Spontaneous Clearance of Vertically Acquired Hepatitis C Infection: Implications for Testing and Treatment

Abstract

Background Current guidelines recommend that infants born to women with hepatitis C (HCV) viremia are screened for HCV antibody at age 18 months, and if positive, referred for RNA testing at 3 years to confirm chronic infection. This policy is based in part on analyses suggesting 25%-40% of vertically acquired HCV infections clear spontaneously within 4-5 years. Methods Data on 179 infants with HCV RNA and/or anti-HCV evidence of vertically acquired infection in three prospective European cohorts were investigated. Ages at clearance of infection were estimated taking account of interval censoring and delayed entry. We also investigated clearance in initially HCV RNA negative infants in whom RNA was not detectable until after 6 weeks. Results Clearance rates are initially high then decline slowly. Apparently, many infections clear before they can be confirmed. An estimated 65.9% (50.1-81.6) of confirmed infections cleared by 5 years, at a median 12.4 (7.1-18.9) months. If treatment began at age 6 months, 18 months or 3 years, at least 59.0% (42.0-76.9), 39.7% (17.9-65.9), and 20.9% (4.6-44.8) of those treated would clear without treatment. In seven (6.6%) confirmed infections, RNA was not detectable until after 6 weeks, and in 2 (1.9%) not until after 6 months. However, all such cases subsequently cleared. Conclusions Most confirmed infection clears by age 3 years. Treatment before age 3, if it was available, would avoid loss to follow-up, but would result in substantial over-treatment.

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

“…HCV vertical transmission rates reported in the literature are based on infection status assessed at different ages, with no consensus on how to take account of spontaneous clearance. We have therefore developed an approach that estimates how many uninfected children may have been infected and cleared before their infection was detected and confirmed, based on a previously estimated clearance rate [ 5 ], and which then calculates VT rates net of clearance at ages from birth to age 5 years.…”

“…Three prospective studies following infants born to HCV antibody (anti-HCV)–positive mothers were included: European Pediatric HCV Network (EPHN) [ 4 , 8–10 ]; the British Paediatric Surveillance Unit (BPSU) study, which included 3 hospitals in Dublin, Irish Republic and centers across the United Kingdom [ 11 ]; and the ALHICE (Alpes-Maritimes, Languedoc, Haute Garonne Infection C chez l’Enfant) study [ 12 ]. The selection of these studies has been described previously [ 5 ], along with details of their pediatric testing schedules. The Faculty of Health Sciences Research Ethics Committee, University of Bristol, approved these analyses of historic data.…”

“…According to a 2014 meta-analysis, vertical transmission (VT) occurs in 5.8% of infants of HCV RNA–positive mothers who are not human immunodeficiency virus (HIV) coinfected, and 10.8% if mothers also have HIV [ 2 ]. A proportion of vertically infected infants clear spontaneously by age 5 years: 20%–40% is cited in reviews and guidelines [ 3 , 4 ], but a recent analysis reported 66% clearance, with rates initially high then declining over the first 3 years [ 5 ].…”

“…The overall (underlying) VT rate is estimated by correcting for infections that may have cleared before they were detected. VT rates net of clearance are then estimated by applying clearance rates, estimated previously from the same data [ 5 ], to the overall VT rate.…”

Defer no more: advances in the treatment and prevention of chronic hepatitis C virus infection in children

“…The recommendation to defer treatment in children under 3 years stems from natural history studies demonstrating potential spontaneous viral resolution in some and slow disease progression in those with persistent infection, high drug costs, practical challenges of drug administration and lack of approved regimens for this age group [23 ▪▪ ,63]. In some challenging clinical situations, DAA administration before age 3 years may be indicated, as described in two children under age 1 year who required liver transplant for non-HCV related indications [55,64 ▪ ].…”