Entecavir Group Research Articles

Tenofovir is superior to entecavir in reducing HCC for patients with HBV-related compensated cirrhosis at high HCC risk scores.

Background:Both tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are known to reduce the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This study aimed to compare the difference in HCC risk reduction between TDF and ETV in treatment-naïve patients with CHB-related compensated cirrhosis.Methods:Patients with compensated cirrhosis initially treated with TDF or ETV at nine Chinese hospitals between June 2014 and March 2021 were enrolled in this retrospective study. The cumulative HCC incidence rates for the two drugs were compared for the entire cohort, and a subgroup analysis was performed according to the HCC risk scores. Propensity score matching (PSM) was used to control confounding biases.Results:The analysis included 1453 patients (TDF group, n = 188; ETV group, n = 1265). Ninety-five patients developed HCC, with a median follow-up period of 26.1 months. The 3-year HCC incidence was 2.0% in the TDF group and 7.5% in the ETV group (log-rank p = 0.005). TDF treatment was associated with a lower risk of HCC than ETV treatment [hazard ratio (HR) = 0.222, 95% confidence interval (CI), 0.070–0.702, p = 0.010] but was similar after PSM (HR = 0.483, 95% CI, 0.144–1.626, p = 0.240; log-rank p = 0.230). However, subgroup analysis showed that the cumulative HCC incidence was lower in the TDF group than in the ETV group among patients with a modified PAGE-B score (mPAGE-B) ⩾9, either before or after PSM (log-rank p = 0.048 and p = 0.023, respectively).Conclusion:Among patients with an mPAGE-B score ⩾9, TDF is associated with a lower HCC incidence than ETV in patients with CHB-related compensated cirrhosis.

Efficacy and Safety of Peginterferon α-2a and Entecavir Tenofovir in the Treatment of Chronic Hepatitis B Genotype C.

This article discusses the clinical value of Pegylated Interferon (PEG-IFN) α-2a combined with entecavir or tenofovir in the treatment of Chronic Hepatitis B (CHB) genotype C patients. 78 patients with CHB genotype C were divided into three groups: control group, entecavir group, and tenofovir group according to different treatment methods. The efficacy and adverse reaction (AR) of the three groups are observed during 12 months of treatment and after drug withdrawal, and the clinical efficacy and safety of the three treatment methods are evaluated. The experimental results show that the sustained response rate (RR) in the tenofovir and entecavir groups is higher than that in the controls. The incidence of total AR in the tenofovir group is significantly higher than that in the control and entecavir groups. PEG-IFN α-2a and entecavir or tenofovir are more effective, and tenofovir has an antiviral effect.

Comparative study of treatment of HBV decompensated cirrhosis of liver patients by tenofovir and entecavir

Background and Aim: Decompensated cirrhosis is defined in patients with cirrhosis as an acute deterioration of their liver function and is characterized for jaundice, ascites, hepatic encephalopathy, hepatorenal syndrome (HRS) and varices. The aim of the study was to compare of Treatment of HBV decompensated Cirrhosis of Liver Patients by Tenofovir and Entecavir. Methods: The study was carried out at the inpatient department of hepatology, Bangabandhu Sheikh Mujib Medical University Hospital and Kurmitola General Hospital, Dhaka, Bangladesh. The study enrolled 100 treatment-naive patients with HBV decompensated cirrhosis of liver on Rntecavir or Tenofovir disoproxil fumarate from January 2013 to December 2018. Results: There are three follow up taken, first follow up was three months after medication. Second and third follow-up was after 06 months and 12-month completion of the treatment. In 3rd follow up (after one year), 100.0% patients were found undetected HBV DNA in Tenofovir group and 97.56% in Entecavir group. The difference was not statistically significant (p>0.05) between two groups. At 01-year total death was found 12 patients, out of them 03 was Tenofovir group and 06 was Entecavir group. In Tenofovir patients, Mean Child Pugh score was found 12.1±1.3 in pretreatment and 5.8±1.3 at 01 years. Mean MELD score was found 25.0±3.1 in pretreatment and 9.3±3.2 at 1 years. In Entecavir patients, Mean Child Pugh score was found 12.0±1.5 in pretreatment and 9.3±0.9 at 01 years. Mean MELD score was found 26.5±2.0 in pretreatment and 17.0±2.1 at 1 years. The difference of MELD and CTP score improvement was statistically significant (p<0.05) between two groups. Conclusions: Entecavir and Tenofovir both are good antiviral drugs for the treatment of HBV infection. In treatment of decompensated cirrhosis of liver Entecavir and Tenofovir both are significantly improved liver function, HBV DNA undetection and patient’s survival. But Tenofovir shown more improvement.

Tenofovir disoproxil fumarate is not associated with a lower risk of hepatocellular carcinoma compared to entecavir in patients with chronic hepatitis B

A paper published several years ago suggested that tenofovir disoproxil fumarate (TDF) was superior to entecavir (ETV) for reducing the risk of hepatocellular carcinoma (HCC). Since then, many observational studies have been conducted comparing TDF and ETV. Many studies in Asia demonstrated similar HCC risks between ETV and TDF groups. Similarly, recent studies involving Caucasian and European did not observe any differences in HCC risk between these groups. In this article, we briefly review studies that compared the incidence rates of HCC between ETV and TDF and discuss potential reasons for the discrepant results.

Tenofovir vs. entecavir on recurrence of hepatitis B virus-related hepatocellular carcinoma beyond Milan criteria after hepatectomy.

Background:Hepatectomy for hepatocellular carcinoma (HCC) beyond the Milan criteria is shown to be beneficial. However, a high rate of post-operative HCC recurrence hinders the long-term survival of the patients. This study aimed to investigate and compare the impacts of tenofovir (TDF) and entecavir (ETV) on the recurrence of hepatitis B viral (HBV)-related HCC beyond the Milan criteria.Methods:Data pertaining to 1532 patients who underwent hepatectomy and received antiviral therapy between January 2014 and January 2019 were collected from five centers. Recurrence-free survival (RFS) analysis was performed using the Kaplan–Meier method. Cox proportional hazards regression analysis was performed to determine prognostic factors for HCC recurrence.Results:The analysis incorporates 595 HBV-related HCC patients. The overall 5-year RFS was 21.3%. Among them, 533 and 62 patients received ETV and TDF treatment, respectively. The 1-, 3-, and 5-year RFS rates were 46.3%, 27.4%, and 19.6%, respectively, in the ETV group compared with 65.1%, 41.8%, and 37.2%, respectively, in the TDF group (P < 0.001). Multivariate analysis showed that TDF treatment (hazard ratio [HR]: 0.604, P = 0.005), cirrhosis (HR: 1.557, P = 0.004), tumor size (HR: 1.037, P = 0.008), microvascular invasion (MVI) (HR: 1.403, P = 0.002), portal vein tumor thrombus (PVTT) (HR: 1.358, P = 0.012), capsular invasion (HR: 1.228, P = 0.040), and creatinine levels (CREA) (HR: 0.993, P = 0.031) were statistically significant prognostic factors associated with RFS.Conclusions:Patients with HCC beyond the Milan criteria exhibited a high rate of HCC recurrence after hepatectomy. Compared to the ETV therapy, TDF administration significantly lowered the risk of HCC recurrence.

Entecavir Prevents HBV Reactivation During Direct Acting Antivirals for HCV/HBV Dual Infection: A Randomized Trial

A strategy to prevent hepatitis B virus (HBV) virologic reactivation (HBVr) and clinical reactivation (CR) during direct acting antiviral (DAA) treatment of hepatitis C virus (HCV)/HBV dual infection remains an unresolved issue. Noncirrhotic patients with dual HCV/HBV infection were enrolled and allocated randomly to 1 of 3 groups as follows: 12 weeks of DAA alone (group 1), 12 weeks of DAA plus 12 weeks of entecavir (group 2), or 12 weeks of DAA plus 24 weeks of entecavir (group 3). The entire study duration was 72 weeks. The primary end point was the occurrence of HBVr (defined by an increase of HBV DNA level >10-fold with quantifiable HBV DNA at baseline or the presence of HBV DNA with prior unquantifiable HBV DNA) and CR (defined by serum alanine aminotransferase level >2-fold the upper limit of normal in addition to HBVr). Fifty-six patients were allocated randomly as follows: 20 patients in group 1, 16 patients in group 2, and 20 patients in group 3. In group 1, HBV DNA levels increased significantly as early as 4 weeks after initiation of DAA and persisted until the end of the study. During DAA treatment, HBVr occurred in 50% in group 1 vs 0% in group 2 and 0% in group 3 (P < .001), whereas the majority of HBVr in groups 2 and 3 occurred 12 weeks after cessation of entecavir (cumulative incidence, 93.8% in group 2 and 94.7% in group 3). Three patients (5.4%; 1 in each group) showed CR at week 48 and did not receive entecavir treatment. Twelve weeks of entecavir is suggested to be co-administered with DAA for HCV/HBV dually infected patients. gov no: NCT04405011.

Longitudinal renal changes in chronic hepatitis B patients treated with entecavir versus TDF: a REAL-B study.

We aimed to compare the longitudinal changes in estimated glomerular filtration rate (eGFR) in chronic hepatitis B (CHB) patients treated with entecavir (ETV) vs. tenofovir disoproxil fumarate (TDF). This is a retrospective study of 6189 adult treatment-naïve CHB patients initiated therapy with TDF (n = 2482) or ETV (n = 3707) at 25 international centers using multivariable generalized linear modeling (GLM) to determine mean eGFR (mL/min/1.73m2) and Kaplan-Meier method to estimate incidence of renal impairment (≥ 1 chronic kidney disease [CKD] stage worsening). We also examined above renal changes in matched ETV and TDF patients (via propensity score matching [PSM] on age, sex, diabetes mellitus [DM], hypertension [HTN], cirrhosis, baseline eGFR, and follow-up duration). In the overall cohort (mean age 49.7years, 66.2% male), the baseline eGFR was higher for TDF vs. ETV group (75.9 vs. 74.0, p = 0.009). PSM yielded 1871 pairs of ETV or TDF patients with baseline eGFR ≥ 60 and 520 pairs for the eGFR < 60 group. GLM analysis of the overall (unmatched) cohort and PSM cohorts revealed lower adjusted mean eGFRs in TDF (vs. ETV) patients (all p < 0.01) during 10years of follow-up. Among PSM eGFR ≥ 60 patients, the 5-year cumulative incidences of renal impairment were 42.64% for ETV and 48.03% for TDF (p = 0.0023). In multivariable Cox regression, TDF vs. ETV (adjusted HR 1.26, 95% CI 1.11-1.43) was associated with higher risk of worsening renal function. Over the 10-year study follow-up, compared to ETV, TDF was associated with a lower mean eGFR and higher incidence of renal impairment.

Real-World Single-Center Comparison of the Safety and Efficacy of Entecavir, Tenofovir Disoproxil Fumarate, and Tenofovir Alafenamide in Patients with Chronic Hepatitis B

Introduction: Chronic hepatitis B (CHB) is a major cause of chronic liver diseases and tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and entecavir (ETV) are recommended as primary treatments. This study aimed to evaluate the efficacy and safety of ETV, TDF, and TAF in a real-world clinical setting. Methods: In this retrospective cohort study, a total of 363 CHB patients who were treated with ETV (n = 163), TDF (n = 154), or TAF (n = 46) from July 2007 to September 2019 were enrolled. Results: Median patient age was 51 years and 66.4% of patients were male. Median duration of treatment with ETV, TDF, or TAF was 49.0 months (interquartile range, 27.0–74.0 months). In terms of safety, cholesterol was mildly increased in the ETV and TAF groups and significantly lowered in the TDF group than baseline (p < 0.001). There was no significant difference in liver cirrhosis-related complications among the 3 groups at 48 weeks (p = 0.235). Hepatitis B e antigen seroconversion, complete virological response, and alanine aminotransferase normalization at 48 weeks as measures of treatment efficacy were not significantly different among the 3 groups (p = 0.142, 0.538, and 0.520, respectively). There was also no significant difference in cumulative incidence rate of hepatocellular carcinoma (HCC) between the ETV and TDF groups (p = 0.894). Conclusions: ETV, TDF, and TAF were safe antiviral agents and showed similar antiviral effect for CHB at 48 weeks. Cirrhosis-related complications and annual HCC incidence rates did not differ significantly between the ETV and TDF groups over the 48 week follow-up period.

Impact of switching to tenofovir alafenamide fumarate in patients with entecavir-treated chronic hepatitis B.

Tenofovir alafenamide (TAF), a new tenofovir prodrug, has been developed to circumvent the less favorable safety profile of tenofovir disoproxil fumarate (TDF). We investigated reductions in hepatitis B surface antigen (HBsAg) levels in patients with HBV infection who received continuous entecavir (ETV) monotherapy or sequential therapy with ETV and TAF. This retrospective cohort study included 286 patients who were divided into two groups: continuous ETV monotherapy (ETV group, n = 168) and sequential therapy with ETV and TAF (ETV-TAF group, n = 108). Factors associated with a 90% reduction in HBsAg levels were analyzed by a Cox proportional hazards model using a time-dependent covariate in both groups. In the multivariate Cox proportional hazards model, the ETV-TAF group [adjusted hazard ratio (aHR) 2.750; 95% confidence interval (CI), 1.265-3.405; P = 0.0038] and BMI ≤ 25.0 kg/m2 (aHR 0.520, 95% CI, 0.308-0.875; P = 0.0139) demonstrated a 90% reduction in HBsAg levels. HBsAg levels of patients in the TAF phase in the ETV-TAF group showed greater yearly percent reductions than those in the ETV group and those in the ETV phase in the ETV-TAF group (P = 0.0361 and P = 0.0022, respectively, Steel-Dwass test). HBsAg levels decreased more rapidly after patients switched from ETV to TAF. Switching to TAF may be an effective treatment option to reduce HBsAg levels.

Association between HBs Ag quantification and the risk of hepatocellular carcinoma in patients treated with tenofovir disoproxil fumarate or entecavir.

This study evaluated the clinical implications of hepatitis B surface antigen quantification (qHBs Ag) in chronic hepatitis B (CHB) patients treated with entecavir (ETV) or tenofovir disoproxil fumarate (TDF) and identified the association between qHBs Ag and the risk of hepatocellular carcinoma (HCC) in these patients.Between January 2007 and December 2018, the qHBs Ag and clinical data of 183 CHB patients who initially received ETV (n = 45, 24.6%) or TDF (n = 138, 75.4%) were analyzed.The mean follow-up period of the 183 CHB patients was 45.3 months, of which 59 (32.2%) patients showed a reduction in qHBs Ag by >50% after 1 year of antiviral treatment (ETV or TDF). The HCC development (P = .179) or qHBs Ag reduction (P = .524) were similar in the ETV and TDF groups. Patients with a ≥50% decrease in qHBs Ag had a significantly lower incidence of HCC or decompensated cirrhosis complications (P = .005). Multivariate analysis showed that a >50% reduction of qHBs Ag (hazard ratio 0.085, P = .018) and the presence of cirrhosis (hazard ratio 3.32, P = .016) were independent factors predicting the development of HCC.Patients whose qHBs Ag value decreased >50% at 1 year after antiviral treatment for CHB showed a significant decrease in HCC or decompensated cirrhosis events. A reduction in qHBs Ag could be used as a predictive factor of HCC development or critical complications in CHB patients treated with TDF or ETV.

Tenofovir Is Superior to Entecavir on Tertiary Prevention for BCLC Stage 0/A Hepatocellular Carcinoma after Curative Resection

Background: It is unclear whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) have different effects on hepatocellular carcinoma (HCC) recurrence and death in patients receiving curative hepatectomy for hepatitis B virus (HBV)-related HCC. Aims: The aim of this study was to compare the long-term efficacy of ETV and TDF in HCC recurrence and overall survival (OS) of patients after curative hepatectomy. Methods: From January 2010 to December 2019, 20,572 patients with HCC who received hepatectomy were screened for study eligibility. Finally, a total of 219 consecutive patients treated with ETV (n = 146) or TDF (n = 73) after curative hepatectomy for HBV-related HCC of Barcelona Clinic Liver Cancer stage 0 or A were analyzed by propensity score matching (PSM) (2:1) analysis and competing risk analysis. HCC recurrence and OS of patients were compared between ETV and TDF groups. Result: After a median follow-up of 52.2 months, 81 patients (37.0%) had HCC recurrence, 33 (15.1%) died, and 5 (2.3%) received liver transplantation. TDF therapy was an independent protective factor for HCC recurrence compared with ETV therapy (HR, 1.687; 95% CI, 1.027–2.770, p = 0.039); however, no difference in the risk of death or liver transplantation. Results were similar in competing risk analysis. We further found that TDF therapy was significantly associated with a lower risk of late recurrence (HR, 4.705; 95% CI, 1.763–12.558, p = 0.002), but not in early recurrence. Conclusions: TDF therapy is associated with a significantly lower risk of HCC recurrence, especially of late recurrence, than ETV therapy among patients who undergo curative hepatectomy for HBV-related early-stage HCC.

Long-term effects of entecavir and tenofovir treatment on the fibrotic burden in patients with chronic hepatitis B.

Antiviral therapy (AVT) induces fibrosis regression in patients with chronic hepatitis B. We investigated long-term effects of entecavir (ETV) versus tenofovir (TDF) on fibrotic burden. Treatment-naïve chronic hepatitis B patients who had begun ETV or TDF were recruited from four tertiary hospitals. The aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) were used to determine fibrotic burden. In the entire population (n=3277), although patients treated with ETV had higher baseline APRI (1.71 vs 1.07, P<0.001) and FIB-4 (3.60 vs 2.80, P<0.001) than those treated with TDF, significant fibrosis regression was identified during 6years of AVT in both ETV (APRI, mean 1.71→0.48, P<0.001; FIB-4, mean 3.60→2.21, P<0.001) and TDF groups (APRI, mean 1.07→0.43, P<0.001; FIB-4, mean 2.80→2.19, P<0.001). In patients without cirrhosis (n=2366), baseline APRI was significantly higher in ETV group than in TDF group (1.72 vs 0.97, P<0.001); however, they became similar after 6months. Similarly, baseline FIB-4 was significantly higher in ETV group than in TDF group (3.25 vs 2.35, P<0.001), but became similar from 4 to 6years. In patients with cirrhosis (n=911), baseline APRI (1.70 vs 1.34, P<0.001) and FIB-4 (4.62 vs 3.91, P=0.005) were higher in ETV group than in TDF, however, both parameters became statistically similar from 6months to 6years. Significant regression of APRI and FIB-4 was observed during long-term ETV and TDF treatment. Despite higher baseline fibrotic burden in ETV group, fibrotic burden between the groups eventually converged through significant fibrosis regression after 1 to 4years of AVT.

Impact of tenofovir alafenamide vs. entecavir on hepatocellular carcinoma risk in patients with chronic hepatitis B.

Whether entecavir (ETV) or tenofovir alafenamide (TAF) is better at preventing hepatocellular carcinoma (HCC) development among patients with chronic hepatitis B (CHB) remains unclear. The present study was conducted to explore the ability of these two antivirals to prevent HCC. From 2012 to 2019, treatment-naïve CHB patients undergoing ETV or TAF therapy were recruited at three academic teaching hospitals. The TAF group comprised patients starting TAF as first-line antiviral and those switching antivirals from tenofovir disoproxil fumarate to TAF. Patients with decompensated cirrhosis or HCC at enrollment were excluded from the analysis. Cumulative probabilities of HCC were assessed using the Kaplan-Meier method. In total, 1810 patients (1525 and 285 in ETV and TAF groups, respectively) were recruited. The annual HCC incidence was statistically not different between the ETV and TAF groups (1.67 vs. 1.19 per 100 person-years, respectively) with an adjusted hazard ratio (HR) of 0.681 (p = 0.255), as determined by multivariate analysis. Male, hypertension, liver cirrhosis, FIB-4 index, and albumin were independent prognostic factors for HCC development. Propensity score-matched and inverse probability of treatment weighting analyses yielded similar results, with non-statistically different HCC incidence between the ETV and TAF groups (1.07 vs. 1.19 per 100 person-years (HR = 0.973; p = 0.953) and 1.67 vs. 1.89 per 100 person-years, respectively (HR = 0.949; p = 0.743). These findings suggest that ETV- and TAF-treated CHB patients have similar risk of developing HCC. Further studies with the larger sample size and longer follow-up are needed to validate these results.

Clinical efficacy of antiviral therapy in patients with hepatitis B-related cirrhosis after transjugular intrahepatic portosystemic shunt.

BACKGROUNDAs a country with a high burden of hepatitis B, China has about 86 million cases of hepatitis B virus infection, ranking the first in the world. Currently, there are about 390000 deaths due to hepatitis B-related complications such as liver cirrhosis and liver cancer every year. Consequently, how to control portal hypertension, improve liver functional reserve, and reduce the incidence of hepatic failure and liver cancer in such patients is the focus of current clinical attention. Previous clinical study in our center suggested that at 24 mo after transjugular intrahepatic portosystemic shunt (TIPS), the liver functional reserve of patients with hepatitis B cirrhosis was better than that of patients with alcohol-induced and immune cirrhosis, which may be related to the effective etiological treatment.AIMTo investigate the clinical efficacy of three first-line antiviral drugs recommended by the guidelines of prevention and treatment for chronic hepatitis B in China (2019) in the treatment of patients with hepatitis B-related cirrhosis who had received a TIPS.METHODSThe clinical data of 137 patients with hepatitis B-related cirrhosis with portal hypertension after receiving TIPS at our centre between March 2016 and December 2020 were analysed retrospectively. According to different anti-viral drugs, the patients were divided into entecavir (ETV) (n = 70), tenofovir alafenamide fumarate (TAF) (n = 32), and tenofovir disoproxil fumarate (TDF) (n = 35) groups. The cumulative incidence of hepatic encephalopathy and hepatocellular carcinoma, survival, and changes in hepatic reserve function and glomerular filtration rate in patients treated with different antiviral drugs within 24 mo after surgery were investigated.RESULTSAt 24 mo after surgery, the Child–Pugh score in the TAF group (6.97 ± 0.86) was lower than that in the TDF (7.49 ± 0.82; t = -2.52, P = 0.014) and ETV groups (7.64 ± 1.17; t = -2.92, P = 0.004). The model for end-stage liver disease score in the TAF group at 24 mo after surgery was 9.72 ± 1.5, which was lower than that in the TDF (10.74 ± 2.33; t = -2.09, P = 0.040) and ETV groups (10.97 ± 2.17; t = -2.93, P = 0.004). At 24 mo after surgery, the estimated glomerular filtration rate (eGFR) in the TAF group (104.41 ± 12.54) was higher than that in the TDF (93.54 ± 8.97) and ETV groups (89.96 ± 9.86) (F = 21.57, P < 0.001).CONCLUSIONAt 24 mo after surgery, compared with TDF and ETV, TAF has significant advantages in the improvement of liver functional reserve and eGFR.

Efficacy of entecavir versus tenofovir in preventing hepatocellular carcinoma in patients with chronic hepatitis B with maintained virologic response.

Several studies suggested that efficacy of tenofovir in reducing the risk of the development of hepatocellular carcinoma (HCC) might be better than that of entecavir. It remains unknown whether a change in therapy can further reduce the risk of HCC in patients receiving entecavir therapy and achieved goal of antiviral therapy, a maintained undetectable hepatitis B virus (HBV) DNA level in the serum. A total of 1336 treatment-naïve chronic HBV mono-infected adult patients, who started entecavir or tenofovir treatment and achieved a maintained virologic response during follow-up were analysed. During a median 4.4years of follow-up (range, 1.0-7.4years) after achieving virologic response, 99 patients developed HCC. The 5-year cumulative HCC incidence rate was 7.3% and 6.3% for the entecavir and tenofovir groups, respectively, with similar risk of HCC between the two groups (adjusted HR, 0.82; 95% CI, 0.52-1.29; p=0.3). The risk of HCC was similar in the propensity score-matched cohort (HR, 1.02; 95% CI, 0.68-1.52; p=0.94) and inverse probability treatment weighting analysis (HR, 1.11; 95% CI, 0.74-1.66; p=0.62). In the subgroup analysis, HCC risk was similar between the two drugs in both patients with and without cirrhosis. In patients showing maintained virologic response, no difference in the risk of HCC between entecavir and tenofovir was observed. This indicates entecavir might be as effective as tenofovir in the prevention of HCC among those patients and suggest that a change in therapy in anticipation of further reducing the risk of HCC might not be necessary for patients receiving entecavir and showing virologic response.

Changes in the Cytokine Profiles of Patients with Chronic Hepatitis B during Antiviral Therapy

ObjectiveTo investigate the changes in the cytokine profiles of chronic hepatitis B (CHB) patients undergoing antiviral treatment. MethodsHepatitis B e antigen (HBeAg)-positive patients were treated with Pegylated interferon (PEG-IFN) and entecavir (ETV). Clinical biochemistry and cytokines were detected at baseline and every 3 months. ResultsIn all, 200 patients completed 48 weeks of treatment, 100 in the PEG-IFN group and 100 in the ETV group. During 3–6 months of treatment, compared with baseline, the PEG-IFN group showed a significant decrease in interferon-gamma (IFN-γ), interleukin-17A (IL-17A), interleukin-6(IL-6), interleukin-10(IL-10), and transforming growth factor beta (TGF-β) (P < 0.001) and a significant increase in interferon-alpha 2(IFN-α2) (P < 0.001). In the ETV group, IL-10 and TGF-β1 decreased significantly (P < 0.001). After 3 months, the levels of IFN-α2, IL-17A, and tumor necrosis factor-alpha(TNF-α) in the PEG-IFN group were significantly higher than those in the ETV group (P < 0.01). The levels of IL-6 and TGF-β3 were significantly lower than those in the ETV group (P < 0.01). After 6 months, the levels of IFN-α2, IFN-γ, and TNF-α in the PEG-IFN group were significantly higher than those in the ETV group (P < 0.01), while the levels of IL-6 and TGF-β3 were significantly lower than those in the ETV group (P < 0.01). Compared with ETV, PEG-IFN had higher HBeAg and HBsAg disappearance rates. ConclusionDuring antiviral therapy, a change in the cytokine profile occurred; in the aspect of immune control and functional cure, PEG-IFN was significantly better than ETV.

Effect of Additional Clostridium butyricum on the Intestinal Flora of Chronic Hepatitis B Patients Treated with Entecavir.

IntroductionTo explore the influence of intestinal flora on the occurrence, development and antiviral therapy of chronic hepatitis B (CHB), 16S rDNA amplification sequencing was performed to investigate the intestinal flora in CHB patients treated with entecavir (ETV) and Clostridium butyricum (CB).MethodsCHB patients were divided into the ETV group (treatment with ETV alone) and ETV + CB group (treatment with ETV and CB). After 8-week treatment, feces samples were collected and processed for 16S rDNA amplicon sequencing; blood samples were collected for the biochemical, immunologic and virologic evaluations, which were compared between groups.ResultsETV treatment for 8 weeks significantly decreased the serum levels of alanine aminotransferase (ALT), interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α) and HBV DNA compared to those before treatment, but there were no marked differences between the ETV group and ETV + CB group. The intestinal flora changed significantly in the CHB patients after ETV + CB treatment: there were marked differences in 13 unique species before treatment and 4 unique species after ETV + CB treatment; at the phylum level, the top five bacteria with significant difference between patients before treatment and ETV + CB patients were Firmicutes, Actinobacteria, Cyanobacteria, Euryarchaeota and Synergistetes. There were significant differences in 25 unique species in the ETV group and 4 unique species in the ETV + CB group; at the phylum level, the top five bacteria with significant difference between ETV patients and ETV + CB patients were Actinobacteria, Fusobacteria, Proteobacteria, Saccharibacteria and Synergistetes.ConclusionETV treatment improves the serum biochemical, immunologic and virologic variables, but additional CB fails to further improve these variables. Of note, additional CB affects the intestinal flora in the CHB patients treated with ETV.

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?

The efficacies of entecavir and tenofovir in terms of enhancing prognosis after curative treatment of hepatitis B virus–related hepatocellular carcinoma

Background/aimsWhether entecavir (ETV) or tenofovir disoproxil fumarate (TDF) affords the better prognosis after curative treatment of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains unclear. We compared recurrence and death rates between patients taking ETV and those taking TDF. MethodsBetween 2013 and 2017, patients with HBV-related HCC who had undergone hepatic resection (n=421) or radiofrequency ablation (n=305) as first-line anti-HCC treatment in three institutes were consecutively enrolled. All patients received ETV or TDF as a first-line antiviral. The cumulative probabilities of recurrence and death were assessed. We adjusted for viral factors, including the HBV-DNA load, and tumor and demographic factors. ResultsDuring the study period (median 46.6 [interquartile range 25.3–58.9] months), 227 patients experienced recurrence and 53 died. In the ETV (n=405) and TDF (n=321) groups, the annual incidences of recurrence (10.61 and 11.21 per 100 person-years, respectively; P=727) and death (2.28 and 1.79 per 100 person-years, respectively; P=277) were similar, with adjusted hazard ratios (aHRs) of 0.932 (P=0.622) and 0.667 (P=0.193), respectively. When stratified by treatment modality and the timing of antiviral therapy commencement, the values were similar (all P>0.05). Inverse probability of treatment weighting (IPTW) analyses yielded results that were similar in the two groups in terms of recurrence (aHR=1.038, P=0.963) and death (aHR=0.799, P=0.431). Furthermore, the early (<2 years) and late (≥2 years) recurrence risks were not statistically different in the two groups (both P=0.400), as confirmed by IPTW analysis (P=0.502 and P=0.377, respectively). ConclusionsThe prognoses in terms of recurrence and death after curative treatment of HBV-related HCC were not statistically different between the ETV and TDF groups. Further validation studies are needed.

Tenofovir Disoproxil Fumarate Is Superior to Entecavir in Reducing Hepatitis B Surface Antigen for Chronic Hepatitis B in China: 2-Year Comprehensive Comparative Result of a Matched Comparative Study.

Aim: Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are equally recommended as the first-line antiviral treatments for chronic hepatitis B (CHB) at present. We aimed to compare the long-term efficacy and safety between ETV and TDF therapy in CHB patients who had not received nucleoside analog treatment.Method: In this single-center retrospective study, 414 patients who received ETV (290 patients) or TDF (124 patients) therapy at our center from January 2017 to May 2019 were included. To reduce the imbalance of baseline variables, propensity score matching (PSM) was employed to yield 124 pairs of patients at a ratio of 1:1 based on the treatment regimen.Result: After PSM, the cumulative rate of patients who achieved complete virological response (CVR) was not different by drug therapy at each inspection time (1, 3, 6, 12, 18, and 24 months). Subgroup analysis on HBeAg status and level of HBV DNA demonstrated that evolution of proportion of achieving CVR was not significantly different between groups. Despite the insignificant incidence of HBsAg seroclearance in either group, patients in TDF group achieved higher on-treatment HBsAg decline at each inspection time (1, 3, 6, 9, 12, 18, and 24 months), 0.39, 0.51, 0.61, 0.64, 0.68, 0.76, and 0.91 log IU/mL, respectively; while the corresponding reduction were 0.27, 0.37, 0.40, 0.45, 0.48, 0.55, and 0.66 log IU/mL in ETV group (p < 0.05). In subgroup analysis, we found that the significant difference still existed in patients with high baseline HBsAg level (>3 log IU/mL). Additionally, the proportion of patients who achieved on-treatment HBsAg decline >1 log IU/mL in TDF and ETV group was 33.3 and 17.1% (p < 0.01) at the 12th month, 44.4 and 29.5% (p = 0.03) at the 24th month, respectively. Mean increase in serum creatinine from baseline was 0.10 and 0.08 mg/dL in TDF and ETV group (p = 0.11), with no patient experienced acute kidney injury.Conclusions: TDF has higher potency in reducing HBsAg than ETV in this study. Considering the effect still existed in patients with high HBsAg level (>3 log IU/mL), TDF might be a superior therapeutic regimen combining with its relatively safety.