Plasma hydroxy metronidazole/metronidazole ratio in anti-HCV carriers with and without apparent liver disease

Abstract

Aims: To evaluate plasma hydroxy-metronidazole/metronidazole ratio as a dynamic liver function test in HCV-infected individuals with/without liver disease, in the absence of liver cirrhosis.

Methods: Metronidazole was administered intravenously in healthy volunteers, asymptomatic anti-HCV-positive blood donors, and in chronic hepatitis C patients. Serology to HCV was determined by a second generation assay and confirmed by gelatin particle agglutination test using recombinant antigens C22-3 and C200. Plasma concentration of metronidazole and hydroxy-metronidazole was measured by high performance liquid chromatography in samples collected 5, 10, 20 and 30 min following the end of metronidazole infusion.

Results: Chronic hepatitis C patients had abnormal liver enzymes, while healthy volunteers and anti-HCV-positive blood donors had normal liver biochemistry tests. Plasma metronidazole concentration was similar in all groups studied. Plasma hydroxy-metronidazole/metronidazole ratio was significantly reduced in HCV-infected subjects, an effect observed 10 min after the end of drug infusion.

Conclusions: Metronidazole clearance is impaired in anti-HCV-positive blood donors and chronic hepatitis C patients, indicating that HCV is capable of affecting liver function at early stages of the disease. The metronidazole clearance test can detect impaired liver function in HCV-infected individuals even in the absence of liver cirrhosis.

Figure 1

Mean±s.e. mean plasma concentration vs time curves obtained for plasma MET (panel a), OHM (panel b) and OHM/MET ratio (panel c) from the three groups of subjects studied: healthy volunteers (•), anti-HCV-positive blood donors (○) and chronic C-virus hepatitis patients (▵). Asterisks denote significant difference compared which healthy volunteers (*P<0.05, **P<0.01 and ***P<0.001).