Clearance of hepatitis C virus RNA from the peripheral blood mononuclear cells of blood donors who spontaneously or therapeutically control their plasma viremia

Bernardin, Flavien; Tobler, Leslie H.; Walsh, Irina; Williams, John; Busch, Mike; Delwart, Eric

doi:10.1002/hep.22184

Cited by 74 publications

(76 citation statements)

References 45 publications

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“…7 This latest observation was confirmed by another recent study with a complete clearance of HCV RNA from the PBMCs of blood donors who spontaneously or therapeutically control their plasma viremia. 8 In conclusion, the excellent review performed by Welker and Zeuzem on occult HCV infection confirm our data and those of two other studies using sensitive assays and liver/PBMC assessment, and reinforce the absence of evidence of occult HCV infection. …”

Section: The Myth Of Occult Hepatitis C Infectionsupporting

confidence: 89%

The myth of occult hepatitis C infection #

Halfon¹,

Martinot‐Peignoux²,

Cacoub³

2009

Hepatology

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We read with interest the review by Welker and Zeuzem on occult hepatitis C virus (HCV) infection and also the reply by Carreno et al. 1,2 The latter reported in their answer to Welker and Zeuzem that HCV can replicate in patients with occult HCV infection. Because this conclusion would have substantial consequences for patients considered cured of their HCV infection, as well as for the health care system, the data must be interpreted most carefully. They reported two studies that "unconvincingly failed to detect occult HCV infection in cryptogenic hepatitis because of several concerns with the methodology employed." 3,4 We would like to correct Carreno et al. on these two important points. In the first study published by Tanari et al., it was shown that the ability for HCV RNA detection is more sensitive in whole blood instead of peripheral blood mononuclear cells (PBMCs), due to circulation of the infectious virus in patient sera in the form of triglyceriderich particles which is present in the whole blood and not in PBMCs. 5 In the second study, we looked for the so-called "occult hepatitis C", in a different population of patients and controls, including patients with long-term normal alanine aminotransferase level, by using an original ultrasensitive validated real-time polymerase chain reaction (PCR) method. We failed to find any occult hepatitis C. 4 Moreover, we would like to underscore that for a long time, Carreno et al. reported the same results on the same cohort of patients. 6 The method proposed used PBMCs from a patient chronically infected with HCV for RNA isolation and HCV RNA detection. Serial dilutions of the isolated RNA cannot be a gold standard due to the limit of detection of HCV RNA by an in-house reverse transcription PCR method. PBMCs from our patients were subjected to HCV RNA transcription-mediated amplification assays without any HCV RNA detectable using this high sensitivity assay. 6 The second issue addressed is related to the concept of the presence of HCV RNA in the liver in the absence of HCV RNA detected in PBMCs. Carreno et al. suggested that negativity for HCV-RNA in PBMC does not exclude the existence of occult HCV infection because the gold standard method to identify this occult infection is by detection of viral RNA in liver cells. To address this question, Maylin et al. recently assessed the presence of residual HCV RNA in serum, liver, and PBMCs using TMA (sensitivity Ͻ9.6 IU/mL) in a long-term follow-up study of patients infected with chronic hepatitis C who achieved a sustained virological response after interferon-based treatment. 6 A total of 114 patients had a posttreatment liver tissue and 156 had PBMCs. Serum HCV RNA remained undetectable (1300 samples), indicating that none of the patients had a relapse. HCV RNA was detectable in 2 of 114 (1.7%) liver specimens, and in none of 156 PBMC specimens. These authors strongly suggest that SVR may be considered to show eradication of HCV infection. 7 This latest observation was confirmed by another recent study with a ...

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Section: The Myth Of Occult Hepatitis C Infectionsupporting

confidence: 89%

The myth of occult hepatitis C infection #

Halfon¹,

Martinot‐Peignoux²,

Cacoub³

2009

Hepatology

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“…Forty-six controllers were followed for a median of 16 months; 39% were female and 37% were African-American (Table 1). The median self-reported duration of HIV diagnosis at study entry was 13 years, and the median baseline CD4 ϩ T-cell count was 753 cells/mm 3 . As a comparison group, we measured plasma HIV RNA levels in 37 long-term HAART-treated subjects who had undetectable plasma levels (when using conventional assays) for at least 5 years.…”

Section: Resultsmentioning

confidence: 99%

“…As a comparison group, we measured plasma HIV RNA levels in 37 long-term HAART-treated subjects who had undetectable plasma levels (when using conventional assays) for at least 5 years. The median duration of viral load suppression was 7 years (interquartile range [IQR], 6 to 7 years), and the median baseline CD4 ϩ T-cell count was 485 cells/mm 3 . The self-reported CD4 nadir of this group was 85 (IQR, 37 to 172).…”

Section: Resultsmentioning

confidence: 99%

Evidence for Persistent Low-Level Viremia in Individuals Who Control Human Immunodeficiency Virus in the Absence of Antiretroviral Therapy

Hatano

Delwart

Norris

et al. 2009

J Virol

186

182

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A subset of antiretroviral-untreated, human immunodeficiency virus (HIV)-infected individuals are able to maintain undetectable plasma HIV RNA levels in the absence of antiretroviral therapy. These "elite" controllers are of high interest as they may provide novel insights regarding host mechanisms of virus control. The degree to which these individuals have residual plasma viremia has not been well defined. We performed a longitudinal study of 46 elite controllers, defined as HIV-seropositive, antiretroviral-untreated individuals with plasma HIV RNA levels of <50 to 75 copies/ml. The median duration of HIV diagnosis was 13 years, the median baseline CD4؉ T-cell count was 753 cells/mm 3 , and the median duration of follow-up was 16 months. Plasma and cellular HIV RNA levels were measured using the transcription-mediated amplification (TMA) assay (estimated limit of detection of <3.5 copies RNA/ml). A total of 1,117 TMA assays were performed (median of five time points/subject and four replicates/time point). All but one subject had detectable plasma HIV RNA on at least one time point, and 15 (33%) subjects had detectable RNA at all time points. The majority of controllers also had detectable cell-associated RNA and proviral DNA. A mixed-effect linear model showed no strong evidence of change in plasma RNA levels over time. In conclusion, the vast majority (98%) of elite controllers had measurable plasma HIV RNA, often at levels higher than that observed in antiretroviraltreated patients. This confirms the failure to eradicate the virus, even in these unique individuals who are able to reduce plasma viremia to very low levels without antiretroviral therapy.

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“…The presence of HCV RNA in plasma samples from 70%-75% of blood donors with indeterminate immunoblot results has also been reported by other groups in Brazil (6,7); however, in contrast, other investigators have reported RNA prevalence in such samples to be ≈2.5% (1,8). Indeterminate RIBA test results can indicate seroconversion or seroreversion or, occasionally, a chronic infection when RNA HCV is detected in plasma (9,10). To provide better understanding of the meaning of these indeterminate results, ongoing follow-up studies are examining the immune status of these persons.…”

Section: Hepatitis C Virus In Blood Donors Brazilmentioning

confidence: 99%