Relapse of hepatitis C in a pegylated‐interferon‐α‐2b plus ribavirin‐treated sustained virological responder

Fujii, Hideki; Itoh, Yoshito; Ohnishi, Naoki; Sakamoto, Masafumi; Ohkawara, Tohru; Sawa, Yoshihiko; Nishida, Koichi; Nishimura, Takeshi; Yamaguchi, Kanji; Yasui, Kohichiroh; Minami, Masahito; Okanoue, Takeshi; Ohkawara, Yasuo; Yoshikawa, Toshikazu

doi:10.1111/j.1872-034x.2010.00641.x

Cited by 9 publications

(11 citation statements)

References 27 publications

(43 reference statements)

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“…These findings were made in a cohort of patients who sporadically tested positive for HCV RNA by nested RT-PCR within the first years after an SVR to IFN-based therapy (8). The results are consistent with reports showing residual virus in approximately 6% of SVRs by highly sensitive transcription-mediated amplification assays or nested RT-PCR (2, 10, 11), even though a relapse with high levels of viremia is exceedingly rare (12)(13)(14)(15).…”

Section: Discussionsupporting

confidence: 78%

Trace amounts of sporadically reappearing HCV RNA can cause infection

Veerapu¹,

Park²,

Tully³

et al. 2014

J. Clin. Invest.

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Section: Discussionsupporting

confidence: 78%

Trace amounts of sporadically reappearing HCV RNA can cause infection

Veerapu¹,

Park²,

Tully³

et al. 2014

J. Clin. Invest.

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“…Studies from Canada7, 20 suggest that 75%‐86% of presumed recovered subjects have HCV RNA in their PBMCs, even in the absence of HCV RNA in plasma. Furthermore, some case reports of HCV reemergence and relapse after sustained virological response (SVR) demonstrated identical sequences during viral reappearance, suggesting that the original infection had persisted at undetectable serum levels, rather than HCV reinfection 10, 12. These reports support the existence of viral reservoirs from which HCV could reemerge and suggest that PBMCs may be an important viral reservoir.…”

Section: Discussionmentioning

confidence: 99%

“…This is a critical issue, because if residual HCV exists, there is the potential for reactivation in the setting of organ transplantation, chemotherapy, or other acquired immunosuppressive states, as reported in occult HBV infection 9. Although HCV reactivation is limited to a few case reports,10‐12 the potential for residual HCV in persons whose serum tests HCV RNA negative raises concern regarding the use of organs from presumed HCV‐recovered subjects in the transplant setting, and raises the potential that such individuals would remain at risk for the subsequent development of HCC. It is thus essential to determine whether residual HCV infection exists in persons whose serum markers suggest full recovery.…”

mentioning

confidence: 99%

Investigation of residual hepatitis C virus in presumed recovered subjects

et al. 2012

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Recent studies have found hepatitis C virus (HCV) RNA in peripheral blood mononuclear cells (PBMCs) of the majority of presumed recovered subjects. We investigated this unexpected finding using samples from patients whose HCV RNA and anti-HCV status had been serially confirmed. HCV RNA was detected in PBMCs from 66/67 chronic HCV carriers. Subpopulation analysis revealed that the viral load (log copies/106 cells) in B cells (4.14 ± 0.71) was higher than in total PBMCs (3.62 ± 0.71, p<0.05), T cells (1.67 ± 0.88, p<0.05), and non-B/T cells (2.48 ± 1.15, p<0.05). HCV negative-strand RNA was not detected in PBMCs from any of 25 chronically infected patients. No residual viral RNA was detected in total PBMCs or plasma of 59 presumed recovered subjects (11 spontaneous, 48 treatment-induced) using nested real-time PCR with a detection limit of 2 copies/μg RNA (from ~1×106 cells). PBMCs from two healthy HCV-negative blood donors became HCV RNA positive, with B-cell predominance, when mixed in vitro with HCV RNA positive plasma, thus passively mimicking cells from chronic HCV carriers. No residual HCV was detected in liver or other tissues from two spontaneously recovered chimpanzees. Conclusion: 1) HCV RNA was detected in PBMCs of most chronic HCV carriers and was predominant in the B cell subpopulation; 2) HCV detected in PBMCs was in a non-replicative form; 3) HCV passively adsorbed to PBMCs of healthy controls in vitro becoming indistinguishable from PBMCs of chronic HCV carriers; 4) Residual HCV was not detected in the plasma or PBMCs of any spontaneous or treatment recovered subjects or in chimpanzee liver suggesting that the classic pattern of recovery from HCV infection is generally equivalent to viral eradication.

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“…Furthermore, a recent report showed that residual HCV RNA, which appears sporadically in treatment‐recovered patients, can be infectious in chimpanzees . However, although HCV reactivation after SVR has been described in case reports, this is a truly unusual event.…”

Section: Introductionmentioning

confidence: 98%

Long-term follow-up of successful hepatitis C virus therapy: waning immune responses and disappearance of liver disease are consistent with cure

Hedenstierna

Weiland

Brass

et al. 2015

Aliment Pharmacol Ther

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Summary Background A sustained viral response (SVR) after interferon‐based therapy of chronic hepatitis C virus (HCV) infection is regarded to represent a cure. Previous studies have used different markers to clarify whether an SVR truly represents a cure, but no study has combined a clinical work‐up with highly sensitive HCV RNA detection, and the determination of immune responses. Aim To determine clinical, histological, virological and immunological markers 5–20 years after SVR. Methods In 54 patients, liver biochemistry, histology and elastography were evaluated. Liver biopsies, plasma and peripheral blood mononuclear cells (PBMCs) were tested for minute amounts of HCV RNA. HCV‐specific T‐cell responses were monitored by ELISpot and pentamer staining, and humoral responses by measuring HCV nonstructural (NS)3‐specific antibodies and virus neutralisation. Results Liver disease regressed significantly in all patients, and 51 were HCV RNA‐negative in all tissues tested. There was an inverse association between liver disease, HCV‐specific T‐cell responses and HCV antibody levels with time from SVR, supporting that the virus had been cleared. The three patients, who all lacked signs of liver disease, had HCV RNA in PBMCs 5–9 years after SVR. All three had HCV‐specific T cells and NS3 antibodies, but no cross‐neutralising antibodies. Conclusions Our combined data confirm that a SVR corresponds to a long‐term clinical cure. The waning immune responses support the disappearance of the antigenic stimulus. Transient HCV RNA traces may be detected in some patients up to 9 years after SVR, but no marker associates this with an increased risk for liver disease.

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Relapse of hepatitis C in a pegylated‐interferon‐α‐2b plus ribavirin‐treated sustained virological responder

Cited by 9 publications

References 27 publications

Trace amounts of sporadically reappearing HCV RNA can cause infection

Trace amounts of sporadically reappearing HCV RNA can cause infection

Investigation of residual hepatitis C virus in presumed recovered subjects

Long-term follow-up of successful hepatitis C virus therapy: waning immune responses and disappearance of liver disease are consistent with cure

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