Different hepatitis C virus (HCV) RNA load profiles following seroconversion among injecting drug users without correlation with HCV genotype and serum alanine aminotransferase levels

Abstract

Hepatitis C virus (HCV) infection often persists in association with chronic hepatitis. Different factors have been proposed to determine the clinical outcome of HCV infection. The aim of this study was to examine three different factors of HCV infection among injecting drug users. Nineteen untreated HCV seroconverters were tested longitudinally for the presence of HCV RNA by reverse transcriptase (RT) PCR, and results were quantified by the branched-DNA (bDNA) assay. HCV genotypes were determined with the first sample taken after HCV seroconversion. To assess the natural course of infection, serum alanine aminotransferase (ALT) levels were measured at three stages in every individual. The concordance between bDNA and RT-PCR was 98.9%. Three distinct patterns were found, according to the HCV RNA load after seroconversion during a mean follow-up period of 5 years (range, 1 to 8 years). HCV genotype 1a was predominant (52.6%). There was a significant increase in serum ALT levels (mean 55.5 U/liter) in the early phase of HCV infection, compared with basal serum ALT levels before HCV seroconversion and at the end of the follow-up period. Three distinct HCV RNA load profiles were found, without apparent relationship to genotype and serum ALT levels in the first 5 years of HCV infection.

FIG. 1

Three examples of viral load profiles found in 19 HCV seroconverters among IDUs. HCV RNA loads were measured longitudinally by bDNA assay. The detection limit of the bDNA assay is shown as a dotted line. Characteristics of each group are indicated at the top of each panel. RT-PCR results in duplicate are indicated by +, ±, or −. SC, seroconversion.

FIG. 2

Comparison of HCV RNA loads with genotypes in the first sample after HCV seroconversion. The horizontal dotted line indicates the detection limit of the bDNA assay. The data points are from the first samples after seroconversion. Horizontal bars represent the median value of each genotype. Statistical analysis was performed with the Mann-Whitney test.

FIG. 3

(A) Differences among serum ALT levels at three different time points in HCV infection. Horizontal bars represent the median value at each time point. Each data point represents the ALT level from one seroconverter. The upper limit of the normal range for the ALT assay is 37 U/liter. Statistical analysis was performed with the Mann-Whitney test. (B) Differences among HCV RNA loads in 19 HCV seroconverters in the early and chronic phases of HCV infection. Each data point represents the HCV RNA level from one seroconverter. Horizontal bars represent the median value of HCV RNA copies per milliliter. The horizontal dotted line depicts the detection limit of the bDNA assay. Statistical analysis was performed with the Mann-Whitney test. The mean preseroconversion period was 9 months (range, 2 to 38 months). The early phase had a mean duration of 6 months (range, 1 to 23 months), and the postseroconversion (post sc) period was 60 months (range, 14 to 91 months).

FIG. 4

(A) Correlation between HCV RNA loads and serum ALT levels in the early phase of HCV infection. Each point represents data from one seroconverter. (B) Correlation between HCV RNA loads and serum ALT levels in the chronic phase of HCV infection. Each point represents data from one seroconverter. The horizontal dotted lines show the detection limit of the bDNA assay. Statistical analysis was performed with the Mann-Whitney test.