HBeAg-positive Chronic Hepatitis Research Articles

Higher detection rates of amino acid substitutions in HBV reverse transcriptase/surface protein overlapping sequence is correlated with lower serum HBV DNA and HBsAg levels in HBeAg-positive chronic hepatitis B patients with subgenotype B2

ObjectivesHepatitis B virus (HBV) subgenotype B2 is prevalent in China and some other parts of Asia. This study aimed to carry out a subgenotype B2 specific mutation analysis on important amino acid (AA) sites in overlapping reverse transcriptase (RT) and surface (S) protein coding regions of HBV. Materials and methodsA total of 143 hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients with HBV subgenotype B2 infection were enrolled. HBV RT/S regions were sequenced focusing on 43 RT resistance AA sites and 31 S AA sites with functional/structural/conformational importance. ResultsAccording to the consensus AA sequence for subgenotype B2, 49.7% (71/143) of RT and 33.6% (48/143) of S protein sequences contained detectable substitutions at 58.1% (25/43) of studied AA sites in RT and 51.6% (16/31) of AA sites in S proteins, respectively. The most frequently detected substitutions were rtN134D/S (44/143, 30.8%) and sT126A/S (22/143, 15.4%), which were located in the RT A–B interdomain region and the corresponding antigenicity determinant region of S protein, respectively. In addition, two patients harboring drug resistance mutations rtL80V+rtM204I and rtL180M+rtM204V were found. Interestingly, the patients with detectable AA substitutions at any of the 74 sites in either/both of RT/S sequences had significantly lower serum HBV DNA and HBsAg levels than that in patients without detectable RT/S AA substitutions (P<0.05). A trend Chi-squared test indicated that a negative association of serum HBsAg level with S protein sequence substitution rate was statistically significant (P=0.047). ConclusionThis subgenotype B2 specific mutation analysis revealed some naturally occurring hot spot substitutions at important AA sites of HBV RT/S proteins, which together might influence the serum HBV DNA and HBsAg levels in HBeAg-positive CHB patients.

HLA-C and KIR combined genotype as new response marker for HBeAg-positive chronic hepatitis B patients treated with interferon-based combination therapy.

Current treatment for chronic hepatitis B infection (CHB) consists of interferon-based therapy. However, for unknown reasons, a large proportion of patients with CHB do not respond to this treatment. Hence, there is a pressing need to establish response markers to select patients who will benefit from therapy and to spare potential nonresponders from unnecessary side effects of antiviral therapy. Here, we assessed whether HLA-C and KIR genotypes were associated with treatment outcome for CHB. Twelve SNPs in or near the HLA-C gene were genotyped in 86 CHB patients (41 HBeAg positive; 45 HBeAg negative) treated with peginterferon alfa-2a + adefovir. Genotyping of killer immunoglobin-like receptors (KIRs) was performed by SSP-PCR. One SNP in HLA-C (rs2308557) was significantly associated with combined response in HBeAg-positive CHB patients (P = 0.003). This SNP is linked to the HLA-C group C1 or C2 classification, which controls KIR binding. The combination of KIR2DL1 with its ligand HLA-C2 was observed significantly more often in HBeAg-positive patients with a combined response (13/14) than in nonresponders (11/27, P = 0.001). Patients with the KIR2DL1/C2 genotype had significantly higher baseline ALT levels (136 vs 50 U/L, P = 0.002) than patients without this combination. Furthermore, KIR2DL1-C2 predicted response independent of HBV genotype and ALT at baseline. HLA-C and KIR genotype is strongly associated with response in HBeAg-positive CHB patients treated with interferon-based therapy. In combination with other known response markers, HLA-C/KIR genotype could enable the selection of patients more likely to respond to interferon-based therapy.

Antiviral therapy with nucleotide/nucleoside analogues in chronic hepatitis B: A meta-analysis of prospective randomized trials.

Nucleotide/nucleoside analogues (antiviral therapy) are used in the therapy of HBeAg positive and HBeAg negative chronic hepatitis B. We analyzed ten selected randomized controlled with 2557 patients to estimate the effect of antiviral drugs in chronic hepatitis B with compared to placebo. Virological response, biochemical response, histological response, seroconversion of HBeAg, and loss of HBeAg were estimated as primary efficacy measures. The included studies were subjected for heterogeneity and publication bias. The heterogeneity was assessed with χ2 and I(2) statistics. Publication bias was assessed by funnel plot. Greater rates of improvement obtained in antiviral group for virological response [43.96% vs. 3.15%, RR = 0.57, 95% CI = 0.54-0.61, p-value <0.00001], biochemical response [58.37% vs. 21.87%, RR = 0.52, 95% CI = 0.48-0.56, p-value <0.00001], histological response [58.99% vs. 27.13%, RR = 0.56, 95% CI = 0.50-0.63, p-value <0.0001], seroconversion of HBeAg [10.66% vs. 5.56%, RR = 0.94, 95% CI = 0.91-0.97, p-value = 0.0005], and HBeAg loss [14.59% vs. 9.64%, RR = 0.92, 95% CI = 0.88-0.96, p-value = 0.0002]. The safety analysis were carried out for adverse events such as headache [17.22% vs. 17.34%, OR = 1.09, 95% CI = 0.81-1.46, p-value = 0.58], abdominal pain [16.46% vs. 14.34%, OR = 1.24, 95% CI = 0.90-1.72, p-value = 0.19], and pharyngitis [22.22% vs. 18.23%, OR = 1.12, 95% CI = 0.86-1.45, p-value = 0.40]. Excluding adverse events, all primary efficacy measures shown statistical significant result for chronic hepatitis treatment (p-value <0.05). Antiviral therapy provided significant benefit for the treatment of chronic hepatitis B with no measurable adverse effects.

Efficacy of peginterferon alpha initially combined with lamivudine or adefovir in treatment of HBeAg-positive Chronic Hepatitis B: A systematic review and meta-analysis

Efficacy of peginterferon alpha initially combined with lamivudine or adefovir in treatment of HBeAg-positive Chronic Hepatitis B: A systematic review and meta-analysis

Mutation Changes in the preC/Core Promoter in HBeAg-Positive Patients With Chronic Hepatitis B During Interferon Therapy.

To study the changes in 3 mutations related with hepatitis B e antigen (HBeAg) in patients with HBeAg-positive chronic hepatitis B (CHB) during interferon therapy.HBeAg seroconversion is a major therapeutic milestone for patients with HBeAg-positive CHB. The precore mutation G1896A and the basal core promoter mutations A1762T/G1764A are 3 important mutations that affect the expression of HBeAg; however, the change of these 3 mutations in CHB patients during interferon therapy has not yet been evaluated.Sixty-four treatment-naive patients with HBeAg-positive CHB were treated with interferon for 48 weeks and followed up for 24 weeks. Serum samples were collected from all of the participants at different time points and then subjected to viral DNA extraction. The precore and basal core promoter sequences were determined using nested PCR and direct sequencing. The treatment outcomes were confirmed both at the end of therapy and the follow-up period, and the results were compared between patients with mutant and wild-type virus.No significant difference in HBeAg loss and HBeAg seroconversion was observed between patients with mutant versus wild-type virus although the portion of patients who achieved HBeAg loss/seroconversion with mutant virus was a little higher than in patients with wild-type virus. Once a mutation exists, it is not replaced with the wild-type sequence during interferon therapy and follow-up; moreover, our results show that mutants stably coexist with the wild-type virus during interferon therapy.This study shows the changes in 3 mutations affecting the expression of HBeAg during interferon therapy. However, additional studies with a larger sample size and more sensitive detection methods are needed to uncover the underlying mechanism and clinical significance of these results.

Spleen, liver and kidney-strengthening formula combined with polyethylene glycol interferon in treatment of chronic hepatitis B

To observe the clinical efficacy of spleen, liver and kidney-strengthening formula combined with polyethylene glycol interferon in the treatment of HBeAg positive chronic hepatitis B(HP-HBV).One hundred and twenty-six patients with HP-HBV, who were treated in the hospital from June 2012 to December 2014, were selected and injected with polyethylene glycol interferon α-2a(or α-2b). The treatment course for the patients lasted for 24 weeks. Base on the level of HBV-DNA, patients are divided into response group and poor response group. According to random number table, the poor response group were randomized into control group and test group. Patients in the control group were injected with polyethylene glycol interferon α-2a(or α-2b), and patients in the test group were treated with spleen, liver and kidney-strengthening formula combined with polyethylene glycol interferon. Clinical efficacies of the 2 groups were observed, and changes in the level of HBeAg, ALT and HBV-DNA were observed before treatment and at the 24th week after treatment, and virological and serological response, biochemical responses, integral clinical symptoms and signs, adverse reactions were observed after 48 weeks of treatment.After 24 weeks of treatment, the response group was significantly better than the poor response group in HBeAg, ALT and the level of HBV-DNA(P<0.05). After 48 weeks of treatment, there was statistical significance in HBV-DNA negative conversion rate, HBeAg negative conversion rate between the 2 groups(P<0.05), and the test group was better in the two indicators. And the test group was significantly lower than the control group in clinical symptoms and signs score at the 48th week after treatment(P<0.05), with a significantly lower adverse reaction rate than the control group(P<0.05).Combination of spleen, liver and kidney-strengthening formula and polyethylene glycol interferon α-2a was effective and safe in the treatment of chronic hepatitis B, and so worth promoting in clinic.

Broad Range of Hepatitis B Virus (HBV) Patterns, Dual Circulation of Quasi-Subgenotype A3 and HBV/E and Heterogeneous HBV Mutations in HIV-Positive Patients in Gabon.

Integrated data on hepatitis B virus (HBV) patterns, HBV genotypes and mutations are lacking in human immunodeficiency virus type 1 (HIV-1) co-infected patients from Africa. This survey was conducted in 2010–2013 among 762 HIV-1-positive adults from Gabon who were predominantly treated with 3TC-based antiretroviral treatment. HBV patterns were identified using immunoassays detecting total antibody to hepatitis B core antigen (HBcAb), hepatitis B surface antigen (HBsAg), IgM HBcAb, hepatitis B e antigen (HBeAg), antibody to HBsAg (HBsAb) and an in-house real-time PCR test for HBV DNA quantification. Occult hepatitis B (OBI) was defined by the presence of isolated anti-HBc with detectable serum HBV DNA. HBV genotypes and HBV mutations were analyzed by PCR-direct sequencing method. Seventy-one (9.3%) patients tested positive for HBsAg, including one with acute hepatitis B (0.1%; 95% CI, 0.0%-0.2%), nine with HBeAg-positive chronic hepatitis B (CHB) (1.2%; 95% CI, 0.6%–2.2%), 16 with HBeAg-negative CHB (2.1%; 95% CI, 1.2%–3.3%) and 45 inactive HBV carriers (5.9%; 95% CI, 4.4%–7.8%). Sixty-one (8.0%; 95% CI, 6.2%–10.1%) patients showed OBI. Treated patients showed similar HBV DNA levels to those obtained in untreated patients, regardless of HBV patterns. Around 15.0% of OBI patients showed high (>1,000 UI/mL) viremia. The mutation M204V/I conferring resistance to 3TC was more common in HBV/A (47.4%) than in HBV/E isolates (0%) (P = .04). Our findings encouraged clinicians to promote HBV vaccination in patients with no exposure to HBV and to switch 3TC to universal TDF in those with CHB.

Predictive Factors for Sustained Remission after Discontinuation of Antiviral Therapy in Patients with HBeAg-positive Chronic Hepatitis B

The optimal timing for discontinuing oral antiviral therapy in patients with HBeAg-positive chronic hepatitis B (CHB) is unclear. The aim of our study was to investigate sustained remission after stopping antiviral therapy in patients with HBeAg-positive CHB. We analyzed the medical records of 58 patients who were HBeAg-positive and had discontinued antiviral therapy. Antiviral therapy was discontinued after HBeAg seroconversion and HBV DNA negativity for 6-12 months with consolidation therapy. Virologic relapse was defined as an increase in serum HBV DNA >2,000 IU/mL. No difference was observed between the virologic non-relapse and virologic relapse groups in baseline HBV DNA level (p=0.441) or duration of seroconversion (p=0.070). Time-to-undetectable HBV DNA during treatment was shorter in the virologic non-relapse group (29 patients) compared to the relapse group (29 patients) (4.9±2.6 vs. 13.2±12.7 months; p<0.01). Cumulative relapse rates were 12.7 in month 3, 32.7 in month 6, 47.3 in month 12, and 52.7% in month 18. We determined by multivariate analysis that the consolidation period (≥18 months, p=0.020) and early virologic response (HBV DNA <20 IU/mL) at six months during antiviral therapy (p=0.017) were significant predictors for sustained remission. A consolidation period of at least 18 months and early virological response at six months during antiviral therapy were associated with sustained remission in patients with HBeAg-positive CHB after treatment.

Efficacy of prolonged pegylated interferon α-2a treatment in HBeAg positive chronic hepatitis B patients with no response to ordinary interferon therapy

Efficacy of prolonged pegylated interferon α-2a treatment in HBeAg positive chronic hepatitis B patients with no response to ordinary interferon therapy

FRI-153 - The Efficacy and Safety of Peginterferona-2a and Nucleos(T)ide Analogues Treatments in Hbeag Positive Chronic Hepatitis B with Acute Exacerbation

FRI-153 - The Efficacy and Safety of Peginterferona-2a and Nucleos(T)ide Analogues Treatments in Hbeag Positive Chronic Hepatitis B with Acute Exacerbation

Efficacy Comparison of Tenofovir and Entecavir in HBeAg-Positive Chronic Hepatitis B Patients with High HBV DNA.

Objectives. To compare entecavir (ETV) and tenofovir disoproxil fumarate (TDF) effects in chronic hepatitis B (CHB) patients with high HBV DNA. Method. 96 patients treated initially with tenofovir (TDF group) or entecavir (ETV group) were included in this retrospective study. The following parameters were assessed: HBeAg and hepatitis B e antibody (anti-HBe) status, serum alanine aminotransferase (ALT), and HBV-DNA levels at weeks 4, 12, 24, 36, 48, 60, 72, and 96; time to ALT normalization, undetectable HBV-DNA levels, and HBeAg seroconversion; total duration of follow-up and adverse reactions. Results. The patients included 66 (69%) and 30 (31%) individuals administered ETV and TDF, respectively, comprising 75% males. They were 35.1 ± 4.5 and 33.7 ± 4.6 years old in ETV and TDF groups, respectively. At 36 weeks, the response rate was significantly higher in the TDF group than in ETV treated patients (90% versus 69.7%, p = 0.03). At 48 weeks, less patients administered ETV showed undetectable HBV-DNA levels compared with the TDF group (86.4% versus 96.7%), a non-statistically significant difference (p = 0.13). Only 1 ETV treated patient developed virological breakthrough at 48–96 w. No adverse reactions were found. Conclusion. ETV and TDF are comparable in efficacy and safety to suppress HBV-DNA replication in HBeAg-positive CHB patients with high HBV DNA.

FRI-134 - Previous Interferon Treatment Failure is Associated with Avery Low Chance of Response to Peginterferon Retreatment in HBeAg-Positive Chronic Hepatitis B: Pooled Analysis of Two Randomized Trials

FRI-134 - Previous Interferon Treatment Failure is Associated with Avery Low Chance of Response to Peginterferon Retreatment in HBeAg-Positive Chronic Hepatitis B: Pooled Analysis of Two Randomized Trials

FRI-123 - Outcome of 3-Year Consolidation Therapy following HBeAg Loss in HBeAg-Positive Chronic Hepatitis B Patients Treated with Nucleos(t)ide Analogues

FRI-123 - Outcome of 3-Year Consolidation Therapy following HBeAg Loss in HBeAg-Positive Chronic Hepatitis B Patients Treated with Nucleos(t)ide Analogues

The effect of peginterferon alpha-2a vs. interferon alpha-2a on intrahepatic covalently closed circular DNA in HBeAg-positive chronic hepatitis B patients

The covalently closed circular DNA (cccDNA), as the template of HBV transcription, plays a key role in the virus infection. The present study aimed to compare the effect of pegylated interferon (IFN)-α-2a with that of conventional IFN-α-2a on intrahepatic covalently closed circular (ccc)DNA in patients with chronic hepatitis B. Seventy-six HBeAg-positive chronic hepatitis B patients were randomly divided into two groups (n=38): group A was treated with interferon alpha-2a (IFN-α-2a) and group B was treated with peginterferon alpha-2a (peg IFN-α-2a). The intrahepatic level of cccDNA and its detection rate, levels of hepatitis B virus (HBV) DNA in liver and serum, histologic inflammation and some biochemistry parameters (alanine aminotransferase, aspartate aminotransferase and total bilirubin levels) were measured. The outcome of 48 weeks therapy showed that the mean level of intrahepatic HBV cccDNA level and its detection rate, the levels of HBV DNA and the histology and biochemistry parameters were significantly decreased following therapy in two groups (P<0.05). While, the reductions in the group treated with peg IFN-α-2a were greater (P<0.05). It may be concluded that the ability of the peg IFN-α-2a to clear and suppress cccDNA and HBV DNA was superior compared with that of conventional IFN-α-2a. Furthermore, the effects of peg IFN-α-2a on histology and biochemistry parameters were also more obvious than conventional IFN-α-2a.

A Better Antiviral Efficacy Found in Nucleos(t)ide Analog (NA) Combinations with Interferon Therapy than NA Monotherapy for HBeAg Positive Chronic Hepatitis B: A Meta-Analysis.

Background: The clinical efficacy of nucleos(t)ide analogues (NAs) combined with interferon (IFN) therapy vs. NAs monotherapy for chronic hepatitis B (CHB) remains inconclusive. The aim of this meta-analysis was to determine whether the NAs plus IFN regimen offers synergistic efficacy that justifies the cost and burden of such a combination therapy in CHB patients. Methods: Related publications covering the period of 1966 to July 2014 were identified through searching MEDLINE, EMBASE, Cochrane library, Chinese Biomedical Literature Database, WANFANG, and CNKI database. A total of 17 studies were enrolled, including 6 in English and 11 in Chinese. Then, we established a final list of studies for the meta-analysis by systematically grading the quality and eligibility of the identified individual studies. We used hepatitis B antigen (HBeAg) loss, HBV-DNA undetectable rate, HBeAg seroconversion, hepatitis B surface antigen (HBsAg) loss, HBsAg seroconversion, and histological score at the end of treatment for efficacy evaluation. A quantitative meta-analysis (Review Manager, Version 5.1.0) was performed to assess the differences between NAs and IFN combination therapy and NAs monotherapy. Results: Our analysis demonstrated that HBeAg loss (RR = 1.73, 95% CI = 1.32–2.26, p < 0.001), HBV-DNA undetectable rate (RR = 1.58, 95% CI = 1.22–2.04, p < 0.001), HBeAg seroconversion (RR = 1.68, 95% CI = 1.36–2.07, p < 0.001), and HBsAg loss (RR = 2.51, 95% CI = 1.32–4.75, p < 0.001) in the combination therapy group were significantly higher than those in the monotherapy group. However, there were no significant differences in HBsAg seroconversion (RR = 4.25, 95% CI = 0.62–29.13, p = 0.14), sustained virological response rates, and biochemical response rates observed between the two groups. The results showed that the combination therapy group had more improved HBV histology than the NAs monotherapy group (RR = 1.14, 95% CI = 0.93–1.39, p = 0.22). Conclusions: NAs and IFN or Peg-IFN combination therapy had a better efficacy in terms of HBeAg loss, HBV-DNA undetectable rate, HBeAg seroconversion, and HBsAg loss, compared to the NA monotherapy group at the end of treatment; however, there was no significant difference in HBsAg seroconversion between the two regimens.

Partial virological response to entecavir treatment in nucleos(t)ide-naïve patients with HBeAg-positive chronic hepatitis B is not caused by reduced sensitivity

Some patients with chronic hepatitis B (CHB) receiving entecavir (ETV) exhibit partial virological response (PVR) to ETV and the mechanism is not clear. In this study, we aim to investigate the in vitro susceptibility of residual clinical strains isolated from the sera of nucleos(t)ide-naïve hepatitis B virus e antigen (HBeAg)-positive patients with CHB and PVR to ETV, and to evaluate the clinical and virological responses to prolonged ETV monotherapy in these patients. We followed 69 nucleos(t)ide-naïve HBeAg-positive CHB patients receiving ETV treatment, with 13 partial responders to ETV. And we found that no genotypic resistance mutants were detected among the 13 PVR patients. Phenotypic analysis revealed that the residual HBV strains had normal replication capacity, and were as susceptible to ETV as wild-type HBV. All PVR patients continued to receive ETV monotherapy, and serum HBV DNA of the majority became undetectable after prolonged treatment. However, none of these patients achieved HBeAg loss. In contrast, 25.6% and 23.2% of the patients with virological response achieved HBeAg loss (P < 0.001) and HBeAg seroconversion (P < 0.001) at week 144, respectively. Thus, we conclude suboptimal response to ETV might not be due to reduced HBV susceptibility to ETV, and prolonging ETV monotherapy in patients with PVR is recommended.

Evaluation of 135 liver biopsy results between 2011 and 2014, according to hepatitis B virus DNA and liver transaminase levels in naive young patients with HBeAg positive and negative chronic hepatitis B infection

Evaluation of 135 liver biopsy results between 2011 and 2014, according to hepatitis B virus DNA and liver transaminase levels in naive young patients with HBeAg positive and negative chronic hepatitis B infection

Potential Efficacy of Pegylated Interferon-α and a Nucleos(t)ide Analogue as Combination Therapy for HBeAg-Positive Chronic Hepatitis B.

Background/AimsDespite the potent suppression of the hepatitis B virus with modern antiviral agents, only a minority of HBeAg-positive patients achieve hepatitis B e antigen seroconversion. We aimed to explore the potential efficacy of combination therapy consisting of pegylated interferon (p-IFN) and an oral antiviral agent in patients with HBeAg-positive chronic hepatitis B.MethodsThe treatment protocol consisted of p-IFN-α-2a at 180 μg/wk for 48 weeks, with either entecavir or tenofovir added 8 weeks after the initiation of p-IFN and continued for at least 6 months after HBe seroconversion was achieved.ResultsTo date, 10 patients have been treated under the protocol (eight adults, mean age 36±8 years; two adolescents, aged 12 and 16 years). All eight adult patients experienced loss of HBeAg at a mean of 72.3±66.9 weeks, including six patients who also developed anti-HBe and one patient who had HBs seroconversion. Although both adolescents remain on therapy, one adolescent had HBs seroconversion without HBe seroconversion. A total of nine of our 10 patients experienced a favorable serological transition.ConclusionsThe combination of p-IFN and a modern oral antiviral agent may be more effective than monotherapy with either class of agent in the treatment of HBeAg-positive chronic hepatitis B patients.

HBsAg Level as Predictor of Liver Fibrosis in HBeAg Positive Patients With Chronic Hepatitis B Virus Infection

Preliminary data suggests lower serum hepatitis B surface antigen level is associated with more severe liver fibrosis in HBeAg positive patients. We evaluated the association of HBsAg level with biochemical, virological, and histological features in asymptomatic patients with chronic HBV infection. HBsAg levels were measured at baseline in 481 asymptomatic, treatment naive patients with chronic HBV infection. Subjects were followed-up prospectively (median, 12; range, 8-36 months). Phases of HBV infection were defined after regular monitoring of HBV-DNA and transaminases. Liver histology was scored using the METAVIR system. HBeAg positive (n, 126) patients were significantly younger than HBeAg negative (n, 355), median age 26 vs 30 years; P<0.01. HBV genotype could be determined in 350 patients, 240 (68.57%) had genotype D and 100 (28.57%) had genotype A. HBsAg level had modest correlation with serum HBV DNA(r=0.6 vs 0.4 in eAg positive & negative respectively). HBeAg+ve patients with fibrosis score≥F2 showed significantly lower median serum HBsAg levels and serum HBV DNA levels compared with patients with F0-F1 score (median, range; 4.51, 2.99-6.10 vs 5.06, 4.13-5.89, P<0.01) and (8.39, 3.85-10.60, P<0.01) respectively. Significant inverse correlation of HBsAg level was found with liver fibrosis in eAg positive group (r=-0.76; P<0.001). HBsAg level cut off value 4.7log10IU/ml predicted moderate to advance fibrosis (F≥2) with 92% sensitivity, 85% specificity & 91% negative predictive value. Lower HBsAg level might reflect the status of advanced liver fibrosis in HBeAg positive chronic hepatitis B subjects.

Naturally occurring deletion/insertion mutations within HBV whole genome sequences in HBeAg-positive chronic hepatitis B patients are correlated with baseline serum HBsAg and HBeAg levels and might predict a shorter interval to HBeAg loss and seroconversion during antiviral treatment

ObjectivesDeletion/insertion (Del/Ins) throughout hepatitis B virus (HBV) genome has not been well studied for HBeA-positive chronic hepatitis B (CHB) patients. This study aimed to characterize the HBV Del/Ins mutations in full-length genome quasispecies sequences in such patients at antiviral baseline and to reveal their potential impacts on HBV serological markers and responses to nucleos(t)ide analogue (NUC) treatment. Materials and methodsA total of 30 HBeAg-positive CHB patients with genotype C infection receiving a 104-week lamivudine (LMV) and adefovir dipivoxil (ADV) combination therapy were enrolled. HBV whole genome sequences in serum samples at baseline were clone sequenced and analyzed using bioinformatics tools. ResultsAmong 306 unspliced clone sequences, 61.8% (189/306) had Del/Ins mutations, 38.2% (117/306) were full-length genomes without any Del/Ins. Due to different combinations of 125 deletion types and 45 insertion types, we identified 55 Del/Ins-harboring HBV genome patterns, which affected a single or several functional genomic regions. Importantly, the proportion of Del/Ins-harboring clones was found to be significantly negatively correlated with HBsAg (r=−0.3985, P=0.0292) and HBeAg (r=−0.3878, P=0.0342) at baseline. Higher percentage of Del/Ins-harboring clones at baseline was found to predict a shorter interval to HBeAg loss and seroconversion. ConclusionDel/Ins mutations within HBV whole genome were prevalent in HBeAg-positive CHB patients prior to antiviral treatment. A higher detection rate of these mutations at baseline might correlate with a better response to LMV and ADV combination therapy.