Rates Of Hepatitis B E Antigen Loss Research Articles

Efficacy and safety of tenofovir alafenamide in patients with chronic hepatitis B exhibiting suboptimal response to entecavir.

Entecavir (ETV) is a potent and safe antiviral agent for patients with chronic hepatitis B (CHB); however, some patients may exhibit suboptimal response or resistance to ETV. Tenofovir alafenamide (TAF) is a novel tenofovir prodrug with improved pharmacokinetics and reduced renal and bone toxicity compared with tenofovir disoproxil fumarate. To evaluate the efficacy and safety of switching from ETV to TAF in patients with CHB exhibiting suboptimal response to ETV. A total of 60 patients with CHB who had been treated with ETV for at least 12 mo and had persistent or recurrent viremia [Hepatitis B virus (HBV) DNA ≥ 20 IU/mL] or partial virologic response (HBV DNA < 20 IU/mL, but detectable) were enrolled in the study. The patients were randomly assigned to either continue ETV (0.5 mg) daily or switch to TAF (25 mg) daily for 48 wk. The primary endpoint was the proportion of patients who achieved a virologic response (HBV DNA level < 20 IU/mL) at week 48. Secondary endpoints included changes in serum alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and anti-HBe levels, and renal and bone safety parameters. At week 48, the proportion of patients who achieved a virologic response was significantly higher in the TAF group than in the ETV group (93.3% vs 66.7%, P = 0.012). The mean reduction in HBV DNA from baseline was also significantly greater in the TAF group than in the ETV group (-3.8 vs -2.4 Log10 IU/mL, P < 0.001). The rates of ALT normalization, HBeAg loss, HBeAg seroconversion, and HBsAg loss were not found to significantly differ between the two groups. None of the patients developed genotypic resistance to ETV or TAF. Both drugs were well tolerated, with no serious adverse events or discontinuations caused by adverse events. No significant changes were observed in the estimated glomerular filtration rate, serum creatinine level, or urine protein-to-creatinine ratio in either group. The TAF group had a significantly lower decrease in bone mineral density at the lumbar spine and hip than the ETV group (-0.8% vs -2.1%, P = 0.004; -0.6% vs -1.8%, P = 0.007, respectively). Switching from ETV to TAF is effective and safe for patients with CHB exhibiting a suboptimal response to ETV and may prevent further viral resistance and reduce renal and bone toxicity.

Clearance of Hepatitis B e Antigen in Untreated Chronic Hepatitis B Virus Infection: A Systematic Review and Meta-analysis.

In people with hepatitis B virus (HBV) infection, persistence of hepatitis B e antigen (HBeAg) is associated with clinical progression and need for treatment. HBeAg loss represents partial immune control and is a critical event in the natural history of chronic HBV. We conducted a systematic review and meta-analysis of cohort studies that report HBeAg loss among people with untreated chronic HBV. We evaluated HBeAg loss using a random-effects model and conducted subanalysis on region. We screened 10 560 publications, performed 196 full-text analyses, and included 26 studies for meta-analysis. The pooled rate of HBeAg loss was 6.46/100 person-years (PYs) (95% confidence interval, 5.17-8.08). Meta-regression showed that older age of participants and studies in Europe were associated with higher rate of HBeAg loss. Rates per 100 PYs were 7.43 (95% confidence interval, 6.30-8.75; 1 study) in Africa, 3.24 (2.61--4.02; 1 study) in the Eastern Mediterranean, 13.67 (11.21-16.66; 4 studies) in Europe, 7.34 (4.61--11.70; 5 studies) in North America, and 5.53 (4.05--7.55; 15 studies) in the Western Pacific. Spontaneous HBeAg loss occurs at a rate of 6.46/100 PYs. Variations by region and age group may reflect epidemiological, immunological, or HBV genotype-related differences.

Long-term benefits of interferon-α therapy in children with HBeAg-positive immune-active chronic hepatitis B.

The long-term benefits of interferon-α (IFN-α) treatment in children with chronic hepatitis B (CHB) remain unclear. We conducted a retrospective and real-world study to evaluate the safety and long-term clearance rates of hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) in CHB children who received IFN-α monotherapy for 72weeks and were with 13-year follow-up visit. Participants treated with IFN-α (n=316) were more likely to become HBeAg negatve (39.87% vs. 27.37%; p<.05) and HBsAg negative (11.08% vs. 3.16%; p<.05) by the end of the treatment period than untreated participants (n=95). Treated participants also had higher cumulative rates of HBeAg loss (74.13% vs. 59.27%; p<.05) and HBsAg loss (46.95 vs. 33.11%; p< 0.05) than untreated participants in parallel by the end of 13-year follow-up. In particular, the cumulative rate of HBsAg loss was higher in treated children aged 1-7years than in those aged 8-17years (71.40% vs. 39.0%; p<.01). Children who were HBeAg-negative at the end of IFN-α treatment or who had serum alanine aminotransferase levels of≥80IU/L at baseline were likely to have higher cumulative HBsAg loss rates. Accordingly, HBeAg loss at 72weeks was positively associated with the cumulative HBsAg loss rate in untreated children. There were no serious adverse events of IFN-α therapy for the treated patients throughout the study period. Overall, IFN-α therapy was effective in obtaining higher long-term cumulative rates of HBeAg and HBsAg loss in children with HBeAg-positive immune-active CHB, especially among those aged 1-7years.

Hepatitis B e antigen loss in adults and children with chronic hepatitis B living in North America: A prospective cohort study.

Hepatitis B e antigen (HBeAg) is a soluble viral protein in plasma of patients with hepatitis B virus infection. HBeAg loss is an important first stage of viral antigen clearance. We determined the rate and predictors of HBeAg loss in a North American cohort with chronic hepatitis B viral infection (CHB). Among children and adults with CHB and without HIV, HCV or HDV co-infection enrolled in the Hepatitis B Research Network prospective cohort studies, 819 were HBeAg positive at their first assessment (treatment naïve or >24weeks since treatment). Of these, 577 (200 children, 377 adults) were followed every 24-48weeks. HBeAg loss was defined as first HBeAg-negative value; sustained HBeAg loss was defined as ≥2 consecutive HBeAg-negative values ≥24weeks apart. During a median follow-up of 1.8years, 164 participants experienced HBeAg loss, a rate of 11.4 (95% CI, 9.8-13.3) per 100 person-years. After adjustment for confounders, HBeAg loss rate was significantly higher in males than females, in older than younger individuals, in Whites or Blacks than Asians, in those with genotype A2 or B versus C, and in those with basal core promoter/pre-core mutations versus wild type. Additionally, during follow-up, an ALT flare and a lower quantitative HBsAg, quantitative HBeAg or HBV DNA level predicted higher rates of HBeAg loss. The majority (88%) with HBeAg loss had sustained HBeAg loss. In conclusion, a number of specific demographic, clinical and viral characteristics impacted rate of HBeAg loss and may prove useful in design and interpretation of future therapeutic studies.

Entecavir combining Chinese herbal medicine for HBeAg-positive chronic hepatitis B patients: a randomized, controlled trial.

Traditional Chinese medicine (TCM) is widely accepted and prescribed in China alongside Nucleoside analogs (NAs). In this double-blind, placebo-controlled, randomized, multi-center trial, we evaluated whether entecavir (ETV) plus TCM formulas Tiao-Gan-Yi-Pi granule (TGYP) and Tiao-Gan-Jian-Pi-Jie-Du granule (TGJPJD) increase the rate of hepatitis B e antigen (HBeAg) loss in Chinese patients. 596 eligible participants were randomly assigned, in a 1:1 ratio, to two study groupsin this 108-week trial: The experiment group was assigned ETV plus the TCM formula. The control group was assigned ETV plus a TCM placebo. We compared the rate of HBeAg loss by the end of week 108 between the two arms as the primary outcome. Secondary outcomes included hepatitis B surface antigen (HBsAg) level, proportion of undetectable HBV-DNA, and liver enzymes (ALT, AST, GGT) at week 108. The combination therapy achieved superior HBeAg loss at 108weeks, without additional adverse events. The rate of HBeAg loss at week 108 was 37.54% (95% CI 31.9-43.2%) in the experiment group and 27.21% (95% CI 22.0-32.4%) in the control group. There was a statistically significant difference between the two arms of 10.33% (95% CI 8.4-12.3%, p = 0.008). The DNA loss rate, serum HBsAg level, and liver enzymes were similar between the groups by the end of 108th week. Combining the Chinese herbal formula with ETV therapy demonstrated superior HBeAg clearance compared with ETV monotherapy. This finding indicates that this combined therapy could produce an improved therapeutic effect and safety profile. ChiCTR-TRC-12002784 (Chinese Clinical Trial Registry).

Predictors of HBeAg loss after nucleos(t)ide analogues treatment for chronic hepatitis B: A preliminary finding

AbstractEntecavir (ETV) and tenofovir (TDF) are both potent antiviral agents for the treatment of chronic hepatitis B virus (HBV) infection. The primary effective endpoints of treatment have been a sustained disappearance of HBV DNA and hepatitis B e‐antigen (HBeAg) loss or seroconversion. We compared the efficacy of ETV and TDF and determined clinical factors that contributed to HBeAg loss at Pao‐Chien Hospital in Pingtung city. We conducted a retrospective study. A total of 36 consecutive patients with chronic hepatitis B (CHB) (e‐positive) antigens were treated with ETV (n = 19) and TDF (n = 17) between January 2010 and January 2018. Demographic and baseline characteristics were used for Cox proportion hazard regression models to identify variables that were predictive of ETV and TDF‐induced HBeAg loss. The alfa fetal protein (AFP) levels were higher in patients with HBeAg loss than in those without loss (P = .006). Of which, 17 (47.2%) of 36 patients achieved HBeAg loss and 12 (33.3%) patients achieved HBeAg seroconversion. None of these seroconversion patients developed serum reversion after consolidation therapy and off treatment. The cumulative rate of HBeAg loss at years 1, 2, and 3 of therapy was 22.2% (8/36), 37.0% (10/27), and 57.7% (15/26), respectively. In cumulative rate at years 1 and 2, the frequency of HBeAg loss was observed greater in virological response at 6 months (13.9% vs 8.3%, P = .013; 40% vs 22%, P = .028, respectively). In multivariate Cox regression analysis for factors associated with HBeAg loss, an increase in virological response at 6 months (adjusted hazard ratio [HR] = 4.780; 95% CI, 1.013‐22.565; P = .048) was only significant factor associated with cumulative HBeAg loss rate at year 2 (adjusted HR = 0.183; 95% CI, 0.043‐0.774; P = .021). The rapidity and efficacy of HBV DNA reduction to undetectable is the predictor of nucleos(t)ide analogue (NUC)‐induced HBeAg loss. Early undetectable HBV DNA in 6 months might be used to predict a higher likelihood of HBeAg loss within 2‐year therapy with NUC.

Adefovir Dipivoxil plus Chinese Medicine in HBeAg-Positive Chronic Hepatitis B Patients: A Randomized Controlled 48-Week Trial.

To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients. A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented. The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns. Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).

Albumin-bilirubin score is associated with response to pegylated interferon and nucleos(t)ide analogues in chronic hepatitis B patients

Background and aimRecently, the role of albumin-bilirubin (ALBI) score in chronic hepatitis B (CHB) has not been well-understood. We aimed to investigate the association of ALBI score with natural history of chronic HBV infection and treatment response of CHB patients. MethodsThe ALBI score in a cohort of 849 individuals including 721 chronic HBV-infected patients naïve to anti-HBV treatment in different phases and 128 healthy controls were estimated. Additionally, the dynamic changes of ALBI score of 243 hepatitis B e antigen (HBeAg)-positive CHB patients treated with pegylated interferon-alpha (PEG-IFN-α) or nucleos(t)ide analogues (NAs) were tested for 72 weeks. ResultsALBI score differed among phases, with the highest score in HBeAg-positive CHB patients, followed by HBeAg-negative CHB patients, HBeAg-positive chronic HBV infection, and HBeAg-negative chronic HBV infection. Besides, CHB patients harbouring high baseline ALBI score exhibited a relatively stronger therapeutic response to PEG-IFN-α or NAs. Moreover, the rate of HBeAg and HBsAg loss in patients with ALBI grade 2 was persistently higher than that in patients with ALBI grade 1 throughout the course of treatment. Furthermore, ALBI score was an independent predictor of sustained response achievement. The combined use of ALBI score, HBeAg and ALT could enhance the predictive value of treatment response. ConclusionsALBI score differed significantly across the natural course of chronic HBV infection and was correlated with PEG-IFN-α and NAs treatment response in HBeAg-positive CHB patients, which suggested that ALBI score could be useful as an auxiliary clinical factor to determine the initiation of therapy and predict stronger antiviral treatment response.

The combination therapy of Peginterferonα and entecavir for HBeAg-positive chronic hepatitis B with high HCC risk

The population of HBV infection with family history of hepatocellular carcinoma (HCC) is the high risk group for the development of HCC. The aim of this study was to evaluate the effect of the de novo combination therapy including pegylated-interferon α-2a (PEG-IFNα-2a) and entecavir (ETV) in this high risk population. The study recruited 58 Hepatitis B e Antigen (HBeAg)-Positive CHB patients patients with HBV-DNA > 107 IU/mL, genotype B or C and HCC family history and were treated for 48 weeks. Patients without HBeAg loss at the 48th week were 40 patients and extended the combination therapy to 96 weeks. All patients were followed up to 120 weeks. The rate of HBeAg loss and HBsAg loss was 12/40(30.0%) and 2/40(5.0%) at week 120 respectively. When logistic regression analysis was used to identify viables of HBeAg loss, HBV-DNA levels <20 IU/mL at week 48 was found to have a 6.02 fold increased probability (95% CI = 1.17–30.40, P = .03) of HBeAg loss. Patients with HBV-DNA levels <20 IU/mL at week 48 had a high probability of HBeAg loss 8/17(47.1%), HBsAg loss 2/17(11.8%), compared to 4/23(17.4%), 0/23(0%) in patients with HBV-DNA ≥ 20 IU/mL. Combination therapy for 96 weeks was well tolerated. During the combination therapy, low-level viremia during treatment is reversely associated with response. The combination therapy of PEG-IFNα and ETV was suggested to extend to 96 weeks when HBV-DNA was completed suppressed at week 48.

Efficacy of long-term treatment with tenofovir in Chinese nucleos(t)ide-naïve chronic hepatitis B patients regardless of baseline viral load.

The aim of the present study was to analyze the efficacy and safety of tenofovir (TDF) treatment for up to 5 years in nucleos(t)ide-naïve chronic hepatitis B (CHB) patients, particularly those with a high viral load, a in real-life scenario. A total of 144 nucleos(t)ide-naïve CHB patients who received TDF monotherapy for at least 3 months were retrospectively analyzed. The primary endpoint measure was the achievement of virological response (VR; undetectable serum HBV DNA, <100 IU/ml). The secondary endpoints were alanine aminotransferase (ALT) normalization (ALT < upper limit of normal), hepatitis B e antigen (HBeAg) seroconversion and safety. The median follow-up period was 120 weeks (range, 12-264 weeks). In total, 144, 130, 114, 78, 67, 40 and 13 patients were followed up for at least 12, 24, 48, 96, 144, 192 and 240 weeks, respectively. An incremental trend was observed in the rate of VR: 73.1, 91.3, 98.1, 100, 100 and 100% of the patients exhibited VR at 24, 48, 96, 144, 192 and 240 weeks, respectively. Furthermore, 29 patients with hepatitis B virus (HBV) DNA ≥8 log10 IU/ml at baseline achieved VR during the follow-up period. The proportions of patients achieving normal ALT levels were 72.1, 78.6, 91.2, 95, 96 and 100%, at 24, 48, 96, 144, 192 and 240 weeks, respectively. The rate of HBeAg loss reached 35.6% at week 240. Among the 130 patients, HBV DNA was detectable [partial VR (PVR)] in 35 patients at 24 weeks of follow-up, and 30 of those 35 patients (85.7%) required >24 weeks of further TDF therapy to achieve VR. No serious adverse events were reported. In conclusion, long-term TDF treatment of nucleos(t)ide-naïve chronic hepatitis B patients, regardless of high viral load at baseline, was effective and safe in a real-life scenario. Adjustment of TDF monotherapy may be unnecessary in nucleos(t)ide-naïve patients with PVR at 24 weeks.

The nucleotide changes within HBV core promoter/precore during the first 12 weeks of nucleos(t)ide treatment might be associated with a better virological response

ObjectivesWe aimed to study the dynamic changes of hepatitis B virus (HBV) core promoter/precore (CP/preC) sequences during antiviral treatment and their associations with virological responses. Materials and methodsThe baseline and 12-week CP/preC sequences (nts 1655–2014) were obtained from 52 chronic hepatitis B patients with positive hepatitis B e antigen (HBeAg), who received a 104-week lamivudine and adefovir dipivoxil combination therapy. The mutations within the CP/preC were analyzed against genotype specific reference sequences. The nucleotide change rates in individuals during therapy were analyzed in a pairwise comparison manner. ResultsThere was no significant difference of the mutation rate at each nucleotide site between baseline and week 12 of treatment (P>0.05). The mutation rates of A1762T/G1764A and G1896A were found to decrease from 46.2% (24/52) at baseline to 36.5% (19/52) at week 12 (P=0.426) and from 28.8% (15/52) to 21.2% (11/52) (P=0.497), respectively. The nucleotide change rates varied from 0.0% - 7.8% in individuals [0.0% in Group 1 (N=26); 0.3% - 7.8% in Group 2 (N=26)] during the first 12-week treatment. HBV DNA levels in Group 2 were significantly lower than those in Group 1 throughout therapy (P<0.01) (e.g., 1.5±1.3log10 IU/ml vs. 2.6±1.0log10 IU/ml at week 104, P=0.001). At week 104 the rates of HBV DNA undetectable and HBeAg loss in Group 2 were significantly higher than those in Group 1 (P<0.05). Along with the increased nucleotide change rates, the rate of HBV DNA undetectable at week 104 tended to increase (odds ratio=0.323, 95% confidence interval=0.138–0.758, P<0.001). ConclusionOur findings suggested that the nucleotide changes within HBV CP/preC region during the first 12-week treatment might be associated with a better virological response.

Clinical implication of serum Wisteria floribunda agglutinin positive Mac-2-binding protein level on hepatitis B e-antigen loss or seroconversion in hepatitis B e-antigen positive patients.

To examine the impact of pretreatment Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA+ -M2BP) level on hepatitis B e-antigen (HBeAg) loss or HBeAg seroconversion (SC) for patients with nucleoside/nucleotide analog (NUC) therapy naive HBeAg positive chronic hepatitis B (CHB). A total of 57 patients were analyzed. All subjects were initially treated with NUC. We examined the impact of pretreatment WFA+ -M2BP level on HBeAg loss and HBeAg SC using univariate and multivariate analyses. There were 36 men and 21 women (median age, 39years). The WFA+ -M2BP cut-off index (COI) level ranged 0.43-12.9 (median, 1.55). WFA+ -M2BP level in patients with F3 or F4 was significantly higher than that with F0-F2. WFA+ -M2BP level in patients with A2 or 3 was significantly higher than that with A0 or 1. For all cases, the 1- and 3-year cumulative HBeAg loss rates were 10.5% and 34.4% and the corresponding cumulative HBeAg SC rates were 8.8% and 29.0%, respectively. In the multivariate analysis, in terms of HBeAg loss, pretreatment HBV DNA of 5log copies/mL or more and pretreatment WFA+ -M2BP level of more than 1.55 COI tended to be significant factors linked to loss of HBeAg, while in terms of HBeAg SC, pretreatment HBV DNA of 5log copies/mL or more was an independent predictor and pretreatment WFA+ -M2BP level of more than 1.55 COI tended to be a significant factor. Pretreatment WFA+ -M2BP level may be a useful predictor for HBeAg loss or SC after NUC therapy for patients with HBeAg positive CHB.

Efficacy of entecavir therapy for hepatitis B e-antigen positive chronic hepatitis B patients with prior exposure to interferon or nucleoside/nucleotide analogues.

AimThe efficacy of entecavir (ETV) in treatment‐experienced chronic hepatitis B (CHB) patients remains unclear. We evaluated the therapeutic responses and virological breakthrough following ETV treatment in hepatitis B e‐antigen (HBeAg) positive CHB patients with prior exposure to interferon or nucleoside/nucleotide analog and treatment‐naive patients.MethodsThis was a retrospective, multicenter study of treatment (&gt;1 year) with 0.5 mg ETV in 248 treatment‐naive and 48 treatment‐experienced HBeAg positive CHB patients (70.5% male; mean age, 40.5 years). The rates of undetectable hepatitis B virus (HBV) DNA, HBeAg loss and virological breakthrough were analyzed.ResultsThe median duration of ETV treatment was 27.3 months (range, 18.4–34.5). The rate of HBeAg loss was 41.9% (104/248) in treatment‐naive and 45.8% (22/48) in treatment‐experienced patients. The baseline serum HBV DNA and alanine aminotransferase levels were significant predictors for HBeAg loss (P = 0.01 and P = 0.04, respectively). There was no statistical difference between the groups in the rates of undetectable HBV DNA and HBeAg loss at any time point. Virological breakthrough occurred in 1.6% (4/248) of treatment‐naive and 8.3% (4/48) of treatment‐experienced patients. The four treatment‐experienced patients with virological breakthrough had received prior lamivudine treatment. After excluding those treated with interferon, lamivudine‐experienced patients had significantly greater virological breakthrough compared with treatment‐naive patients (log–rank test, P = 0.034; univariate Cox regression, P = 0.047).ConclusionETV treatment efficacy, including virological response and HBeAg loss, was comparable between treatment‐naive and treatment‐experienced HBeAg positive CHB patients. Lamivudine‐experienced patients had a higher risk of virological breakthrough than treatment‐naive patients.

Younger age and female sex predict a better therapeutic response in HBeAg-positive chronic hepatitis B patients to entecavir therapy

Summary Background Clinical trials and real-world data confirm the efficacy of entecavir treatment for chronic hepatitis B (CHB); however, the factors associated with a favorable response remain unknown. Methods In a retrospective multicenter study, 132 treatment-naive hepatitis B e antigen (HBeAg)-positive CHB patients (71% male; median age, 40.2 years) received entecavir therapy for >2 years. At baseline, 15% of these patients had cirrhosis. The primary endpoint was HBeAg loss at 2 years of entecavir treatment. Results The rates of serum alanine aminotransferase (ALT) normalization at treatment Year 1 and Year 2 were 86% and 88%, respectively. The cumulative rate of HBeAg loss at treatment Year 1 and Year 2 were 17% and 33.3%, respectively. The rates of undetectable levels of serum hepatitis B virus (HBV) deoxyribonucleic acid (DNA) at treatment Year 1 and Year 2 were 64% and 80.8%, respectively. In univariate analysis, HBeAg loss at 2 years was associated with a young age (≤35 years; p = 0.007) and a high baseline ALT level ( p 5 times the upper limit of normal (ULN)] showed that a young age (odds ratio, 2.66; 95% confidence interval, 1.2–5.92) and male sex (odds ratio, 0.36; 95% confidence interval, 0.16–0.83) were independent factors associated with HBeAg loss at 2 years of therapy. Conclusion Two-year entecavir therapy has good biochemical and virologic responses; however, the rate of HBeAg loss is modest in HBeAg-positive CHB patients. A young age (i.e., ≤35 years) and female sex were also associated with a better serologic response.

Serological and clinical outcomes of horizontally transmitted chronic hepatitis B infection in New Zealand Māori: results from a 28-year follow-up study

BackgroundChronic hepatitis B infection is endemic in New Zealand and has high prevalence in New Zealand Māori. Previous longitudinal studies in populations with predominantly vertically acquired chronic hepatitis B have...

Is increasing the dose of Entecavir effective in partial virological responders?

ObjectiveTo analyze the effect of increasing Entecavir (ETV) dosage in patients with chronic hepatitis B (CHB) who partially responded to ETV after 1 year.MethodsTwenty-three hepatitis B e antigen (HBeAg)-positive and 36 HBeAg-negative patients with CHB were treated with ETV 0.5 mg daily. After 1 year of the treatment, those with detectable hepatitis B virus (HBV-DNA) were randomized to either ETV 0.5 mg or 1 mg daily. The resistance to ETV was excluded. Both groups received ETV for 3 years. The groups were compared in aspects of undetectable DNA.ResultsGroup 1 was given 0.5 mg ETV and included 32 patients (20 HBeAg-negative and 12 HBeAg-positive). Group 2 was given 1 mg ETV and consisted of 27 patients (16 HBeAg-negative and eleven HBeAg-positive). Group 2 had more effective suppression of HBV-DNA while both groups had comparable rates of HBeAg loss (58% and 63% for group 1 and group 2, respectively) and alanine transaminase (ALT) normalization at the end of 4 years.ConclusionIncreasing ETV dose from 0.5 mg to 1 mg after 1 year of ETV treatment may provide an effective suppression of viral replication.

Telbivudine Versus Entecavir for Nucleos(t)ide-Naive HBeAg-Positive Chronic Hepatitis B: A Meta-analysis

BackgroundWe performed a meta-analysis to compare the efficacies of entecavir and telbivudine in treatment-naive hepatitis B e-antigen (HBeAg)-positive Asian patients with chronic hepatitis B (CHB). MethodsRandomized controlled trials (January 1, 2000 to March 30, 2012) directly comparing entecavir 0.5mg/d and telbivudine 600mg/d, used for a minimum of 12 weeks in nucleos(t)ide-naive Asian patients with HBeAg-positive CHB, were searched in the PubMed, Embase, OVID, Cochrane Library, CNKI, VIP and WanFang databases. Publication quality was assessed using the Jadad quality scale. The rates of viral response, biochemical response, HBeAg loss and HBeAg seroconversion were analyzed using forest plots. ResultsSeven eligible articles (867 patients in total) were included in this meta-analysis. With regard to the rates of hepatitis B virus DNA suppression, there were no significant differences between patients treated with entecavir or telbivudine at 12 and 48 weeks, but telbivudine was superior at 24 weeks. Twelve, 24 and 48 weeks after the start of therapy, the rates of alanine aminotransferase normalization were similar between the 2 drugs, and patients treated with telbivudine had higher HBeAg loss and seroconversion rates than patients treated with entecavir. ConclusionsIn nucleos(t)ide-naive Asian patients with HBeAg-positive CHB, assessed 12, 24, and 48 weeks after beginning treatment, telbivudine was as potent as entecavir in viral suppression, but superior with regard to HBeAg loss and seroconversion. Telbivudine seems to be more effective and suitable for these patients.

Efficacy and safety of peginterferon alfa-2a in patients with lamivudine-resistant HBeAg-positive chronic hepatitis B

Lamivudine resistance develops in up to 80% of patients with chronic hepatitis B (CHB) after 5 years of treatment. Cross-resistance between nucleoside/nucleotide analogues limits management options in these patients. To investigate the role of pegylated interferon-α2a as rescue therapy in these patients, the efficacy and safety of pegylated interferon-α2a between treatment-naive patients and lamivudine-resistant patients with hepatitis B e antigen (HBeAg)-positive CHB were compared. A total of 150 HBeAg-positive CHB patients were stratified according to prior treatment. Lamivudine-resistant patients (n=64) and treatment-naive patients (n=86) received pegylated interferon-α2a once-weekly for 48 weeks and were followed-up for an additional 24 weeks. Primary end points were HBeAg loss and HBV DNA <100,000 copies/ml at end of follow-up. A total of 65 (76%) treatment-naive patients and 49 (77%) lamivudine-resistant patients completed treatment and 24 weeks of follow-up. Rates of HBeAg loss were comparable at end of follow-up between treatment-naive patients and lamivudine-resistant patients (20.9% and 23.4%, respectively; P=0.8423). Similarly, rates of HBV DNA<100,000 copies/ml were comparable at end of follow-up between treatment-naive patients and lamivudine-resistant patients (20.9% and 21.9%, respectively; P=1.000). There was no statistically significant difference in alanine aminotransferase normalization rates between treatment-naive patients and lamivudine-resistant patients (36.0% and 29.7%, respectively; P=0.4848). A total of one patient in each group achieved hepatitis B surface antigen (HBsAg) loss and seroconversion. The most common adverse events were those known to occur with pegylated interferon-α2a therapy, and safety profiles were similar between both patient populations. Pegylated interferon-α2a may be effective as a rescue therapy in patients with lamivudine-resistant HBeAg-positive CHB.

Viral load and alanine aminotransferase correlate with serologic response in chronic hepatitis B patients treated with entecavir

Although entecavir has been shown to have good efficacy and low resistance for the treatment of chronic hepatitis B (CHB), factors associated with a favorable response remain unknown. This was a retrospective, multicenter study of 248 treatment-naïve hepatitis B e antigen (HBeAg)-positive patients (69.4% male; median age, 39.4 years) treated with entecavir for more than 1 year, and 15.7% of them had cirrhosis at baseline. The primary endpoints were HBeAg loss and/or seroconversion. The median baseline levels of alanine aminotransferase (ALT) and hepatitis B virus (HBV) DNA were 201 U/L (range, 27-2415 U/L) and 7.6 log(10) IU/mL (range, 2.2-13.18), respectively. The median treatment period was 25.3 months (range, 12-69.6). The rates of ALT normalization at years 1, 2, and 3 were 83.1%, 87.9%, and 94.9%, respectively. The cumulative rates of HBeAg loss at years 1, 2, and 3 were 20.3%, 38.0%, and 48.9%, respectively. The rates of undetectable HBV-DNA at years 1, 2, and 3 were 52.1%, 78.9%, and 82.5%, respectively. Using Cox proportional hazards model, multivariate analysis showed that baseline ALT greater than five times the upper limit of normal, and viral load were independent factors associated with HBeAg loss (hazard ratio: 1.81, and 0.812; 95% confidence interval: 1.062-3.085; 0.7-0.942, respectively). Entecavir treatment for 3 years can achieve good biochemical and virologic responses in HBeAg-positive CHB patients, but has a modest effect on HBeAg loss and/or seroconversion. In addition, baseline serum ALT and HBV-DNA levels are independent factors associated with favorable treatment responses.

Efficacy of Entecavir With or Without Tenofovir Disoproxil Fumarate for Nucleos(t)ide-Naïve Patients With Chronic Hepatitis B

Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are potent antiviral agents that might have additive or synergistic antiviral activity in treatment of patients with chronic hepatitis B (CHB). We compared the efficacy and safety of ETV monotherapy with those of a combination of ETV and TDF. We performed a randomized, open-label, multicenter, superiority study of 379 nucleos(t)ide-naïve patients with hepatitis B e antigen (HBeAg)-positive (n = 264) or HBeAg-negative (n = 115) CHB. Subjects were given ETV 0.5 mg (n = 182) or a combination of ETV 0.5 mg and TDF 300 mg (n = 197) for 100 weeks. At week 96, comparable proportions of patients in each study arm achieved the primary end point of a level of hepatitis B virus (HBV) DNA <50 IU/mL (83.2% vs 76.4%; P = .088). Among HBeAg-positive patients, a greater proportion given combination therapy achieved levels of HBV DNA <50 IU/mL than those given ETV alone (80.4% vs 69.8%; P = .046). However, this difference was observed only in patients with baseline levels of HBV DNA ≥ 10(8) IU/mL (79% vs 62%) and not in those with baseline levels of HBV DNA <10(8) IU/mL (83% in both arms). Rates of HBeAg loss and HBeAg seroconversion were comparable between groups, whereas the rate of alanine aminotransferase normalization was greater in the ETV monotherapy group. No HBV variants associated with ETV or TDF resistance were detected. Safety profiles were consistent with previous reports of ETV or TDF monotherapy. The antiviral efficacy of ETV monotherapy is comparable to that of ETV plus TDF in a mixed population of nucleos(t)ide-naïve patients with CHB (70% HBeAg positive). The combination therapy could provide an incremental benefit to HBeAg-positive patients with baseline levels of HBV DNA ≥ 10(8) IU/mL.