Consolidation treatment needed for sustained HBsAg-negative response induced by interferon-alpha in HBeAg positive chronic hepatitis B patients

Hepatitis B surface antigen(HBsAg)clearance is considered as functional cure in patients with chronic hepatitis B(CHB).This study aimed to assess the durability of HBsAg clearance achieved by interferon-based therapies in patients with CHB who were originally positive for hepatitis B envelope antigen(HBeAg).In this prospective study,HBeAg-positive CHB patients with confirmed HBsAg loss under interferon-based therapies were enrolled within 12 weeks from end of treatment and followed up for 48 weeks.Virological markers,biochemical indicators,and liver imaging examinations were observed every 3–6 months.Sustained functional cure was analysed as primary outcome.Factor associated with sustained HBsAg loss or reversion was also investigated.The rate of HBsAg loss sustainability was 91.8%(212/231).Patients receiving consolidation treatment for 12–24weeks or≥24 weeks had higher rates of sustained HBsAg negativity than those receiving consolidation treatment for<12 weeks(98.3%and 91.2%vs.86.7%,P=0.068),and the former groups had significantly higher anti-HBs levels than the later(P<0.05).The cumulative incidence of HBsAg reversion and HBV DNA reversion was 8.2%and 3.9%,respectively.Consolidation treatment of≥12 weeks[odd ratio(OR)3.318,95%confidence interval(CI)1.077–10.224,P=0.037)was a predictor of sustained functional cure,and HBeAg-positivity at cessation of treatment(OR 12.271,95%CI 1.076–139.919,P=0.043)was a predictor of HBsAg reversion.Interferon-alpha induced functional cure was durable and a consolidation treatment of≥12–24 weeks was needed after HBsAg loss in HBeAg-positive CHB patients.

Efficacy compared between entecavir and adefovir dipivoxil on HBeAg-positive nucleos(t)ide-naive patients with chronic hepatitis B at week 12 and week 48

Objective:To evaluate the efficacy of entecavir and adefovir dipivoxil on HBeAg-positive nucleos(t)ide-naive patients with chronic hepatitis B with the method of Meta analysis.Methods:We searched PUBMED,EMBASE,CNKI (China National Knowledge Infrastructure),the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews with reference to all data documented before May 2010.The dosage of entecavir and adefovir dipivoxil was 0.5 mg/d and 10 mg/d,respectively.Heterogeneity was examined by Chi-square test,the relative risk calculated and forest plot drawn.Rates of undetected serum HBV DNA,serum alanine aminotransferase (ALT) normalization,HBeAg clearance,HBeAg seroconversion and adverse effect occurrence were analyzed.Results:Six articles were included,which fit well in with this study.Meta analysis showed that the rate of undetected serum HBV DNA(P=0.000 2 at week 12,P=0.002 at week 48)and that of serum ALT normalization(P=0.04 at week 12,P=0.008 at week 48)in the entecavir group were higher than those in the adefovir dipivoxil group.However,no statistic significance existed between the two groups in the rate of HBeAg clearance (P=0.17),the rate of HBeAg seroconversion(P=0.53)or the rate of adverse effect occurrence(P=0.92)at week 48.Conclusion:Entecavir was superior to adefovir dipivoxil in decreasing serum HBV DNA and normalizing serum ALT in the HBeAg-positive nucleos(t)ide-naive patients with chronic hepatitis B.

Correlation between constitution of Yin deficiency syndrome and polymorphism of HLADQA1 / treatment response of Peg-IFNα therapy in HBeAg positive chronic hepatitis B patients

Objective To observe the correlation between constitution of yin deficiency syndrome(YDS)and polymorphism of HLA-DQA1/treatment response of Peg-IFNαtherapy in HBe Ag positive chronic hepatitis B(CHB)patients,and to explore constitution of Chinese medicine(CM)in response to interferon therapy.Methods Totally 120 HBe Ag positive CHB patients who were

Change of Cytokines in Chronic Hepatitis B Patients and HBeAg are Positively Correlated with HBV RNA, Based on Real-world Study

Background and Aims:The natural course of chronic hepatitis B virus(HBV)infection is widely studied;however,follow-up studies of the same patients are scanty.Here,we studied the dynamic changes of serum HBV RNA and cytokines in hepatitis B virus e antigen(HBeAg)-positive patients treated with entecavir(ETV)to explore the relationship between the HBV serum viral nucleic acids and host immunity.Methods:Thirty-three chronic hepatitis B patients who are HBeAg-positive,with high virus load(HBV DNA>20,000 IU/mL),and received standard nucleos(t)ide analogue(NA)antiviral therapy(ETV)for more than 48 weeks were included.The serum levels of HBV nucleic acids and selected cytokines were measured at 0,12,24,and 48 weeks respectively.Results:Serum HBV RNA could still be detected while serum HBV DNA had fallen below the detection limit in patients treated with ETV.There was a strong positive correlation between HBV RNA and HBeAg,with a concomitant decrease in the secretion of cytokines from type 1 helper T(Th1)/type 2 helper T(Th2)/interleukin(IL)-17 producing T(Th17)cells.IL-4 and IL-10 were the main cytokines negatively associated with serum HBV RNA.Conclusions:HBeAg can be used to reflect the load of HBV RNA indirectly,because serum HBV RNA has not been widely used in clinical practice.Meanwhile,serum IL-4 and IL-10 might be explored in combination with HBV RNA in guiding future clinical antiviral therapy.

Differences of Efficacy Between Tenofovir Alafenamide Fumarate and Tenofovir Disoproxil Fumarate in Pregnant Women With Different Hepatitis B Virus DNA Loads

Tenofovir alafenamide fumarate(TAF)has been endorsed by guidelines for blockade ofmother-to-child transmission of hepatitis B virus(HBV),given that its efficacy and safety are comparable to tenofovir disoproxil fumarate(TDF).However,there is a lack of comparative studies regarding the treatment efficacy in patients with diverse viral loads.This study retrospectively analyzed 96 hepatitis B e antigen(HBeAg)–positive pregnant women with HBV DNA levels of≥2×10^(5) IU/mL.Based on viral loads(HBV DNA levels),participants in the TAF and TDF groups were stratified into three subgroups,namely,the High-G(titer≥8 log10 IU/mL),Middle-G(7 log10 IU/mL≤titer<8 log10 IU/mL)and Low-G(titer<7 log10 IU/mL)subgroups.The primary endpoint was effectiveness of TAF and TDF in patients with varying viral loads,whereas secondary endpoints were hepatitis B surface antigen(HBsAg)positivity in infants at 7 to 12 months and the safety profile for mothers and children.Compared with baseline levels,median HBV DNA levels in mothers were decreased by 4.51 and 4.09 log10 IU/mL in the TAF andTDF groups(P=0.04)predelivery,respectively.In the High-G subgroup,the titers were significantly lower in the TAF group(P=0.045).A higher proportion of patients experienced a virus decline of≥4 log10 IU/mL in the TAF group compared with the TDF group,with rates of 78.26% versus 58%(P=0.034),respectively.Moreover,the median serum phosphate levels significantly decreased frombaseline to predelivery in the TDF group(P=0.04).Finally,infants in both cohorts tested negative for HBsAg at 7–12 months after delivery.Overall,our findings indicate that TAF can be considered the preferred option for the treatment of HBeAgpositive pregnant women with HBV DNA levels of≥8 log10 IU/mL.

Association between CISH polymorphisms and spontaneous clearance of hepatitis B virus in hepatitis B extracellular antigen-positive patients during immune active phase

Background Some hepatitis B extracellular antigen （HBeAg）-positive chronic hepatitis B （CHB） patients in their immune active phase can clear the virus spontaneously and enter into an inactive hepatitis B virus （HBV） carrier state,indicating a benign prognosis.In this study,the association between cytokine-inducibie SRC homology 2 domain protein （C/SH） gene polymorphisms at-292 （rs414171） and the spontaneous clearance of HBV in HBeAg-positive CHB patients in immune the active phase was investigated.Methods Seventy HBeAg-positive CHB patients in the immune active phase were followed up for 76 weeks without antiviral therapy.The alanine transaminase,aspartate transaminase,HBV DNA,HBeAg and hepatitis B extracellular antibody levels were tested regularly.At week 76,27 patients were classified into group A （HBV DNA level below 2 104 IU/ml and the value of HBeAg declined below 10％ of the baseline at week 76）,and 43 patients were classified into group B （HBV DNA level higher than 2×104 IU/ml or the value of HBeAg did not decline substantially at week 76）.CISH （rs414171） polymorphisms were also tested using the iPLEX system.Results The HBV DNA levels at week 12 were significantly greater in group B compared with group A （group A：（6.87±1.40） log10IU/ml; group B：（7.61±1.38） log10IU/ml,P=0.034） and the HBeAg values were greater in group B at week 28 compared with group A （P=0.001）.The differences in HBV DNA and HBeAg values increased between the groups over time.Sixteen patients in group A and 11 in group B were genotype AA.Those with genotype AT or TT included 11 in group A and 31 in group B （AA vs.AT and TT,odds ratio 4.10 （95％ confidence interval：1.462-11.491）,P=0.006）.Conclusion CISH gene polymorphisms at-292 （rs414171） are associated with HBV clearance in HBeAg-positive CHB patients in the immune active phase,and AA is a favorable genotype for this effect.