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1.
Current pegylated interferon-α (PEG-IFN) treatment for chronic hepatitis B (CHB) e-antigen (HBeAg)-positive patients are suboptimal, and effective ways of improving PEG-IFN treatment efficacy are needed.This retrospective cohort study compared the efficacy of a PEG-IFN stepwise optimization treatment (PEG-IFN SOT) strategy with that of a 48-week PEG-IFN standard therapy (PEG-IFN ST) in HBeAg-positive CHB patients.A total of 110 patients were included in our study. Of these, 70 received the PEG-IFN SOT and 40 received the PEG-IFN ST (control group). We based the decision whether to add adefovir and/or extend the PEG-IFN–based treatment to 96 weeks on the patients’ 12-week or 24-week early virological response (12W EVR, at least a 2 log10 reduction in HBV DNA copies/mL at week 12; 24W EVR, at least 1 log10 reduction in HBsAg IU/mL or HBsAg <1500 IU/mL at week 24) and their 48-week partial response (48W PR, 1.0 ≤HBeAg ≤10.0 S/CO or HBeAg >10.0 S/CO but HBsAg <1000 IU/mL).The HBeAg seroconversion rate 24 weeks post-PEG-IFN treatment was significantly higher in the PEG-IFN SOT than the PEG-IFN ST group (50% vs 22.5%, P = 0.005). The HBsAg clearance rates in the PEG-IFN SOT and ST groups were 10% and 0% (P = 0.04), respectively. Receiving PEG-IFN SOT (OR = 0.26, P = 0.01), ALT × ULN at baseline (OR = 0.74, P = 0.003), and achieving 12 and 24W EVR (OR = 0.29, P = 0.03) were independent factors associated with HBeAg seroconversion.PEG-IFN SOT is a promising strategy for achieving high rates of serological response in HBeAg-positive CHB patients. 相似文献
2.
Lin-Yan Zeng Jiang-Shan Lian Jian-Yang Chen Hong-Yu Jia Yi-Min Zhang Dai-Rong Xiang Liang Yu Jian-Hua Hu Ying-Feng Lu Lin Zheng Lan-Juan Li Yi-Da Yang 《World journal of gastroenterology : WJG》2014,20(27):9178-9184
AIM: To determine the baseline hepatitis B surface antigen (HBsAg) levels during the different phases of chronic hepatitis B (CHB) patients in China.METHODS: Six hundred and twenty-three hepatitis B virus or un-infected patients not receiving antiviral therapy were analyzed in a cross-sectional study. The CHB patients were classified into five phases: immune-tolerant (IT, n = 108), immune-clearance (IC, n = 161), hepatitis B e antigen negative hepatitis (ENH, n = 149), low-replicative (LR, n = 135), and liver cirrhosis (LC, n = 70). HBsAg was quantified (Abbott ARCHITECT assay) and correlated with hepatitis B virus (HBV) DNA, and serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) in each phase of CHB was also determined.RESULTS: Median HBsAg titers were different in each phase of CHB (P < 0.001): IT (4.85 log10 IU/mL), IC (4.36 log10 IU/mL), ENH (2.95 log10 IU/mL), LR (3.18 log10 IU/mL) and LC (2.69 log10 IU/mL). HBsAg titers were highest in the IT phase and lowest in the LC phase. Serum HBsAg titers showed a strong correlation with HBV viral load in the IC phase (r = 0.683, P < 0.001). No correlation between serum HBsAg level and ALT/AST was observed.CONCLUSION: The mean baseline HBsAg levels differ significantly during the five phases of CHB, providing evidence on the natural history of HBV infection. HBsAg quantification may predict the effects of immune-modulator or oral nucleos(t)ide analogue therapy. 相似文献
3.
Er-Li Gu Yi-Qi Yu Jia-Li Wang Yan-Yan Ji Xiu-Yun Ma Qing Xie Hong-Ying Pan Shan-Min Wu Jun Li Cheng-Wei Chen Xiao-Wei Xu Yue-Er Wang Guang-Bi Yao Hong Wang Wen-Hong Zhang 《World journal of gastroenterology : WJG》2015,21(2):653-660
AIM: To observe the effect of response-guided add-on therapy with adefovir(ADV) and lamivudine(LAM) in cirrhotic hepatitis B(CHB) patients.METHODS: A total of 100 patients with CHB and cirrhosis were divided into three arms according to hepatitis B virus(HBV) DNA level after 24 wk LAM monotherapy: Arm A(complete response, HBV DNA ≤ 60 IU/m L, n = 49), Arm B(partial response, HBV DNA: 60-2000 IU/m L, n = 31) and Arm C(inadequate response, HBV DNA 2000 IU/m L, n = 20). ADV was added to LAM at week 48 in Arms A and B, but at week 24 in Arm C. Virological response, YMDD mutations, biochemical response, and liver function were evaluated.RESULTS: Comparison of the three arms demonstrated that early complete virologic response at week 24was associated with maintained viral suppression(undetectable rate of HBV DNA at week 144 was 95.96%, 66.67% and 35.29%, respectively, P = 0.000) and reduced YMDD mutations(mutation rate at week 144 was 0%, 3.23% and 15%, respectively, P = 0.015) after 144 wk treatment. For patients who failed to achieve complete virological response at week 24, switching to combination therapy further decreased HBV DNA level by 1 log10 IU/m L. All three arms obtained biochemical benefits including decline of alanine aminotransferase and elevation of albumin. In patients who developed HBV DNA breakthrough for YMDD mutations, ADV add-on therapy did not induce further multiple drug resistance to LAM or ADV.CONCLUSION: Optimized response-guided add-on therapy of ADV and LAM maintains long-term suppression of HBV DNA and improves liver function in CHB patients with compensated liver cirrhosis. 相似文献
4.
Ming-Hui Li Yao Xie Lu Zhang Yao Lu Ge Shen Shu-Ling Wu Min Chang Cai-Qin Mu Lei-Ping Hu Wen-Hao Hua Shu-Jing Song Shu-Feng Zhang Jun Cheng Dao-Zhen Xu 《World journal of hepatology》2016,8(15):637-643
AIM: To examine the association between interferon(IFN) therapy and loss of hepatitis B surface antigen(HBs Ag) in inactive HBs Ag carriers. METHODS: This was a retrospective cohort study in inactive HBs Ag carriers, who were treatment-naive, with a serum HBs Ag level 100 IU/m L and an undetectable hepatitis B virus(HBV) DNA level( 100 IU/m L). All the 20 treated patients received subcutaneous PEG-IFN alfa-2a 180 μg/wk for 72 wk and were then followed for 24 wk. There were 40 untreated controls matched with 96 wk of observation. Serum HBs Ag, HBV DNA, and alanine aminotransferases were monitored every 3 mo in the treatment group and every 3-6 mo in the control group. RESULTS: Thirteen(65.0%) of 20 treated patients achieved HBs Ag loss, 12 of whom achieved HBs Ag seroconversion. Mean HBs Ag level in treated patients decreased to 6.69 ± 13.04 IU/m L after 24 wk of treatment from a baseline level of 26.22 ± 33.00 IU/m L. Serum HBV DNA level remained undetectable( 100 IU/m L) in all treated patients during the study. HBs Ag level of the control group decreased from 25.72 ± 25.58 IU/m L at baseline to 17.11 ± 21.62 IU/m L at week 96(P = 0.108). In the control group, no patient experienced HBs Ag loss/seroconversion, and two(5.0%) developed HBV reactivation.CONCLUSION: IFN treatment results in HBs Ag loss and seroconversion in a considerable proportion of inactive HBs Ag carriers with low HBs Ag concentrations. 相似文献
5.
Yi-Min Zhang Yi-Da Yang Hong-Yu Jia Lin-Yan Zeng Wei Yu Ning Zhou Lan-Juan Li 《World journal of gastroenterology : WJG》2014,20(15):4407-4413
AIM:To investigate hepatitis B surface antigen(HBsAg)levels in patients with HBeAg-positive chronic hepatitis B(CHB)and different immune conditions.METHODS:HBeAg-positive CHB patients with different immune conditions were enrolled in this cross-sectional study.These patients were grouped according to the following criteria:immune-tolerant patients,IT group;patients with a mild immune response in the immune clearance phase,IC-Mild group;and patients with a dramatic immune response in the immune clearance phase and exhibiting acute on chronic liver failure(ACLF),ACLF group.All these patients had not previously received antiviral therapy and were enrolled at a pre-settled ratio of2:2:1.Serum HBsAg levels and the correlation between serum HBsAg level and serum hepatitis B virus(HBV)DNA level were evaluated in these groups.RESULTS:In total,180 HBeAg-positive CHB patients[IT group(n=72),IC-Mild group(n=72),and ACLF group(n=36)]were enrolled in this study.The median serum HBsAg levels varied among the groups(P<0.001):IT,4.86 log10IU/mL;IC-Mild,3.97 log10IU/mL;and ACLF,3.57 log10IU/mL.Serum HBsAg level showed a moderate positive correlation with serum HBV-DNA level in the IC-Mild group(r=0.60,P<0.001),but exhibited a weaker correlation in the IT(r=0.52,P<0.001)and ACLF groups(r=0.51,P=0.001).The ratio of HBsAg/HBV DNA did not differ significantly among the IT,IC-Mild,and ACLF groups(medians:0.56,0.55,and 0.56,respectively;P=0.179).CONCLUSION:Serum HBsAg levels varied significantly in HBeAg-positive patients with different immune conditions.These findings may have important implications for understanding the immune clearance of HBV in HBeAg-positive CHB patients. 相似文献
6.
Koji Takayama Norihiro Furusyo Eiichi Ogawa Hiroaki Ikezaki Motohiro Shimizu Masayuki Murata Jun Hayashi 《World journal of gastroenterology : WJG》2015,21(15):4696-4706
AIM: To investigate the impact of telaprevir-based triple therapy on the serum alpha-fetoprotein (AFP) level of chronic hepatitis C patients.METHODS: A total of 210 patients with chronic hepatitis C genotype 1 of high viral load (baseline serum hepatitis C virus RNA > 5.0 log10 IU/mL) were divided into two groups by type of treatment: triple therapy with telaprevir, pegylated-interferon-α (PEG-IFNα), and ribavirin (RBV) for 24 wk (n = 88), or dual therapy with PEG-IFNα and RBV for 48 wk (n = 122). The relationship between virological response and the change in the serum AFP level from baseline to 24 wk after the end of treatment was examined.RESULTS: No significant difference in mean baseline AFP level was found between the triple and dual therapy groups (8.8 ng/mL vs 7.8 ng/mL). Triple therapy produced significant declines in the AFP level in sustained virological response (SVR) and non-SVR patients (7.8 ng/mL at baseline to 3.5 ng/mL at 24 wk after the end of treatment, P < 0.001 and 14.3 ng/mL to 9.5 ng/mL, P = 0.004, respectively). In contrast, dual therapy resulted in a significant decline in AFP level only in SVR patients (4.7 ng/mL to 2.8 ng/mL, P < 0.001), but not in non-SVR patients (10.2 ng/mL to 10.1 ng/mL). Among patients with a high-baseline AFP level (≥ 10 ng/mL), the decline in the AFP level was significantly higher in the triple therapy than in the dual therapy group (15.9 ng/mL vs 1.6 ng/mL, P = 0.037).CONCLUSION: Regardless of virological response, telaprevir-based triple therapy reduced the serum AFP level. 相似文献
7.
R. Moucari N. Boyer M.‐P. Ripault C. Castelnau V. Mackiewicz A. Dauvergne D. Valla M. Vidaud M.‐H. N. Chanoine P. Marcellin 《Journal of viral hepatitis》2011,18(8):580-586
Summary. To assess the impact of sequential therapy with adefovir dipivoxil (ADV) and pegylated interferon alfa‐2a (PEG‐IFN) on virological (serum HBV‐DNA) and serological (serum HBsAg) response in 20 consecutive HBeAg‐negative patients. Patients received ADV for 20 weeks, then ADV and PEG‐IFN for 4 weeks and lastly PEG‐IFN for 44 weeks. Serum HBV‐DNA and HBsAg were assessed at baseline, during therapy (weeks 20, 44 and 68) and follow‐up (weeks 92 and 116). Sustained virological response (SVR) was defined as serum HBV‐DNA <10 000 copies/mL (partial) or <70 copies/mL (complete) 24 weeks after stopping treatment. A serological response was defined as a serum HBsAg decrease ≥1 log10IU/mL at the end of treatment. Baseline median serum HBV‐DNA and HBsAg levels were 7.6 log10copies/mL and 3.8 log10IU/mL, respectively. Ten patients (50%) achieved SVR, six of them had partial response and four complete response. Four patients (20%) achieved serological response. Complete SVRs showed a major and steep decline in HBsAg level with a median decrease of 0.5, 1.6 and 2.0 log10IU/mL at treatment week 20, 44 and 68, respectively. Partial SVRs showed a slight and slow decline in serum HBsAg level (0.1, 0.4, and 0.6 log IU/mL at weeks 20, 44 and 68, respectively). On‐treatment serum HBsAg decrease had a high accuracy to predict SVR (AUROC = 0.88). Our results suggest that sequential therapy might be an interesting strategy for HBeAg‐negative patients. Serum HBsAg kinetics seem to be an accurate tool to predict SVR. Large clinical trials are needed to explore this strategy with more potent analogues. 相似文献
8.
Tzu-Ning Tseng Yuan-Hung Kuo Tsung-Hui Hu Chao-Hung Hung Jing-Houng Wang Sheng-Nan Lu Chien-Hung Chen 《Viruses》2022,14(6)
This study investigated the kinetics in HBsAg and the HBsAg loss rate after entecavir or tenofovir disoproxil fumarate (TDF) cessation in patients with chronic hepatitis B (CHB) who achieved virological suppression after virological relapse without clinical relapse. A total 504 HBeAg-negative, non-cirrhotic patients who previously received entecavir or TDF with post-treatment and who were followed up for at least 30 months were included. Of the 504 patients, 128 achieved sustained virological suppression (Group I), and 81 experienced virological relapse without clinical relapse. Of the 81 patients, 52 had intermittent or persistent HBV DNA > 2000 IU/mL (Group II), and 29 achieved persistent virological suppression (HBV DNA < 2000 IU/mL) for at least 1.5 years (Group III) after virological relapse. A generalized estimating equations analysis showed that Groups I and III experienced larger off-treatment HBsAg declines than Group II (both, p < 0.001). The post-treatment HBsAg declines of Group I and Group III were similar (p = 0.414). A multivariate analysis showed that there were no differences in the HBsAg change and HBsAg decline (p = 0.920 and 0.886, respectively) or HBsAg loss rate (p = 0.192) between Group I and Group III. The patients who achieved persistent viral suppression after HBV relapse without clinical relapse have a similar decline in HBsAg and the HBsAg loss rate as the sustained responders. 相似文献
9.
Wei Jia Liu-Wei Song Yu-Qing Fang Xiao-Feng Wu Dan-Yang Liu Chun Xu Xiao-Mei Wang Wen Wang Dong-Xia Lv Jun Li Yong-Qiong Deng Yan Wang Na Huo Min Yu Hong-Li Xi Dan Liu Yi-Xing Zhou Gui-Qiang Wang Ning-Shao Xia Ming-Xiang Zhang 《Medicine》2014,93(29)
Previous studies have revealed antibody to hepatitis B core antigen (anti-HBc) levels as a predictor of treatment response in hepatitis B early antigen (HBeAg)-positive chronic hepatitis B (CHB) patients in both interferon and nucleos(t)ide analog therapy cohorts. However, there is no information about anti-HBc levels in the natural history of CHB.This study aimed to define anti-HBc levels of different phases in the natural history of CHB.Two hundred eleven treatment-naive CHB patients were included in the study. They were classified into 4 phases: immune tolerance (IT) phase (n = 39), immune clearance (IC) phase (n = 48), low or no-replicative (LR) phase (n = 55), and HBeAg-negative hepatitis (ENH, n = 69). Fifty patients who were HBsAg negative and anti-HBc positive were also recruited as past HBV infection (PBI) control group. Anti-HBc levels were measured by a newly developed double-sandwich immunoassay. Correlation of anti-HBc levels with alanine aminotransferase (ALT) and other HBV-related markers within each phase was performed.Serum anti-HBc levels were statistically significant between patients in different phases of CHB (P < 0.001). The median anti-HBc levels were: IT (3.17 log10 IU/mL), IC (4.39 log10 IU/mL), LR (3.29 log10 IU/mL), ENH (4.12 log10 IU/mL), and PBI (0.61 log10 IU/mL). There existed a strong correlation in IC (r = 0.489, P < 0.001), a poor correlation in ENH (r = 0.275, P = 0.042), and no correlation in patients with ALT reached 5 times upper limit of normal (r = 0.120, P = 0.616).Anti-HBc levels show significant differences during the natural course of CHB. These results may provide some potentially useful insights into hepatitis B pathogenesis and immune activation against hepatitis B virus. 相似文献
10.
Fahad Alsohaibani Noura Alturaif Ahmed Abdulshakour Saad Alghamdi Alfadel Alshaibani Hamad Alashgar Khalid Alkahtani Ingvar Kagevi 《Saudi Journal Of Gastroenterology》2015,21(5):295-299