Effects of different intervention methods on psychological flexibility,negative emotions and sleep quality in chronic hepatitis B

BACKGROUND Patients with chronic hepatitis B(CHB)experience various problems,including low psychological flexibility,negative emotions,and poor sleep quality.Therefore,effective nursing interventions are required to reduce adverse events.Acceptance and commitment therapy(ACT)combined with enabling cognitivebehavioral education(ECBE)can improve patients'psychological and sleep.Therefore,we speculate that this may also be effective in patients with CHB.AIM To investigate the effects of different intervention methods on psychological flexibility,negative emotions,and sleep quality in patients with CHB.METHODS This retrospective study examined clinical and evaluation data of 129 patients with CHB.Intervention methods were divided into a conventional group(routine nursing,n=69)and a combination group(ACT combined with ECBE,n=60).We observed changes in psychological flexibility,negative emotions,sleep quality,and self-care ability in both groups.Observation items were evaluated using the Acceptance and Action Questionnaire-2nd Edition(AAQ-II),Self-Rating Anxiety Scale(SAS),Self-Rating Depression Scale(SDS),Pittsburgh Sleep Quality Index(PSQI),and Exercise of Self-Care Agency Scale(ESCA).RESULTS Compared with the conventional group,the AAQ-II score of the combined group was lower(F_(between-group effect)=8.548;F_(time effects)=25.020;F_(interaction effects)=52.930;all P<0.001),the SAS score(t=5.445)and SDS score(t=7.076)were lower(all P<0.001),as were the PSQI dimensions(tsleep quality=4.581,tfall sleep time=2.826,tsleep time=2.436,tsleep efficiency=5.787,tsleep disorder=5.008,thypnotic drugs=3.786,tdaytime dysfunction=4.812);all P<0.05).The ESCA scores for all dimensions were higher(thealth knowledge level=6.994,t self-concept=5.902,tself-responsibility=19.820,tself-care skills=8.470;all P<0.001).CONCLUSION ACT combined with ECBE in patients with CHB can improve psychological flexibility and sleep quality,alleviate negative emotions,and improve self-care.

Treatment of HBeAg-Negative Chronic Hepatitis B Patients with Nucleos(t)ide Analogues in Burkina Faso

The treatment of chronic hepatitis B (CHB) has increased significantly in recent years. In patients affected by HBeAg-negative CHB, it is necessary to distinguish the inactive carriers (low viral DNA 2000 IU/mL, normal ALT, histological lesions absent or minimal) who does not need treatment, and patients suffering from active CHB (DNA > 2000 IU/ml, high transaminases or fluctuating, significant fibrosis and/or necro-inflammatory activity > 1) who must be treated. The main purpose of treatment is to obtain a long-lasting viral suppression to improve the histological lesions and reduce the risk of evolution towards cirrhosis, liver failure and hepatocellular carcinoma (HCC). It about an indefinite treatment (unless HBsAg seroclearance) expensive and often inaccessible for the majority of our patients. Our study aimed to report the results of four years follow-up of HBeAg-negative patients treated by Nucleos(t)ide analogues (NAs) in Ouagadougou (Burkina Faso). It was a clinical observational study with 133 patients including 95 men;the average age was 41.2 years, completing the criteria of treatment. One hundred and twelve patients were treated by tenofovir (TDF), fourteen by lamivudine and seven co-infected HIV/HBV patients by Atripla® (combination TDF, Emtricitabine and Efavirenz). Virological and biochemical responses were respectively 100% and 94% after 4 years. The rate of HBsAg seroclearance was 1.5%. Twelve of fourteen patients (85.7%) had lamivudine resistance and no cases of resistance in the TDF and Atripla® groups. One co-infected patient developed HCC during treatment. Among patients treated by TDF, two cases of hypophosphatemia were noticed and no case of kidney failure. The treatment of CHB is certainly progressing;updated guidelines (EASL, AASLD) exist but should be adapted to the African context.

HBeAg negative variants and their role in the natural history of chronic hepatitis B virus infection

Molecular virology methods including polymerase chain reaction, cloning and sequencing have revolutionised our understanding of viral genome variation. In the case of hepatitis B virus (HBV), sequencing studies have identified a number of virus variants normally found during the natural course of chronic infection. The appearance of the precore stop codon (with G-for-A substitution at position 1896) and basal core promoter (BCP) (with A-for-T and G-for-A, at positions 1762 and 1764, respectively) variants which reduce or abrogate hepatitis B e antigen (HBeAg) production, heralds the initiation of the seroconversion phase from HBeAg to anti-HBe positivity. The gradual removal of the tolerogenic effect of HBeAg leads to the awakening of the immune response (immune clearance phase). Most patients after HBeAg seroconversion become &#x0201c;inactive HBsAg carriers&#x0201d;. However during the course of infection precore and/or BCP variants may emerge and be selected leading to HBeAg negative chronic hepatitis B (CHB) with high viremia levels (reactivation phase). The prevalence of HBeAg negative CHB has been increasing over the last few decades and has become the commonest type of HBV infection in many countries of the world. This probably reflects the aging of existing HBV carriers and the effective prevention measures restricting new HBV infections. Frequent acute exacerbations accompanied by high viral replication, elevated alanine aminotransferase levels and histological activity are a common feature of HBeAg negative CHB leading to cirrhosis much faster than in HBeAg positive CHB patients.

Biochemical response to lamivudine treatment in HBeAg negative chronic hepatitis B patients in Iran

AIM： To study the effect of a one-year lamivudine regimen in patients with chronic hepatitis B. METHODS： Medical records of HBeAg negative hepatitis B patients who attended a hepatitis clinic in Tehran between March 2002-March 2004 were evaluated. The patients received 100 mg lamivudine tablets once daily for at least 12 mo. Liver enzymes and complete blood count were checked at baseline and the end of treatment （12th mo） and 6 mo after discontinuation of treatment. RESULTS： Of all patients, 24 were excluded. Of 71 patients left, 58 （81.7%） were men. Mean age of the patients was 38 ± 14 years. Mean level of ALT in serum was 1437 ± 205 nkat/L at baseline with a significant reduction at the end of treatment to a mean level of 723 ± 92 nkat/L （P = 0.002）. In 38 patients （53.5%）, the ALT level was normal after one-year treatment. Five patients （7.3%） relapsed （biochemically） within 6 mo after discontinuing lamivudine therapy （the patients with good end of treatment response）. Mean level of AST in serum was 1060 ± 105 nkat/L at baseline which decreased significantly to 652 ± 75 nkat/L at the end of treatment （P = 0.002）. CONCLUSION： Over half （53.5%） of chronic hepatitis B patients with HBeAg negative have normal liver enzyme level at 12-mo lamivudine therapy.

Predictive Value of Serum pgRNA on HBeAg Clearance in Patients with Chronic Hepatitis B with Low HBeAg Levels Treated with Pegylated Interferon

Objective:To study the predictive value of serum pregenomic RNA(pgRNA)on HBeAg clearance in patients with chronic hepatitis B with low HBeAg levels during pegylated interferon therapy.Methods:Twenty chronic hepatitis B patients with HBeAg positive and quantitative<50S/CO were selected for this study.The subjects underwent pegylated interferon therapy for 48-96 weeks and were followed up in the outpatient clinic after treatment.The patients were then divided into groups based on whether their HbeAg turned negative.The predictive ability of each indicator for HBeAg negative conversion was evaluated in the HBeAg negative group and the HBeAg positive group.Results:The results of logistic regression analysis suggested that pgRNA and HBcrAg were better indicators for predicting the clearance of HBeAg after treatment.Conclusion:For patients with chronic hepatitis B with low HBeAg levels,pgRNA is a good indicator in predicting HBeAg clearance during pegylated interferon therapy.

聚乙二醇干扰素α-2b联合替诺福韦二吡呋酯治疗HBeAg阳性慢性乙肝的临床效果

目的观察聚乙二醇干扰素α-2b联合替诺福韦二吡呋酯治疗乙肝e抗原(HBeAg)阳性慢性乙肝的临床效果。方法选取2019年1月—2023年1月厦门市第三医院收治的HBeAg阳性慢性乙肝患者80例,按随机数字表法分为联合组(n=40)和单药组(n=40)。单药组予替诺福韦二吡呋酯治疗,联合组在单药组基础上予聚乙二醇干扰素α-2b治疗,2组均持续治疗6个月。比较2组HBeAg及乙肝病毒脱氧核糖核酸(HBV-DNA)转阴率,治疗前后肝功能指标[天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、总胆红素(TBil)]、血清炎性因子[肿瘤坏死因子-α(TNF-α)、白介素(IL)-6、IL-10]、肝纤维化指标[透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、层粘连蛋白(LN)]及不良反应。结果与单药组比较,联合组HBeAg及HBV-DNA转阴率均更高(χ^(2)=10.208,P=0.001;χ^(2)=4.507,P=0.034);与治疗前比较,治疗6个月后,2组AST、ALT、TBil、TNF-α、IL-6、IL-10、HA、PCⅢ、LN水平均降低,且联合组低于单药组(P<0.01)。联合组与单药组不良反应总发生率比较差异不明显(12.50%vs.7.50%,χ^(2)=0.139,P=0.709)。结论HBeAg阳性慢性乙肝患者应用聚乙二醇干扰素α-2b联合替诺福韦二吡呋酯治疗效果确切,有助于提高HBeAg、HBV-DNA转阴率,改善肝功能,减轻炎性反应及肝纤维化程度,且安全性较高。

Effect of lamivudinein in BeAg-positive chronic hepatitis B: Discordant effect on HBeAg and HBV DNA according to pretreatment ALT level

AM: To clarify differences in antiviral effect of the drug in patients with different ALT levels, we examined the changes in HBV markers in patients with high or low ALT levels with or without lamivudine treatment. METHODS: Thirty-seven HBeAg-positive patients were studied. Ten patients with ALT levels higher than 200 IU/L (group 1) and 8 patients with ALT below 200 IU/L (group 2) were treated orally with 100 mg/d of lamivudine. As untreated control, 9 patients with ALT above 200 IU/L (group 3) and 10 patients with ALT below 200 IU/L (group 4) were examined. ALT level, HBeAg/HBeAb status, and HBV DNA level were examined monthly for 11.9±0.4 mo. RESULTS: The ALT level normalized in all 10 patients of group 1, 7/8 of group 2, 4/9 of group 3, and 1/10 of group 4 within 6 mo (groups 1 vs2, P= NS; groups 1 vs 3, P= 0.002; groups 1 vs4, P<0.0001). HBV DNA fell below the detection limit in all 10 patients of group 1, 7/8 of group 2, 0/9 of group 3, and 0/10 of group 4 within 6 mo (groups 1 vs 2, P - NS). HBeAg became seronegative in 7/10 patients of group 1, 1/8 of group 2, 3/9 of group 3, and 0/10 of group 4 within 12 mo (groups 1 vs2, P= 0.02; groups 1 vs 3, P= NS). CONCLUSION: Our data suggest that HBeAg-positive patients with higher ALT levels can be considered good candidates for lamivudine therapy, probably because lamivudine accelerates the natural seroconversion of HBeAg, accompanied by HBV DNA loss, in these patients.

Interferon and lamivudine combination therapy versus lamivudine monotherapy for hepatitis B e antigen-negative hepatitis B treatment:a meta-analysis of randomized controlled trials

BACKGROUND: It has been demonstrated that only a minority of patients with hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) obtain a sustained response after either interferon (IFN) or nucleos (t)ide analogue monotherapy. Therefore, combination therapy of drugs with synergistic antiviral effects was proposed to have a sustained response in these patients. We compared the effect and safety of lamivudine monotherapy and its combination with IFN including conventional interferon (CON-IFN) and pegylated interferon (PEG-IFN) for HBeAg-negative CHB patients. DATA SOURCES: A group of three independent reviewers identified 9 eligible randomized controlled trials through electronic searches (MEDLINE, OVID, EMBASE, the Cochrane Library Clinical Trials Registry, and the Chinese Medical Database), manual searches, and contact with experts. Sustained virological and biochemical responses were defined as primary efficacy measures. We performed quantitative meta-analyses to assess differences between CON-IFN plus lamivudine combination and lamivudine monotherapy groups. RESULTS: No greater sustained virological and biochemical rates were found in patients receiving CON-IFN/lamivudine combination therapy [29.1% vs. 26.7%, odds ratio (OR)=0.98, 95% confidence interval (CI) 0.65-1.50, P=0.94, and 41.8% vs. 40.3%, OR=1.13, 95% CI 0.78-1.65, P=0.51, respectively],though a reduced YMDD mutation rate was achieved in the combination group [8.39% vs. 30.0%, OR=0.16, 95% CI 0.076-0.33, P<0.001]. However, data from one PEG-IFN trial showed greater sustained virological and biochemical rates in patients receiving combination therapy [response rate 19.5% vs. 6.6%, OR=3.42, 95% CI 1.71-6.84, P<0.001 and 60.0% vs. 44.2%, OR=1.88, 95% CI 1.23-2.85, P=0.003, respectively]. CONCLUSIONS: Addition of CON-IFN to lamivudine did not improve treatment efficacy but suppressed YMDD mutation by lamivudine. Combination of PEG-IFN and lamivudine might increase the sustained response, and further clinical trials are needed for confirmation.

Cytokine Profiles and Virological Marker Monitoring during 48 Weeks Peginterferon Alfa Treatment for HBeAg-Positive Chronic Hepatitis B

Objective This study aimed to investigate whether cytokine profiles and virological markers might add value in monitoring the effects of peginterferon(PEG-IFN)therapy for hepatitis B e-antigen(HBeAg)positive chronic hepatitis B(CHB).Methods HBeAg positive patients with CHB were treated with PEG-IFN for 48 weeks.Clinical biochemical,and HBV serological indexes,as well as cytokines,were detected at baseline and every12 weeks.Results A total of 116 patients with CHB were enrolled in this study;100 patients completed the 48-week treatment and follow-up,of whom 38 achieved serum HBeAg disappearance,25 achieved HBeAg seroconversion,37 showed HBsAg decreases≥1 log10 IU/mL,9 showed HBsAg disappearance,and 8became HBsAb positive.The cytokine levels at baseline and during treatment were similar between the HBeAg disappearance group and non-disappearance group.The disappearance of HBeAg was independently associated with HBeAg levels at weeks 12 and 24,and with the HBeAg decline at week 24(P<0.05).The HBsAg response was independently associated with HBsAg,the HBsAg decline,HBeAg,the HBeAg decline at week 12,and HBsAg at week 24(P<0.05).Conclusion There was no significant correlation between the response to interferon(IFN)and cytokines during PEG-IFN treatment.The changes in virological markers predicted the response to IFN after 48 weeks.

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.

TLR10基因多态性与HBeAg阳性慢性乙型肝炎患者PEG-IFNα治疗临床转归的相关性分析

目的:探讨分析TLR10基因多态性与HBeAg阳性慢性乙型肝炎(CHB)患者聚乙二醇化干扰素α(PEG-IFNα)治疗临床归转的相关性。方法:选取2019年8月至2020年8月收治的92例HBeAg阳性CHB患者,均予以PEG-IFNα进行治疗,6个月后根据HBeAg、HBeAb情况将患者分为应答组44例和非应答组48例。提取全血基因组DNA,测定TLR10基因多态性点位(RS10004195位点和RS11096957位点),分析其不同点位基因型和等位基因分布与乙型肝炎病毒感染的关系,进而探讨TLR10基因多态性与临床转归的相关性。结果:TLR10基因RS10004195位点基因型中,应答组AA+AT型基因分布频率为77.27%显著高于非应答组的52.08%,A等位基因频率65.91%显著高于非应答组的41.67%,差异有统计学意义(P<0.05);TLR10基因RS11096957位点基因型中,应答组AC+AA型基因分布频率为70.45%,与非应答组的62.50%差异无统计学意义(P>0.05),应答组A等位基因频率为61.36%显著高于非应答组的39.58%,差异有统计学意义(P<0.05);TLR10基因RS10004195位点中,A型基因、A等位基因频率和RS11096957位点中A等位基因频率是HBeAg阳性CHB患者PEG-IFNα治疗临床转归的独立危险因素(OR>1,P<0.05)。结论:TLR10基因RS10004195位点A型基因携带、A等位基因频率,RS11096957位点A等位基因频率是HBeAg阳性CHB患者PEG-IFNα治疗临床转归的独立危险因素,对CHB患者治疗应答反应具有较好评估作用,可为临床治疗提供指导依据。

Serum hepatitis B virus RNA is a predictor of HBeAg seroconversion and virological response with entecavir treatment in chronic hepatitis B patients

BACKGROUND Characteristics of alterations of serum hepatitis B virus(HBV) RNA in different chronic hepatitis B(CHB) patients still cannot be fully explained. Whether HBV RNA can predict HBeAg seroconversion is still controversial.AIM To investigate whether HBV RNA can predict virological response or HBeAg seroconversion during entecavir(ETV) treatment when HBV DNA is undetectable.METHODS The present study evaluated 61 individuals who were diagnosed and treated with long-term ETV monotherapy at the Department of Infectious Diseases of Peking University First Hospital(China) from September 2006 to December 2007.Finally, 30 treatment-naive individuals were included. Serum HBV RNA were extracted from 140 μL serum samples at two time points. Then they were reverse transcribed to cDNA with the HBV-specific primer. The product was quantified by real-time quantitative PCR(RT-PCR) using TAMARA probes. Statistical analyses were performed with IBM SPSS 20.0.RESULTS Level of serum HBV RNA at baseline was 4.15 ± 0.90 log10 copies/mL. HBV RNA levels showed no significant difference between the virological response(VR)and partial VR(PVR) groups at baseline(P = 0.940). Serum HBV RNA significantly decreased among patients who achieved a VR during ETV therapy(P < 0.001). The levels of HBV RNA in both HBeAg-positive patients with seroconversion group and those with no seroconversion increased after 24 wk of treatment. Overall, HBV RNA significantly but mildly correlated to HBsAg(r =0.265, P = 0.041), and HBV RNA was not correlated to HBV DNA(r = 0.242, P =0.062). Furthermore, serum HBV RNA was an independent indicator for predicting HBeAg seroconversion and virological response. HBeAg seroconversion was more likely in CHB patients with HBV RNA levels below4.12 log10 copies/mL before treatment.CONLUSION The level of serum HBV RNA could predict HBeAg seroconversion and PVR during treatment. In the PVR group, the level of serum HBV RNA tends to be increasing.

Add-on pegylated interferon augments hepatitis B surface antigen clearance vs continuous nucleos(t)ide analog monotherapy in Chinese patients with chronic hepatitis B and hepatitis B surface antigen≤1500 IU/mL:An observational study

BACKGROUND Nucleos(t)ide analog(NA)has shown limited effectiveness against hepatitis B surface antigen(HBsAg)clearance in chronic hepatitis B(CHB)patients.AIM To evaluate the efficacy and safety of add-on peginterferonα-2a(peg-IFNα-2a)to an ongoing NA regimen in CHB patients.METHODS In this observational study,195 CHB patients with HBsAg≤1500 IU/m L,hepatitis B e antigen(HBeAg)-negative(including HBeAg-negative patients or HBeAg-positive patients who achieved HBeAg-negative after antiviral treatment with NA)and hepatitis B virus-deoxyribonucleic acid<1.0×10^2 IU/mL after over 1 year of NA therapy were enrolled between November 2015 and December2018 at the Second Affiliated Hospital of Xi'an Jiaotong University,China.Patients were given the choice between receiving either peg-IFNα-2a add-on therapy to an ongoing NA regimen(add-on group,n=91)or continuous NA monotherapy(monotherapy group,n=104)after being informed of the benefits and risks of the peg-IFNα-2a therapy.Total therapy duration of peg-IFNα-2a was 48 wk.All patients were followed-up to week 72(24 wk after discontinuation of peg-IFNα-2a).The primary endpoint was the proportion of patients with HBsAg clearance at week 72.RESULTS Demographic and baseline characteristics were comparable between the two groups.Intention-to-treatment analysis showed that the HBsAg clearance rate in the add-on group and monotherapy group was 37.4%(34/91)and 1.9%(2/104)at week 72,respectively.The HBsAg seroconversion rate in the add-on group was 29.7%(27/91)at week 72,and no patient in the monotherapy group achieved HBsAg seroconversion at week 72.The HBsAg clearance and seroconversion rates in the add-on group were significantly higher than in the monotherapy group at week 72(P<0.001).Younger patients,lower baseline HBsAg concentration,lower HBsAg concentrations at weeks 12 and 24,greater HBsAg decline from baseline to weeks 12 and 24 and the alanine aminotransferase≥2×upper limit of normal during the first 12 wk of therapy were strong predictors of HBsAg clearance in patients with peg-IFNα-2a add-on treatment.Regarding the safety of the treatment,4.4%(4/91)of patients in the add-on group discontinued peg-IFNα-2a due to adverse events.No severe adverse events were noted.CONCLUSION Peg-IFNα-2a as an add-on therapy augments HBsAg clearance in HBeAg-negative CHB patients with HBsAg≤1500 IU/m L after over 1 year of NA therapy.

Pegylated interferon α-2b up-regulates specific CD8+ T cells in patients with chronic hepatitis B

AIM:To investigate the effect of pegylated interferon (IFN) α-2b on specific CD8+ T lymphocytes in patients with chronic hepatitis B (CHB). METHODS:Twenty-one patients with CHB were treated with pegylated IFN α-2b. Periphery blood mononuclear cells were isolated from fresh heparinized blood by Ficoll-Hypaque density gradient centrifugation (density:1.077 g/L,Pharmingen) at weeks 0,4,8,12,and 24,respectively. Frequency of circulating hepatitis B virus (HBV) epitope-specific CD8 T cells was detected by flow cytometry. Cytokines were detected by cytometric bead assay. RESULTS:The frequency of circulating HBV core or env-specific CD8 T cells was higher (P < 0.05),the number of HBV core specific CD8 T cells was greater at week 24 (P < 0.05),the level of Th1-type cytokines [interleukin (IL)-12,tumor necrosis factor-α,and IFN-γ] was higher,while that of Th2-type cytokines (IL-4,IL-6,and IL-10) was lower in responders than in nonresponders (P < 0.05) after pegylated IFN α-2b treatment. The IL-6 level was correlated with HBV DNA (r = 0.597,P = 0.04),while the inducible protein-10 (IP-10) level was correlated with serum alanine aminotransferase (ALT) (r = 0.545,P = 0.005). The IP-10 level at week 8 after pegylated IFN α-2b treatment could predict the normalization of ALT in CHB patients (positive predict value = 56%,negative predict value = 92%). CONCLUSION:Pegylated IFN α-2b can enhance the immune response of CHB patients by increasing the frequency of HBV specific CD8+ T cells and regulating the Th1/Th2 cytokines.

Effect of switching from treatment with nucleos(t)ide analogs to pegylated interferon α-2a on virological and serological responses in chronic hepatitis B patients

AIM To investigate the efficacy of switching to pegylated interferon-α-2a(Peg IFNα-2a) treatment in nucleos(t)ide analog(NA)-treated chronic hepatitis B(CHB) responder patients. METHODS A 48-wk prospective and retrospective treatment trial of NA-treated CHB patients who had received entecavir(ETV) for at least 48 wk and had serum hepatitis B virus(HBV)-DNA < 500 IU/m L, serum hepatitis B envelope antigen(HBe Ag) < 100 S/CO, serum alanine aminotransferase, and aspartate aminotransferase levels < 2 × the upper limit of normal of 40 IU/L was performed. The effects on virological and serological responses and adverse reactions to 0.5 mg daily ETV for 48 wk vs switching to Peg IFNα-2a were compared. Forty-four patients were randomized to be switched from NA treatment to the Peg IFNα-2a group, and 44 patients were simultaneously randomized to the ETV group. RESULTS After 48 wk of therapy, the decrease in hepatitis B surface antigen(HBs Ag) levels was greater in the Peg IFNα-2a group than in the ETV group(3.1340 log10 IU/m L vs 3.6950 log10 IU/m L, P = 0.00). Seven patients who were anti-HBs-positive at baseline achieved HBs Ag loss when switched to Peg IFNα-2a(15.91% vs 0%,P = 0.018). The HBe Ag serological conversion rate was higher in the Peg IFNα-2a group than in the ETV group; however, the difference was not significant because of the small sample sizes(34.38% vs 21.88%, P = 0.232). In the Peg IFNα-2a group, patients with HBs Ag levels < 1500 IU/m L at baseline had higher HBe Ag seroconversion and HBs Ag loss rates at week 48 than those with HBs Ag levels ≥ 1500 IU/m L(HBe Ag seroconversion: 17.86% vs 62.5%, P = 0.007; HBs Ag loss: 41.67% vs 6.25%, P = 0.016). Moreover, patients with HBs Ag levels < 1500 IU/m L at week 24 had higher HBs Ag loss rates after therapy than those with HBs Ag levels ≥ 1500 IU/m L(36.84% vs 0%, P = 0.004). However, there were no statistically significant differences in HBe Ag seroconversion rates(47.06% vs 25.93%, P = 0.266). CONCLUSION NA-treated CHB patients switched to sequential Peg IFNα-2a achieved highly potent treatment termination safely.

Clinical significance of hepatitis B e antigen level measurement during long-term lamivudine therapy in chronic hepatitis B patients with e antigen positive

AIM： To determine the changes of quantitative hepatitis B e antigen （HBeAg） that predicts early detection of non-response or breakthrough to long-term lamivudine （LAM） therapy. METHODS： Among HBeAg positive chronic hepatitis B patients who failed to achieve HBeAg seroconversion within 12 too, we retrospectively analyzed 220 patients who had received LAM more than 24 too. RESULTS： The mean duration of LAM therapy was 36 （range, 24-72） mo. HBeAg seroconversion after the first 12 mo of LAM therapy was achieved in 53 （24.1%） patients. Viral breakthrough was observed in 105 （47.7%） patients. To find out whether the changing patterns of HBeAg levels can predict the outcome of LAM therapy, we analyzed the reduction rates of HBeAg levels during LAM therapy. Using the decrease more than 90% of pretreatment HBeAg levels, the sensitivity and specificity of response were 96.2% and 70.1%, respectively. Patients were divided into 3 groups according to the reduction patterns of the decrease of quantitative HBeAg： decrescendo, decrescendo-crescendo, no change or fluctuating groups. The optimal time to predict non-response or breakthrough was the first 9 mo of therapy. At 9 mo of therapy, 49 （92.5%） of 53 patients who had achieved HBeAg seroconversion were included in the decrescendo group. On the contrary, in the no change or fluctuating group, only four （7.5%） had achieved HBeAg seroconversion. Among patients who did not show the continuous decrease of HBeAg levels at 9 too, 95.2% （negative predictive value） failed to achieve HBeAg seroconversion. CONCLUSION： Almost all patients who failed to show a continuous decrease of HBeAg levels at 9 mo of LAM therapy were non-response or breakthrough. Therefore, monitoring changes of HBeAg levels during LAM therapy in HBeAg positive chronic hepatitis B may be valuable for identifying patients who are at high risk of non-response or breakthrough.

Association of promoter polymorphism of the CD14 C (-159) T endotoxin receptor gene with chronic hepatitis B

AIM: To investigate whether single-nucleotide polymor- phisms in the promoter regions of endotoxin-responsive genes CD14 C (-159) T is associated with chronic hepatitis B. METHODS: We obtained genomic DNA from 80 patients with established diagnosis of chronic hepatitis B and 126 healthy subjects served as a control population. The CD 14 C (-159) T polymorphism was investigated using an allele specific PCR method. RESULTS: Twenty seven percent of chronic hepatitis B patients and 75% of controls were heterozygous for CT genotype. The difference between the chronic hepatitis B and control groups was statistically significant [P < 0.0001; Odds ratio (OR) = 2.887; 95% CI: 1.609-5.178]. Twenty four point six percent of chronic hepatitis B and patients 12.3% of the control group were heterozygous for TT genotype. The difference between groups was not statistically significant (P = 0.256; OR = 0.658; 95% CI: 0.319-1.358). Forty eight point four percent of chronic hepatitis B patients and 12.7% of control were homozy- gote for CC genotype (P < 0.004; OR = 0.416; 95% CI: 0.229-0.755). The frequency of allele C was 61.9% and allele T was 38.1% in hepatitis B patients group. The frequency of allele C was 55.2% and allele T was 44.8% for the control group (P = 0.179; OR = 1.319; 95% CI: 0.881-1.977). CONCLUSION: The TT heterozygous genotype was not a risk factor for chronic hepatitis B. CC homozygote genotype is protective for hepatitis B. Lack of heterozy- gosis of genotype CT is a risk factor for chronic hepatitis B. Alleles C or T were not risk factors for chronic hepatitis B. These findings show the role of a single-nucleotide polymorphism at CD14/-159 on the development ofchronic hepatitis B. Endotoxin susceptibility may play a role in the pathogenesis of chronic hepatitis B.

Pegylated IFN-α2b added to ongoing lamivudine therapy in patients with lamivudine-resistant chronic hepatitis B

AIM： To investigate the role of pegylated-interferon （IFN）α-2b in the management of patients with lamivudineresistant chronic hepatitis B. METHODS： Twenty consecutive anti-HBe positive patients were treated with pegylated IFN α-2b （100 IJg sc once weekly） for 12 mo. There was no interruption in lamivudine therapy. Hematology, liver biochemistry, serum HBV DNA levels were detected by PCR, and vital signs were also assessed. Liver histology was assessed in some patients at entry and at wk 52 for comparison. RESULTS： Nine patients （45%） had a partial virological end-treatment response; seven patients （35%） showed complete virological end-treatment response. Eight patients （40%） showed biochemical end-treatment response. There was a trend for higher virological response rates in patients who had previously responded to IFN and relapsed compared to IFN non-responders （four out of seven patients vs none out of six patients, respectively; P=0.1）. Patients without virological endtreatment response showed significant worsening of fibrosis [median score 2 （range, 1 to 3） vs median score 3 （range, 1 to 4）], in the first and second biopsy respectively （P=0.014）, whereas necroinflammatory activity was not significantly affected. Patients with complete or partial virological end-treatment response did not show any significant changes in histological findings, possibly due to the small number of patients with paired biopsies （n = 5）. Nevertheless, after 12 mo of follow-up, only onepatient （5%） showed sustained virological response and only 2 patients （10%） showed sustained biochemical response. Two patients （10%） discontinued pegylated ]FN both after 6 mo of treatment due to flu-like symptoms. CONCLUSION： Pegylated IFNα-2b, when added to ongoing lamivudine therapy in patients with lamivudineresistant chronic hepatitis B, induces sustained responses only in a small minority of cases.

The effect of patients with chronic hepatitis B HBeAg(+)with poor response to treatment by converting to sequential treatment with tenofovir dipivoxil

Objective:To explore the effect of switching to sequential treatment of tenofovir disoproxil in patients with chronic hepatitis B HBeAg(+)who have a poor response to treatment,and to provide a theoretical basis for better clinical treatment of chronic hepatitis B HBeAg(+)patients.Methods:Totally 90 patients with chronic hepatitis B HBeAg(+)treated in our hospital from December 2016 to December 2018 were selected as the research subjects and randomly divided into the extension group treated tenofovir disoproxil fumarate tablets and the diversion group treated with tenofovir disoproxil,45 cases in each group.Compare the statistical differences of the content of HBeAg and HBV-DNA,liver function indicators(TBIL,TC,INR ratio),serological and biochemical responses,adverse reactions(gastrointestinal symptoms and nausea/weakness,rash)in the two groups of patients before and after treatment.Results:Comparing the efficacy of the 12-month extension group with the diversion group.It was found that the HBeAg(0.69±0.10PEI/mL)and HBV-DNA(3.26±0.94IU/mL)in the diversion group were lower than those in the extension group(0.90±0.17 PEI/mL)and HBV-DNA(4.37±1.26IU/mL),and the differences were statistically significant(P<0.05).Comparing the efficacy of the 12-month extended group with the diversion group,it was found that the TBIL content in the diversion group(1035.72±92.44umol/L)was higher than that in the extension group(234.72±27.56umol/L)and the the TBILINR ratio was lower(2.70±0.39),and the differences were statistically significant(P<0.05).Comparing the 12-month difference between the extension and diversion groups,it was found that the HBeg reversion rate in the diversion group(36 cases,80.00%)was higher than that in the extended group(27 cases,60.00%),and the HBeg LT recovery rate It was also higher than the extended use group(22 cases,48.89%),and the differences were statistically significant(P<0.05).The incidence of adverse reactions in the extension group(17 cases,37.78%)was higher than that in the diverted group(8 cases,17.78%),and the difference was statistically significant(P<0.05).Conclusion:For patients with chronic hepatitis B HBeAg(+)with poor response to treatment,switching to tenofovir disoproxil sequential treatment can not only improve the treatment effect,but also effectively reduce the occurrence of adverse reactions.

Safety and efficacy of oral HD-03/ES given for six months in patients with chronic hepatitis B virus infection

AIM： To investigate the safety and efficacy of the formulation HD-03/ES capsules in the management of patients with chronic hepatitis B infection.METHODS： A total of 25 patients were recruited to the study and were given HD-03/ES, two capsules twice daily for six months. Clinical assessment of symptoms and signs were done using the ＂clinical observation table＂ once a month before and after the treatment. Biochemical investigations of total bilirubin, ALT, AST, serum protein for liver function tests were done every month after initiating treatment. Serum was analyzed for HBV markers for HBsAg, HBeAg and HBV DNA at baseline, 4 and 6 mo alter therapy using ELISA kits from Roche.RESULTS： After 6 mo of therapy with HD-03/ES, a significant reduction of ALT values from 66.5 ± 11.1 to 39.1 ± 5.2 （P 〈 0.01） and a significant HBsAg loss （52%, P 〈 0.001）, HBeAg loss （60%, P 〈 0.05） and HBV DNA loss （60%, P 〈 0.05） was observed. Adverse effects were mild and never warranted withdrawal of the drug.CONCLUSION： The results of this pilot study indicate that HD-03/ES might be a safe and effective treatment for chronic hepatitis B infection and a long-term multicentric comparator trial is warranted and under way.