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1.
Hepatology ; 73(1): 53-67, 2021 01.
Article in English | MEDLINE | ID: mdl-32246499

ABSTRACT

BACKGROUND AND AIMS: GS-9688 (selgantolimod) is an oral selective small molecule agonist of toll-like receptor 8 in clinical development for the treatment of chronic hepatitis B. In this study, we evaluated the antiviral efficacy of GS-9688 in woodchucks chronically infected with woodchuck hepatitis virus (WHV), a hepadnavirus closely related to hepatitis B virus. APPROACH AND RESULTS: WHV-infected woodchucks received eight weekly oral doses of vehicle, 1 mg/kg GS-9688, or 3 mg/kg GS-9688. Vehicle and 1 mg/kg GS-9688 had no antiviral effect, whereas 3 mg/kg GS-9688 induced a >5 log10 reduction in serum viral load and reduced WHV surface antigen (WHsAg) levels to below the limit of detection in half of the treated woodchucks. In these animals, the antiviral response was maintained until the end of the study (>5 months after the end of treatment). GS-9688 treatment reduced intrahepatic WHV RNA and DNA levels by >95% in animals in which the antiviral response was sustained after treatment cessation, and these woodchucks also developed detectable anti-WHsAg antibodies. The antiviral efficacy of weekly oral dosing with 3 mg/kg GS-9688 was confirmed in a second woodchuck study. The antiviral response to GS-9688 did not correlate with systemic GS-9688 or cytokine levels but was associated with transient elevation of liver injury biomarkers and enhanced proliferative response of peripheral blood mononuclear cells to WHV peptides. Transcriptomic analysis of liver biopsies taken prior to treatment suggested that T follicular helper cells and various other immune cell subsets may play a role in the antiviral response to GS-9688. CONCLUSIONS: Finite, short-duration treatment with a clinically relevant dose of GS-9688 is well tolerated and can induce a sustained antiviral response in WHV-infected woodchucks; the identification of a baseline intrahepatic transcriptional signature associated with response to GS-9688 treatment provides insights into the immune mechanisms that mediate this antiviral effect.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis B Virus, Woodchuck/drug effects , Hepatitis B Virus, Woodchuck/genetics , Hepatitis B, Chronic/drug therapy , Hexanols/therapeutic use , Pyrimidines/therapeutic use , Toll-Like Receptor 8/agonists , Animals , Antiviral Agents/pharmacology , DNA, Viral/blood , Disease Models, Animal , Hepatitis Antibodies/blood , Hepatitis Antigens/blood , Hepatitis B Virus, Woodchuck/immunology , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/immunology , Hexanols/pharmacology , Humans , Marmota , Pyrimidines/pharmacology , Virus Replication/drug effects
2.
Zhonghua Gan Zang Bing Za Zhi ; 30(10): 1044-1049, 2022 Oct 20.
Article in Zh | MEDLINE | ID: mdl-36727249

ABSTRACT

Objective: To investigate the sero-epidemiological characteristics of the hepatitis D virus (HDV) infection among hepatitis B virus (HBV)-infected patients in Xinjiang region. Methods: A single-center cross-sectional analysis method was used to select 264 cases of hepatitis B virus infection who were hospitalized in the Center for Infectious Diseases and Liver Diseases of the First Affiliated Hospital of Xinjiang Medical University from August 2021 to January 2022. All patients were tested for HDV Ag, HDV IgM, HDV IgG, and HDV RNA. The infection status of hepatitis D virus was analyzed by grouping according to their clinical type, HBV viral load, and HBsAg level. A paired t-test was used for data with measurement data conforming to normal distribution. A paired rank sum test was used for data that did not conform to normal distribution before and after treatment. Results: A total of 36 cases (13.64%) and 26 cases (9.85%) were positive for HDV serological markers and HDV RNA. According to clinical type grouping, the positive rates of HDV serum markers in patients with chronic hepatitis B, hepatitis B-related cirrhosis, liver cancer, and liver failure were 13.46%, 12.43%, and 20.83%, respectively, and there was no statistically significant difference among the three groups (χ2=0.86, P=0.649). The positive rates of HDV RNA were 11.54%, 8.11%, and 20.83%, respectively, and there was no statistically significant difference among the three groups (χ2=4.015, P=0.134). According to HBV viral load grouping, the positive rates of HDV serum markers among patients with viral loads <20, 20-2 000, and >2 000 IU/ml were 17.15%, 7.81%, and 6.67%, respectively, and the difference was not statistically significant among the three groups (χ2=4.846, P=0.089). The positive rates of HDV RNA were 9.47%, 10.94%, and 10%, respectively, and the difference was not statistically significant among the three groups (χ2=0.113, P=0.945). According to HBsAg level grouping, the positive rates of HDV serum markers in HBsAg<0.05, 0.05~250, and >250 IU/ml were 14.29%, 16.67%, and 10.85%, respectively, and there was no statistically significance between the three groups (χ2=1.745, P=0.418). The positive rates of HDV RNA were 4.76%, 8.77%, and 11.63%, respectively, and there was no statistically significant difference among the three groups (χ2=1.221, P=0.543). Clinical outcome, disease course, HBV DNA, serological markers of viral hepatitis, routine blood test, biochemical indicators, coagulation function, and other laboratory indicators were compared between HDV serum marker and/or nucleic acid positive and negative patients, and there was no statistically significant difference (P>0.05). Conclusion: The positive rate of HDV serological markers and HDV RNA is 13.64% and 9.85%, respectively, at a single center in the Xinjiang region, and there is still a high HDV infection rate among the HBV-infected patients with low levels of viral load and HBsAg.


Subject(s)
Hepatitis B , Hepatitis D , Humans , Biomarkers/blood , Cross-Sectional Studies , Hematologic Tests , Hepatitis Antibodies/blood , Hepatitis Antibodies/immunology , Hepatitis B/blood , Hepatitis B/epidemiology , Hepatitis B/immunology , Hepatitis B Surface Antigens/immunology , Hepatitis B virus/immunology , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/immunology , Hepatitis D/blood , Hepatitis D/epidemiology , Hepatitis D/immunology , Hepatitis Delta Virus/immunology , China/epidemiology , Viral Load , Hepatitis Antigens/blood , Hepatitis Antigens/immunology , Seroepidemiologic Studies , RNA, Viral/blood , RNA, Viral/immunology
3.
J Hepatol ; 62(6): 1237-45, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25559326

ABSTRACT

BACKGROUND & AIMS: New therapies for chronic hepatitis B (CHB) are urgently needed since current treatments rarely lead to cure. We evaluated whether the oral small molecule toll-like receptor (TLR7) agonist GS-9620 could induce durable antiviral efficacy in woodchucks chronically infected with woodchuck hepatitis virus (WHV), a hepadnavirus closely related to human hepatitis B virus (HBV). METHODS: After evaluating the pharmacokinetics, pharmacodynamics and tolerability of oral GS-9620 in uninfected woodchucks, adult woodchucks chronically infected with WHV (n = 7 per group) were dosed with GS-9620 or placebo for 4 or 8 weeks with different treatment schedules. RESULTS: GS-9620 treatment induced rapid, marked and sustained reduction in serum viral DNA (mean maximal 6.2log10 reduction), and hepatic WHV DNA replicative intermediates, WHV cccDNA and WHV RNA, as well as loss of detectable serum WHV surface antigen (WHsAg). GS-9620 treatment also induced a sustained antibody response against WHsAg in a subset of animals. Strikingly, treatment reduced the incidence of hepatocellular carcinoma (HCC) from 71% in the placebo group to 8% in GS-9620-treated woodchucks with sustained viral load reduction. GS-9620 treatment was associated with reversible increases in serum liver enzymes and thrombocytopenia, and induced intrahepatic CD8(+) T cell, NK cell, B cell and interferon response transcriptional signatures. CONCLUSIONS: The data demonstrate that short duration, finite treatment with the oral TLR7 agonist GS-9620 can induce a sustained antiviral response in the woodchuck model of CHB, and support investigation of this compound as a therapeutic approach to attain a functional cure in CHB patients.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis B Virus, Woodchuck , Hepatitis B/drug therapy , Hepatitis B/immunology , Pteridines/therapeutic use , Toll-Like Receptor 7/agonists , Animals , Antiviral Agents/pharmacokinetics , DNA, Viral/blood , Disease Models, Animal , Hepatitis Antibodies/blood , Hepatitis Antigens/blood , Hepatitis B/complications , Hepatitis B Virus, Woodchuck/drug effects , Hepatitis B Virus, Woodchuck/genetics , Hepatitis B Virus, Woodchuck/isolation & purification , Humans , Liver Neoplasms, Experimental/etiology , Liver Neoplasms, Experimental/prevention & control , Male , Marmota , Pteridines/pharmacokinetics , Seroconversion/drug effects , Time Factors , Treatment Outcome
4.
J Clin Microbiol ; 53(3): 782-8, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25540394

ABSTRACT

Hepatitis E virus (HEV) is a serious public health problem. The commonly used tests that are specific for current HEV infection diagnosis include the detection of anti-HEV IgM and HEV RNA. Here, we report an improved enzyme-linked immunosorbent assay (ELISA) method for HEV antigen detection with a linear range equivalent to 6.3 × 10(3) to 9.2 × 10(5) RNA copies per ml. The monoclonal antibody (MAb) 12F12, a high-ability MAb that binds HEV virus, was selected as the capture antibody from a panel of 95 MAbs. The positive period of HEV antigenemia in infected monkeys using this test was, on average, 3 weeks longer than previously reported and covered the majority of the acute phase. The positive detection rates of IgM, RNA, and new antigen from the first serum samples collected from 16 confirmed acute hepatitis E patients were 81% (13/16), 81% (13/16), and 100% (16/16), respectively. In three patients, the initial serum specimens that tested negative for IgM, despite the presence of symptoms of acute hepatitis and elevated alanine aminotransferase (ALT) levels, were positive for HEV antigen and HEV RNA. In contrast, the serum samples of the three RNA-negative patients were antigen positive (and IgM positive), possibly due to the degradation of HEV nucleic acids. Our results suggest that this new antigen detection method has acceptable concordance with RNA detection and could serve as an important tool for diagnosing acute hepatitis E.


Subject(s)
Antibodies, Monoclonal , Clinical Laboratory Techniques/methods , Diagnostic Tests, Routine/methods , Hepatitis Antibodies , Hepatitis Antigens/blood , Hepatitis E/diagnosis , Animals , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay/methods , Hepatitis Antibodies/blood , Hepatitis E virus/genetics , Hepatitis E virus/immunology , Hepatitis E virus/isolation & purification , Humans , Macaca mulatta , RNA, Viral/blood
5.
J Clin Microbiol ; 51(3): 1052-6, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23303497

ABSTRACT

We report an autochthonous hepatitis E virus (HEV)-hepatitis B virus co-primary infection in a 41-year-old man having sex with men and infected with human immunodeficiency virus (HIV). This case prompts testing for HEV in HIV-infected patients with acute hepatitis even if primary infection with another hepatitis virus is diagnosed.


Subject(s)
HIV Infections/complications , Hepatitis B/diagnosis , Hepatitis E/diagnosis , Adult , HIV-1/isolation & purification , Hepatitis Antibodies/blood , Hepatitis Antigens/blood , Homosexuality, Male , Humans , Male , RNA, Viral/blood
6.
Arch Virol ; 158(2): 359-65, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23053523

ABSTRACT

Until now, the risk of HEV infection in schizophrenia was unknown. The present results showed that the seroprevalence of anti-HEV IgG and anti-HEV IgM in schizophrenia were significantly higher than that in healthy controls. Anti-HEV IgG positivity increased with age and with the duration of disease in schizophrenia patients. Moreover, schizophrenia patients with increased CD4(+)/CD8(+) T-cell ratios (>2.03) had higher anti-HEV IgG detection rates than those with normal ratios (1.05-2.03). Compared with the schizophrenia patients who tested anti-HEV IgG negative, the levels of interleukin-4 and interleukin-10 (Th2 cytokines) were significantly higher, while the interleukin-12 (Th1 cytokine) level was significantly lower, in those with anti-HEV IgG positivity. Of five schizophrenia patients who were anti-HEV IgM positive, four had elevated CD4(+)/CD8(+) T-cell ratios. HEV RNA was isolated from one of these four patients and classified as genotype 4. Anti-HEV IgM positivity was not detected among healthy controls. Therefore, schizophrenia patients exhibited a higher risk of HEV infection than controls.


Subject(s)
Hepatitis Antibodies/blood , Hepatitis Antigens/blood , Hepatitis E virus/immunology , Hepatitis E/epidemiology , Schizophrenia/complications , Adolescent , Adult , Aged , CD4-CD8 Ratio , Cytokines/blood , Female , Genotype , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , RNA, Viral/blood , RNA, Viral/genetics , RNA, Viral/isolation & purification , Risk Assessment , Seroepidemiologic Studies , Young Adult
7.
Eksp Klin Gastroenterol ; (1): 38-43, 2013.
Article in Russian | MEDLINE | ID: mdl-23951897

ABSTRACT

UNLABELLED: THE AIM OF THE RESEARCH: Improving the effectiveness of diagnostics and treatment of viral and drug-induced lesions of the liver (DILL) at a tuberculosis in children by identifying the frequency of their distribution, peculiarities of diagnostics and clinics. MATERIALS AND METHODS: We examined 242 children in the age from 2 months to 17 years, the patients with different forms of tuberculosis. RESULTS: The prevalence of hepatitis in children with tuberculosis: B - 1,2%, C-0.4%, G - 4,6%, TT - 8,7%. DILL was diagnosed in 67.5% of children - TB patients, in 48% of the children with DILL an asymptomatic course of the disease was noted, however, in 54.4% of the children with DILL cytolitic syndrome was expressed (ALT> standards). CONCLUSION: The prevalence of viral hepatitis B and C among children with TB is low. The infection with viruses of hepatitis G and TT is more often, but has no significant impact as on the course of tuberculosis, and on the severity of the liver damage. Drug-induced liver damage is a dominant view of pathology of the liver in children - TB patients and is mostly asymptomatic, but with a pronounced cytolitic syndrome.


Subject(s)
Chemical and Drug Induced Liver Injury/complications , Hepatitis, Viral, Human/complications , Tuberculosis/complications , Adolescent , Antitubercular Agents/administration & dosage , Antitubercular Agents/adverse effects , Antitubercular Agents/therapeutic use , Biomarkers/blood , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/epidemiology , Child , Child, Preschool , Hepatitis Antigens/blood , Hepatitis, Viral, Human/diagnosis , Hepatitis, Viral, Human/epidemiology , Humans , Infant , Liver/drug effects , Liver/pathology , Liver Function Tests , Moscow , Prevalence , Tuberculosis/diagnosis , Tuberculosis/drug therapy , Tuberculosis/epidemiology
8.
Scand J Gastroenterol ; 47(6): 692-701, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22229496

ABSTRACT

OBJECTIVE: Infection with hepatitis B virus (HBV) is endemic among Arctic populations where it may have a benign course. However, the relation of HBV to migration to low endemic areas is unknown, as it is for hepatitis D and C, and details on the influence of delta virus at a population level are lacking. MATERIAL AND METHODS: Population-based investigation of Greenlanders living in Denmark (n = 136) and in Greenland (n = 441). We tested for HBsAg, anti-HBs, anti-HBc, HBeAg, anti-HBe, HBV-DNA, HBV genotypes, anti-HDV, HDV-RNA, anti-HCV, HCV-Elisa test, HCV-RNA, aspartate aminotransferase, gamma-glutamyl transferase, bilirubin, and albumin, and performed a physical examination. RESULTS: Participation rate was 52/95% in Denmark/Greenland. Half of participants in Denmark had lived more than half of their lives in Denmark, and 54.5% had been exposed to HBV. This was similar to 53% among Greenlanders living in West Greenland (p = 0.76). HBsAg was positive in 4.4% of Greenlanders in Denmark (n = 6), who all were anti-HBe positive and had low viral load. Serological signs of HBV infection associated with having both parents born in Greenland (p = 0.007) and with IV drug use (p = 0.03). We found serological signs of HDV exposure among participants in Denmark/Greenland in 0.7/1.1% (n = 1/5) and HCV exposure in 1.5/0.0% (n = 2/0). Liver biochemistry was elevated in Greenlanders exposed to HDV. CONCLUSIONS: Hepatitis B, D, and C occurrences among Greenlanders in Denmark mirrored that of Greenland. Importantly, previously undetected exposure to delta virus associated with elevated liver biochemistry, and the introduction of delta virus is a liability to Greenlanders and to Greenland.


Subject(s)
Endemic Diseases , Hepatitis B/ethnology , Hepatitis C/ethnology , Hepatitis D/ethnology , Inuit , Adult , Aged , DNA, Viral/analysis , Denmark/epidemiology , Emigrants and Immigrants , Female , Greenland/epidemiology , Greenland/ethnology , Hepacivirus/genetics , Hepacivirus/immunology , Hepacivirus/isolation & purification , Hepatitis Antibodies/blood , Hepatitis Antigens/blood , Hepatitis B/blood , Hepatitis B/virology , Hepatitis B virus/genetics , Hepatitis B virus/immunology , Hepatitis B virus/isolation & purification , Hepatitis C/blood , Hepatitis C/virology , Hepatitis D/blood , Hepatitis D/virology , Hepatitis Delta Virus/genetics , Hepatitis Delta Virus/immunology , Hepatitis Delta Virus/isolation & purification , Humans , Male , Middle Aged , Reverse Transcriptase Polymerase Chain Reaction , Seroepidemiologic Studies , Viral Load
9.
Indian J Med Res ; 136(1): 74-81, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22885267

ABSTRACT

BACKGROUND & OBJECTIVES: Safe blood and blood products should be offered to all patients in need for blood transfusion. The objectives of the present study were to establish prevalence estimates for hepatitis B and hepatitis C virus infections as a foundation for safe blood transfusion in rural Vietnam, and to check the accuracy of the laboratory analysis used for hepatitis testing of blood donors in Vietnam. METHODS: A cross-sectional study was conducted in two rural communities in Quang Tri, Vietnam. A total of 1,200 blood samples collected from potential blood donors were tested by an enzyme immunoassay technique (EIA) for detection of hepatitis surface antigen (HBsAg), antibodies to hepatitis B core antigen (anti-HBc), and antibodies to hepatitis C antigen (anti-HCV). The EIA test outcome was validated by a chemiluminescent micro particle immunoassay technique (CMIA). RESULTS: The prevalence of HBsAg and anti-HBc in the study population was 11.4 per cent (95% CI 9.6 - 13.2) and 51.7 per cent (95% CI 48.8 - 54.5), respectively, the prevalences being higher in males than females. The prevalence of anti-HCV was 0.17 per cent. The test agreement between the EIA and CMIA techniques was high both for HBsAg detection (κ = 0.91; 95% CI: 0.83 - 0.99) and for anti-HBc detection (κ = 0.89; 95% CI 0.81 - 0.97). Compared to CMIA results, the positive and negative predictive values of the EIA tests were found to be 94.9 per cent (95% CI 87.5 - 98.6) and 97.5 per cent (95% CI 86.8 - 99.9) for HBsAg, and 92.4 per cent (95% CI 84.2 - 97.2) and 100 per cent (95% CI 91.2 - 100) for anti-HBc. INTERPRETATION & CONCLUSIONS: The study shows that hepatitis B virus infection is endemic in rural areas of Vietnam and that almost half of the population is or has been infected. Hepatitis C infection is rare, but false negative test results cannot be ruled out. Also, the results indicate that the EIA performance in blood donor screening in Vietnam may be sub-optimal, missing 2.5 per cent of hepatitis B virus carriers and falsely excluding more than 7 per cent of blood donors. As the prevalence of hepatitis B infection is high, occult hepatitis B infection may represent a threat to safe blood transfusion. Therefore, nucleic acid amplification testing for HBV should be considered for blood donor screening in Vietnam.


Subject(s)
Blood Donors/statistics & numerical data , Hepatitis B/epidemiology , Hepatitis C/epidemiology , Rural Health/statistics & numerical data , Cross-Sectional Studies , Female , Hepatitis Antigens/blood , Humans , Immunoenzyme Techniques , Luminescent Measurements/methods , Male , Prevalence , Sex Factors , Vietnam/epidemiology
10.
Ann Hepatol ; 11(2): 202-12, 2012.
Article in English | MEDLINE | ID: mdl-22345337

ABSTRACT

AIM: The present study aimed to evaluate the changes in the serum N-glycome profiles in chronic hepatitis B (CHB) patients and to assess the role of N-glycome-derived markers in the noninvasive diagnosis of liver fibrosis. MATERIALS AND METHODS: After liver biopsy for pathological grading and staging, 128 CHB patients underwent serum N-glycomic analysis using DNA sequencer-assisted fluorophore-assisted carbohydrate electrophoresis (DSA-FACE) and sensitive markers were screened. RESULTS: Peaks 1, 2, 8 and 10 in the N-glycome profiles could, to some extents, distinguish liver fibrosis at different stages. In addition, the N-glycome-derived marker log(peak2/peak8) possessed the highest diagnostic accuracy. The areas under the receiver operating characteristic (AUROCs) curves of the log(peak2/peak8) were 0.675, 0.736 and 0.754 in the diagnosis of significant fibrosis, advanced fibrosis and early cirrhosis, respectively. In combination with some marker panels (SLFG, S index, Fibrometer, Hui, Forns, APRI and Hepascore), it showed the best diagnostic potency in distinguishing significant fibrosis (SLFG + log[peak2/peak8], AUROC = 0.813) from advanced fibrosis (SLFG + log[peak2/peak8], AUROC = 0.899) and a better diagnostic potency in the identification of early cirrhosis (S index + log[peak2/peak8], AUROC = 0.903, lower than Hui model [AUROC = 0.927]) in the validation cohort. CONCLUSIONS: N-glycomic changes are present in the serum of CHB patients with liver fibrosis, and N-glycan profiling is a noninvasive and effective tool to assess the liver fibrosis, especially in combination with serum marker panels.


Subject(s)
Glycomics , Hepatitis B, Chronic/diagnosis , Liver Cirrhosis/diagnosis , Polysaccharides/blood , Adult , Area Under Curve , Biomarkers/blood , Blood Proteins/analysis , Female , Hepatitis Antigens/blood , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/enzymology , Humans , Liver/pathology , Liver Cirrhosis/blood , Liver Cirrhosis/etiology , Male , ROC Curve
11.
Afr J Med Med Sci ; 41 Suppl: 187-91, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23678655

ABSTRACT

Primary HepatoCellular Carcinoma (PHCC) has been strongly associated with HBV and HCV infections among other aetiological factors. However; do the patients still spread the viruses? This study involved forty one Nigerian adult patients with PHCC and 45 controls who were tested for HBsAg, HBeAg, Anti-HBe, Anti-HBs, anti-HCV IgM and IgG, anti-HDV and HDV antigen using ELISA. Statistical analysis was carried out with the student - t - test and Mc Nemar test at p < 0.05. The subjects consisted of male:female ratio of 3:1 for both the PHCC patients and controls. Evidence of exposure to hepatitis B, C and D viruses was detected in 95.1%, 44% and 0% of the patients respectively while the respective values of 24%, 11.1% and 0% were obtained for the controls. Indication for high (HBeAg) and low (anti HBe) HBV viral replication, and acute HBV infection were detected in 12.5%, 92.7% and 2.2% respectively among the patients while only 35.6% of the controls had low HBV viral replication. Acute and chronic infections of HCV were also found in 26.8% and 24.4% of the patients respectively compared to the respective values of 2.2% and 11.1% of the controls. Occult HBV infection occurred in equal proportions (11%) of both the patients (31.7%) and controls (35.6%). In conclusion, infectious HBV and HCV particles are present among Nigerian patients with PHCC while HDV infection is uncommon. Hence, safe medical care should be practised for all patients with PHCC while relatives should be screened for these viruses.


Subject(s)
Carcinoma, Hepatocellular , Hepatitis B , Hepatitis C , Hepatitis D , Hepatitis Viruses/immunology , Liver Neoplasms , Adult , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/microbiology , Comorbidity , Female , Hepatitis Antibodies/blood , Hepatitis Antigens/blood , Hepatitis B/epidemiology , Hepatitis B/immunology , Hepatitis C/epidemiology , Hepatitis C/immunology , Hepatitis D/epidemiology , Hepatitis D/immunology , Humans , Liver Neoplasms/epidemiology , Liver Neoplasms/immunology , Liver Neoplasms/microbiology , Male , Middle Aged , Nigeria/epidemiology , Serologic Tests/methods
15.
Eksp Klin Gastroenterol ; (6): 76-85, 2012.
Article in Russian | MEDLINE | ID: mdl-23402196

ABSTRACT

Questions of diagnostics, feature of clinic, treatment and preventation of active virus hepatites with parenteral mechanism of transmission of an infection (hepatites B, C, D, G) which make up a significant number of all acute virus hepatites are considered. A wide circulation, features of modern diagnostics and frequency of progress of chronic forms define a problem of diagnostics and treatment of a virus hepatites, as one of important for domestic healthcare. Data about the importance and features serological markers of viruses of a hepatites B, C, D, G, are presented and their clinical interpretation is analyzed. Modern drug therapy is in detail resulted including preparations of interferon. The need of specific preventive actions, post-exposure preventive maintenance and passive immunization is considered.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis, Viral, Human/diagnosis , Hepatitis, Viral, Human/prevention & control , Immunization, Passive , Interferons/therapeutic use , Acute Disease , Biomarkers/blood , Chronic Disease , Female , Hepatitis Antigens/blood , Hepatitis, Viral, Human/blood , Humans , Male
16.
Viruses ; 14(2)2022 02 01.
Article in English | MEDLINE | ID: mdl-35215896

ABSTRACT

Screening and linkage to care are essential to achieve viral hepatitis elimination before 2030. The accurate identification of endemic areas is important for controlling diseases with geographic aggregation. Viral activity drives prognosis of chronic hepatitis B and hepatitis C virus infection. This screening was conducted in Chiayi County from 2018-2019. All residents aged 30 years or older were invited to participate in quantitative HBsAg (qHBsAg) and HCV Ag screening. Among the 4010 participants (male:female = 1630:2380), the prevalence of qHBsAg and HCV Ag was 9.9% (396/4010) and 4.1% (163/4010), respectively. High-prevalence townships were identified, three for qHBsAg > 15% and two for HCV Ag > 10%. The age-specific prevalence of qHBsAg was distributed in an inverse U-shape with a peak (16.0%, 68/424) for subjects in their 40 s; for HCV, prevalence increased with age. Concentrations of qHBsAg < 200 IU/mL were found in 54% (214/396) of carriers. The rate of oral antiviral treatment for HCV was 75.5% (114/151), with subjects younger than 75 years tending to undergo treatment (85.6% vs. 57.4%, p < 0.001). QHBsAg and HCV Ag core antigens can reflect the concentration of the viral load, which serves as a feasible screening tool. Using quantitative antigen screening for hepatitis B and C in community-based screening, two hyperendemic townships were identified from an endemic county.


Subject(s)
Hepacivirus/isolation & purification , Hepatitis Antigens/blood , Hepatitis B virus/isolation & purification , Hepatitis B/virology , Hepatitis C/virology , Adult , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , DNA, Viral/genetics , Female , Hepacivirus/classification , Hepacivirus/genetics , Hepacivirus/immunology , Hepatitis Antigens/immunology , Hepatitis B/blood , Hepatitis B/drug therapy , Hepatitis B/epidemiology , Hepatitis B virus/classification , Hepatitis B virus/genetics , Hepatitis B virus/immunology , Hepatitis C/blood , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Humans , Male , Mass Screening , Middle Aged , Prevalence , Taiwan/epidemiology
17.
Breast Cancer Res Treat ; 127(3): 705-12, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21445574

ABSTRACT

Over the past four decades, chemotherapy has played an important role in prolonging survival in breast cancer patients. However, it may also result in undesirable side effects such as hepatitis B virus (HBV) reactivation seen in this study. With the increasing use of chemotherapy paralleling the rise in breast cancer incidence, the occurrence of HBV reactivation is likely to further increase. Several strategies use lamivudine to deal with this problem. Initially, lamivudine had been used to treat patients who developed alanine transaminase elevation attributable to HBV reactivation during chemotherapy. However, using this strategy, fatal reactivation has also been reported. Later studies have suggested that prophylactic lamivudine significantly reduces HBV reactivation and its associated morbidity. However, these studies were based mainly on patients with lymphoma, whereas studies on breast cancer patients were few. Moreover, these studies were retrospective. Recently, a prospective study has recommended that deferred preemptive lamivudine could be a comparable alternative to the prophylactic strategy. However, it was not a randomized controlled study. In this study, it was examined the efficacy of the prophylactic strategy in hepatitis B s-antigen seropositive breast cancer patients during chemotherapy using a prospective, randomized controlled study. Two groups were studied. One group consisted of 21 patients who were treated with prophylactic lamivudine, the other group consisted of 21 patients who were not treated with prophylactic lamivudine. The results showed that the prophylactic lamivudine strategy significantly decreased the incidence of HBV reactivation (0 vs. 28.6%, P = 0.021). It was conclude that the prophylactic lamivudine strategy significantly reduces the incidence of HBV reactivation for hepatitis B s-antigen seropositive breast cancer undergoing chemotherapy.


Subject(s)
Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Hepatitis B virus/drug effects , Hepatitis B/drug therapy , Hepatitis B/virology , Lamivudine/therapeutic use , Virus Activation/drug effects , Adult , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antiviral Agents/therapeutic use , Female , Hepatitis Antigens/blood , Hepatitis B/prevention & control , Hepatitis B virus/physiology , Humans , Lamivudine/administration & dosage , Liver Function Tests , Middle Aged , Prospective Studies , Secondary Prevention , Treatment Outcome
18.
Liver Int ; 30(3): 396-405, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19912529

ABSTRACT

BACKGROUND/AIM: Recently, we documented that hepatocytes can eliminate contacted cells via the CD95 ligand (CD95L)-CD95 pathway and that they are also equipped in perforin and granzyme B and can eradicate other cells via the granule exocytosis mechanism. The aim of this study was to assess whether hepadnaviral infection modifies hepatocyte-mediated cell killing. METHODS: Primary hepatocytes from woodchucks with progressing or resolved hepadnaviral hepatitis and hepatocyte lines transfected with woodchuck hepatitis virus (WHV) genes were examined for cytotoxic effector activity against cell targets susceptible to CD95L and/or perforin-dependent killing. Hepatocytes from healthy animals served as controls. RESULTS: Actively progressing and resolved hepadnaviral hepatitis is associated with a significantly greater capacity of hepatocytes to kill contacted cells. Both hepatocyte CD95L- and perforin-dependent cytotoxicity were augmented. Hepatocytes transfected with WHV X gene, but not those with complete WHV genome or virus envelope or core gene, transcribed significantly more CD95L and perforin and killed cell targets more efficiently. Exposure to interferon-gamma profoundly enhanced hepatocyte cell killing. CONCLUSIONS: Hepatocyte cytotoxic potential is significantly augmented during and following resolution of active hepadnaviral hepatitis. Hepatocyte cytotoxic activity may contribute to both liver physiological functions and the pathogenesis and progression of liver disease, including viral hepatitis.


Subject(s)
Fas Ligand Protein/immunology , Hepadnaviridae Infections/immunology , Hepatitis B Virus, Woodchuck , Hepatocytes/immunology , Perforin/immunology , Animals , CD3 Complex/metabolism , Cell Line, Tumor , Granzymes/metabolism , Hepadnaviridae Infections/pathology , Hepatitis Antibodies/blood , Hepatitis Antigens/blood , Interferon-gamma/metabolism , Liver/metabolism , Liver/pathology , Marmota , Recombinant Proteins , Transfection , Tumor Cells, Cultured , Tumor Necrosis Factor-alpha/metabolism , fas Receptor/immunology
19.
Infection ; 38(5): 395-400, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20589522

ABSTRACT

BACKGROUND: Hepatitis B vaccination in children born to hepatitis B surface antigen (HBsAg)-positive mothers considerably decreases the risk of vertical transmission. However, whether this protection against carriage of hepatitis B virus is maintained into early adulthood is as yet unknown. PATIENTS AND METHODS: A combined passive-active immunization programme for newborns of HBsAg-positive mothers was initiated in the north-eastern part of the Czech Republic in 1988. The number of immunized newborns had reached 665 newborns by the end of 2006. All mothers of immunized infants were HBsAg-positive during pregnancy, and 34 (5%) were also hepatitis B e antigen (HBeAg)-positive. The immunization programme consists of providing newborns with protection at birth with hepatitis B immunoglobulin, followed by three 10-µg doses of plasma-derived or, since 1990, recombinant vaccine administered at 0, 1 and 6 months of life. Only 29 children of HBeAg-positive mothers received vaccine at 0, 1 and 2 months of life. Blood samples were obtained after immunization, at 2 years of age, and biennially thereafter. Samples were tested for HBsAg and hepatitis B surface and core antibodies (anti-HBs, anti-HBc). RESULTS: The immunization schedules were completed in 640 children. A protective anti-HBs level after immunization was proven in 574 of 620 children (93%). Persistence of protective anti-HBs antibodies was detected in 70, 40 and 25% of children at 5, 10 and 15 years of age. Vertical transmission with chronic HBsAg carrier status was detected in two infants. Anti-HBc seroconversion was proven in ten children from 3 to 15 years of age. Natural boosting with an anti-HBs increase was detected in 38 children (twice in one child). CONCLUSION: Our results show that combined active-passive immunization of newborns against hepatitis B provides persistent protection up to adolescence despite a frequent waning of anti-HBs antibodies, suggesting there is no need for booster vaccination during adolescence.


Subject(s)
Hepatitis B Vaccines/administration & dosage , Hepatitis B virus/immunology , Hepatitis B/prevention & control , Infectious Disease Transmission, Vertical/prevention & control , Adolescent , Child , Child, Preschool , Female , Follow-Up Studies , Hepatitis Antigens/blood , Hepatitis Antigens/immunology , Hepatitis B/immunology , Hepatitis B/virology , Hepatitis B Antibodies/blood , Hepatitis B Antibodies/immunology , Hepatitis B Vaccines/immunology , Humans , Immunization Schedule , Infant , Infant, Newborn , Male , Pregnancy , Time , Vaccination
20.
Virol J ; 6: 186, 2009 Nov 04.
Article in English | MEDLINE | ID: mdl-19887014

ABSTRACT

BACKGROUND: Swine hepatitis E virus (swHEV) is a zoonotic disease that is considered a major problem in pig production and presents a threat to human health. Elucidation of the major antigenic epitopes of swHEV is essential for the effective control of swHEV epidemics. RESULTS: By bioinformatic analysis, we identified and then synthesized 12 peptides from open reading frames (ORFs) ORF1, ORF2 and ORF3, including swHEV-1 - swHEV-12. Using the results from ELISA, we selected swHEV-11 as the best candidate antigen and used it as a coating antigen for the development of peptide-based swine anti-HEV ELISA kits. The coefficient of variation (CV) the coefficient of variation (CV) varied between 4.3-7.2% in the same batch, and between 8.2-17.7% in six different batches. When comparing our swine peptide-based kit with the commercial recombinant-based kit, the humane anti-HEV IgG test had a 73.4% correspondence rate for them. CONCLUSION: This is the first systemic study to screen the diagnostic peptides of swHEV and our findings strongly suggest that peptide swHEV-11 is a potent diagnostic reagent of swHEV that could be used in the development of highly efficient diagnostic assays for the specific and highly sensitive detection of anti-HEV activity in swine serum samples.


Subject(s)
Enzyme-Linked Immunosorbent Assay/methods , Hepatitis Antigens/blood , Hepatitis E virus/immunology , Hepatitis E/veterinary , Peptides/blood , Swine Diseases/blood , Swine Diseases/diagnosis , Amino Acid Sequence , Animals , Hepatitis Antigens/chemistry , Hepatitis Antigens/immunology , Hepatitis E/diagnosis , Hepatitis E/immunology , Hepatitis E virus/chemistry , Humans , Molecular Sequence Data , Open Reading Frames , Peptides/chemistry , Peptides/immunology , Protein Structure, Secondary , Reproducibility of Results , Swine , Swine Diseases/immunology
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