Zidovudine-Associated Type B Lactic Acidosis and Hepatic Steatosis in an HIV-Infected Patient

Acosta, Brick; Grimsley, Edwin W.

doi:10.1097/00007611-199904000-00015

Cited by 39 publications

(22 citation statements)

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“…Because most of the patients were also receiving protease inhibitors or nonnucleoside reverse transcriptase inhibitors, neither class of which has been associated with lactic acidosis, we cannot exclude a metabolic interaction among these drug classes. Similar to other reports describing the lactic acidosis/hepatic steatosis syndrome, our patients had received nucleoside analogue therapy for several months before presentation, and most of them were overweight, had gastrointestinal complaints, hepatomegaly, slightly elevated aminotransaminases, and evidence of hepatic steatosis, either by imaging or biopsy [1,[4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. In contrast, our patients had much milder elevations in lactate levels.…”

Section: Discussionsupporting

confidence: 61%

“…Previous series have reported a mortality rate 150% [1,5,10,16]. Of 36 cases reported in the literature, the majority required hospitalization, and two-thirds died [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. These higher morbidity and mortality rates may be from spectrum bias resulting in identification of only the most severe cases.…”

Section: Discussionmentioning

confidence: 99%

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Hyperlactatemia and Hepatic Abnormalities in 10 Human Immunodeficiency Virus-Infected Patients Receiving Nucleoside Analogue Combination Regimens

Lonergan

Behling

Pfander

et al. 2000

Clinical Infectious Diseases

188

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During a 6-and-a-half month period, we identified 10 human immunodeficiency virus (HIV)-infected men who were receiving antiretroviral regimens, including nucleoside analogues, and who developed unexplained reproducible hyperlactatemia in association with either abdominal symptoms or an unaccounted-for elevated alanine aminotransferase level, or both. After careful consideration of the possible etiologies, antiretrovirals were discontinued; lactate levels normalized in all patients. The estimated incidence of this phenomenon in our clinic was 20.9 cases per 1000 person-years of nucleoside analogue treatment. These observations extend the spectrum of the nucleoside analogue-induced lactic acidosis/hepatic steatosis syndrome by the identification of a subtle and perhaps earlier form, which has characteristic symptoms and laboratory abnormalities, and a favorable prognosis on discontinuation of antiretroviral therapy.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Hyperlactatemia and Hepatic Abnormalities in 10 Human Immunodeficiency Virus-Infected Patients Receiving Nucleoside Analogue Combination Regimens

Lonergan

Behling

Pfander

et al. 2000

Clinical Infectious Diseases

188

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“…However, long-term use of AZT is associated with significant hematologic disorders, cardiomyopathy and hepatotoxicity (Chariot et al, 1999; Desai et al, 2012; Szabados et al, 1999). With regard to hepatotoxicity, AZT is known to cause mitochondrial dysfunction and apoptosis, however, the detailed mechanisms are not completely understood (Acosta and Grimsley, 1999; Banerjee et al, 2013; Chariot et al, 1999; de la Asuncion et al, 1999; Freiman et al, 1993). …”

Section: Introductionmentioning

confidence: 99%

Acrolein enhances epigenetic modifications, FasL expression and hepatocyte toxicity induced by anti-HIV drug Zidovudine

Ghare

Donde

Chen

et al. 2016

Toxicology in Vitro

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Zidovudine (AZT) remains the mainstay of antiretroviral therapy against HIV in resource-poor countries; however, its use is frequently associated with hepatotoxicity. Not all HIV patients on AZT develop hepatotoxicity, and the determining factors are unclear. Alcohol consumption and cigarette smoking are known risk factors for HIV hepatotoxicity, and both are significant sources of acrolein, a highly reactive and toxic aldehyde. This study examines the potential hepatotoxic interactions between acrolein and AZT. Our data demonstrate that acrolein markedly enhanced AZT-induced transcriptionally permissive histone modifications (H3K9Ac and H3K9Me3) allowing the recruitment of transcription factor NF-kB and RNA polymerase II at the FasL gene promoter, resulting in FasL upregulation and apoptosis in hepatocytes. Notably, the acrolein scavenger, hydralazine prevented these promoter-associated epigenetic changes and inhibited FasL upregulation and apoptosis induced by the combination of AZT and acrolein, as well as AZT alone. Our data strongly suggest that acrolein enhancement of promoter histone modifications and FasL upregulation are major pathogenic mechanisms driving AZT-induced hepatotoxicity. Moreover, these data also indicate the therapeutic potential of hydralazine in mitigating AZT hepatotoxicity.

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“…The most commonly implicated drugs include metformin, isoniazid, propylene glycol, and nucleoside reverse-transcriptase inhibitors such as zidovudine and stavudine in patients with HIV. [4][5][6][7] The pathogenesis for this abnormal accumulation of lactate is diverse and ranges from derangements in enzymatic processes, 3,8 preferential switches in catabolic pathways, 9,10 and various levels of mitochondrial dysfunction. [11][12][13][14][15] We report the first case of type B lactic acidosis that was caused by the overdose of the serotonin-norepinephrine reuptake inhibitor, venlafaxine.…”

Section: Introductionmentioning

confidence: 99%

Type B Lactic Acidosis Associated With Venlafaxine Overdose

Iragavarapu

Gupta

Chugh

et al. 2016

American Journal of Therapeutics

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Lactic acidosis that is not secondary to tissue hypoperfusion or hypoxemia (type B lactic acidosis) is a rare but potentially fatal condition that has been associated with drugs like metformin, linezolid, and nucleoside reverse-transcriptase inhibitors in patients with HIV. We report the first case of type B lactic acidosis caused by overdose of the serotonin-norepinephrine reuptake inhibitor, venlafaxine. A 55-year-old man with no significant medical history was brought to the emergency department after intentional ingestion of around 80 capsules of venlafaxine (a total dose of over 6000 mg) in an attempt to commit suicide. Complete blood count and comprehensive metabolic panel were unremarkable except for a bicarbonate level of 13 mEq/L and an anion gap of 22 mEq/L. An arterial blood gas revealed a pH of 7.39, partial pressure of CO2 of 19 mm Hg, calculated bicarbonate of 11.5 mEq/L, and a lactate level of 8.6 mmol/L. The patient was started on aggressive intravenous hydration with normal saline along with oral activated charcoal with sorbitol. Repeat laboratory work after 4 hours showed an improvement in anion gap (15 mEq/L) and serum lactate (5.6 mmol/L). The patient remained stable throughout the hospital stay and lactic acidosis resolved in 24 hours. In the absence of hypotension, hypoxemia, kidney or liver dysfunction, myopathy, malignancy, or use of other medications, venlafaxine was the most likely cause of lactic acidosis in our case. Rapid improvement of acidosis was probably related to clearance of the drug.

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Zidovudine-Associated Type B Lactic Acidosis and Hepatic Steatosis in an HIV-Infected Patient

Cited by 39 publications

References 0 publications

Hyperlactatemia and Hepatic Abnormalities in 10 Human Immunodeficiency Virus-Infected Patients Receiving Nucleoside Analogue Combination Regimens

Hyperlactatemia and Hepatic Abnormalities in 10 Human Immunodeficiency Virus-Infected Patients Receiving Nucleoside Analogue Combination Regimens

Acrolein enhances epigenetic modifications, FasL expression and hepatocyte toxicity induced by anti-HIV drug Zidovudine

Type B Lactic Acidosis Associated With Venlafaxine Overdose

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