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

To evaluate the efficacy and safety of Gantaishu Capsules in the treatment of viral B hepatitis. The randomized controlled trials( RCT) retrieved from Cochrane Library,PubMed,Sino Med,CNKI,Wan Fang and VIP were enrolled. The methodology quality of the included studies was evaluated,and a Meta-analysis was performed using Rev Man 5. 3 software. A total of six randomized controlled trials were included. Meta-analysis results showed that the similarities in the negative conversion rate of HBe Ag( RR = 2. 09,95%CI[0. 90,4. 85],P = 0. 09,I2= 0%),the HBV-DNA negative rate( RR = 1. 49,95% CI[0. 56,3. 95],P = 0. 43,I2= 0%) and the changes in ALT levels before and after treatment( RR =-6. 28,95%CI[-72. 83,60. 27],P = 0. 85,I2= 99%),with no statistical difference. In terms of quality of life,Gantaishu Capsules can significantly alleviate the symptoms of hepatitis B patients,with less adverse reactions. Gantaishu Capsules and Dongbao Gantai Tablets were similar in antiviral effect. In this term,Gantaishu Capsules was superior to Dangfei Liganning Capsules. It can significantly alleviate the symptoms of chronic hepatitis B patients,with a good clinical safety.Therefore,it can be applied in the case of syndrome differentiation and treatment. In view of the low quality of the included studies,more high-quality clinical trials were required to confirm its efficacy.
Antiviral Agents ; therapeutic use ; Capsules ; DNA, Viral ; blood ; Drugs, Chinese Herbal ; therapeutic use ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; Humans ; Quality of Life

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

Chronic hepatitis B virus (HBV) infection remains a major world public health problem. Current guidelines for the prevention and treatment of chronic hepatitis B (CHB) have suggested clinical cure (also known as functional cure) as the ideal therapeutic goal, which is associated with decreased risk of cirrhosis and hepatocellular carcinoma. Clinical cure is defined as sustained, undetectable serum HBsAg, HBeAg and HBV DNA with or without seroconversion to anti-HBs, but with the persistence of residual cccDNA, accompanied by resolution of liver injury after the completion of a finite course of treatment. Accumulating data from a series of randomized controlled trials as well as clinical practice have confirmed certain clinical benefit of optimal sequential/ combination strategies of direct acting antiviral drugs (DAA) [such as nucleoside analogues (NA)] or immunomodulators (such as pegylated interferon alpha (Peg-IFN)] for appropriately selected CHB patients. This consensus provides an updated and comprehensive analysis of the data supporting the use of combination therapies and summarizes the roadmap towards clinical cure of CHB to guide decision-making in clinical practice.
Antiviral Agents/therapeutic use* ; Consensus ; DNA, Viral/blood* ; Hepatitis B Surface Antigens/blood* ; Hepatitis B e Antigens/blood* ; Hepatitis B virus ; Hepatitis B, Chronic/therapy* ; Humans ; Practice Guidelines as Topic ; Randomized Controlled Trials as Topic

BACKGROUND: To improve Rh-related antigen negative blood supply effectively, the Korean Red Cross (KRC) blood centers have performed Rh phenotype screening tests of C, c, E and e antigens for all donors since April, 2013. Especially for rare ‘-D-/-D-’ blood supply and donor recruitment, we have implemented Rh phenotype confirmation test for all C, c, E and e antigen negative donors. In this study, we report the test results of 7 donors with ‘-D-/-D-’ phenotype. METHODS: All three KRC Blood Laboratory Centers performed Rh phenotype screening tests using the automatic machine, PK7300 (Beckman Coulter, Japan), for all 876,920 donors from January 1, 2018 to April 30, 2018. We then performed the Rh phenotype confirmation test using the tube method manually, at room temperature, 37℃ and antihuman globulin phase. RESULTS: Among 876,920 donors, 14 were Rh antigen C, c, E, e negative as results of Rh phenotype screening test. The results of Rh phenotype confirmation test of these 14 donors showed that 7 donors were Rh antigen C, c, E, e negative. The ratio of -D-/-D- phenotype for all donors was 0.000798%. CONCLUSION: Our data suggests that -D-/-D- phenotype is one of the rare blood groups among Koreans. Although ‘-D-/-D-’ phenotype was confirmed by serologic tests, it is necessary to re-confirm it by molecular genetic techniques.
Blood Group Antigens ; Hepatitis B e Antigens ; Humans ; Mass Screening ; Methods ; Molecular Biology ; Phenotype* ; Red Cross ; Serologic Tests ; Tissue Donors*

Background: Cytokines play an important role in occurrence and recovery of hepatitis B virus (HBV) infection. The aim of this study was to investigate the changes of cytokines concentration and its correlation to alanine aminotransferase (ALT), HBV deoxyribonucleic acid (HBV-DNA), hepatitis B envelope antigen (HBeAg), and HBV surface antigen (HBsAg) in the development of chronic hepatitis B (CHB). Methods: Thirteen healthy individuals (HI), 30 chronic HBV-infected patients in immune tolerant (IT) phase, and 55 CHB patients were enrolled between August 2015 and May 2017. The peripheral blood samples were collected from all individuals. The levels of interferon (IFN)-α2, interleukin (IL)-10, transforming growth factor (TGF)-β1, HBV-DNA, HBsAg, and HBeAg and liver function were measured. The quantitative determinations of cytokines levels, including IFN-α2, IL-10, and TGF-β1 were performed using Luminex multiplex technology. The correlation of cytokines to ALT, HBV-DNA, HBsAg, and HBeAg was analyzed by linear regression analysis. Results: IFN-α2 levels were similar between HI and IT groups (15.35 [5.70, 67.65] pg/ml vs. 15.24 [4.07, 30.73] pg/ml, Z = -0.610, P = 0.542), while it elevated significantly in CHB group (35.29 [15.94, 70.15] pg/ml vs. 15.24 [4.07, 30.73] pg/ml; Z = -2.522, P = 0.012). Compared with HI group (3.73 [2.98, 11.92] pg/ml), IL-10 concentrations in IT group (5.02 [2.98, 10.11] pg/ml), and CHB group (7.48 [3.10, 18.00] pg/ml) slightly increased (χ = 2.015, P = 0.365), and there was no significant difference between IT and CHB group (Z = -1.419, P = 0.156). The TGF-β1 levels among HI (3.59 ± 0.20 pg/ml), IT (3.62 ± 0.55 pg/ml), and CHB groups (3.64 ± 0.30 pg/ml) were similar (χ = 2.739, P = 0.254). In all chronic HBV-infected patients (including patients in IT and CHB groups), the elevation of IFN-α2 level was significantly associated with ALT level (β= 0.389, t = 2.423, P = 0.018), and was also negatively correlated to HBV-DNA load (β = -0.358, t = -2.308, P = 0.024), HBsAg (β = -0.359, t = -2.288, P = 0.025), and HBeAg contents (β = -0.355, t = -2.258, P = 0.027). However, when both ALT level and cytokines were included as independent variable, HBV-DNA load, HBsAg, and HBeAg contents were only correlated to ALT level (β = -0.459, t = -4.225, P = 0.000; β = -0.616, t = -6.334, P = 0.000; and β = -0.290, t = -2.433, P = 0.018; respectively). Conclusions IFN-α2 elevation was associated with ALT level in patients with chronic HBV infection. However, in CHB patients, only ALT level was correlated to HBV-DNA, HBsAg and HBeAg contents.
Adult ; Alanine Transaminase ; blood ; Antigens, Surface ; Case-Control Studies ; Cytokines ; blood ; DNA, Viral ; Female ; Hepatitis B ; Hepatitis B Surface Antigens ; analysis ; Hepatitis B e Antigens ; Hepatitis B virus ; Hepatitis B, Chronic ; blood ; immunology ; Humans ; Male ; Young Adult

<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*

<b>OBJECTIVEb>To explore the predictive value of baseline HBsAg level and early response for HBsAg loss in patients with HBeAg-positive chronic hepatitis B during pegylated interferon alpha-2a treatment.

<b>METHODSb>A total of 121 patients with HBeAg-positive chronic hepatitis B who achieved HBsAg loss were enrolled; all patients were treated with PEG-IFNα-2a 180 μg/week. Serum HBV DNA and serological indicators (HBsAg, anti-HBs, HBeAg, and anti-HBe) were determined before and every 3 months during treatment.

<b>RESULTSb>The median treatment time for HBsAg loss was 84 weeks (7-273 weeks), and 74.38% (90 cases) of the patients needed extended treatment (> 48 weeks). The correlation between baseline HBsAg levels and the treatment time of HBsAg loss was significant (B = 14.465, t = 2.342, P = 0.021). Baseline HBsAg levels together with the decline range of HBsAg at 24 weeks significantly correlated with the treatment time of HBsAg loss (B = 29.862, t = 4.890, P = 0.000 and B = 27.993, t = 27.993, P = 0.005).

<b>CONCLUSIONb>Baseline HBsAg levels and extended therapy are critical steps toward HBsAg loss. Baseline HBsAg levels together with early response determined the treatment time of HBsAg loss in patients with HBeAg-positive chronic hepatitis B during pegylated interferon alpha-2a treatment.

Adolescent ; Adult ; Antiviral Agents ; therapeutic use ; Child ; Child, Preschool ; DNA, Viral ; blood ; Drug Administration Schedule ; Female ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; blood ; drug therapy ; Humans ; Interferon-alpha ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Polyethylene Glycols ; administration & dosage ; therapeutic use ; Recombinant Proteins ; administration & dosage ; therapeutic use ; Retrospective Studies ; Young Adult

BACKGROUND: Thalassemia patients are treated with chronic blood transfusion to relief symptoms. The prevalence of thalassemia in Korea has been increasing recently in response to an increase in the number of immigrants from Southeast Asian countries. Currently, there is no guidelines of blood transfusion outlined by the policy of transfusion of thalassemia, like other inherited hemolytic anemia. Herein, we survey the opinion of transfusion specialists about the policy of blood transfusion of thalassemia in Korea. METHODS: E-mail survey was conducted between July and September of 2017; a total of 40 laboratory medicine specialists working at a general hospital and participating transfusion medicine were included. The questionnaire consisted of blood transfusion experience and blood transfusion policy in patients with thalassemia. RESULTS: Finally, 36 (90%) responders answered the questionnaire; of them, 32 (88.9%) agreed on the necessity of establishing a transfusion guideline for thalassemia patients, and 2 (5.6%) conditionally agreed. Thirty-five (97.2%) respondents agreed on the need for extended matching of RBC antigens for blood transfusion in patients with thalassemia. Thirty-five (97.2%) specialists agreed on the need for extended matching of RBC antigens beyond ABO and RhD to include C, c, E, and e. CONCLUSION: In conclusion, the transfusion guideline for thalassemia, including other inherited hemolytic anemia, is required in Korea. Extended matching of RBC antigens should be considered when developing such guidelines, at least C, c, D, E, e antigens of the Rh blood group are essential for extended matching of RBC antigens.
Anemia, Hemolytic ; Asian Continental Ancestry Group ; Blood Transfusion ; Electronic Mail ; Emigrants and Immigrants ; Hepatitis B e Antigens ; Hospitals, General ; Humans ; Korea* ; Prevalence ; Specialization* ; Surveys and Questionnaires ; Thalassemia* ; Transfusion Medicine

<b>BACKGROUNDb>We aimed to evaluate the usefulness of serum hepatitis B virus core-related antigens (HBcrAg) for predicting hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive chronic hepatitis B patients treated with conventional interferon (IFN) alfa-2b or pegylated IFN.

<b>METHODSb>Fifty-eight patients were enrolled: 29 for the training group and 29 for the validating group. HBcrAg was measured at baseline, week 12, end of the treatment, and 12- and 24-week follow-ups. Sixteen patients in the training group were enrolled in the long-term follow-up (LTFU), during which time the dynamics of the HBcrAg was monitored.

<b>RESULTSb>The serum HBcrAg level gradually declined during treatment among the HBeAg seroconversion patients of the training group (from baseline, week 12, end of the treatment, 12-week follow-up to 24-week follow-up were 110,245 kU/ml, 3760 kU/ml, 7410 kU/ml, 715 kU/ml, 200 kU/ml, respectively). HBcrAg <19,565 kU/ml at week 24, HBcrAg <34,225 kU/ml at 12-week follow-up, and HBcrAg decrease ≥0.565 log10kU/ml from the baseline to the end of treatment (EOT) had negative predictive values (NPVs) of 100% for HBeAg seroconversion at the end of follow-up, whereas the positive predictive values (PPVs) were 30.77%, 26.67%, and 25.00%, respectively. The patients with HBeAg seroconversion at the end of 24-week follow-up remained in seroconversion during the LTFU, during which time their serum HBcrAg levels steadily declined or even became undetectable, ranging from 0 to 2.1 kU/ml.

<b>CONCLUSIONSb>Effective antiviral treatment can decrease HBcrAg levels in the serum. The NPVs of HBcrAg for predicting HBeAg seroconversion at 24-week follow-up was 100%, but the PPVs were not satisfactory (all <31%). The serum HBcrAg levels of the patients with HBeAg seroconversion at the end of the 24-week follow-up steadily declined or even became undetectable during the LTFU.

Adult ; Antiviral Agents ; therapeutic use ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; blood ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Polyethylene Glycols ; therapeutic use ; Recombinant Proteins ; therapeutic use ; Seroconversion ; drug effects ; Treatment Outcome ; Young Adult