Entecavir In Chronic Hepatitis Research Articles

Review on article of effects of tenofovir alafenamide and entecavir in chronic hepatitis B virus patients.

This letter comments on the article which reported that tenofovir alafenamide may increase blood lipid levels compared with entecavir in patients with chronic hepatitis B published on World J Hepatol 2023 August 27. We review the related research content, topic selection, methodology, conclusions, strengths and weaknesses of this article. And evaluate it in relation to other published relevant articles.

Cost-effectiveness of tenofovir alafenamide and entecavir in chronic hepatitis B in Saudi Arabia.

Cost-effectiveness of tenofovir alafenamide and entecavir in chronic hepatitis B in Saudi Arabia.

Long-term health and economic benefits of switching to tenofovir alafenamide versus continuing on entecavir in chronic hepatitis B patients with low-level viremia in Saudi Arabia.

Despite the success of current treatments, many chronic hepatitis B (CHB) patients still live with low-level viremia [LLV] resulting in liver disease progression. This study evaluated the long-term health and economic impact of switching to tenofovir alafenamide (TAF) from entecavir (ETV) in Saudi Arabia (SA) in chronic hepatitis B (CHB) LLV patients. A hybrid decision tree Markov state-transition model was developed to simulate a cohort of patients with CHB LLV treated with ETV and switched to TAF over a lifetime horizon in SA. While on treatment, patients either achieved complete virologic response (CVR) or maintained LLV. CVR patients experienced slower progression to advanced liver disease stages as compared to LLV patients. Demographic data, transition probabilities, treatment efficacy, health state costs, and utilities were sourced from published literature. Treatment costs were sourced from publicly available databases. Base case analysis found that over a lifetime horizon, switching to TAF versus remaining on ETV increased the proportion of patients achieving CVR (76% versus 14%, respectively). Switching to TAF versus remaining on ETV resulted in a reduction in cases of compensated cirrhosis (-52%), decompensated cirrhosis (-5%), hepatocellular carcinoma (-22%), liver transplants (-12%), and a 37% reduction in liver-related deaths. Switching to TAF was cost-effective with an incremental cost-effectiveness ratio of $57,222, assuming a willingness-to-pay threshold of three times gross national income per capita [$65,790/QALY]. This model found that switching to TAF versus remaining on ETV in SA CHB LLV patients substantially reduced long-term CHB-related morbidity and mortality and was a cost-effective treatment strategy.

Analysis of efficacy and factors influencing sequential combination therapy with tenofovir alafenamide fumarate after treatment with entecavir in chronic hepatitis B patients with low-level viremia

Objective: To observe the efficacy and factors influencing sequential or combined tenofovir alafenamide fumarate (TAF) after treatment with entecavir (ETV) in patients with chronic hepatitis B (CHB) with low-level viremia (LLV). Methods: 126 CHB cases treated with ETV antiviral therapy in the Department of Infectious Diseases of the First Affiliated Hospital of Nanchang University from January 2020-September 2022 were retrospectively collected. Patients were divided into a complete virologic response (CVR) group (n = 84) and a low-level viremia (LLV) group (n = 42) according to the HBV DNA level during treatment. Clinical characteristics and laboratory indicators of the two groups at baseline and 48 weeks were analyzed by univariate analysis. Patients in the LLV group were divided into three groups according to their continued antiviral treatment regimen until 96 weeks: continued use of ETV as a control group; replacement of TAF as a sequential group; and combination of ETV and TAF as a combined group. The data of the three groups of patients were analyzed by one-way analysis of variance for 48 weeks. HBV DNA negative conversion rate, HBeAg negative conversion rate, alanine aminotransferase (ALT), creatinine (Cr), and liver stiffness test (LSM) were compared among the three groups after 96 weeks of antiviral treatment. Multivariate logistic regression was used to analyze the independent factors influencing the occurrence of HBV DNA non-negative conversion in LLV patients at 96 weeks. Receiver operating characteristic curve (ROC) was used to evaluate the effectiveness of predicting the occurrence of HBV DNA non-negative conversion in LLV patients at 96 weeks. Kaplan-Meier was used to analyze the cumulative negative rate of DNA in LLV patients, and the Log-Rank test was used for comparison. HBV DNA and HBV DNA negative conversion rates during treatment were observed dynamically. Results: Univariate analysis showed statistically significant differences in age, BMI, HBeAg positivity rate, HBV DNA, HBsAg, ALT, AST, and LSM at baseline between the CVR group and the LLV group (P < 0.05). Univariate analysis of variance revealed no statistically significant difference among the three groups of LLV patients at 48 weeks (P > 0.05). HBV-DNA negative conversion rate in the sequential group and the combination group was significantly higher than that in the control group after 96 weeks of treatment (88.89% vs. 41.18%, 85.71% vs. 41.18%, χ (2) = 10.404, P = 0.006). HBeAg negative conversion rate was higher than that of the control group, with no statistically significant difference (P > 0.05).Compared with the control group, ALT, Cr, and LSM in the sequential group and the combined group were equally improved to varying degrees, with a statistically significant difference (P < 0.05). Subsequent use of ETV and HBV DNA at 48 weeks were independent risk factors for HBV DNA positivity at 96 weeks in LLV patients (P < 0.05). The AUC of HBV DNA at 48 weeks was 0.735 (95%CI: 0.578 ~ 0.891), the cut-off value was 2.63 log(10) IU/ml, and the sensitivity and specificity were 76.90% and 72.40%, respectively. DNA conversion rate was significantly lower in LLV patients receiving 48-week ETV and 48-week HBV DNA≥2.63 log10 IU/mL than in patients receiving sequential or combined TAF and 48-week HBV DNA < 2.63 log(10) IU/mL. HBV DNA negative conversion rates in the sequential group and combined group at 72 weeks, 84 weeks, and 96 weeks were higher than those in the control group during the period from 48 weeks to 96 weeks of continuous treatment, and the differences were statistically significant (P < 0.05). Conclusion: Sequential or combined TAF antiviral therapy could more effectively improve the 96-week CVR rate, as well as hepatic and renal function, and alleviate the degree of hepatic fibrosis in CHB patients with LLV following ETV treatment. Subsequent use of ETV and HBV DNA load at 48 weeks were independent predictors of HBV DNA positivity at 96 weeks in LLV patients.

Meta-analysis of the occurrence of hepatocellular carcinoma after the treatment of entecavir and tenofovir for chronic hepatitis B.

Tenofovir and Entecavir are recommended as the first-line medicine of treatment for chronic hepatitis B. The occurrence of hepatocellular carcinoma after the treatment of chronic hepatitis B is a major problem. For the time being it is still unclear whether there remains a difference in risk correlation of hepatocellular carcinoma after the treatment of Tenofovir and Entecavir for chronic hepatitis B. Since previous studies have raised different ideas, this article aims to come to a conclusion targeting such a topic through analyzing the latest data. We searched some databases, such as PubMed, Web of Science, and Cochrane Library, for related studies on patients with chronic hepatitis B receiving the treatment of Tenofovir and Entecavir and then developing hepatocellular carcinoma. The search time was set to begin from the establishment time of the above-mentioned databases to May 2022. Two researchers were designated to screen the literature independently according to the inclusion and exclusion criteria set in this study; they then evaluated the quality of the literature included and extracted the data. Revman 5.3 software was used for meta-analysis. After screening the literature, a total of 20 pieces of cohort study literature conformed to the inclusion criteria. Among which were 62,860 cases of patients receiving Entecavir, and 27,544 cases of patients receiving Tenofovir; there were 3669 cases with the occurrence of hepatocellular carcinoma in the Entecavir group and 1089 cases with the occurrence of hepatocellular carcinoma in Tenofovir group. The result of Meta analysis of these 20 pieces of literature shows that compared with the Tenofovir group, the Entecavir group has a lower occurrence rate of hepatocellular carcinoma, and the difference is statistically significant. The results are expressed as odd ratio (OR) and 95% confident interval (95%CI), (OR = 1.66, 95%CI: 1.35-2.05, P < .05). The result of Meta analysis of 10 studies related to Korea shows that the occurrence rate of hepatocellular carcinoma in the Tenofovir group is lower than that of the Entecavir group, and the difference is statistically significant (OR = 1.59, 95%CI: 1.29-1.95, P < .05). The result of meta-analysis of 5 studies related to China shows that the occurrence rate of hepatocellular carcinoma of Tenofovir group is lower than that of Entecavir group, and the difference is statistically significant (OR = 2.35, 95%CI: 1.15-4.81, P < .05). The occurrence rate of hepatocellular carcinoma after the treatment of tenofovir for chronic hepatitis B is lower than that of the treatment of entecavir.

EE592 Long-Term Health and Economic Benefits of Switching to Tenofovir Alafenamide Versus Continuing on Entecavir in Chronic Hepatitis B Patients With Low-Level Viremia in Saudi Arabia

EE592 Long-Term Health and Economic Benefits of Switching to Tenofovir Alafenamide Versus Continuing on Entecavir in Chronic Hepatitis B Patients With Low-Level Viremia in Saudi Arabia

Antiviral therapy after curative treatment of hepatocellular carcinoma in patients with chronic hepatitis B infection: Is tenofovir or entecavir preferred?

Antiviral therapy after curative treatment of hepatocellular carcinoma in patients with chronic hepatitis B infection: Is tenofovir or entecavir preferred?

Hepatocellular carcinoma incidence with tenofovir versus entecavir in chronic hepatitis B: a systematic review and meta-analysis

It is unclear whether tenofovir disoproxil fumarate and entecavir differ in their association with risk of hepatocellular carcinoma in patients with chronic hepatitis B, and previous meta-analyses have shown conflicting conclusions with substantial heterogeneity. We aimed to analyse the updated data and elucidate the source of heterogeneity. We searched PubMed, Embase, Web of Science, and the Cochrane library for relevant studies with time-to-event data for incident hepatocellular carcinoma occurring in patients with chronic hepatitis B who received tenofovir disoproxil fumarate or entecavir monotherapy with follow-up of at least 1 year. Studies published between Jan 1, 2006, and April 17, 2020, and abstracts from international conferences in 2018 and 2019 were included. We pooled covariate adjusted hazard ratios (HRs) for hepatocellular carcinoma using a random-effects model, assessed heterogeneity among included studies using the I2 statistic and Cochran's Q test, and identified the source of heterogeneity using prespecified subgroup analyses. This study is registered with PROSPERO, ID CRD42020176513. 31 studies involving 119 053 patients were analysed. The 5-year cumulative incidence of hepatocellular carcinoma was 5·97% (95% CI 5·81-6·13, 28 studies) for entecavir and 3·06% (2·86-3·26, 13 studies) for tenofovir disoproxil fumarate in studies with unmatched populations (p<0·0001). For all eight studies matched by propensity score, the 5-year cumulative incidence was 3·44% (95% CI 3·08-3·80) for entecavir and 3·39% (2·94-3·83) for tenofovir disoproxil fumarate (p=0·87). Analysis of 14 comparative studies with covariate adjustment found that tenofovir disoproxil fumarate and entecavir had similar risk of hepatocellular carcinoma (primary outcome); adjusted HR 0·88, 95% CI 0·73-1·07; p=0·20), although heterogeneity was significant (I2=56·4%, p=0·0038). In a subgroup analysis for hospital-based clinical cohorts, there was no difference in hepatocellular carcinoma incidence between the two regimens (adjusted HR 1·03, 95% CI 0·88-1·21; I2=0%). However, tenofovir disoproxil fumarate was associated with a lower risk of hepatocellular carcinoma compared with entecavir in administrative database research (adjusted HR 0·67, 0·59-0·76; I2=0%). Our study found no significant difference between tenofovir disoproxil fumarate and entecavir in their association with incident hepatocellular carcinoma. We suggest that treatment should be guided by patient tolerability and affordability rather than whether one drug is more effective than the other. Supported in part by E-DA Hospital (EDAHP 106008; EDAHP 103046).

Treatment with tenofovir disoproxil fumarate or entecavir in chronic hepatitis B virus-infected patients with renal impairment: results from a 7-year, multicentre retrospective cohort study.

SummaryBackgroundLimited data exist regarding tenofovir disoproxil fumarate (TDF) safety and effectiveness in chronic hepatitis B virus–infected (CHB) patients with renal impairment (RI).AimsTo compare real‐world data on renal safety and effectiveness of TDF vs entecavir (ETV) in CHB patients with moderate‐to‐severe RI.MethodsRetrospective, non‐interventional, cohort study analysing medical records for TDF/ETV‐treated CHB patients (54 European centres). Included patients experienced moderate‐to‐severe RI (creatinine clearance 20‐60 mL/min [Cockcroft‐Gault]) either before TDF/ETV initiation (‘before’ subgroup [baseline = treatment initiation]) or after TDF/ETV initiation (‘after’ subgroup [baseline = first RI occurrence]). The primary objective was TDF safety, particularly renal‐related adverse events of special interest (AESI). TDF and ETV safety and effectiveness were compared and multivariate analyses were performed using inverse probability treatment weighting.Results‘Before’ subgroup included 107 TDF‐ and 91 ETV‐treated patients; ‘after’ subgroup included 212 TDF‐ and 77 ETV‐treated patients. Mean baseline creatinine clearance was higher for TDF‐ vs ETV‐treated patients (both subgroups). Median follow‐up was 3.1 years (both treatments). AESI were more frequent with TDF vs ETV (‘before’: 18.7% vs 8.8%; ‘after’: 9.9% vs 3.9%); however, differences were not significant by multivariate analysis. Only TDF‐treated patients experienced renal tubular dysfunction (6.5% ‘before’; 1.9% ‘after’) as well as renal adverse events leading to treatment discontinuation (8.4% ‘before’; 7.1% ‘after’). Effectiveness was similar between treatments.ConclusionsOverall safety was similar for TDF vs ETV (both subgroups). Given that renal tubular dysfunction occurred with TDF and not with ETV, renal safety concerns may be greater with TDF in CHB patients with RI.

Kushenin combined with entecavir for chronic hepatitis B: A protocol for a systematic review and meta-analysis.

Background:A recent study has reported that there are >240 million patients infected with chronic hepatitis B (CHB) worldwide. Once patients with CHB start antiviral treatment, they need to take antiviral drugs for a long period, which may lead to a series of side effects, and the resistance to the antiviral drugs may also emerge. We aim to evaluate the efficacy and safety of kushenin (KS) combined with entecavir (ETV) for chronic hepatitis B.Methods:Randomized controlled trials (RCTs) of KS combined with ETV for CHB will be identified from PubMed, EMBASE, Web of Science, The Cochrane Library, Chinese Biomedical Database, China National Knowledge Infrastructure, Chongqing VIP, Wangfang Data. Literature screening and data extraction will be independently performed by 2 researchers. The cochrane collaboration tool for assessing risk of bias will be applied to evaluate the risk of bias of the RCTs included. The extracted data will be analyzed by Rev-man 5.3.0 software.Results:A high-quality synthesis of current evidence on the efficacy and safety of KS combined with ETV for CHB will be provided in this study.Conclusion:This systematic review will aim to evaluate the efficacy and safety of KS combined with ETV for CHB.PROSPERO registration number:CRD42019124790.

1360. Disseminated Mycobacterium abscessus Infections in Patients with Neutralizing Anti-interferon-gamma Autoantibodies Treated with Rifabutin-based Combination Regimens

BackgroundThis prospective study aimed to describe the treatment and safety outcomes of rifabutin-based combinations which has been shown to be synergistic in vitro, for patients with refractory M. abscessus infections and neutralizing anti-IFNγ antibodies.MethodsPatients failing at least two standard macrolide-based regimens were recruited from hospitals across Taiwan since August 2017. They received rifabutin (RFB > 300 mg/day) initially with azithromycin (AZR 500 mg/day) and at least one parenteral agent and were monitored thereafter clinically on a monthly basis and by 3–6 monthly PET-CT imaging.ResultsOf 12 referred patients, only four had complete evaluations. The median age was 41 years and follow-up duration was 543 (range 307–668) days. All patients had lung and lymph node disease, two also had liver, bone and joint involvements and all were HLA-DR 16:02, HLA-DQ 05:02 positive. Prior to starting RFB–AZR, they had received at least four successive antimycobacterial regimens, but showed progression of existing lesions (2) or new lesions (2). Following RFB–AZR, all four patients experienced adverse reactions, including reactive dermatoses (2), fevers (2), leukopenia (2), thrombocytopenia (1), hearing loss (1), acute kidney injury (1), which necessitated withdrawal of rifabutin (4), short-term steroid use (2), and replacement of tenofovir with entecavir for chronic hepatitis B (1). All patients recovered fully from these adverse effects. Rifabutin was successfully restarted on first attempt (3) and on third attempt (1). The longest symptom-free interval on RFB–AZR was 331 days and the lowest maintenance dose was RFB 150–AZR 250 thrice weekly. Follow-up PET-CT confirmed good resolution of previous hot spots (mean SUVmax −4.5) except for the patient who did not tolerate RFB 300 due to fever and nausea on the first re-challenge, whose PET-CT detected a slight increase in mean SUVmax +0.6 and was hospitalized for dry cough on daily AZR–ciprofloxacin. The latter eventually tolerated a lower daily dose RFB 150–AZR 250 and became asymptomatic.ConclusionRifabutin is an oral agent that can be effectively combined with azithromycin in long-term maintenance regimens against M. abscessus in immunodeficient adults. Adverse effects are frequent early on; however, rechallenge appears to be safe and outcomes favorable. Disclosures All authors: No reported disclosures.

Tenofovir is a more suitable treatment than entecavir for chronic hepatitis B patients carrying naturally occurring rtM204I mutations.

BACKGROUNDHepatitis B virus (HBV) DNA polymerase mutations usually occur to long term use of nucleos(t)ide analogues (NAs), but they can occur spontaneously in treatment-naïve chronic hepatitis B (CHB) patients. The naturally occurring HBV DNA polymerase mutations might complicate antiviral therapy with NAs, leading to the generation of drug-resistant viral mutants and disease progression. The most common substitutions are known to be YMDD-motif mutations, but their prevalence and the influence on antiviral therapy is unclear.AIMTo investigate prevalence of the naturally occurring rtM204I mutations in treatment-naïve CHB genotype C2 patients and their influence on antiviral therapy.METHODSA total of 410 treatment-naïve CHB patients infected with HBV genotype C2 strains were enrolled in this retrospective study. Among the 410 patients, 232 were treated with NAs for at least 12 mo. Significant fibrosis was defined as fibrosis-4 index > 3.25 or aspartate aminotransferase to platelet ratio index > 1.5. Complete viral response (CVR) during NAs was defined as undetectable serum HBV DNA (< 24 IU/mL). The rtM204I variants were analyzed by a newly developed locked nucleotide probe (LNA probe) based real-time PCR (LNA-RT-PCR) method.RESULTSThe LNA-RT-PCR could discriminate rtM204I mutant-type (17 patients, 4.2%) from rtM204 wild-type (386 patients, 95.8%) in 403 of 410 patients (98.3% sensitivity). Multivariate analysis showed that naturally occurring rtM204I variants were more frequently detected in patients with significant fibrosis [odd-ratio (OR) 3.397, 95% confidence-interval (CI) 1.119-10.319, P = 0.031]. Of 232 patients receiving NAs, multivariate analysis revealed that achievement of CVR was reversely associated with naturally occurring rtM204I variants prior to NAs treatment (OR 0.014, 95%CI 0.002-0.096, P < 0.001). Almost patients receiving tenofovir achieved CVR at 12 mo of tenofovir, irrespective of pre-existence of naturally occurring rtM204I mutations (CVR rates: patients with rtM204I, 100%; patients without rtM204I, 96.6%), whereas, pre-existence of naturally-occurring rtM204I-mutations prior to NAs significantly affects CVR rates in patients receiving entecavir (at 12 mo: Patients with rtM204I, 16.7%; patients without rtM204I, 95.6%, P < 0.001).CONCLUSIONThe newly developed LNA-RT-PCR method could detect naturally occurring rtM204I mutations with high-sensitivity. Theses mutations were more frequent in patients with liver fibrosis. Tenofovir is a more suitable treatment than entecavir for CHB patients carrying the naturally occurring rtM204I mutations.

Efficacy of Real-world Entecavir Therapy in Treatment-naïve Chronic Hepatitis B Patients.

Background:Entecavir (ETV) has been shown to be effective in randomized controlled trials in highly selected patients with hepatitis B virus (HBV) infection. This study aimed to evaluate the efficacy of ETV in chronic hepatitis B (CHB) patients in the real-world setting.Methods:A total of 233 treatment-naïve, CHB patients who received at least 12 months of ETV treatment were included in this retrospective study. Rates of virological response (VR), hepatitis B s antigen (HBsAg) loss, hepatitis B e antigen (HBeAg) clearance/seroconversion, virological breakthrough, cirrhosis, and hepatocellular carcinoma were evaluated.Results:Of 233 patients, 175 patients were male, with mean age of 43 years old, and 135 patients were HBeAg positive. The mean baseline levels of serum alanine aminotransferase and HBV DNA in all patients were 230 U/L and 6.6 log 10 IU/ml, respectively. The mean follow-up period was 28 months. The cumulative rates of achieving VR increased from 3.4% at 3 months to 94.4% at 60 months. Primary nonresponse occurred in 3 (1.3%) patients. Partial VR (PVR) occurred in 61 (26.2%) patients at 12 months. The baseline serum HBV DNA level (hazard ratio [HR], 2.054; P < 0.001) was an independent risk factor for PVR. HBsAg loss did not occur. The cumulative rates of HBeAg clearance increased from 2.2% at 3 months to 28.2% at 60 months. PVR was the significant determinant of HBeAg clearance (HR, 0.341; P = 0.026). Age (HR, 1.072; P = 0.013) and PVR (HR, 5.131; P = 0.017) were the significant determinants of cirrhosis.Conclusions:ETV treatment was effective for HBV DNA suppression in this study, but HBsAg loss and HBeAg clearance/seroconversion rates were lower compared with previous clinical trials. PVR was associated with HBeAg clearance and cirrhosis.

Retrospective-Prospective Study on Efficacy &amp; Safety of Entecavir in Chronic Hepatitis B West Asian Patients with Genotype D

Aim: To assess the long term efficacy and safety of Entecavir in the treatment of CHB in Asian-Arabic patients with genotype D, for both nucleoside-naïve as well as experienced, comparing HBeAg positive and negative group. Methods: This study included 70 CHB consecutive patients who were maintained on Entecavir for at least 36 months retrospectively and followed up prospectively every 3 months for a total of 18 months, at 2 centers in Kuwait (October 2012 and April 2014). Results: It showed that 23 (32.8%) were HBeAg +ve. All were found to be HBV genotype D, 47.1% naive, 22 (31.4%) females, with a mean age of 42.9 ± (13), 14 (20%) cirrhotic and 1(1.4%) decompensated. There were no significant differences in the pre-treatment HBV-DNA level among HBeAg+ve and HBeAg-ve group, with a mean± SD log 10 of 7.9 ± 5.4 and 7.4 ± 5.0 respectively (P=0.237). There was a significant viral load reduction in both groups after 6 months of treatment with Entecavir. The reduction was more pronounced in the HBeAg–ve compared to HBeAg +ve group. In HBeAg +ve, 19 patients (82.61%) had complete HBV-DNA suppression after a median period of 7 month, while in HBeAg –ve group; all (100%) had complete HBV-DNA suppression after a median period of 5 month duration (P<0.05). None showed primary non response to Entecavir in both groups. In the HBeAg-ve group; one (2.13%) had HBsAg loss at 45 month compared to non in HBeAg+ve group (P<0.001), while in the HBeAg+ve group; 5 (21.74%) showed HBeAg clearance after a median of 16 month during Entecavir treatment. Multivariate analysis identified HBeAg negative status, pre-treatment as the only independent factor affecting complete viral suppression on Entecavir treatment. The drug showed 100% safety, as there were no serious adverse events throughout 54 month of follow up. None showed hepatic decompensation, HCC or need for liver transplantation during follow up. Also, there was no reported death throughout study period in both groups. Conclusions: In real life data; long term Entecavir treatment for up to 54 months in West Asian CHB patients, with genotype D suppressed HBV-DNA to an undetectable level in 100% of HBeAg-ve, compared to 82% in HBeAg +ve group. Entecavir is considered an effective and safe choice on long term use for treatment CHB patients.

Tenofovir and entecavir for chronic hepatitis B infection treatment: a single-center experience

BACKGROUND AND AIM: The current treatment of chronic hepatitis B infection (CHBV) has achieved several step-ups thanks to the introduction of the new-generation nucleos(t)ide analogs. Entecavir and tenofovir have shown a high genetic resistance barrier and a low rate of side effects. In literature, there are a few studies comparing entecavir and tenofovir in the treatment of CHBV. Thus, we describe the results of our experience in managing CHBV patients with tenofovir vs. entecavir.MATERIALS AND METHODS: We have retrospectively evaluated, from 2007 to date, 20 CHBV patients treated with entecavir and tenofovir. All the patients underwent basal and periodical clinical follow-up, blood tests, virological tests, Fibroscan® test or liver biopsy and also upper abdominal ultrasound examination. Study endpoints were: viral replication inhibition, viral antigens seroconversion and transaminases normalization. Drug-associated side effects were also registered.RESULTS: After 12 weeks of therapy, entecavir and tenofovir lead to HBV-DNA negativization in 44% and 62% of patients, respectively. A case of viral seroconversion for HBeAg and HBsAg was evident in entecavir group, while no cases were registered in tenofovir group. After 12 weeks, 11% of entecavir treated patients and 37% of tenofovir treated patients showed normalization of transaminases.DISCUSSION: Tenofovir seems to exert a better viral replication inhibition (though not statistically significant) and to show transaminases improvement in comparison with entecavir, which, in turn, results more effective in HBeAg/HBsAg seroconversion. Both drugs have a high safety profile in terms of side effects.[Article in Italian]

Impact of prior lamivudine use on the antiviral efficacy and development of resistance to entecavir in chronic hepatitis B patients.

Background/AimsTo determine the efficacies of entecavir (ETV) in nucleos(t)ide analogue (NA)-naïve chronic hepatitis B (CHB) patients and in those with prior lamivudine (LAM) use who did not develop resistance.MethodsWe retrospectively enrolled 337 patients with CHB who were treated with ETV (0.5 mg daily) for at least 30 months. The study included 270 (80.1%) NA-naïve patients and 67 (19.9%) LAM-use patients. Ten of the LAM-use patients were refractory to LAM therapy without developing resistance.ResultsGenotypic resistance to ETV developed more frequently in the LAM-use group (13.1%) than in the NA-naïve group (2.6%) at 60 months (P=0.009). In subgroup analysis, after excluding the 10 patients who were refractory to LAM therapy, the cumulative probability of ETV resistance did not differ significantly between the two groups (P=0.149). Prior LAM refractoriness and a higher hepatitis B virus DNA level at month 12 were independent predictive factors for the development of ETV resistance.ConclusionsETV resistance developed more frequently in LAM-use patients with CHB. However, prior LAM use without refractoriness did not affect the development of ETV resistance. The serum hepatitis B virus DNA level at month 12 was a major predictor for the development of ETV resistance.

Effective antiviral therapy with entecavir in chronic hepatitis B virus carriers

To evaluate the short-term effect and safety of entecavir for the treatment of chronic hepatitis B (CHB) virus carriers. Ninety-three cases of CHB virus infection (hepatitis B surface antigen (HBsAg)-positive, hepatitis B e antigen (HBeAg)-positive, hepatitis B core antibody (HBcAb)-positive, HBV DNA≥1x10(5) copies/mL) were divided into two groups: CHB virus carrier (47 cases) and CHB (46 cases). All of the 93 cases were given 0.5 mg entecavir orally once a day for 48 weeks. Virology, serology and biochemistry tests were perrmed at treatment weeks 0, 4, 12, 24 and 48. Side effects of entecavir and the incidence of liver cirrhosis and hepatocellular carcinoma were recorded. The CHB virus carrier and CHB group had complete virological response rates of 14.9% and 17.4% at week 4, 51.1% and 63.0% at week 12, 76.6% and 89.1% at week 24, and 97.9% and 100% at week 48, respectively; there was no significant difference between the two groups (P>0.05). The CHB virus carrier and CHB group had partial virological response rates of 42.6% and 47.8% at week 4, 57.44% and 65.2% at week 12, 85.0% and 89.1% at week 24, and 100% and 100% at week 48, respectively; there was no significant difference between the two groups (P>0.05). No cases in either group experienced virologic breakthrough during the treatment course. The CHB virus carrier and CHB group had serological response (HBeAg-negative) rates of 0 and 4.3% at week 4, 2.1% and 8.7% at week 12, 4.3% and 13.0% at week 24, and 8.5% and 21.7% at week 48, respectively; there was no significant difference between the two groups (P>0.05). The CHB virus carrier and CHB group had HBeAg seroconversion rates of 0 and 0 at week 4, 0 and 4.4% at week 12, 2.1% and 10.9% at week 24, and 6.4% and 17.4% at week 48, respectively; there was no significant difference between the two groups (P>0.05). No case in either group showed HBsAg-negativity and seroconversion during the treatment course. The CHB group had a biochemical response (alanine aminotransferase normalization) rate of 26.1% at week 4, 65.2% at week 12, 91.3% at week 24, and 97.8% at week 48.No case in either group showed biochemical breakthrough during the treatment course. There were no cases of liver cirrhosis or hepatocellular carcinoma in either group. There were no side effects of the entecavir treatment experienced in either group. Antiviral therapy with entecavir is effective, safe and well tolerated in CHB virus carriers.

Efficacy and safety of long term entecavir in chronic hepatitis B treatment naïve patients in clinical practice

Background and aims. Entecavir (ETV) is effective and safe in patients with chronic hepatitis B in the short term, but its long term efficacy and safety has not been established.Material and methods. We evaluated HBV DNA clearance, HBeAg/antiHBe and HBsAg/antiHBs seroconversion rates in HBeAg-positive and negative NUC naïve HBV patients treated with ETV for more than 6 months, and predictors of response.Results. A hundred and sixty nine consecutive patients were treated with ETV for a median of 181 weeks. 61% were HBeAg positive, 23% were cirrhotics, and mean HBV-DNA levels were 6,88 ± 1,74 log10 lU/mL. Overall, 156 (92%) patients became HBV DNA undetectable, 92 (88%) HBeAg positive and 64 (98%) HBeAg negative patients. Seventy four (71%) patients cleared HBeAg after a median of 48 weeks of treatment, 23 (14%) patients cleared HBsAg (19 HBeAg positive and 4 HBeAg negative, p 0.025) after a median of 96 weeks of treatment, and 22 (13%) patients developed protective titers of anti-HBs. At the end of the study, 35 (20%) patients had discontinued therapy: 33 HBeAg positive and 2 HBeAg negative; 9 of them (26%) developed virological relapse after a median of 48 weeks of stopping treatment. None of the patients had primary non response and one patient developed breakthrough. Two patients developed HCC, three underwent liver transplantation and 3 deaths were attributable to liver-related events. No serious adverse events were reported.Conclusion. Long term ETV treatment showed high virological response rates, and a favorable safety profile for NUC-naive HBeAg-positive and negative patients treated in clinical practice.

Efficacy of Entecavir in Chronic Hepatitis B Patients with Persistently Normal Alanine Aminotransferase: Randomized, Double-Blind, Placebo-Controlled Study

It is still inconclusive whether chronic hepatitis B (CHB) patients with persistently normal alanine aminotransferase (PNALT) should receive nucleoside/nucleotide analogues. This study is to evaluate the efficacy of entecavir in improving liver histology in CHB patients with PNALT. In this prospective randomized, double-blind, placebo-controlled study, 380 CHB patients with PNALT were screened, 82 patients received biopsy and 43 patients met the HBV DNA and histology criteria and were randomly assigned to either an entecavir or placebo group for 52 weeks, with 22 and 21 in each group, respectively. The primary objective was to evaluate histological improvement. The secondary objective is to evaluate virological efficacy. A total of eight (38.1%) patients in the entecavir group and eight (44.4%) in the placebo group (P=0.752) showed histological improvement. The decrease in total Knodell scores (±sd) was 1.3 ±1.9 in the entecavir group and 1.5 ±2.2 in the placebo group (P=0.803). The subjects with undetectable HBV DNA at week 52 were 16/21 (76.2%) in the entecavir group and 0/18 (0%) in the placebo group (P<0.001). The mean HBV DNA reduction from baseline to week 52 was 4.73 ±0.83 in the entecavir and 0.25 ±0.81 in the placebo group (P<0.001). CHB patients with PNALT receiving entecavir therapy for one year achieved virological efficacy, but not histological benefit. ClinicalTrials.gov number NCT01833611.

A 96-Week Randomized Trial of Switching to Entecavir in Chronic Hepatitis B Patients with a Partial Virological Response to Lamivudine

Growing numbers of chronic hepatitis B (CHB) patients in the Asia-Pacific region have failed first-line therapy with low genetic barrier drugs. This prospective, 96-week study investigated the antiviral efficacy, safety and tolerability of switching to entecavir versus maintaining lamivudine in CHB patients with a partial virological response to lamivudine. A total of 72 hepatitis B e antigen (HBeAg)-positive patients, with serum HBV DNA≥60 IU/ml after ≥6 months lamivudine monotherapy were randomized 1:1 to receive either entecavir 1.0 mg/day, or continued lamivudine 100 mg/day. Mean duration of prior lamivudine treatment was 15.1 months in the lamivudine-maintained patients and 16.1 months in the entecavir-switch patients, with mean baseline HBV DNA levels of 4.66 and 4.55 log(10) IU/ml, respectively. A greater proportion of entecavir-switch than lamivudine-maintained patients achieved undetectable HBV DNA at all time points (67.6% versus 11.4% at week 96; P<0.001). Entecavir-switch patients achieved a greater mean decrease in HBV DNA level by week 4, maintained through week 96. Entecavir-switch patients with baseline HBV DNA<5 log(10) IU/ml were more likely to achieve a virological response at week 96. A total of 6 (17.6%) entecavir-switch and 2 (5.7%) lamivudine-maintained patients achieved HBeAg loss, and 3 (8.8%) entecavir and 1 (2.9%) lamivudine patients achieved HBeAg seroconversion. Genotypic resistance to the assigned intervention emerged in 82.9% (29/35) of lamivudine-maintained patients, and in 3% (1/34) of entecavir-switch patients after 96 weeks. Switching to entecavir in patients with a partial virological response to lamivudine resulted in increased virological efficacy and lower rates of antiviral resistance than maintaining lamivudine.