Entecavir Treatment In Patients Research Articles

Retrospective cohort evaluation study in terms of cardiovascular and metabolic diseases in chronic hepatitis B patients.

Chronic hepatitis B (CHB) and nucleotide analogues [entecavir (ETV) and tenofovir disoproxil fumarate (TDF)] used in its treatment have been shown to affect metabolic parameters in many studies. In this study, we aimed to investigate the effects of metabolic events associated with CHB and nucleotide analogues (NAs) used in CHB treatment on ischemic heart diseases (IHD) and cardiovascular diseases (CVD). This retrospective study was conducted between June 2022 and January 2024 with a total of 241 patients diagnosed with non-cirrhotic CHB in the gastroenterology outpatient clinic, 96 of whom did not receive hepatitis B treatment, 110 of whom received TDF, and 35 of whom received ETV treatment. Patients were evaluated in terms of metabolic, CVD, and hepatology depending on whether they received antiviral treatment or not. In our study, the triglyceride-glucose (TyG) index and triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C) were calculated in patients to evaluate potential risk factors for CVD. Again, while the total cholesterol-to-HDL-C ratio (TC/HDL-C), which is associated with CVD\IHD, was evaluated, the '4-factor fibrosis index' (FIB-4) score, which is a non-invasive indicator of liver fibrosis, was also evaluated. Diabetes mellitus (DM), fasting blood sugar (FBS), oral antidiabetic drug (OAD) usage rate, and insulin usage rate were high in patients receiving ETV treatment. The TyG index of patients receiving ETV was higher than patients in the other group (p = 0.035; p<0.05). It was determined that the probability of detecting ETV treatment in patients with a TG/HDL-C ratio of ≥1.82 cut-off value was 4.250 times higher. The odds ratio for TG/HDL-C measurements was 4.250 (95% CI: 1.384-13.054). FIB-4 score, which is a non-invasive indicator of liver fibrosis, was found to be higher in patients receiving ETV than in other groups. In patients with CHB, a relationship was observed between markers used to predict CVD risk, such as the TyG index and TG/HDL-C ratio. The group with high levels of these two markers and a high potential for developing CVD was patients receiving ETV treatment. In this first study in the literature showing the relationship between CHB and CVD, we found that the relative risk of CVD was increased in patients using ETV.

CAGE-B and SAGE-B models better predict the hepatitis B virus-related hepatocellular carcinoma after 5-year of entecavir treatment than PAGE-B.

The PAGE-B model consists of variables at the initiation of antiviral therapy (AVT), whereas the SAGE-B and CAGE-B models consist of variables after 5 years of AVT. We compared the predictive accuracy of three risk prediction models for hepatocellular carcinoma (HCC) development after 5 years of AVT in patients with chronic hepatitis B (CHB). A total of 1,335 patients who initiated entecavir (ETV) treatment between 2006 and 2011 and were followed up for more than 5 years were enrolled in the stduy. At ETV initiation, the median age of the patients was 49 years and the median of the PAGE-B model was 14. After 5 years of ETV treatment, the median SAGE-B and CAGE-B values were 6 and 6, respectively. During the study period, 93 (7.0%) patients developed HCC after 5-year treatment. In multivariate analysis, PAGE-B (hazard ratio [HR], 1.151; 95% confidence interval [CI], 1.087-1.219), SAGE-B (HR, 1.340; 95% CI, 1.228-1.463), and CAGE-B (HR, 1.327; 95% CI, 1.223-1.440) models independently predicted HCC development after 5 years of treatment (all P<0.001). The high-risk groups of the three risk prediction models showed a significantly higher risk of HCC development compared to the medium- and low-risk groups (all P<0.05). The areas under the receiver operating characteristic curves of the SAGE-B (0.772-0.844) and CAGE-B (0.785-0.838) models were significantly higher than those of the PAGE-B model (0.696-0.745) in predicting HCC development after 5 years of treatment (all P<0.05). The SAGE-B and CAGE-B models might be better than the PAGE-B model in predicting HCC development after 5 years of ETV treatment in patients with CHB.

Lower risk of hepatocellular carcinoma with tenofovir than entecavir treatment in subsets of chronic hepatitis B patients: an updated meta-analysis.

Previous smaller meta-analyses comparing the incidence of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients treated with tenofovir disoproxil fumarate (TDF) versus entecavir (ETV) provided controversial results. This updated meta-analysis aimed to reliably identify any difference in the HCC incidence between TDF-treated or ETV-treated CHB patients in general or in specific subgroups. PubMed, EMBASE, Web of Science, and Cochrane Library were systematically searched for relevant studies with hazard ratios (HRs) for HCC between TDF-treated and ETV-treated CHB patients. Retrieved dates ranged from January 2009 to October 2021. HRs with or without adjustment were pooled with random-effects model. Twenty-four comparative studies involving 37771 CHB patients treated with TDF and 72094 treated with ETV were included. TDF was associated with lower risk of HCC compared with ETV, with pooled unadjusted HR of 0.76 (95% confidence interval [CI]: 0.67-0.86) (24 studies) and adjusted HR of 0.81 (95% CI: 0.72-0.91) (21 studies). In propensity score matching cohorts, the TDF superiority was confirmed for unadjusted HR 0.83 (95% CI: 0.71-0.97) (14 studies) and was close to significance for adjusted HR (0.78, 95% CI: 0.58-1.04) (8 studies). Subgroup analyses showed that TDF was associated with lower HCC risk than ETV treatment in CHB patients who were from Asia (adjusted HR: 0.76, 95% CI: 0.66-0.87; 15 studies) or nucleos(t)ide naïve (adjusted HR:0.74, 95% CI: 0.65-0.84; 18 studies). Current evidence from a sizable population suggests that TDF is associated with significantly lower HCC risk compared with ETV treatment in patients who are from Asia and/or nucleos(t)ide naïve.

Health-related quality of life improves after entecavir treatment in patients with compensated HBV cirrhosis.

Antiviral therapy is effective in decreasing disease progression in HBV cirrhosis. However, the long-term effect of antiviral therapy on health-related quality of life (HRQoL) in patients with compensated HBV cirrhosis is unknown. The patients with compensated HBV cirrhosis enrolled in a randomized controlled trial of entecavir-based therapy were recruited in the present study, if they had HRQoL score at 5-year follow-up or who developed liver-related events (LRE) during follow-up were included. HRQoL was measured with 36-Item Short-Form Health Survey (SF-36) and EuroQol-5D (EQ-5D) at baseline and yearly during follow-up. LRE was defined as the development of decompensation, HCC, or death. A total of 161 patients were included in the present study, with a median age of 48.0 (41.0, 53.0) years, 77.6% being male and 37.2% being HBeAg-positive. During 5years, 45 patients developed LRE. All eight dimensions of SF-36 were significantly improved after 5years of antiviral therapy (all p < 0.001), with all dimensions improved more than five points except for physical functioning. Proportion of patients reporting no problems in all five dimensions in EQ-5D increased from 57.8 to 72.0%; visual analogue scale (VAS) and utility index (UI) increased significantly (VAS 79.8 ± 16.4 to 84.4 ± 13.2, UI 0.91 ± 0.13 to 0.95 ± 0.10, both p < 0.001). HRQoL improved or kept stable in the majority of patients who had LRE during follow-up, even stratified by Baveno VI criteria for clinically significant portal hypertension. After 5years of ETV treatment, HRQoL significantly improved in patients with compensated HBV cirrhosis. (NCT01943617, NCT02849132).

Effect of Entecavir on the Intestinal Microflora in Patients with Chronic HepatitisB: A Controlled Cross-Sectional and Longitudinal Real-World Study.

IntroductionThis study aimed to analyze the diversity of intestinal flora in patients with chronic hepatitis B (CHB) and investigate the effect of entecavir on the intestinal flora in these patients.MethodsThirty patients with CHB and 30 healthy controls were recruited from the Department of Infectious Diseases and Department of Gastroenterology of Shanghai Tongji Hospital between January 2017 and December 2018. Stool samples were collected for the detection of intestinal flora by high-throughput sequencing. Patients with CHB received antivirus therapy with entecavir for 8 weeks. The biochemical and virological responses were assessed and the intestinal flora were compared.ResultsAfter entecavir treatment, the blood levels of alanine aminotransferase (ALT), interleukin-6 (IL-6), IL-8, tumor necrosis factor (TNF), and hepatitis B virus (HBV) DNA reduced significantly in patients with CHB and the species abundance of intestinal flora increased markedly. In patients with CHB, the unique genera included Butyrivibrio, Phaseolus acutifolius, and Prevotellaceae NK3B31 group before treatment and Howardella, Candidatus Stoquefichus, Citrobacter, Dysgonomonas, Faecalicoccus, Methanobrevibacter, Mitsuokella, Mobilitalea, Succinivibrio, Gluconobacter, and Plesiomonas after treatment. The abundance of the following genera increased significantly after entecavir treatment in patients with CHB: Clostridium sensu stricto 1, Erysipelotrichaceae UCG-007, and Intestinibacter. The abundance of Streptococcus, Atopobium, and Murdochiella reduced markedly after entecavir treatment in patients with CHB.ConclusionAfter 8-week entecavir treatment, the blood biochemical, immunological, and virological responses improved significantly, the species abundance of intestinal flora increased markedly, and there were unique genera in patients with CHB before and after treatment.Electronic supplementary materialThe online version of this article (10.1007/s40121-020-00355-w) contains supplementary material, which is available to authorized users.

Tenofovir Treatment Has Lower Risk of Hepatocellular Carcinoma than Entecavir Treatment in Patients with Chronic Hepatitis B: A Systematic Review and Meta-Analysis

Purpose: Tenofovir (TDF) and entecavir (ETV) are both equally recommended as first-line treatments for patients with chronic hepatitis B (CHB). They have comparable efficacy in virologic response, but their effect on the development of hepatocellular carcinoma (HCC) in CHB is controversial. Therefore, we aimed to compare TDF and ETV evaluating the risk of HCC development in CHB patients. Methods: A systematic literature search was conducted up to November 2019 in MEDLINE/PubMed, SCOPUS, and Web of Science databases without language and time restrictions. DerSimonian and Laird random-effects models were used to estimate combined hazard ratios (HRs) and 95% CIs. Results: Seven studies containing 35,785 participants were included in this systematic review and meta-analysis. The pooled HR (95% CI) of HCC in the patients who used TDF versus patients who used ETV was 0.75 (0.56–0.96). There was no significant heterogeneity detected among the included studies results (I² = 47.5%). There was no significant publication bias detected among the included studies (Begg’s p = 0.88 and Egger’s regression test p = 0.96). Conclusions: Evidence to date suggests that TDF treatment is associated with significantly fewer cases of HCC when compared to ETV.

LBO-03-Tenofovir treatment has lower risk of hepatocellular carcinoma than entecavir treatment in patients with chronic hepatitis B

LBO-03-Tenofovir treatment has lower risk of hepatocellular carcinoma than entecavir treatment in patients with chronic hepatitis B

The Effect of Entecavir Therapy on Immune Status in Chronic Hepatitis B Patients.

Entecavir (ETV) is an antiviral medication effective in suppressing hepatitis B virus (HBV) replication and improving liver function. However, the relationship between antiviral effect and immune modulation after ETV therapy is not clearly understood. The objective of this study is to investigate the immunoregulatory effect of ETV treatment in patients with chronic hepatitis B (CHB). The frequencies of immune cells, including IFN-γ-producing CD4+ and CD8+ T cells, Th9 cells, regulatory T (Treg) cells, and myeloid-derived suppressor cells (MDSC) were determined in the peripheral blood from treatment-naïve and ETV-treated CHB patients. The plasma levels of IL-10, TGF-β, IL-9, TNF-α, IFN-γ, and Arg-1 were measured using enzyme-linked immunosorbent assay. The results showed that ETV treatment significantly reduced the levels of liver function indices as well as HBV DNA loads in CHB patients. However, no significant difference in the immune cells percentage was found between the treatment-naïve and ETV-treated patients. Additionally, ETV treatment did not influence the production of TGF-β, IL-9, Arg-1, IFN-γ, and TNF-α. In contrast, the level of IL-10 was remarkably reduced after ETV therapy. IL-10 was a more sensitive effector to ETV-induced inhibition of HBV replication in chronic HBV patients.

Long-term outcome of entecavir treatment of nucleos(t)ide analogue-naïve chronic hepatitis B patients in Japan.

We determined the antiviral potency and viral breakthrough rate after 10years of continuous entecavir treatment in patients with chronic hepatitis B (CHB) infection. The cumulative rates of undetectable hepatitis B virus DNA (HBV-DNA, < 2.1logcopies/mL), alanine aminotransferase (ALT) normalization, hepatitis B e antigen (HBeAg) seroclearance, hepatitis B surface antigen (HBsAg) seroclearance, and viral breakthrough of 1094 nucleos(t)ide analogue-naïve CHB patients (HBeAg-positive: 47%) who were on continuous entecavir treatment for 10years were calculated. The median age was 50years and follow-up period was 5.5years, with 999, 804, 591, 390, 182 and 87 patients followed up for at least 1, 3, 5, 7, 9 and 10years, respectively. Incremental increases were noted in the rates of undetectable HBV-DNA, ALT normalization, HBeAg seroclearance, and HBsAg seroclearance, reaching 96, 79, 38 and 3.7%, respectively, by the tenth year. The mean decline in HBsAg level from baseline was - 0.08logIU/mL/year. Multivariate analysis identified HBsAg level and genotype (A) as independent predictors of HBsAg seroclearance. Sixteen patients experienced viral breakthrough. The cumulative percentages of patients with viral breakthrough analyzed by the Kaplan-Meier test were 1.5 and 2.5% at years 5 and 10, respectively. There were no serious adverse events during treatment. Long-term entecavir treatment of nucleos(t)ide analogue-naïve CHB patients was associated with an excellent viral response and a low rate of entecavir-resistant mutations at 10years. Baseline HBsAg levels and genotype were predictors of HBsAg seroclearance during entecavir treatment.

Changes of FibroScan, APRI, and FIB-4 in chronic hepatitis B patients with significant liver histological changes receiving 3-year entecavir therapy.

Noninvasive fibrosis tests have been used widely for evaluation of liver fibrosis in patients with chronic hepatitis B (CHB). We aimed to investigate the influence of antiviral treatment on FibroScan, APRI, and FIB-4 in CHB patients with significant liver histological changes (SLHC) defined as inflammatory grade≥A2 and/or fibrosis stage≥F2. A total of 104 CHB patients with SLHC at the baseline were included. FibroScan, APRI, and FIB-4 values were compared before and after 3-year entecavir (ETV) treatment. Liver stiffness measurement values decreased significantly after 3-year ETV treatment in cirrhosis group (from 13.6 to 9.6kPa, p=0.018), significant fibrosis group (from 8.4 to 5.8kPa, p=0.001), and mild fibrosis group (from 5.5 to 4kPa, p<0.001). APRI decreased significantly after 3-year ETV treatment in patients with cirrhosis (from 0.80 to 0.25, p<0.001), patients with significant fibrosis (from 0.54 to 0.24, p<0.001), and those with mild fibrosis (from 0.35 to 0.23, p<0.001). FIB-4 decreased significantly after 3-year ETV treatment in patients with cirrhosis (from 1.27 to 0.81, p=0.007) and significant fibrosis (from 1.12 to 0.78, p<0.001), while did not decrease significantly in patients with mild fibrosis (from 0.90 to 0.80, p=0.389). FibroScan, APRI, and FIB-4 values decreased significantly after 3-year ETV treatment in CHB patients, whichindicates that these noninvasive fibrosis tests might be useful for monitoring regression of liver fibrosis and assessing treatment efficacy during long-term ETV treatment.

LIVER FBROSIS RESPONSE TO ENTECAVIR TREATMENT IN PATENTS WITH CHRONIC ACTVE HEPATTS B

Background: While biochemical and virological responses are clearly proved with anti HBV therapy, the response in liver fibrosis was still uncertain. In Vietnam, data about the improve in liver fibrosis was still very limited. This study was aimed at assessing the response in liver fibrosis, determined by ARFI, to entecavir treatment in patients with chronic active hepatitis B. Patients and methods: 92 patients with chronic active hepatitis B were enrolled. All received entecavir 0.5 mg a day and followed in 24 months. Liver fibrosis was determined by technique of Acoustic Radiation Forced Imaging (ARFI) after 3, 6, 12 and 24 months. Results: improves in liver fibrosis were found after 12 months (16.3%) and especially after 24 months (28.3%) of entecavir treatment. Age less than 60, early responses in AST and HBV DNA were the good predictors of subsequent liver fibrosis improve. Conclusion: Entecavir treatment may provide an improve in liver fibrosis, especially in long-term therapy. Key words: entecavir, HBV, liver fibrosis, ARFI

Profile of HBV polymerase gene mutations during entecavir treatment in patients with chronic hepatitis B

We investigated the efficacy of entecavir (ETV) monotherapy in 54 naïve patients and 27 lamivudine (LMV) and/or adefovir (ADV) experienced patients. Eighty-one chronic hepatitis B patients with a viral load above 4 log 10 copies/ml and high levels of serum alanine aminotransferase were treated with ETV 0.5mg daily. The viruses of patients were sequenced before ETV therapy and after every three months of ETV therapy. Eight LAM-experienced and ADV-experienced patients emerged mutations in the ETV treatment. In one of these experienced patients, the ETV-resistant mutations were detected during ETV treatment, with the virological and the biochemical breakthrough. Two LAM-experienced and ADV-naïve patients were detected mutation during 1-2 years ETV therapy. All three LAM-naïve and ADV-experienced patients were detected mutations in the ETV treatment. Five in fifty for LAM-naïve and ADV-naïve patients showed mutations in the ETV monotherapy. ETV has a high genetic barrier to resistance and the efficacy in LAM-experienced and/or ADV-experienced patients were much lower than in naïve patients.

Impact of fatty liver on hepatitis B virus replication and virologic response to tenofovir and entecavir.

We aimed to evaluate the impact of non-alcoholic fatty liver disease (NAFLD) on viral kinetics and virologic response to tenofovir and entecavir treatment in patients with chronic hepatitis B virus (HBV) infection. This study was designed as a retrospective multicenter cohort study. The impact of hepatosteatosis on pre-treatment serum HBV DNA levels and also on the virologic response to either tenofovir or entecavir at 6 and 12 months of therapy was investigated. A total of 145 cases were involved in the study [median age 40 (18-73) years, 90 (62%) males]. In multivariate analysis, it was detected that patients with NAFLD were older and had a higher body mass index (BMI) [Odds ratio (95% confidence interval) and p-value for age were 1.040 (1.003-1.079) and 0.033 and for BMI were 1.348 (1.190-1.528) and 0.0001, respectively]. When only the 43 patients who were younger than 35.5 years old and who had a BMI less than 27.59 were investigated, serum high-density lipoprotein (HDL) levels and serum HBV DNA levels were lower in patients with NAFLD in multivariate analysis [Odds ratio (95% confidence interval) and p-values for serum HDL level and HBV DNA level were 0.864 (0.061-0.980) and 0.023 and 0.995 (0.990-0.999) and 0.025, respectively]. Totally, 57 and 75 of the patients had received entecavir and tenofovir, respectively. Viral replication decreases in patients with chronic HBV infection in the presence of NAFLD, and NAFLD had no impact on the virologic response to entecavir and tenofovir treatment.

Association Between Level of Hepatitis B Surface Antigen and Relapse After Entecavir Therapy for Chronic Hepatitis B Virus Infection

We investigated the rate of relapse of hepatitis B virus (HBV) infection after entecavir therapy for chronic hepatitis B and the association between level of hepatitis B surface antigen (HBsAg) and relapse. In a retrospective study, we analyzed data from 252 patients with chronic HBV infection who were treated with entecavir and met the Asian Pacific Association for the Study of the Liver treatment stopping rules (mean time, 164 ± 45 weeks) from January 2007 through June 2011 in Taiwan. Eighty-three were hepatitis B e antigen (HBeAg)-positive, and 169 were HBeAg-negative. Patients had regular post-treatment follow-up examinations for at least 12 months. Virologic relapse was defined on the basis of serum HBV DNA >2000 IU/mL after entecavir therapy. Clinical relapse was defined as a level of alanine aminotransferase > 2-fold the upper limit of normal and HBV DNA > 2000 IU/mL. Two years after therapy ended, 42% of HBeAg-positive patients had a virologic relapse, and 37.6% had a clinical relapse; 3 years after therapy ended, these rates were 64.3% and 51.6% for HBeAg-negative patients, respectively. On the basis of Cox regression analysis, factors independently associated with virologic and clinical relapse included old age, HBV genotype C, and higher baseline levels of HBsAg for HBeAg-positive patients and old age and higher end-of-treatment levels of HBsAg for HBeAg-negative patients. In HBeAg-positive patients, risk of HBV relapse increased with age ≥ 40 years and HBsAg level ≥ 1000 IU/mL at baseline (P < .001). In HBeAg-negative patients, the combination of age (< 55 years) and HBsAg level (< 150 IU/mL) at the end of treatment was associated with a lower rate of virologic relapse (4.5% of HBeAg-negative patients had viral relapse at year 3). The decrease in level of HBsAg from month 12 of treatment until the end of treatment was greater in patients who did lose HBsAg after entecavir therapy compared with those who did not. The combination of age and level of HBsAg is associated with relapse of HBV infection after treatment with entecavir. HBsAg levels might be used to guide the timing of cessation of entecavir treatment in patients with chronic HBV infection.

Association of serum IgG N-glycome and transforming growth factor-β1 with hepatitis B virus e antigen seroconversion during entecavir therapy

Aberrant serum IgG N-glycome has been demonstrated in various autoimmune diseases and viral infections. However, the correlation between serum IgG N-glycome and cytokine is unclear. In addition, the clinical relevance of IgG glycosylation and cytokine changes in the treatment outcome of chronic hepatitis B (CHB) has never been assessed. One hundred and three treatment-naive patients with CHB and 101 healthy controls were enrolled in this retrospective cohort study. Serum samples in patients before and after 48weeks of entecavir treatment were collected. In-gel trypsinized serum IgG heavy chain was analyzed using liquid chromatography–tandem mass spectrometry. Selected ion chromatograms corresponding to 10 N-glycoforms on asparagine 297 were individually extracted to calculate the percentage of each glycoforms. Serum cytokine profiles were examined using enzyme-linked immunosorbent assay. Forty-eight weeks of entecavir treatment resulted in decreases in galactose-deficient (total G0) IgG and transforming growth factor (TGF)-β1 levels (both P<0.001) in patients with CHB. The changes in TGF-β1 (ΔTGF-β1) and IgG total G0 (Δtotal G0) levels during treatment were significantly correlated (r=0.403, P<0.001). Furthermore, higher levels of Δtotal G0 (P<0.01) and ΔTGF-β1 (P<0.001) were found in hepatitis B virus e antigen (HBeAg)-positive patients than in HBeAg-negative patients and were also found in patients with HBeAg seroconversion at week 48. The area under the receiver operating characteristic (ROC) curves for Δtotal G0 and ΔTGF-β1 to discriminate a week-48 HBeAg seroconversion were 0.835 and 0.830, respectively. These results suggested a correlation between serum cytokine and IgG N-glycome and its effect on the outcome of entecavir treatment in patients with CHB.

Epidemiology of hepatocellular carcinoma in the United States: where are we? Where do we go?

Epidemiology of hepatocellular carcinoma in the United States: where are we? Where do we go?

Risk Assessment of Liver-related Events Using Transient Elastography in Patients With Chronic Hepatitis B Receiving Entecavir

We investigated whether liver stiffness (LS) values can predict liver-related events (LREs) development in patients with chronic hepatitis B (CHB). LS values using transient elastography provides accurate assessment of liver fibrosis in patients with chronic liver disease. Between June 2007 and May 2010, a total of 162 patients with CHB who completed 2-year entecavir (ETV) treatment were evaluated. The primary endpoint was LRE development (hepatic decompensation, hepatocellular carcinoma, or liver-related death) during the 2-year ETV treatment. The median age of the patients (99 men, 63 women) was 51 years, and the median LS value was 14.8 kPa. During the 2-year ETV treatment, 15 (9.3%) patients experienced LREs. On univariate analysis, age, the proportion of patients with liver cirrhosis, platelet counts, and baseline LS values were significantly associated with LRE development (all P<0.05). Together with age, multivariate analysis identified baseline LS values as an independent predictor of LRE development (P=0.046; hazard ratio, 1.040; 95% confidence interval, 1.101-1.084). The cutoff LS value maximizing the sum of sensitivity and specificity was 12.0 kPa (area under the receiver operating characteristics curve, 0.736; P=0.003; sensitivity, 93.3%; specificity, 42.2%). In addition, the changes in LS values between baseline and 1-year ETV treatment showed significant correlations with LRE development (P=0.030). Our data suggest that LS values are predictive of LRE development during 2-year ETV treatment in patients with CHB. The potential role of LS value as a monitoring tool for predicting dynamic changes in the risk of LRE development during long-term ETV treatment should be investigated further.

A comparison of efficacy and safety of 2-year telbivudine and entecavir treatment in patients with chronic hepatitis B: a match–control study

There are limited data comparing the clinical outcomes between telbivudine and entecavir. We consecutively enrolled 115 telbivudine-naive and 115 entecavir-naive chronic hepatitis B patients, who were matched for age, sex, hepatitis B e antigen (HBeAg) status and cirrhosis, and treated for at least 2 years or less than 2 years but had developed resistance. Except for the rate of HBeAg seroconversion, which was similar, patients in the entecavir group had better clinical outcomes than those in the telbivudine group for alanine aminotransferase normalization (85.2% vs 78.4%, p <0.048), undetectable HBV DNA (96.5% vs 74.8%, p <0.001), and viral resistance (0.9% vs 21.7%, p <0.001) after 2 years of treatment, After applying roadmap or super-responders concepts, entecavir still had better outcomes than telbivudine in undetectable HBV DNA and viral resistance. The cumulative incidence of hepatocellular carcinoma development was similar between telbivudine-naive and entecavir-naive patients (p 0.565). In renal function analysis, there were significantly more patients with estimated glomerular filtration rate (eGFR) category improvement in both the telbivudine and entecavir groups at year 1 (p 0.006 and p 0.047, respectively). The rate of virological improvement was significantly higher with entecavir than with telbivudine after 2 years of treatment, whether applying the concepts of roadmap or super-responders. The incidence of hepatocellular carcinoma was similar between telbivudine and entecavir. Both telbivudine and entecavir were associated with eGFR improvement, especially in patients with renal insufficiency.

Early Entecavir Treatment for Chronic Hepatitis B with Severe Acute Exacerbation

A previous study found that lamivudine, if started early enough, may improve the chance of survival in chronic hepatitis B virus (HBV) with severe acute exacerbation (SAE). The aim of this study was to investigate the effect of early entecavir treatment before the bilirubin level exceeds 20 mg/dl for chronic HBV with SAE. Consecutive patients with chronic HBV with SAE and a serum bilirubin level of <20 mg/dl who received lamivudine or entecavir were enrolled. Short-term (4 months) survival was evaluated. One hundred fourteen patients received lamivudine, and 53 patients received entecavir. The baseline characteristics were similar for the two groups except that the entecavir group was older and had a lower alanine aminotransferase (ALT) level. Three patients (8.0%) in the entecavir group and 9 patients (7.9%) in the lamivudine group died (P=1.000). If only patients who started antiviral treatment before serum bilirubin level rose to more than 15 mg/dl were included, 3 patients (8.3%) in the entecavir group and 3 patients (3.0%) in the lamivudine group died (P=0.189). If only patients with an HBV DNA level higher than 10(5) copies/ml and a bilirubin level lower than 15 mg/dl were included, 5 out of 40 patients (12.5%) in the entecavir group died and 1 out of 59 patients (1.7%) in the lamivudine group died. Multivariate analysis found that entecavir treatment was associated with more mortality than lamivudine (P=0.035). Early entecavir treatment in patients with high viral load is associated with more short-term mortality than lamivudine for chronic HBV with severe acute exacerbation.

Results of Entecavir treatment in patients with chronic hepatitis B

Amac: Bu calismada kronik hepatit B hastalarinda 96 haftalik Entekavir (ETV) tedavi etkinliginin ve guvenliginin degerlendirilmesi amaclandi.Yontemler: Kronik Hepatit B tanisiyla 38 hasta calismaya alindi. Entekavir tedavisine baslama kriterleri: yukselmis ALT duzeyleri, (>normalin iki katinda fazla), HBe Ag pozitif hastalarda HBV DNA ≥5 log10 kopya/ml (≥20000 IU/ml), HBe Ag negatif hastalarda ≥4 log10 kopya/ml (≥ 2000 IU/ml) karaciger hasarinin histopatolojik olarak gosterilmesi (Knodell HAI ≥4, fibrozis ≥1). Hastalar 12 haftada bir biyokimyasal ve virolojik testlerle takip edildi. Bulgular: Hastalarin 24’u (%63,2) erkekti. Yas ortalamasi 38,6 yildi. Tum hastalarin 14’unde (%36,8) HBe Ag pozitifti. Baslangic ortalama ALT duzeyleri 106,7 IU/ml, HBV DNA duzeyleri 4,8 x 107 kopya/ml ve Knodell HAI skoru dokuz idi. HBe Ag pozitif hastalarin 11’i (%78,6) naivdi. Hicbirinde direnc mutasyonu yoktu. Biyokimyasal yanit (BY) 48. ve 96. haftalarda %100, virolojik yanit (VY) sirasiyla %57,1 ve %50 idi. Serolojik yanit (SY) sirasiyla %35,7 ve %42,8 olarak saptandi. HBeAg negatif hastalarin 15’i (%62,5) naivdi; iki hastada lamuvidin direnc mutasyonu saptandi. Kirksekizinci ve 96. haftalarda sirasiyla BY %95,8 ve %100, VY %83,3 saptandi.Sonuc: Calismamizda iki yillik entakavir tedavisi sonucunda, ozellikle HBe Ag negatif hastalarda tedaviye yuksek oranda yanit saglanmistir