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

Abstract

Background It is widely accepted that the risk of HCV vertical transmission (VT) is 5-6% in mono-infected 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 re-analysed 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 three days of birth, and differences between elective caesarean and non-elective caesarean deliveries. Findings Overall VT rates were 7.2% (95% credible interval 5.6-8.9) in mothers who were HIV negative and 12.1% (8.6-16.8) in HIV-co-infected women. The corresponding rates net of clearance at 5 years were 2.4% (1.1-4.1) and 4.1% (1.7-7.3). We estimated that 24.8% (12.1-40.8) of infections occur early in utero, 66.0% (42.5-83.3) later in utero, and 9.3% (0.5-30.6) during delivery. Conclusion 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 to prevent or treat pediatric HCV infection, and strategies to manage children exposed in utero.

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

“…The pattern of clearance reported here underscores the need to estimate vertical transmission rates “net” of clearance at different ages. This is the subject of a companion article based on the same 3 cohorts [ 33 ].…”

Modeling-Based Response-Guided Hepatitis C Treatment During Pregnancy and Postpartum

“…At the time of delivery, HCV was not detected in the patient ( Figure 1 ), dramatically reducing the probability of HCV transmission to the newborn compared with the average pretreatment viral load of 433 000 IU/mL [ 16 , 17 ]. Theoretically, reaching the cure boundary with DAA therapy before delivery, defined as <1 virus particle in the entire extracellular body fluid by modeling [ 10 ], should also prevent vertical transmission.…”

CDC Recommendations for Hepatitis C Testing Among Perinatally Exposed Infants and Children — United States, 2023

“…A systematic review and meta-analysis of 109 articles found that the risk for perinatally acquired infection from an HCV antibody-reactive pregnant person with detectable HCV RNA was 5.8% (95% CI = 4.2%–7.8%) in the absence of HIV infection and 10.8% (95% CI = 7.6%–15.2%) among those with poorly controlled HIV coinfection ( 13 ). A statistical reanalysis of data, including 1,749 children in three prospective cohorts that corrected for infections that might have cleared before they were detected, calculated an overall perinatal transmission rate of 7.2% (95% CI = 5.6%–8.9%) among pregnant persons who were HIV negative and 12.1% (95% CI = 8.6%–16.8%) among those with poorly controlled HIV coinfection ( 14 ). This study also estimated that 24.8% of perinatal infections occur early in utero, 66% later in utero, and 9.3% during delivery.…”