ETV Group Research Articles

Real-world study on the efficacy and safety of different treatment regimens in treatment-naïve CHB patients with high viral load

Evaluate the real-world effectiveness and safety of different treatment regimens for treatment-naïve high viral load chronic hepatitis B (CHB) patients. Between January 2021 and August 2022, CHB patients with HBV DNA ≥ 107 IU/mL were collected from four medical centers in Shenzhen. Patients treated with mono or combine antiviral therapy. The primary endpoint was the cumulative incidence of virological response at 48 weeks, and other endpoints included changes in HBsAg, HBeAg, ALT, and eGFR at 48 weeks. We used propensity score-based inverse probability of treatment weighting (IPTW) to balance the bias. Weighted logistics regression was used to estimate the factors affecting virological response. A total of 391 patients were included in the study, with 296 patients undergoing statistical analysis after IPTW. The patients were distributed into four groups: ETV (n = 62), TDF (n = 89), TAF (n = 36), TDF + LdT/ETV (n = 109). The 48-week cumulative incidence of virological response was significantly lower in ETV group (52.3%) compared to TDF (71.7%), TAF (74.2%), and TDF + LdT/ETV groups (77.9%) (P < 0.05). There were no significant differences in HBsAg loss among the four groups, but the HBeAg seroconversion rate was significantly higher in the TAF group. The ALT normalization rate was significantly higher in the TAF group (72.2%) compared to the others at 48 weeks (P < 0.05). In treatment-naïve CHB patients with high viral load, combination therapy was not superior to TDF or TAF monotherapy in virological response. Patients treated with TDF or TAF showed superior virological response compared to those treated with ETV. The TAF group demonstrated superiority in terms of ALT normalization and HBeAg seroconversion.

The Comparison of Outcome of Ventriculoperitoneal Shunts vs. Endoscopic Third Ventriculostomy in Patients with Idiopathic Normal Pressure Hydrocephalus

Objective: To compare functional outcomes in terms of INPGHS score and overall improvement in patients of iNPH treated with ETV vs. VP shunting. Materials &amp; Methods: A Randomized control trial was conducted for 6 months at the Department of Neurosurgery, Rawalpindi Medical University and Allied Hospitals, Rawalpindi. 62 patients (31 in each group) were enrolled &amp; allocated into two groups. In group A patients ETV was done and in group B VP shunting. Post-operatively, Patients were followed up for 1 month. Results: The mean age of the patients in the ETV &amp; VP shunting groups was 63.19 ± 6.95 &amp; 63 ± 6.82 years respectively. Males were 64.5% (n = 20) in both groups. Improvement was noted in 9 (29%) patients in the ETV group &amp; 15 (48.4%) patients in the latter group (p-value = 0.118). Conclusion: Ventriculoperitoneal shunts are superior to endoscopic third ventriculostomy in terms of functional neurological outcomes and improvement in symptoms. Keywords: Endoscopic Third Ventriculostomy, Ventriculoperitoneal Shunt, Idiopathic Normal Pressure Hydrocephalus Grading Scale (iNPHGS), Aqueductal CSF Stroke Volume (ACSV).

Tenofovir alafenamide versus entecavir for treating hepatitis B virus-related acute-on-chronic liver failure: real-world study.

Real-world data regarding hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients receiving tenofovir alafenamide (TAF) as an antiviral drug are limited. Hence, we evaluated the efficacy and kidney safety of TAF among this population. A total of 272 HBV-related ACLF patients hospitalized at Xiangya Hospital of Central South University were enrolled in this retrospective research. All patients received antiviral therapy with TAF (n = 100) or ETV (n = 172) and comprehensive medical treatments. Through 1:1 propensity score matching, 100 patients were finally included in each group. At week 48, the survival rates without transplantation of the TAF group and ETV group were 76.00 and 58.00%, separately (P = 0.007). After 4 weeks of treatment, the TAF treatment group exhibited a significantly decline in HBV DNA viral load (P = 0.029). The mean estimated glomerular filtration rate was apparently improved in the TAF group compared with the ETV group (TAF 5.98 ± 14.46 vs. ETV 1.18 ± 18.07 ml/min/1.73 m2) (P < 0.05). There were 6 patients in TAF group and 21 patients in ETV group with chronic kidney disease (CKD) stage progression ≥ 1. By contrast, the ETV treatment group has a greater risk of renal function progression in CKD 1 stage patients (P < 0.05). This real-world clinical study showed that TAF is more effective than ETV in reducing viral load and improving survival rate in HBV-ACLF patients and the risk of renal function decline is lower. https://ClinicalTrials.gov, identifier NCT05453448.

The Outcome of Surgical Intervention (Ventriculoperitoneal Shunt and Endoscopic Third Ventriculostomy) in Patients With Hydrocephalus Secondary to Tuberculous Meningitis: A Systematic Review.

The objective of this study is to analyze the outcome of the safety and efficiency of the surgical interventions (ventriculoperitoneal shunt [VPS] and endoscopic third ventriculostomy [ETV]) in patients with hydrocephalus due to tuberculous (TB) meningitis. A systematic literature search has been conducted using PubMed, Google Scholar, PMC, and ScienceDirect databases from 2001 to 2022 April. A total of 16 studies have been included, irrespective of their design. These studies include patients diagnosed with hydrocephalus secondary to TB meningitis (TBM) treated with VPS or ETV. A systematic review was conducted to determine the efficiency of surgical procedures based on the outcomes and complications associated with these procedures. A total of 2207 patients (aged one month to 68 years) have been included in this study, out of which 1723 underwent VPS and 484 underwent ETV. The overall success rate in the VPS group varied from 21.1% to 77.5%. The overall success rate in the ETV group ranged from 41.1% to 77%. The overall complications rate in the VPS group varied from 10% to 43.8%, and the complications rate in the ETV group varied from 3.8% to 22.5%. After ruling out the significant differences in the average percentages of outcomes and complications followed by VPS and ETV, ETV is suggested in patients with chronic phases of illness because the chances of ETV failure are high during the initial stage. The uncertainty of the ETV gradually decreases over time. To attain favourable long-term outcomes with ETV in patients with TBM hydrocephalus (TBMH), ETV should be performed after chemotherapy, anti-tubercular treatment, and steroids. In addition, ETV is considered beneficial over VP shunt as associated long-term complications are significantly less compared to VP shunt. In contrast, VP shunt is suggested as a modified Vellore grading which shows a more favourable outcome in patients with acute illness than ETV.

Effects of nucleos(t)ide analogs on hepatitis B surface antigen reduction with interferon-lambda 3 induction in chronic hepatitis B patients.

Benefits of nucleos(t)ide analogs (NAs) on hepatitis B surface antigen (HBsAg) reduction and interferon-lambda3 (IFN-λ3) induction are still not known. This study aimed to investigate the effects of NAs on HBsAg reduction and association with serum IFN-λ3 levels in chronic hepatitis B (CHB) patients. A total of 91 patients [51 treated with nucleoside analog entecavir hydrate (ETV) and 40 treated with nucleotide analog adefovir dipivoxil (ADV) or tenofovir disoproxil fumarate (TDF)] with clinically evident CHB (chronic hepatitis, 57; liver cirrhosis, 34) were enrolled in this study. Serum IFN-λ3 levels among patients receiving ETV and ADV/TDF were measured before the initiation of therapy and 1, 3, and 5years post-therapy. The change (mean±standard deviation) in serum HBsAg levels from baseline to year five was -0.38±0.46 and -0.84±0.64 log10 IU/ml in ETV and ADV/TDF groups, respectively (p=0.0004). Higher serum IFN-λ3 levels were observed in ADV/TDF group compared with ETV group during treatment (p<0.001). Serum IFN-λ3 levels showed negative correlation with HBsAg reduction in ADV/TDF group (r = -0.386, p = 0.038) at week 48. Nucleotide analogs (ADV/TDF) treatment has associated factors with -0.3 log HBsAg decline at 1year, -0.5 log HBsAg decline at 3years, and -0.8 log HBsAg decline at 5years after NAs treatment on multivariate analysis. Nucleotide analog (ADV/TDF) treatment reduced HBsAg levels greater compared with nucleoside analog (ETV) in parallel with IFN-λ3 induction.

Endoscopic third ventriculostomy versus ventriculoperitoneal shunt for treatment of hydrocephalus in infants in a tribal population in India

Study design: Prospective long term follow-up study Background: Hydrocephalus remains a common cause of admission in pediatric neurosurgery units. Of the two prevalent modalities of treatment for hydrocephalus in infants, i.e. endoscopic third ventriculostomy and ventriculoperitoneal shunt, which one is a better option, especially in a tribal setting, is a matter of debate. Aim: To determine and compare the effectiveness of endoscopic third ventriculostomy versus ventriculoperitoneal shunt for the treatment of infants in a tribal population. Methods: A prospective follow-up study was carried out on 70 patients of hydrocephalus with age less than or equal to 12 months during a period of 7 years from August 2014 to June 2021. A detailed history, physical examination, and computed tomography scan were done in all the cases. Based on patient condition, aetiology and parents choice, 30 patients were treated by Endoscopic third ventriculostomy and 40 patients were treated by ventriculoperitoneal shunt. At enrolment, baseline clinical data were collected. Postoperative data were collected, including assessments of complications and treatment failures. Results: A total of 70 infants with hydrocephalus were enrolled in the study and out of them, 30 (42.86%) underwent ETV and 40 (57.14%) underwent VP shunt for the initial treatment of their hydrocephalus. The mean age of patients was 6.4±1.2 months with a range of 18 days to 342 days. Clinical improvement was shown in 76.67% and 70% in ETV and VP shunt groups respectively. No significant difference (p=0.53) was observed in clinical outcomes in both groups. In the 1 to 6 months of age group, 07 (30.43%) clinically improved patients were from the ETV group, while in the VP shunt group, 10 (35.71%) patients showed improvement. In the 7 to 12 months age group, 16 (69.57%) clinically improved patients were from the ETV group and 18 (64.29%) patients were from the VP shunt group (p=0.69). Association of treatment success with gender, term of gestation and aetiology of hydrocephalus was not statistical significant (p&gt;0.05). Out of 70 patients with hydrocephalus, postoperative complications such as infection, CSF leak, haemorrhage and blockage was found in 09 (12.86%), 08 (11.43%), 05 (7.14%) and 08 (11.43%) patients respectively. A significant higher proportion of infection (p=0.043) and blockage (p=0.023) was found in the VP shunt group than in the ETV group. Conclusion: Treatment success was high in both procedures. VP shunt was found to be more successful than ETV in terms of clinical outcome in both age groups. However, the results were statistically insignificant. A significantly higher proportion of complications was found with VP shunt than ETV therefore greater benefits can be achieved using ETV. Thus for a tribal population, where patient compliance is poor and healthcare accessibility, as well as regular follow-up, is difficult, a procedure like ETV can be considered better than VP shunt.

Correlation of qAnti-HBc with antiviral efficacy in children with chronic hepatitis B and exploration of its possible immune mechanism

Objective: To compare the baseline difference in the quantitative hepatitis B core antibody levels (qAnti-HBc) between non-response and response group in children with HBeAg-positive chronic hepatitis B (CHB) who received antiviral therapy, and further explore the proportion and functional activity of CD8 + memory T lymphocyte subsets with different qAnti-HBC levels in peripheral blood of children. Methods: The baseline anti-HBc quantification (qAnti-HBc) levels of 85 children with HBeAg-positive CHB who visited the Department of Infectious Diseases, Children's Hospital of Chongqing Medical University from June 2018 to December 2020 were detected retrospectively. The relationship between the baseline qAnti-HBc level and HBeAg serological response in 37 children who received antiviral therapy was analyzed. The proportion of CD8(+) memory T lymphocyte subsets and the secretion levels of interferon (IFN) γ, and tumor necrosis factor (TNF) α in peripheral blood of 59 children at baseline were detected by flow cytometry. The relationship between qAnti-HBc level and the proportion and functional activity of CD8(+) memory T lymphocyte subsets was analyzed. Pearson's Chi-square test was used to compare the count data. Mann-Whitney U test or Kruskal-Wallis test was used to compare measurement data between two or more groups, and Spearman's rank correlation analysis was used for the correlation between continuous variables. Results: Among 37 children who received entecavir (ETV, 21/37 cases) or pegylated interferon (Peg-IFN, 16/37 cases), 18 cases had developed HBeAg seroconversion (10/ 21 cases in the ETV group, 8/16 cases in the Peg-IFN group). The baseline qAnti-HBc level was significantly higher in the response group [4.71 (4.64~4.81) log(10)IU/ml] than the non-response group children [4.54 (4.45~4.64) log(10)IU/ml, Z = -3.316, P = 0.001]. The proportion of CD8(+) Tem, CD38(+)CD8(+) Tem, CD38(+)CD8(+) Temra cells and the levels of IFNγ and TNFα secreted by CD8(+) T lymphocytes were significantly higher in the high-qAnti-HBc group than the low-qAnti-HBc group (P < 0.05). The proportion of CD8(+) Tem, CD38(+)CD8(+) Tem and CD38(+)CD8(+) Temra cells was significantly higher in ALT > 1× upper limit of normal value (ULN) group than ALT≤1×ULN group (P < 0.05). However, there were no significant differences in the levels of IFNγ and TNFα secreted by CD8(+) T lymphocytes between the two groups (P > 0.05). Spearman's correlation analysis showed that qAnti-HBc was positively correlated with the proportion of CD8(+) Tem, CD38(+)CD8(+) Tem, CD38(+)CD8(+) Temra cells and the level of IFNγ secreted by CD8(+)T lymphocytes (P < 0.05). Additionally, ALT was only positively correlated with the proportion of CD38(+)CD8(+) TEM and CD38(+) CD8(+) Temra cells (P < 0.05). Conclusion: Raised baseline qAnti-HBc level is related to the HBeAg serological response to antiviral therapy in children with CHB. Peripheral blood effector CD8+ T lymphocytes of CHB children with higher qAnti-HBc show stronger phenotype and functional activation characteristics, which may shed some light on the underlying immune mechanism related to antiviral therapy efficacy in children with CHB.

Efficacy of different nucleoside analog rescue therapies for entecavir-resistant chronic hepatitis B patients

BackgroundEntecavir (ETV) is recommended as a first-line anti-HBV treatment. However, many chronic hepatitis B patients initiate anti-HBV treatment such as lamivudine and telbivudine with low genetic barriers in China, which leads to compensatory mutations and increases the rate of ETV resistance. The management of ETV resistance in China is an essential clinical issue.MethodsPatients from 2011 to 2017 with nucleos(t)ide analog resistance were screened and 72 patients with ETV resistance were included. These patients received different rescue therapies including an ETV and adefovir (ADV) combination therapy group (n = 25), a tenofovir (TDF) monotherapy group (n = 27), and an ETV and TDF combination therapy group (n = 20). Virologic, biochemical, and serologic responses were compared among the three groups.ResultsThe rate of ETV resistance among all HBV-resistant variants increased from 6.04% in 2011 to 15.02% in 2017. TDF monotherapy and TDF combination groups showed similar rates of negative HBV DNA at 48 weeks (74.07% vs 70.00%, P > 0.05), while the ETV and ADV group showed the worst virologic response (28.00%). Also, TDF monotherapy and TDF combination therapy showed similar decline of HBV DNA at weeks 12, 24, and 48. There was no significant difference in the rates of HBeAg clearance, ALT normalization, and abnormal renal function among the three groups.ConclusionsTDF monotherapy showed a comparable virologic response to TDF and ETV combination therapy and a better virologic response than ETV and ADV combination therapy. Thus, TDF monotherapy is the preferred rescue therapy for ETV resistance.

Short-term and long-term safety and efficacy of tenofovir alafenamide, tenofovir disoproxil fumarate and entecavir treatment of acute-on-chronic liver failure associated with hepatitis B

Background & AimsThere is limited evidence on the efficacy and safety of nucleos(t) ide analogues (NAs) in the treatment of HBV-ACLF. Our objective was to evaluate the outcomes among TAF, TDF and ETV, three first-line antivirals against chronic hepatitis B, in patients with HBV-ACLF.MethodsPatients with HBV-related ACLF were recruited and received daily TAF (25 mg/d), TDF (300 mg/d) and ETV (0.5 mg/d). They were prospectively followed-up. The primary endpoint was overall survival at week 12 and week 48, the secondary endpoints were virological response and biochemical response.ResultsForty gender and age matched eligible subjects were recruited and divided into three groups: TAF group, TDF group and ETV group. By week 48, 8 (80%) patients in TAF group, 6 (60%) patients in TDF group and 17 (85%) patients in ETV group survived without liver transplantation (P = 0.251). After 4 weeks of NAs treatment, all three groups showed paralleling reduction of HBV DNA levels. All three groups presented similar biochemical responses at week 4, patients treated with TAF showed a priority in total bilirubin reduction, albumin and cholesterol maintenance. Additionally, although there was no significant difference in changes of serum urea, serum creatinine, serum cystatin C and estimated GFR among the three groups by treatment week 4, TDF showed unfavorable renal safety even in short -term treatment. The treatment using NAs was well-tolerated and there was no serious drug-related adverse event reported.ConclusionsTAF, TDF and ETV are of similar efficacy and safety in short-term and long-term treatment of HBV-ACLF.Trial registrationThis study is ongoing and is registered with ClinicalTrials.gov, NCT03640728 (05/02/2019).

The 48-week safety and therapeutic effects of tenofovir alafenamide in hbv-related acute-on-chronic liver failure: A prospective cohort study.

Tenofovir alafenamide (TAF) has been available in China for a short time, little is known about its safety and efficacy in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF). We conducted this study to further verify the safety and efficacy of TAF in these patients. Eighty-eight eligible subjects were included and divided into three groups: TAF group, TDF group and ETV group. Clinical and laboratory test results were collected and the survival status, virus suppression status and liver and renal function improvement were observed during follow-up. No drug-related adverse events were observed within a 48-week observation period. At week 48, the survival rates of the three groups were 56.5%, 78.3% and 59.5% (p=0.262). HBV DNA undetectable rates were similar (80.0% vs.75.0% vs.84.6%, respectively, p=0.863). Liver function improved in all the three groups over time. Compared with the other two groups, patients in the TAF group had a greater decrease in serum creatinine (CR) and an increase in estimated glomerular filtration rate (eGFR), especially at week 12. At week 48, the median changes of CR were -0.7 (IQR -3.0, 13.0) vs. 15.0 (IQR -3.0, 21.0) vs. 5.0 (IQR -9.0, 14.0), respectively (p = 0.334), while the median changes of eGFR were -2.12 (IQR -13.87, 1.44) vs. -10.43 (IQR -20.21, 3.18) vs. -5.31 (IQR -14.72, 5.44) ml/min/1.73m2 , respectively (p = 0.592). In this real-world clinical study, TAF is as effective as TDF and ETV, and may be more beneficial in protecting renal function in the early stages of antiviral therapy.

Genotypic Resistance Remains A Concern In Chronic Hepatitis B Patients With High Viral Load After Lamivudine And Adefovir Combination Therapy.

AimsPrevious studies have shown that baseline high viral load is closely related to treatment response in chronic hepatitis B (CHB). This study was designed to evaluate the differences of treatment responses between de novo lamivudine (LAM) plus adefovir (ADV) combination therapy compared with entecavir monotherapy (ETV).MethodsA total of 185 HBeAg-positive CHB patients with high viral load were enrolled and assigned to the LAM+ADV group (n=90) or ETV group (n=95). Clinical variables are extracted from medical records.ResultsNo significant differences in baseline variables were found between the two groups before antiviral treatment. After 104 weeks of antiviral therapy, the mean HBV DNA viral load in the LAM+ADV group decreased from 8.01±0.65 log10 copies/mL to 0.41±1.04 log10 copies/mL, compared with 8.04±0.57 log10 copies/mL to 0.57±1.28 log10 copies/mL in the ETV group (P=0.35). The virological response rate of LAM+ADV group was 82.2% (74/90) at 104 weeks of treatment, and 80.0% (76/95) in the ETV group (P=0.70). For HBeAg serological responses, HBeAg loss occurred in 23.3% (21/90) and 17.9% (17/95) in the LAM+ADV group and the ETV group, respectively (P=0.36). HBeAg seroconversion was observed in 15.6% (14/90) and 15.8% (15/95) in the LAM+ADV group and ETV group, respectively (P=0.96). However, after 104 weeks of treatment, genotypic resistance was confirmed in 8 cases in the LAM+ADV group, a proportion of 8.8% (8/90), compared with an absence of genotypic resistance in the ETV group (P=0.003).ConclusionBoth de novo combination therapy of LAM+ADV and ETV monotherapy could effectively inhibit HBV replication in patients with high viral load. However, the rate of genotypic resistance in LAM+ADV treatment remains a concern. For CHB patients with high viral load, ETV treatment may be superior.

Entecavir monotherapy versus de novo combination of lamivudine and adefovir for compensated hepatitis B virus-related cirrhosis: a real-world prospective multicenter cohort study.

BackgroundDe novo combination of lamivudine (Lam) and adefovir (Adv) was not rarely used in clinical practice. However, head-to-head comparisons of entecavir (Etv) monotherapy with this combination in hepatitis B virus (HBV)-related compensated cirrhosis patients are unavailable. This study aimed to compare the efficacy and safety of Etv monotherapy with combination therapy in patients with HBV-related compensated liver cirrhosis.MethodsTreatment-naïve patients with HBV-related compensated liver cirrhosis were recruited to receive either Etv monotherapy or a de novo combination of Lam and Adv. Data were collected at baseline and every 6 months thereafter.ResultsA total of 578 patients (485 in Etv group, 93 in combination group) were included. Baseline characteristics were comparable between the two groups. At the end of 1, 2, and 3 years, HBV DNA was undetectable in 82.7%, 96.2%, and 94.3% of patients in the Etv group and 88.9%, 81.7%, and 84.6% in the combination group, respectively (all P>0.05). The cumulative virological breakthrough rate at 1, 2, and 3 years was 2.7%, 6.7%, and 9.8% in the Etv group and 2.9%, 13.3%, and 32.2% in the combination group, respectively (P=0.003). After propensity-score adjustment for age, sex, and baseline HBeAg, ALT, and total bilirubin, virological breakthrough was higher in the de novo combination of Lam and Adv (HR 2.83, 95% CI 1.37–5.86; P<0.01). The cumulative rate of liver-related events, including decompensation and hepatocellular carcinoma, at 1, 2, and 3 years was 2.9%, 4.2%, and 6.1% in the Etv group and 2.2%, 2.2%, and 6.7% in combination group, respectively (P=0.83). Biochemical response and serological response were similar between the groups.ConclusionEtv treatment had less virological breakthrough and potentially higher HBV-DNA suppression than de novo combination of Lam and Adv during 3 years in treatment-naïve HBV-related compensated liver cirrhosis.

Comparison of efficacy and safety between entecavir versus adefovir dipivoxil in the treatment of HBeAg positive chronic hepatitis B

Objective To compare the efficacy and safety of entecavir versus adefovir dipivoxil in the treatment of HBeAg positive chronic hepatitis B (CHB). Methods Ninety-six cases with HBeAg positive CHB were divided into ETV group and ADV group according to different medication.In addition to conventional treatment, ETV group received entecavir 0.5 mg/d, ADV group received adefovir dipivoxil 10 mg/d.HBV DNA negative conversion rate, alanine aminotransferase (ALT) recurrence rate and HBeAg negative conversion rate in 24 weeks, 48 weeks and 96 weeks were compared as well as the adverse reactions and liver function in 96 weeks. Results HBV DNA negative conversion rates in ETV group were significantly higher than those in ADV group in 24 weeks, 48 weeks and 96 weeks (24 weeks: 64.6%(31/48) vs.41.7%(20/48); 48 weeks: 83.3%(40/48) vs.52.1%(25/48); 96 weeks: 97.9%(47/48) vs.62.5%(30/48), χ2=5.06, 10.72, 18.96, P 0.05). There was no significant difference in HBeAg negative conversion rate between the two groups through treatment(χ2=0.07, 0.22, 0.44, P>0.05). After 96 weeks, ALT in both groups decreased significantly(t=13.56, 11.85, P 0.05). Conclusion Entecavir has a higher rate of HBV DNA negative conversion rate, ALT recurrence rate and HBeAg negative conversion rate in the treatment of HBeAg positive CHB.It is an ideal antiviral drug. Key words: Entecavir; Adefovir dipivoxil; HBeAg positive; Chronic hepatitis B; Efficacy

Comparison between tenofovir disoproxil fumarate and entecavir treatment in real‐world clinical practice

SummaryBackground and aimsEntecavir (ETV) and tenofovir disoproxil fumarate (TDF) are effective as two first‐line anti‐viral therapies for chronic hepatitis B (CHB); however, data are limited on directly comparing the safety and effectiveness of these two antivirals. Hence, we compared the efficacy and safety of TDF and ETV on treatment‐naïve patients with CHB.MethodsWe performed a hospital‐based, retrospective cohort study of 257 treatment‐naïve patients with CHB receiving TDF (n = 79) or ETV (n = 178). Virological and biochemical response as well as nephrotoxicity were assessed between TDF and ETV treatment groups.ResultsAt month 12, TDF group had faster on HBV DNA complete suppression than ETV group (p = 0.001). Multivariate analysis indicated that treatment with TDF was a significant predictor of HBV DNA suppression (HR = 1.33; 95% CI = 1.01 – 1.76; p = 0.045). In addition, HBeAg positivity (HR = 0.70; 95% CI = 0.52 – 0.96; p = 0.025) and higher baseline HBV DNA level (HR = 0.84; 95% CI = 0.76 – 0.92; p &lt; 0.001) were significant negative predictors for viral suppression. The ALT normalization rate between these two treatment groups were similar (p = 0.114). TDF group had more populations in ≧ 20% decrease of eGFR MDRD at month 24 than ETV group (31.5% vs. 17.2%, p = 0.044), but only the baseline eGFR was the independent factor by multivariate analysis (OR = 1.05; 95% CI = 1.03 – 1.07; p &lt; 0.001).ConclusionsTDF was significantly more effective in achieving complete viral suppression beyond month 12, and there was no significance in nephrotoxicity than ETV group.Copyright © 2017, The Gastroenterological Society of Taiwan, The Digestive Endoscopy Society of Taiwan and Taiwan Association for the Study of the Liver.

LAM add-on ADV combination therapy or ETV monotherapy for CHB patients with suboptimal response to ADV

Introduction. Among the available nucleos(t)ide analogues adefovir dipivoxil (ADV) is relatively cheap and widely used in rural area in China. However, there are insufficient data on recommendation for patients with suboptimal response to ADV after 48 weeks of treatment in order to reduce the resistance rate in the long term. The aim of this study was to compare the efficacy and safety of LAM add-on combination therapy versus ETV monotherapy for patients with suboptimal response to ADV.Material and methods. 136 patients with suboptimal response to ADV were randomly assigned to the add-on LAM with ADV combination therapy (68 patients) group and the ETV monotherapy (68 patients) group. Patients in the add-on group were prescribed 100 mg LAM and 10 mg ADV per day, while the monotherapy group received 0.5 mg ETV per day for 48 weeks. Tests for liver and kidney function, HBV serum markers, HBV DNA load, were performed every 3 months.Results. The mean patient age in LAM add-on group and ETV monotherapy was 38.59 ± 7.65 and 37.56 ± 8.67 years respectively. The HBV DNA undetectable rate in the LAM add-on group and the ETV group were not significant difference at week 4, 12 and 24 (P > 0.05). However, the HBV undetectable rate in the ETV group was higher than that in the LAM add-on group at week 36 and 48 (P = 0.043 for week 36 and P = 0.038 for week 48). There was no significant difference both for HBeAg loss and HBeAg seroconversion between two groups (P > 0.05) at 48 weeks. Meanwhile, our study also demonstrated that the mean eGFR levels in LAM add-on group was decreased from 99.6 ± 8.71 at baseline to 86.4 ± 9.83 at the end of 48 weeks, which was significantly higher than that in the ETV monotherapy group (P < 0.05). 8.8% of patients in LAM add-on group experienced eGFR reduction by 20-30% from baseline at 48 weeks. No patients developed hyposphosphatemia in our study.Conclusion. Our study clearly showed that switch to ETV monotherapy was the more effective and more safe than that of LAM add-on combination therapy for patients with suboptimal response to ADV.

Comparative analysis of the efficacies of entecavir capsules and lamivudine in chronic hepatitis B patients

To investigate the efficacy profile of entecavir capsule (ETV) as a chronic hepatitis B therapy, as compared to lamivudine (LAM). In this multicenter, randomized, double-blind, parallel group evaluation of ETV, 232 subjects were administered a 96-week course of 0.5 mg/day ETV or 100 mg/day LAM. PCR measurement of hepatitis B virus (HBV) was conducted throughout the treatment course to determine achievement of complete virologic response (CVR; defined as less than 500 copies/ml of HBV DNA) or experience of virology rebound ( more than 500 copies/ml of HBV DNA after achievement of CVR). After week-48 of treatment, the ETV group showed a higher CVR rate (90.3% vs. LAM: 59.4%) and lower virology rebound rate (1.9% vs. LAM: 13.9%). After week-96 of treatment, the ETV group continued to have a higher CVR rate (86.0% vs. LAM: 71.4%), and virology rebound was experienced by significantly less subjects in the ETV group (1.2% vs. LAM: 11.9%, P = 0.005). ETV therapy can quickly and continuously suppress HBV replication in chronic hepatitis B patients, and has a lower resistance rate than LAM. Compared to LAM, ETV may be a superior long-term treatment choice for chronic hepatitis B.

Analysis of a randomized, double-blind, double-dummy, controlled, multicenter study confirmed the similar therapeutic efficacies of entecavir maleate and entecavir for treatment of HBeAg-positive chronic hepatitis B

To evaluate the efficacy and safety of entecavir maleate (ETV) versus ETV in Chinese patients with hepatitis B e antigen(HBeAg)-positive chronic hepatitis B(CHB). The patient population of this previously published randomized, double-blind, double-dummy, controlled, multicenter study was expanded by patients in the 0.5 mg/day ETV maleate group (total n = 110) and patients in the 0.5 mg/day ETV group (total n = 108). At treatment weeks 12, 24 and 48, hepatitis B virus (HBV) DNA levels were measured by the Roche Cobas Ampliprep/Cobas Taqman PCR assay. Adverse events (AE) were recorded. As in the original analysis, the two treatment groups showed similar characteristics at baseline. In addition, the results for the all therapeutic effects showed identical trends to the results obtained in the original analysis, including the statistically similar effects of ETV and ETV maleate treatment-induced decreases in mean HBV DNA level at weeks 12, 24, and 48 (ETV: by 4.28, 5.00, and 5.53 log10 IU/ml vs. ETV maleate: by 4.46, 4.99, and 5.51 log10 IU/ml, respectively; all vs. baseline P more than 0.05), achievement of undetectable levels of serum HBV DNA ( less than 20 IU/ml) at week 48 (ETV: 38.18% vs. ETV maleate: 35.19%; P more than 0.05), HBeAg loss rates at week 48 (ETV: 10.91% vs. ETV maleate: 12.96%; P more than 0.05), HBeAg seroconversion rates at week 48 (ETV: 7.77% vs. ETV maleate: 10.38%; P more than 0.05), normalization of alanine aminotransferase at week 48 (ETV: 75.47% vs. ETV maleate: 82.86%; P more than 0.05), and overall incidence of AE (ETV: 18.02% vs. ETV maleate: 17.43%; P more than 0.05). Performing analysis of the therapeutic efficacies of entecavir maleate versus entecavir with a larger study population confirmed our original findings of similar efficacy and safety profiles for these two drugs in patients with HBeAg-positive CHB.

Sa1012 Virological Response Does Not Lower Liver Disease Progression Among Chronic Hepatitis B Cirrhotic Patients Treated With Long-Term Nucleos(T)Ide-Analogue

Background: A large number of chronic hepatitis B patients with cirrhosis are on long-term nucleos(t)ide-analogue therapy. The impact of anti-viral treatment on liver disease progression among these cirrhotics remains to be characterized. Method: CHB cirrhotics treated with long-term LAM-ADV combination therapy or ETV monotherapy in our center were enrolled and followed for outcomes. Liver disease progression was defined as liver decompensation, development of hepatocellular carcinoma and death. Cumulative probability of virological and clinical outcomes was evaluated by Kaplan–Meier analysis, logrank test and Cox-regression analysis. Results: A total of 264 cirrhotics (compensated disease 87.5%) fulfilled enrollment criteria, of which 143 and 121 were treated with LAM-ADV and ETV respectively. In LAM-ADV group, 57 (39.9%) were HBeAg-positive, mean HBV-DNA was 5.8 (5.5–6.1) log IU/mL, mean LAM-ADV duration was 41.4 (14.5–68.3) months and mean follow-up was 72.8 (31.5–114.1) months. In ETV group, 48 (39.7%) were HBeAg-positive, mean HBV-DNA was 4.4 (4.1–4.7) log IU/mL, mean ETV duration was 33.3 (15.2–51.4) months and mean follow-up was 45.7 (16.8–74.6) months. Among LAM-ADV group, cumulative probability of (a) virological response were 59.9%, 92.2%, 95.6% and (b) liver disease progression was 4.5%, 17.6%, 32.9%, at year 1, 3 and 5 respectively. Among ETV group, cumulative probability of (a) virological response was 74.5%, 94.8%, 100% and (b) liver disease progression was 7.8%, 12.5%, 17.7% at year 1, 3 and 5 respectively. The probability of liver disease progression was not influenced by virological response (p = 0.174). When stratified by treatment group, virological response again did not impact on the cumulative probability of liver disease progression (LAM-ADV group: p =0.173 and ETV group: p =0.433). Among virological responders, there was also no difference between LAM-ADV combination and ETV monotherapy group (p =0.199). Cox-regression showed baseline decompensated disease status was a significant predictor of disease progression (HR 4.96; 95%CI 2.61–9.44; p < 0.01) whereas virological response had no impact (p = 0.196). Conclusion: Among cirrhotics treated with long-term LAM-ADV combination therapy or ETV monotherapy, despite the excellent anti-viral efficacy, there was still significant probability of liver disease progression. LAM-ADV combination or ETV-monotherapy induced virological response did not lower the probability of liver disease progression in these patients.

742 EFFICACY AND SAFETY OF ENTECAVIR (ETV) PROPHYLAXIS IN INACTIVE HBV CARRIERS WHO UNDERWENT CHEMOTHERAPY FOR SOLID OR HAEMATOLOGICAL CANCER: INTERIM ANALYSIS OF A COHORT STUDY

seroconversion rate at 48 weeks were 40.7% and 37% in PEG-IFN a-2a group, respectively, which are both higher than those in ETV group (16.7% and 13.3%, P all 0.05). The mean qHBsAg level in PEG-IFN a-2a group declined over time during treatment. The qHBsAg level at 48 weeks was significantly lower than that in ETV group ((2866.0±2580.4) vs (4335.8±2650.0) IU/mL, P = 0.027). A greater HBsAg decline was observed in HBeAg seroconverters compared with nonseroconverters. The decline from baseline was significantly different between seroconverters and non-seroconverters especially at 36 weeks ((1763.4±3116.2) vs (1333.5±2483.4) IU/mL, P = 0.036), and 48 weeks (1979.6±2897.1) vs (1631.8±2395.8) IU/mL, P = 0.01) as well. Although 11.1% of participants in PEG-IFN a-2a group developed HBVDNA relapse (>500 copies/mL) at 48 weeks, which did not occur in ETV group, there was no statistical difference between the two groups at virological relapse rate. Conclusion: For HBeAg-positive CHB patients who fail to achieve satisfactory endpoint with ETV therapy, sequential PEG-IFN a-2a treatment is an appropriate treatment option to achieve sustained immune control.

Risk Factors of Gene-Resistant Mutations in Different Nucleosides

To explore the risk factors of gene-resistant mutations during nucleotide treatment. A total of 320 patients with CHB were randomly divided into lamivudine (LAM, 107 cases), adefovir (ADV, 106 cases) and entecavir (ETV, 107 cases) groups, and P gene mutations of HBV were regularly detected. Kaplan-Meier and Cox regression analysis were performed. There was no statistical significance in baseline data between the three groups. The gene-resistant mutation rates were 20.0%, 0.0% and 0.0% one year later, 37.1%, 3.8% and 0.0% two years later, 42.8%, 9.5% and 0.9% three years later, and 64.7%, 25.7% and 0.9% four years later in LAM, ADV and ETV groups, respectively. In LAM group, rtL180M combined with rtM204V mutations accounted for 32.7% and in ADV group, rtN236T mutation accounted for 12.3%. The gene-resistant mutation rate was the most strong in LAM group. With an extension of time, gene-resistant mutation rates are increased, but it is the highest in LAM group and the lowest in ETV group. Family history, the negative conversion time of HBV DNA and different nucleosides are independent risk factors of gene-resistant mutations.