Clinicopathological Features of Telbivudine-Associated Myopathy

Ambang, T.; Tan, Jully; Ong, Sheila; Wong, Kum-Thong; Goh, Khean Jin

doi:10.1371/journal.pone.0162760

Cited by 19 publications

(9 citation statements)

References 20 publications

(36 reference statements)

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“…Telbivudine-associated myopathy generally occurred after taking drugs for more than one year, more common in male patients, presenting as myalgia, muscle weakness and elevated CPK [ 6 ]. Without any management, it possibly develops to RM.…”

Section: Discussionmentioning

confidence: 99%

Case report: lactic acidosis and rhabdomyolysis during telbivudine and tenofovir treatment for chronic hepatitis B

Jin

et al. 2018

BMC Gastroenterol

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BackgroundCurrent treatment options for chronic hepatitis B (CHB) are pegylated interferon alpha and nucleoside analogues (NAs). NAs have relatively fewer side effects than interferon alpha, and generally well tolerated. Previously 12.9% of patients on telbivudine treatment were reported to develop severe elevation of serum creatine phosphokinase (CPK) levels, but related clinical disease, like lactic acidosis (LA) and rhabdomyolysis (RM) were rare. The pathophysiology may be mitochondrial toxicity, for the NAs inhibit not only hepatitis B virus (HBV) polymerase, but also the host mitochondrial DNA polymerase γ. As mitochondria are the main sites of oxidative phosphorylation, there will be an increase of pyruvate reduction to lactic acid and insufficient adenosine triphosphate. The accumulation of lactic acid causes LA, while lack of energy leads to cell dysfunction and mitochondria-associated disease, including RM. All five NAs, except tenofovir, have been reported causing LA and RM. Here we report the first case of CHB patients developing fatal LA and RM during telbivudine and tenofovir treatment.Case presentationThe patient is a 51-year-old man who was hospitalized in November 2015. He had taken telbivudine regularly because of CHB. Later, tenofovir was added to antiviral treatment because of HBV resistance. Then he had myalgia, chest tightness and anorexia. The blood lactate was 12.7 mmol/L. The arterial blood gas analysis showed pH 7.25, base excess 21.1 mmol/L. CPK was 991 U/L, myoglobin was 1745 ng/ml and creatine was 83 μmol/L. Abdomen magnetic resonance revealed cirrhosis. Muscle biopsy revealed myogenic lesion with abnormality of mitochondria and fat metabolism. The patient was diagnosed with Hepatitis B envelope Antigen positive CHB, cirrhosis, LA and RM characterized by myalgia and elevated myoglobin. He was given tenofovir alone as antiviral treatment instead. After hemodialysis and 4 weeks` treatment of corticosteroids, his symptoms recovered, and blood lactate gradually returned to a normal range.ConclusionsThis case shows that tenofovir may trigger muscle damage and fatal RM in combination with telbivudine treatment in CHB patients. Thus, patients receiving tenofovir and telbivudine should be closely monitored for muscular abnormalities, blood lactate level and other mitochondrial toxicity associated side effects.

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Section: Discussionmentioning

confidence: 99%

Case report: lactic acidosis and rhabdomyolysis during telbivudine and tenofovir treatment for chronic hepatitis B

Jin

et al. 2018

BMC Gastroenterol

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“…Muscle biopsy of left rectus femoris revealed degenerative muscle fibres with variation in fibre size, regeneration, angulated fibres (Figure A), numerous enlarged and abnormally shaped mitochondria under electronic microscopy (Figure B), consistent with mitochondrial myopathies. He was diagnosed telbivudine‐associated mitochondrial myopathy and telbivudine was switched to entecavir. After that, the patient regained his muscle strengths gradually and serum CPK level reduced (from more than 2000 drop to 367 U/L) in follow‐up.…”

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confidence: 99%

“…, numerous enlarged and abnormally shaped mitochondria under electronic microscopy ( Figure 1B), consistent with mitochondrial myopathies. He was diagnosed telbivudine-associated mitochondrial myopathy [2][3][4] and telbivudine was switched to entecavir.…”

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confidence: 99%

Telbivudine associated mitochondrial myopathy

Lim

Liao

Tsai

2018

Liver International

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“…Zidovudine causes damage to mitochondria by impairment of respiratory chain and mitochondrial protein synthesis ( 16 ). Recently, telbivudine, another L-nucleoside analogue for HBV infection, has been reported to show evidence of mitochondrial toxicity with a clinical pattern similar to that of fifteen patients ( 17 ).…”

Section: Discussionmentioning

confidence: 99%

Clevudine Induced Mitochondrial Myopathy

Park

Kim

et al. 2017

J Korean Med Sci

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Clevudine was approved as an antiviral agent for hepatitis B virus, which showed marked, rapid inhibition of virus replication without significant toxicity. However, several studies have reported myopathy associated with clevudine therapy. Also, we experienced seven patients who suffered from myopathy during clevudine therapy. To characterize clevudine-induced myopathy, we collected previously reported cases of clevudine myopathy and analyzed all the cases including our cases. We searched electronic databases that were published in English or Korean using PubMed and KoreaMed. Ninety-five cases with clevudine myopathy, including our seven cases, were selected and analyzed for the demographic data, clinical features, and pathologic findings. The 95 patients with clevudine-induced myopathy comprised 52 women and 43 men aged 48.9 years (27–76 years). The patients received clevudine therapy for about 14.2 months (5–24 months) before the development of symptoms. Weakness mainly involved proximal extremities, especially in the lower extremities, and bulbar and neck weakness were observed in some cases (13.7%). Creatine kinase was elevated in the majority of patients (97.9%). Myopathic patterns on electromyography were observed in most patients examined (98.1%). Muscle biopsy presented patterns compatible with mitochondrial myopathy in the majority (90.2%). The weakness usually improved within about 3 months after the discontinuation of clevudine. Though clevudine has been known to be safe in a 6-month clinical trial, longer clevudine therapy for about 14 months may cause reversible mitochondrial myopathy. Careful clinical attention should be paid to patients with long-term clevudine therapy.

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Clinicopathological Features of Telbivudine-Associated Myopathy

Cited by 19 publications

References 20 publications

Case report: lactic acidosis and rhabdomyolysis during telbivudine and tenofovir treatment for chronic hepatitis B

Case report: lactic acidosis and rhabdomyolysis during telbivudine and tenofovir treatment for chronic hepatitis B

Telbivudine associated mitochondrial myopathy

Clevudine Induced Mitochondrial Myopathy

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