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: 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

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

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

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/AIMS: Entecavir (ETV) and clevudine (CLV) are potent inhibitors of hepatitis B virus (HBV) DNA polymerase and have demonstrated clinical efficacy. No comparative study has reported on these two medications among patients with naive chronic hepatitis B (CHB). We assessed the clinical outcome of CHB patients treated with either ETV or CLV. METHODS: A nonrandomized comparative study was conducted retrospectively. The clinical results from treatments of either 0.5 mg ETV (n=56) or 30 mg CLV (n=45) were analyzed during a 1 year period. The median reduction in serum HBV DNA, undetectable HBV DNA, HBeAg seroconversion, and normalization of alanine transaminase (ALT) were compared between the two groups. RESULTS: After 1 year on antiviral therapy, the median reduction in serum HBV DNA from baseline to the endpoint was greater in patients in the ETV group than in those in the CLV (5.73 vs. 4.5 log copies/mL, p=0.009) group. ALT normalization occurred in 85.5% (47/55) of the ETV cases and 77.3% (34/40) of the CLV cases (p=0.215). HBV DNA was undetectable in 80.0% (44/55) of the ETV group and 78.0% (32/41) of the CLV group (p=0.505). HBeAg seroconversion occurred in 15.4% (6/39) of those administered ETV and in 14.3% (4/28) administered CLV (p=0.593). Within 12 months, a virological breakthrough was documented in three patients undergoing CLV treatment, and CLV-related myopathy developed in three other patients. CONCLUSIONS: ETV and CLV showed excellent antiviral effects in patients with CHB. ETV was superior for viral suppression and showed fewer side effects than CLV.
Alanine Transaminase ; Arabinofuranosyluracil ; DNA ; Guanine ; Hepatitis B e Antigens ; Hepatitis B virus ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Humans ; Muscular Diseases ; Retrospective Studies

A 47-year-old woman underwent orthotopic liver transplantation (OLT) for hepatitis B virus (HBV)-related end-stage liver cirrhosis. The patient received hepatitis B immunoglobulin prophylaxis after OLT. Despite the protective level of the serum anti-hepatitis-B surface antibody, HBV recurred at 22 months post-OLT and induced subacute hepatic failure. The pre-OLT HBV genome contained a complex mutation pattern in overlapping frame regions of the surface (S) and polymerase (P) genes, which is the same mutation pattern as seen in post-OLT HBV DNA. G145R and K141R mutations in the "a" determinant were detected only in the post-OLT sample. Clevudine (30 mg once daily) was administered for recurrent hepatitis B. Hepatitis B was reactivated with a flare-up, and a M204I mutation (YIDD mutant type) appeared with a higher viral load at 9 months after clevudine treatment. We report here a case of a YIDD mutation that developed in recurrent hepatitis B after OLT induced by an S-escape mutant.
Arabinofuranosyluracil ; DNA ; Female ; Genome ; Hepatitis ; Hepatitis B ; Hepatitis B virus ; Humans ; Immunoglobulins ; Liver ; Liver Cirrhosis ; Liver Failure ; Liver Transplantation ; Middle Aged ; Viral Load

A 40-year-old man with chronic hepatitis B complained of progressive weakness of the proximal muscles and edema of both legs. He had been receiving long-term clevudine (nucleoside analogue reverse transcriptase inhibitor, NRTI) therapy for his hepatitis. The serum creatine kinase level was increased on the laboratory tests. His electromyography showed a generalized myopathic process. The muscle biopsy showed numerous ragged-red fibers, degenerating myofibers with variable sized cytoplasmic bodies, the prominence of type 1 fibers with type 2 fiber atrophy and an endomysial mononuclear cell infiltration. The electron microscopic examination revealed necrotic myofibers, including extremely dysmorphic mitochondria with extensive loss, blunting and focal clumping of the cristae and concentric cristae. Although clevudine is known to be a less cytotoxic agent among the various NRTIs, careful clinical attention should be paid to the patients who are receiving long-term clevudine therapy for the occurrence of myopathy.
Adult ; Arabinofuranosyluracil ; Atrophy ; Biopsy ; Creatine Kinase ; Cytoplasm ; Edema ; Electromyography ; Electrons ; Hepatitis ; Hepatitis B, Chronic ; Humans ; Leg ; Mitochondria ; Mitochondrial Myopathies ; Muscles ; Muscular Diseases ; RNA-Directed DNA Polymerase

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

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