• Korean Journal of Clinical Pharmacy
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• v.21 no.3
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• pp.224-227
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• 2011

Entecavir is a potent and selective guanosine analogue that has demonstrated a significant antiviral efficacy against hepatitis B virus (HBV). The aim of this study was to evaluate the safety and pharmacokinetic profile after a single dose of entecavir 1 mg administration in Korean healthy male subjects. Eight volunteers were enrolled. After a single dose of 1 mg entecavir was orally administered, blood samples were collected at specific time intervals from 0-168 hours. The plasma concentrations of entecavir were determined by LC-MS/MS. The pharmacokinetic parameters were determined from the plasma concentration-time profiles. The mean values for $AUC_{last}$ and $AUC_{inf}$ were $14.84{\pm}7.81ng{\cdot}hr/mL$ and $20.71{\pm}8.80ng{\cdot}hr/mL$, respectively. The mean value for $C_{max}$ was $9.19{\pm}4.91ng/ml$ and median value for $t_{max}$ was 0.58 hr. No adverse events were reported by subjects or found on analysis of vital signs or laboratory tests. The results are suggested to be useful in clinical trials of entecavir in Korean subject including bioequivalence study.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.13 no.1
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• pp.44-50
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• 2010

Purpose: To estimate the viral suppressive effect of entecavir monotherapy in Korean children and adolescents with lamivudine-resistant chronic hepatitis B (CHB). Methods: One milligram of entecavir was administered once daily to 6 patients (4 boys; mean age, 17.5 years; range, 15.10~24.6 years) with lamivudine-resistant CHB for a mean duration of therapy of 13.4 months (range, 1~21.1 months). The therapeutic results were compared with 11 patients who received adefovir (0.3 mg/kg/day [maximal dose 10 mg]) for at least 12 months (mean, 33.4 months; range, 12.4~58.3 months). The serum HBV DNA level and serologic markers were measured every 2 months. Results: The interval to a HBV DNA titer decrement (>1 $log_{10}$) was 1.2${\pm}$0.2 and 4.4${\pm}$5.2 months (p=0.185) for the entecavir and adefovir groups, respectively. The interval to a HBV DNA titer decrement (>2 $log_{10}$) was 2.4${\pm}$2.3 and 9.2${\pm}$7.3 months (p=0.025), for the entecavir and adefovir groups, respectively. Conclusion: The therapeutic efficacy of entecavir was favorable in children and adolescents, especially in shortening the interval to a >2 $log_{10}$ decrement in the HBV DNA titer. Long-term follow up is needed to determine the therapeutic efficacy of entecavir for lamivudine-resistant CHB in children and adolescents.

• The Journal of Internal Korean Medicine
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• v.38 no.2
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• pp.284-288
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• 2017

The patient presented to the clinic with the complaint of severe fatigue. The patient had been diagnosed with chronic hepatitis B a number of years earlier. Although he had used entecavir, an antiviral agent, for over two years, his HBV-DNA level had not dropped below undetectable levels. The fatigue seemed to be associated with chronic hepatitis B. Traditional Korean medicine (TKM) therapy for chronic hepatitis B was administered in conjunction with entecavir and at the same dose. The excessive fatigue gradually decreased following the treatment. On the 28th day, laboratory tests revealed that the patient's bilirubin level was slightly lower and that his HBV-DNA level had dropped below undetectable levels. The addition of TKM therapy may have contributed to the HBV-DNA clearance. No similar cases have been reported in Korea. Herein, we summarize the patient's progress.

• Journal of Yeungnam Medical Science
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• v.25 no.1
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• pp.31-40
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• 2008

Background/Aims : Entecavir is a synthetic nucleoside analogue, cyclopentyl guanine nucleoside, which has a potent antiviral effect and the least viral breakthrough in hepatitis B virus (HBV) replication. Entecavir has been available in Korea since 2007 but there are few reports on its effects. The aim of this study was to evaluate the virological response (VR) and biochemical response (BR) to entecavir in HBV patients at 3, 6 and 9 months after treatment with entecavir. Materials and Methods : Thirty-three chronic hepatitis B patients who took entecavir for at least 9 months were enrolled. We investigated VR and BR by retrospectively reviewing medical records. Patients who satisfied the following criteria were chosen: 1) initial alanine aminotransferase (ALT) levels = 1.5upper limit of normal (ULN) and 2) initial HBV DNA levels = $5\;log_{10}\;copies/ml$. We measured ALT levels every 3 months until month 9. HBV DNA was measured every 2 or 3 months by polymerase chain reaction (PCR) method. Results : Most patients taking entecavir showed good BR (ALT < 40 IU/L). The BR rates were 61%, 73% and 67% at months 3, 6 and 9, respectively. VR (HBV DNA < $5\;log_{10}\;copies/ml$ or 2 log lower than initial HBV DNA) rates were 82%, 91% and 91% at months 3, 6 and 9, respectively. Undetectable HBV DNA (HBV DNA < 4 log10 copies/ml) rates were 49%, 73% and 85% at months 3, 6 and 9, respectively. Two patients presented with virological breakthrough without adverse effects until month 9. Conclusions : Entecavir showed good BR and VR from month 3 and these effects continued through the 9-month observation period. This suggests that entecavir is also a good choice for the first line treatment of chronic hepatitis B (CHB). Further studies are needed to determine the long-term efficacy and drug resistance of entecavir in Korean CHB patients.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8665-8670
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• 2016

Background and Aims: 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. Conclusion: 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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.4
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• pp.743-747
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• 2011

Here we describe a case of lamivudine and entecavir resistant chronic hepatitis B, treated with western medicine plus traditional korean medicine combination therapy. We administered Injinchunggan-Tang(茵蔯淸肝湯), a traditional Korean herb remedy, with entecavir to a 45-year-old chronic hepatitis B patient who didn't have achieved HBV-DNA suppression, in spite of 18 month lamivudine mono therapy and 14 month entecavir mono therapy. HBV-DNA decreased more than one thousandth from 98,100 IU/mL to 53 IU/mL just in 23 days, and resultingly it seems that the combination therapy could be very potent, at least to some chronic hepatitis B patients.

• Korean Journal of Clinical Pharmacy
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• v.22 no.1
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• pp.81-86
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• 2012

This study was aimed to examine the prescribing patterns of antivirals in outpatients with chronic hepatitis B (CHB), using National Health Insurance adjudicated claims data (total 1,426,065 claims) dated March 19, 2008 submitted from nationwide healthcare providers to Health Insurance Review and Assessment Service. From the data, there were 2,965 claims with CHB diagnosis (ICD-10 code B18.0 and B18.1), and 44.2% (1,311 claims) of the CHB related claims included antivirals such as lamivudine, clevudine, adefovir and entecavir. Lamivudine, adefovir, clevudine and entecavir shared 54.9%, 19.9%, 13.2% and 11.9%, respectively, among antiviral prescriptions. Adefovir and entecavir 1mg presumed as the 2nd line therapy for HBV resistant cases were shared 23.3% of overall antiviral prescriptions. There were statistically significant difference in prescription patterns according to age and institution type: Lamivudine usage was higher in younger (< 20 years old) and older age group (> 70 years old) than the others (p = 0.016), and adefovir and entecavir, which were relatively newer antivirals, had higher prescription rates in higher level of institutions such as tertiary hospitals than the others (p < 0.001). This study would be of help to make an appropriate drug therapy plan for patients with CHB.

• Molecules and Cells
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• v.40 no.6
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• pp.418-425
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• 2017

Interferon-${\gamma}$-inducible protein 10 (IP-10), also known as chemokine C-X-C motif ligand (CXCL) 10, is closely associated with antiviral immunity and the progression of chronic hepatitis B (CHB). However, the value of baseline serological and histological IP-10 expression levels in predicting the efficacy of the antiviral response to nucleoside/nucleotide analogues (NAs) is still unknown. In our research, intrahepatic and peripheral IP-10 expression levels were systemically examined before and after treatment with entecavir (ETV). Baseline serological and histological IP-10 expression levels were significantly increased in patients with CHB, particularly in patients with higher degrees of liver inflammation and liver fibrosis. Moreover, higher baseline intrahepatic IP-10 levels indicated better prognoses in patients with CHB after entecavir therapy. The baseline IP-10 level was also positively associated with several clinical parameters, including baseline levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatitis B virus (HBV) DNA, and hepatitis B surface antigen (HBsAg), and with the decrease in HBsAg levels after treatment. In addition, monocyte-derived IP-10 was expressed at higher levels in patients with CHB than in patients with liver cirrhosis (LC) and healthy controls (HC). According to the results of our in vitro experiments, IP-10 directly promoted hepatocyte apoptosis. Based on these findings, baseline serological and histological IP-10 levels might predict CHB severity and the decrease in HBsAg levels after entecavir therapy.

• Korean Journal of Clinical Pharmacy
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• v.26 no.3
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• pp.220-229
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• 2016

Background: The treatment goal for patients with chronic hepatitis B infection is to prevent progression of the disease to cirrhosis and hepatocellular carcinoma. Current therapies include standard and pegylated interferon-alfa and nucleoside/nucleotide analogues: lamivudine, adefovir, entecavir, telbivudine, clevudine, and tenofovir. This study aims to analyze changes in the prescribing patterns of chronic hepatitis B (CHB) medications in South Korea between 2013 and 2014. Methods: A cross-sectional study was conducted using National Patients Sample data compiled by the Health Insurance Review and Assessment Service from 2013 and 2014. Patients with CHB were identified with Korean Standard Classification of Diseases code-6 (B18.0 and B18.1) and those who were maintaining active prescriptions with CHB medications covering the index date (December $1^{st}$, each year) were included. The utilization of antiviral therapy was investigated during 2013 and 2014. Results: A total of 4,204 and 4,552 patients in 2013 and 2014 respectively, were included in the analysis. The proportion of male patients was two of third and the patients 41-60 years old accounted for 60% of all analyzed patients. The most utilized drug was entecavir (55.1% in 2013 and 44.8% in 2014) and the second most utilized drug was tenofovir in both years (18.8% in 2013 and 29.0% in 2014). The percentage of combination therapy was 13.6% and 13.1% in 2013 and 2014, respectively. The proportion of tenofovir prescriptions was increased in 2014 compared with 2013. Conclusion: With the development of new drugs and the changes in clinical practice guidelines, the prescription pattern of the antiviral agents for patients with CHB has changed. The rate of utilization of tenofovir has increased.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.15 no.2
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• pp.63-73
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• 2012

Development of antiviral resistance to lamivudine is the most important factor for the treatment failure. It is necessary to establish proper guidelines to overcome drug resistance for children with chronic hepatitis B. Primary treatment with lamivudine should be considered if patients are in immune-clearance phase and have persistently elevated ALT levels more than twice the upper limit of normal value. Before initiating the therapy, careful consideration of the patient's status is required to exclude abnormal liver function tests due to other causes. The treatment option should be carefully decided to suppress the viral replication effectively. To obtain good compliance, clinicians should educate patients and their parents. Appropriate monitoring for virologic breakthrough and genotypic resistance is important in deciding to change the treatment plan. Sequential monotherapy should be avoided and a combination of drugs in other categories is recommended. New antiviral agents, such as entecavir and tenofovir, which have high potency and high genetic barrier, are soon expected to be available for use with children.