Occult Hepatitis C Virus Infection: Are We Digging Too Deep?

Koutsoudakis, George; Pérez‐del‐Pulgar, Sofía; Forns, Xavier

doi:10.1053/j.gastro.2016.12.015

Cited by 7 publications

(6 citation statements)

References 22 publications

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“…As mentioned, the definition of HCV “positivity” is important because of the misconception that HCV antibody–positive/NAT‐negative donors could have transmissible HCV RNA . The prevailing opinion is that residual liver tissue HCV RNA represents degraded viral particles that are unable to replicate and spread disease.…”

Section: Transmission and Treatment Concernsmentioning

confidence: 99%

The American Society of Transplantation Consensus Conference on the Use of Hepatitis C Viremic Donors in Solid Organ Transplantation

Levitsky¹,

Formica

Bloom

et al. 2017

American Journal of Transplantation

291

342

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The availability of direct-acting antiviral agents for the treatment of hepatitis C virus (HCV) infection has resulted in a profound shift in the approach to the management of this infection. These changes have affected the practice of solid organ transplantation by altering the framework by which patients with end-stage organ disease are managed and receive organ transplants. The high level of safety and efficacy of these medications in patients with chronic HCV infection provides the opportunity to explore their use in the setting of transplanting organs from HCV-viremic patients into non-HCV-viremic recipients. Because these organs are frequently discarded and typically come from younger donors, this approach has the potential to save lives on the solid organ transplant waitlist. Therefore, an urgent need exists for prospective research protocols that study the risk versus benefit of using organs for hepatitis C-infected donors. In response to this rapidly changing practice and the need for scientific study and consensus, the American Society of Transplantation convened a meeting of experts to review current data and develop the framework for the study of using HCV viremic organs in solid organ transplantation.

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Section: Transmission and Treatment Concernsmentioning

confidence: 99%

The American Society of Transplantation Consensus Conference on the Use of Hepatitis C Viremic Donors in Solid Organ Transplantation

Levitsky¹,

Formica

Bloom

et al. 2017

American Journal of Transplantation

291

342

View full text Add to dashboard Cite

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“…The intriguing finding is somehow anticipated because many studies suggest that patients with elimination of serum HCV are perceived to achieve regression of liver fibrosis or cirrhosis than non-SVR patients [29,30]. Nevertheless, argument against the clinical relevance of OCI proposed that the persisting histological alteration in a small portal of individuals after SVR may bear the reverse of immune intolerance after withdraw of antiviral therapy [14]. However, this seems unlikely, because one study investigating OCI in patients with unknown cause of persistent abnormal liver tests suggested that occult intrahepatic HCV-RNA was independently linked to inflammatory and fibrosis [13].…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, the existence of OCI is disputed owing to the controversy on whether it has clinical impact. Although OCI in a subset of individuals was found to coincide with elevated liver function tests and/or various degree of fibrosis, some other studies argued that the persistent aminotransferase or histological abnormalities might be related to long-term inflammation or reactivation of tolerant immunologic microenvironment after antiviral therapy [14,15]. It is well-known that chronic HCV infection is associated with exhaustion of HCV-specific CD8+ T cells.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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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.

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“…The detection of OCI in blood banks can significantly reduce the spread of HCV infections, thus significantly reducing medical costs for the care and treatment of patients with CHC. The detection of OCI is important, not only in blood banks but also in molecular biology laboratories, where the presence of HCV is monitored in liver transplant patients, dialysis patients, multi-transfused hemophiliacs, and in patients who, after having reached sustained viral response (SVR), have relapsed [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

Prevalence and risk factors of Occult Hepatitis C infections in blood donors from Mexico City

et al. 2018

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BackgroundThe circulatory system is the main mechanism for transmission of the Hepatitis C Virus (HCV). A new class of HCV infections, Occult HCV infection (OCI), is defined as the presence of HCV-RNA in hepatocytes with the absence of HCV in the serum/plasma utilizing current laboratory assays. Different groups have reported the prevalence of OCI; however, its associated risk factors have not been established. In Mexico, there are no reports about OCI, so the objective of our study was to determine the prevalence of OCI in total blood donors in Mexico City, as well as its associated risk factors.MethodsBlood donors that were considered eligible for donation, according to NOM 253-SSA1-2012, were randomly selected. Demographic data was collected from 1,037 donors. Plasma and peripheral blood mononuclear cells were assessed for HCV-RNA. The presence of HCV-RNA was determined by nested PCR for the 5'-UTR region. Logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (95%CI) to determine the level of association.ResultsThe prevalence of OCI was 3.4% among blood donors. Homosexual relationships (OR = 5.52, 95%CI: 1.53–19.92, p<0.05) and acupuncture (OR = 3.56, 95%CI: 1.41–8.98, p<0.05) were significantly associated with OCI.ConclusionThere is a significant presence of OCI in the blood donor population in Mexico City. The main risk factors for OCI transmission are homosexual relationships and acupuncture. This study supports the increased use of sensitive and specific screening tests for blood bank testing.

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Occult Hepatitis C Virus Infection: Are We Digging Too Deep?

Abstract: See "Detection of occult hepatitis C virus infection in patients who achieved a sustained virologic response to direct-acting antiviral agents for recurrent infection after liver transplantation," by Elmasry S, Wadhwa S, Bang B-R, et al, on page 550.

Cited by 7 publications

References 22 publications

The American Society of Transplantation Consensus Conference on the Use of Hepatitis C Viremic Donors in Solid Organ Transplantation

The American Society of Transplantation Consensus Conference on the Use of Hepatitis C Viremic Donors in Solid Organ Transplantation

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

Prevalence and risk factors of Occult Hepatitis C infections in blood donors from Mexico City

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