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

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

BACKGROUND: Clevudine (Revovir(R)) is a recently introduced antiviral drug, and clinical trials have demonstrated its potent, sustained antiviral activity without specific adverse events. However, several studies have found severe myopathy during clevudine therapy. Our study aimed to summarize the clinical and pathological features of clevudine-induced myopathy. METHODS: We analyzed the demographic data, clinical features, and pathologic findings of 18 consecutive hepatitis-B patients who developed skeletal myopathy during clevudine therapy. RESULTS: The 18 patients comprised 11 women and 7 men aged 48.2+/-14.0 years (mean+/-standard deviation; range 28-74 years). Each of the 18 patients was treated with clevudine for at least 5 months (range 5-20 months) before the development of symptoms. In all patients the main symptom was proximal muscular weakness that progressed slowly over several months. Elevated creatine kinase and myopathic patterns on electromyography were found. Muscle biopsies revealed severe myonecrosis associated with numerous ragged red fibers and cytochrome-c-oxidase-negative fibers, mitochondrial proliferation, and predominant type-II fiber atrophy. The muscle weakness gradually improved within 20 weeks after discontinuation of clevudine. CONCLUSIONS: Clevudine therapy can induce myopathy associated with mitochondrial toxicity. Careful clinical and laboratory monitoring of the skeletal muscle dysfunction is required in patients receiving clevudine therapy.
Aged ; Arabinofuranosyluracil ; Atrophy ; Biopsy ; Creatine Kinase ; Electromyography ; Female ; Hepatitis ; Humans ; Male ; Muscle Weakness ; Muscle, Skeletal ; Muscles ; Muscular Diseases

BACKGROUND/AIMS: Clevudine (CLV) has potent antiviral activity against chronic hepatitis B (CHB) virus infection. The long-term efficacy and safety of CLV therapy in naive patients with CHB were investigated. METHODS: In this retrospective study, 152 naive Korean patients with CHB who received 30 mg of CLV once daily for at least 12 months were investigated. RESULTS: The cumulative rates at months 12, 24, and 36, respectively, were 65.8%, 74.7%, and 74.7% for undetectable serum hepatitis B virus (HBV) DNA (<12 IU/mL); 77.6%, 86.2%, and 86.2% for normalization of serum alanine aminotransferase (<40 IU/L); 17.6%, 23.5%, and 23.5% for hepatitis B e antigen (HBeAg) loss or seroconversion; and 6.6%, 22.5%, and 30.0% for viral breakthrough. HBeAg positivity (p=0.010), baseline serum HBV DNA level > or =6 log10 IU/mL (p=0.032) and detectable serum HBV DNA (> or =12 IU/mL) at week 24 (p=0.023) were independently associated with the development of viral breakthrough. During follow-up, CLV-induced myopathy developed in 5.9% of patients. CONCLUSIONS: The results of long-term CLV therapy for the treatment of naive patients with CHB showed a high frequency of antiviral resistance and substantial associated myopathy. Therefore, we advise that CLV should not be used as a first-line treatment for naive patients given the availability of other more potent, safer antiviral agents.
Alanine Transaminase ; Antiviral Agents ; Arabinofuranosyluracil ; DNA ; Follow-Up Studies ; Hepatitis B ; Hepatitis B e Antigens ; Hepatitis B virus ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Humans ; Muscular Diseases ; Retrospective Studies ; Treatment Outcome ; Viruses

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

BACKGROUND/AIMS: The clinical effects of clevudine have been reported in patients with chronic hepatitis B virus infections (CHIs). In this investigation, we assessed whether clevudine induced biochemical and virological improvements in hepatocellular carcinoma (HCC) patients with CHI. METHODS: Fifty-four patients who received 30 mg clevudine for more than 24 weeks between 2007 and 2009 at the National Cancer Center Hospital, Korea, were enrolled. Among these cases, 39 had HCC (CHI/HCC group) and 15 did not (CHI group). RESULTS: In relation to the CHI group, the CHI/HCC group was older (55.5 years.) and had a higher liver cirrhosis rate (79.5%) (p<0.05). Median changes in serum hepatitis B virus (HBV) DNA levels from baseline at weeks 12, 24, and 36 of treatment in the CHI/HCC group were not significantly different from those of the CHI group (-2.3, -2.7, -2.6 vs -1.7, -1.8, -2.4, respectively). HBV DNA <2,000 copies/mL was achieved in 76.5% of the CHI/HCC group at 24 weeks. Rates of ALT normalization in the CHI/HCC and CHI groups were 62.5% and 66.7%, respectively (p>0.05). Liver function was preserved with clevudine treatment in patients displaying response or stable disease under anti-cancer therapy. Four patients (7.4%) developed viral resistance during clevudine therapy. Among these, one was naive, and three had previously received antiviral therapy. One CHI/HCC patient (1.9%) discontinued clevudine treatment due to symptomatic myopathy. CONCLUSIONS: Our findings clearly indicate that clevudine has comparable antiviral and biochemical effects in patients with CHI and with CHI/HCC and preserves the underlying liver function in HBV-related HCC patients.
Arabinofuranosyluracil ; Carcinoma, Hepatocellular ; DNA ; Hepatitis B virus ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Humans ; Korea ; Liver ; Liver Cirrhosis ; Viruses

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

BACKGROUND/AIMS: Clevudine is a pyrimidine analogue with potent activity against hepatitis B virus (HBV) replication in vitro. In a previous pivotal phase III clinical study, 24 weeks treatment with clevudine 30 mg has been shown to profoundly suppress HBV replication and normalize serum alanine aminotransferase level. METHODS: In this study, we compare the efficacy and safety of clevudine (30 mg daily) versus lamivudine (100 mg daily) for 48 weeks in treatment-naive chronic hepatitis B e antigen (HBeAg) positive patients. RESULTS: Ninety-two chronic HBeAg positive patients were randomized to receive clevudine 30 mg daily or lamivudine 100 mg daily in a 1:1 ratio. The clevudine group demonstrated greater viral suppression at week 48 when compared with the lamivudine group (median reduction: 4.27 vs. 3.17 log(10) copies/ml at week 48, p<0.0001). At week 48, serum HBV DNA level was below 300 copies/mL in 73% and 40% in the clevudine and lamivudine groups, respectively (p=0.001). HBeAg seroconversion occurred in 18% of patients in the clevudine group versus 12% in the lamivudine group at week 48. Lamivudine-resistant mutations were detected in 11 (24%) patients in the lamivudine group, who showed viral rebound during lamivudine therapy but no resistance was found in the clevudine group during 48-week treatment period. CONCLUSIONS: A 48-week dosing with clevudine 30 mg daily was superior to lamivudine 100 mg daily in suppressing HBV replication, with no emergence of viral breakthrough in patients with HBeAg positive chronic hepatits B.
Adult ; Alanine Transaminase/blood ; Antiviral Agents/*administration & dosage ; Arabinofuranosyluracil/administration & dosage/*analogs & derivatives ; DNA, Viral/blood ; Double-Blind Method ; Drug Administration Schedule ; Drug Resistance, Viral ; Female ; Genotype ; Hepatitis B e Antigens/blood ; Hepatitis B, Chronic/*drug therapy ; Humans ; Lamivudine/*administration & dosage ; Male ; Middle Aged

Several studies have documented that various agents can induce diabetes mellitus, such as steroids, thiazides, anti-psychotic agents, and anti-viral agents. Many antiviral agents are also reported to impair insulin resistance and induce diabetes mellitus in patients infected with human immunodeficiency virus (HIV). However, there are no reports of diabetes mellitus induced by clevudine, one of the antiviral agents used to treat chronic hepatitis B virus (HBV) infection. We report a case of diabetes mellitus induced by clevudine in a patient with chronic hepatitis B.
Antiviral Agents ; Arabinofuranosyluracil ; Diabetes Mellitus ; Hepatitis B, Chronic ; Hepatitis, Chronic ; HIV ; Humans ; Insulin Resistance ; Steroids ; Thiazides ; Viruses

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