Assessment of Hepatitis C Virus RNA Levels by Quantitative Competitive RNA Polymerase Chain Reaction: High-Titer Viremia Correlates with Advanced Stage of Disease

Gretch, David R.; Corey, Lawrence; Wilson, Jeffrey J.; Rosa, Corazon dela; Willson, Richard A.; Carithers, Robert L.; Busch, Michael P.; Hart, Jaime; Sayers, Merlyn; Han, Jang H.

doi:10.1093/infdis/169.6.1219

Cited by 207 publications

(120 citation statements)

References 26 publications

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“…It might be reasonable to speculate that an increased number of HCV particles in peripheral blood may enter, infect and activate a larger number of peripheral B cells expressing CD5 and CD81, as occurs when a higher level of HCV viraemia is associated with more advanced stage of liver disease [36]. In support of this hypothesis are recent data indicating that HCV infection and clonal expansion of B cells within the liver preferentially involve RF-producing cells [37].…”

Section: Discussionmentioning

confidence: 98%

Peripheral B-cell CD5 expansion and CD81 overexpression and their association with disease severity and autoimmune markers in chronic hepatitis C virus infection

Zuckerman¹,

Slobodin²,

Kessel

et al. 2002

Clinical and Experimental Immunology

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SUMMARYHepatitis C virus (HCV) infection is associated with immune-mediated abnormalities and B-cell lymphoproliferation evolving to an overt lymphoma. Recently, CD81 was identified as an HCV receptor on B-lymphocytes, providing a mechanism by which B cells are infected and activated by the virus. In addition, expansion of CD5 + B lymphocytes was described to be associated with various non-HCV related autoimmune disorders. Therefore, we studied the possible role of peripheral B cells CD81 and CD5 over-expression in the development of HCV-related autoimmunity and their association with disease severity in chronic HCV infection. Peripheral B cells CD5 expression and mean fluorescence intensity (MFI) of CD81 were determined in 30 HCV-infected patients, 30 healthy controls and 15 patients with hepatitis B virus infection using fluorescence-activated cell scan (FACS). We have also investigated the association between peripheral CD5 and CD81 B-cell over-expression and markers of autoimmunity and disease severity in patients chronically infected by HCV. CD5 + B-cells were increased in chronic HCV infection (23·2 ± 7·2%) compared with those of healthy controls (15 ± 5·5%) (P < 0·0001) and chronic HBV infection (19 ± 3·7%) (P = 0·08). CD81 MFI was significantly higher in HCVinfected compared to HBV-infected patients and healthy controls. Both increased CD81 MFI and CD5 + B-cell expansion were associated with the production of rheumatoid factor and mixed cryoglobulins and positively correlated with HCV viral load and histological activity index. The overexpression of CD81 and the expansion of CD5 + peripheral B-cells in HCV-infected patients may possibly play a role in the development of HCV-associated autoimmunity and lymphoproliferation.

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Section: Discussionmentioning

confidence: 98%

Peripheral B-cell CD5 expansion and CD81 overexpression and their association with disease severity and autoimmune markers in chronic hepatitis C virus infection

Zuckerman¹,

Slobodin²,

Kessel

et al. 2002

Clinical and Experimental Immunology

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“…Several clinical relations with replication activity of the virus, including grade of disease and response to antiviral drugs, have been based on singletime-point determinations of viremia. 10,[19][20][21][22][23][24][25][26][27][28] To date, conflicting results have been reported on long-term monitoring of viral replication. Different time intervals, ranging from diurnal to monthly determinations, have been evaluated using different methods of measurement, and discordant conclu- sions might result from the above-mentioned variables.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 1999

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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...

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“…1,2 A direct correlation between HCV RNA levels and the liver histological grading and staging is reported. 3,4 Some data suggest that liver injury in chronic HCV patients may be immunologically mediated, but definitive conclusions cannot yet be drawn. 5 Other host cofactors in addition or in alternative to viral factors or host immune response to the virus may play a role.…”

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confidence: 99%

Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity

et al. 2001

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The role of steatosis in the progression of liver damage in chronic hepatitis C (CHC) was studied. Enrolled were 180 consecutive liver biopsy-proven CHC patients and 41 additional subjects with a known duration of infection. We evaluated the histological activity index (HAI), grade of fibrosis and steatosis, body mass index (BMI; kg/m 2 ), distribution of body fat, HCV genotype, and levels of HCV RNA. Eighty six (48%) patients showed steatosis, and a higher prevalence was observed in genotype 3a infection (P < .01). A correlation between the grade of steatosis and fibrosis was observed (P < .001). Fibrosis was also associated with age (P < .001). After adjusting for age, the association between steatosis and fibrosis remained significant. The grade of steatosis also correlated with the HAI (P < .007) with a significant increase in periportal necrosis. No relation was found between steatosis and age, gender, iron storage, or levels of HCV RNA. Patients with a high grade of steatosis (>30%) showed higher serum levels of ␥-GT and ALT (P < .001). Overall, steatosis was not significantly associated to BMI. Analysis by single genotype showed a significant association between the grade of steatosis and BMI in type 1 infection r ‫؍‬ .689; P < .001) and with levels of HCV RNA in type 3a infection r ‫؍‬ .786; P < .001). Visceral fat distribution rather than BMI proved to be associated with steatosis (P < .001). Data obtained from patients with a known date of infection confirmed that steatosis grades 3-4 were associated with a higher annual rate of fibrosis progression, and showed that alcohol and steatosis act together in increasing fibrosis (P < .05). Our data indicate that steatosis is an important cofactor in increasing liver necroinflammatory activity and in accelerating fibrosis in CHC. Visceral obesity and genotype 3a play a role in the development of steatosis. (HEPATOLOGY 2001;33: 1358-1364

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Assessment of Hepatitis C Virus RNA Levels by Quantitative Competitive RNA Polymerase Chain Reaction: High-Titer Viremia Correlates with Advanced Stage of Disease

Cited by 207 publications

References 26 publications

Peripheral B-cell CD5 expansion and CD81 overexpression and their association with disease severity and autoimmune markers in chronic hepatitis C virus infection

Peripheral B-cell CD5 expansion and CD81 overexpression and their association with disease severity and autoimmune markers in chronic hepatitis C virus infection

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

Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity

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