1.Modeling the Long-term Antibody Response and Duration of Immune Protection Induced by an Inactivated, Preservative-free Hepatitis A Vaccine (Healive) in Children.
Yong Pei YU ; Jiang Ting CHEN ; Zhi Wei JIANG ; Ling WANG ; Cheng Kai YU ; Xiao Yan YAN ; Chen YAO ; Jie Lai XIA
Biomedical and Environmental Sciences 2020;33(7):484-492
Objective:
Long-term seroprotection the hepatitis A vaccine is essential for the prevention of disease from the hepatitis A virus (HAV). Due to documented difficulties during decade-long follow-ups after receiving vaccines, statistical-modeling approaches have been applied to predict the duration of immune protection.
Methods:
Based on five-year follow-up data from a randomized positive-controlled trial among Chinese children (1-8 years old) following a 0, 6 months vaccination schedule, a power-law model accounting for the kinetics of B-cell turnover, as well as a modified power-law model considering a memory-B-cell subpopulation, were fitted to predict the long-term immune responses induced by HAV vaccination (Healive or Havrix). Anti-HAV levels of each individual and seroconversion rates up to 30 years after vaccination were predicted.
Results:
A total of 375 participants who completed the two-dose vaccination were included in the analysis. Both models predicted that, over a life-long period, participants vaccinated with Healive would have close but slightly higher antibody titers than those of participants vaccinated with Havrix. Additionally, consistent with previous studies, more than 90% of participants were predicted to maintain seroconversion for at least 30 years. Moreover, the modified power-law model predicted that the antibody titers would reach a plateau level after nearly 15 years post-vaccination.
Conclusions
Based on the results of our modeling, Healive may adequately induce long-term immune responses following a 0, 6 months vaccination schedule in children induction of memory B cells to provide stable and durable immune protection.
Adolescent
;
Child
;
Child, Preschool
;
China
;
Female
;
Hepatitis A
;
immunology
;
Hepatitis A Antibodies
;
blood
;
Hepatitis A Vaccines
;
administration & dosage
;
Humans
;
Immunity, Active
;
Infant
;
Male
;
Models, Statistical
;
Vaccination
;
statistics & numerical data
2.Data analysis on hepatitis B through pilot surveillance reporting system in Henan province, 2012-2016.
Y H GUO ; Y Y LYU ; J H YANG ; J XU ; J LI ; Y YE ; Y Y ZHANG
Chinese Journal of Epidemiology 2018;39(4):500-504
Objective: To standardize the reporting system on hepatitis B in order to improve the quality of monitoring program in Henan province. Methods: A total of 6 sites of Hepatitis B pilot surveillance were selected in Xinzheng of Zhengzhou city, Linzhou of Anyang city, Shanyang district of Jiaozuo city, Shaoling district of Luohe city, Yongcheng of Shangqiu city, Pingqiao district of Xinyang city in Henan province. Subjects under study were those reported hepatitis B cases, from 2012 to 2016. Cases diagnosed in 2011 were chosen as controls. Data on classification of hepatitis B, time that HBsAg became positive and ALT value of the cases were analyzed annually. 5 ml venous blood was collected and anti-HBc IgM confirmed test was made for those suspected acute cases on hepatitis B. Based on the 2016 data from the monitoring system, the incidence of acute hepatitis B in Henan province was estimated. Results: The number of reported hepatitis B cases had declined in 6 sites of Hepatitis B pilot surveillance substantially. A total of 17 436 hepatitis B reported in 2011 but only 2 632 cases were reported in 2016, with a reduction of 84.90%(14 804/17 436) in these six monitoring sites. The number of unclassified hepatitis B cases also dropped sharply. In 2011, 36.87% of the cases were unclassified, but the figure reduced to 0.08% in 2016, from the six sites. The rate on ALT detection also gradually improved. The rate of misdiagnosis on HBV carrier from hepatitis B almost disappeared. From 2013 to 2016, 777 blood samples were collected from six pilot sites. 29.34% (228/777) of the blood samples were tested positive for anti-HBc IgM after confirmed by the hepatitis laboratory of the China Center for Disease Control and Prevention. Conclusions: Since the development of the pilot surveillance program, the quality of reporting system on hepatitis B had been improved, as well as the accuracy of diagnosis. Rate on the accuracy of reporting on hepatitis B and the methods of testing should be improved at the monitoring sites.
China/epidemiology*
;
Cities
;
Disease Notification/statistics & numerical data*
;
Hepatitis A/epidemiology*
;
Hepatitis B/epidemiology*
;
Hepatitis B Antibodies/blood*
;
Hepatitis B Surface Antigens/blood*
;
Humans
;
Incidence
;
Pilot Projects
;
Population Surveillance
;
Sentinel Surveillance
3.Relationship between the HBsAg-positive infection status of mothers and the non/low-response to hepatitis B vaccine of their infants.
Z Q YANG ; H Y HAO ; X H SHI ; Z D FU ; F ZHANG ; X F WANG ; X X XU ; B WANG ; H X WEN ; S Y FENG ; B WANG ; S P WANG
Chinese Journal of Epidemiology 2018;39(6):805-809
Objective: To explore the relationship between the status of HBsAg-positive infection of mothers and the non/low-response to hepatitis B vaccine of their infants. Methods: A total of 225 pairs of mothers and their infants were recruited in our cohort from June 2011 to July 2013. Infants were given three doses of hepatitis B vaccine at hour 24, first month and month 6(t)h respectively and were followed up for one year after birth. HBV serological markers and HBV DNA in the peripheral blood of both mothers and infants were detected by Electro-chemiluminescence immunoassay and fluorescence quantitative Polymerase Chain Reaction. Results: Six HBV infection models were detected in HBsAg-positive mothers, and "HBsAg (+), HBeAg (+), anti-HBc (+)" (model one) and "HBsAg (+), anti-HBe (+), anti-HBc (+)" (model two) accounted for 92.5%(208/225) of all the models. Rate of non/low-response to hepatitis B vaccine in infants born to mothers in model one was lower than those in model two, the differences are statistically significant (χ(2)=4.80, P=0.029). The rate of non/low-response to hepatitis B vaccine in infants showed a downward trend with the rising of HBeAg level in their mothers (χ(2)=4.86, P=0.028). Results from the unconditional logistic regression analysis showed that the HBeAg of the HBsAg-positive mothers was significantly correlated with the low risk of non/low-response to hepatitis B vaccine in infants (OR=0.598, 95%CI: 0.378-0.947). The positive rate of serum HBV DNA in HBsAg-positive mothers was 54.2%, while the rate of non/low-response to hepatitis B vaccine in infants born to HBV DNA positive mothers was similar to those infants born to HBV DNA negative mothers (χ(2)=0.22, P=0.640). Conclusions: "HBsAg (+), HBeAg (+), anti-HBc (+)" and "HBsAg (+), anti-HBe(+), anti-HBc (+)" were the common models seen in HBsAg-positive mothers, and the rate of non/low-response to hepatitis B vaccine was different between the two models. HBeAg of HBsAg-positive mothers might have positive effects on the immune response to hepatitis B vaccine in infants but the mechanisms remained not clear. HBV DNA of the HBsAg-positive mothers did not seem to be correlated with the immune response to hepatitis B vaccine in infants.
Adult
;
Biomarkers/blood*
;
DNA, Viral/blood*
;
Diagnostic Tests, Routine
;
Female
;
Hepatitis B/prevention & control*
;
Hepatitis B Antibodies/blood*
;
Hepatitis B Surface Antigens/blood*
;
Hepatitis B Vaccines/pharmacology*
;
Hepatitis B e Antigens/blood*
;
Hepatitis B virus/isolation & purification*
;
Humans
;
Infant
;
Infectious Disease Transmission, Vertical/prevention & control*
;
Mothers
;
Pregnancy
;
Pregnancy Complications, Infectious/virology*
4.Prevalence of hepatitis B, hepatitis C and human immunodeficiency viral infections in patients with inflammatory bowel disease in north India.
Parnita HARSH ; Vipin GUPTA ; Saurabh KEDIA ; Sawan BOPANNA ; Sucharita PILLI ; SURENDERNATH ; Govind Kumar MAKHARIA ; Vineet AHUJA
Intestinal Research 2017;15(1):97-102
BACKGROUND/AIMS: Patients with inflammatory bowel disease (IBD) often require immunosuppressive therapy and blood transfusions and therefore are at a high risk of contracting infections due to hepatitis B (HBV) and hepatitis C (HCV) and human immunodeficiency virus (HIV). In the present study, we assessed the prevalence of these infections in patients with IBD. METHODS: This retrospective study included 908 consecutive patients with IBD (ulcerative colitis [UC], n=581; Crohn's disease [CD], n=327) who were receiving care at a tertiary care center. Ninety-five patients with intestinal tuberculosis (ITB) were recruited as disease controls. Prospectively maintained patient databases were reviewed for the prevalence of HBV surface antigen, anti-HCV antibodies, and HIV (enzyme-linked immunosorbent assay method). HCV RNA was examined in patients who tested positive for anti-HCV antibodies. Prevalence data of the study were compared with that of the general Indian population (HBV, 3.7%; HCV, 1%; HIV, 0.3%). RESULTS: The prevalence of HBV, HCV, and HIV was 2.4%, 1.4%, and 0.1%, respectively, in the 908 patients with IBD. Among the 581 patients with UC, 2.2% (12/541) had HBV, 1.7% (9/517) had HCV, and 0.2% (1/499) had HIV. Among the 327 patients with CD, 2.8% (8/288) had HBV, 0.7% (2/273) had HCV, and 0% (0/277) had HIV. One patient with CD had HBV and HCV coinfection. The prevalence of HBV, HCV, and HIV in patients with ITB was 5.9% (4/67), 1.8% (1/57), and 1.2% (1/84), respectively. CONCLUSIONS: The prevalence of HBV, HCV, and HIV in north Indian patients with IBD is similar to the prevalence of these viruses in the general community. Nonetheless, the high risk of flare after immunosuppressive therapy mandates routine screening of patients with IBD for viral markers.
Antigens, Surface
;
Biomarkers
;
Blood Transfusion
;
Coinfection
;
Colitis
;
Colitis, Ulcerative
;
Crohn Disease
;
Hepatitis B*
;
Hepatitis C Antibodies
;
Hepatitis C*
;
Hepatitis*
;
HIV
;
Humans*
;
India*
;
Inflammatory Bowel Diseases*
;
Mass Screening
;
Prevalence*
;
Prospective Studies
;
Retrospective Studies
;
RNA
;
Tertiary Care Centers
;
Tuberculosis
5.A Korean patient with Guillain-Barré syndrome following acute hepatitis E whose cholestasis resolved with steroid therapy.
Sung Bok JI ; Sang Soo LEE ; Hee Cheul JUNG ; Hong Jun KIM ; Hyun Jin KIM ; Tae Hyo KIM ; Woon Tae JUNG ; Ok Jae LEE ; Dae Hyun SONG
Clinical and Molecular Hepatology 2016;22(3):396-399
Autochthonous hepatitis E virus (HEV) is an emerging pathogen in developed countries, and several cases of acute HEV infection have been reported in South Korea. However, there have been no reports on HEV-associated Guillain-Barré syndrome (GBS) in Korea. We recently experienced the case of a 58-year-old Korean male with acute HEV infection after ingesting raw deer meat. Persistent cholestasis was resolved by the administration of prednisolone. At 2.5 months after the clinical presentation of HEV infection, the patient developed weakness of the lower limbs, and was diagnosed with GBS associated with acute hepatitis E. To our knowledge, this is the second report on supportive steroid therapy for persistent cholestasis due to hepatitis E, and the first report of GBS in a Korean patient with acute HEV infection.
Acute Disease
;
Alanine Transaminase/blood
;
Antibodies, Viral/blood
;
Aspartate Aminotransferases/blood
;
Bilirubin/analysis
;
Cholestasis/*drug therapy
;
Guillain-Barre Syndrome/complications/*diagnosis
;
Hepatitis E/*diagnosis/etiology
;
Hepatitis E virus/immunology
;
Humans
;
Immunoglobulin M/blood
;
Liver/pathology
;
Male
;
Middle Aged
;
Prednisolone/therapeutic use
;
Republic of Korea
;
Steroids/*therapeutic use
6.Immunosuppression status of liver transplant recipients with hepatitis C affects biopsy-proven acute rejection.
Jong Man KIM ; Kwang Woong LEE ; Gi Won SONG ; Bo Hyun JUNG ; Hae Won LEE ; Nam Joon YI ; ChoonHyuck David KWON ; Shin HWANG ; Kyung Suk SUH ; Jae Won JOH ; Suk Koo LEE ; Sung Gyu LEE
Clinical and Molecular Hepatology 2016;22(3):366-371
BACKGROUND/AIMS: The relationship between patient survival and biopsy-proven acute rejection (BPAR) in liver transplant recipients with hepatitis C remains unclear. The aims of this study were to compare the characteristics of patients with and without BPAR and to identify risk factors for BPAR. METHODS: We retrospectively reviewed the records of 169 HCV-RNA-positive patients who underwent LT at three centers. RESULTS: BPAR occurred in 39 (23.1%) of the HCV-RNA-positive recipients after LT. The 1-, 3-, and 5-year survival rates were 92.1%, 90.3%, and 88.5%, respectively, in patients without BPAR, and 75.7%, 63.4%, and 58.9% in patients with BPAR (P<0.001). Multivariate analyses showed that BPAR was associated with the non-use of basiliximab and tacrolimus and the use of cyclosporin in LT recipients with HCV RNA-positive. CONCLUSION: The results of the present study suggest that the immunosuppression status of HCV-RNA-positive LT recipients should be carefully determined in order to prevent BPAR and to improve patient survival.
Antibodies, Monoclonal/therapeutic use
;
Biopsy
;
Cyclosporine/therapeutic use
;
Drug Therapy, Combination
;
Genotype
;
Graft Rejection/mortality/*prevention & control
;
Hepacivirus/genetics/isolation & purification
;
Hepatitis C/drug therapy/*virology
;
Humans
;
Immunosuppressive Agents/*therapeutic use
;
*Liver Transplantation/adverse effects
;
Polymerase Chain Reaction
;
RNA, Viral/blood
;
Recombinant Fusion Proteins/therapeutic use
;
Recurrence
;
Retrospective Studies
;
Survival Rate
;
Tacrolimus/therapeutic use
7.Long-term efficacy of neonatal hepatitis B vaccination against chronic hepatitis B virus infection and chronic liver disease: a cross-sectional study based on Qidong Hepatitis B Intervention Study.
Taoyang CHEN ; Chunfeng QU ; Hongyu YAO ; Lingling LU ; Jian FAN ; Yuting WANG ; Fei HUANG ; Jianhua LU ; Zhengping NI ; Chunsun FAN ; Yawei ZHANG ;
Chinese Journal of Epidemiology 2016;37(1):64-67
OBJECTIVETo evaluate the long-term protection efficacy of neonatal hepatitis B vaccination on chronic hepatitis B (CHB) and liver fibrosis and cirrhosis in adults.
METHODSFrom January to October, 2013, a cross-sectional study was conducted among the participants from Qidong Hepatitis B Intervention Study (QHBIS), who were selected through stratified random sampling. The detections of serum alanine aminotransferase (ALT), HBsAg, anti-HBs, anti-HBc, HBeAg, and anti-HBe were conducted and ultrasonography on liver, gallbladder and spleen was performed for them. The positive rates of each serologic markers, the prevalence of active CHB and liver fibrosis and cirrhosis were calculated, the gender specific differences between vaccination group and control group were compared with Chi-square test.
RESULTSA total of 4 421 participants aged (25.59±1.84) years in vaccination group and 3 880 participants aged (26.61±2.24) years in control group were surveyed. The positive rates of HBsAg, anti-HBs, anti-HBc, HBeAg and anti-HBe were 2.38%, 37.73%, 3.78%, 0.57% and 2.15% in vaccination group, and 9.02%, 29.41%, 16.83%, 2.73% and 8.87% in control group, respectively, the differences between two groups were statistically significant (all P<0.05). The prevalence of active CHB and liver fibrosis and cirrhosis were 0.45% and 0.16% in vaccination group, 1.29% and 0.39% in control group, the differences between two groups were statistically significant (P<0.05). The active CHB prevalence was lower in females than in males in both vaccination group and control group (P<0.05). The liver fibrosis and cirrhosis prevalence was lower in females than in males in control group (P<0.05); whereas, no statistical significant difference in liver fibrosis & cirrhosis prevalence between males and females was found in vaccination group (P>0.05).
CONCLUSIONSProtection conferred by neonatal hepatitis B vaccination could last to marrying age. The gender specific difference in protection efficacy needs further study.
Adult ; China ; Cross-Sectional Studies ; Female ; Hepatitis B Antibodies ; blood ; Hepatitis B Surface Antigens ; blood ; Hepatitis B Vaccines ; therapeutic use ; Hepatitis B virus ; Hepatitis B, Chronic ; prevention & control ; Humans ; Liver Cirrhosis ; Male ; Prevalence ; Vaccination ; statistics & numerical data
8.Distribution of both HBsAg and HBsAb negative adults in Mianyang, Sichuan province.
Shuwen CHENG ; Chuan XIAO ; Min WANG ; Lan WANG ; Juan WANG ; Tao REN ; Liping WANG ; Xiaohua WEN ; Wenhao ZHANG ; Ping YUAN
Chinese Journal of Epidemiology 2016;37(1):60-63
OBJECTIVETo understand the distribution of both HBsAg and HBsAb negative adults in Mianyang, Sichuan province, and provide evidences for the development of adult immunization policy.
METHODSFrom June 2013 to April 2014, a total of 200 929 people aged ≥15 years were selected in Mianyang through stratified cluster random sampling to conduct an interview with standard questionnaire. The blood samples were collected from them for the detection of HBsAg and HBsAb with enzyme-linked immunosorbent assay (ELISA).
RESULTSAmong the people surveyed, 13 903 were HBsAg positive (7.0%), 93 763 were HBsAb positive (46.6%), and 93 122 were both HBsAg and HBsAb negative (46.3%). The negative rate of both HBsAg and HBsAb in females (47.1%) was higher than that in males (45.4%). The negative rate of both HBsAg and HBsAb increased with age. The negative rate of both HBsAg and HBsAb was highest in people aged ≥65 years (50.3%) and lowest in people aged 15-24 years (42.9%). The negative rate of both HBsAg and HBsAb was highest in farmers (51.1%) and lowest in medical workers (24.1%). The negative rate of both HBsAg and HBsAb was highest in the widowed (51.1%) and lowest in the unmarried (41.6%). The negative rate of both HBsAg and HBsAb was lower in people with family history of hepatitis B (36.5%) than in people without family history of hepatitis B (46.6%). The negative rate of both HBsAg and HBsAb in Han ethnic group was lower (46.3%) than that in Qiang ethnic group (53.1%), but higher than that in other ethnic groups (43.9%). The negative rate of both HBsAg and HBsAb was higher in rural area (48.9%) than in urban area (43.0%). The negative rate of both HBsAg and HBsAb was lower in people who had received hepatitis B immunization (43.7%) than in people who had received no hepatitis B immunization (47.3%). The differences were all statistical significant (P<0.01).
CONCLUSIONThe negative rate of both HBsAg and HBsAb was 46.3% in people aged ≥15 years in Mianyang. General population are susceptible to hepatitis B virus infection. It is necessary to develop and implement appropriate hepatitis B immunization strategy for local adult population.
Adolescent ; Adult ; Aged ; China ; epidemiology ; Enzyme-Linked Immunosorbent Assay ; Ethnic Groups ; Female ; Health Personnel ; Hepatitis B ; epidemiology ; Hepatitis B Antibodies ; blood ; Hepatitis B Surface Antigens ; blood ; Hepatitis B Vaccines ; administration & dosage ; Hepatitis B virus ; Humans ; Male ; Middle Aged ; Seroepidemiologic Studies ; Surveys and Questionnaires ; Vaccination ; statistics & numerical data ; Young Adult
9.Characteristics of lymphocyte phenotypes in HBV transgenic mice and the effect of interferon-α: a preliminary study.
Xin YAN ; Rui-Hua ZHONG ; Jin-Hong LIU ; Yang ZHOU ; Li-Bo TANG ; Yong-Yin LI ; Guang-Ze LIU ; Jin-Lin HOU
Journal of Southern Medical University 2016;36(6):870-874
OBJECTIVETo analyze the characteristics of lymphocyte phenotypes in hepatitis B virus (HBV) transgenic mice and the effect of exogenous interferon-α on virological profiles and lymphocytes phenotypes of the mice.
METHODSHBV transgenic mice and wild-type (WT) mice were examined for serum levels of HBsAg, HBcAb, IL-21, and IL-6 using ELISA. The frequencies of CD4(+)T and CD19(+)B cells separated from the liver, spleen, and peripheral blood were detected by flow cytometry. Nine HBV transgenic mice were injected subcutaneously with recombinant mouse interferon alpha (rmIFN-α) and another 9 transgenic mice were injected with PBS, and their HBsAg, HBV DNA, IL-6, and IL-21 levels and frequencies of peripheral blood CD4(+)T and CD19(+)B cells were detected.
RESULTSHBV transgenic mice showed a high level of HBsAg with a detectable level of HBcAb and significantly increased serum levels of IL-21 and IL-6 as compared with WT mice (P<0.05). The transgenic mice had a significantly lower frequency of CD4(+) T cells in the peripheral blood, liver and spleen (P<0.05) but a significantly higher frequency of CD19(+) B cells in the liver (P<0.05). An inverse correlation between intrahepatic CD4(+) T cell frequency and serum HBsAg level while a positive correlation between intrahepatic CD19(+) B cell frequency and HBcAb level were found in HBV transgenic mice. Administration of rmIFN-α significantly increased the frequencies of CD4(+) T and CD19(+) B cells in the peripheral blood and the serum level of IL-6 in HBV transgenic mice (P<0.05).
CONCLUSIONHBV transgenic mice have lymphocyte subset dysregulation and exogenous interferon-α can modulate the immune function of the mice by regulating the frequencies of lymphocyte subsets.
Animals ; Antiviral Agents ; pharmacology ; B-Lymphocytes ; drug effects ; DNA, Viral ; blood ; Hepatitis B ; drug therapy ; immunology ; Hepatitis B Antibodies ; blood ; Hepatitis B Surface Antigens ; blood ; Hepatitis B virus ; Interferon-alpha ; pharmacology ; Interleukin-6 ; blood ; Interleukins ; blood ; Liver ; immunology ; Lymphocyte Subsets ; cytology ; drug effects ; Mice ; Mice, Transgenic ; Phenotype ; T-Lymphocytes ; drug effects
10.Comparison of the clinical outcomes between antiviral-naïve patients treated with entecavir and lamivudine-resistant patients receiving adefovir add-on lamivudine combination treatment.
Hong Joo KIM ; Soo Kyung PARK ; Hyo Joon YANG ; Yoon Suk JUNG ; Jung Ho PARK ; Dong Il PARK ; Yong Kyun CHO ; Chong Il SOHN ; Woo Kyu JEON ; Byung Ik KIM ; Kyu Yong CHOI
Clinical and Molecular Hepatology 2016;22(3):350-358
BACKGROUND/AIMS: To analyze the effects of preexisting lamivudine (LAM) resistance and applying antiviral treatment (adefovir [ADV] add-on LAM combination treatment) on long-term treatment outcomes, and comparing the clinical outcomes of antiviral-naïve chronic hepatitis B patients receiving entecavir (ETV) monotherapy. METHODS: This study enrolled 73 antiviral-naïve patients who received 0.5-mg ETV as an initial therapy and 54 patients who received ADV add-on LAM combination treatment as a rescue therapy from July 2006 to July 2010. RESULTS: During 24-month treatments, the decreases in serum log10HBV-DNA values (copies/mL) were significantly greater in the antiviral-naïve patients treated with ETV than the patients receiving ADV add-on LAM combination treatment. The biochemical response rates for alanine aminotransferase normalization at 6 months (ETV) and 12 months (ADV add-on LAM) were 90.4% (66/73) and 77.8% (42/54), respectively (P=0.048). A Kaplan-Meier analysis indicated that the rates of serologic response, viral breakthrough, and emergence of genotypic resistance did not differ significantly between the two patient groups. There were also no significant intergroup differences in the rates of disease progression (PD) and new development of hepatocellular carcinoma (HCC). CONCLUSION: The long-term clinical outcomes of antiviral-naïve patients treated with ETV and LAM-resistant patients receiving ADV add-on LAM combination treatment were comparable in terms of the emergence of HCC and disease progression.
Adenine/*analogs & derivatives/pharmacology/therapeutic use
;
Adult
;
Alanine Transaminase/blood
;
Antibodies, Viral/blood
;
Antiviral Agents/*therapeutic use
;
DNA, Viral/blood
;
Disease Progression
;
Drug Resistance, Viral/drug effects
;
Drug Therapy, Combination
;
Female
;
Follow-Up Studies
;
Genotype
;
Guanine/analogs & derivatives/pharmacology/therapeutic use
;
Hepatitis B e Antigens/blood
;
Hepatitis B virus/drug effects/genetics/isolation & purification
;
Hepatitis B, Chronic/*drug therapy
;
Humans
;
Lamivudine/pharmacology/therapeutic use
;
Male
;
Middle Aged
;
Organophosphonates/pharmacology/*therapeutic use
;
Treatment Outcome

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