1.Epidemiological distribution of genotypes and sub-genotypes of hepatitis B virus in 15 ethnic groups in China.
Xiao Qi GUO ; Shuang ZHANG ; Hui ZHENG ; Feng WANG ; Ning MIAO ; Qiu Dong SU ; Sheng Li BI ; Guo Min ZHANG ; Fu Zhen WANG ; Li Ping SHEN
Chinese Journal of Epidemiology 2023;44(5):759-764
Objective: To understand the distribution of genotypes and sub-genotypes of HBV in different ethnic groups in China. Methods: The HBsAg positive samples were selected by stratified multi-stage cluster sampling from the sample base of national HBV sero-epidemiological survey in 2020 for the amplification of S gene of HBV by nested PCR. A phylogeny tree was constructed to determine the genotypes and sub-genotypes of HBV. The distribution of genotypes and sub-genotypes of HBV were analyzed comprehensively by using laboratory data and demographic data. Results: A total of 1 539 positive samples from 15 ethnic groups were successfully amplified and analyzed, and 5 genotypes (B, C, D, I and C/D) were detected. The proportion of genotype B was higher in ethnic group of Han (74.52%, 623/836), Zhuang (49.28%, 34/69), Yi (53.19%, 25/47), Miao (94.12%, 32/34), Buyi (81.48%, 22/27). The proportions of genotype C were higher in ethnic groups of Yao (70.91%, 39/55). Genotype D was the predominant genotype in Uygur (83.78%, 31/37). Genotype C/D were detected in Tibetan (92.35%,326/353). In this study, 11 cases of genotype I were detected, 8 of which were distributed in Zhuang nationality. Except for Tibetan, sub-genotype B2 accounted for more than 80.00% in genotype B in all ethnic groups. The proportions of sub-genotype C2 were higher in 8 ethnic groups, i.e. Han, Tibetan, Yi, Uygur, Mongolian, Manchu, Hui and Miao. The proportions of sub-genotype C5 were higher in ethnic groups of Zhuang (55.56%, 15/27) and Yao (84.62%, 33/39). For genotype D, sub-genotype D3 was detected in Yi ethnic group and sub-genotype D1 was detected in both Uygur and Kazak. The proportions of sub-genotype C/D1 and C/D2 in Tibetan were 43.06% (152/353) and 49.29% (174/353). For all the 11 cases of genotype I infection, only sub-genotype I1 was detected. Conclusions: Five genotypes and 15 sub-genotypes of HBV were found in 15 ethnic groups. There were significant differences in the distribution of genotypes and sub-genotypes of HBV among different ethnic groups.
Humans
;
Asian People
;
China/epidemiology*
;
Ethnicity
;
Genotype
;
Gerbillinae
;
Hepatitis B virus/genetics*
;
Hepatitis B/virology*
3.The clinical value of von Willebrand factor and VITRO score in evaluating disease progression in patients with HBV infection.
Ya Lan GUAN ; Da Zhi ZHANG ; Yi Xuan YANG ; Ren Jun WAN ; Lu Qi TANG ; Wei Qiong ZENG ; Juan KANG
Chinese Journal of Hepatology 2022;30(3):309-315
Objective: To explore the clinical value of von Willebrand Factor (vWF) and VITRO score (vWF:Ag/platelet count) in assessing disease progression in patients with HBV infection. Methods: Randomly collect relevant clinical data of 308 patients with HBV infection (including 154 cases of chronic hepatitis B, 66 cases of hepatitis B cirrhosis in compensatory period, 88 cases of hepatitis B cirrhosis in decompensated period) from December 1, 2018 to January 5, 2021 in the Second Affiliated Hospital of Chongqing Medical University. The vWF values are measured by a uniform optical method, and all data are included using a uniform standard. Analyze the difference and significance of plasma vWF level and VITRO score in chronic hepatitis B, hepatitis B cirrhosis in the compensatory phase and decompensated phase. Results: The plasma vWF level and VITRO score of the chronic hepatitis B group were (139.47±76.44) and (0.86±0.8), respectively, and the hepatitis B cirrhosis compensated group was (164.95±67.12 and 1.44±1.14), respectively. Hepatitis cirrhosis decompensated group were (317.48±103.32 and 6.81±4.98), respectively; plasma vWF level and VITRO score increased with the progression of HBV infection, and the difference was statistically significant (F=133.669,P=0.000F=137.598,P=0.000).The plasma vWF level and VITRO score in patients with hepatitis B cirrhosis were (185.65±85.07 and 2.3±2.37) in the Child-Pugh A group, (304.74±105.81 and 6.37±5.19) in the B grade group, and (369.48±73.238.28±5.38) in the C grade group; plasma vWF level and VITRO score in patients with hepatitis B cirrhosis increased with the increase of Child-Pugh grade, and the difference was statistically significant (F=60.236, P=0.000F=32.854, P=0.000). The area under the curve (AUC) of plasma vWF level and VITRO score for diagnosing the decompensated stage of hepatitis B cirrhosis were 0.897 [95% confidence interval (CI): 0.855-0.940, P<0.01], 0.949 [95% CI: 0.916-0.982, P<0.01). When the vWF level and VITRO score were taken as cut-off values of 238.5% and 1.65, respectively, the sensitivity of diagnosing the decompensated stage of hepatitis B cirrhosis was 79.5% and 94.3%, the specificity was 92.3% and 87.7%, and the positive predictive value was 80.5% and 94.3%, the negative predictive value was 91.9% and 97.5%, and the diagnostic accuracy was 88.6% and 89.3%. Among the patients with decompensated hepatitis B cirrhosis, the level of vWF in the group with gastrointestinal bleeding (367.24±68.29)% was significantly higher than that in the group without gastrointestinal bleeding (286.15±109.69)%, and the difference was statistically significant (P<0.001) The VITRO score of the group with gastrointestinal bleeding (9.12±5.4) was significantly higher than that of the group without gastrointestinal bleeding (5.36±4.13), and the difference was statistically significant (P<0.01). The vWF level in the spontaneous peritonitis group was (341.73±87.92)% higher than that in the non-spontaneous peritonitis group (296.32±111.74)%, and the difference was statistically significant (P<0.05). There was no statistical difference in VITRO score between the two groups. significance. Conclusion: Plasma vWF level and VITRO score can evaluate the progression of liver disease and the degree of decompensation of liver cirrhosis in patients with HBV infection, and have a predictive effect on various complications after decompensation of liver cirrhosis, and have certain guiding significance for early intervention measures.
Disease Progression
;
Gastrointestinal Hemorrhage/etiology*
;
Hepatitis B/complications*
;
Hepatitis B virus
;
Hepatitis B, Chronic/diagnosis*
;
Humans
;
Liver Cirrhosis/virology*
;
Peritonitis/complications*
;
von Willebrand Factor/analysis*
5.Association of baseline alanine aminotransferase levels with therapeutic effects of entecavir and interferon- in patients with chronic hepatitis B.
Zhiqi XIAO ; Fuyuan ZHOU ; Bin ZHOU ; Jie YANG
Journal of Southern Medical University 2019;39(2):150-155
OBJECTIVE:
To evaluate the therapeutic effects of entecavir (ETV) and interferon- (IFN-) treatments for 48 weeks for chronic hepatitis B (CHB) in patients with different baseline alanine aminotransferase (ALT) levels.
METHODS:
We retrospectively analyzed the data of 369 CHB patients receiving ETV and IFN- treatments for 48 weeks. We compared the virological response rates, HBsAg clearance, and HBsAg reduction between the patients receiving ETV and IFN- treatments with different baseline ALT levels[≤ 5×upper limits of normal (ULN) level (subgroup 1), 5-10×ULN (subgroup 2), and > 10× ULN (subgroup 3)].
RESULTS:
In patients receiving ETV treatment, the virological response rate was 83.3% in subgroup 1, 91.4% in subgroup 2, and 95.5% in subgroup 3, as compared with 19.7%, 40%, and 42.9% in the 3 subgroups with IFN- treatment, respectively, showing significantly differences both among different subgroups with the same treatment and between the same subgroup with different treatments ( < 0.05). HBeAg clearance rates in the 3 subgroups were 8.3%, 16.7% and 35.5% in patients with ETV treatment and were 1.8%, 41.9%, and 38.1% in patients with IFN- treatment, respectively, showing significant differences among the 3 subgroups with the same treatment ( < 0.05); in the same subgroups with different treatments, the rates differed significantly only between subgroups 2 ( < 0.05). In ETV group, the rate of HBsAg reduction to below 200 IU/ml was 2.5% in subgroup 1 and 13.8% in subgroup 2, showing no significant difference between the two subgroups; in IFN- group, the rates were also similar between subgroups 1 and 2 (30.6% 33.3%, > 0.05); but the rates differed significantly between the same subgroups with different treatments ( < 0.05).
CONCLUSIONS
In all the subgroups with different baseline ALT levels, ETV treatment for 48 weeks results in significantly higher virological response rates than IFN- treatment in patients with CHB. In patients with a baseline ALT of 5-10 ×ULN, IFN- can result in a higher HBeAg clearance rate than ETV. In patients with comparable baseline ALT level, IFN- more effectively reduces HBsAg level than ETV. The patients with a relatively high baseline ALT level (> 5 × ULN) show better responses to both ETV and IFN- treatment than those with ALT level below 5×ULN. We thus recommend IFN- for patients with a baseline ALT of 5-10×ULN and ETV for patients with a baseline ALT either below 5 × ULN or beyond 10×ULN.
Alanine Transaminase
;
blood
;
Antiviral Agents
;
therapeutic use
;
DNA, Viral
;
Guanine
;
analogs & derivatives
;
therapeutic use
;
Hepatitis B Surface Antigens
;
blood
;
Hepatitis B e Antigens
;
blood
;
Hepatitis B virus
;
immunology
;
Hepatitis B, Chronic
;
drug therapy
;
enzymology
;
immunology
;
virology
;
Humans
;
Interferon-alpha
;
therapeutic use
;
Retrospective Studies
;
Time Factors
;
Treatment Outcome
;
Viral Load
;
drug effects
6.High-performance liquid chromatography-mass spectrometry-based serum metabolic profiling in patients with HBV-related hepatocellular carcinoma.
Lei ZHANG ; Zhijuan FAN ; Hua KANG ; Yufan WANG ; Shuye LIU ; Zhongqiang SHAN
Journal of Southern Medical University 2019;39(1):49-56
OBJECTIVE:
To explore the diagnostic value of the serum metabolites identified by high-performance liquid chromatography-mass spectrometry (HPLC/MS) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).
METHODS:
A total of 126 patients admitted to Tianjin Third Central Hospital were enrolled, including 27 patients with HBV-related hepatitis with negative viral DNA (DNA-N), 24 with HBV-related hepatitis with positive viral DNA, 24 with HBV-related liver cirrhosis, 27 with HBV-related HCC undergoing surgeries or radiofrequency ablation, and 24 with HBV-related HCC receiving interventional therapy, with 25 healthy volunteers as the normal control group. Serum samples were collected from all the subjects for HPLC/MS analysis, and the data were pretreated to establish an orthogonal partial least- squares discriminant analysis (OPLS-DA) model. The differential serum metabolites were preliminarily screened by comparisons between the HBV groups and the control group, and the characteristic metabolites were identified according to the results of non-parametric test. The potential clinical values of these characteristic metabolites were evaluated using receiver operator characteristic curve (ROC) analysis.
RESULTS:
A total of 25 characteristic metabolites were identified in the HBV- infected patients, including 9 lysophosphatidylcholines, 2 fatty acids, 17α-estradiol, sphinganine, 5-methylcytidine, vitamin K2, lysophosphatidic acid, glycocholic acid and 8 metabolites with few reports. The patients with HBV- related HCC showed 22 differential serum metabolites compared with the control group, 4 differential metabolites compared with patients with HBV-related liver cirrhosis; 10 differential metabolites were identified in patients with HBV-related HCC receiving interventional therapy compared with those receiving surgical resection or radiofrequency ablation. From the normal control group to HBV-related HCC treated by interventional therapy, many metabolites underwent variations following a similar pattern.
CONCLUSIONS
We identified 25 characteristic metabolites in patients with HBV-related HCC, and these metabolites may have potential clinical values in the diagnosis of HBV-related HCC. The continuous change of some of these metabolites may indicate the possibility of tumorigenesis, and some may also have indications for the choice of surgical approach.
Carcinoma, Hepatocellular
;
blood
;
diagnosis
;
virology
;
Case-Control Studies
;
Chromatography, High Pressure Liquid
;
DNA, Viral
;
blood
;
Hepatitis B virus
;
genetics
;
Hepatitis B, Chronic
;
blood
;
virology
;
Humans
;
Liver Cirrhosis
;
virology
;
Liver Neoplasms
;
blood
;
diagnosis
;
virology
;
Mass Spectrometry
;
Metabolome
;
Metabolomics
;
ROC Curve
7.Relationship between Maternal PBMC HBV cccDNA and HBV Serological Markers and its Effect on HBV Intrauterine Transmission.
Dan Dan WANG ; Lin Zhu YI ; Li Na WU ; Zhi Qing YANG ; Hai Yun HAO ; Xiao Hong SHI ; Bo WANG ; Shu Ying FENG ; Yong Liang FENG ; Su Ping WANG
Biomedical and Environmental Sciences 2019;32(5):315-323
OBJECTIVE:
To investigate the relationship between maternal peripheral blood mononuclear cells (PBMC) hepatitis B virus (HBV) covalenty closed circular deoxyribonucleic acid (cccDNA) and other HBV serological markers and its effects on HBV intrauterine transmission.
METHODS:
We enrolled 290 newborns and their hepatitis B surface antigen (HBsAg) positive mothers. HBV cccDNA in PBMC and HBV DNA in serum were detected by a real-time PCR-TaqMan probe while HBV serological markers were detected with an electrochemiluminescence immunoassay.
RESULTS:
There was a positive correlation between the levels of PBMC HBV cccDNA and serum HBV DNA and HBeAg (r = 0.436 and 0.403, P < 0.001). The detection rate of pattern A ['HBsAg (+), HBeAg (+), and anti-HBc (+)'] was significantly higher in the PBMC HBV cccDNA positive group than in the control group (χ2 = 48.48, P < 0.001). There was a significant association between HBV intrauterine transmission and PBMC HBV cccDNA (χ2 = 9.28, P = 0.002). In the presence of serum HBV DNA, HBeAg, and PBMC HBV cccDNA, the risk of HBV intrauterine transmission was three times higher (OR = 3.69, 95% CI: 1.30-10.42) than that observed in their absence. The risk of HBV intrauterine transmission was the greatest (OR = 5.89, 95% CI: 2.35-14.72) when both PBMC HBV cccDNA and pattern A were present. A Bayesian network model showed that maternal PBMC HBV cccDNA was directly related to HBV intrauterine transmission.
CONCLUSION
PBMC HBV cccDNA may be a direct risk factor for HBV intrauterine transmission. Our study suggests that serological markers could be combined with PBMC-related markers in prenatal testing.
Adolescent
;
Adult
;
DNA, Viral
;
blood
;
Disease Transmission, Infectious
;
Female
;
Hepatitis B
;
congenital
;
transmission
;
Hepatitis B e Antigens
;
blood
;
Humans
;
Infant, Newborn
;
Leukocytes, Mononuclear
;
virology
;
Male
;
Middle Aged
;
Young Adult
8.DNA sequences homologous to hepatitis C virus (HCV) in the extrachromosomal circular DNA in peripheral blood mononuclear cells of HCV-negative subjects.
Reinhard H DENNIN ; Jian-Er WO
Journal of Zhejiang University. Science. B 2019;20(8):637-646
OBJECTIVE:
This study aimed to investigate DNA sequences that are substantially homologous to the corresponding RNA sequence sections of the hepatitis C virus (HCV). These DNA sequences are present in the whole DNA extracted from peripheral blood mononuclear cells (PBMCs) of HCV-negative subjects. We presumed that these experimentally proven 5'-noncoding region (5'-NCR) homologous DNA sequences could be contained in the extrachromosomal circular DNA (eccDNA) fraction as part of the whole cellular DNA.
METHODS:
Home-made polymerase chain reaction (PCR) with whole cellular and isolated eccDNA, nucleotide basic local alignment search tool (BLASTn) alignments, and tests for patterns of methylation in selected sequence sections were performed.
RESULTS:
The PCR tests revealed DNA sequences of up to 320 bp that broadly matched the corresponding sequence sections of known HCV genotypes. In contrast, BLASTn alignment searches of published HCV 5'-NCR sequences with human genome databases revealed only sequence segments of up to 36 bp of the 5'-NCR. The composition of these sequences shows missing base pairs, base pair mismatches as well as complete homology with HCV reference sequences. These short sequence sections are present in numerous copies on both the same and different chromosomes. The selected sequence region within the DNA sequences of the 5'-NCR revealed a broad diversity of individual patterns of methylation.
CONCLUSIONS
The experimental results confirm our assumption that parts of the HCV 5'-NCR genomic RNA sequences are present at the DNA level in the eccDNA fraction of PBMCs. The tests for methylation patterns therein revealed individual methylomes which could represent an epigenetic feature. The respective sequence section might be subject to genetic regulation.
Computational Biology
;
DNA Methylation
;
DNA, Circular/genetics*
;
DNA, Viral/genetics*
;
Genome, Human
;
Genomics
;
Genotype
;
Hepacivirus/genetics*
;
Hepatitis C/virology*
;
Humans
;
Leukocytes, Mononuclear/virology*
;
Polymerase Chain Reaction
;
RNA, Viral/genetics*
;
Sequence Alignment
9.The guidelines of prevention and treatment for chronic hepatitis B (2019 version).
Chinese Journal of Hepatology 2019;27(12):938-961
Based on the progression of clinical and basic research in hepatitis B virus (HBV), we updated the previous HBV guidelines from 2015. The guidelines included the prevention, diagnosis, and antiviral therapy of chronic hepatitis B, which accelerates ro achieve the goal of "the elimination of viral hepatitis as a public health threat by 2030" proposed by the World Health Organization.
Antiviral Agents/therapeutic use*
;
Hepatitis B virus/isolation & purification*
;
Hepatitis B, Chronic/virology*
;
Humans
;
Practice Guidelines as Topic
;
Public Health
;
World Health Organization
10.Guidelines for the prevention and treatment of hepatitis C (2019 version).
Chinese Journal of Hepatology 2019;27(12):962-979
In order to standardize and update the prevention, diagnosis and antiviral therapy of hepatitis C and to achieve the World Health Organization's goal of eliminating viral hepatitis as a public health threat by 2030, Chinese Medical Association, the Chinese Society of Hepatology, and the Society of Infectious Diseases organized relevant native experts in 2019 to revise the guideline for the prevention and treatment of hepatitis C (2019 version) based on the basic, clinical and prophylactic research progress of hepatitis C infection at home and abroad, combined with the present actual situation of our country, so as to provide an important basis for the prevention, diagnosis and treatment of hepatitis C.
Antiviral Agents/therapeutic use*
;
Hepacivirus/isolation & purification*
;
Hepatitis C/virology*
;
Humans
;
Practice Guidelines as Topic
;
Public Health
;
World Health Organization

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