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J.J. Bakhronov, R.N. Muhiddinzoda, M.N. Nigmatullaev, M.M. Kuddusov, Sh.B. Jamoliddinov
HEPATITIS C IN PREGNANT WOMEN AND NEWBORNS
This review outlines the global incidence of hepatitis C among pregnant women. It describes the association between hepatitis C incidence and the quality of screening for hepatitis C. It also discusses the effect of hepatitis C on pregnancy and vice versa. There is a description of possible pregnancy complications related to hepatitis C, as well as the risk of vertical virus transmission to the fetus. We provide a management strategy for pregnant women infected with hepatitis C. We demonstrated that operative delivery does not reduce the risk of vertical transmission of hepatitis C.
Key words: pregnancy, vertical transmission of infections, hepatitis C, newborn, complications, fetus.
To date, viral hepatitis C (HCV) remains a global public health problem. This disease is one of the very few in which an infected person does not consider himself ill, since in 75% of cases HCV occurs without severe clinical symptoms. According to the World Health Organization, 5% of people in the world are aware of their disease. It is noted that without treatment, patients develop cirrhosis of the liver (LC) or hepatocellular carcinoma (HCC) within 20 years.
The literature of recent years provides data on the level of HCV infection in the world - more than 70 million. At the same time, according to the European Association for the Study of Liver Diseases, in the Republic of Uzbekistan there are approximately 1.8% of all infected in the world. HCV is comprehensively studied by the medical scientific community, the issues of epidemiology, clinic, diagnostics, immunology, as well as the socioeconomic significance of this disease are quite fully covered. However, a special problem, quite serious and insufficiently studied, remains the question of the relationship between HCV and pregnancy. When analyzing this problem, it is necessary to study a number of issues, in particular: the prevalence of HCV in pregnant women; the impact of HCV on pregnancy and childbirth; the impact of pregnancy on the course of HCV; vertical transmission of infection from mother to fetus, and how do surgery and breastfeeding affect this process?
© J.J. Bakhronov, R.N. Muhiddinzoda, M.N. Nigmatullaev, M.M. Kuddusov, Sh.B. Jamoliddinov, 2023.
Before answering these questions, it is necessary to understand the prevalence of HCV in pregnant women. This question is far from unambiguous, as it is directly related to the level of testing of pregnant women for hepatitis C virus (HCV). It should be noted that screening for HCV can be universal, when all pregnant women are tested, and risk-based, when only those pregnant women who are at risk are tested (migrants from areas with a high incidence of HCV; people who inject drugs; those who have tattoos), or jaundice, or a history of blood transfusion).
Currently, universal screening for HCV during pregnancy is only recommended in France, Poland, Italy, Pakistan, and Taiwan. In most countries, however, risk-based screening is carried out, which does not detect a large proportion of pregnant women with HCV, and, importantly, up to 27% of pregnant women with HCV who do not have risk factors for HCV infection do not undergo this screening. In a 2017 risk-based screening for HCV in Irish maternity hospitals, 4655 pregnant sera were tested and 20 (0.43%) cases were found to be anti-HCV antibodies, and 5 (0.11%) cases were found to be HCV antigen. The authors note that the detection rate of HCV infection in risk-based screening is 65% lower compared to universal screening conducted a year earlier in the same maternity hospitals, i.e. it is concluded that risk-based screening misses a significant part of the infection.
In recent years, age has been taken into account when considering HCV detection rates in pregnant women, as in most Western countries and the United States, there has been an increase in pregnancy rates in women over 40 years of age, who are at higher risk of HCV infection. Therefore, the US Centers for Disease Control offered screening for all pregnant women over 40 years of age, as well as those born in 1945-1965. due to the high prevalence of HCV in the US during these years.
In connection with the above, it is problematic to determine the true level of HCV prevalence among pregnant women, and this issue has not been unambiguously resolved anywhere in the world. Researchers from different countries give different figures for this prevalence. However, most researchers are inclined to believe that these figures can be from 8 to 15%. Some authors give relatively low figures - 0.15-2.4% - in developed countries (Europe, USA) and quite high - in Africa: up to 9% in Egypt, followed by Nigeria and Ethiopia, in Benin - 7.4%, in the Congo - 4.1%, in the city of Cotonou - 1.2%. Other authors refer to the lower prevalence of HCV in pregnant women in Egypt: in a survey of 3000 pregnant women in 2015-2016. HCV was detected in 46 (1.5%) women.
In the Republic of Uzbekistan, HCV among pregnant women was noted in 0.28-0.65%, but among pregnant women over 40 years old it reaches 3.2%, and in risk groups - up to 6%.
Thus, the prevalence of HCV in pregnant women is contradictory, because is closely related to the level of testing for HCV. Even in Italy, where HCV testing is free for pregnant women, many women are not tested and hence HCV prevalence is declining in this category.
Speaking about the effect of HCV on the course of pregnancy, the following can be noted: some authors believe that HCV does not affect the course of pregnancy and does not cause any complications, other authors note a slight effect of HCV on pregnancy and childbirth. However, many researchers show the inhibitory effect of HCV on the course of pregnancy, since at this time the immune system of women undergoes significant changes, and the presence of HCV often leads to immunosuppression and other aggravating consequences, in connection with which there are insufficient growth and weight of the fetus, complicated and premature births, spontaneous miscarriages. Thus, the vast majority of researchers still believe that HCV disease is associated with complications during pregnancy and childbirth.
One of the important questions during pregnancy of women with HCV is the question of the possibility of infection of the fetus. At this time, it has been established that the most likely and main cause of infection of the fetus from an infected mother is the vertical route of transmission of the virus, which occurs during pregnancy, childbirth or breastfeeding. More often this happens during childbirth, as the placental barrier is broken, however, the mechanisms of this transmission, factors and timing have not been studied enough. It is believed that intrauterine infection occurs due to direct infection of the trophoblast or due to infection of the endothelial cells of the placenta and umbilical cord. The greatest risk factors are considered to be those that increase fetal contact with infected maternal blood, such as when amniotic membranes rupture or invasive fetal monitoring is used. It has now been established that a high viral load is the main and important factor determining the vertical transmission of HCV from mother to child.
Among the many risk factors for mother-to-child transmission is maternal intravenous drug use. Another additional and very important risk factor is the presence of HIV infection in the mother, which reduces the mother's immune response to HCV, in addition, HIV infection can infect trophoblasts, disrupting the integrity of the placenta and increasing the possibility of transmitting the virus through the broken placental barrier. The frequency of transmission of the virus during pregnancy with HCV monoinfection is 5-7%, and with co-infection - 15-18%.
Speaking about the timing of infection of a child from the mother, it should be noted that infection is considered intrauterine if a positive test for HCV RNA is detected during the examination of the child immediately at birth or during the first three days of his life. If HCV RNA was detected in a child during the first three years of
life, then the child was infected in the postpartum (peripartum) period. According to individual authors, intrauterine transmission of the virus is 30%, and perinatal - up to 50% of cases.
For the prevention of intrauterine infection of the fetus, the use of caesarean section was proposed. However, this procedure is not effective, as it has been shown that in more than 50% of cases, infection of the fetus occurs before the 34th week of pregnancy, in most cases between the 25th and 36th weeks.
Thus, it can be stated that currently the growing prevalence of HCV in pregnant women and women of reproductive age is a big problem. This is especially important in low- and middle-income countries, where about 90% of all people live and HCV treatment coverage in most of these countries is <10%.
Conclusion. Despite the successes achieved in the field of HCV therapy associated with the emergence of direct-acting antiviral drugs, as for pregnant women, there are no ready-made drugs for their treatment, and effective therapy for pregnant women infected with HCV is under development and its use is a matter of the future. Therefore, it is clear that the growing prevalence of HCV in pregnant women, which entails the transmission of infection to the child born, forces us to look for new ways of prevention in the detection of HCV in women of childbearing age. This can be done by using universal screening for HCV in women of reproductive age, and in pregnant women - not only in the first pregnancy, but also in all subsequent ones. In addition, the most comprehensive testing for HCV of newborns and children under 3 years of age is needed in order to determine the mode of infection and develop ways to prevent possible risks of infection of children from mothers with HCV. Such additional and timely expanded measures will influence the effective development of therapeutics and vaccines for both children and adults, i.e. new strategies are needed to address these challenges.
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BAKHRONOV JAKHONGIR JASUROVICH - student of the 521st group of the pediatric faculty of the Samarkand State Medical University, Samarkand, Uzbekistan.
MUHIDDINZODA RUKHSHONABONUNUMONKIZI - student of the 221st group of the medical faculty of the Samarkand State Medical University, Samarkand, Uzbekistan.
NIGMATULLAEV MUHAMMADJON NURALIYEVICH - student of the 522st group of the pediatric faculty of the Samarkand State Medical University, Samarkand, Uzbekistan.
KUDDUSOVMUSLIMBEK MUHSIN UGLI - student of the 522th group of the pediatric faculty of the Samarkand State Medical University, Samarkand, Uzbekistan.
JAMOLIDDINOVSHERALIBAXTIYOR UGLI - student of the 507th group of the pediatric faculty of the Samarkand State Medical University, Samarkand, Uzbekistan.