Strong Correlation between Liver and Serum Levels of Hepatitis C Virus Core Antigen and RNA in Chronically Infected Patients

Abstract

HCV core antigen (Ag) and HCV RNA levels were evaluated in matched liver biopsy samples and sera from 22 patients with hepatitis C infection by using the quantitative Architect HCV Ag immunoassay and a real-time RT-qPCR assay, respectively. The data showed a strong correlation between liver and serum compartments of HCV Ag levels (r ‫؍‬ 0.80) and HCV RNA levels (r ‫؍‬ 0.87). In summary, the serum HCV Ag and RNA levels reflect the intrahepatic values. Hepatitis C virus (HCV) is an important human pathogen; worldwide, over 170 million people are chronically infected. The standard virologic diagnosis of infection is based on the detection of specific anti-HCV antibodies and cannot distinguish between past and active infections. Therefore, assays of the HCV RNA load in serum or plasma have become essential for confirming active infections and guiding the initiation and continuation of treatment with pegylated interferon and ribavirin or other antivirals. At present, real-time PCR is the benchmark technique for detecting and quantitating HCV RNA in clinical practice, with limits of detection of 10 to 15 IU/ml (4, 7, 15). However, these assays require high levels of technical skill and are labor-intensive in routine use.Hepatitis C virus particles contain a core antigen (Ag) which encapsidates the viral RNA. The core Ag is present in the serum of infected individuals, probably in both complete virions and RNAfree core protein structures (18). Recently, a highly sensitive and quantitative immunoassay for HCV Ag was developed (the Architect HCV Ag test; Abbott Diagnostics, Rungis, France). It has a cutoff of 3 fmol/liter (0.06 pg/ml). Previous studies using this assay have indicated that (i) the time course of HCV Ag levels is similar to those of HCV RNA for all phases of infection (11,17) and (ii) the serum concentrations of HCV Ag and RNA are closely correlated (8-10, 12, 17).However, the HCV Ag assay has not previously been applied to the measurement of intrahepatic HCV Ag levels. The liver is the primary site of HCV replication, and previous work revealed a direct correlation between liver and serum HCV RNA levels (16,(20)(21)(22). Here, we sought to investigate the applicability of the assay to quantitation of HCV Ag in paired serum and liver biopsy specimens from treatment-naïve, HCV-infected patients. We also investigated the relationship between the intrahepatic viral load and the serum viral load, as determined by Ag and RNA assays.We retrospectively evaluated liver biopsy specimens and sera collected from 22 chronically HCV-infected patients and 3 HCVnegative patients. For each patient, a percutaneous liver biopsy specimen and a serum sample were simultaneously collected and stored at Ϫ80°C. Epidemiological, clinical, and biochemical data (age, gender, HCV genotype, fibrosis, and alanine aminotransferase levels [IU/liter]) were also recorded (Table 1).Each sample of frozen liver tissue was weighed and cut into two similar portions. One portion was used for total protein extraction and homogenized in passive ly...

Correlation between hepatitis C viral load and hepatitis C Core antigenaemia among Egyptians

“…Several other studies using HCVcAg testing reported a significant correlation between serum levels of HCV-RNA and HCVcAg with different linear regression coefficients ranging from 0.6 to 0.8 (22,24,36,30−33), which is higher than seen in our study. In addition, the weak correlation reported in our study is lower than that reported elsewhere among those infected with HCV genotype 4 or other genotypes (9)(10)(11)34,35). This could be attributed to viral genetic differences and/or patient characteristics.…”

Hepatitis C Core Antigen Testing for Diagnosis of Hepatitis C Virus Infection

“…The ten remaining studies did not have data to calculate specificity (11, 38, 41–43, 50, 53, 57, 61, 63) and were only included in the univariate pooled sensitivity estimate. For the bivariate analysis there were 12,670 total samples.…”

The Correlation between Hepatitis C Core Antigen and Hepatitis C Virus RNA Levels with Respect to Human Immunodeficiency Virus Status, Hepatitis C Virus Genotype and Interferon-Lambda-4 Polymorphism

“…Several recent data have demonstrated that serum HCVcAg concentrations correlate well with HCV RNA levels in HCV monoinfected patients [6,7,8,9,10,11,12]. In the present study, we further investigated the use of HCVcAg measurement in HCV/HIV coinfected patients.…”

“…A number of studies have demonstrated good correlation between HCVcAg and HCV RNA levels, particularly in HCV-monoinfected individuals [6,7,8,9,10,11,12,13]. As a result, HCVcAg testing is considered to be an alternative assay to conventional HCV RNA quantification with the advantages of rapidity, reproducibility and feasibility in settings with limited resources [14].…”