No abstract available.
Antiviral Agents/*adverse effects ; Arabinofuranosyluracil/adverse effects/*analogs & derivatives ; Female ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B, Chronic/*drug therapy ; Humans ; Male ; Muscular Diseases/*chemically induced

No abstract available.
Antiviral Agents/*therapeutic use ; Arabinofuranosyluracil/*analogs & derivatives/therapeutic use ; Drug Resistance, Viral ; Hepatitis B, Chronic/*drug therapy ; Humans ; Lamivudine/therapeutic use ; Practice Guidelines as Topic

BACKGROUND/AIMS: Clevudine, a pyrimidine nucleoside analogue, has potent antiviral effects in patients with chronic viral hepatitis B (CHB). We report the efficacy of initial treatment with clevudine in naive patients with CHB living in Daejeon and Chungcheong Province, South Korea. METHODS: One hundred five adults with CHB were administered 30 mg of clevudine per day for an average of 51 weeks. We evaluated viral markers and liver biochemistry retrospectively every 3 months. RESULTS: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and hepatitis B virus (HBV) DNA before the treatment were 184 +/- 188 IU/L, 150 +/- 138 IU/L, and 7.1 +/- 1.2 log copies/mL, respectively. Undetectable rates (< 60 IU/mL) of DNA were 36.2%, 68.9%, 83.6%, 76.2%, and 75.8% at 12, 24, 36, 48, and 60 weeks, respectively. Seroconversion rates were 9.1%, 13.6%, 24.6%, 26.5%, and 26.1% and ALT normalization rates were 64.5%, 78.1%, 87.9%, 90.0% at 12, 24, 36, and 48 weeks, respectively. Six patients (5.7%) had a viral breakthrough. CONCLUSIONS: Clevudine is a useful drug in the initial treatment of patients with CHB, with a potent antiviral effect and low incidence of viral breakthrough.
Adult ; Alanine Transaminase/blood ; Antiviral Agents/*therapeutic use ; Arabinofuranosyluracil/*analogs & derivatives/therapeutic use ; Female ; Hepatitis B e Antigens/blood ; Hepatitis B, Chronic/drug therapy/virology ; Humans ; Male ; Middle Aged ; Retrospective Studies

The authors assessed the efficacy and antiviral resistance of 48-week clevudine therapy versus lamivudine in treatment of naive patients with HBeAg positive chronic hepatitis B. In this retrospective study, a total of 116 HBeAg positive patients, who received 30 mg of clevudine once daily (n=53) or 100 mg of lamivudine once daily (n=63) for 48 weeks, were included. At week 48, clevudine therapy produced a significantly greater mean reductions in serum HBV DNA levels from baseline than lamivudine therapy (-5.2 vs. -4.2 log(10)IU/mL; P=0.005). Furthermore, a significantly higher proportion of patients on clevudine achieved negative serum HBV DNA by PCR (<13 IU/mL) at week 48 (60.4% vs. 38.1%; P=0.025). The incidence of virologic breakthrough in the clevudine group was significantly lower than in the lamivudine group (9.4% vs. 25.4%; P=0.031). However, rates of alanine aminotransferase normalization and HBeAg loss or seroconversion were similar in the two groups (83.0% vs. 81.0%, 11.3% vs. 11.1%; P=0.813, 1.000, respectively). In conclusion, clevudine is more potent for viral suppression and lower for antiviral resistance at week 48 than lamivudine in treatment of naive patients with HBeAg positive chronic hepatitis B.
Adult ; Antiviral Agents/administration & dosage ; Arabinofuranosyluracil/administration & dosage/*analogs & derivatives ; Drug Resistance, Viral ; Female ; Hepatitis B e Antigens/*blood ; Hepatitis B, Chronic/diagnosis/*drug therapy/*immunology ; Humans ; Lamivudine/*administration & dosage ; Male ; Treatment Outcome

Substantial progress has been made in the treatment of chronic hepatitis B during the past decade. Nucleos(t)ide analogues are now widely used due to their convenience, less side effects, and considerable response rates. However, development of antiviral resistance is a major problem being considered as the most important factor for the treatment failure. Viral breakthrough associated with selection of antiviral-resistant hepatitis B virus (HBV) is usually followed by biochemical breakthrough, clinical deterioration, and even progressive liver failure. Therefore, appropriate management of antiviral resistance is critical for improving treatment outcomes. Strategies for the management of antiviral-resistant chronic HBV infection are described herein considering recently published guidelines. Lamivudine/telbivudine resistance can be managed by adding adefovir. Switching to adefovir or entecavir is also a viable option. However, careful follow-up of viral load is mandatory to detect any primary or secondary treatment failure in case of sequential monotherapy. Interferon or peg-interferon therapy can also be considered in case of young patients with compensated liver disease. For adefovir resistance, lamivudine can be added, but adding or switching to entecavir is a more reasonable option. Likewise, adding or switching to adefovir can be considered for entecavir resistance. Adding or switching to tenofovir needs to be considered upon availability. Experiences for clevudine resistance are still lacking, and need to be studied further upon the isolation of clinically resistant strains. To avoid emergence of resistant mutations, antiviral therapy should be initiated after careful balance of risk and benefit, and the most potent antiviral agent with the lowest resistance rate should be selected.
Adenine/analogs & derivatives/therapeutic use ; Antiviral Agents/therapeutic use ; Arabinofuranosyluracil/analogs & derivatives/therapeutic use ; *Drug Resistance, Multiple, Viral ; Guanine/analogs & derivatives/therapeutic use ; Hepatitis B virus/*drug effects/isolation & purification ; Hepatitis B, Chronic/*drug therapy ; Humans ; Lamivudine/therapeutic use ; Mutation ; Nucleosides/therapeutic use ; Phosphonic Acids/therapeutic use ; Practice Guidelines as Topic ; Pyrimidinones/therapeutic use ; Treatment Outcome

Chronic hepatitis B (CHB) is a serious health problem in Korea. The natural history of chronic HBV infection has been divided into 4 phases: immune tolerance, immune clearance, inactive HBsAg carrier state and reactivation. During the phases of immune tolerance and inactive HBsAg carrier state, no treatment is required. Patients in the immune clearance or reactivation phases are candidates for therapy. In the last years, treatment effects of CHB have considerably improved. Several agents are currently approved for the treatment of CHB: interferon alpha, pegylated interferon alpha, lamivudine, adefovir, entecavir, telbivudine and clevudine in Korea. The treatment recommendations from the 2004 Korean Association for the Study of the Liver guideline on the management of CHB have been updated to incorporate new therapeutic options. What is uncertain is which agent or combination of agents is most effective, how long therapy should last, and which criteria should be used to start, continue, switch or stop therapy. Issues for consideration include efficacy, safety and incidences of resistance, and method of administration of antiviral therapy in treatment-naive patients.
Adenine/analogs & derivatives/therapeutic use ; Antiviral Agents/*therapeutic use ; Arabinofuranosyluracil/analogs & derivatives/therapeutic use ; Guanine/analogs & derivatives/therapeutic use ; Hepatitis B, Chronic/*drug therapy ; Humans ; Interferon Alfa-2a/therapeutic use ; Interferon Alfa-2b/therapeutic use ; Korea ; Lamivudine/therapeutic use ; Phosphonic Acids/therapeutic use ; Polyethylene Glycols/therapeutic use ; Practice Guidelines as Topic

BACKGROUND/AIMS: Chronic hepatitis B infection is a common cause of secondary membranous nephropathy (MN) in endemic areas. Lamivudine treatment improves renal outcome in patients with hepatitis B virus-associated MN (HBV-MN), but prolonged use leads to the emergence of lamivudine-resistant variants. We describe our experience treating lamivudine-resistant and other strains of HBV-MN with new antiviral drugs. METHODS: Of the 89 patients biopsied and diagnosed with MN from 1996 to 2011, 10 positive for hepatitis B surface antigen were recruited for this study. We investigated the clinical courses, therapeutic responses, and prognoses of patients with HBV-MN. RESULTS: The incidence of HBV-MN among the original 89 patients was 11.2%. Of these patients, four were treated with supportive care and six with antiviral drugs. One of the four patients treated with supportive care had a spontaneous remission. Four of the six patients treated with antiviral drugs were given lamivudine, and the other two were given entecavir. Two of the four patients treated with lamivudine achieved complete remission with seroconversion (i.e., development of anti-hepatitis B e antigen antibodies), whereas the other two had lamivudine-resistant strains, which were detected at 22 and 23 months after lamivudine treatment, respectively. We added adefovir to the treatment regimen for one of these patients, and for the other patient we substituted clevudine for lamivudine. Both of these patients experienced complete remission, as did the two patients initially treated with entecavir, neither of whom showed resistance to the drug. CONCLUSIONS: New nucleoside analogues, such as entecavir, adefovir, and clevudine, can be effective for treatment of HBV-MN, including lamivudine-resistant strains.
Adenine/analogs & derivatives/therapeutic use ; Adult ; Antiviral Agents/*therapeutic use ; Arabinofuranosyluracil/analogs & derivatives/therapeutic use ; Drug Resistance, Viral ; Female ; Glomerulonephritis, Membranous/*drug therapy/*etiology ; Guanine/analogs & derivatives/therapeutic use ; Hepatitis B, Chronic/*complications/*drug therapy ; Humans ; Lamivudine/*therapeutic use ; Male ; Middle Aged ; Organophosphonates/therapeutic use ; Young Adult

Adenine ; analogs & derivatives ; chemistry ; pharmacology ; Animals ; Anti-HIV Agents ; chemistry ; pharmacology ; Antiviral Agents ; chemistry ; pharmacology ; Arabinofuranosyluracil ; analogs & derivatives ; chemistry ; pharmacology ; Cytosine ; analogs & derivatives ; chemistry ; pharmacology ; Dioxolanes ; chemistry ; pharmacology ; Humans ; Molecular Structure ; Nucleosides ; chemistry ; pharmacology ; Organophosphonates ; chemistry ; pharmacology ; Purine Nucleosides ; chemistry ; pharmacology ; Tenofovir

BACKGROUND/AIMS: Clevudine is a potent antiviral agent against HBV. However, long-term clevudine therapy may cause myopathy. This study was carried out to identify the efficacy of entecavir switching therapy in chronic hepatitis B patients experiencing clevudine-induced myopathy. METHODS: One hundred forty six patients with chronic hepatitis B treated with 30 mg of clevudine per day for 73 weeks (range, 36-132 weeks) were enrolled. Among them, clevudine-induced myopathy occurred in 21 patients (14.4%) which was diagnosed if the patients had symptoms related to myopathy with concurrent CK and AST elevation. All the patients who were diagnosed as clevudine-induced myopathy stopped the therapy, and 17 patients (81%) were switched to entecavir 0.5 mg. RESULTS: The patients with clevudine-induced myopathy were switched to entecavir 0.5 mg for median 68 weeks, and all of them showed disappearance of clinical myopathic symptoms and normalization of CK and AST level within median 2.2 months. Eight patients (47%) were HBeAg positive before entecavir treatment, and HBeAg seroconversion was achieved in 2 patients (25%). HBV DNA level was elevated in 3 patients (17.6%) at the time when the patients were diagnosed as myopathy, all of them achieved virological response with entecavir switching therapy. ALT level was elevated in 3 patients (17.6%) before entecavir treatment, all of them showed normalization of ALT level. During entecavir therapy, genotypic resistance to entecavir or virological breakthrough was not noted. CONCLUSIONS: In chronic hepatitis B patients experiencing clevudine-induced myopathy, switching to entecavir 0.5 mg per day showed a resolution of myopathy and adequate viral suppression.
Adult ; Aged ; Alanine Transaminase/analysis ; Antiviral Agents/*adverse effects/therapeutic use ; Arabinofuranosyluracil/adverse effects/*analogs & derivatives/therapeutic use ; Creatine Kinase/analysis ; DNA, Viral/blood ; Drug Resistance, Viral ; Female ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B e Antigens/blood ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/*drug therapy ; Humans ; Male ; Middle Aged ; Muscular Diseases/*chemically induced

BACKGROUND/AIMS: Clevudine is a potent antiviral agent that has demonstrated efficacy in patients with chronic hepatitis B. This study compared the efficacy of clevudine (C), entecavir (E) and lamivudine (L) in treatment-naive patient with HBeAg-positive chronic hepatitis B. METHODS: A total of 146 treatment-naive patients with HBeAg-positive chronic hepatitis B received clevudine, entecavir or lamivudine. C group (n=39) received 30 mg of clevudine, E group (n=39) received 0.5 mg of entecavir and L group (n=68) received 100 mg of lamivudine once a day for more than 48 weeks. The efficacy analysis estimated the mean changes of the HBV DNA levels as a virologic response, the normalization of the ALT levels (less than 35 IU/L) as a biochemical response and loss of HBeAg or seroconversion as a serologic response. The serum HBV DNA level was quantified by hybrid capture and real-time PCR assay. RESULTS: Before the administration of clevudine, entecavir and lamivudine, the mean HBV DNA and ALT levels and the gender and age were well balanced among the three groups (p>0.05). For the virologic response at 48 weeks, the mean changes of the HBV DNA levels from baseline of the C, E and L groups were -3.8+/-2.2, -4.5+/-1.9 and -2.5+/-2.1 log copies/mL. C and E group showed superior antiviral activity compared to that of L group (p<0.0001), but no significant differences in antiviral response were noted between C and E groups. For the biochemical response at 48 weeks, the normalization of the ALT levels (less than 35 IU/L) among the C, E and L groups was 82%, 74% and 71%, respectively (p=0.46). The rates of undetectable serum HBV DNA (less than 300 copies/mL) of the C, E and L groups were 39%, 69% and 27%, respectively (p<0.0001). For the serologic response at 48 weeks, the loss of HBeAg was 13%, 31% and 24% and the seroconversion was 10%, 23% and 17%, respectively. There was no difference of efficacy among the three groups regarding ALT normalization or serologic response (p>0.05). Viral breakthrough in C group was noted at 24 weeks (5%) and 48 weeks (21%), but no biochemical breakthrough was noted. The elevation of the serum CK level was noted in only 1 patient of group C at 48 weeks (2.56%) after therapy. For the patients without or with liver cirrhosis (LC), C and E group showed superior antiviral activity compared to that of the L group, but the antiviral activity was more effective in non- LC group than LC group (p<0.0001 vs p=0.036). CONCLUSIONS: Clevudine therapy compared with lamivudine for 48 weeks showed significantly potent antiviral efficacy in treatment-naive patients with HBeAg-positive chronic hepatitis B, and especially in the non-LC patients. However, the antiviral efficacy of clevudine was similar to that of entecavir even though taking into account relatively short follow up period and retrospective study.
Adult ; Alanine Transaminase/blood ; Antiviral Agents/*administration & dosage ; Arabinofuranosyluracil/administration & dosage/*analogs & derivatives ; DNA, Viral/blood ; Drug Administration Schedule ; Drug Resistance, Viral ; Female ; Guanine/administration & dosage/*analogs & derivatives ; Hepatitis B e Antigens/*blood ; Hepatitis B, Chronic/*drug therapy ; Humans ; Lamivudine/*administration & dosage ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome