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HCV DAAs During Pregnancy
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Download PDF here
Download PDF here
Does HCV increase risk for worse/adverse pregnancy outcomes thus supporting the treatment of HCV during pregnancy? The controversy includes that pregnant women with daily drug use & chaotic lives the accompany this lifestyle may be under so much stress that the focus should be on drug abuse management before DAA treatment, that the risk for MTT is only 5% although it can be much er higher when HIV & STIs are present and that the newborn may clear HCV anyway. So should DAAs be deferred until after birth or when the mother has been able to receive management care for her drug use & chaotic lifestyle, or is this gender bias? Apparently, soon the CDC will issue new Guidelines recommending HCV screening for all pregnant women, further supporting the already same recommendation by OBGYN guidelines. But there are and will be barriers to screening & providing care to pregnant women for many reasons including they may not want to be screened, they are afraid of having child taken away or being incarcerated or being in the "system". Their drug lifestyles may prevent them from pre-natal care. Doctors may refuse to follow guidelines. NYS was I think the first to adopt "mandatory" HCV screening fr all but many doctors never followed this recommendation & nationally Universal screening is recommended but I do't think its been adopted & implemented very much. So Guidelines only go so far, they do not have to be accepted by clinicians in their practice. So where are we on treating with DAAs during pregnancy? The AASLD Guidelines say with full informed discussion between patient & doctor it can be implemented and we have 1 small study showing high rates of cure with no safety concern with SOF/ledipasvir, and we ongoing is a larger study with SOF/Vel examining safety because safety is the remaining question. Without addressing this problem head on we cannot eliminate HCV. Certainly we need better support & services for pregnant women using drugs.
Jules Levin
Maternal HCV infection is associated with intrauterine fetal growth disturbance
A meta-analysis of observational studies
Abstract
Since the evidence regarding the association between maternal hepatitis C virus (HCV) infection and impaired intrauterine fetal growth had not been conclusive, the aim of the present study was to evaluate the risk of maternal HCV infection in association with intrauterine fetal growth restriction (IUGR) and/or low birth weight infants (LBW). We performed an extensive literature search of PubMed, MEDLINE, and EMBASE through December 1, 2015. The odds ratios (ORs) of HCV infection and IUGR/LBW were calculated and reported with 95% confidence intervals (95% CIs). Statistical analysis was performed using RevMen 5.3 and Stata 10.0. Seven studies involving 4,185,414 participants and 5094 HCV infection cases were included. Significant associations between HCV infection and IUGR (OR = 1.53, 95% CI: 1.40–1.68, fixed effect model) as well as LBW were observed (OR = 1.97, 95% CI: 1.43–2.71, random effect model). The results still indicated consistencies after adjusting for multiple risk factors which could affect fetal growth, including maternal age, parity, maternal smoking, alcohol abuse, drugs abuse, coinfected with HBV/HIV and preeclampsia. Our findings suggested that maternal HCV infection was significantly associated with an increased risk of impaired intrauterine fetal growth. In clinical practice, a closer monitoring of intrauterine fetal growth by a series of ultrasound might be necessary for HCV-infected pregnant population.
Chronic hepatitis C virus infection is associated with increased risk of preterm birth: a meta-analysis of observational studies
Summary
Although several epidemiological studies reported that maternal chronic hepatitis C virus (HCV) infection had significantly increased risk of undergoing adverse obstetrical and perinatal outcomes, studies on the relationship between HCV infection and risk of preterm birth (PTB) have yielded inconclusive and inconsistent results. Therefore, we conducted a meta-analysis to investigate the association between HCV infection and PTB. The electronic database was searched until 1 September 2014. Relevant studies reporting the association between HCV infection and the risk of PTB were included for further evaluation.
Statistical analysis was performed using revmen 5.3 and stata 10.0. Nine studies involving 4186698 participants and 5218 HCV infection cases were included. A significant association between HCV infection and PTB was observed (odds ratio = 1.62, 95% CI 1.48–1.76, P < 0.001, fixed-effects model). Stratification according to maternal smoking/alcohol abuse, maternal drug abuse or coinfected with HBV and/or HIV matched groups still demonstrated that women with HCV infection had a high risk for PTB. Findings from our meta-analysis suggested that maternal HCV infection was significantly associated with an increased risk of PTB. In the future, pathophysiological studies are warranted to ascertain the causality and explore the possible biological mechanisms involved.
Preterm birth (delivery before 37 weeks' gestation) is the most common cause of neonatal morbidity and mortality and is also a leading global health issue 14, 15. The rates of preterm birth (PTB) have increased over recent decades. It was reported that the annual social economic burden associated with PTB in the United States had reached $26.2 billion as early as in 2005 16. Several epidemiological studies reported that maternal chronic HCV infection had significantly increased risk of undergoing adverse obstetrical and perinatal outcomes such as gestational diabetes mellitus 17-19, premature rupture of membranes 19, low birthweight infants and stillbirth 17-20. However, the influence of HCV infection on preterm birth is not fully explored. During recent years, a number of studies assessed preterm birth in women with HCV infection 17-25, but the results are inconsistent 20-25. Thus, the possible role of HCV infection in the pathogenesis of preterm birth remains an important but unresolved issue.
To clarify these issues, we conducted a systematic review of the literature and a meta-analysis to investigate whether HCV infection was associated with an increased risk of PTB.
Stratification according to maternal smoking/alcohol abuse, maternal drug abuse or coinfected with HBV and/or HIV matched groups still demonstrated that women with HCV infection have a high risk for PTB with no or mild heterogeneity observed.
Discussion
While previous studies demonstrated that maternal HCV infection was associated with increased risk of gestational diabetes mellitus, premature rupture of membranes, low birthweight infants and stillbirth 17-20, one intriguing observation was regarding the occurrence of PTB 20-25. Previous reports on the association between HCV infection and risk of PTB have yielded inconsistent results. Our result demonstrated that maternal chronic HCV infection was significantly associated with increased risk of PTB.
Several mechanisms may be involved in the association between HCV infection and increased risk for PTB. Although the pathophysiology of PTB is not completely understood, local and/or systemic inflammations have been implicated as independent etiological factors of PTB 30, 31. Diseases characterized by chronic inflammation, such as Crohn's disease 32 and rheumatoid arthritis 33, were associated with an increased risk of PTB. Currently, a growing body of evidence indicated that chronic HCV infection was associated with both excessive hepatic and systemic inflammations 34, 35. Compared to HCV-negative individuals, increased levels of pro-inflammatory cytokines and a higher ratio of pro-inflammatory/anti-inflammatory cytokines have been reported in nondiabetic, nonobese HCV-infected patients 36, 37. Previous studies showed that a significant proportion of preterm births are associated with overproduction of pro-inflammatory cytokines 34. Therefore, one possible biological interpretation for the higher incidence of PTB in women with HCV may be the results of excessive local and/or systemic inflammations triggered by the virus infection.
A growing body of evidence linked placental dysfunction with increased incidence of pregnancy complications, especially low birthweight infants and PTB 38-40. Prior studies suggested placental dysfunction in women with chronic HCV infection by providing consistent results of higher prevalence of low birthweight infants delivered by this specific population 17-20. Moreover, although HCV is a hepadnavirus, mounting evidence suggested that it could also exist in extrahepatic tissues including kidneys 41, pancreas as well as ovaries 42, 43, and even in placenta 44. Trophoblasts are the main component cell types of placenta. A previous study showed that HCV could infect trophoblasts and alter the cellular ultrastructure 44, thus might lead to a compromised pregnancy. Therefore, another possible biological interpretation for the higher incidence of PTB may be the results of impaired trophoblasts and placental function caused by HCV infection.
Mounting evidence indicated that maternal cigarette smoking 45, alcohol abuse 46 and drugs abuse 47 before conception or during pregnancy were associated with higher incidence of PTB. Moreover, prior studies found that patients with HCV were associated with elevated rate of coinfected with HBV and/or HIV 48, which might negatively affect the obstetrical outcomes.It should be noted that several studies included in this meta-analysis also reported higher prevalence of maternal cigarette smoking, alcohol abuse, drugs abuse as well as coinfected with HBV and/or HIV in women with HCV infection 17-20, 25. Therefore, one might concern about whether these potential confounders could affect the overall pooled result. Our meta-analysis could avoid the influence of these crucial confounders, as we used adjusted ORs to estimate the effect sizes in this meta-analysis. Moreover, we performed a subgroup analysis according to maternal cigarette smoking, alcohol abuse, drugs abuse and coinfected status with HBV and/or HIV so as to further avoid the influence of these potential confounders. Although lower pooled ORs were observed when compared these crucial confounders between matched and unmatched groups, our results still demonstrated significantly positive association between HCV infection and PTB according to the matched groups, which indicated that maternal chronic HCV infection might be an independent risk factor for PTB.
Our meta-analysis has some strengths. First, a large number of participants and cases guaranteed the sufficient statistical power to get the reliable conclusions. Second, our findings provided a good estimation of the association between HCV infection and the risk of PTB, as no publication bias was observed and the heterogeneity was low among the studies included. Last but not least, our findings could avoid the influence of some potential confounders, as our results still demonstrated significantly positive association between HCV infection and PTB after subgroup analysis.
However, several limitations should be also addressed. First, the included studies were mainly performed in North America and Europe. Therefore, our findings might be not suitable to be applied to other populations. Second, two of the studies selected in this meta-analysis were case–control studies. Evidence from case–control studies could be probably of less accuracy and more influenced by recall bias when compared to those from cohort studies. In the future, prospective cohorts with larger samples sizes are warranted to ascertain the causality. Third, previous studies demonstrated that the copy number of HCV was highly associated with systemic inflammation and severity of diseases 49, 50. However, most studies included in this meta-analysis confirmed the HCV infection status through qualitative methods. Thus, we cannot perform a dose–response analysis to further investigate the association among HCV infection, systemic inflammation and the risk of PTB more precisely.
In conclusion, this meta-analysis evaluated the association between HCV infection and the risk of PTB and suggested that maternal HCV infection is significantly associated with an increased risk of PTB. In the future, pathophysiological studies are warranted to ascertain the causality and explore the possible biological mechanisms involved.
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