• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.22
• /
• pp.9635-9641
• /
• 2014

Background: This retrospective study was aimed to investigate the efficacy of prophylactic agents in hepatocellular carcinoma (HCC) patients receiving TACE and compare the difference between lamivudine and entecavir. Materials and Methods: A consecutive series of 203 HBV-related HCC patients receiving TACE were analyzed including 91 patients given prophylactic agents. Virologic events, defined as an increase in serum HBV DNA level to more than 1 log10 IU/ml higher than the nadir level, hepatitis flares due to HBV reactivation and progression free survival (PFS) were the main endpoints. Results: Some 48 (69.6%) reached virologic response. Prophylaxis significantly reduced virologic events (8.8% vs 58.0%, p=0.000) and hepatitis flares (1.1% vs 13.4%, p=0.001). Patients presenting undetectable HBV DNA levels displayed a significantly improved PFS as compared to those who never achieved undetectable HBV DNA. Prophylaxis and e-antigen positivity were the only significant variables associated with virologic events. In addition, prophylaxis was the only independent protective factor for hepatitis flares. Liver cirrhosis, more cycles of TACE, HBV DNA negativity, a lower Cancer of the Liver Italian Program score, non-metastasis and no hepatitis flares were protective factors for PFS. Prophylactic lamivudine demonstrated similar efficacy as entecavir. Conclusions: Prophylactic agents are efficacious for prevention of HBV reactivation in HCC patients receiving TACE. Achievement of undetectable HBV DNA levels displayed a significant capability in improving PFS. Moreover, persistent tumor residual lesions, positive HBV DNA and hepatitis B flares might be causes of tumor progression in these patients.

• YAKHAK HOEJI
• /
• v.51 no.3
• /
• pp.194-198
• /
• 2007

The mouse hepatitis virus (MHV-2) induces broad collapses, focal necrosis and cytolysis of hepatocytes, and leads to death after three to five days of intraperitoneal injection in mice. The present study investigated whether the combinatorial treatment of dimethyl dicarboxylate/amantadine (2:1) showed hepatoprotective and/or antiviral properties in MHV-2 infected ICR mice. In the study, we found that dimethyl dicarboxylate/amantadine group (VDDBA) increased the survival rate (30.8%) when compared to positive control, VL (7.7%) and that VDDBA lengthened the survival time (4.2 d)after MHV-2 infection. In addition, ALT and AST were well regulated when treated with VDDBA (p<0.01). Finally, we concluded that those results were probably from the inhibition of viral replication and at least antiproliferative effect on MHV-2.

• International Journal of Industrial Entomology and Biomaterials
• /
• v.7 no.2
• /
• pp.139-144
• /
• 2003

Over 350 million people worldwide are chronic carriers of hepatitis B virus (HBV). Chronic viral infections of the liver can progress to cirrhosis, which may ultimately lead to hepatic failure or the development of hepatocellular carcinoma. There are two antiviral drugs on the market approved for clinical management of chronic HBV infections; interferon-alpha and the nucleoside analog lamivudine. However, they showed adverse side-effects. In the rational drug design for such therapies we would like to utilize antiviral drugs that inhibit the HBV replication in the liver. Investigation of natural extracts of silkworm exhibiting antiviral potential was held in the functional HBV polymerase activity and the release of virion particle in the HepG2.2.15 cell lines. HBV-producing transgenic mouse fed with silkworm DNJ molecule was shown as an inhibitor of serum HBV particles. We could represent this DNJ molecule as an antiviral potential complementing conventional therapies after preclinical tests against WHBV-infected animal model, woodchuck.

• Korean Journal of Clinical Pharmacy
• /
• v.22 no.2
• /
• pp.95-102
• /
• 2012

HIV 치료를 위한 강력한 항바이러스 약물요법이 널리 사용됨에 따라 HIV에 감염된 상태에서 신장질환 발생 위험성을 지닌 채 오랜 기간 생존하는 환자들이 증가하고 있다. 본 연구는 국립중앙의료원 감염병 센터를 내원한 만18세 이상의 HIV 감염 환자를 대상으로 HIV 감염 환자에게 신기능 장애를 유발하는 위험인자를 평가하고자 환자군 대조군 연구를 후향적으로 실시하였다. 2006년 1월부터 2011년 3월까지 5년 3개월 동안 신기능이 저하된 모든 HIV 감염 환자를 환자군으로 하며, 정상 신기능을 가진 HIV 감염 환자들 중 대조군을 무작위로 선정하여 환자군과 대조군을 1:2의 비율로 하였다. 환자군과 대조군을 비교해 만성신질환을 유발하는 위험인자를 평가하기 위한 분석변수로 성별, 연령, CD4+ 세포수, 혈중 바이러스 수, HAART 56일 이상 여부, 당뇨병과 C형 간염을 선정하였다. 또한 추가적으로 개별 antiretroviral 약물들 사용과 신기능이 얼마나 관련되어 있는지 알아보기 위해 각각의 약물과 eGFR의 상관관계를 분석하였다. 환자군은 CD4+ 세포수가 < $200{\times}10^6$ cells/l 인 군이 7.7배(OR: 7.7; 95% CI, 1.8-32.9) 단백뇨가 있는 환자의 경우 7.8배(OR: 7.8; 95% CI, 1.6-37.8) 더 유의하게 만성신질환 발생위험이 높았다. 개별 antiretroviral 약물들과 eGFR의 상관관계를 분석한 결과, lamivudine 이 eGFR 과 약한 음적 상관관계를 보이는 것으로 나타났으며(r = -.211, p < .05), 다른 약물들의 경우 통계적으로 유의한 값을 보이지 않았다. 이번 환자군-대조군 연구는 HIV 감염 환자들이 만성 신질환으로 발전하는데 여러 인자들의 역할에 대해 평가하고자 하였다. 여러 변수들을 평가해 본 결과, 만성 신질환 환자들의 경우 CD4+ 세포수가 < $200{\times}10^6$ cells/l 이거나 단백뇨를 동반한 경우가 통계적으로 유의하게 많았다.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.21
• /
• pp.9423-9426
• /
• 2014

Objective: Hapatitis B visus (CHB)-induced fibrosis is a precancerous condition of liver. To explore the influence of Chongcao Preparation (Chongcao Yigan Capsule) on the function of intestinal flora and chemoprevention for patients with CHB-induced liver fibrosis. Methods: A total of 136 patients with CHB-induced liver fibrosis were randomly divided into control group treated with lamivudine (LAM) and research group added with Chongcao Yigan Capsule for totally 48 weeks. The changes of intestinal flora, secretory immunoglobin A (SIgA), serum albumin (ALB), prealbumin (PALB), IgA and IgG at different time points in both groups were observed. Results: Before treatment, there was no significant difference between two groups in each index (P>0.05). After treatment, the intestinal flora were evidently optimized in research group than treatment before (P<0.05 or P<0.01), and were apparently better than those in control group (P<0.05 or P<0.01); SIgA was obviously increased and ALB, PALB, IgA and IgG were markedly improved in research group than treatment before (P<0.05 or P<0.01), and were significantly better than those in control group (P<0.05 or P<0.01). Conclusions: Chongcao Yigan Capsule could regulate the intestinal flora, increase SIgA, serum ALB and PALB concentrations and significantly improve serum IgA and IgG as well as strengthen the immunological function and autologous repair capacity of patients with CHB-induced liver fibrosis.

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

• Toxicological Research
• /
• v.32 no.4
• /
• pp.317-325
• /
• 2016

Increased access to highly active antiretroviral therapy (HAART) has made the management of drug toxicities an increasingly crucial component of HIV. This study investigated the effects of adjuvant use of coconut oil and HAART on testicular morphology and seminal parameters in Sprague-Dawley rats. Twelve adult male Sprague-Dawley rats, weighing 153~169 g were distributed into four groups (A-D) and treated as follows: A served as control (distilled water); B (HAART cocktail-Zidovudine, Lamivudine and Nevirapine); C (HAART + Virgin coconut oil 10 mL/kg) and D (Virgin coconut oil 10 mL/kg). After 56 days of treatment, animals were killed and laparotomy to exercise the epididymis for seminal fluid analyses done whilst testicular tissues were processed for histo-morphometric studies. Result showed a significant decline in sperm motility (P < 0.05) and count (P < 0.0001) in HAART-treated animals while there was insignificant changes in other parameters in groups C and D except count that was reduced (P < 0.0001) when compared with controls. Histomorphological studies showed HAART caused disorders in seminiferous tubular architecture with significant (P < 0.01) decline in epithelial height closely mirrored by extensive reticulin framework and positive PAS cells. Adjuvant Virgin coconut oil + HAART resulted in significant decrease in seminiferous tubular diameter (P < 0.05), but other morphometric and histological parameters were similar to control or Virgin coconut oil alone (which showed normal histoarchitecture levels). While derangements in testicular and seminal fluid parameters occurred following HAART, adjuvant treatment with Virgin coconut oil restored the distortions emanating thereof.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.9
• /
• pp.5489-5494
• /
• 2013

In the current study we aimed to show the common YMDD motif mutations in viral polymerase gene in chronic hepatitis B patients during lamivudine and adefovir therapy. Forty-one serum samples obtained from chronic hepatitis B patients (24 male, 17 female; age range: 34-68 years) were included in the study. HBV-DNA was extracted from the peripheral blood of the patients using an extraction kit (Invisorb, Instant Spin DNA/RNA Virus Mini Kit, Germany). A line probe assay and direct sequencing analyses (INNO-LIPA HBV DR v2; INNOGENETICS N.V, Ghent, Belgium) were applied to determine target mutations of the viral polymerase gene in positive HBV-DNA samples. A total of 41 mutations located in 21 different codons were detected in the current results. In 17 (41.5%) patients various point mutations were detected leading to lamivudin, adefovir and/or combined drug resistance. Wild polymerase gene profiles were detected in 24 (58.5%) HBV positive patients of the current cohort. Eight of the 17 samples (19.5%) having rtM204V/I/A missense transition and/or transversion point mutations and resistance to lamivudin. Six of the the mutated samples (14.6%) having rtL180M missense transversion mutation and resistance to combined adefovir and lamivudin. Three of the mutated samples (7.5%) having rtG215H by the double base substituation and resistance to adefovir. Three of the mutated samples (7.5%) having codon rtL181W due to the missense transversion point mutations and showed resistance to combined adefovir and lamivudin. Unreported novel point mutations were detected in the different codons of polymerase gene region in the current HBV positive cohort fromTurkish population. The current results provide evidence that rtL180M and rtM204V/I/A mutations of HBV-DNA may be associated with a poor antiviral response and HBV chronicity during conventional therapy in Turkish patients.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.6 no.1
• /
• pp.32-38
• /
• 2003

Purpose: Hepatic allografts from donors with hepatitis B core antibody have been demonstrated to transmit hepatitis B virus (HBV) infection to recipients after liver transplantation (LT). The efficacy of hepatitis B immune globulin (HBIg) to prevent de novo hepatitis B was investigated by comparing active immunization in the early phase to HBIg monotherapy in the late phase of pediatric liver transplants at Samsung Medical Center. Methods: Among pediatric liver transplants, from May, 1996 to June, 2002, 15 recipients who were hepatitis B surface antigen (HBsAg) (-) received an allograft from a donor with hepatitis B core antibody (HBcAb) (+). Except two who died from unrelated causes, eleven of 13 recipients were HBsAb (+), and 2 were naive (HBsAb(-), HBcAb(-)). All patients were vaccinated for HBV before LT. In the early phase (January, 1997~November, 1997, 3 patients), HBsAb (+) recipients received booster vaccination after LT. In the late phase (December, 1997~, 10 patients), all recipients were given booster vaccination and received HBIg therapy in order to maintain HBsAb titer greater than 200 IU/L. Lamivudine was given in one case because of severe side effect of HBIg. We retrospectively analyzed the effect of the preventive therapy for de novo hepatitis B through medical records. Results: De novo hepatitis B developed in three of 13 recipients (23.1%). All of 3 patients who received active immunization in the early phase became HBsAg (+) at 7~19 months after transplantation. One of them was naive before LT and the other two were HBsAb (+). All of 10 recipients who were given HBIg in the late phase remained HBsAg (-) at 7~55 months' follow-up. Conclusion: Passive immunization with HBIg was effective for prevention of de novo hepatitis B in HBsAg (-) recipients of hepatic allografts from HBcAb (+) donors.

• Journal of Yeungnam Medical Science
• /
• v.25 no.1
• /
• pp.1-18
• /
• 2008

Although Lamivudine and adefovir dipivoxil are efficacious drugs for preventing hepatocellular carcinoma (HCC) in chronic hepatitis B patients, their efficacy is far from completely satisfactory. The risk of liver cirrhosis and HCC begins to increase at an HBV DNA level of $10^4$ copies/ml. Even with latent or past HBV infection, episomal covalently closed circular DNA(cccDNA) plays a key rolein the persistence, relapse and resistance of HBV in its natural course or during therapy. The annual incidence of HCC in YUMC is 1.8% and 4.7% patients/year in the antiviral treatment and control groups, respectively. The ability to achieve a high rate of sustained HBV suppression with low risk of drug resistance is the ultimate goal in the treatment of chronic HBV infection. The efficacy of universal immunization with striking reductions in the prevalence of HBV in localized countries needs to be spread worldwide. With hepatitis B immunization and effective antiviral therapy, global control of HBV infection and HBV-related complications, including HCC, are possible by the end of the first half of the $21^{st}$ century.