Comparison of the Effects of Telbivudine and Entecavir Treatment on Estimated Glomerular Filtration Rate in Patients with Chronic Hepatitis B

Background/Aims

The aim of this study was to evaluate the estimated glomerular filtration rate (eGFR) during telbivudine (LdT) versus entecavir (ETV) treatment in chronic hepatitis B (CHB) patients with underlying comorbidities such as diabetes mellitus (DM), hypertension, and cirrhosis.

Methods

From 2010 to 2012, 116 CHB patients treated with LdT and 578 treated with ETV were compared in this real-practice cohort. The mean changes in eGFR (Modification of Diet in Renal Disease [MDRD] formula) from baseline to months 6, 12, and 18 were analyzed using a linear mixed model.

Results

In LdT-treated patients, the mean eGFR increased by 7.6% at month 18 compared with the eGFR at baseline (MDRD formula in mL/min/1.73 m²). However, in ETV-treated patients, the mean eGFR decreased by 4.1% at month 18 compared with the eGFR at baseline. In the LdT-treated patients with DM, hypertension, cirrhosis or low eGFR <90 mL/min/1.73 m², the mean eGFR showed a steady improvement, whereas the mean eGFR was reduced in the same subgroups of ETV-treated patients.

Conclusions

The eGFR gradually increased over time during LdT treatment, especially in patients with mild abnormal eGFR at baseline, and in those with DM, hypertension, and cirrhosis, whereas a reduction in eGFR was seen with ETV treatment.     

恩替卡韦治疗乙型肝炎肝硬化伴肝源性糖尿病的临床疗效研究

目的探究恩替卡韦治疗乙型肝炎肝硬化伴肝源性糖尿病的临床疗效。方法选取该院于2017年1月—2019年2月收治的160例乙型肝炎肝硬化伴肝源性糖尿病患者作为该次的研究对象,采用随机数表法将其平均分为两组,对照组患者采取常规护肝及降糖药物治疗,观察组患者在常规药物治疗的基础上联合恩替卡韦进行治疗,治疗后对比两组患者的肝功能各项指标以及血糖水平改善情况。结果采用不同药物进行治疗后,观察组患者的谷丙转氨酶(ALT)、天门冬氨酸氨基转移酶(AST)、血清白蛋白(ALB)、总胆红素(TBIL)等各项肝功能指标均优于对照组,差异有统计学意义(P<0.05);观察组患者的空腹血糖、餐后2 h血糖以及糖化血红蛋白的水平均明显低于对照组,差异有统计学意义(P<0.05)。结论在对乙型肝炎肝硬化伴肝源性糖尿病患者进行治疗时,在常规药物治疗的基础上联合恩替卡韦进行治疗,能够有效改善患者的各项肝功能指标,具有更高的降糖效果,值得广大医院进行推广和研究。     

Hepatitis B Core Antigen Expression in Hepatocytes Reflects Viral Response to Entecavir in Chronic Hepatitis B Patients

Background/Aims

Hepatitis B core antigen is known to be a major target for virus-specific T cells and also reflects the progression of liver dissease and viral replication. Hepatitis B core antigen expression in hepatocytes leads to altered histological activity, viral replication, and immune response. The purpose of this study is to evaluate whether the topographical distribution of hepatitis B core antigen expression can predict the viral response to entecavir in patients with chronic hepatitis B.

Methods

We enrolled 91 patients with treatment-naïve chronic hepatitis B. All the patients underwent liver biopsy, and the existence and pattern of hepatitis B core antigen evaluated by immunohistochemistry. All patients received 0.5 mg of entecavir daily following a liver biopsy. We checked the viral response at 3, 6, and 12 months during antiviral therapy.

Results

Of the 91 patients, 64 (70.3%) had hepatitis B core antigen expression. Of the subcellular patterns, the mixed type was dominant (n=48, 75%). The viral response was significantly higher in the hepatitis B core antigen-negative group than in the hepatitis B core antigen-positive group (88.9% and 54.7%, respectively; p=0.001) after 12 months of entecavir therapy.

Conclusions

Chronic hepatitis B patients who are hepatitis B core antigen-negative have a better response to entecavir therapy than do hepatitis B core antigen-positive patients.     

Seroconversion of Hepatitis B Envelope Antigen (HBeAg) by Entecavir in a Child with Chronic Hepatitis B

Hepatitis B virus (HBV) infection is a worldwide health problem. Consensus guidelines for the treatment of chronic HBV in children have not been established, and indications for antiviral therapy in adults with chronic HBV infection may not be applicable to children. The medications that are Food and Drug Administration approved for the treatment of children with HBV include interferon (IFN)-alpha and lamivudine. Nondetectable serum HBV deoxyribonucleic acid, Hepatitis B envelope antigen (HBeAg) loss, and HBeAg seroconversion following 1 year duration of entecavir treatment. A review of the literature of entecavir treatment of chronic hepatitis B in children is also provided.     

Comparison of First-year Results of Tenofovir and Entecavir Treatments of Nucleos(t)ide-naive Chronic Hepatitis B Patients with Hepatosteatosis

Background/Aim:Hepatic steatosis may influence the response to antivirals in chronic hepatitis B patients. This study aimed to compare the efficacy of entecavir and tenofovir in nucleos(t) ide-naive chronic hepatitis B patients with hepatosteatosis during 48 weeks of therapy.Results:Of the 63 patients, 21 received entecavir and 42 received tenofovir. Baseline characteristics of the patients were similar except for body mass index. At the end of week 48, there was no statistically significant difference between tenofovir and entecavir treatment regarding total HBV-DNA negativity and alanine transferase normalization in patients with chronic hepatitis B and hepatosteatosis.Conclusions:Entecavir and tenofovir are similarly effective in nucleos(t)ide-naive chronic hepatitis B patients with hepatosteatosis after 48 weeks of therapy.     

Quasispecies and Pre-Existing Drug-Resistant Mutations of Hepatitis B Virus in Patients with Chronic Hepatitis B

Background/Aims

To investigate pre-existing hepatitis B virus (HBV) quasispecies and the genotypic evolution of several variants.

Methods

From six patients with lamivudine (LAM) failure, serum samples at pretreatment, 6 months of LAM therapy, and virologic breakthrough were obtained. One hundred clones with HBV inserts in each patient were sequenced at each time point. Pretreatment serum samples were also analyzed from six patients who achieved good responses to LAM therapy.

Results

Among the six patients with LAM failure, the analysis of 100 clones from patient 1 revealed the substitutions L180M in 1% of clones and V173L in 2% of clones. Patient 2 had substitutions of L80V, W153Q, and L180M. In patient 3, mutations conferring resistance to adefovir at V84I (5%), I169L (1%), and N236H (7%) and entecavir at S202G (2%) were detected. Patient 4 had mutations at T128N (1%), I169L (1%), V173L (2%), A181V (1%), and Q215H (1%). In patient 5, M204V/I was detected in 1% and 2% of clones, respectively. L80I and V173L were also identified in patient 6. In the six patients who responded to LAM, the degree of overall quasispecies was less than those with LAM failure.

Conclusions

Various HBV quasispecies associated with drug resistance existed before treatment, and the quasispecies dynamically changed through LAM therapy.     

Efficacy of Entecavir and Adefovir Combination Therapy for Patients with Lamivudine- and Entecavir-Resistant Chronic Hepatitis B

Background  

The optimal treatment of patients with chronic hepatitis B (CHB) who develop resistance to both lamivudine (LMV) and entecavir (ETV) after sequential monotherapy of LMV and ETV remains little known.     

Potential Effects of Telbivudine Versus Entecavir on Renal Function in Patients With Chronic Hepatitis B Virus Receiving Glucocorticoids Therapy

Data remains limited about the optimal nucleos(t)ide analogue therapy for patients infected with hepatitis B virus (HBV) while treated with glucocorticoids because of kidney diseases. We aim to evaluate the safety and efficacy of long‐term antiviral therapy with telbivudine (LdT) and entecavir (ETV) in this specific population. In this prospective randomized controlled study, a total of 60 patients with both kidney diseases and chronic hepatitis B were randomly divided into LdT group and ETV group. We analyzed changes in estimated glomerular filtration rate (eGFR), variation in HBV DNA, seroconversion of hepatitis B e antigen (HbeAg) and hepatitis B surface antigen (HBsAg). During the 18 month follow‐up period, serum HBV DNA load was decreased significantly at 3, 6, 12, 18 months, compared to the pre‐treatment value in both LdT and ETV cohorts. No patients achieved HBeAg loss‐seroconversion or HBsAg loss‐seroconversion with ETV therapy whilst one patient experienced HBeAg and HBsAg loss‐seroconversion with LdT therapy. No significant changes in eGFR were seen in patients with ETV therapy compared to baseline. However, eGFR increased 7.43, 18.97 mL/min/1.73m², respectively at 12 and 18 months in LdT group and the changes were significant compared to baseline. Further analysis also demonstrated that eGFR significantly improved 11.8, 23.25 mL/min/1.73m² at 12 and 18 months in LdT group for patients with impaired renal function. LdT is superior to ETV in patients with chronic hepatitis B and kidney diseases because of the renal protection it confers by increasing eGFR.     

Entecavir Versus Lamivudine Therapy for Patients With Chronic Hepatitis B-Associated Liver Failure: A Meta-Analysis

Background:

Nucleoside analogues are recommended as antiviral treatments for patients with hepatitis B virus (HBV)-associated liver failure. Clinical data comparing entecavir (ETV) and lamivudine (LAM) are inconsistent in this setting.

Objectives:

To compare the efficacy and safety of ETV and LAM in patients with chronic hepatitis B (CHB)-associated liver failure.

Patients and Methods:

A literature search was performed on articles published until January 2014 on therapy with ETV and LAM for patients with CHB-associated liver failure. Risk ratio (RR) and mean difference (MD) were used to measure the effects. Survival rate was the primary efficacy measure, while total bilirubin (TBIL), prothrombin activity (PTA) changes and HBV DNA negative change rates were secondary efficacy measures. A quantitative meta-analysis was performed to compare the efficacy of the two drugs. Safety of ETV and LAM was observed.

Results:

Four randomized controlled trials and nine retrospective cohort studies comprising a total of 1549 patients were selected. Overall analysis revealed comparable survival rates between patients received ETV and those received LAM (4 weeks: RR = 1.03, 95%CI [0.89, 1.18], P = 0.73; 8 weeks: RR = 0.98, 95% CI [0.85, 1.14], P = 0.84; 12 weeks: RR = 0.98, 95% CI [0.90, 1.08], P = 0.70; 24 weeks: RR = 1.02, 95% CI [0.94, 1.10], P = 0.66). After 24 weeks of treatment, patients treated with ETV had a significantly lower TBIL levels (MD = -37.34, 95% CI [-63.57, -11.11], P = 0.005), higher PTA levels (MD = 11.10, 95% CI [2.47, 19.73], P = 0.01) and higher HBV DNA negative rates (RR = 2.76, 95% CI [1.69, 4.51], P < 0.0001) than those treated with LAM. In addition, no drug related adverse effects were observed in the two treatment groups.

Conclusions:

ETV and LAM treatments had similar effects to improve 24 weeks survival rate of patients with CHB-associated liver failure, but ETV was associated with greater clinical improvement. Both drugs were tolerated well during the treatment. It is suggested to perform further studies to verify the results.     

Distribution of Hepatitis B Virus Genotypes in Azerbaijani Patients With Chronic Hepatitis B Infection

Background:

Hepatitis B virus (HBV) has been classified into ten genotypes (A-J) based on genome sequence divergence, which is very important for etiological and clinical investigations. HBV genotypes have distinct geographical distributions worldwide.

Objectives:

The aim of this study was to investigate the distribution of HBV genotypes among Azerbaijani patients with chronic hepatitis B, came from the Republic of Azerbaijan country to Iran to receive medical care.

Patients and Methods:

One hundred and three patients with chronic HBV infection, referred to hospitals related to Iran University of Medical Sciences and Tehran Hepatitis Center from August 2011 to July 2014, were enrolled in this cross sectional study. About 3-milliliter of peripheral blood was taken from each patient. After viral DNA extraction, HBV genotypes were tested using the INNO-LiPA™ HBV kit (Innogenetics, Ghent, Belgium). HBV genotyping was confirmed using sequencing of hepatitis B surface antigen (HBsAg) and polymerase (pol) regions of HBV.

Results:

The mean age of patients was 35.9 ± 11.7 years (19-66). Of 103 patients, 72 (69.9%) were male. In the present study, the predominant HBV genotype was D (93.2%) followed by genotype A (5.8%) and concurrent infection with A and D genotypes (0.97%).

Conclusions:

The main and frequent HBV genotype among Azerbaijani patients with chronic hepatitis B virus infection was genotype D followed by genotype A.     

Intrahepatic Expression of C-C Motif ligand 5 in Patients with Chronic Hepatitis B

Background: C-C motif ligand 5 (CCL5) is reported to play a key role in acute and chronic liver diseases. However, the association between CCL5 and chronic hepatitis B (CHB) remains to be explored. We aimed to investigate the CCL5 expression in the liver tissues of CHB patients and compared the CCL5 expression among CHB patients with different stages of liver inflammation and fibrosis. Methods: Liver tissue specimens from 51 CHB patients who underwent liver biopsy and twelve healthy liver donors were included in the present study. CCL5 expression in the liver tissues was analyzed using immunohistochemistry. The hepatic inflammation grades and fibrotic stages of CHB patients were assessed by the Scheuer classification system. Results: Livers of CHB patients exhibited significantly accumulated CCL5+ cells when compared to those of healthy controls (42.80 ± 4.37 vs. 7.25 ± 0.99/HPF, P < .001). CHB patients with higher hepatic inflammation grades had more CCL5+ cells in their livers than those with lower grades (P < .05). However, the numbers of CCL5+ cells were not correlated with the fibrotic stages in CHB patients (r = .073, P = .61). The number of CCL5+ cells in the liver tissues of CHB patients was positively correlated with alanine transaminase levels (r = .278, P = .041) and aspartate aminotransferase levels (r = .328, P = .009). Conclusions: CHB patients have a significant accumulation of CCL5+ cells in the liver, and CCL5 may play a pathological role in hepatic inflammation of CHB.     

Effects of Long-Term Tenofovir and Entecavir Treatment on Bone Mineral Density in Patients with Chronic Hepatitis B

BackgroundWe aimed to investigate the long-term effects of tenofovir disoproxil fumarate and entecavir treatment on bone mineral density and evaluated the fracture risk assessment tool score in patients with chronic hepatitis B.MethodsA total of 58 chronic hepatitis B patients treated with tenofovir disoproxil fumarate (n = 40) and entecavir (n = 18) were included in this prospective study from 2012 to 2016. To evaluate bone mineral density, dual-X-ray absorptiometry, fracture risk assessment tool, and laboratory examinations were performed in all patients first at baseline and second at the end of the study.ResultsAge, sex, body mass index, fibrosis score, and viral load were similar in both groups. The mean follow-up was 33 months in the tenofovir disoproxil fumarate group and 31 months in the entecavir group. In patients treated with entecavir, there was no statistically significant difference between baseline and second bone mineral density including lumbar spine (L) and total hip T score. In patients treated with tenofovir disoproxil fumarate, there was a significant difference in the second bone mineral density compared with baseline bone mineral density for L3 (P = .033) and the major fracture risk assessment tool score (P = .03). When patients were divided into 3 groups (normal bone mineral density, osteopenic, and osteoporotic), there was a significant increase in the number of osteopenic patients in the total hip T score after tenofovir disoproxil fumarate treatment (P = .034).ConclusionOur results suggest a decrease in the bone mineral density for lumbar spine (L3), an increase in the number of patients with hip osteopenia, and major fracture risk assessment tool score after long-term tenofovir disoproxil fumarate treatment in patients with rechronic hepatitis B.     

High Rates of Viral Suppression After Long-term Entecavir Treatment of Asian Patients With Hepatitis B e Antigen-Positive Chronic Hepatitis B

There are limited data on the effects of long-term entecavir therapy in Asian patients with chronic hepatitis B (CHB). We performed a post hoc analysis of 94 Asian hepatitis B e antigen-positive (HBeAg+), nucleos(t)ide analogue-naive patients who received 5 years of therapy with entecavir (up to 2 years in study ETV-022 and the remainder in study ETV-901). Among patients completing week 240, 95% (63 of 66) had levels of hepatitis B virus DNA <300 copies/mL, and 76% (50 of 66) had normalized levels of alanine aminotransferase. In addition to patients who achieved a serologic response during ETV-022, a further 40% (26 of 65) achieved HBeAg loss, and 18% (12 of 65) underwent HBeAg seroconversion through year 5 of entecavir therapy. No resistance to entecavir was detected, and the safety profile was consistent with previous reports. The long-term efficacy and safety of entecavir are therefore comparable between Asians and the overall population of HBeAg+ patients with CHB.     

恩替卡韦治疗慢性HBV感染者KIR基因多态性与疗效的相关性研究

目的探讨慢性HBV感染者杀伤细胞免疫球蛋白样受体(killer immunoglobulin-like receptor,KIR)基因多态性及其与应用恩替卡韦疗效差异相关性。方法采用序列特异性引物聚合酶链反应(PCR-SSP)法,对60例应用恩替卡韦治疗的慢性HBV感染者(试验组)和60例健康对照者(对照组)的KIR基因进行基因分析,比较试验组和对照组的差异。60例患者中18例为治疗完全应答者(完全应答组),42例为非完全应答者(非完全应答组),比较2组之间差异。结果通过试验组和对照组的16种KIR基因分析,框架基因KIR2DL4、3DL2、3DL3和3DP1存在于所有个体中,其基因频率均为1.0。试验组KIR 2DS2和KIR2DS3基因型频率高于对照组(P值依次为0.038和0.035);完全应答组KIR2DS1、KIR3DS1和KIR2DL5基因型频率高于非完全应答组(P值依次为0.010、0.029和0.018)。结论 KIR2DS2、KIR2DS3可能是HBV的易感基因型,KIR2DS1、KIR3DS1、KIR2DL5可能与恩替卡韦抗HBV治疗有效应答有关。