Tsunami Of Miscarriages in Hcv Patients- Time to Wake Up

Abstract

Introduction: There are conflicting results of studies done regarding miscarriage in HCV patients. Most studies indicate that the miscarriage rate in pregnant women with Hepatitis C Virus (HCV) is higher than the general population, but some studies project that there is no substantial evidence suggesting HCV directly increases the risk of miscarriage; however, severe liver disease from advanced HCV infection could potentially impact pregnancy outcomes, including miscarriage risk. The primary concern with HCV during pregnancy is the potential for transmitting the virus to the baby, which is relatively low (around 5%) and depends on the mother’s viral load.
Aims and objectives: To determine miscarriage rate m pregnant patients with confirmed HCV infection. Materials & Methods: It was a prospective study conducted at Medical Gastroenterology in collaboration with Obstetrics & Gynecology, PGIMS, Rohtak over a period of seven years from 1.1.2017 to 31.12.2024. Three hundred (300) pregnant patients who were confirmed to be positive for anti HCV antibody test on Enzyme Linked Immunoassay Test (ELISA) and HCV RNA on PCR testing and HbsAg and anti-HIV antibody negative were enrolled in the study and followed. These three hundred patients were followed throughout pregnancy, delivery, post-partum period and till 12 weeks SVR testing. The data of these 300 HCV confirmed pregnant patients was analysed in final analysis.
Results: Out of these 300 HCV patients, 78 patients (26%) had miscarriage. In these 78 patients with miscarriage, majority belonged to 21-30 yrs age group (73.07%). Majority of miscarriages were seen in first trimester of pregnancy (74.34%) and out of it also, maximum was seen in second month of pregnancy. Two -third (66.66%) had single miscarriage followed by twice miscarriage and multiple ones were least common. Majority patients (71.79%) were non-cirrhotic with normal fibroscan score i.e. below 7 Kpa, followed by patients in F2 & F3 group. F1 fibrosis and F4 Cirrhosis was not seen in any HCV patient who had miscarriage. One characteristic finding in our pool was high viral load i.e. > 105 HCV viral load in majority of patient i.e. 79.50%.
Conclusion: Our study has re-confirmed the findings available in literature regarding high prevalence of miscarriages in HCV females in comparison to normal population. Moreover, the prominent risk factors associated with miscarriage are high viral load, young age and first trimester of pregnancy.

Keywords:Anti HCV antibody, HCV RNA Quantitative, Miscarriage. Pre-term delivery, Breast feeding, anti-viral treatment

Introduction

Hepatitis B and C are the most common causes of chronic viral hepatitis in children and adults worldwide. In industrialized nations, because of vaccination programs against hepatitis B, Hepatitis C Virus (HCV) has become the primary cause of chronic viral hepatitis in children, with vertical transmission becoming the leading source of infection. With the discovery of direct-acting antivirals to treat Hepatitis C Virus (HCV), attention is turning to interventions either in pregnancy or in infancy to prevent or treat vertically acquired infection. The World Health Organization’s target of HCV elimination by 2030 [1] has added further urgency to this issue. According to a 2014 meta-analysis, Vertical Transmission (VT) occurs in 5.8% of infants of HCV RNA–positive mothers, and 10.8% if mothers also have HIV [2]. Women with the Hepatitis C Virus (HCV) have fewer live births and face a higher risk of miscarriage, infertility, gestational diabetes and pre-eclampsia during pregnancy, researchers in Italy have found. HCV-positive women of childbearing age undergo premature ovarian deterioration which causes pregnancy-related issues including low birth weight for the baby. The HCV-positive women had lower levels of Anti-Müllerian Hormone (AMH), an indicator of ovarian reserve and was associated with a high rate of miscarriage [3]. It has been estimated that up to 29,000 HCV-infected women gave birth each year from 2011 to 2014 [4]. Additionally, there has been an increase in HCV among young adults, including women of childbearing age [5-7]. Pregnancy itself does not appear to negatively affect chronic HCV infection. In general, serum ALT levels decrease during the first and third trimesters of pregnancy and increase after delivery. HCV RNA levels rise during the first and third trimesters, reaching a peak during the third trimester, and decrease postpartum [8]. These effects are likely due to the immunosuppressive effects of pregnancy and increased maternal plasma volume. HCV-infected pregnant persons have a higher incidence of Intrahepatic Cholestasis of Pregnancy (ICP) when compared to noninfected pregnant persons [9] which is associated with an increased rate of adverse maternal and fetal outcomes. Although some studies show an increased risk of adverse perinatal outcomes (preterm delivery, low birth weight infants, and congenital anomalies) with maternal HCV infection, these risks are confounded by comorbid conditions, such as substance use [10]. However, pregnant persons with cirrhosis are at increased risk for poor maternal outcomes (preeclampsia, cesarean section, hemorrhagic complication, and death) and neonatal outcomes (preterm delivery, low birth weight, and neonatal death) [11,12].

Figure 1:Electrons in the atomic shell of a gas.

Aims And Objectives

To determine miscarriage rate in pregnant patients with confirmed HCV infection.

Material and Methods

It was a prospective study conducted at Medical Gastroenterology in collaboration with Obstetrics & Gynecology, PGIMS, Rohtak over a period of seven years from 1.1.2017 to 31.12.2024. Three hundred (300) pregnant patients who were confirmed to be positive for anti HCV antibody test on Enzyme Linked Immunoassay Test (ELISA) and HCV RNA on PCR testing and HbsAg & anti-HIV antibody negative were enrolled in the study and followed. As per guidelines, antiviral treatment for HCV cannot be given during pregnancy or breast feeding, hence treatment of these mothers was started only after six months of breastfeeding. Once, breastfeeding was stopped, then these oral antiviral drugs were started for 12- 24 weeks. These three hundred patients were followed throughout pregnancy, delivery, post-partum period and till 12 weeks SVR testing. The data of these 300 HCV confirmed pregnant patients was analysed in final analysis.

Stastical Analysis

All the data was entered in Microsoft Excel Data and analysed using SPSS 15.0 version.

Observation and Results

Three hundred (300) patients who were confirmed to be positive for anti HCV antibody test on Enzyme Linked Immunoassay Test (ELISA) and HCV RNA on PCR testing were enrolled in the study and followed. Out of these 300 patients, 78 patients (26%) had miscarriage. In these 78 patients with miscarriage, majority belonged to 21-30 yrs age group (73.07%). Majority of miscarriages were seen in first trimester of pregnancy (74.34%) and out of it also, maximum was seen in second month of pregnancy. Two -third (66.66%) had single miscarriage followed by twice miscarriage and multiple ones were least common. Majority patients (71.79%) were non-cirrhotic with normal fibroscan score i.e. below 7 Kpa, followed by patients in F2 & F3 group. F1 fibrosis and F4 Cirrhosis was not seen in any HCV patient who had miscarriage. One characteristic finding in our pool was high viral load i.e. > 105 HCV viral load in majority of patient i.e. 79.50% (Tables 1-6).

Table 1:Showing Percentage of HCV Patients with Miscarriages.

Table 2: Showing Age Group Distribution of HCV Patients with Miscarriages.

Table 3:Showing Number of Miscarriages in HCV Patients.

Table 4:Showing Distribution of Miscarriages according to Gestational Age in HCV Patients.

Table 5:Showing Fibrosis/Cirrhosis in HCV Patients with Miscarriages on Basis of Fibroscan.

Table 6:Showing HCV Viral Load in Patients with Miscarriages.

Discussion

Hepatitis C infection is a leading cause of liver diseases such as cirrhosis and hepatocellular carcinoma. It is a significant cause of morbidity and mortality worldwide, with approximately 71 million people infected, 3.26 million of them being children [13-14]. Hepatitis C is a viral infection affecting approximately 1% of women of childbearing years [15]. HCV infection is associated with adverse pregnancy outcomes. A population-based, retrospective cohort study from Washington state by Pergam et al 15 compared 506 HCV-positive pregnant women with 2022 HCV-negative pregnant controls. In multivariable analysis, it was found that infants born to women infected with HCV were more likely to be small for gestational age, have low birthweight, require admission to the neonatal intensive care unit, and require assisted ventilation [16]. Another population-based retrospective cohort study based in Florida by Connell et al 16 compared 988 HCV-positive women with 1,669,370 controls. Using multivariate analysis, it was found that HCV-infected women were more likely to deliver infants with poor birth outcomes, including preterm birth, low birthweight, and congenital anomalies [17]. A recent meta-analysis that included these 2 studies and 5 others reported that maternal HCV infection was significantly associated with fetal growth restriction and low birthweight [18]. It is difficult to know with certainty whether the increased risk of such adverse fetal outcomes is due to the viral effect of HCV or to potential confounders in the population being studied. In another study, women with HCV RNA+ pregnancies were more likely to have preterm delivery, post-partum hemorrhage and low median infant birth weight [19]. A recent study conducted by Karampatou et al. suggests that premature ovarian senescence, characterized by a decline in anti-Müllerian hormone, is observed in women with hepatitis C and higher rates of miscarriage in patients with hepatitis C as compared to those with hepatitis B [20]. One Indian Study showed that in general population, miscarriages occurred often in India (4.9%), with 23% of cases occurring in the first trimester (≤12 weeks). On bivariate analysis, they identified several factors associated with a higher prevalence of miscarriages in India, like mothers aged thirty years or older, residing in urban areas, with less than ten years of education, belonging to the richest wealth quantile, expressing a desire for more children, having no demand for contraception, and possessing no parity experienced a higher prevalence of miscarriage in total pregnancies in India [21]. According to recent studies, the prevalence of miscarriage in general population in India is around 7%, of all pregnancies based on data from the National Family Health Survey (NFHS), indicating that a significant portion of pregnancies in India end in miscarriage; with some studies reporting a slightly higher rate, around 11% pregnancy loss across the country. According to available research, studies suggest that women with Hepatitis B infection in India have a higher prevalence of miscarriages compared to those without the virus, with some studies indicating a significant increase in miscarriage rates among pregnant women carrying Hepatitis B; however, the exact prevalence of miscarriages specifically related to Hepatitis B in India is difficult to pinpoint due to limited data and variations in study methodologies. Studies have shown an increased risk of both newborn and maternal morbidity associated with HBV infection, including fetal distress, gestational diabetes mellitus, preterm delivery, and meconium peritonitis [22-26]. Also, antepartum hemorrhage causing placental abruption and placenta previa can increase.

A lower Apgar score is the only perinatal complication [22,26]. However, there isn’t much research on the mechanisms underlying these results. In our study group, miscarriage rate of 26% was seen with maximum number (73.07%) of patients belonging to 21-30 yrs of age group. Majority of miscarriages were seen in first trimester of pregnancy (74.34%) and out of it also, maximum was seen in second month of pregnancy. Two -third (66.66%) had single miscarriage followed by twice miscarriage and multiple ones were least common. Majority patients (71.79%) were non-cirrhotic with normal fibroscan score i.e. below 7 Kpa, followed by patients in F2 & F3 group. F1 fibrosis and F4 Cirrhosis was not seen in any HCV patient who had miscarriage. One characteristic finding in our pool was high viral load i.e. > 105 HCV viral load in majority of patient i.e. 79.50%. Our study clearly highlights the significant higher miscarriage rate in HCV in comparison to HBV and general population. Moreover, as majority of patients were with normal liver and none was having cirrhosis, it excluded cirrhosis reason for causing miscarriage. It stresses the need of timely recognition and treatment of HCV before conception, as same cannot be treated during pregnancy and breastfeeding. Moreover, it warrants screening for HCV in pregnancy as well as in cases of recurrent pregnancy loss.

Conflict of Interest

The authors declare that there was no conflict of interest and no financial aid was taken for the same.

Conclusion

Our study has re-confirmed the findings available in literature regarding high prevalence of miscarriages in HCV females in comparison to normal population. Moreover, the prominent risk factors associated with miscarriage are high viral load, young age and first trimester of pregnancy. It will be wise decision to get tested for HCV before conceiving, at least in those areas which have high prevalence of HCV and get treated for the same because antiviral treatment cannot be given during pregnancy or breastfeeding, unlike HBV infection. Moreover, it warrants screening for HCV in cases of recurrent pregnancy loss.

Conflict of Interest

None.

Acknowledgements

None.

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