/core and their clinical implications

[Cloning of ACE-2 gene encoding the functional receptor for the SARS coronavirus and its expression in eukaryotic cells].

[Molecular cloning and expression of the severe acute respiratory syndrome-associated coronavirus nucleocapsid protein and its clinical application].

[Genetic polymorphism of dendritic cell-specific ICAM-3 grabbing nonintegrin and DC-SIGNR's exon 4 in Chinese hepatitis C patients].

[The association of genetic polymorphism of dendritic cell-specific ICAM-grabbing nonintegrin and hepatitis C infection].