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

Abstract Background Current 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 t...

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Main Authors: Yue Ying, Yue-Kai Hu, Jia-Lin Jin, Ji-Ming Zhang, Wen-Hong Zhang, Yu-Xian Huang
Format: Article
Language:English
Published: BMC 2018-04-01
Series:BMC Gastroenterology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12876-018-0773-3
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author Yue Ying
Yue-Kai Hu
Jia-Lin Jin
Ji-Ming Zhang
Wen-Hong Zhang
Yu-Xian Huang
author_facet Yue Ying
Yue-Kai Hu
Jia-Lin Jin
Ji-Ming Zhang
Wen-Hong Zhang
Yu-Xian Huang
author_sort Yue Ying
collection DOAJ
description Abstract Background Current 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 presentation The 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. Conclusions This 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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spelling doaj.art-a20a84b4a51846fabb1e77289ad5c0e62022-12-21T23:40:06ZengBMCBMC Gastroenterology1471-230X2018-04-011811610.1186/s12876-018-0773-3Case report: lactic acidosis and rhabdomyolysis during telbivudine and tenofovir treatment for chronic hepatitis BYue Ying0Yue-Kai Hu1Jia-Lin Jin2Ji-Ming Zhang3Wen-Hong Zhang4Yu-Xian Huang5Department of Infectious Diseases, Huashan Hospital Affiliated to Fudan UniversityDepartment of Infectious Diseases, Huashan Hospital Affiliated to Fudan UniversityDepartment of Infectious Diseases, Huashan Hospital Affiliated to Fudan UniversityDepartment of Infectious Diseases, Huashan Hospital Affiliated to Fudan UniversityDepartment of Infectious Diseases, Huashan Hospital Affiliated to Fudan UniversityDepartment of Infectious Diseases, Huashan Hospital Affiliated to Fudan UniversityAbstract Background Current 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 presentation The 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. Conclusions This 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.http://link.springer.com/article/10.1186/s12876-018-0773-3Lactic acidosisRhabdomyolysisMitochondrial toxicityMyopathyTelbivudineTenofovir
spellingShingle Yue Ying
Yue-Kai Hu
Jia-Lin Jin
Ji-Ming Zhang
Wen-Hong Zhang
Yu-Xian Huang
Case report: lactic acidosis and rhabdomyolysis during telbivudine and tenofovir treatment for chronic hepatitis B
BMC Gastroenterology
Lactic acidosis
Rhabdomyolysis
Mitochondrial toxicity
Myopathy
Telbivudine
Tenofovir
title Case report: lactic acidosis and rhabdomyolysis during telbivudine and tenofovir treatment for chronic hepatitis B
title_full Case report: lactic acidosis and rhabdomyolysis during telbivudine and tenofovir treatment for chronic hepatitis B
title_fullStr Case report: lactic acidosis and rhabdomyolysis during telbivudine and tenofovir treatment for chronic hepatitis B
title_full_unstemmed Case report: lactic acidosis and rhabdomyolysis during telbivudine and tenofovir treatment for chronic hepatitis B
title_short Case report: lactic acidosis and rhabdomyolysis during telbivudine and tenofovir treatment for chronic hepatitis B
title_sort case report lactic acidosis and rhabdomyolysis during telbivudine and tenofovir treatment for chronic hepatitis b
topic Lactic acidosis
Rhabdomyolysis
Mitochondrial toxicity
Myopathy
Telbivudine
Tenofovir
url http://link.springer.com/article/10.1186/s12876-018-0773-3
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