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. 2023 Mar 4;76(5):905-912.
doi: 10.1093/cid/ciac270.

Overall Vertical Transmission of Hepatitis C Virus, Transmission Net of Clearance, and Timing of Transmission

Anthony E Ades  1 , Fabiana Gordon  1 , Karen Scott  2 , Intira J Collins  2 , Thorne Claire  3 , Lucy Pembrey  4 , Elizabeth Chappell  2 , Eugènia Mariné-Barjoan  5 , Karina Butler  6 , Giuseppe Indolfi  7 , Diana M Gibb  2 , Ali Judd  2
Affiliations

Overall Vertical Transmission of Hepatitis C Virus, Transmission Net of Clearance, and Timing of Transmission

Anthony E Ades et al. Clin Infect Dis. .

Abstract

Background: It is widely accepted that the risk of hepatitis C virus (HCV) vertical transmission (VT) is 5%-6% in monoinfected women, and that 25%-40% of HCV infection clears spontaneously within 5 years. However, there is no consensus on how VT rates should be estimated, and there is a lack of information on VT rates "net" of clearance.

Methods: We reanalyzed data on 1749 children in 3 prospective cohorts to obtain coherent estimates of overall VT rate and VT rates net of clearance at different ages. Clearance rates were used to impute the proportion of uninfected children who had been infected and then cleared before testing negative. The proportion of transmission early in utero, late in utero, and at delivery was estimated from data on the proportion of HCV RNA positive within 3 days of birth, and differences between elective cesarean and nonelective cesarean deliveries.

Results: Overall VT rates were 7.2% (95% credible interval [CrI], 5.6%-8.9%) in mothers who were human immunodeficiency virus (HIV) negative and 12.1% (95% CrI, 8.6%-16.8%) in HIV-coinfected women. The corresponding rates net of clearance at 5 years were 2.4% (95% CrI, 1.1%-4.1%), and 4.1% (95% CrI, 1.7%-7.3%). We estimated that 24.8% (95% CrI, 12.1%-40.8%) of infections occur early in utero, 66.0% (95% CrI, 42.5%-83.3%) later in utero, and 9.3% (95% CrI, 0.5%-30.6%) during delivery.

Conclusions: Overall VT rates are about 24% higher than previously assumed, but the risk of infection persisting beyond age 5 years is about 38% lower. The results can inform design of trials of interventions to prevent or treat pediatric HCV infection, and strategies to manage children exposed in utero.

Keywords: HCV; hepatitis C virus; net transmission; spontaneous clearance; vertical transmission.

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Conflict of interest statement

Potential conflicts of interest. C. T. has received honoraria for presentations from ViiV Healthcare (paid to author); reports grants or contracts unrelated to this work (paid to institution) from the European Commission, Child Health CIO, Public Health England, Penta Foundation, and ViiV Healthcare via Penta Foundation; and has participated on the Infectious Disease in Pregnancy Screening Programme Advisory Board. I. J. C. reports a Medical Research Council Global Health Trials development grant and a Gilead HCV Elimination competitive grant, both paid to institution and unrelated to this work. E. C. reports a contract or grant from ViiV Healthcare paid to institution via the Penta Foundation. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
A1, Assumed proportion of uninfected children remaining hepatitis C virus antibody (anti-HCV) positive at each age up to 18 months. B1, Assumed proportion of infected children who are not initially RNA positive remaining RNA negative by age up to 6 weeks. C1, Proportion of infection not yet cleared, by age up to 5 years. A2, Proportion of indeterminates with last anti-HCV positive at each age. B2, Proportion of uninfected and indeterminate with last RNA negative at each age (<6 weeks). C2, Proportion of uninfected children with the first test indicating they were uninfected at each age.
Figure 2.
Figure 2.
Overall vertical transmission (horizontal lines) and vertical transmission net of clearance at different ages: by mother's human immunodeficiency virus (HIV) status and weighted average of HIV negative (HIV–) and HIV positive (HIV+).
Figure 3.
Figure 3.
Left bar: Vertical transmission (VT) rate of 5.8% (95% credible interval [CrI], 4.2%–7.8%) in hepatitis C virus–monoinfected women [2], and spontaneous clearance of 32.5% (25%–40%) [14, 15]. Right bar: This study, with VT rate of 7.2% (95% CrI, 5.6%–8.9%) with 65.1% clearance (95%CrI, 50.1%–81.6%). Blue segments: infection that clears within 5 years. Red segments: infection remaining after 5 years.
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