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1

Li, Guo-Jun, Yi-Qi Yu, Shao-Long Chen, Ping Fan, Ling-Yun Shao, Jia-Zhen Chen, Chang-Shui Li, et al. "Sequential Combination Therapy with Pegylated Interferon Leads to Loss of Hepatitis B Surface Antigen and Hepatitis B e Antigen (HBeAg) Seroconversion in HBeAg-Positive Chronic Hepatitis B Patients Receiving Long-Term Entecavir Treatment." Antimicrobial Agents and Chemotherapy 59, no. 7 (May 4, 2015): 4121–28. http://dx.doi.org/10.1128/aac.00249-15.

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ABSTRACTNucleos(t)ide analogues rarely result in a durable off-treatment response in chronic hepatitis B infection, whereas pegylated interferon (Peg-IFN) induces a long-lasting response only in a subset of patients. We assessed the effect of sequential combination therapy with Peg-IFN-α2a and entecavir in hepatitis B e antigen (HBeAg)-positive patients with prior long-term entecavir therapy and investigated the predictors of response to treatment. HBeAg-positive individuals who did not achieve HBeAg seroconversion during previous long-term entecavir therapy, receiving Peg-IFN-α2a added to ongoing entecavir therapy (sequential combination [S-C] therapy;n= 81) for 48 weeks or remaining on entecavir monotherapy (n= 116), were retrospectively included. A matched pair was created at a 1:1 ratio from each treatment group. The primary endpoint was HBeAg seroconversion at week 48. Subgroup analysis of response prediction was conducted for 81 patients with S-C therapy. More patients in the S-C therapy group achieved HBeAg seroconversion than those in the entecavir group (44% versus 6%;P< 0.0001). An HBeAg level of <200 signal-to-cutoff ratio (S/CO) at baseline was a strong predictor for higher HBeAg seroconversion than that achieved when HBeAg was ≥200 S/CO (64.2% versus 17.9%;P< 0.0001). Hepatitis B surface antigen (HBsAg) levels at baseline and the decrease in HBsAg levels predicted HBsAg loss in the S-C therapy group. The combination of baseline HBeAg of <200 S/CO and HBsAg of <1,000 IU/ml and an HBsAg decline at week 12 of ≥0.5 log10IU/ml provided the highest rate of HBeAg seroconversion (92.31%) and HBsAg loss (83.3%) at week 48. Patients receiving sequential combination therapy have a higher rate of HBeAg seroconversion and are more likely to experience HBsAg clearance than do those continuing entecavir monotherapy. Sequential combination therapy can be guided by baseline HBsAg/HBeAg levels and on-treatment HBsAg dynamics.
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Hu, Yao-ren, Hua-dong Yan, Guo-sheng Gao, Cheng-liang Zhu, and Ji-fang Cheng. "Liver Histopathological Features Influencing HBeAg Seroconversion in Patients with HBeAg-positive Chronic Hepatitis B Treated with Pegylated Interferon α." Infection International 3, no. 1 (March 1, 2014): 10–15. http://dx.doi.org/10.1515/ii-2017-0067.

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Abstract Objective To investigate the efficiency of pegylated interferon α therapy for patients with HBeAg-positive chronic hepatitis B (CHB) and explore whether liver histopathological features and other factors might influence HBeAg seroconversion. Methods Total of 80 HBeAg-positive CHB patients who received liver puncture were treated with pegylated interferon α once a week for 48 weeks. The rate of HBeAg seroconversion was determined after therapy, and the factors influencing HBeAg seroconversion were analyzed. Results The rate of HBeAg seroconversion was 30.00% at the end of treatment. The rate of HBeAg seroconversion gradually increased with the elevation of liver inflammatory activity (χ2 = 9.170, P = 0.027). But liver fibrosis has little correlation with the rate of HBeAg seroconversion (χ2 = 5.917, P = 0.116). Except HBeAg, other baseline indexes including gender, age, serum ALT and serum HBV DNA 1evels had no statistical difference between the patients with HBeAg seroconversion and the patients without HBeAg seroconversion. By binary logistic regression analysis, liver inflammation and HBeAg were influencing factors for HBeAg seroconversion. Conclusions Pegylated interferon α therapy induces a higher rate of HBeAg seroconversion in HBeAg-positive chronic hepatitis B patients with severe liver inflammation, so the liver biopsies should be performed in time.
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3

Kessler, Harald H., Sabine Preininger, Evelyn Stelzl, Elisabeth Daghofer, Brigitte I. Santner, Egon Marth, Herwig Lackner, and Rudolf E. Stauber. "Identification of Different States of Hepatitis B Virus Infection with a Quantitative PCR Assay." Clinical Diagnostic Laboratory Immunology 7, no. 2 (March 1, 2000): 298–300. http://dx.doi.org/10.1128/cdli.7.2.298-300.2000.

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ABSTRACT The level of hepatitis B virus (HBV) DNA in serum reflects the replicative activity of HBV. To compare serum HBV DNA levels in different states of hepatitis B, 47 sera of patients with HBeAg-positive chronic hepatitis B, 4 sera of patients with HBeAg-negative chronic hepatitis B, 40 samples of patients after HBeAg seroconversion during alpha interferon treatment, 57 sera of inactive HBsAg carriers, and 42 sera of patients who had recovered from chronic hepatitis B more than 12 months prior to blood collection were checked for the presence of HBV DNA with the Amplicor HBV Monitor Test. In patients with HBeAg-positive chronic hepatitis B, the median of serum HBV DNA levels (8.3 × 108 copies/ml) was significantly higher than that for patients after HBeAg seroconversion (6.2 × 103 copies/ml) and than that for inactive HBsAg carriers (5.6 × 103 copies/ml). None of the patients who had recovered from hepatitis B had detectable HBV DNA in serum. Quantitative PCR proved to be a valuable tool for identification of different states of HBV infection. This technique was found to be a good method for determination of serum HBV DNA levels both for patients with HBeAg seroconversion and for inactive carriers who showed low viremia not detectable by conventional hybridization assays.
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Sbarigia, Urbano, Talitha Vincken, Peter Wigfield, Mahmoud Hashim, Bart Heeg, and Maarten Postma. "A comparative network meta-analysis of standard of care treatments in treatment-naïve chronic hepatitis B patients." Journal of Comparative Effectiveness Research 9, no. 15 (October 2020): 1051–65. http://dx.doi.org/10.2217/cer-2020-0068.

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Objective: Published network meta-analyses of chronic hepatitis B (CHB) treatments are either out-of-date or excluded key treatments. Therefore, we aimed to comprehensively update the efficacy evidence for the following end points: Hepatitis B surface antigen (HBsAg) loss, hepatitis B early antigen (HBeAg) seroconversion and hepatitis B virus DNA (HBV DNA) suppression. Materials & methods: Approved treatments in CHB and their combinations were evaluated. A systematic literature review was conducted to identify all randomized controlled trials in treatment-naïve CHB patients. Included studies reported at least one of the end points of interest. A frequentist probability network meta-analysis was performed for each end point. The choice of fixed effect or random-effect model was based on the I-square statistic, a measure of variation in study outcomes between studies. The analyses were performed separately for HBeAg-positive and HBeAg-negative patients. For the primary analyses, end points measured 48 ± 4 weeks after treatment initiation were considered. Results: A total of 47 randomized controlled trials (13,826 patients), covering 23 unique treatment regimens, were included: a total of 29 reported HBsAg loss, 36 reported HBeAg seroconversion and 37 reported HBV DNA suppression. For both HBsAg loss and HBeAg seroconversion, pegylated interferon-based regimens were the most effective strategy in both HBeAg-positive and HBeAg-negative patients. On the other hand, for HBV DNA suppression, nucleosides-based regimens were the most effective strategy in both HBeAg-positive and HBeAg-negative patients. Conclusion: Our findings confirm available evidence around the comparative efficacy of available CHB treatments. Therefore, they can be used to update relevant cost–effectiveness analyses and clinical guidelines.
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Hees, Chi, Hansen, Bourgeois, Vlierberghe, Sersté, Francque, et al. "Caucasian Ethnicity, but Not Treatment Cessation is Associated with HBsAg Loss Following Nucleos(t)ide Analogue-Induced HBeAg Seroconversion." Viruses 11, no. 8 (July 26, 2019): 687. http://dx.doi.org/10.3390/v11080687.

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It is well appreciated that ethnicity influences the natural history and immune responses during a chronic hepatitis B infection. In this study, we explore the effect of ethnicity and treatment cessation on Hepatitis B surface Antigen (HBsAg) seroclearance in patients with Nucleos(t)ide Analogue (NA)-induced Hepatitis B e Antigen (HBeAg) seroconversion. We performed a multi-ethnic, multicentric observational cohort study. The analyzed cohort consisted of 178 mono-infected, predominantly male (75.3%) chronic hepatitis B patients of mixed ethnicity (44.4% Asians, 48.9% Caucasians) with nucleos(t)ide analogue-induced HBeAg seroconversion. Treatment was withdrawn in 105 patients and continued in 73, leading to HBsAg loss in 14 patients off- and 16 patients on-treatment, respectively. Overall, HBsAg loss rates were not affected by treatment cessation (hazard ratio 1.45, p = 0.372), regardless of consolidation treatment duration. Caucasian ethnicity was associated with an increased chance of HBsAg loss (hazard ratio 6.70, p = 0.001), but hepatitis B virus genotype was not (p = 0.812). In conclusion, ethnicity is the most important determinant for HBsAg loss after NA-induced HBeAg seroconversion, with up to six-fold higher HBsAg loss rates in Caucasians compared to Asians, irrespective of treatment cessation and consolidation treatment duration.
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Hoa, Pham Thi Le, Nguyen Tien Huy, Le The Thu, Cao Ngoc Nga, Kazuhiko Nakao, Katsumi Eguchi, Nguyen Huu Chi, Bui Huu Hoang, and Kenji Hirayama. "Randomized Controlled Study Investigating Viral Suppression and Serological Response following Pre-S1/Pre-S2/S Vaccine Therapy Combined with Lamivudine Treatment in HBeAg-Positive Patients with Chronic Hepatitis B." Antimicrobial Agents and Chemotherapy 53, no. 12 (September 21, 2009): 5134–40. http://dx.doi.org/10.1128/aac.00276-09.

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ABSTRACT The aim of the current study was to evaluate viral suppression following combined treatment with an S/pre-S1/pre-S2 vaccine and lamivudine in patients with chronic hepatitis B. We established a randomized, controlled clinical trial to compare the responses of three different treatment groups: those receiving vaccine monotherapy, lamivudine monotherapy, or combination treatment. Viral response was evaluated via hepatitis B virus (HBV) DNA suppression using different levels of classification. Seroconversion was evaluated via HBeAg loss, HBeAg seroconversion, HBsAg loss, and anti-HBs response. We found that the group receiving combination treatment demonstrated a significant increase in viral suppression over that for the lamivudine or vaccine monotherapy group, although the HBeAg seroconversion rate was not different. This enhanced suppression effect in the combination group was reversed after the discontinuation of vaccine treatment, suggesting that booster doses are required for a sustained viral response. Anti-HBs was detected in 55/120 vaccine recipients, but only 3 patients demonstrated HBsAg loss, indicating that the vaccine-induced anti-HBs was unable to completely neutralize HBsAg in the serum. At the study end point, anti-HBs responders showed significantly higher HBeAg seroconversion rates, greater suppression of HBV DNA levels, and a lower median reduction in HBV DNA levels than those of anti-HBs nonresponders. Our results suggest that combined treatment with the vaccine and lamivudine was significantly more effective than lamivudine monotherapy in the short term and was especially successful in producing viral suppression and an enhanced anti-HBs antibody response.
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Villeneuve, Jean-Pierre, and Bernard Willems. "Treatment of Chronic Hepatitis B with Interferon: Long Term Follow-Up." Canadian Journal of Gastroenterology 10, no. 1 (1996): 21–25. http://dx.doi.org/10.1155/1996/683012.

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The aim of treatment of chronic hepatitis B with interferon is to induce a transition from the replicative phase of the disease to a nonreplicative state, with loss of hepatitis B virus (HBV)-DNA, seroconversion from hepatitis B e antigen (HBeAg)-positive to anti-HBe antibody-positive, and normalization of liver enzymes. The authors’ experience in 22 patients with chronic hepatitis B treated with recombinant human interferon alpha-2b (5 MU/m2 subcutaneously three times/week for 16 weeks) is reported. Before treatment all patients had been positive for hepatitis B surface antigen (HBsAg) and HBeAg for at least six months, had abnormal serum aminotransferases, had no evidence of hepatitis D or human immunodeficiency virus (HIV) infection and had compensated liver disease. Eleven of 22 patients (50%) responded to treatment with loss of HBeAg and appearance of anti-HBe antibodies, and normalization of serum aminotransferases within six months of interferon cessation. Patients were followed for 3.4±1.2 years after treatment. Ten of 11 responders remained negative for HBeAg and HBV-DNA; one patient relapsed and responded to a second course of interferon with loss of HBeAg and HBV-DNA. Seven of the 11 nonresponders underwent spontaneous (n=5) or retreatment-induced (n=2) seroconversion from HBeAg to anti-HBe and loss of HBV-DNA during follow-up. The other four nonresponders remained positive for HBeAg and HBV-DNA; three of the four progressed to decompensated liver disease. It is concluded that interferon is an effective treatment of chronic hepatitis B in 50% of patients with features similar to those used as selection criteria in the present study. These criteria probably also identify patients who have a high likelihood of spontaneous HBeAg to anti-HBe seroconversion, and it is possible that the benefit of interferon is its acceleration of this seroconversion.
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Ecin, Seval Müzeyyen, Nursel Çalık Başaran, and Murat Aladağ. "Evaluation of the Effectiveness of Tenofovir in Chronic Hepatitis B Patients." Acta Medica 51, no. 1 (March 17, 2020): 9–14. http://dx.doi.org/10.32552/0.actamedica.423.

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Introductıon: HBV infection is a global public health problem. Tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) are nucleotide reverse transcriptase inhibitors (NRTIs) that are used for the treatment of CHB infection. The aim of this study was to evaluate the treatment response and efficacy of TDF, which was a new treatment regimen in Turkey Materials and Methods: This descriptive, retrospective study was conducted between January 2009 and January 2011 at Inonu University Faculty, Turgut Ozal Medicine Center, Department of Internal Medicine, Division of Hepatology Outpatient Clinic. We included hepatitis B positive patients who started to use Tenofovir (TDF). We retrospectively reviewed the electronic medical files of Hepatitis B patients. HBsAg, Hepatit B surface antibody (Anti-HBsAb), HBeAg, Hepatit B e antibody (Anti-HBeAb), HBV-DNA, aspartate aminotransferase (AST), alanine aminotransferase (ALT) values were evaluated in the 1, 3., 6., 9., and 12. months. Result: None of the patients under TDF treatment were “primary resistant”. ALT normalization at 12th month was seen in 80.4% of study population. HBsAg seroconversion were detected only in one patient (0.85%) at 9 months and HBeAg seroconversion were observed in 9 (8.3%) under TDF treatment. At the sixth month of TDF treatment, complete response were found in 77 (65.8%), partial response in 21 (18%) and inadequate response were in 19 (16.2%). Among HBeAg positive patients, 44 (80 %) patients had undetectable HBV DNA levels at the end of 12th month and among HBeAg negative patients, 52 (91.2%) patients had undetectable HBV DNA levels at the end of 12th month (p<0.01). Discussion and Conclusion: among patients with chronic HBV infection, Tenofovir had satisfying antiviral efficacy. There is no primary resistance in patients treated with Tenofovir. Patients had statistically significant improvement in AST, ALT, HBV DNA levels
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Lee, Hyun Woong, Jae-Cheol Kwon, In Soo Oh, Hye Young Chang, Young Joo Cha, Ik-Seong Choi, and Hyung Joon Kim. "Prolonged Entecavir Therapy Is Not Effective for HBeAg Seroconversion in Treatment-Naive Chronic Hepatitis B Patients with a Partial Virological Response." Antimicrobial Agents and Chemotherapy 59, no. 9 (June 22, 2015): 5348–56. http://dx.doi.org/10.1128/aac.01017-15.

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ABSTRACTThe aims of this study were to investigate the efficacy of prolonged entecavir (ETV) therapy in treatment-naive chronic hepatitis B (CHB) patients and to determine whether continuous ETV therapy is feasible to achieve HBeAg seroconversion, particularly in patients with partial virological response (PVR). A total of 142 treatment-naive patients with CHB were enrolled. The mean duration of treatment was 65 (range, 26 to 90) months, and 86 patients (60.6%) were HBeAg positive. PVR was defined as detectable hepatitis B virus (HBV) DNA (>116 copies/ml) at year 1. The cumulative incidence of virological response (VR) increased from 54.9% at year 1 to 98.2% at year 7. HBeAg positivity (odds ratio [OR], 4.146;P= 0.001) and initial alanine aminotransferase (ALT) (OR, 0.997;P= 0.004) were independent risk factors for PVR. Among the 64 patients with PVR, 47 patients (73.4%) achieved VR within 4 years after prolonged ETV therapy without treatment adaptation. Three patients (2.1%) experienced virological breakthrough and HBV variants with genotypic resistance. The cumulative rate of HBeAg seroconversion was significantly higher in the patients with VR than in the patients with PVR (P= 0.018). None of the PVR patients with HBV DNA at ≥5,000 copies/ml at year 1 ever experienced HBeAg seroconversion. Multivariate analysis identified VR at year 1 as the only determinant of HBeAg seroconversion (hazard ratio [HR], 3.009;P= 0.010). In conclusion, although there were patients with PVR, prolonged ETV therapy showed excellent VR, with only 2.1% emergence of viral resistance during a 7-year follow-up. However, to achieve HBeAg seroconversion, drug modification is needed for HBeAg-positive patients with PVR (especially those with HBV DNA at ≥5,000 copies/ml at year 1).
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KIMURA, Akihiko, Masayoshi KAGE, Ken YUGE, and Eiichiro ONO. "HBsAg positive chronic hepatitis in children : Seroconversion from HBeAg to anti-HBe and HBcAg in liver." Kanzo 27, no. 10 (1986): 1363–70. http://dx.doi.org/10.2957/kanzo.27.1363.

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He, Qing, Qi-yuan Tang, Xiao-hua Le, De-liang Lv, Xiang-mei Zhang, Fei-jian Ao, Yi-min Tang, Shan Huang, John Nunnari, and Gui-lin Yang. "The Relationship between Intrahepatic Distribution of Hepatitis B Virus Core Antigen and Serum ALT, HBV DNA Levels and HBeAg Status." Infection International 1, no. 2 (June 1, 2012): 84–90. http://dx.doi.org/10.1515/ii-2017-0013.

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Abstract Objective The clinical significance of differential distribution of hepatitis B virus (HBV) nucleocapsid antigen in hepatocytes remains unknown. The goal of this study is to determine the relationship between distinct HBV core antigen distribution pattern and alanine transaminase (ALT), liver histological inflammatory activity grades, serum HBeAg status and HBV DNA level.Methods Total of 958 cases with chronic hepatitis B were recruited into this study. Liver function tests, serum HBV DNA level, serological HBV markers and liver immunohistochemistry were examined according to the conventional instructions. Chi Square tests were performed to analyze the differences among these groups.Results It was found that 552 (58%) cases were tested positive for HBV core antigen by immunohistochemical staining. Cytoplasmic hepatitis B core antigen (HBcAg) expression correlated with ALT level and serum HBV DNA and liver inflammatory activity scores, however, nuclear HBcAg expression in hepatocytes was associated with normal ALT level, lower liver inflammatory activity score and higher serum HBV DNA level and rate of HBeAg positivity. Both nuclear and cytoplasmic HBcAg expression in hepatocytes associated with a middle ALT level and liver inflammatory activity score, higher rate of serum detectable HBeAg and a higher HBV DNA level. However, undetectable core antigen was related to a lower ALT level and histological inflammatory activity grade, lower positive HBeAg rate and HBV DNA level.Conclusions Undetectable liver HBcAg is associated with HBV clearance, ALT normalization and hepatitis B e antigen (HBeAg) seroconversion, and cytoplasmic HBcAg expression associated with higher hepatic inflammatory activity. However, nuclear HBcAg expression correlates with immune tolerance characterized with normal ALT and lower liver inflammatory activity, higher HBV replication level and higher rate of HBeAg positivity.
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12

&NA;. "HBeAg seroconversion and longterm outcome with interferon-??" Inpharma Weekly &NA;, no. 1040 (June 1996): 12. http://dx.doi.org/10.2165/00128413-199610400-00024.

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Ma, Hui, Rui-feng Yang, and Lai Wei. "Quantitative serum HBsAg and HBeAg are strong predictors of sustained HBeAg seroconversion to pegylated interferon alfa-2b in HBeAg-positive patients." Journal of Gastroenterology and Hepatology 25, no. 9 (February 3, 2010): 1498–506. http://dx.doi.org/10.1111/j.1440-1746.2010.06282.x.

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Tarsetti, Fabio, Giuseppe Tarantino, Piergiorgio Mosca, Emidio Scarpellini, and Giammarco Fava. "[Tenofovir and entecavir for chronic hepatitis B infection treatment: a single-center experience]." Clinical Management Issues 9, no. 4 (December 22, 2015): 95–100. http://dx.doi.org/10.7175/cmi.v9i4.1202.

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BACKGROUND AND AIM: The current treatment of chronic hepatitis B infection (CHBV) has achieved several step-ups thanks to the introduction of the new-generation nucleos(t)ide analogs. Entecavir and tenofovir have shown a high genetic resistance barrier and a low rate of side effects. In literature, there are a few studies comparing entecavir and tenofovir in the treatment of CHBV. Thus, we describe the results of our experience in managing CHBV patients with tenofovir vs. entecavir.MATERIALS AND METHODS: We have retrospectively evaluated, from 2007 to date, 20 CHBV patients treated with entecavir and tenofovir. All the patients underwent basal and periodical clinical follow-up, blood tests, virological tests, Fibroscan® test or liver biopsy and also upper abdominal ultrasound examination. Study endpoints were: viral replication inhibition, viral antigens seroconversion and transaminases normalization. Drug-associated side effects were also registered.RESULTS: After 12 weeks of therapy, entecavir and tenofovir lead to HBV-DNA negativization in 44% and 62% of patients, respectively. A case of viral seroconversion for HBeAg and HBsAg was evident in entecavir group, while no cases were registered in tenofovir group. After 12 weeks, 11% of entecavir treated patients and 37% of tenofovir treated patients showed normalization of transaminases.DISCUSSION: Tenofovir seems to exert a better viral replication inhibition (though not statistically significant) and to show transaminases improvement in comparison with entecavir, which, in turn, results more effective in HBeAg/HBsAg seroconversion. Both drugs have a high safety profile in terms of side effects.[Article in Italian]
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Yang, Jiezuan, Jiajia Chen, Ping Ye, Linfeng Jin, Wei Wu, Guoping Sheng, and Lan-Juan Li. "HBsAg as an important predictor of HBeAg seroconversion following antiviral treatment for HBeAg-positive chronic hepatitis B patients." Journal of Translational Medicine 12, no. 1 (2014): 183. http://dx.doi.org/10.1186/1479-5876-12-183.

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Wang, B., I. Carey, M. Bruce, S. Montague, G. Dusheiko, and K. Agarwal. "HBsAg and HBcrAg as predictors of HBeAg seroconversion in HBeAg-positive patients treated with nucleos(t)ide analogues." Journal of Viral Hepatitis 25, no. 8 (April 2, 2018): 886–93. http://dx.doi.org/10.1111/jvh.12889.

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Ichida, F., A. Yoshikawa, A. Yachi, Y. Goto, S. Furuta, N. Hattori, S. Kakumu, et al. "Treatment of HBeAg-Positive Chronic Hepatitis with a Streptococcal Preparation (OK-432)." Journal of International Medical Research 13, no. 1 (January 1985): 59–67. http://dx.doi.org/10.1177/030006058501300109.

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Forty-two patients with hepatitis Be antigen (HBeAg)-positive chronic hepatitis were treated by intramuscular injections with OK-432, an immunopotentiator possessing interferon-inducing activity. They were monitored with serial measurements of virological parameters to evaluate therapeutic effectiveness, and compared with a group of seventy-five untreated patients (natural course group). In the group receiving OK-432 therapy, twenty-seven patients (64·3% of the forty-two patients) became negative for HBeAg in an average observation period of 20·1 months. Of these, fourteen patients (33·3% of the forty-two patients) underwent seroconversion from HBeAg to anti-HBe antibody (anti-HBe). In the natural course group, twenty-three patients (30·7% of the seventy-five patients) lost HBeAg reactivity in a mean follow-up period of 32·3 months, and thirteen patients (17·3% of the seventy-five patients) became seroconverted. Thus, the drug group showed significantly higher percentages of patients with disappearance of HBeAg and seroconversion, notwithstanding the shorter duration of the follow-up. Young males and females, females generally, or patients with high serum GPT levels were more likely to respond to the therapy. The serum GPT level tended to stabilize more inpatients receiving OK-432.
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Parfieniuk-Kowerda, Anna, Kamil Grubczak, Andrzej Eljaszewicz, Magdalena Świderska, Magdalena Maciaszek, Anatol Panasiuk, Jerzy Jaroszewicz, Robert Flisiak, and Marcin Moniuszko. "High CD163 Expression on Classical Monocytes Is Associated with Immune Control of HBV Infection in Noncirrhotic Patients." Mediators of Inflammation 2020 (March 29, 2020): 1–13. http://dx.doi.org/10.1155/2020/6364258.

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Background and Aims. The functional impairment of monocytes may contribute to the persistence of HBV infection. This study aims to assess monocyte subpopulations, monocyte expression of CD163, plasma sCD163, and sTWEAK in patients with chronic HBeAg-negative HBV infection at different phases of disease. Methods. Fifty-nine patients with CHB, 9 with a history of HBsAg/anti-HBs seroconversion, were enrolled. The control group consisted of 15 healthy volunteers. Subpopulations of peripheral blood monocytes were distinguished by CD14 and CD16. Membrane expression of CD163 was assessed by flow cytometry, plasma sCD163 concentration by ELISA, and sTWEAK by bead-based multiplexed immunoassay system. Results. CD163 expression was increased in classical and intermediate monocytes in CHB patients and those with HBsAg/anti-HBs seroconversion. CD163 expression on classical monocytes was associated with status of immune control and thus significant in HBV infection as compared to active hepatitis. Plasma sCD163 concentration was increased in CHB patients and those with HBsAg/anti-HBs seroconversion vs. the control group. Positive correlations between plasma sCD163 and ALT, as well as APRI, were observed. Plasma sTWEAK concentration was lower in CHB patients in comparison to patients with HBsAg/anti-HBs seroconversion. Conclusions. Exposure to HBV antigens alters monocyte subsets’ frequencies and activation. The expression of CD163 on classical monocytes increased in parallel with improved immune control of the HBV infection. Patients who seroconverted HBsAg had the highest expression of CD163 on monocytes, which suggests involvement of monocytes in immune control of HBV infection. Persistent inflammation is accompanied by higher CD163 expression and sCD163 level and lower sTWEAK level.
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Liaw, Y. F., S. M. Lin, I. S. Sheen, and C. M. Chu. "Acute hepatitis C virus superinfection followed by spontaneous HBeAg seroconversion and HBsAg elimination." Infection 19, no. 4 (July 1991): 250–51. http://dx.doi.org/10.1007/bf01644957.

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Chen, Zhe, Xiao Ma, Yanling Zhao, Jiabo Wang, Yaming Zhang, Yun Zhu, Lifu Wang, et al. "Kushenin Combined with Nucleos(t)ide Analogues for Chronic Hepatitis B: A Systematic Review and Meta-Analysis." Evidence-Based Complementary and Alternative Medicine 2015 (2015): 1–12. http://dx.doi.org/10.1155/2015/529636.

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Objective. To evaluate the efficacy and safety of Kushenin (KS) combined with nucleoside analogues (NAs) for chronic hepatitis B (CHB).Methods. Randomized controlled trials (RCTs) of KS combined with NAs for CHB were identified through 7 databases. Frequencies of loss of serum HBeAg, HBeAg seroconversion, undetectable serum HBV-DNA, ALT normalization, and adverse events at 48 weeks were abstracted by two reviewers. The Cochrane software was performed to assess the risk of bias in the included trials. Data were analyzed with Review Manager 5.3 software.Results. 18 RCTs involving 1684 subjects with CHB were included in the analysis. KS combined with NAs including lamivudine (LAM), entecavir (ETV), adefovir dipivoxil (ADV), and telbivudine (TLV) showed different degree of improvement in CHB indices. KS combined with NAs increased the frequency of loss of serum HBeAg, HBeAg seroconversion, undetectable HBV-DNA levels, and ALT normalization compared with single agents. It also decreased serum ALT and AST level after one-year treatment. However, KS combined with TLV did not show a significant difference in CHB indices. The side-effects of KS combined with NAs were light and of low frequency.Conclusion. KS combined with NAs improves the efficacy of NAs in CHB.
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Lim, Seng-Gee. "CS1-02 The Roleof HBV Viral Quasispeciesin HBeAg Seroconversion." International Journal of Infectious Diseases 13 (August 2009): S3—S4. http://dx.doi.org/10.1016/s1201-9712(09)60248-4.

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Liem, Kin Seng, Scott Fung, David K. Wong, Colina Yim, Seham Noureldin, Jiayun Chen, Jordan J. Feld, Bettina E. Hansen, and Harry L. A. Janssen. "Limited sustained response after stopping nucleos(t)ide analogues in patients with chronic hepatitis B: results from a randomised controlled trial (Toronto STOP study)." Gut 68, no. 12 (August 28, 2019): 2206–13. http://dx.doi.org/10.1136/gutjnl-2019-318981.

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ObjectiveAlthough most patients with chronic hepatitis B (CHB) reach effective virological suppression with long-term nucleos(t)ide analogues (NA) therapy, some might not need to continue treatment for life. In this randomised, controlled, phase IV trial, we evaluated off-therapy outcomes in patients after discontinuing long-term NA therapy.DesignPatients who had received NA therapy for ≥1 year and achieved virological suppression (hepatitis B e antigen (HBeAg) seroconversion combined with undetectable hepatitis B virus (HBV) DNA ≥12 months in HBeAg-positive patients or undetectable HBV DNA ≥36 months in HBeAg-negative patients) were randomised 2:1 to stop or continue NA therapy for 72 weeks. Sustained disease remission (HBeAg negative, HBV DNA <2000 IU/mL and normal alanine aminotransferase (ALT)) was evaluated at 72 weeks after stopping NA therapy.ResultsAmong 67 enrolled patients, sustained disease remission was observed in 13/45 (29%) stop versus 18/22 (82%) continue patients. Hepatitis B surface antigen (HBsAg) loss occurred in two patients (one in each group). The median HBsAg decline from randomisation to week 72 was similar in both groups (0.2 (0.0–0.4) vs 0.1 (0.0–0.2) log IU/mL in stop vs continue patients). Among patients who stopped, 15/45 (33%) had virological or biochemical relapse and 17/45 (38%) were retreated according to predefined criteria. A total of 11/18 (61%) pretreatment HBeAg-positive versus 6/27 (22%) HBeAg-negative patients required retreatment (p=0.01). Fourteen (31%) patients developed ALT >10× upper limit of normal (ULN) and another 7 (16%) had ALT >5× ULN. No patients experienced liver decompensation or died.ConclusionThe findings of this prospective study suggest limited benefit of stopping NA therapy in chronic hepatitis B.Trial registration numberNCT01911156.
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Benias, Petros C., and Albert D. Min. "Goals of Antiviral Therapy for Hepatitis B: HBeAg Seroconversion, HBsAg Seroconversion, Histologic Improvement, and Possible Impact on Risk of Hepatocellular Carcinoma." Current Hepatitis Reports 10, no. 4 (September 8, 2011): 292–96. http://dx.doi.org/10.1007/s11901-011-0112-4.

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Fung, J., C. L. Lai, D. K. H. Wong, J. Yuen, and M. F. Yuen. "359 INCREASE RISK OF HBeAg-NEGATIVE CHRONIC HEPATITIS B WITH OLDER AGE AT HBeAg SEROCONVERSION." Journal of Hepatology 50 (April 2009): S137. http://dx.doi.org/10.1016/s0168-8278(09)60361-5.

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Ye, Zhen, Min Zhao, He Jiao, Yang Feng, Ying-zi Li, Cui-fang Nie, Yan-mei Zhang, et al. "Meta-analysis on Treatment of Chronic Hepatitis B with Telbivudine and Entecavir." Infection International 1, no. 4 (December 1, 2012): 216–23. http://dx.doi.org/10.1515/ii-2017-0031.

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Objective To evaluate the therapeutic effects of telbivudine and entecavir on patients with chronic hepatitis B by meta-analysis method. Methods Databases including the Cochrane Library, PubMed, EMBASE and HighWire were searched from January 2008 to October 2012. Randomized controlled trials on treatment of chronic hepatitis B with telbivudine and entecavir were included. According to the Cochrane systematic reviews, the methodological quality of the included studies was evaluated and effective data was extracted from these studies and analyzed. Results Six studies were included eventually. The telbivudine group included 417 cases and the entecavir group included 396 cases. For 12-week antiviral treatment of chronic hepatitis B, the rate of undetectable HBV DNA was 39.1% with telbivudine and 38.6% with entecavir [OR = 1.04, 95% CI (0.62, 1.73), P > 0.05]; for treatment of HBeAg (+) hepatitis B, the HBeAg clearance rate was 23.8% with telbivudine and 3.8% with entecavir [OR= 8.07, 95% CI (2.69, 24.21), P < 0.05], and the HBeAg seroconversion rate was 6.7% with telbivudine and 3.8% with entecavir [OR = 4.95, 95% CI (1.60, 15.31), P < 0.05]; the ALT normalization rate was 54.3% with telbivudine and 58.5% with entecavir [OR = 0.84, 95% CI (0.49, 1.45), P > 0.05]; and for early-stage treatment, the incidence of adverse events was 17.2% with telbivudine and 22.0% with entecavir [OR = 0.66, 95% CI (0.33, 1.32), P > 0.05]. For 1-year antiviral treatment of chronic hepatitis B, the rate of undetectable HBV DNA was 79.4% with telbivudine and 89.7% with entecavir [OR = 0.46, 95% CI (0.28, 0.74), P < 0.05]; for treatment of HBeAg (+) hepatitis B, the HBeAg clearance rate was 28.9% with telbivudine and 15.6% with entecavir [OR = 2.21, 95% CI (1.06, 4.58), P < 0.05], and the HBeAg seroconversion rate was 31.2% with telbivudine and 18.5% with entecavir [OR = 2.31, 95% CI (1.23, 4.31), P < 0.05]; the ALT normalization rate was 85.8% with telbivudine and 84.9% with entecavir [OR = 0.90, 95% CI (0.29, 2.84), P > 0.05]; and the resistance rate was 6.0% with telbivudine and 0.76% with entecavir [OR = 5.71, 95% CI (1.67, 19.47), P < 0.05]. Conclusions For 1-year treatment of chronic hepatitis B, the difference in ALT normalization between telbivudine and entecavir was not statistically significant; and telbivudine was superior over entecavir in terms of HBeAg undetectable and HBeAg seroconversion; entecavir was superior over telbivudine in terms of HBV DNA undetectable and resistance; and both drugs had similar rates of adverse events in early-stage treatment and no severe adverse event was noted. Both telbivudine and entecavir are effective antiviral drugs against hepatitis B.
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Sacchi, Viola. "Entecavir (Baraclude) in patients with chronic hepatitis B virus (HPV) infection." Farmeconomia. Health economics and therapeutic pathways 9, no. 3 (September 15, 2008): 157–61. http://dx.doi.org/10.7175/fe.v9i3.228.

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Hepatitis B is the most common serious liver infection in the world, with about 350 million people who are infected with the hepatitis B virus (HBV) and about 1 million deaths annually.Hepatitis B is characterized by an acute and a chronic phase, if the subject fails to produce adequate immune response. About 5-10% of adults infected with HBV go on to develop chronic infection and become chronic carriers (CHB); moreover, the liver damage, if not stopped, continues until cirrhosis or hepatocellular carcinoma. In the natural history of HBV infection, the most important event is HBeAg seroconversion, characterized by loss of HBeAg (a specific antigen of the virus) and development of Anti-HBe antibodies (HBeAg-positive patients). If the seroconversion has occurred early (when liver damage is not yet significant) and is maintained,long-term prognosis is excellent. The disease can follow a more aggressive course if active viral replication persists despite anti-HBe positivity. This state, characterized by continuing viral replication, has been termed as HBeAg-negative CHB, and is the most prevalent form in Italy. At the moment, there are 4 approved antiviral drug classes, with different antiviral efficacy, for the treatment of chronic hepatitis B: interferons, nucleoside analogues, nucleotide analogues, and cyclopents. The primary target of the treatment is a prolonged suppression of viral replication, in order to avoid long term complications and increase survival.
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Sacchi, Viola. "Telbivudine (Sebivo) in patients with hepatitis B virus (HBV) chronic infection." Farmeconomia. Health economics and therapeutic pathways 9, no. 4 (January 15, 2008): 215–18. http://dx.doi.org/10.7175/fe.v9i4.238.

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Hepatitis B is the most common serious liver infection in the world, with about 350 million people who are infected with the hepatitis B virus (HBV) and about 1 million deaths annually.Hepatitis B is characterized by an acute and a chronic phase, if the subject fails to produce adequate immune response.About 5-10% of adults infected with HBV go on to develop chronic infection and become chronic carriers (CHB); moreover, the liver damage, if not stopped, continues until cirrhosis or hepatocellular carcinoma. In the natural history of HBV infection, the most important event is HBeAg seroconversion, characterized by loss of HBeAg (a specific antigen of the virus) and development of anti-HBe antibodies (HBeAg-positive patients). If the seroconversion has occurred early (when liver damage is not already significant) and is maintained, long-term prognosis is excellent. The disease can follow a more aggressive course if active viral replication persists despite anti-HBe positivity. This state, characterized by continuing viral replication, has been termed as HBeAg-negative CHB, and is the most prevalent form in Italy. At the moment, there are 4 approved antiviral drug classes, with different antiviral efficacy, for the treatment of chronic hepatitis B: interferons, nucleoside analogues, nucleotide analogues, and cyclopents.The primary target of the treatment is a prolonged suppression of viral replication, in order to avoid long term complications and increase survival.
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Hao, Zhang, Zhu Biqing, Yang Ling, and Zeng Wenting. "The Effectiveness of Antiviral Treatments for Patients with HBeAg-Positive Chronic Hepatitis B: A Bayesian Network Analysis." Canadian Journal of Gastroenterology and Hepatology 2018 (September 12, 2018): 1–9. http://dx.doi.org/10.1155/2018/3576265.

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This network analysis is to determine the most effective treatment in HBeAg-positive patients. PubMed databases were searched for randomized controlled trials. Bayesian network meta-analysis was used to calculate the pairwise hazard ratios, 95% credible intervals, and ranking of surrogate outcomes. 9 studies were identified. The results show that NA add-on PEG IFN might be a better antiviral approach for HBeAg-positive patients in end point of treatment, with a comparable results of nucleoside/nucleotide analogs (NA), PEG IFN, PEG IFN add-on NA, PEG IFN combined NA, and PEG IFN combined placebo in alanine aminotransferase (ALT) normalization and HBV DNA undetectable. Cumulative probabilities of being the most efficacious treatment were NA add-on PEG IFN (30%) for HBeAg loss. The second efficacious (23%) is HBeAg seroconversion. This network analysis shows that NA add-on PEG IFN might be a better antiviral approach for HBeAg-positive patients in end point of treatment. But the long-term efficiency should be further determined.
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Chen, Chien-Hung, Sheng-Nan Lu, Chuan-Mo Lee, Chao-Hung Hung, Jing-Houng Wang, and Tsung-Hui Hu. "Patients with interferon-induced HBeAg seroconversion have a higher risk of HBV reactivation and HBeAg seroreversion." Hepatology International 8, no. 3 (May 31, 2014): 365–74. http://dx.doi.org/10.1007/s12072-014-9542-8.

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30

Ingman, M., B. Lindqvist, and K. Kidd-Ljunggren. "Novel mutation in Hepatitis B virus preventing HBeAg production and resembling primate strains." Journal of General Virology 87, no. 2 (February 1, 2006): 307–10. http://dx.doi.org/10.1099/vir.0.81562-0.

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Chronic carriers of hepatitis B infection often harbour virus strains with mutations in the precore region. These mutations are temporally associated with the development of HBeAg loss and seroconversion to anti-HBe. The most common precore mutation is a stop codon at position 1896, but other mutations leading to abolished HBeAg secretion have been described. Here, a novel precore mutation introducing a lysine in the precore position 28, a sequence shared by non-human primates but not by other human isolates, is described. However, the insertion causes a frame-shift preventing the expression of HBeAg by introducing a stop codon 5 aa downstream of the mutation. Analysis of the predicted RNA secondary structure indicates that the insertion could occur without fatally affecting the stability of the stem–loop encapsidation signal.
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31

Song, Guangjun, Huiying Rao, Bo Feng, and Lai Wei. "Prediction of spontaneous HBeAg seroconversion in HBeAg-positive chronic hepatitis B patients during the immune clearance phase." Journal of Medical Virology 86, no. 11 (August 2, 2014): 1838–44. http://dx.doi.org/10.1002/jmv.24032.

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32

Kim, Hyoung Su, Ha Jung Kim, Woon Geon Shin, Kyung Ho Kim, Jin Heon Lee, Hak Yang Kim, and Myoung Kuk Jang. "Predictive Factors for Early HBeAg Seroconversion in Acute Exacerbation of Patients With HBeAg-Positive Chronic Hepatitis B." Gastroenterology 136, no. 2 (February 2009): 505–12. http://dx.doi.org/10.1053/j.gastro.2008.10.089.

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33

Tseng, Yu-Ru, Jia-Feng Wu, Yen-Hsuan Ni, Huey-Ling Chen, Chih-Cheng Chen, Wan-Hsin Wen, Hong-Yuan Hsu, and Mei-Hwei Chang. "Long-term effect of maternal HBeAg on delayed HBeAg seroconversion in offspring with chronic hepatitis B infection." Liver International 31, no. 9 (June 28, 2011): 1373–80. http://dx.doi.org/10.1111/j.1478-3231.2011.02574.x.

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34

Budzinska, Magdalena Agnieszka, Nicholas Adam Shackel, Stephan Urban, and Thomas Tu. "Sequence analysis of integrated hepatitis B virus DNA during HBeAg-seroconversion." Emerging Microbes & Infections 7, no. 1 (August 8, 2018): 1–12. http://dx.doi.org/10.1038/s41426-018-0145-7.

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35

Wong, D., M. Littlejohn, L. Yuen, K. Jackson, H. Mason, A. Gaggar, K. Kitrinos, et al. "On-treatment decline in HBeAg level at week 24 predicts for HBeAg seroconversion during long-term tenofovir therapy for HBeAg-positive CHB." Journal of Hepatology 66, no. 1 (2017): S259—S260. http://dx.doi.org/10.1016/s0168-8278(17)30829-2.

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36

Zhu, Xiao-Jun, Xue-Hua Sun, Zheng-Hua Zhou, Shun-Qing Liu, Hua Lv, Man Li, Lu Li, and Yue-Qiu Gao. "Lingmao Formula Combined with Entecavir for HBeAg-Positive Chronic Hepatitis B Patients with Mildly Elevated Alanine Aminotransferase: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial." Evidence-Based Complementary and Alternative Medicine 2013 (2013): 1–7. http://dx.doi.org/10.1155/2013/620230.

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Objective. To determine the efficacy and safety of Lingmao Formula combined with entecavir for HBeAg-positive chronic hepatitis B patients with mildly elevated alanine aminotransferase (ALT).Methods. 301 patients were randomly assigned to receive Lingmao Formula combined with entecavir (treatment group) or placebo combined with entecavir (control group) for 52 weeks. The outcomes of interest included the reduction of serum HBV DNA level, HBeAg loss, HBeAg seroconversion, ALT normalization, and histological improvement.Results. The mean decrease of serum HBV DNA level from baseline and the percentage of patients who had reduction in serum HBV DNA level ≥2 lg copies/mL in treatment group were significantly greater than that in control group (5.5 versus 5.4 lg copies/mL,P=0.010; 98.5% versus 92.6%,P=0.019). The percentage of HBeAg loss in treatment group was 22.8%, which was much higher than a percentage of 12.6% in control group (P=0.038). There was no significant difference between the two groups in histological improvement. Safety was similar in the two groups.Conclusions. The combination of Lingmao Formula with entecavir could result in significant decrease of serum HBV DNA and increase of HBeAg loss for HBeAg-positive chronic hepatitis B patients with mildly elevated ALT without any serious adverse events. Clinical trial registration number isChiCTR-TRC-09000594.
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37

Heathcote, Jenny, George Germanidis, Geoffrey M. Dusheiko, Ira M. Jacobson, Robert A. De Man, Paul Nikolaidis, Patrick Marcellin, et al. "M1782 Characteristics of HBeAg-Positive Patients with HBsAg Loss/Seroconversion Following Treatment with Tenofovir Disoproxil Fumarate (TDF)." Gastroenterology 136, no. 5 (May 2009): A—837. http://dx.doi.org/10.1016/s0016-5085(09)63856-7.

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38

Heathcote, E. J., G. Germanidis, G. Dusheiko, I. Jacobson, R. deMan, P. Nikolaidis, P. Marcellin, et al. "909 CHARACTERISTICS OF HBeAg-POSITIVE PATIENTS WITH HBsAg LOSS/SEROCONVERSION FOLLOWING TREATMENT WITH TENOFOVIR DISOPROXIL FUMARATE (TDF)." Journal of Hepatology 50 (April 2009): S330. http://dx.doi.org/10.1016/s0168-8278(09)60911-9.

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39

Yang, Shih-Cheng, Sheng-Nan Lu, Chuan-Mo Lee, Tsung-Hui Hu, Jing-Houng Wang, Chao-Hung Hung, Chi-Sin Changchien, and Chien-Hung Chen. "Combining the HBsAg decline and HBV DNA levels predicts clinical outcomes in patients with spontaneous HBeAg seroconversion." Hepatology International 7, no. 2 (June 22, 2012): 489–99. http://dx.doi.org/10.1007/s12072-012-9382-3.

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Yao, Chih-Chien, Chuan-Mo Lee, Chao-Hung Hung, Jing-Houng Wang, Tsung-Hui Hu, Sheng-Nan Lu, Chi-Sin Changchien, Mei-Chin Hsu, and Chien-Hung Chen. "Combining age and HBsAg level predicts post-treatment durability of nucleos(t)ide analogue-induced HBeAg seroconversion." Journal of Gastroenterology and Hepatology 30, no. 5 (April 10, 2015): 918–24. http://dx.doi.org/10.1111/jgh.12874.

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41

Matthews, Gail V., Rachel J. Ali, Anchalee Avihingsanon, Janaki Amin, Rachel Hammond, Scott Bowden, Sharon R. Lewin, et al. "Quantitative HBsAg and HBeAg Predict Hepatitis B Seroconversion after Initiation of HAART in HIV-HBV Coinfected Individuals." PLoS ONE 8, no. 4 (April 9, 2013): e61297. http://dx.doi.org/10.1371/journal.pone.0061297.

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42

Lau, George K. K. "Current treatments for patients with HBeAg-positive chronic hepatitis B virus infection: a comparison focusing on HBeAg seroconversion." Liver International 30, no. 4 (April 2010): 512–20. http://dx.doi.org/10.1111/j.1478-3231.2009.02198.x.

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43

Chen, Chien-Hung, Chuan-Mo Lee, Jing-Houng Wang, Tsung-Hui Hu, Chao-Hung Hung, Chi-Sin Changchien, and Sheng-Nan Lu. "Combination and evolution of HBV mutant strains in the HBeAg-positive status predict clinical outcomes after HBeAg seroconversion." Hepatology International 7, no. 2 (June 21, 2012): 477–88. http://dx.doi.org/10.1007/s12072-012-9381-4.

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Lin, Chunjing, Hai Zou, and Shumin Wang. "Hepatitis B e Antigen Seroconversion Is Related with the Function of Dendritic Cells in Chronic Hepatitis B Virus Infection." Gastroenterology Research and Practice 2014 (2014): 1–6. http://dx.doi.org/10.1155/2014/413952.

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Aim. To investigate the relationship between hepatitis B e antigen seroconversion and the function of dendritic cells (DC) in patients with hepatitis B virus.Methods. The peripheral blood mononuclear cells (PBMC) from 21 chronic HBV patients in immune tolerance state, 23 patients in inactive HBsAg carrier state, and 10 healthy HBV-naive blood donors were incubated and induced into DC in presence of granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4), respectively. The expressions of surface markers on DC were detected by flow cytometry, and the stimulatory capacity of DC in allogenic mixed leukocyte reaction (MLR) was tested by CCK-8, and the level of cytokines released by DC was analyzed by enzyme-linked immunosorbent assay (ELISA).Results. DC from patients in immune tolerance showed a remarkably lower surface expression of CD80, CD86, and HLA-DR and exhibited an impaired stimulatory capacity in MLR and reduced secretion of IL-12, as compared to the patients in inactive HBsAg carrier state. There was no significant difference between the indicators from the patients in inactive HBsAg carrier state and healthy subjects. There was a significant difference of HBV DNA level between immune tolerance and inactive HBsAg carrier group (P<0.01) and a negative correlation between HBV DNA level and the expressions of dendritic cells in both groups, respectively (P=0.01).Conclusion. DC from patients in inactive HBsAg carrier state shows stronger function in comparison with patients in immune tolerance, the expressions of dendritic cells correlate with HBV DNA level, and the function stage of DC may play an important role in HBeAg seroconversion.
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Noguchi, Akinori, Jun Hayashi, Koya Nakashima, Miki Hirata, Hideyuki Ikematsu, and Seizaburo Kashiwagi. "HBsAg subtypes among HBsAg carriers in Okinawa, Japan. Evidence of an important relationship in seroconversion from HBeAg to anti-HBe." Journal of Infection 28, no. 2 (March 1994): 141–50. http://dx.doi.org/10.1016/s0163-4453(94)95560-3.

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46

Fan, Rong, Jie Peng, Qing Xie, Deming Tan, Min Xu, Junqi Niu, Hao Wang, et al. "Combining Hepatitis B Virus RNA and Hepatitis B Core–Related Antigen: Guidance for Safely Stopping Nucleos(t)ide Analogues in Hepatitis B e Antigen–Positive Patients With Chronic Hepatitis B." Journal of Infectious Diseases 222, no. 4 (March 25, 2020): 611–18. http://dx.doi.org/10.1093/infdis/jiaa136.

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Abstract Background Safe nucleos(t)ide analogue discontinuation in chronic hepatitis B (CHB) is an unmet need. We aimed to investigate whether combining hepatitis B virus (HBV) RNA and hepatitis B core–related antigen (HBcrAg) could perform satisfactorily in predicting off-treatment outcomes. Methods The evaluation cohort included 127 hepatitis B e antigen (HBeAg)–positive patients from a multicenter prospective trial who stopped telbivudine-based therapy after achieving HBeAg seroconversion and HBV DNA &lt; 50 IU/mL for &gt; 48 weeks. As validation, 59 patients treated with entecavir or tenofovir before discontinuation were analyzed. Results At the end of treatment (EOT), HBV RNA and HBcrAg were significant independent predictors of the clinical relapse risk. In the evaluation cohort, no clinical relapse occurred among patients with negative HBV RNA and HBcrAg &lt; 4 log10 U/mL at EOT (low-risk group), whereas 46.8% patients with positive HBV RNA and HBcrAg ≥ 4 log10 U/mL (high-risk group) experienced clinical relapse during 4-year posttreatment follow-up (P &lt; .001); the corresponding incidences in the validation cohort were 0% and 69.4% (P &lt; .001), respectively. More patients in the low-risk group achieved HBsAg loss than the other patients after treatment cessation (16.1% vs 1.3%, P = .002). Conclusions Combining HBV RNA and HBcrAg performed satisfactorily in predicting clinical relapse and HBsAg loss after treatment cessation in HBeAg-positive patients with CHB. The combination of hepatitis B virus RNA and hepatitis B core–related antigen performed satisfactorily in predicting clinical relapse and hepatitis B surface antigen loss after stopping nucleos(t)ide analogue treatment among noncirrhotic hepatitis B e antigen–positive patients with chronic hepatitis B and could be used to guide safe discontinuation.
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Murata, Kazumoto. "Relative predictive factors for hepatocellular carcinoma after HBeAg seroconversion in HBV infection." World Journal of Gastroenterology 11, no. 43 (2005): 6848. http://dx.doi.org/10.3748/wjg.v11.i43.6848.

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Warner, B. G., W. G. H. Abbott, and A. G. Rodrigo. "Frequency-dependent selection drives HBeAg seroconversion in chronic hepatitis B virus infection." Evolution, Medicine, and Public Health 2014, no. 1 (December 13, 2013): 1–9. http://dx.doi.org/10.1093/emph/eot023.

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49

Cho, S. "Effect of virologic response on posttreatment durability of lamivudine-induced HBeAg seroconversion." Journal of Hepatology 34 (April 2001): 172. http://dx.doi.org/10.1016/s0168-8278(01)80631-0.

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Cho, S. W., K. M. Lee, K. B. Hahm, J. H. Kim, K. H. Ko, and H. J. Kim. "Effect of virologic response on posttreatment durability of lamivudine-induced HBeAg seroconversion." Journal of Hepatology 34 (April 2001): 172. http://dx.doi.org/10.1016/s0168-8278(01)81506-3.

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