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Global prevalence of hepatitis C virus in women of childbearing age in 2019: a modelling study - HCV Elimination
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COMMENT
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.
⋅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.
⋅In high-income countries, universal antenatal (or prenatal) HCV testing has been shown to be cost-effective, and is now recommended in the USA.
Labour pains: eliminating HCV in women and children
January 27, 2021 -
Lancet Gastroenterol Hepatol
Ali Judd, Intira Jeannie Collins, Sarah Pett, Di M Gibb
Hepatitis C virus (HCV) is a major global public health problem and a leading cause of death worldwide. 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. 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 colleagues 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 colleagues 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.
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, 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. 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, and is now recommended in the USA. 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, 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, 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. 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. 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 study
January 27, 2021
Ellen Dugan, Sarah Blach, Mia Biondi, Zongzhen Cai, Mindi DePaola, Chris Estes, Jordan Feld, Ivane Gamkrelidze, Shyamasundaran Kottilil, Siya Ma, Poonam Mathur, Shauna Montoya, Devin Razavi-Shearer, Kathryn Razavi-Shearer, Sarah Robbins-Scott, Jonathan Schmelzer, Homie Razavi
Summary
Background
Treatment for infection with hepatitis C virus (HCV) during pregnancy has not yet been approved; however, interventions specifically targeting women, especially those of childbearing age (15-49 years), could prevent vertical transmission and community spread. To assess the impact of such interventions, improved prevalence estimates in this group are needed. We aimed to estimate the global prevalence of viraemic HCV in 2019 among women of childbearing age.
Methods
In this modelling study, we used previously developed models for 110 countries inputted with country-specific demographic and HCV epidemiology data. We did a literature review, searching PubMed, Embase, and grey literature for studies published between Jan 1, 2000, and June 30, 2018, reporting HCV antibody or viraemic prevalence in women of childbearing age. Studies from the literature review and studies in models were compared by use of a data quality scoring system and models were updated, as appropriate, when a better study was identified. We used these HCV disease burden models to calculate the 2019 prevalence of viraemic HCV in women of childbearing age. In countries without a model, prevalence was extrapolated by Global Burden of Disease (GBD) region.
Findings
An estimated 14 860 000 (95% uncertainty interval [UI] 9 667 000-18 282 000) women aged 15-49 years had HCV infection worldwide in 2019, corresponding to a viraemic prevalence of 0⋅78% (95% UI 0⋅62-0⋅86).
Globally, HCV prevalence increased with age, rising from 0⋅25% (95% UI 0⋅20-0⋅27) in women aged 15-19 years to 1⋅21% (0⋅97-1⋅34) in women aged 45-49 years.
China (16% of total infections) and Pakistan (15%) had the greatest numbers of viraemic infections, but viraemic prevalence was highest in Mongolia (5⋅14%, 95% CI 3⋅46-6⋅28) and Burundi (4⋅91%, 3⋅80-18⋅75).
Of the countries with 500 cases or more, viraemic prevalence was lowest in Chile (0⋅07%, 95% UI 0⋅04-0⋅12). Among the GBD regions, eastern Europe had the highest viraemic prevalence (3⋅39%, 95% UI 1⋅88-3⋅54). By WHO region, the Eastern Mediterranean region had the highest viraemic prevalence (1⋅75%, 95% UI 1⋅26- 1⋅90).
Interpretation
Most 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.
Funding
Gilead Sciences, John C Martin Foundation, private donors.
Introduction
Women of childbearing age (15-49 years) account for nearly a quarter of the world's population. With a global fertility rate of 2⋅4 births per woman, the health of many women in this group is inextricably tied to the wellbeing of neonates, especially considering vertical transmission of hepatitis C virus (HCV). For HCV RNA-positive women who become pregnant, perinatal transmission occurs in about 5% of individuals. An estimated 224 000 children aged 0-2 years are infected with HCV globally; however, a successful intervention to prevent vertical transmission is currently unavailable. Although direct-acting antivirals are 95-99% effective in curing HCV, their use is not recommended during pregnancy because safety and efficacy data are sparse. Ribavirin, a common antiviral medication used to treat HCV in resource-limited settings, is a known teratogen. In addition, no data exist to guide treatment during breastfeeding. Because of these considerable barriers to peripartum and post-partum treatment for HCV, women of childbearing age could be considered a key population for screening.
In some areas, such as the USA, increases in injection drug use among women of childbearing age are believed to have increased the incidence of HCV infection in this cohort and their children. From 2011 to 2016, anti-HCV antibody positivity increased by 36% in women of childbearing age and 13% in children younger than 5 years in the USA. Globally, an estimated 3⋅2 million women aged 15-64 years inject drugs and, in 2015, people who inject drugs accounted for 6 063 500 (8⋅5%) of 71 146 000 viraemic HCV infections. Isolated transmission outbreaks and reuse of medical or dental equipment also result in infection among women of childbearing age. Additionally, pregnant women with HCV infection who also have substance use disorders or liver cirrhosis are at an increased risk for poor maternal and fetal health outcomes. Curing disease before pregnancy could dually reduce vertical and horizontal HCV transmission. Outcomes of chronic HCV infection, such as liver damage, can take 20 years post-infection to develop. The average age of people who inject drugs coincides with the average reproductive age, meaning that, in the absence of a comprehensive or universal screening campaign, asymptomatic transmission (including vertical) can continue undetected, especially among populations of women at high risk.
The burden of HCV is a global health concern as liver-related morbidity and mortality continue to rise. To date, the prevalence of HCV has been evaluated in the general population and in groups at high risk of infection, such as people living with HIV, hepatitis B, or both, and people who inject drugs.
However, estimates are scarce for other key populations, including women of childbearing age. Leading health-care organisations across the globe are working towards the 2030 elimination targets for HCV incidence, diagnosis, treatment, and mortality.
Calculating the global number of viraemic HCV infections among women of childbearing age and identifying regional hotspots of disease are needed to frame screening and treatment plans. We aimed to combine a literature search, modelling work, and extrapolation to estimate the global prevalence of viraemic HCV among women of childbearing age in 2019.
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