Hepatitis C virus RNA profiles in chronically infected individuals: Do they relate to disease activity?

Abstract

Fluctuations of hepatitis C virus (HCV)-RNA serum levels were monitored in a multicenter study in 76 chronic HCV carriers who had been followed longitudinally without receiving antiviral therapy to assess their relation with the course of liver disease activity. Forty-four patients had normal transaminases over more than 2 years, while 32 additional patients had fluctuating levels. Viral load was measured in serial serum samples prospectively collected for 10 to 12 months in 54 patients and in sera stored yearly up to 8 years in an additional 22 patients. In patients tested monthly, a lesser extent of fluctuations was detected in cases with constantly normal transaminases as compared with those with fluctuating transaminases. In the former group, the mean difference between maximum and minimum values observed in each individual patient was 0.7 Log, while in the latter group, it was 1.3 Log (P ‫؍‬ .0004). Most of these patients experienced, on average, three peaks of viremia over 1 year. The range of variation observed upon yearly testing was between 0.2 and 2.2 Log and did not reach statistical significance between the two groups. In conclusion, a careful viral replication profile can be achieved only by monthly testing, because longer time intervals could miss viremia fluctuations. HCV-RNA levels are more stable in asymptomatic HCV carriers than in patients with biochemical activity of liver disease. (HEPATOLOGY 1999;29: 585-589.)Chronic infection with hepatitis C virus (HCV) is characterized by persistent viremia. HCV RNA is usually detected in serum by sensitive polymerase chain reaction (PCR)-based techniques and has become a useful tool for diagnosis and monitoring. Besides methods for qualitative detection of viremia, a number of procedures to quantify serum HCV RNA have been developed, including end-point dilution PCR, 1 competitive PCR, 2,3 isothermal nucleic acid amplification, 4 and signal-amplification branched DNA. 5 Routine use of these techniques in a wide clinical setting is hampered by problems of specificity and sensitivity, lack of reproducibility, poor standardization, and high cost. 6 Recently, methods for quantitative assessment of HCV-RNA levels have become commercially available and are being extensively evaluated in clinical studies, particularly in patients treated with interferons and antivirals. 7 Little is known about viral kinetics in untreated patients, because most evaluations of the level of viremia are based on single determinations. If wide spontaneous fluctuations occur, they could mimic treatment-induced effects or lead to under-or overestimate baseline values. In a few published studies, different time intervals have been evaluated and discordant conclusions have been reported. Either trivial or consistent differences of viral load over time have been described after observation periods ranging from days to months. [8][9][10][11][12] To assess the spontaneous behavior of serum HCV-RNA levels over a reasonable length of time upon close observation, we monitored chronic HCV car...

Hepatitis C virus dynamics and pathology: the role of CTL and antibody responses

“…Hence, the model suggests that there is no obvious correlation between pathology and virus load. This is consistent with clinical data (de Araujo et al, 2002;Manzin et al, 1997;Pontisso et al, 1999;Puoti et al, 1999).…”

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

“…Others determined that BMI and histopathologic changes were independent predictors of the response to interferon-based therapy (2). While reports pertaining to correlations between [HCV RNA] and the extent of liver disease have been inconsistent (13,14,19,23,43,49,53,64,70), at least one of our [HCV RNA] BL -HAI score associations appeared to be sample size dependent; i.e., regression of the [HCV RNA] BL and the fibrosis score yielded a P value of 0.0029 for 1,304 patients of all ages (Table 3) The most remarkable conclusion from these studies is that we do not understand a great deal about the determinants of [HCV RNA]. In our study, less than 5% of the interpersonal differences in the baseline HCV gt1 RNA concentration could be explained by the sociodemographic, HCV subtype, biochemical, and histopathologic characteristics that we analyzed.…”

“…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.…”

A Viral Infection Model with a Nonlinear Infection Rate

“…Static and dynamical bifurcations, including saddle-node bifurcation, Hopf bifurcation, homoclinic bifurcation, and bifurcation of cusp-type with codimension two i.e., Bogdanov-Takens bifurcation , have been exhibited. Thus, besides the Allee effect, our model 1.6 shows that the viral oscillation behaviors can occur in the host based on the appropriate conditions, which was observed in chronic HBV or HCV carriers see [29][30][31] . These results inform that the viral infection is very complex in the development of a better understanding of diseases.…”