Elsevier

Clinical Biochemistry

Volume 38, Issue 6, June 2005, Pages 531-534
Clinical Biochemistry

The quantification of cytochrome P-450 (CYP 3A4) mRNA in the blood of patients with viral liver diseases

https://doi.org/10.1016/j.clinbiochem.2005.01.005Get rights and content

Objective:

We quantified cytochrome P-450 (CYP) 3A4 mRNA in the blood and liver of patients with viral liver diseases to determine whether CYP 3A4 expression is related to disease progression.

Design and methods:

Total RNA was extracted from 10 mL of blood from 12 normal volunteers, from 6 patients with acute hepatitis, 17 with chronic hepatitis, 12 with liver cirrhosis, and 16 with hepatocellular carcinoma. Total RNA from 1 mg of liver tissue was extracted simultaneously in 10 patients. CYP 3A4 mRNA was quantified by competitive reverse-transcription polymerase chain reaction and expressed as log copies/microliter.

Results:

The CYP 3A4 mRNA titer in blood correlated with that of the liver (r = 0.65, P < 0.05). The CYP 3A4 mRNA titer was 1.6 ± 0.4 in normal controls, 1.0 ± 0.5 in acute hepatitis, 0.7 ± 0.2 in chronic hepatitis, 0.5 ± 0.2 in liver cirrhosis, 0.5 ± 0.2 in hepatocellular carcinoma, and decreased with progression of liver disease (P < 0.05).

Conclusion:

These data suggest that the CYP 3A4 mRNA level in blood relates to progression of liver disease.

Introduction

Cytochrome P-450 (CYP) is an important drug metabolic enzyme primary distributed in the liver [1]. The most highly expressed CYP is the CYP3A subfamily, which includes the isoforms 3A4, 3A5, 3A7, and 3A43. The most abundant CYP3A isoform expressed in the liver and gut is CYP 3A4 [2]. CYP 3A4 expression in liver and its enzymatic activity may vary between 20- and 50-fold among normal individuals [2], [3].

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are worldwide health problems. Chronic hepatitis (CH) due to HBV and HCV may progress to liver cirrhosis (LC) or hepatocellular carcinoma (HCC) over the course of 20–30 years. In LC, liver function, including CYP 3A4 enzymatic activity, is decreased [4]. In addition, CYP 3A4 is also a procarcinogen metabolizer [1] and thus may play a role in hepatocarcinogenesis. However, the level of CYP 3A4 expression in blood and liver and its role in viral liver diseases is unclear. To clarify whether CYP 3A4 expression in blood and liver is related to hepatitic activity, progression of viral liver diseases, and occurrence of HCC, we quantified CYP 3A4 mRNA in the blood and liver of patients with viral liver diseases.

Section snippets

Patients

The study population was comprised of 51 patients (40 males, 11 females, mean age ± SD: 52.4 ± 14.7 years, range: 22–77 years) including 6 with acute hepatitis (AH), 17 with CH, 12 with LC, and 16 with HCC, admitted to our hospital between February 2001 and September 2002, consecutively. The number of HBs antigen positive and HCV antibody positive patients in CH was 14 and 3, respectively, and was 9 and 3 in LC, and 14 and 2 in HCC. In AH, 1 patient was HBs antigen positive, 3 were HCV antibody

Results

CYP 3A4 mRNA could not be detected in the peripheral mononuclear cells or serum isolated from the 10 mL of blood from the normal controls, but was detectable in 10 mL of whole blood (1.6 ± 0.4) from the same subjects. The CYP 3A4 mRNA titer varied about 20 fold in the 12 normal subjects.

In the 7 CH and 3 LC patients, the CYP 3A4 mRNA titer in the blood correlated with that of the liver (r = 0.65, P < 0.05). Table 1 shows the CYP 3A4 mRNA titer in the blood of the various liver disease patients.

Discussion

Examination of CYP 3A4 activity in liver disease is difficult. Sumida reported that CYP 3A4 activity is related to the CYP 3A4 mRNA titer in the liver [8]. To investigate CYP 3A4 expression and its role in viral liver diseases, we determined the CYP 3A4 mRNA titer in whole blood and liver tissue. A close relationship was detected between the CYP 3A4 mRNA titers in blood and liver, suggesting that the CYP 3A4 mRNA titer in blood is a surrogate marker for the CYP 3A4 mRNA titer and enzymatic

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  • Cited by (12)

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