Hepatic steatosis zidovudine

All NRTIs may be associated with mitochondrial toxicity, probably owing to inhibition of mitochondrial DNA polymerase gamma. Less commonly, lactic acidosis with hepatic steatosis may occur, which can be fatal. NRTI treatment should be suspended in the setting of rapidly rising aminotransferase levels, progressive hepatomegaly, or metabolic acidosis of unknown cause. The thymidine analogues zidovudine and stavudine may be particularly associated with dyslipidemia and insulin resistance. Also,... 

Antiretroviral nucleoside analogues have been associated with hepatic steatosis and lactic acidosis. These compounds require phosphorylation to active triphosphate derivatives by cellular phosphokinases. The triphosphate nucleotide inhibits the growing proviral DNA chain, but it also inhibits host DNA polymerases, and this can result in compensatory glycolysis and lactic acidosis. Abnormal mitochondrial oxidation of free fatty acids causes the accumulation of neutral fat in liver cells, and this manifests as hepatomegaly with macrovesicular steatosis. Hepatic steatosis and lactic acidosis have been reported previously with zidovudine, didanosine, zalcita-bine, Combivir (zidovudine plus lamivudine), and lamivudine. Of 349 Australian patients studied for 18 months (516 patient-years) taking NRTIs only two had severe lactic acidosis (847). 

The most common adverse effect with stavudine is peripheral neuropathy which occurs in -12% of patients. Combining stavudine with zidovudine leads to increased risk and severity of peripheral neuropathy and potentially fatal pancreatitis, and these drugs shorrld not be used together under most circumstances. Lactic acidosis and hepatic steatosis also have been seen and are more common with stavudine than with zidovudine or abacavir. Of aU the nucleoside analogs, stavudine is most strongly linked to the HIV lipodystrophy syndrome, perhaps due to toxic effects on adipocytes. 

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