6th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 25–28 October 2004 - Washington, DC, USA

NON-INVASIVE ASSESSMENT OF HEPATIC MITOCHONDRIAL TOXICITY IN HIV-INFECTED PATIENTS WITH NORMAL SERUM LACTATE BY ¹³C-METHIONINE BREATH TEST

Antiviral Therapy 2004; 9(6):L19 (abstract no. 25)

M Banasch¹, O Goetze², I Hollborn¹, B Hochdorfer³, N Brockmeyer³, WE Schmidt¹ and F Schmitz^1
1Department of Internal Medicine 1, University of Bochum, St Josef Hospital, Bochum, Germany; ²Department of Gastroenterology and Hepatology, University of Zurich, Zurich, Switzerland; and ³Department of Dermatology, University of Bochum, Bochum, Germany

OBJECTIVES: Mitochondrial toxicity related to HIV-infection and antiretroviral therapy (ART) is associated with a broad range of metabolic disorders such as hepatic steatosis, lactic acidosis and lipodystrophy syndrome. Recently the non-invasive, non-radioactive ¹³C-methionine breath test (MBT) has been proven to detect mitochondrial impairment in HIV-infected patients with symptomatic hyperlactacidaemia. Since elevated serum lactate is no precondition for mitochondrial toxicity we investigated the validity of the ¹³C-methionine breath test in various patient groups with normal serum lactate values.

METHODS: The MBT was performed in 14 healthy controls and 46 patients with chronic HIV infection: 13 patients with no treatment experience, 23 patients with asymptomatic disease who had received ART for longer than 1 year and 10 patients with long-term ART (>5 years) and clinical signs of lipoatrophy. After an overnight fast, the volunteers received 2 mg/kg body weight [methyl-¹³C]-labelled methionine. Hepatic mitochondrial decarboxylation was measured by breath ¹³CO₂ enrichment expressed as delta over baseline (DOB) every 10 min for 120 min by isotope ratio infrared spectroscopy. Allowing for the different body weights, the kinetic variable cPDR (cumulative percentage ¹³C dose recovered over test period) was obtained by mathematical analysis.

RESULTS: ANOVA analysis showed significantly decreased ¹³C-exhalation in HIV-infected patients with evidence of lipoatrophy compared with healthy subjects (cPDR 2.42 ±0.9 vs 6.74 ±1.4, P<0.01). There was no statistical significance between healthy volunteers and patients with asymptomatic disease in our study (cPDR 6.74 ±1.4 vs 7.02 ±1.1, P>0.5). Surprisingly, treatment-naïve patients also exhibited significantly decreased hepatic mitochondrial decarboxylation function compared with healthy volunteers (cPDR 4.92 ±1.90 vs 6.74 ±1.4, P<0.05).

CONCLUSIONS: The MBT is a simple, non-invasive method of detecting hepatic mitochondrial impairment in HIV-infected patients. The altered ¹³C-metabolism in patients with long-term treatment and signs of lipoatrophy was expected, reflecting the chronic mitochondrial toxicity of ART. We are the first to show that therapy-naïves also exhibit significant impairment of mitochondrial decarboxylation function. We hypothesize that mitochondrial dysfunction might rapidly improve after initiating ART. Our results provide evidence that the MBT is an invaluable diagnostic tool for both screening and follow-up monitoring of hepatic mitochondrial function.

2004-10-25
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