Abnormal Development - Hepatitis Virus

Embryology - 2 Dec 2023        Expand to Translate
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Educational Use Only - Embryology is an educational resource for learning concepts in embryological development, no clinical information is provided and content should not be used for any other purpose.

Introduction

Hepatitis A virions (CDC)

Hepatitis B virions (CDC)

Hepatitis (inflammation of the liver) is caused in humans by one of 7 viruses (A, B, C, D, E) with the 2 additional F has not been confirmed as a distinct genotype; and G is a newly described flavivirus. CDC states that all of these viruses can cause an acute disease with symptoms lasting several weeks including yellowing of the skin and eyes (jaundice); dark urine; extreme fatigue; nausea; vomiting and abdominal pain. It can take several months to a year to feel fit again.

An estimated 400 million people worldwide are living with chronic hepatitis B infection.

liver | liver histology

Some Recent Findings

Hepatitis E virus: advances and challenges "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." The Ribavirin Pregnancy Registry: An Interim Analysis of Potential Teratogenicity at the Mid-Point of Enrollment "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. 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. 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. 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. ClinicalTrials.gov identifier: NCT00114712."

More recent papers

This table allows an automated computer search of the external PubMed database using the listed "Search term" text link. This search now requires a manual link as the original PubMed extension has been disabled. The displayed list of references do not reflect any editorial selection of material based on content or relevance. References also appear on this list based upon the date of the actual page viewing. References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability. More? References | Discussion Page | Journal Searches | 2019 References | 2020 References Search term: Teratogen Hepatitis Virus

Older papers

These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table. See also the Discussion Page for other references listed by year and References on this current page. Update on childhood and adolescent immunizations: selected review of US recommendations and literature: part 2 "Vaccine coverage is relatively static or improving for the vaccines included in the 2010 annual harmonized immunization schedules. Providers should be reviewing patients' immunization records at each visit to take advantage of any opportunity to administer indicated, age-appropriate vaccines. There have been infectious disease outbreaks among highly immunized populations, although unvaccinated or undervaccinated individuals continue to play large roles in the spread of disease. Infants, many of whom are too young to be vaccinated, continue to bear a large disease burden, which underscores the importance of cocooning and, in some cases, vaccination of pregnant women. Influenza, measles, mumps, and rubella, varicella, hepatitis A, meningococcal conjugate, human papillomavirus, diphtheria and tetanus toxoids and acellular pertussis, and tetanus and diphtheria toxoids and acellular pertussis vaccines are reviewed in this second of two articles."

Hepatitis Virus

Virus particles measure 42nm in overall diameter and contain a 27nm diameter DNA-based core.

Hepatitis Transmission Risk to the Fetus

Hepatitis A

• Fetal transmission of virus occurs with extreme rarity.

Hepatitis B

• Can occur as a consequence of intrapartum exposure, transplacental transmission, and breastfeeding.
• 20% - 30% of HBsAg-positive/HbeAg-negative women will transmit virus to their infants.
• 90% of HBsAg- and HBeAg-positive women will transmit virus to their infants.
• Immunoprophylaxis at birth with both HBIG and Hepatitis B vaccine within 12 hours of birth decreases the risk of transmission.
• Passive (HBIG) and active immunization is 85-95% effective in preventing neonatal HBV infection.
• Chronic infection occurs in almost all children who are infected with hepatitis B during the perinatal period and in up to 50% of children who become infected between 1 and 5 years of age.

Hepatitis C

• The overall risk of transmission is approximately 2-6% with unknown maternal viral titers.
• All pregnant women with HCV should have viral titers performed.
• The placenta appears to act as an immunological organ providing antiviral protection against hepatitis C viral transmission in the majority of cases.
• Children and adolescents with chronic infection generally have no symptoms.
• Breast-feeding does not appear to transmit virus.

Data Sources

Hepatitis E virions (CDC)

Adult Hepatitis B Treatment

Women who are HBsAg-positive have a very high risk for vertical transmission to their infants. NIH currently recommends that infants of HBsAg-positive women receive hepatitis B immunoglobulin and hepatitis B vaccination within 12 hours of birth and receive a complete set of 3 vaccinations and long-term follow-up. This has been shown to substantially reduce the risk for perinatal transmission.

U.S. Food and Drug Administration have approved 7 agents, used as monotherapy or in combination, for use in the treatment of adults with Hepatitis B.

• interferons (interferon-α2b and peginterferon-α2a)
  • Interferon use has a defined self-limited course.
• nucleoside or nucleotide analogues (lamivudine, adefovir, entecavir, tenofovir, and telbivudine)
  • therapy can be long-term or indefinite treatment.

Ribavirin

Ribavirin (tribavirin) an antiviral drug used to treat hepatitis C, RSV infection, and viral hemorrhagic fever. For hepatitis C, it is used in combination with other medications such as simeprevir, sofosbuvir, peginterferon alfa-2b or peginterferon alfa-2a. Formula: C8H12N4O5.

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. In the USA a voluntary registry has been established for pregnant women (272 pregnant women, with 180 live births) with prenatal exposure to ribavirin.

Exposure is classified as

• direct-women taking ribavirin during pregnancy
• 6 months prior to conception
• 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.

A preliminary report from this study states: "Patterns suggesting a common etiology or relationship with ribavirin exposure are not seen. 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." ClinicalTrials.gov identifier: NCT00114712.

Liver Damage

Sequelae of chronic Hepatitis C infection are progressive liver fibrosis leading to cirrhosis, end-stage liver disease, and Hepatocellular Carcinoma (HCC).

References

Books

• Medical Microbiology. 4th edition. Baron S, editor. Galveston (TX): University of Texas Medical Branch at Galveston; 1996.
  • Chapter 70 Hepatitis Viruses
• Molecular Biology of the Cell. 4th edition. Alberts B, Johnson A, Lewis J, et al. New York: Garland Science; 2002.
  • Viruses Exploit Host Cell Machinery for All Aspects of Their Multiplication
  • Some Viruses Use Transpositional Site-specific Recombination to Move Themselves into Host Cell Chromosomes
• Guidelines for the Screening, Care and Treatment of Persons with Hepatitis C Infection. Geneva: World Health Organization; 2014 Apr. Available from: http://www.ncbi.nlm.nih.gov/books/NBK263483/

Reviews

Yogeswaran K & Fung SK. (2011). Chronic hepatitis B in pregnancy: unique challenges and opportunities. Korean J Hepatol , 17, 1-8. PMID: 21494071 DOI.

Articles

Giles ML, Visvanathan K, Lewin SR & Sasadeusz J. (2012). Chronic hepatitis B infection and pregnancy. Obstet Gynecol Surv , 67, 37-44. PMID: 22278077 DOI.

Kumar A. (2012). Hepatitis B virus infection and pregnancy: a practical approach. Indian J Gastroenterol , 31, 43-54. PMID: 22528342 DOI.

Connell LE, Salihu HM, Salemi JL, August EM, Weldeselasse H & Mbah AK. (2011). Maternal hepatitis B and hepatitis C carrier status and perinatal outcomes. Liver Int. , 31, 1163-70. PMID: 21745298 DOI.

Search Pubmed

Search PubMed: term = Hepatitis Virus teratology | embryo infection | fetal infection | neonatal infection

External Links

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.

• International Committee on Taxonomy of Viruses
• Australian Government The Australian Immunisation Handbook 9th Edition 2008
• NIH (USA) Consensus Development Conference Management of Hepatitis B October 20–22, 2008 Bethesda, Maryland | Management of Hepatitis C: 2002 June 10-12, 2002

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Glossary Links

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Cite this page: Hill, M.A. (2023, December 2) Embryology Abnormal Development - Hepatitis Virus. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Hepatitis_Virus

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© Dr Mark Hill 2023, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G