Entecavir In Hepatitis Research Articles

Tenofovir Is Associated With a Better Prognosis Than Entecavir for Hepatitis B Virus–Related Hepatocellular Carcinoma

Whether tenofovir or entecavir has different effects on the prevention of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in secondary and tertiary preventive settings is still a matter of debate. This study aimed to compare the long-term prognosis of HCC between tenofovir and entecavir in patients with chronic hepatitis B. Chronic hepatitis B patients diagnosed with HCC between November 2008 and December 2018 and treated with either entecavir or tenofovir at a tertiary center in Korea were included. The effect of tenofovir compared with entecavir on the prognosis of HBV-related HCC was assessed using multivariable-adjusted Cox and propensity score (PS)-matched analyses. Various predefined subgroup analyses were conducted. During a median follow-up period of 3.0 years, the mortality rate for entecavir-treated patients (n= 3469) was 41.2%, while tenofovir-treated patients (n= 3056) had a mortality rate of 34.6%. Overall survival (OS) was better in the tenofovir group (adjusted hazard ratio [aHR], 0.79; P < .001), which were consistently observed in the PS-matched analysis. The magnitude of the risk difference in OS was more prominent 2 years after the diagnosis of HCC (aHR, 0.50; P < .001) than 2 years before (aHR, 0.88; P= .005), and it was more pronounced in patients with earlier HCC stages. In all subgroups, except for those with shorter life expectancy, such as those with compromised liver function, tenofovir was associated with better OS compared with entecavir. Among patients with HBV-related HCC, those treated with tenofovir had a better prognosis than those treated with entecavir, particularly among those with prolonged survival.

Risk factors for relapse after discontinuation of tenofovir or entecavir in hepatitis B e antigen-negative patients.

This study aimed to define the relapse frequency and risk determinants in chronic hepatitis B (CHB) patients who discontinued nucleoside analog (NA) treatment, were HBeAg-negative, and had achieved both a virological and biochemical response. This retrospective cohort study reviewed patients with HBeAg-negative CHB who received antiviral therapy for at least 65 months between January 1, 2013, and December 31, 2020. These patients discontinued treatment after demonstrating a biochemical and virological response and were evaluated at 6, 12, and 24 months post-treatment discontinuation. Sixty-seven patients with CHB who received NA therapy for at least 65 months, discontinued treatment, and had undetectable HBV DNA and normal ALT values were evaluated. After cessation of NA therapy, a relapse was observed in 38 patients (56.7%). The relapse rate was 71.0% in patients treated with tenofovir disoproxil fumarate (TDF) as the last NA type and 37.9% in patients treated with entecavir (ETV) (p=0.017). The cutoff value for the best estimate of age for predicting relapse was 42 years. The relapse rate was 69.2% in patients aged ≥42 years and 39.2% in patients aged <42 years (p=0.007). The relapse rate was 51.3% in patients with a pre-treatment fibrosis score of 2, 56.0% in those with a fibrosis score of 3, and 100% in those with a fibrosis score of 4 (p=0.089). Among HBeAg-negative CHB patients who achieved a virological and biochemical response to long-term antiviral therapy, those aged 42 years and older, those with high fibrosis scores before treatment, and those who used TDF before treatment cessation should be closely monitored for relapse, especially in the first 12 months after stopping NA treatment.

Polymyositis concomitant with hepatitis B virus infection: Treatment challenges.

Polymyositis is a chronic autoimmune disease that presents with symmetrical progressive proximal muscle weakness. The cause of this disease due to abnormal activation of macrophages that might be associated with systemic diseases such as other autoimmune diseases, malignancy or viral infections including hepatitis B virus. The aim of this case report was to highlight treatment challenges in a patient with polymyositis concomitant with hepatitis B. A 28-years-old man with history of completed hepatitis B treatment with negative viral load presented with symmetrical progressive weakness on both inferior proximal extremities. The patient complained of pain predominantly in both tights and calves. No dermatological manifestation was observed. Elevated muscle enzymes and liver function were observed. Along with the course of the disease, hepatitis B reactivation was discovered as hepatitis B virus DNA was re-detected. Treatment options of this patient (polymyositis concomitant with hepatitis B viral infection) remain challenging. The main treatment of polymyositis consists of high dose methylprednisolone and this immunosuppressant could worsen the hepatitis B virus infection. The patient was finally treated with combination of mycophenolic acid and methylprednisolone for polymyositis and entecavir for hepatitis B. After one month of treatment, the patient showed a clinical improvement. This case highlights that viral screening must be done prior to starting polymyositis treatment as it could concomitant with viral infections such as hepatitis B. Antiviral prophylaxis must be given 1-2 weeks before immunosuppression starts. Management for both polymyositis and hepatitis B is important with entecavir or tenofovir as the optimal agents against hepatitis B virus.

CLINICAL, BIOCHEMICAL AND VIROLOGICAL RESPONSES TO ENTECAVIR IN PATIENTS WITH HBV - RELATED CIRRHOSIS

Background: Limited data is available from Vietnam on the outcome and efficacy of entecavir in hepatitis B virus (HBV) - related cirrhosis. This study aims to investigate clinical, biochemical and virological responses in patients with HBV - related cirrhosis treated with entecavir. &#x0D; Subjects and methods: 93 patients with HBV - related cirrhosis were examined and treated at Danang Hospital from Dec 2016 to June 2019. Of these, 59 patients with compensated cirrhosis and 34 patients with decompensated cirrhosis. Drugs: Entecavir (BaracludeR) was given a dose of 0.5mg and 1mg per day for compensated and decompensated cirrhosis, respectively, 2 hours after breakfast, monitor for 12 months. &#x0D; Results: Entecavir treatment of 12 months resulted in a marked improvement in common clinical symptoms including anorexia, fatigue, jaundice (p &lt; 0.001) and edema (p &lt; 0.01). Significantly decreased the Child - Pugh score (5.75 ± 1.06 compared to 6.43 ± 1.63 points). Normalized rates of AST and ALT were 67.74% and 78.49%, respectively, of which the compensated cirrhotic group had a higher rate than the decompensated group (AST: 76.27% vs 52.94%; ALT: 88.14% vs 61.76%). The rate of achieving HBV DNA &lt; 20IU/mL increased with time of treatment after 6 months was 34.4% and after 12 months reached 76.3%. There is no significant effect of entecavir on renal function and metabolism of serum calcium and lactate. Conclusion: Entecavir is an effective and safe treatment option for patients with HBV - related cirrhosis, especially exerts a better effect on patients with compensated cirrhosis that may improve the prognosis of cirrhotic patients.

Dynamic changes of cytokine profiles and virological markers during 48 weeks of entecavir treatment for HBeAg-positive chronic hepatitis B.

ObjectiveThe aims of this study were to investigate the kinetic changes of serum, virological, and immunological markers during entecavir (ETV) antiviral therapy and to explore whether these indicators can predict the antiviral efficacy of ETV in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients.MethodsHBeAg-positive CHB patients were enrolled and treated with ETV 0.5 mg/day. Clinical biochemical, virological, and serological tests were performed at baseline and every 12 weeks during the 48-week treatment. Plasma levels of cytokines (Flt-3L, IFN-α2, IFN-γ, IL-10, IL-17A, IL-6, TGF-β1, TGF-β2, TGF-β3, and TNF-α) were measured at baseline and at 12 and 24 weeks after treatment. Analysis of the trends of these clinical indicators in ETV antiviral therapy was performed.ResultsA total of 105 HBeAg-positive CHB patients were enrolled, and 100 of them completed 48 weeks of ETV treatment and follow-up. After 48 weeks of treatment, hepatitis B s antigen (HBsAg) decline ≥ 1 log10 was found in seven patients, but no patient achieved HBsAg disappearance. serological HBeAg disappeared in 13 patients, and serological HBeAg transformed in 3 patients. The baseline HBsAg and HBeAg levels, HBV DNA load, IL-10, and TGF-β1 levels in the complete virological response group were lower than those in the incomplete virological response group, while the ALT level in the complete virological response group was higher than that in the incomplete virological response group. Both univariate analysis and multivariate analysis showed that baseline biochemical indexes, virological indexes, and cytokine levels had no correlation with the complete virological response at 48 weeks. In multivariate analysis, low baseline HBV DNA load, and HBeAg and IL-10 levels were significantly associated with ALT normalization after 48 weeks of ETV treatment (HBeAg OR = 1.003, 95% CI 1.001–1.006, p = 0.007; HBV DNA OR = 0.184, 95% CI 0.046–0.739, p = 0.017; IL-10 OR = 0.040, 95% CI 0.972–0.999, p = 0.040).ConclusionCytokine levels changed dynamically during ETV antiviral therapy. Low baseline HBV DNA load, and HBeAg and IL-10 levels were significantly associated with ALT normalization after 48 weeks of ETV treatment.

Comparison of tenofovir alafenamide and entecavir for hepatitis B virus-related acute-on-chronic liver failure.

Hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) is the most common type of liver failure in China, with a high mortality. Early rapid reduction of HBV-DNA load can improve the survival rate of HBV-ACLF patients. At present, the commonly used drugs are nucleoside (acid) analogues, such as entecavir (ETV), tenofovir, and so on. The newly listed tenofovir alafenamide fumarate (TAF) has attracted great attention of clinicians because of its stronger antiviral effect, higher transaminase normalization rate, better bone and kidney safety, and zero drug resistance. However, there are few clinical research data on the efficacy and safety of TAF in the treatment of Chinese HBV-ACLF patients, and there is a lack of pharmacoeconomic evaluation. This study aims to compare the efficacy, safety, and cost-effectiveness between TAF and ETV in patients with HBV-ACLF. The data were collected from 196 HBV-ACLF patients (80 patients in the TAF group and 116 patients in the ETV group) who were hospitalized in Xiangya Hospital, Central South University from May 2020 to March 2021. Biochemistry and virology were detected before and after treatment (at baseline, Week 2, 4, and 12). Clinical features, disease prognosis, and cost-effectiveness were compared between the 2 groups. According to the baseline, HBV-ACLF patients were divided into 4 stages including pre-liver failure stage, early stage, medium stage, and end stage. And the liver transplantation rate and mortality was also compared. Pharmacoeconomic evaluation was taken using cost-effectiveness analysis and cost minimization analysis．. After 4 weeks of treatment, there were no significant differences in the efficacy (liver function, viral load) between the 2 groups (all P>0.05). The TAF group showed lower creatinine [(80.35±18.77) μmol/L vs (105.59±82.32) μmol/L, P<0.05] and higher estimated glomerular filtration rate (eGFR) levels [(95.65±23.21) mL/(min·1.73 m2) vs (82.68±26.32) mL/(min·1.73 m2), P<0.05] than the ETV group. After 12 weeks of treatment, the analysis of overall the liver transplantation rate and mortality between the 2 groups showed similar conclusion. However, the TAF group had a lower the liver transplantation rate and mortality than the ETV group in patients with pre-liver failure (0vs13.89%, P<0.05). No evident distinction was found in the liver transplantation rate and mortality during the early, medium, or end stages of liver failure (13.04% vs 17.65%, 37.50% vs 37.04%, and 54.55% vs 68.42%, respectively). Ratio of cost to effectiveness in the ETV group was higher than that in the TAF group. TAF is not more efficient than ETV group in improving liver function and reducing viral load for HBV-ACLF patients and they also show similar safety. However, TAF has a greater advantage over ETV not only in preserving renal function, but also in reducing the liver transplantation rate and mortality in patients with pre-liver failure. TAF can provide economic benefit to patients with HBV-ACLF.

The role of hepatitis B virus core-related antigen in predicting hepatitis B virus relapse after cessation of entecavir in hepatitis B e antigen-negative patients.

This study investigated the ability of hepatitis B core-related antigen (HBcrAg) to predict hepatitis B virus (HBV) relapse in HBeAg-negative patients after cessation of entecavir therapy. A total of 301 HBeAg-negative patients without cirrhosis who had stopped entecavir therapy for at least 12months were recruited. All patients fulfilled the stopping criteria proposed by the APASL 2012 guidelines. The five-year cumulative rates of virological relapse, clinical relapse and HBsAg loss were 71.6%, 57.3% and 18.7%, respectively. Serum HBsAg at end of treatment (EOT) was an independent predictor of virological relapse, clinical relapse and HBsAg loss; an EOT HBsAg of 150IU/ml was the optimal cut-off value. The 5-year virological relapse rates for patients with <150 and ≥150IU/ml HBsAg at EOT were 43.3% and 82.2% (p<0.001), clinical relapse rates were 32.3% and 66.3% (p<0.001), and HBsAg loss rates were 46.1% and 5.2% (p<0.001), respectively. A baseline HBcrAg of 4IU/ml was the optimal cut-off value for predicting HBV relapse. Among patients with an EOT HBsAg <150IU/ml, the five-year virological relapse rates for patients with baseline HBcrAg levels ≤4 and >4 log U/ml were 27.9% and 59.1% (p=0.006) and the clinical relapse rates were 18% and 48.1% (p=0.014), respectively. EOT HBcrAg was not a significant predictor of virological or clinical relapse after cessation of entecavir. In conclusion, the combination of an EOT HBsAg of 150IU/ml and baseline HBcrAg of 4 log U/ml can effectively predict the risk of HBV relapse after stopping entecavir therapy.

C3 glomerulonephritis in post transplanted patient with MGRS (A case report)

C3 glomerulopathy includes several rare forms of glomerulonephritis with underlying defects in the alternative pathway of complement cascade. It is characterized by predominant C3 deposition in glomeruli due to abnormal activation of the alternative pathway of the complement system. C3 GN has been reported to be associated with several systemic diseases. Methods We MEDICUS / No. 4, 2021 13 will describe a case presenting C3 GN in a patient with monoclonal gammopathy of renal significance (MGRS) Results A 61 years old man patient presented with gross hematuria,anemia ,renal disfunction (creatinemia 2,4 mg/dl), proteinuria 814 mg/24 h. The patient was transplanted two years ago and he was taking corticosteroids ,MMF,tacrolimus and entecavir for hepatitis B .Serum protein electrophoresis ; hypogammaglobulinemia with a small homogeneous spike-like peak. Serum Kappa free light chains 32,4 mg/dl ,serum Lambda free light chains 9.3 mg/dl.Ratio 3,4 . Autoimmune tests ANA, ANCA, Anti ds DNA C3 and C4 were negative.Urine Kappa Light Chains 26,4 mg/24 h,urine Lambda Light Chains 6,6 mg/24h.Urine Kappa/Lambda ratio 4. After consultation with haematolgist results of bone narrow biopsy came for monoclonal gammopathy , and FISH conclusion is presence of t(11,14)(q13,q32)which originated from IgH / CCND1 retraction and 1q21 acquisition. Renal biopsy is C3 glomerulopathy with mesengial and diffuse endocapillary proliferation under light microscope and diffuse deposition of C3 and no immunoglobulin under immunofluorescence microscope. Conclusions Monoclonal gammopathy of renal significance MGRS is a term to describe a group of haematological disorders associated with kidney disease that fail to meet the standard definitions for MM or lymphoma. In such cases, the renal impairment is often linked to the underlying hematological disorder. The intention was to make a clear distinction between MGUS, a benign asymptomatic condition, and MGRS, which may be associated with significant morbidity and mortality.

Prospective and Randomized Comparison of Tenofovir and Entecavir in Hepatitis B Reactivation Prophylaxis in Patients Receiving Immunosuppressive Therapy

Prospective and Randomized Comparison of Tenofovir and Entecavir in Hepatitis B Reactivation Prophylaxis in Patients Receiving Immunosuppressive Therapy

Low hepatitis B surface antigen and HBV DNA levels predict response to the addition of pegylated interferon to entecavir in hepatitis B e antigen positive chronic hepatitis B.

SummaryBackgroundVarious treatment combinations of peginterferon (PEG‐IFN) and nucleos(t)ide analogues have been evaluated for chronic hepatitis B (CHB), but the optimal regimen remains unclear.AimsTo study whether PEG‐IFN add‐on increases response compared to entecavir (ETV) monotherapy, and whether the duration of ETV pretreatment influences response.MethodsResponse was evaluated in HBeAg positive patients previously treated in two randomized controlled trials. Patients received ETV pretreatment for at least 24 weeks and were then allocated to 24‐48 weeks of ETV+PEG‐IFN add‐on, or continued ETV monotherapy. Response was defined as HBeAg loss combined with HBV DNA <200 IU/mL 48 weeks after discontinuing PEG‐IFN.ResultsOf 234 patients, 118 were assigned PEG‐IFN add‐on and 116 continued ETV monotherapy. Response was observed in 38/118 (33%) patients treated with add‐on therapy and in 23/116 (20%) with monotherapy (P = 0.03). The highest response to add‐on therapy compared to monotherapy was observed in PEG‐IFN naive patients with HBsAg levels below 4000 IU/mL and HBV DNA levels below 50 IU/mL at randomization (70% vs 34%; P = 0.01). Above the cut‐off levels, response was low and not significantly different between treatment groups. Duration of ETV pretreatment was associated with HBsAg and HBV DNA levels (both P < 0.005), but not with response (P = 0.82).ConclusionsPEG‐IFN add‐on to ETV therapy was associated with higher response compared to ETV monotherapy in patients with HBeAg positive CHB. Response doubled in PEG‐IFN naive patients with HBsAg below 4000 IU/mL and HBV DNA below 50 IU/mL, and therefore identifies them as the best candidates for PEG‐IFN add‐on (Identifiers: NCT00877760, NCT01532843).

Comparison of the long-term efficacy between entecavir and tenofovir in treatment- na\xefve chronic hepatitis B patients

BackgroundThere have been limited studies directly comparing the long-term efficacy between entecavir (ETV) and tenofovir disoproxil fumarate (TDF). This study was aimed to compare the long-term efficacy between them in treatment-naïve chronic hepatitis B (CHB).MethodsOut of 345 CHB patients who received first line therapy with ETV (n = 200) or TDF (n = 145) in a cohort, 210 patients were analyzed using propensity score matching, at a ratio of 1:1.ResultsTwo groups showed no difference in baseline characteristics. During the follow-up of 12 months, HBV DNA levels were similarly suppressed in both groups (ETV vs. TDF; −5.01 vs. -5.242 log10IU/mL, P = 0.559). At month 12, both groups showed no difference in terms of the serologic, biochemical and virologic (VR) response. In multivariate analysis, the initial virologic response at 3 months (IVR-3) was independent factor for VR at 1 year. During the long-term follow-up, HBV DNA levels were more strongly suppressed by TDF than ETV in hepatitis B e antigen (HBeAg) positive patients (P = 0.035), especially with high viral load (P = 0.012), although there was no significant difference in overall VR between two groups. The type of antivirals was not an independent factor for long-term VR.ConclusionsAlthough either ETV or TDF, overall, may show a comparable long-term antiviral efficacy in treatment-naïve CHB, TDF might be better regimen than ETV in the subgroup of HBeAg-positive CHB, especially with a higher HBV DNA levels.

Co-treatment with pegylated interferon alfa-2a and entecavir for hepatitis D: A randomized trial.

To investigate the efficacy of pegylated interferon alfa (PEG-IFNα) therapy with and without entecavir in patients with chronic hepatitis D. Forty hepatitis D virus (HDV) RNA positive patients were randomized to receive either PEG-IFNα-2a 180 μg weekly in combination with entecavir 0.5 mg daily (n = 21) or PEG-IFNα alone (n =19). Patients who failed to show 2 log reduction in HDV RNA level at 24 wk of treatment, or had detectable HDV RNA at 48 wk of therapy were considered as treatment failure. Treatment was continued for 72 wk in the rest of the patients. All the patients were followed for 24 wk post treatment. Intention to treat analysis was performed. The mean age of the patients was 26.7 ± 6.8 years, 31 were male. Two log reduction in HDV RNA levels at 24 wk of therapy was achieved in 9 (43%) patients receiving combination therapy and 12 (63%) patients receiving PEG-IFNα alone (P = 0.199). Decline in hepatitis B surface antigen (HBsAg) levels was insignificant. At the end of treatment, HDV RNA was negative in 8 patients (38%) receiving combination therapy and 10 patients (53%) receiving PEG-IFNα-2a alone. Virological response persisted in 7 (33%) and 8 (42%) patients, respectively at the end of the 24 wk follow-up period. One responder patient in the combination arm lost HBsAg and became hepatitis B surface antibody positive. Six out of 14 baseline hepatitis B e antigen reactive patients seroconverted and four of these seroconverted patients had persistent HDV RNA clearance. Administration of PEG-IFNα-2a with or without entecavir, resulted in persistent HDV RNA clearance in 37% of patients. The addition of entecavir did not improve the overall response.

Prolonged use of tenofovir and entecavir in hepatitis B virus-related cirrhosis.

Limited data is available from India on outcome and efficacy of tenofovir and entecavir in hepatitis B virus (HBV)-related cirrhosis when used for prolonged time. We report the long-term efficacy and outcome of these antiviral drugs in patients with chronic HBV infection, with compensated or decompensated cirrhosis. We retrospectively analyzed laboratory and clinical data of 400 HBV-related cirrhotic patients without access to liver transplantation, who were treated with tenofovir/entecavir therapy, from January 2007 to January 2014. Two hundred and ten (52.5%) patients had at least one of the components of decompensation at baseline. Two hundred and twenty (55%) and 180 (45%) patients were initiated tenofovir and entecavir, respectively. Follow up period was 45 (12-68) months for tenofovir and 36 (11-60) months for entecavir. At the end of 1year, levels of HBV DNA <20IU/mL were achieved in 91.8 % and 88.8% of patients, and alanine aminotransferase normalized in 54.5 % and 55.5% of patients who received tenofovir and entecavir, respectively. At the last visit, Child-Turcotte-Pugh scores improved among 29.5% of patients who received tenofovir, 25% of those who received entecavir, and remained stable in 61.9 % and 65% patients, respectively, in both groups. The 5-year cumulative rate of liver decompensation, hepatocellular carcinoma, and cirrhosis-related complications were 3.1 %, 1.9 %, and 2.1% with an annual incidence of 0.8 %, 0.3 %, and 0.5% per person-year, respectively. Tenofovir and entecavir were effective and potent drugs for prolonged treatment of HBV cirrhosis and improved the overall clinical course.

Sequential combination therapy with pegylated interferon leads to loss of hepatitis B surface antigen and hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive chronic hepatitis B patients receiving long-term entecavir treatment.

Nucleos(t)ide analogues rarely result in a durable off-treatment response in chronic hepatitis B infection, whereas pegylated interferon (Peg-IFN) induces a long-lasting response only in a subset of patients. We assessed the effect of sequential combination therapy with Peg-IFN-α2a and entecavir in hepatitis B e antigen (HBeAg)-positive patients with prior long-term entecavir therapy and investigated the predictors of response to treatment. HBeAg-positive individuals who did not achieve HBeAg seroconversion during previous long-term entecavir therapy, receiving Peg-IFN-α2a added to ongoing entecavir therapy (sequential combination [S-C] therapy; n = 81) for 48 weeks or remaining on entecavir monotherapy (n = 116), were retrospectively included. A matched pair was created at a 1:1 ratio from each treatment group. The primary endpoint was HBeAg seroconversion at week 48. Subgroup analysis of response prediction was conducted for 81 patients with S-C therapy. More patients in the S-C therapy group achieved HBeAg seroconversion than those in the entecavir group (44% versus 6%; P < 0.0001). An HBeAg level of <200 signal-to-cutoff ratio (S/CO) at baseline was a strong predictor for higher HBeAg seroconversion than that achieved when HBeAg was ≥200 S/CO (64.2% versus 17.9%; P < 0.0001). Hepatitis B surface antigen (HBsAg) levels at baseline and the decrease in HBsAg levels predicted HBsAg loss in the S-C therapy group. The combination of baseline HBeAg of <200 S/CO and HBsAg of <1,000 IU/ml and an HBsAg decline at week 12 of ≥0.5 log10 IU/ml provided the highest rate of HBeAg seroconversion (92.31%) and HBsAg loss (83.3%) at week 48. Patients receiving sequential combination therapy have a higher rate of HBeAg seroconversion and are more likely to experience HBsAg clearance than do those continuing entecavir monotherapy. Sequential combination therapy can be guided by baseline HBsAg/HBeAg levels and on-treatment HBsAg dynamics.

The efficacy and risk of prophylactic entecavir for hepatitis B virus-related hepatocellular carcinonma receiving transcatheter arterial chemoembolization.

388 Background: Hepatitis B virus (HBV) reactivation was reported to be induced by transcatheter arterial chemoembolization (TACE) in HBV-related hepatocellular carcinonma (HCC) patients with a high incidence. The effective strategy to reduce hepatitis flares due to HBV reactivation in this specific group of patients was limited to lamivudine. This retrospective study was aimed to investigate the efficacy of prophylactic entecavir in HCC patients receiving TACE. Methods: A consecutive series of 191 HBV-related HCC patients receiving TACE were analyzed including 44 patients received prophylactic entecavir. Virologic events, defined as an increase in serum HBV DNA level to more than 1 log10 copies/ml higher than nadir the level, and hepatitis flares due to HBV reactivation were the main endpoints. Results: Patients with or without prophylactic were similar in host factors and the majorities of characteristics regarding to tumor factors, HBV status, liver function and LMR. Notably, cycles of TACE were parallel between the groups. Ten (22.7%) patients receiving prophylactic entecavir reached virologic response. The patients receiving prophylactic entecavir presented significantly reduced virologic events (6.8% vs 54.4%, p=0.000) and hepatitis flares due to HBV reactivation (0.0% vs 11.6%, p=0.039) compared with patients without prophylaxis. Kaplan-Meier analysis illustrated that the patients in the entecavir group presented significantly improved virologic events free survival (p=0.000) and hepatitis flare free survival (p=0.017). Female and Eastern Cooperative Oncology Group (ECOG) performance status 2 was the only significant predictors for virological events in patients without prophylactic antiviral. Rescue antiviral therapy did not reduce the incidence of hepatitis flares due to HBV reactivation. Conclusions: Prophylactic entecavir presented promising efficacy in HBV-related cancer patients receiving TACE. Lower performance status and female gender might be the predictors for HBV reactivation in these patients.

Efficacy and tolerability of Entecavir for hepatitis B virus infection after hematopoietic stem cell transplantation.

IntroductionHepatitis B virus (HBV) flare is a serious problem following hematopoietic stem cell transplantation (HSCT), and the mortality rate is high if severe hepatitis occurs.Case descriptionAlthough Entecavir (ETV) is a standard antiviral drug for HBV infection, the efficacy and safety of ETV therapy in HSCT are still unclear.Discussion and EvaluationTo examine the efficacy and tolerability of ETV treatment in HSCT, we retrospectively identified 5 patients who received ETV for treatment of HBsAg carrier among patients undergoing HSCT in our institute. We reviewed their clinical information such as clinical course of serum HBV DNA levels, administration period and dose of ETV, and adverse events. There were no episodes of HBV flare or reactivation after HSCT in all patients during the observation period, as a 10-fold rise in HBV DNA levels or positive conversion of HBsAg were not observed.ConclusionETV monotherapy is effective and safe for HBsAg carrier patients following HSCT.

HBV-DNA level at 6 months of entecavir treatment predicts HBeAg loss in HBeAg-positive chronic hepatitis B patients

To evaluate whether on-treatment HBV-DNA level could predict the treatment response to entecavir in hepatitis B e antigen (HBe)-positive chronic hepatitis B (CHB) patients. A total of 68 treatment-naïve HBeAg-positive patients (75% male, mean age at 46.6 ± 11.9 years) receiving at least 2 years of entecavir therapy were enrolled. The primary therapeutic endpoint was HBeAg loss. On-treatment complete virological response was defined as serum HBV-DNA < 63 IU/mL. The median baseline alanine aminotransferase (ALT) and HBV-DNA levels were 199.5 (27-1622) U/L and 7.7 (3.8-13.2) log10 IU/mL, respectively. The median treatment duration was 31.7 (24.3-69.6) months. The rate of HBeAg loss at 2 years was 30.9%. By univariate analysis, on-treatment complete virological response at Month 6 was associated with HBeAg loss at 2 years (p = 0.019). After adjustment for age, sex, cirrhosis, baseline ALT, and HBV-DNA levels, this factor remained significant in multivariate analysis (odds ratio: 4.35; 95% confidence interval: 1.24-15.24, p = 0.021). On-treatment complete virological response at Month 6 is a favorable factor predictive of HBeAg loss at 2 years of entecavir therapy. Therefore, measurement of serum HBV-DNA level at 6 months of entecavir therapy is optimal to predict HBeAg loss at 2 years of therapy in HBeAg-positive CHB patients.

Efficacy of entecavir in hepatitis B related acute liver failure

Background and Aims: Recently available nucleoside analog, such as entecavir, has been found to be efficacious in hepatitis B related acute liver failure. We evaluated in placebo-controlled trial role of entecavir in 33 patients with acute liver failure hepatitis B related.

Suppressive effects of entecavir on hepatitis B virus and hepatocellular carcinoma

We investigated the efficacy and effectiveness of entecavir in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients. We enrolled 231 nucleoside-naïve chronic hepatitis B (CHB) patients primarily treated with entecavir 0.5 mg/day for at least 6 months in our institution. Of these, 71 patients had HCC at the start of entecavir treatment (HCC group) and 160 did not (non-HCC group). We compared antiviral responses to entecavir in the two groups, and evaluated the effects of entecavir on the clinical outcomes of curatively-treated HCC patients. The HCC and non-HCC groups had similar cumulative rates of HBV-DNA negativity, alanine aminotransferase normalization, and hepatitis e antigen loss in year 2 (100% vs 95.4%, 94.7% vs 97.3%, and 40.8% vs 41.8%, respectively; P > 0.05). Entecavir treatment for 12 months decreased mean Model for End-Stage Liver Disease scores in patients with cirrhosis and HCC (7.2 vs 5.6, P < 0.001). Of the 71 HCC patients, 16 underwent curative therapies concurrently with entecavir; hepatectomy in six and radiofrequency ablation in 10, and the 55 remaining patients received transarterial chemoembolization or conservative treatment. In a subgroup of 16 HCC patients receiving curative treatments, patients who became serum HBV DNA negative by week 24 had better overall survival (P = 0.039), but not recurrence-free survival (P = 0.961), than those who did not. First-line entecavir monotherapy is comparably effective in CHB patients with and without HCC, and improves hepatic function in HBV-related HCC patients. An early virological response to entecavir is prognostic of improved survival following curative therapy against HBV-related HCC.

Lack of an effect of human immunodeficiency virus coinfection on the pharmacokinetics of entecavir in hepatitis B virus-infected patients.

Entecavir is a guanosine nucleoside analogue approved for the treatment of chronic hepatitis B virus (HBV) infection. The impact of human immunodeficiency virus (HIV) coinfection on the pharmacokinetics (PK) of entecavir was examined by nonlinear mixed-effects modeling. Plasma concentration data from HIV- and HBV-coinfected patients were analyzed in conjunction with data from HBV-monoinfected patients, and HIV coinfection was tested as a covariate on oral clearance (CL/F). The estimated population averages of intercompartmental clearance and the volumes of distribution in the central and peripheral compartments obtained with a 1-mg dose were 34.2 liters/h (interindividual variability, 30.2%), 115 liters (interindividual variability, 39.2%), and 1,830 liters (interindividual variability, 74%), respectively. CL/F was found to be a function of creatinine clearance, but HIV confection did not show any effect on CL/F. The geometric mean (GM) of individual Bayesian estimates of the steady-state area under the concentration-time curve following 1-mg daily doses were 39.3 and 38.8 ng x h/ml in HIV- and HBV-coinfected and HBV-monoinfected patients, respectively. The adjusted GM ratio (1.01; 90% confidence interval, 0.91 to 1.12) was within the bioequivalence criteria boundary (0.80 to 1.25). In conclusion, the proposed model adequately described the entecavir PK in HBV- and HIV-coinfected patients and HBV-monoinfected patients, and the entecavir exposures were comparable in the two patient populations.