Talk:Abnormal Development - Hepatitis Virus

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Cite this page: Hill, M.A. (2019, August 18) Embryology Abnormal Development - Hepatitis Virus. Retrieved from


Hepatitis E virus: advances and challenges

Nat Rev Gastroenterol Hepatol. 2018 Feb;15(2):96-110. doi: 10.1038/nrgastro.2017.150. Epub 2017 Nov 22.

Nimgaonkar I1, Ding Q1, Schwartz RE2, Ploss A1.

At least 20 million hepatitis E virus (HEV) infections occur annually, with >3 million symptomatic cases and ∼60,000 fatalities. Hepatitis E is generally self-limiting, with a case fatality rate of 0.5-3% in young adults. However, it can cause up to 30% mortality in pregnant women in the third trimester and can become chronic in immunocompromised individuals, such as those receiving organ transplants or chemotherapy and individuals with HIV infection. HEV is transmitted primarily via the faecal-oral route and was previously thought to be a public health concern only in developing countries. It is now also being frequently reported in industrialized countries, where it is transmitted zoonotically or through organ transplantation or blood transfusions. Although a vaccine for HEV has been developed, it is only licensed in China. Additionally, no effective, non-teratogenic and specific treatments against HEV infections are currently available. Although progress has been made in characterizing HEV biology, the scarcity of adequate experimental platforms has hampered further research. In this Review, we focus on providing an update on the HEV life cycle. We will further discuss existing cell culture and animal models and highlight platforms that have proven to be useful and/or are emerging for studying other hepatotropic (viral) pathogens.

PMID: 29162935


The Ribavirin Pregnancy Registry: An Interim Analysis of Potential Teratogenicity at the Mid-Point of Enrollment

Drug Saf. 2017 Dec;40(12):1205-1218. doi: 10.1007/s40264-017-0566-6.

Sinclair SM1,2, Jones JK3, Miller RK4, Greene MF5, Kwo PY6, Maddrey WC7.

INTRODUCTION: Significant teratogenic effects have been demonstrated in all animal species exposed to ribavirin. Ribavirin is prescribed for chronic hepatitis C and is contraindicated in women who are pregnant and in the male sexual partners of women who are pregnant. Both sexes are advised to avoid pregnancy for 6 months after exposure. The Ribavirin Pregnancy Registry was established in 2003 to monitor pregnancy exposures to ribavirin for signals of possible human teratogenicity.

METHODS: This voluntary registry enrolls pregnant women with prenatal exposure to ribavirin. Exposure is classified as direct-women taking ribavirin during pregnancy or the 6 months prior to conception-or indirect-women exposed through sexual contact, 6 months prior to or during pregnancy, with a man who is taking or has taken ribavirin in the past 6 months. Women are followed until delivery and infants for 1 year. When enrollment is complete, birth defect rates will be compared with the Metropolitan Atlanta Congenital Defects Program's published rate of 2.67. Using data collected since inception in 2003 through February 2016, preliminary rates were calculated.

RESULTS: The registry has enrolled 272 pregnant women, with 180 live births: there were seven birth defect cases among 85 directly exposed women [7/85 (8.2%) (95% confidence interval (CI) 3.4-16.2)] and four birth defect cases among 95 indirectly exposed women [4/95 (4.2%) (95% CI 1.2-10.4)]. Of the 11 infants, nine had structural defects and two had chromosomal anomalies. Patterns suggesting a common etiology or relationship with ribavirin exposure are not seen.

CONCLUSION: Based on the patterns of birth defects reported, preliminary findings do not suggest a clear signal of human teratogenicity for ribavirin. However, the current sample size is insufficient for definitive conclusions, and ribavirin exposure should be avoided during pregnancy and during the 6 months prior to pregnancy, in accordance with prescribing information.


Comment in Is Ribavirin Teratogenic in Humans? No Evidence So Far. [Drug Saf. 2017] PMID: 28689333


Antiviral treatment among pregnant women with chronic hepatitis B

Infect Dis Obstet Gynecol. 2014;2014:546165. doi: 10.1155/2014/546165. Epub 2014 Dec 7.

Fan L1, Owusu-Edusei K Jr1, Schillie SF1, Murphy TV1.

Abstract OBJECTIVE: To describe the antiviral treatment patterns for chronic hepatitis B (CHB) among pregnant and nonpregnant women.

METHODS: Using 2011 MarketScan claims, we calculated the rates of antiviral treatment among women (aged 10-50 years) with CHB. We described the pattern of antiviral treatment during pregnancy and ≥1 month after delivery.

RESULTS: We identified 6274 women with CHB during 2011. Among these, 64 of 507 (12.6%) pregnant women and 1151 of 5767 (20.0%) nonpregnant women received antiviral treatment (P < 0.01). Pregnant women were most commonly prescribed tenofovir (73.4%) and lamivudine (21.9%); nonpregnant women were most commonly prescribed tenofovir (50.2%) and entecavir (41.3%) (P < 0.01). Among 48 treated pregnant women with an identifiable delivery date, 16 (33.3%) were prescribed an antiviral before pregnancy and continued treatment for at least one month after delivery; 14 (29.2%) started treatment during the third trimester and continued at least one month after delivery.

CONCLUSION: Among this insured population, pregnant women with CHB received an antiviral significantly less often than nonpregnant women. The most common antiviral prescribed for pregnant women was tenofovir. These data provide a baseline for assessing changes in treatment patterns with anticipated increased use of antivirals to prevent breakthrough perinatal hepatitis B virus infection.

PMID 25548510


Hepatitis B virus infection and pregnancy: a practical approach

Indian J Gastroenterol. 2012 Apr 21. [Epub ahead of print]

Kumar A. Source Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital, New Delhi, 110 060, India,


Hepatitis B virus (HBV) infection is a global problem and the world has 350 million carriers of chronic hepatitis B. Over 50 % of these have acquired their infection vertically from their mothers (mother-to-child transmission [MTCT]). Majority (>90 %) of vertically-acquired infection results into chronic infection, due to induction of an immune-tolerant state. Hence, management of chronic HBV during pregnancy and strategies to prevent MTCT would go a long way in global control of HBV infection and the morbidity and mortality associated with it. However, chronic HBV infection in pregnancy presents a unique challenge, because of existence of a complex relationship between the physiological changes of pregnancy and the pathophysiological response of body to HBV. This relationship may lead to a varied presentation of the patient to the doctor depending on the period of her pregnancy and stage of her liver disease. Each of these modes of presentation raises issues that need to be addressed for successful maternal and fetal outcome, including prevention of MTCT of HBV. This review will try to give a practical approach in addressing these issues.

PMID 22528342

Altered microRNA expression profile in maternal and fetal liver of HBV transgenic mouse model

J Matern Fetal Neonatal Med. 2012 Apr 21. [Epub ahead of print]

Guo L, Yang X, Duan T. Source Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine , Shanghai, PR-China, Shanghai , China.


Objective: MicroRNAs (miRNAs) regulate gene expression in a post-transcriptional sequence-specific manner. Expression profile analysis of miRNAs in liver is necessary to understand the possible roles of miRNAs in hepatitis B virus (HBV) infection. Methods: We obtained HBV-positive liver samples from mice, using HBV transgenic mouse model. MicroRNA expression was analyzed with Agilent microRNA Array and validated using quantitative real-time PCR analysis. Results: RNA samples from liver of HBV transgenic mouse liver exhibited notably different miR profiles from negative controls for both maternities and fetuses. Significant differences in expression profile of miRNAs were also found in fetal and maternal group of HBV transgenic mouse model. Expression of miR-1892 and miR-1187 decreased by approximately 2-fold (p < 0.01), whereas expression of miR-92a increased by more than 6-fold (p < 0.001) in the fetal group, as validated by qPCR. Conclusion: Deregulation of miRNAs expression in fetal livers could be implicated in HBV intrauterine infection. Further study is warranted to identify the target genes of these miRNAs and their function. Besides, these data might offer new ideas for blocking HBV intrauterine infection.

PMID 22462411

Chronic hepatitis B infection and pregnancy

Obstet Gynecol Surv. 2012 Jan;67(1):37-44.

Giles ML, Visvanathan K, Lewin SR, Sasadeusz J. Source Department of Infectious Diseases, Monash Medical Centre, and Infectious Disease Unit, The Alfred Hospital, Melbourne, Australia.


It is estimated that 350 to 400 million individuals worldwide are chronically infected with hepatitis B virus (HBV). In regions of high endemicity, many of these are females of reproductive age who are an important source for perinatal transmission. There are a number of issues specific to the women of childbearing age who have chronic HBV infection, including the safety of antiviral therapy during pregnancy and breast-feeding, the changes in the immune system during pregnancy and postpartum that may impact on the natural history of HBV, and the emerging role of antivirals to reduce perinatal transmission of HBV. For women in their reproductive years who require treatment, many of the available antivirals have not been studied in pregnant or breast-feeding women and their use requires the development of a carefully considered strategy, considering the impact of both the disease and treatment on the mother and fetus/infant. The purpose of this article is to (1) review data regarding the mechanisms and timing of perinatal HBV infection; (2) review data on interventions, particularly antiviral therapy, to reduce perinatal transmission beyond the protection afforded by hepatitis B immunoglobulin and vaccination; (3) summarize the immunological changes associated with pregnancy and the potential effect these may have on the natural history of HBV infection; and (4) summarize the information currently available for antiviral therapy available for HBV treatment, focusing specifically on safety data pertaining to reproduction, pregnancy, and breast-feeding.

TARGET AUDIENCE: Obstetricians & Gynecologists and Family Physicians.

LEARNING OBJECTIVES: After completing this CME activity physicians should be better able to classify the interventions to reduce mother-to-child transmission of hepatitis B including antivirals, caesarean section, hepatitis B immunoglobulin and hepatitis B vaccine, assess the immunological changes associated with pregnancy and the potential effect this may have on the natural history of HBV infection and apply the information currently available for antiviral therapy licensed for HBV treatment, focusing specifically on safety data in pregnancy and during breastfeeding.

PMID 22278077