Overall vertical transmission of HCV, transmission net of clearance, and timing of transmission

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

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

Modelling the potential effectiveness of hepatitis C screening and treatment strategies during pregnancy in Egypt and Ukraine

BACKGROUND & AIMS: Hepatitis C (HCV) test and treat campaigns currently excludes pregnant women. Pregnancy offers a unique opportunity for HCV screening and to potentially initiate direct-acting-antiviral treatment. We explored HCV screening and treatment strategies in two lower middle-income countries with high HCV prevalence, Egypt and Ukraine. METHODS: Country-specific probabilistic decision models were developed to simulate a cohort of pregnant women. We compared five strategies: S0, targeted risk-based screening and deferred treatment (DT) to after pregnancy/breastfeeding; S1, WHO risk-based screening and DT; S2, WHO risk-based screening and targeted treatment (treat women with risk factors for HCV vertical transmission (VT)); S3, universal screening and targeted treatment during pregnancy; S4, universal screening and treatment. Maternal and infant HCV outcomes were projected. RESULTS: S0 resulted in the highest proportion of women undiagnosed:59% and 20% in Egypt and Ukraine, respectively, with 0% maternal cure by delivery and VT estimated at 6.5% and 7.9%, respectively. WHO risk-based screening and DT (S1) increased the proportion of women diagnosed with no change in maternal cure or VT. Universal screening and treatment during pregnancy (S4) resulted in the highest proportion of women diagnosed and cured by delivery (65% and 70% respectively), and lower levels of VT (3.4% and 3.6% respectively). CONCLUSIONS: This is one of the first models to explore HCV screening and treatment strategies in pregnancy, which will be critical in informing future care and policy as more safety/efficacy data emerge. Universal screening and treatment in pregnancy could potentially improve both maternal and infant outcomes. IMPACT AND IMPLICATIONS: In the context of two lower middle-income countries with high HCV burden (Egypt and Ukraine), we designed a decision analytic model to explore five different HCV testing and treatment strategies for pregnant women, with the assumption that treatment was safe and efficacious for use in pregnancy. Assuming DAAs in pregnancy reduced vertical transmission, model findings indicate optimal maternal and infant benefits with provision of universal (rather than risk-based targeted) screening and treatment during pregnancy: the proportion of women diagnosed and cured by delivery would be 65% in Egypt and 70% in Ukraine (versus 0% with standard of care), and the proportion of infants that would be infected at the age of 6 months would decrease from 6.5% to 3.4% in Egypt, and from 7.9% to 3.6% in Ukraine, compared to standard of care. While future trials are needed to assess safety and efficacy of DAA treatment in pregnancy and impact on VT, there is increasing recognition that the elimination of HCV cannot leave entire subpopulations of pregnant women and young children behind. Our findings will be critical in informing policymakers in improving screening and treatment recommendations for pregnant women

Overall vertical transmission of HCV, transmission net of clearance, and timing of transmission.

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.

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