Long-Term Treatment Efficacy and Safety of Clevudine Therapy in Naïve Patients with Chronic Hepatitis B
1
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
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 naïve patients with CHB were investigated. Methods: In this retrospective study, 152 naïve 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 ≥6 log10 IU/mL (p=0.032) and detectable serum HBV DNA (≥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 naïve 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 naïve patients given the availability of other more potent, safer antiviral agents.
Abstract
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 naïve patients with CHB were investigated. Methods: In this retrospective study, 152 naïve 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 ≥6 log10 IU/mL (p=0.032) and detectable serum HBV DNA (≥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 naïve 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 naïve patients given the availability of other more potent, safer antiviral agents.
참고문헌 (19)
- Balakrishna Pai S, "Inhibition of hepatitis B virus by a novel L-nucleoside, 2’-fluoro-5-methyl-beta-L-arabinofuranosyl uracil", Antimicrob Agents Chemother, 40, pp.380~386 (1996)
- Liu SH, "Unique metabolism of a novel antiviral L-nucleoside analog, 2’-fluoro-5-methyl-beta-L-arabinofuranosyluracil: a substrate for both thymidine kinase and deoxycytidine kinase", Antimicrob Agents Chemother, 42, pp.833~839 (1998)
- Yoo BC, "Twenty-four-week clevudine therapy showed potent and sustained antiviral activity in HBeAg-positive chronic hepatitis B", HEPATOLOGY, 45, pp.1172~1178
- Yoo BC, "Clevudine is highly efficacious in hepatitis B e antigen-negative chronic hepatitis B with durable off-therapy viral suppression", HEPATOLOGY, 46, pp.1041~1048
- 김민환, "만성 B형간염에서 클레부딘의 48주 치료 효과", Clinical and Molecular Hepatology, 15(3), pp.331~337 (2009), 대한간학회
- George KK Lau, "Forty-eight weeks treatment with clevudine 30 mg qd versus lamivudine 100 mg qd for chronic hepatitis B infection: a double-blind randomized study", Clinical and Molecular Hepatology, 16(3), pp.315~320 (2010), 대한간학회
- 김인희, "Treatment Outcomes of Clevudine versus Lamivudine at Week 48 in Naive Patients with HBeAg Positive Chronic Hepatitis B", Journal of Korean Medical Science, 25(5), pp.738~745 (2010), 대한의학회
- 양현웅, "Efficacy of Initial Treatment with Clevudine in Naive Patients with Chronic Hepatitis B", The Korean Journal of Internal Medicine, 25(4), pp.372~376 (2010), 대한내과학회
- 신수린, "A comparison of 48-week treatment efficacy between clevudine and entecavir in treatment-na < ve patients with chronic hepatitis B", HEPATOLOGY INTERNATIONAL, 5(2), pp.664~670, SPRINGER
- Seok JI, "Long-term therapy with clevudine for chronic hepatitis B can be associated with myopathy characterized by depletion of mitochondrial DNA", Hepatology, 49, pp.2080~2086 (2009)
- Kim BK, "Clevudine myopathy in patients with chronic hepatitis B", J Hepatol, 51, pp.829~834 (2009)
- Tak WY, "Clinical, biochemical, and pathological characteristics of clevudine-associated myopathy", J Hepatol, 53, pp.261~266 (2010)
- Chang TT, "A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B", N Engl J Med, 354, pp.1001~1010 (2006)
- 김동준, "Telbivudine versus lamivudine in patients with chronic hepatitis B", NEW ENGLAND JOURNAL OF MEDICINE, 357(25), pp.2576~2588, MASSACHUSETTS MEDICAL SOC
- Yuen MF, "Hepatitis B virus DNA levels at week 4 of lamivudine treatment predict the 5-year ideal response", Hepatology, 46, pp.1695~1703 (2007)
- Hadziyannis SJ, "Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years", Gastroenterology, 131, pp.1743~1751 (2006)
- European Association for the Study of the Liver, "EASL Clinical Practice Guidelines: management of chronic hepatitis B", J Hepatol, 50, pp.227~242 (2009)
- Keeffe EB, "A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2008 update", Clin Gastroenterol Hepatol, 6, pp.1315~1341 (2008)
- Kwon SY, "Identification and characterization of clevudine-resistant mutants of hepatitis B virus isolated from chronic hepatitis B patients", J Virol, 84, pp.4494~4503 (2010)