To the Editor:

We read with great interest the article by Lange and coworkers.1 It is known that mitochondrial toxicity related to the nucleoside analogues can result in macrovesical hepatic steatosis and lactic acidosis. In vivo, these results were shown as side effects of long-term lamivudine use in patients with human immunodeficiency virus (HIV).2 It was noted that the amount of mitochondrial DNA defects is a predictive marker for the clinical expression of mitochondrial toxicity.2 In case of the severity of the underlying liver dysfunction due to cirrhosis, or acute exacerbation of chronic liver disease, the function of mitochondria in hepatocytes declines immediately. In light of these data, severe mitochondrial dysfunction leading to lactic acidosis can be aggravated by nucleoside analogues in patients with an underlying disease, as discussed above. Moreover, hepatic steatosis may be an additional risk factor for these patients with hyperlactatemia who are using entecavir. Obesity was reported as a possible risk factor for mitochondrial toxicity in patients with HIV who are undergoing highly active antiretroviral therapy.3 So, in spite of the small numbers of patients with lactic acidosis under entecavir, we worry about the effect of body mass index on treatment toxicity.


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  • 1
    Lange CM, Bojunga J, Hofmann WP, Wunder K, Mihm U, Zeuzem S, et al. Severe lactic acidosis during treatment of chronic hepatitis B with entecavir in patients with impaired liver function. HEPATOLOGY 2009; 50: 20012006.
  • 2
    Brinkman K, Hadewych JM. Adverse effects of reverse transcriptase inhibitors: mitochondrial toxicity as common pathway. AIDS 1998; 12: 17351744.
  • 3
    Olano JP, Borucki MJ, Wen JW, Haque AK. Massive hepatic steatosis and lactic acidosis in a patient with AIDS who was receiving zidovudine. Clin Infect Dis 1995; 21: 973976.

Akif Altınbas MD*, Fuat Ekiz MD*, Osman Yuksel MD, Assoc. Prof.*, * Dışkapı Yıldırım Beyazit, Education and Research Hospital, Department of Gastroenterology, Ankara, Turkey.