Hepatic immunopathology during occult hepacivirus re-infection

Manickam, Cordelia; Martinot, Amanda J.; Jones, Rhianna; Varner, Valerie; Reeves, R. Keith

doi:10.1016/j.virol.2017.08.037

Cited by 7 publications

(13 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is also important to point out that pre-depletion of NK cells and CD8 + T cells did not lead to chronic infection in this study, indicating that CD4 + T cells play primary roles in viral clearance. This is consistent with HCV and GBV-B studies that showed association of early and vigorous CD4 + T cell responses with viral clearance (14–17). While NrHV is highly infectious and hepatotropic in mice, severe pathology and fibrosis were not obvious in the liver.…”

supporting

confidence: 89%

A mouse model for hepatitis C virus infection: are we there yet?

Manickam

Reeves

2017

Ann Infect

Self Cite

View full text Add to dashboard Cite

supporting

confidence: 89%

A mouse model for hepatitis C virus infection: are we there yet?

Manickam

Reeves

2017

Ann Infect

Self Cite

View full text Add to dashboard Cite

“…While longer‐term studies are required to determine whether GBV‐B replicates in the liver for protracted periods to establish a true occult infection, as has been reported for the common marmoset 9 we have demonstrated that an infection may persist in the liver in the absence of detectable virus in the serum. To our knowledge this is the first report of fibrosis in tamarins; it supports data observed in the common marmoset 8,9,13,14 . Our observation that fibrosis affects male tamarins over female animals, is novel and mirrors the gender bias seen in HCV‐infected humans.…”

Section: Discussionsupporting

confidence: 62%

Development of hepatic pathology in GBV‐B‐infected red‐bellied tamarins (Saguinus labiatus)

Dale

Hood

Bowen

et al. 2020

Journal of Medical Virology

View full text Add to dashboard Cite

GB virus B (GBV‐B) is a new world monkey‐associated flavivirus used to model acute hepatitis C virus (HCV) infection. Critical for evaluation of antiviral or vaccine approaches is an understanding of the effect of HCV on the liver at different stages of infection. In the absence of longitudinal human tissue samples at defined time points, we have characterized changes in tamarins. As early as 2 weeks post‐infection histological changes were noticeable, and these were established in all animals by 6 weeks. Despite high levels of liver‐associated viral RNA, there was reversal of hepatic damage on clearance of peripheral virus though fibrosis was demonstrated in four tamarins. Notably, viral RNA burden in the liver dropped to near undetectable or background levels in all animals which underwent a second viral challenge, highlighting the efficacy of the immune response in removing foci of replication in the liver. These data add to the knowledge of GBV‐B infection in New World primates which can offer attractive systems for the testing of prophylactic and therapeutic treatments and the evaluation of their utility in preventing or reversing liver pathology.

show abstract

“…The patients in their study cohort were all negative for anti-HCV antibodies and for serum HCV-RNA, and never received antiviral therapy, precluding the role of antiviral therapy mediated immune imbalance in histological abnormality. Recently study in animal indicated that occult hepacivirus re-infections occur and that new liver pathological lesions, including lymphocyte infiltration and fibrosis, are appeared even in the absence of high viraemia [31]. Refer to the underline explanation, there are two ways of interpreting the association between OCI and persistent histological change: a) A mechanistically cause-effect relationship may exist.…”

Section: Discussionmentioning

confidence: 99%

Detection of residual HCV-RNA in patients who have achieved sustained virological response is associated with persistent histological abnormality

et al. 2019

View full text Add to dashboard Cite

Background Whether achieving sustained virological response (SVR) in patients with hepatitis C attains complete elimination of hepatitis C virus (HCV) is unknown, because occult HCV infection (OCI), defined as the detection of HCV-RNA in hepatocytes or peripheral blood mononuclear cells (PBMC) in absence of serum HCV-RNA, may occur. We thus investigated the prevalence and clinical relevance of OCI. Methods Subjects from three hospitals who had achieved serum HCV clearance, including 60 of Direct-acting antiviral agents (DAAs) induced SVR, 50 of pegylated interferon plus ribavirin (PR) induced SVR, and 30 of spontaneous resolution, were subjected to detect HCV-RNA in liver by robust RNAscope assay and PBMC by qPCR. Paired liver biopsies at baseline and at SVR24 were analyzed. Results OCI was detected in 16 of 140 subjects (11.4%), with 15.0% in DAA-based group, 10.0% in PR group and 6.7% in spontaneously resolved group. In DAA-based subgroups, the incidence of OCI was gradually increased in group of solely DAA(s) therapy, combining DAA and PR therapy and combining DAA and ribavirin therapy. OCI is more frequent in patients with genotype 3. No correlation between baseline viral load, interleukin-28B genotype, baseline transaminases, post-SVR transaminases and OCI were found. However, OCI was significantly linked with severity of fibrosis and active inflammation at post-SVR, even considering basal fibrosis status. In addition, both the magnitude and the frequency of fibrosis regression were lower in patients with OCI than in those without OCI. In the multivariate analysis, PR therapy was identified an independent negative prognostic factor for both hepatic inflammation ( P = .022) and fibrosis regression ( P = .015). Importantly, we found HCV relapse in one of the OCI patients at 48 weeks after the end of PR treatment. Conclusions HCV-RNA can persist in hepatocytes and/or PBMC in a certain of patients who achieved spontaneous or treatment-induced HCV RNA clearance from serum and associated with persistent histological abnormality. Our findings provide new insights into cure of HCV and could influence the following-up scenario after SVR.

show abstract

Hepatic immunopathology during occult hepacivirus re-infection

Cited by 7 publications

References 42 publications

A mouse model for hepatitis C virus infection: are we there yet?

A mouse model for hepatitis C virus infection: are we there yet?

Development of hepatic pathology in GBV‐B‐infected red‐bellied tamarins (Saguinus labiatus)

Detection of residual HCV-RNA in patients who have achieved sustained virological response is associated with persistent histological abnormality

Contact Info

Product

Resources

About