Natural fluctuations of hepatitis C viral load in a homogeneous patient population: A prospective study

Abstract

Hepatitis C virus (HCV) infection is the main cause of parenteral non-A, non-B hepatitis. 1-5 HCV consists of a heterogeneous mix of isolates defined by genotype, each of which is further classified into subtypes. A number of factors have been identified as important in predicting the outcome of disease progression. These include age at infection, viral type/subtype, viral load, quasispecies, and mode of infection. [6][7][8][9][10] Clinical heterogeneity in disease progression may reflect either viral heterogeneity or variations in host response. However, the fluctuations in viral load during the natural history of hepatitis C infection are poorly understood. The purpose of the present study was to determine if viral load remains at a steady state or is in dynamic flux during the course of an HCV infection. To avoid heterogeneity of risk factors and confounding variables in viral type/subtype, we studied a unique cohort of individuals all infected by anti-D/ blood product from a single source of HCV 1b. The sole source of the infectious agent was identified as HCV 1b-contaminated anti-D immunoglobulin. The contaminating HCV 1b was derived from a single donor. [11][12][13] The patients were of similar ethnogeographic background and had an absence of other risk factors for liver disease.Serum HCV RNA can be quantitated by a range of different technologies (reverse transcription-polymerase chain reaction [RT-PCR], RT-PCR coupled to different signal amplification systems such as colorimetric assays, and the branched chain technology). [14][15][16][17][18][19][20] The level of sensitivity achieved by the more recent versions of these technologies has improved qualitative assessment of HCV serum status. Clinically relevant sensitivities of 100 viral genomes per mL of serum are now readily achievable.The work reported here used the Roche Monitor system for amplification of the HCV. The high degree of reproducible quantification of viral load and a uniform linear range of amplification between the different versions of the Roche HCV Monitor assays for HCV of genotype 1b provide a means in which quantifications over several generations of assays are suitable for longitudinal studies. In addition, amplification of HCV genotype 1b by the Monitor system does not suffer from the reported difficulties associated with other genotypes. 21

Factors Affecting Serum Concentrations of Hepatitis C Virus (HCV) RNA in HCV Genotype 1-Infected Patients with Chronic Hepatitis

“…Imprecision may have been relatively high (due to the use of several testing laboratories, technologists, runs, and reagent lots), but the same well-characterized HCV RNA assay was used for all six trials. If these trials' HCV RNA testing yielded within-patient variability of approximately Ϯ0.5 log 10 IU/ml, as others have reported (1,9,12,18,22,34,39,44,49,63), such "noise" in single [HCV RNA] values would not have affected our analyses more they did than in earlier studies. (21).…”

“…We therefore analyzed the baseline characteristics of 2,472 HCV genotype 1-infected patients to identify correlations with gender, age, race, weight, body mass index (BMI), HCV acquisition mode, HCV subtype, alanine aminotransferase concentration, or histopathologic changes in the liver. After separation of the data according to four [HCV RNA] BL groups (<5.0, >5.0 to 5.6, >5.6 to 5.9, and >5.9 log 10 IU/ml), we determined that increasing The serum levels of hepatitis C virus (HCV) RNA represent the abundance of HCV production versus clearance and are usually stable in humans with untreated chronic hepatitis C (CHC) (1,9,12,18,22,34,39,44,49,63). Between individuals, however, these baseline HCV RNA concentrations ([HCV RNA] BL ) vary by 3 to 4 log 10 IU/ml and the factors that determine these differences are poorly understood.…”

“…The serum levels of hepatitis C virus (HCV) RNA represent the abundance of HCV production versus clearance and are usually stable in humans with untreated chronic hepatitis C (CHC) (1,9,12,18,22,34,39,44,49,63). Between individuals, however, these baseline HCV RNA concentrations ([HCV RNA] BL ) vary by 3 to 4 log 10 IU/ml and the factors that determine these differences are poorly understood.…”

Prospective Multicenter Clinical Evaluation of AMPLICOR and COBAS AMPLICOR Hepatitis C Virus Tests

“…The manufacturer has shown that the second-generation tests can detect 100% of samples containing as little as 50 IU/ml (approximately 100 copies/ml) (13). Although the fluctuations in viral load that occur in patients chronically infected with HCV are not well defined, it is rare to find patients with viral loads of Ͻ10 4 copies/ml in the absence of therapy (8,12,14,15,(17)(18)(19)(20). Thus, it appears that the analytical sensitivity of the AMPLICOR tests is at least 100-fold lower than the lowest value likely to be encountered in patients being evaluated for HCV infection prior to therapy.…”

The Irish paradigm on the natural progression of hepatitis C virus infection: An investigation in a homogeneous patient population infected with HCV 1b (review)

“…Interperson variability in viraemia was investigated in the HAD-1b group of 47 patients (58). None of the patients included in the study had received anti-viral therapy.…”