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Labour pains: eliminating HCV in women and children

2021; Elsevier BV; Volume: 6; Issue: 3 Linguagem: Inglês

10.1016/s2468-1253(20)30373-3

2468-1253

Ali Judd, Intira Jeannie Collins, Sarah Pett, Diana M. Gibb,

Hepatitis B Virus Studies

Hepatitis C virus (HCV) is a major global public health problem and a leading cause of death worldwide.1Cooke GS Andrieux-Meyer I Applegate TL et al.Accelerating the elimination of viral hepatitis: a Lancet Gastroenterology & Hepatology Commission.Lancet Gastroenterol Hepatol. 2019; 4: 135-184Summary Full Text Full Text PDF PubMed Scopus (166) Google Scholar However, HCV is a problem that can be remedied with enough public health investment. Curative treatment with safe, short-course, direct-acting antivirals has been available for several years, and elimination is in reach.2WHOGlobal hepatitis report, 2017. World Health Organization, Geneva2017Google Scholar Thus, the priority now is to identify and treat all those who are infected, reduce morbidity and mortality, and prevent new infections, including those that are acquired through mother-to-child transmission. Ellen Dugan and colleagues3Dugan E Blach S Biondi M et al.Global prevalence of hepatitis C virus in women of childbearing age in 2019: a modelling study.Lancet Gastroenterol Hepatol. 2021; (published online Jan 27.)https://doi.org/10.1016/S2468-1253(20)30359-9Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar provide an important contribution to the field with their modelled estimates of 2019 global prevalence of HCV in women of childbearing age (15–49 years). Dugan and colleagues3Dugan E Blach S Biondi M et al.Global prevalence of hepatitis C virus in women of childbearing age in 2019: a modelling study.Lancet Gastroenterol Hepatol. 2021; (published online Jan 27.)https://doi.org/10.1016/S2468-1253(20)30359-9Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar found that almost 15 million women aged 15–49 years might be living with HCV, accounting for a fifth of the global population with viraemic HCV. Importantly, the authors estimated prevalence at a national and regional level. The huge burden of infections in predominantly low-income and middle-income countries is striking, with China, Pakistan, Russia, and India accounting for nearly half the global HCV infections in women of childbearing age. This wealth imbalance in the global distribution of infections has implications for how we target women for testing, treatment, and prevention of onward transmission to infants. There are also implications for the prevention of reinfection, given that the primary driver of transmission is unsafe health-care practices in many low-income and middle-income settings.2WHOGlobal hepatitis report, 2017. World Health Organization, Geneva2017Google Scholar The authors recommend preconception test and treat strategies, suggesting that routine gynaecological visits for the general population of women are a way to identify those with HCV. Although this approach might be feasible in high-income countries, with delivery through established cervical screening programmes, it might not be feasible or cost-effective in many low-income and middle-income countries, where gynaecological access is rarely available. For example, some of the countries estimated to have the highest burden of HCV also have a high burden of cervical cancer,4Arbyn M Weiderpass E Bruni L et al.Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis.Lancet Glob Health. 2020; 8: e191-e203Summary Full Text Full Text PDF PubMed Scopus (499) Google Scholar reflecting failures in rolling out cervical screening and vaccination against human papillomavirus. Even in high-income settings with concentrated HCV epidemics like the USA, HCV testing linked to gynaecological visits is likely to miss women at the highest risk of HCV, namely those who inject drugs.5Schillie S Wester C Osborne M Wesolowski L Ryerson AB CDC recommendations for hepatitis C screening among adults—United States, 2020.MMWR Recomm Rep. 2020; 69: 1-17Crossref Google Scholar Other universal health interventions include community-based mass HCV screening and treatment programmes, as in Egypt, although these efforts exclude pregnant and lactating women because of the paucity of treatment options available to them. In high-income countries, universal antenatal (or prenatal) HCV testing has been shown to be cost-effective,6Chaillon A Rand EB Reau N Martin NK Cost-effectiveness of universal hepatitis C virus screening of pregnant women in the United States.Clin Infect Dis. 2019; 69: 1888-1895Crossref PubMed Scopus (27) Google Scholar and is now recommended in the USA.5Schillie S Wester C Osborne M Wesolowski L Ryerson AB CDC recommendations for hepatitis C screening among adults—United States, 2020.MMWR Recomm Rep. 2020; 69: 1-17Crossref Google Scholar However, as direct-acting antivirals have yet to be approved in pregnant or lactating women due to sparse safety data, these groups have been completely left out of the treatment cascade, creating a huge gap in treatment access. Small studies suggest that direct-acting antiviral regimens without ribavirin, given in the second and third trimester of pregnancy, are safe, with a high rate of maternal cure, no vertical transmissions, and few (often mild) adverse effects,7Chappell CA Scarsi KK Kirby BJ et al.Ledipasvir plus sofosbuvir in pregnant women with hepatitis C virus infection: a phase 1 pharmacokinetic study.Lancet Microbe. 2020; 1: e200-e208Summary Full Text Full Text PDF PubMed Scopus (11) Google Scholar, 8Yattoo GN Treatment of chronic hepatitis C with ledipasvir/sofosbuvir combination during pregnancy.Hepatol Int. 2018; 12 (abstr).: S292-S293Google Scholar but much larger trials are needed to confirm these findings. In the meantime, the strategy is to keep women linked into care post-partum and treat them after they stop breastfeeding. Unfortunately, all evidence to date (mainly from high-income settings) show very poor engagement in the post-partum care cascade,9Bhardwaj AM Mhanna MJ Abughali NF Maternal risk factors associated with inadequate testing and loss to follow-up in infants with perinatal hepatitis C virus exposure.J Neonatal Perinatal Med. 2020; (published online Feb 3.)https://doi.org/10.3233/NPM-190264Crossref PubMed Scopus (1) Google Scholar and engagement could be worse in many low-income and middle-income countries like Pakistan, where women breastfeed for a median of 2 years. This treatment gap serves as a gender imbalance and effectively obstructs women from benefitting from the advantages of cure; aside from the harmful effects of HCV on maternal and infant outcomes, there is also the risk of vertical transmission to successive children.10Kushner T Terrault NA Hepatitis C in pregnancy: a unique opportunity to improve the hepatitis C cascade of care.Hepatol Commun. 2018; 3: 20-28Crossref PubMed Google Scholar Importantly, there are no treatment options for infants younger than 3 years, and the net result is that few women and children with HCV are receiving timely treatment, and so they remain at risk of progressive liver disease. Dugan and colleagues' paper is important because it clearly shows how women of childbearing age need to be recognised as a key risk population for HCV prevention, treatment, and cure, if we are serious about elimination.3Dugan E Blach S Biondi M et al.Global prevalence of hepatitis C virus in women of childbearing age in 2019: a modelling study.Lancet Gastroenterol Hepatol. 2021; (published online Jan 27.)https://doi.org/10.1016/S2468-1253(20)30359-9Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar Multiple approaches are needed to diagnose and treat all women of childbearing age, including mass community-based screening and treatment programmes and universal antenatal screening, which is the cornerstone of maternal and child health. Additionally, the risk of reinfection needs to be reduced through continued focus on improving safety in medical practices. However, these efforts will have little benefit without well conducted, large clinical trials to ascertain the safety of direct-acting antivirals in pregnancy and during the lactation period, which have the potential to cure the mother and prevent HCV in the baby. Such trials are crucial in paving the way for equitable access to treatment for all women living with HCV. AJ reports grants from ViiV Healthcare, Gilead Sciences, the Medical Research Council (MRC), AbbVie, National Health Service England, and the International AIDS Society, outside the submitted work. IJC reports grants from ViiV Healthcare, Gilead Sciences, and AbbVie, outside the submitted work. SP reports grants from Gilead Sciences and the MRC, outside the submitted work. DMG reports grants from ViiV Healthcare, Gilead Sciences, the MRC, Janssen Pharmaceuticals, and the European and Developing Countries Clinical Trials Partnership, outside the submitted work. Global prevalence of hepatitis C virus in women of childbearing age in 2019: a modelling studyMost research on HCV disease burden among women aged 15–49 years focuses on pregnant women. Using modelling, this analysis provides global and national estimates of HCV prevalence in all women of childbearing age. These data can inform preconception test-and-treat strategies to reduce vertical transmission and total disease burden. Full-Text PDF