Efficacy of Entecavir Switching Therapy in Chronic Hepatitis B Patients with Clevudine-in-duced Myopathy

Ji Won Lee; Young Jun Lee; Jong Joon Lee; Jung Ho Kim; Young Kul Jung; Duck Joo Choi; Yun Soo Kim; Ju Hyun Kim; Oh Sang Kwon

doi:10.4166/kjg.2013.61.1.30

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Lee, Lee, Lee, Kim, Jung, Choi, Kim, Kim, and Kwon: Efficacy of Entecavir Switching Therapy in Chronic Hepatitis B Patients with Clevudine-in-duced Myopathy

Original Article

Korean J Gastroenterol 2013;61(1):30-36.

Published online: 4 October 2013

DOI: https://doi.org/10.4166/kjg.2013.61.1.30

Efficacy of Entecavir Switching Therapy in Chronic Hepatitis B Patients with Clevudine-in-duced Myopathy

Ji Won Lee, Young Jun Lee, Jong Joon Lee, Jung Ho Kim, Young Kul Jung, Duck Joo Choi, Yun Soo Kim, Ju Hyun Kim, Oh Sang Kwon

Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University of Medicine and Science, Incheon, Korea

Correspondence to: Yun Soo Kim, Department of Internal Medicine, Gachon University Gil Medical Center, 21 Namdong-daero 774beon-gil, Namdong-gu, Incheon 405-760, Korea. Tel: +82-32-460-3778, Fax: +82-32-460-3408, E-mail: kimys@gilhospital.com

Received 7 July 20125 September 2012 Accepted 25 September 2012

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.

Keywords: Clevudine, Entecavir, Chronic hepatitis B, Muscular diseases

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Fig. 1.

Cumulative incidence of biochemical, virologic, serologic responses and drug resistance during clevudine therapy.

Fig. 2.

Cumulative incidence of clevudine myopathy. Clevudine-induced myopathy occurred in 21 patients (14.4%) as early as 18 weeks and gradually increased during the treatment of 64 weeks.

Fig. 3.

Screening and follow-up of patients diagnosed as clevudine-induced myopathy.

Fig. 4.

Changes of HBV DNA (log₁₀ IU/mL) with entecavir switching therapy in HBV DNA-positive and HBV DNA-negative patients. (A) In 3 patients who had detectable HBV DNA at time point of myopathy, virologic response after entecavir switching therapy were noted. (B) Also 14 patients with virologic response with clevudine therapy maintained HBV DNA negativity during switching to entecavir therapy.

Table 1.

Baseline Characteristics of the Patients

Characteristic	Value
Age (yr)	42.2±10.4 (22–76)
Gender (male)	90 (61.6)
BMI (kg/m²)	24.0±3.1 (17.5–32.7)
HBV DNA (log₁₀ IU/mL)	7.4±7.2 (2.1–8.6)
HBeAg positive	84 (57.5)
Anti-HBe positive	59 (40.4)
AST (IU/L)	188.2±289.5 (27–2,817)
ALT (IU/L)	265.3±345.9 (16–2,357)
Albumin (g/dL)	4.1±0.5 (2.8–5.1)
Bilirubin (mg/dL)	2.0±3.8 (0.2–29.3)
Prothrombin time (sec) Platelet count (10³/mm³)	13.1±2.0 (10.1–27.2)193.1±74.4 (13–383)
Liver cirrhosis	36 (23.5)

Values are presented as mean±SD (range) or number (%).

Table 2.

Comparisons of Baseline Characteristics between Patients with Clevudine-induced Myopathy and without Myopathy

Characteristic	Myopathy(+) (n=21)	Myopathy(−) (n=125)	p-value
Age (yr)	43±8.7 (27–58)	41.8±10.5 (22–76)	0.38
Gender (male)	9 (42.8)	81 (64.8)	0.18
BMI (kg/m²)	24.1±2.82 (19.4–28.2)	24.0±3.23 (17.5–32.7)	0.48
HBV DNA (log₁₀ IU/mL)	7.4±7.4 (3.2–8.6)	7.4±7.1 (2.1–8.6)	0.65
HBeAg positive	16 (76.2)	68 (54.4)	0.12
Anti-HBe positive	6 (28.6)	53 (42.4)	0.12
AST (IU/L)	160.5±141.8 (27–640)	201±332.8 (28–2,817)	0.24
ALT (IU/L)	243.6.3±259.1 (34–1,373)	269.7±140 (16–2,357)	0.21
Albumin (g/dL)	4±0.47 (2.8–5.0)	4.6±0.47 (3.0–5.1)	0.29
Bilirubin (mg/dL)	1.2±0.8 (0.4–4.5)	2.3±4.4 (0.2–29.3)	0.13
Prothrombin time (sec)	12.8±1.1 (10.1–16.0)	13.2±2.2 (10.1–27.2)	0.38
Platelet count (10³/mm³)	195.1±72.0 (72–383)	192.2±75.7 (13–382)	0.84
Liver cirrhosis	4 (19.0)	32 (25.6)	0.32
Clevudine resistance	0 (0)	21 (16.8)	0.04

Values are presented as mean±SD (range) or number (%).

Table 3.

Characteristics of the 17 Patients at the Time Point of Clevudine-induced Myopathy

Characteristic	Value
Creatine kinase (IU/L)	551.4±314.5 (210–1,262)
AST (IU/L)	54.4±46.3 (27–221)
ALT (IU/L)	31.5±15.5 (17–79)
HBeAg, positive Anti-HBe, positive	8 (47) 9 (53)
HBV DNA (IU/mL)	45,358±15,686 (0–493,353)

Values are presented as mean±SD (range) or number (%).

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