Entecavir Research Articles (Page 1)

In this multicenter, retrospective study involving 62 patients, we investigated whether switching from entecavir (ETV) or tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) represents a superior treatment strategy for patients with chronic hepatitis B (CHB) experiencing low-level viremia (LLV). The study determined that TAF significantly improved both virological and biochemical outcomes. At 48 weeks, the complete virological response (CVR) rate was 77.8% for those who switched from ETV and 81.8% for those who switched from TDF, with Hepatitis B virus deoxyribonucleic acid (HBV DNA) negativity reaching 81% by month 12. Additionally, significant normalization of liver enzymes, albumin, and platelet counts was observed across the cohort. While the switch from TDF was associated with a significant increase in triglycerides and high-density lipoprotein (HDL) and a decrease in estimated glomerular filtration rate (eGFR), no such changes were detected in the ETV group. This evidence suggests that TAF provides robust virological control in LLV patients and is associated with favorable biochemical improvements. However, due to the study’s limitations, the strong assertion that TAF promotes the regression of liver fibrosis and reduces the risk of hepatocellular carcinoma (HCC) must be interpreted with caution.

Background/Objectives: Fatality of cirrhotic patients greatly increases when they progress to the decompensated state. Only a few studies to date have applied machine learning (ML) methods to predict decompensation in cirrhosis patients. In the present study, we attempted to apply self-developed ML models for validating their capability of predicting different complications in hepatitis B virus (HBV)-related cirrhosis patients. Methods: Data were extracted from electronic health records of 50,047 patients who were tested and diagnosed with HBV in a tertiary hospital. Four different algorithms (Support Vector Machine (SVM), Logistic Regression (LR), Decision Tree (DT), Random Forest (RF)) were utilized, and a total of 32 ML models were trained and tested to predict variceal bleeding, ascites, jaundice, and multiple complications (≥2 complications) in HBV-related cirrhosis patients. The use of two antiviral drugs were considered: entecavir (ETV) and lamivudine (LAM). Performance of the models was assessed using area under receiver operating characteristic curve (AUROC) and accuracy score. Results: SVM and RF classifications produced the best overall predictions for decompensation in HBV-related cirrhosis patients, with AUROCs ranging from 0.85 to 0.93 and accuracy scores between 0.77 to 0.88 for ascites, jaundice, and multiple complications. The SVM and LR algorithms generated the best performance in differentiating ascites among ETV users, with AUROC of 0.93 and 0.92 and accuracy of 0.88 and 0.86, respectively. Antiviral treatment (type, length of use, adherence), and other routinely collected clinical information may serve as informative markers in differentiating decompensated cirrhosis. Conclusions: ML-based prediction of decompensation using electronic health records may assist clinicians in decision making. Findings of this study also underline the impact of antiviral therapy as a key predictor for decompensation.

Hepatitis B virus (HBV) infection is a global health concern with an estimated 254 million people with chronic HBV infection. The utilization of immunosuppressive therapies (ISTs) is increasing and expanding continuously with new agents being implemented across multiple medical disciplines. The occurrence of HBV reactivation (HBVr) during or after IST varies from 15% to 50% in HBsAg-positive individuals and can be higher than 75% after stem cell transplantation. HBVr is gaining increasing significance in contemporary clinical practice. The American Gastroenterological Association (AGA) in 2025, the European Association for the Study of the Liver (EASL) in 2025, and the Asian Pacific Association for the Study of the Liver (APASL) in 2021, published their most recent clinical guidelines as major societies in the area, which enables us to better predict and manage HBVr. This narrative review focuses on comparing these three current guidelines, highlighting key similarities and differences to provide valuable guidance for practitioners navigating the complex, sometimes conflicting recommendations, thereby aiding clinicians in their decision-making. The risk of HBVr during IST has been stratified into three categories in all three guidelines: high (>10%), moderate (1–10%), and low (<1%). The effectiveness of prophylaxis scales with baseline risk for HBV reactivation. Prophylaxis is clearly cost-effective for high-risk patients, potentially beneficial for those at moderate risk, and generally may not be justified for low-risk individuals. Entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) are all highly effective in preventing HBV reactivation during immunosuppression and all are considered to be economically viable options for HBVr high risk patients. When selecting among these agents, safety considerations—particularly renal and bone toxicity—and insurance coverage remain the primary factors directing clinical decision-making.

ABSTRACTTenofovir disoproxil fumarate (TDF) and entecavir (ETV) are first‐line antiviral agents for chronic hepatitis B (CHB), yet comparative real‐world data in Southeast Asian populations remain limited. This retrospective cohort study aimed to compare the efficacy, biochemical response, antifibrotic effect, and renal safety of TDF versus ETV in treatment‐naïve Vietnamese patients with CHB over a 48‐week period. A total of 348 patients (TDF: 181; ETV: 167) were included and evaluated at baseline, Weeks 12, 24, and 48. Both groups demonstrated comparable virologic suppression at Week 48 (TDF: 58.0%, ETV: 52.1%, p > 0.05). TDF achieved significantly higher ALT normalization at Week 24 (72.9% vs. 59.9%, p = 0.01) and Week 48 (84.0% vs. 69.5%, p = 0.001). In contrast, ETV led to faster AST normalization and greater early reductions in APRI and FIB‐4 at Week 12. Renal function mildly declined in the TDF group (mean eGFR change: −3.84 ± 11.98, p < 0.001) but improved in the ETV group (+3.02 ± 12.34, p = 0.002). Both treatments were well tolerated with no virologic breakthrough or serious adverse events. In conclusion, both TDF and ETV offer effective antiviral therapy for Vietnamese CHB patients. TDF may be preferable in patients with active hepatic inflammation, whereas ETV may benefit those with baseline renal concerns or early fibrotic progression. These findings support a tailored approach to HBV management based on individual patient profiles.

Patients with chronic hepatitis B (CHB) are at a higher risk of chronic kidney disease (CKD) compared to the general population. This study compared renal outcomes in treatment-naive CHB patients receiving tenofovir alafenamide (TAF) or entecavir (ETV) using South Korea's nationwide health insurance database. Two cohorts were analyzed: patients with normal renal function (cohort 1) and those with CKD but not end-stage renal disease (ESRD) (cohort 2). Propensity score matching (PSM) balanced baseline characteristics. Before PSM, ETV users had higher CKD (10.88 vs. 4.48 per 1000 person-years, incidence rate ratio [IRR] 2.43, 95% CI 2.13-2.77) and ESRD rates (40.33 vs. 22.13, IRR 1.82, 95% CI 1.26-2.63) than TAF users. Post-PSM, CKD and ESRD incidence showed no significant difference (CKD IRR 1.20, 95% CI 0.69-2.10; ESRD IRR 1.49, 95% CI 0.81-2.75). Cox regression confirmed that the antiviral agent was not a significant predictor of CKD or ESRD. In conclusion, TAF and ETV demonstrated similar renal safety profiles in CHB patients. These findings provide robust evidence for clinical decision-making, particularly for patients at risk of renal impairment.

Low-level viremia (LLV) during antiviral therapy predicts poor outcomes in chronic hepatitis B (CHB). Although bile acids (BAs) regulate HBV transcription, their role in LLV remains unclear. This study aimed to determine whether specific BAs affect antiviral efficacy and to identify potential therapeutic targets. We analyzed 111 CHB patients, including LLV and lower detection limit (LDL) groups. Serum BAs were profiled by mass spectrometry. Propensity score matching (PSM), correlation, and ROC analyses evaluated the association between BAs and HBV DNA. Invitro, deoxycholic acid (DCA) was tested in HBV-producing HepG2.2.15 and HBV-infected HepG2-NTCP cells. Invivo, HBV-transgenic (HBV-Tg) mice were used to assess hepatic DCA and HBV DNA correlation. Treatments included entecavir (ETV), antibiotics, and DCA supplementation. Molecular docking and mutagenesis were conducted to explore DCA-HBV surface protein (HBs) interactions. After PSM, LLV patients had elevated DCA, LCA, and TUDCA levels, which correlated with HBV DNA. DCA modestly predicted LLV by ROC analysis. Invitro, DCA promoted HBV Dane particle secretion and infection without altering viral protein expression. In HBV-Tg mice, hepatic DCA correlated positively with HBV DNA. ETV and antibiotics reduced DCA and HBV DNA, whereas DCA supplementation reversed these effects. Mechanistically, DCA bound to LXXLL motifs in the HBs transmembrane domains, particularly TM2. TM2 mutations disrupted DCA binding, HBs-HBc interaction, and Dane particle formation. Elevated DCA promotes viral persistence by enhancing Dane particle formation and stabilizing HBs-HBc interactions, contributing to LLV during treatment. Modulating BA metabolism may offer new strategies to improve CHB therapy.

Oral nucleos(t)ide analogues (NAs) are widely used in managing hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). Among first-line therapies, entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) are commonly prescribed. However, their comparative efficacy and safety remain unclear in HBV-ACLF. We performed a systematic search of PubMed, Embase, Cochrane Library, and Web of Science up to January 2025 for studies evaluating ETV, TDF, and TAF in HBV-ACLF. The data were analyzed using standardized mean differences (SMD), 95% confidence intervals (95% CI), and surface under the cumulative ranking curve (SUCRA). Nine studies (five prospective, four retrospective) were included. TDF significantly improved 12-week survival compared to ETV (SMD = -0.21; 95% CI -0.36 to -0.06), with no significant difference between TDF and TAF. For 12-week HBV-DNA clearance, TAF outperformed ETV (SMD = -0.40; 95% CI -0.77 to -0.02), ranking highest in SUCRA (83.5%). TAF also showed superior virological suppression at 4weeks (SUCRA: TAF 72.2% > ETV 49.1% > TDF 28.8%). TDF improved 12-week model for end-stage liver disease (MELD) scores more than ETV (SMD = 1.05; 95% CI 0.15-1.94). The drugs did not differ significantly in improving liver function at 4weeks, as measured by alanine aminotransferase (ALT) and total bilirubin (TBIL) levels. Regarding renal function, ETV had a greater impact on the 4-week estimated glomerular filtration rate (eGFR) than TAF (SMD = -0.35; 95% CI -0.52 to 0.18), and both TDF and ETV showed a more significant effect on the 4-week creatinine (cr) levels than TAF (TDF: SMD = 0.29; 95% CI 0.00-0.57; ETV: SMD = 0.30; 95% CI 0.09-0.51). Overall, TDF and TAF provide superior survival and antiviral benefits over ETV in HBV-ACLF, with three drugs showing similar effects in improving liver function. Moreover, TAF demonstrated the most favorable profile in viral suppression and renal safety.

Comparative risk of osteoporosis and fractures in chronic hepatitis B patients: Tenofovir disoproxil fumarate vs. entecavir in a Korean nationwide cohort.

Besifovir dipivoxil maleate (BSV) has potent antiviral efficacy against chronic hepatitis B (CHB). This study investigated the efficacy of BSV in reducing hepatocellular carcinoma (HCC) development compared to other antiviral therapy (AVT) agents. We conducted a retrospective cohort study on treatment-naïve patients with CHB who initiated an AVT between 2017 and 2022 with BSV (n = 486), entecavir (ETV) (n = 852), tenofovir alafenamide (TAF) (n = 801), or tenofovir disoproxyl fumarate (TDF) (n = 750). The incidence and hazard ratio (HR) of HCC were calculated. The incidence of HCC in BSV users (n = 6, 4.3 per 1000 person-years [PYs]) was similar to that in TAF users (n = 21, 9.2 per 1000 PYs, log-rank P = 0.086, HR = 2.191, 95% confidence interval [CI] 0.884–5.434), but significantly lower than that in ETV users (n = 38, 12.5 per 1000PYs, log-rank P = 0.026, HR = 2.627, 95% CI 1.103–6.255) and TDF users (n = 32, 12.3 per 1000PYs, log-rank P = 0.028, HR = 2.623, 95% CI 1.090–6.311). Similarly, compared to BSV users, the adjusted HRs for ETV, TAF, and TDF users were higher after stabilized inverse probability of treatment weighting (2.836, 2.784, and 3.294, respectively) and pairwise propensity score matching (3.200, 3.250, and 3.750, respectively) (all P < 0.05). BSV demonstrated comparable efficacy in HCC reduction compared to other AVTs.

IntroductionLow-level viremia (LLV) is associated with the progression of liver fibrosis and a high risk of hepatocellular carcinoma in patients with chronic hepatitis B (CHB). The present study aimed to compare the efficacy between nucleos(t)ide analogs (NAs) therapy and combination therapy of NAs and pegylated interferon-α (pegIFN-α) in entecavir (ETV)-treated CHB patients with LLV.MethodsThis was a retrospective cohort study. ETV-treated CHB patients with LLV were included and divided into the NA group and the NA+IFN group. The NA group comprised patients switching to tenofovir alafenamide fumarate, whereas the NA+IFN group comprised those adding on pegIFN-α additionally. We compared changes in HBV markers and complete virological response (CVR) between the two groups.ResultsA total of 127 patients were enrolled, including 51 in NA+IFN group and 76 in NA group. In the NA+IFN group, the decline in HBsAg level from baseline (△ HBsAg) was significantly greater (−0.17 log10IU/mL vs. −0.06 log10IU/mL, P = 0.011) at week 24, and HBsAg clearance rate and △ HBsAg were significantly higher (8.9% vs. 0%, P = 0.017; −0.27 log10IU/mL vs. −0.11 log10IU/mL, P = 0.023) at week 48. The 48-week CVR rate in the NA+IFN group was 66.7% (34/51), which was comparable to 68.4% (52/76) in the NA group (P = 0.836).ConclusionIn ETV-treated patients with LLV, receiving NAs plus pegIFN-α tends to increase the effect of HBsAg clearance.

Objective: To analyze Hepatitis B virus(HBV)drug resistance mutations in patients with chronic hepatitis B(CHB)infection who have undergone long-term monotherapy with Entecavir(ETV)and those receiving combination therapy with ETV and Lamivudine(LAM), and to explore the related factors affecting HBV drug resistance mutations. Methods: The study retrospectively analyzed patients with CHB, compensated cirrhosis, decompensated cirrhosis, and liver cancer who received long-term nucleotide analogue antiviral therapy at the Fifth Medical Center of PLA General Hospital from August 2012 to August 2019.The patients were divided into an ETV monotherapy group and a combined LAM+ETV therapy group.Chi-square tests, independent sample t-tests, and Wilcoxon rank-sum tests were used to compare the clinical baseline characteristics and HBV drug resistance mutation features between the two therapy groups.A multivariate logistic regression model was used to analyze the factors related to HBV drug resistance mutations. Results: A total of 533 patients were enrolled in this study, 357 in the ETV monotherapy group and 176 in the LAM+ETV group. The ETV monotherapy group had 122 (34.17%) patients with resistance mutations, while the LAM+ETV group had 126 (71.59%).In general, the difference in gene mutation rate between the two therapy groups was statistically significant(χ2=66.337, P<0.001). The median age and alanine aminotransferase levels of patients with drug resistance mutations in the two therapy groups were higher than those in the non-mutation group[(t=-4.743, P<0.001)/(Z=-4.809, P<0.001), (Z=-2.667, P=0.007)/(Z=-2.001, P=0.045)].Age(OR=1.044, 95%CI:1.023-1.066), compensated cirrhosis(OR=2.163, 95%CI:1.193-3.922), liver cancer(OR=4.017, 95%CI:2.170-7.436) and the treatment regimen(OR=6.075, 95%CI:3.889-9.489) were associated with drug resistance gene mutations(P<0.001).The mutation rates in different stages of chronic liver disease(CHB, cirrhosis, and liver cancer)showed statistically significant(χ2=41.038, P<0.001;χ2=15.894, P<0.001).The overall mutation rates of ETV-related genes in the two therapy groups were 25.49% and 32.39%, respectively.Additionally, 10 mutation sites and 38 variant combinations were identified, containing five common combinations being rtL180M, rtM204V, rtS202G;rtL180M, rtM204V, rtT184A; rtL180M, rtM204V, rtT184L;rtM204I and rtL180M, rtM204V. Conclusion: In CHB patients undergoing long-term therapy, the rate of HBV resistance mutations is higher in those receiving ETV and LAM combination therapy than in those receiving ETV monotherapy.Monitoring older patients and those with cirrhosis or liver cancer is especially important for preventing resistance mutations.

Safety and efficacy of GST-HG141, a novel HBV capsid assembly modulator, for the treatment of chronic hepatitis B patients with low-level viremia: a randomized, double-blind, placebo-controlled, multicenter phase II study

A potent GalNAc-siRNA drug, RBD1016, leads to sustained HBsAg reduction and seroconversion in mouse models of HBV infection

Evidence supports the long-term efficacy of Nucleos(t)ide Analogs (NAs) therapy in improving chronic hepatitis B (CHB) prognosis. However, determining the most cost-effective first-line NAs remains unclear. China's implementation of the New Volume-Based Procurement Policy (NVBP Policy) in 2019 led to substantial price reductions for entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF). This study assesses the cost-effectiveness of ETV, TDF, and TAF, both with and without NVBP, for CHB in China. A state-transition model, parameterized using data from published literature, was utilized to compare treatment strategies encompassing non-NAs best support care (BSC), ETV, TDF, and TAF, with or without NVBP. A simulated lifetime cohort was employed, measuring outcomes such as predicted liver-related deaths, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). In comparison to Non-NAs BSC, TAF yielded an additional 2.68 QALYs per person, with an ICER of 7,853.22 USD/QALY. Subsequently, TDF generated an additional 2.61 QALYs/person at an ICER of 7,153.39 USD/QALY, and ETV produced an additional 2.01 QALYs/person with an ICER of 9,366.74 USD/QALY without NVBP. Incorporating NVBP, the ICERs for TAF, TDF, and ETV decreased to -745.62 USD/QALY, -729.33 USD/QALY, and -871.11 USD/QALY, respectively, compared to non-NAs BSC. At willingness-to-pay (WTP) thresholds ranging from 12,500 USD/QALY to 37,500 USD/QALY, TAF with NVBP showed an increased probability (51.15-52.47%) of being the optimal treatment strategy, followed by TDF and ETV with NVBP exhibiting a reduced likelihood 43.09-42.45% and 6.40-4.48% in the iterations. Our analysis suggests that TAF with NVBP represents the most cost-effective long-term therapy for CHB. Both TDF and ETV, with or without NVBP, and TAF without NVBP were considered cost-ineffective.

Studies have shown that off-therapy clinical relapses occur much more frequently within 24 weeks and seems more severe in tenofovir disoproxil fumarate (TDF)-treated than in entecavir (ETV)-treated patients. A small retrospective study reported a significantly lower 24-week clinical relapse rate in 40 non-ETV (including 3 TDF) treated patients after switching to ETV for ≥12 weeks before the end of therapy (EOT). To confirm the effect of the ETV-switching strategy, a retrospective cohort study was conducted. TDF or tenofovir alafenamide (TAF) treatment in 18 HBeAg-negative patients was switched to ETV for ≥12 weeks before EOT. Two control groups each 1:2 matched in age, sex, genotype, cirrhosis, baseline HBV DNA, and quantitative HBsAg (qHBsAg) were recruited. All patients were followed up every 1-3 months for ≥6 months after EOT. Compared to the TDF/TAF-control, the incidence of clinical relapse and hepatitis flare by week 24 was lower (16.7 vs 58.3%; p=0.009; 11.1 vs 50%; p=0.013, respectively). The rate of hepatitis flare with ALT >10 times upper limit of normal was also lower than TDF/TAF-control group (5.6 vs 33.3%; p=0.040). All differences compared to ETV-control group were non-significant. The results confirm that the timing of clinical relapse is associated with the last antiviral agent used before EOT. Furthermore, the ETV-switching strategy may reduce clinical relapse and hepatitis flare and the severity of hepatitis flare within 24 weeks after EOT. This strategy seems clinically useful and important for a safer cessation of TDF-based treatment.

Improvement in renal function after switching from entecavir to tenofovir alafenamide in chronic hepatitis B patients with low estimated glomerular filtration rates.

Efficacy and Safety of Tenofovir Plus Entecavir Combination Therapy Versus Tenofovir Monotherapy in Chronic Hepatitis B Virus Patients With Resistance or Partial Response to Entecavir: A Systematic Review and Meta-analysis.

Serum Golgi Protein 73 as a Predictor of Virologic Response to Entecavir Antiviral Therapy in Patients with Chronic Hepatitis B and Liver Fibrosis: A Retrospective Study.

This study aims to investigate antiviral effectiveness, side effects, and disease outcomes in patients who have been using entecavir (ETV) and tenofovir disoproxil fumarate (TDF) for a long-term in chronic hepatitis B. Patients with chronic hepatitis B who had been using TDF or ETV for at least 10 years were included in this retrospective study. Co-infected patients, those receiving immunosuppressive therapy, and transplant patients were excluded. Of the study’s total 173 patients (baseline mean age 43.4 ± 11.7 years), 110 (63.6%) were men. Thirty-three (19.1%) patients were cirrhotic, and hepatitis B e-antigen was negative in 131 (75.7%) patients at the baseline. Ninety-two (53.2%) patients used TDF and 81 (46.8%) used ETV for a mean of 156.76 ± 21.60 (120–204) months. Hepatitis B virus (HBV)-DNA negativity (<10 IU/mL) was achieved in 97.7% of all patients. Biochemical remission was achieved in 98.3% of all patients at the last visit. HBsAg became negative in only 5 (2.9%). Hepatocellular carcinoma (HCC) developed in 9 (5.2%) patients. All HCCs occurred after the 5th year of treatment. The age at HBV diagnosis was higher in HCC patients (P = .023), but the most important risk factor for the development of HCC was to have cirrhosis at baseline. Eight (4.6%) patients died in the follow-up, and 2 were due to liver disease and the remaining non-liver disease. At the end of follow-up, HBV-DNA negativity was achieved in almost all patients, and HBsAg sero-clearance was rarely achieved. Very few patients developed HCC and the long-term mortality rate was similar to the general population.

Abstract Nucleobase modifications offer a promising route for the discovery of novel antiviral compounds. The synthetic entry of 7H‐pyrrolo[2,3‐d]pyrimidine with alterations at the 4‐position has been thoroughly investigated in the search for bioactive Neplanocin analogs. A key intermediate (4) was synthesized and explored to yield a series of modified carbo‐nucleosides (3a–i). Modified 7‐deazapurine has been installed to get the targeted 7‐deaza carbocyclic nucleosides with an alkyl or aryl. This was accomplished by Pd‐cross‐coupling reactions with alkyl or aryl organometallics/aryl boronic acids on 7‐deazapurines, followed by Mitsunobu coupling and deprotection to produce the final molecules (3a–i). In HBV replication, the anti‐HBV activity of 3a–i was evaluated in HepG2.2.15.7 cells. Compounds 3a, 3c, 3d, 3f, 3 g, and 3i showed promise as lead compounds by exhibiting micromolar‐level activity on the HBV replicon. The tested compounds demonstrated a dose‐dependent inhibition of HBV replication, as demonstrated by the reduced secretion of HBsAg in HepG2.2.15.7 cells, in contrast to the currently approved nucleoside analogue, entecavir (ETV). These findings suggest that the mechanism of action of these analogues is distinct and likely resembles that of previously reported neplanocin derivatives (I &amp; II), which promote the degradation of pregenomic RNA (pgRNA) via a novel pathway. Importantly, S‐adenosylhomocysteine hydrolase (SAHase) does not appear to be involved in their antiviral activity, highlighting a unique mechanism for these neplanocin analogues in suppressing HBV replication.