Objective: Despite the remarkable progress in efforts to control disease spread, the nationwide elimination of hepatitis B in China is still hindered by the persistently high rate of hepatitis B virus (HBV) infection in Western China. This study aimed to evaluate the strategy of hepatitis B prevention and control in Western China and identify potential areas and strategies for improvement. Methods: Susceptible population vaccination, health education, professional training of doctors, and other prevention and control measures have been implemented in Wuwei city since 2010. Data were obtained from three representative cross-sectional serosurveys conducted in 2010, 2013, and 2015. The serum samples were subjected to enzyme-linked immunosorbent assays to detect the following seromarkers: HBV surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs), and antibody against hepatitis B core antigen (anti-HBc). Estimates of variance were determined using Taylor series linearization methods. Results: The three serosurveys revealed decreases in the prevalence of HBsAg (7.19% in 2010 Conclusion Although vaccine-based prevention and control measures reduced the rate of HBV infection in Wuwei City over time, the hepatitis B infection rate in children younger than 10 years was still higher than the national average level. Therefore, the prevention and control of mother-to-child transmission and the management of the infected should be the focus of future prevention and control work.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; China/epidemiology* ; Communicable Disease Control/statistics & numerical data* ; Cross-Sectional Studies ; Female ; Hepatitis B/prevention & control* ; Hepatitis B virus/isolation & purification* ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Prevalence ; Seroepidemiologic Studies ; Young Adult

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

<b>Objective:b> 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. <b>Methods:b> 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. <b>Results:b> 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). <b>Conclusions:b> "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*

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

BACKGROUND/AIMS: This study aimed to clarify the effect of obesity on the development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients receiving antiviral treatment. METHODS: This study applied a retrospective analysis to a historical cohort in Bundang Jesaeng Hospital. In total, 102 CHB patients were treated with entecavir as an initial treatment for CHB and checked for obesity using a body composition analyzer. Hepatic steatosis was measured semiquantitatively using Hamaguchi’s scoring system in ultrasonography. Risk factors for the development of HCC were analyzed, including obesity-related factors (body mass index [BMI], waist circumference [WC], waist-to-hip ratio [WHR], visceral fat area [VFA], and hepatic steatosis). RESULTS: The median follow-up duration of the patients was 45.2 months (interquartile range: 36.0-58.3 months). The cumulative incidence rates of HCC at 1 year, 3 years, and 5 years were 0%, 5.3%, and 9.0%, respectively. Univariable analysis revealed that the risk factors for HCC development were a platelet count of <120,000 /mm² (hazard ratio [HR]=5.21, P=0.031), HBeAg negativity (HR=5.61, P=0.039), and liver cirrhosis (HR=10.26, P=0.031). Multivariable analysis showed that the significant risk factor for HCC development was liver cirrhosis (HR=9.07, P=0.042). However, none of the obesity-related risk factors were significantly associated with HCC: BMI ≥25 kg/m² (HR=0.90, P=0.894), WC ≥90 cm (HR=1.10, P=0.912), WHR ≥0.9 (HR=1.94, P=0.386), VFA ≥100 cm² (HR=1.69, P=0.495), and hepatic steatosis (HR=0.57, P=0.602). CONCLUSION: HCC development is associated with liver cirrhosis but not obesity-related factors in CHB patients receiving entecavir.
Adult ; Antiviral Agents/*therapeutic use ; Body Mass Index ; Carcinoma, Hepatocellular/epidemiology/*etiology ; Cohort Studies ; DNA, Viral/blood ; Female ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B virus/genetics/isolation & purification ; Hepatitis B, Chronic/complications/*drug therapy/virology ; Humans ; Incidence ; Liver Cirrhosis/complications ; Liver Neoplasms/epidemiology/*etiology ; Male ; Middle Aged ; Obesity/*complications ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Viral Load

BACKGROUND/AIMS: The optimal timing for discontinuing oral antiviral therapy in patients with HBeAg-positive chronic hepatitis B (CHB) is unclear. The aim of our study was to investigate sustained remission after stopping antiviral therapy in patients with HBeAg-positive CHB. METHODS: We analyzed the medical records of 58 patients who were HBeAg-positive and had discontinued antiviral therapy. Antiviral therapy was discontinued after HBeAg seroconversion and HBV DNA negativity for 6-12 months with consolidation therapy. Virologic relapse was defined as an increase in serum HBV DNA >2,000 IU/mL. RESULTS: No difference was observed between the virologic non-relapse and virologic relapse groups in baseline HBV DNA level (p=0.441) or duration of seroconversion (p=0.070). Time-to-undetectable HBV DNA during treatment was shorter in the virologic non-relapse group (29 patients) compared to the relapse group (29 patients) (4.9+/-2.6 vs. 13.2+/-12.7 months; p<0.01). Cumulative relapse rates were 12.7 in month 3, 32.7 in month 6, 47.3 in month 12, and 52.7% in month 18. We determined by multivariate analysis that the consolidation period (> or =18 months, p=0.020) and early virologic response (HBV DNA <20 IU/mL) at six months during antiviral therapy (p=0.017) were significant predictors for sustained remission. CONCLUSIONS: A consolidation period of at least 18 months and early virological response at six months during antiviral therapy were associated with sustained remission in patients with HBeAg-positive CHB after treatment.
Adult ; Aged ; Antiviral Agents/*therapeutic use ; DNA, Viral/analysis ; Female ; Hepatitis B e Antigens/*blood ; Hepatitis B virus/genetics/isolation & purification ; Hepatitis B, Chronic/*drug therapy ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Proportional Hazards Models ; Recurrence ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Withholding Treatment

BACKGROUND/AIMS: Before tenofovir (TDF) become available in South Korea, combination therapy with entecavir (ETV) and adefovir (ADV) was the most potent regimen for chronic hepatitis B (CHB) patients who fail to respond to rescue therapy for drug resistance. We analyzed the efficacy of ETV-ADV combination therapy and investigated the clinical and clonal results of TDF-based rescue therapy in CHB patients refractory to this combination. METHODS: We retrospectively reviewed the medical records of CHB patients treated for up to 3 years with ETV-ADV combination therapy as a rescue therapy for drug resistance. In cases refractory to this combination, clinical and clonal analyses were performed for TDF-based rescue therapy. RESULTS: The analysis was performed on 48 patients. Twelve patients achieved a virological response (VR) within 3 years. A VR was subsequently achieved in nine of the ten patients without a VR who switched to TDF monotherapy. A VR was also achieved in six of the seven patients who switched to lamivudine-TDF combination therapy, and in two of the two patients who switched to ETV-TDF combination therapy. In an in vitro susceptibility test, viral replication was detected with TDF monotherapy but not with ETV-TDF combination therapy. CONCLUSIONS: The efficacy of ETV-ADV combination therapy was insufficient in CHB patients who were refractory to rescue therapy. A more potent regimen such as ETV-TDF combination therapy may be considered in such refractory cases.
Adenine/*analogs & derivatives/therapeutic use ; Adult ; Aged ; Antiviral Agents/*therapeutic use ; DNA, Viral/analysis/metabolism ; Drug Resistance, Viral ; Drug Therapy, Combination ; Female ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B virus/genetics/isolation & purification ; Hepatitis B, Chronic/*drug therapy/virology ; Humans ; Male ; Middle Aged ; Organophosphonates/*therapeutic use ; Polymerase Chain Reaction ; Republic of Korea ; Retrospective Studies ; Tenofovir/*therapeutic use ; Treatment Outcome

BACKGROUND/AIMS: Before tenofovir (TDF) become available in South Korea, combination therapy with entecavir (ETV) and adefovir (ADV) was the most potent regimen for chronic hepatitis B (CHB) patients who fail to respond to rescue therapy for drug resistance. We analyzed the efficacy of ETV-ADV combination therapy and investigated the clinical and clonal results of TDF-based rescue therapy in CHB patients refractory to this combination. METHODS: We retrospectively reviewed the medical records of CHB patients treated for up to 3 years with ETV-ADV combination therapy as a rescue therapy for drug resistance. In cases refractory to this combination, clinical and clonal analyses were performed for TDF-based rescue therapy. RESULTS: The analysis was performed on 48 patients. Twelve patients achieved a virological response (VR) within 3 years. A VR was subsequently achieved in nine of the ten patients without a VR who switched to TDF monotherapy. A VR was also achieved in six of the seven patients who switched to lamivudine-TDF combination therapy, and in two of the two patients who switched to ETV-TDF combination therapy. In an in vitro susceptibility test, viral replication was detected with TDF monotherapy but not with ETV-TDF combination therapy. CONCLUSIONS: The efficacy of ETV-ADV combination therapy was insufficient in CHB patients who were refractory to rescue therapy. A more potent regimen such as ETV-TDF combination therapy may be considered in such refractory cases.
Adenine/*analogs & derivatives/therapeutic use ; Adult ; Aged ; Antiviral Agents/*therapeutic use ; DNA, Viral/analysis/metabolism ; Drug Resistance, Viral ; Drug Therapy, Combination ; Female ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B virus/genetics/isolation & purification ; Hepatitis B, Chronic/*drug therapy/virology ; Humans ; Male ; Middle Aged ; Organophosphonates/*therapeutic use ; Polymerase Chain Reaction ; Republic of Korea ; Retrospective Studies ; Tenofovir/*therapeutic use ; Treatment Outcome

BACKGROUND/AIMS: Clear indicators for stopping antiviral therapy in chronic hepatitis B (CHB) patients are not yet available. Since the level of hepatitis B surface antigen (HBsAg) is correlated with covalently closed circular DNA, the HBsAg titer might be a good indicator of the off-treatment response. This study aimed to determine the relationship between the HBsAg titer and the entecavir (ETV) off-treatment response. METHODS: This study analyzed 44 consecutive CHB patients (age, 44.6±11.4 years, mean±SD; men, 63.6%; positive hepatitis B envelope antigen (HBeAg) at baseline, 56.8%; HBV DNA level, 6.8±1.3 log₁₀ IU/mL) treated with ETV for a sufficient duration and in whom treatment was discontinued after HBsAg levels were measured. A virological relapse was defined as an increase in serum HBV DNA level of >2000 IU/mL, and a clinical relapse was defined as a virological relapse with a biochemical flare, defined as an increase in the serum alanine aminotransferase level of >2 × upper limit of normal. RESULTS: After stopping ETV, virological relapse and clinical relapse were observed in 32 and 24 patients, respectively, during 20.8±19.9 months of follow-up. The cumulative incidence rates of virological relapse were 36.2% and 66.2%, respectively, at 6 and 12 months, and those of clinical relapse were 14.3% and 42.3%. The off-treatment HBsAg level was an independent factor associated with clinical relapse (hazard ratio, 2.251; 95% confidence interval, 1.076–4.706; P=0.031). When patients were grouped according to off-treatment HBsAg levels, clinical relapse did not occur in patients with an off-treatment HBsAg level of ≤2 log10 IU/mL (n=5), while the incidence rates of clinical relapse at 12 months after off-treatment were 28.4% and 55.7% in patients with off-treatment HBsAg levels of >2 and ≤3 log₁₀ IU/mL (n=11) and >3 log₁₀ IU/mL (n=28), respectively. CONCLUSION: The off-treatment HBsAg level is closely related to clinical relapse after treatment cessation. A serum HBsAg level of <2 log₁₀ IU/mL is an excellent predictor of a sustained off-treatment response in CHB patients who have received ETV for a sufficient duration.
Adult ; Alanine Transaminase/blood ; Antiviral Agents/*therapeutic use ; DNA, Viral/blood ; Female ; Follow-Up Studies ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B Surface Antigens/blood ; Hepatitis B virus/genetics/isolation & purification ; Hepatitis B, Chronic/*drug therapy ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Polymerase Chain Reaction ; Recurrence ; Treatment Outcome

We wished to undertake molecular genetic typing and evaluate recombinants of the hepatitis-B virus (HBV) in Tibet (China). Multistage random sampling was used to collect HBsAg-positive samples. Nested polymerase chain reactions were used to amplify the whole sequence of the HBV. DNAstar, MEGA6 and SimPlot were used to assemble sequences, create phylogenetic trees, and undertake recombination analyses. Twelve whole sequences of the HBV of a Tibetan population were collected using these methods. Results showed that all 12 strains were C/D recombinants. Nine of the recombinations were at nt750, and the other three at nt1526. Therefore, the 12 strains could be divided into two types of recombinants: C/Da and C/Db. Analyses of the sequence of the whole genome revealed that the 12 strains belonged to genotype C, and that the nucleotide distance was > 4% between the 12 strains and sub-genotypes C1 to C15 in Genbank. The most likely sub-genotype was C1. Individuals with C/Da were from central and northern Tibet (e.g., Lasa, Linzhi, Ali) and those with C/Db recombinants were from Shannan in southern Tibet. These data suggest that the two types of recombinants had a good distribution in Tibet. Also, they can provide important information for studies on HBV recombination, gene features, virus evolution, as well as the control and prevention of HBV infection in Tibet.
Adult ; Female ; Genotype ; Hepatitis B ; virology ; Hepatitis B virus ; classification ; genetics ; isolation & purification ; Humans ; Male ; Phylogeny ; Recombination, Genetic ; Sequence Analysis, DNA ; Tibet ; Young Adult