The document provides an overview of hepatitis A and E, detailing their history, epidemiology, transmission, diagnosis, clinical features, treatment, and prevention. Hepatitis A is primarily transmitted via fecal-oral routes and has a significant incidence in developing regions, while hepatitis E transmission typically occurs through contaminated water and can cause severe complications, particularly in pregnant women. Vaccination is key in preventing hepatitis A, with specific guidelines for various risk groups, whereas hepatitis E treatment options are limited and vaccine development is ongoing.

1. Hepatitis A and E
Rwanda Endoscopy Week
10/31/2023

2. Overview
• History
• HAV
• Epidemiology
• Transmission
• Diagnosis
• Clinical Features
• Treatment
• Prevention

3. Hepatitis A

4. History
• Epidemic jaundice first described by Hippocrates
• Outbreaks of jaundice reported in 17th
and 18th
centuries in
association with military campaigns
• “Infectious Hepatitis” was differentiated by epidemiology from
hepatitis B in the 1940s
• Serologic tests in 1970s differentiated hepatitis A from non-B hepatitis
• First isolated in 1979
• Vaccines first licensed in US in 1995

5. HAV
• Picornavirus (RNA)
• Virus can be stable in
environment for months
• Humans are only natural
host
• Replicates in the liver
• 10-12 days after infection,
virus is present in blood and
is excreted via biliary system
to the feces
Shin et al 2018

6. Transmission
• Transmission is fecal-oral
• Rare cases of confirmed transmission with blood transfusion or solid-organ
transplant
• Most infectious 1-2 weeks prior to onset of clinical illness when viral
concentration in stool is highest
• Incubation period ~28 days

7. Epidemiology
• 100 million HAV infections and 1.5 million symptomatic cases annually
worldwide
• 15,000 to 30,000 deaths/year
• Greater prevalence in developing and low-income regions
• Hyperendemic in sub-Saharan Africa and South Asia
• Intermediate endemicity in Latin America, Middle East, North Africa,
Eastern Europe and middle-income regions in Asia

8. US
Epidemiology
• Vaccine first available in
US 1996
• Over 95% reduction of
cases from 1996 to
2011
• Reemerged in 2016 with
widespread outbreaks in
people who use IV drugs
and in homeless
population
CDC

9. Risk Factors
• International travelers (especially those with travel to rural or hig- risk
regions)
• Adoptees or immigrants from high-risk countries
• MSM population
• Homelessness
• IVDU

10. Migures et al, 2021

11. Diagnosis
• Cannot be distinguished from other viral hepatitis based on clinical
features
• Serologic testing:
• Acute hepatitis A: detectable IgM anti-HAV in serum
• Becomes detectable 5-10 days prior to symptom onset, can persist for up to 6 months
• Convalescent/prior infection: IgG anti-HAV in serum
• IgG anti-HAV confers immunity
• PCR can be used to amplify/sequence virus, used to investigate
hepatitis A outbreaks

12. Shin et al, 2018

13. Clinical Features
• Abrupt onset of fever, malaise, anorexia, nausea, abdominal pain, jaundice
• Clinical illness generally improves by 2 months, though 10% will have
prolonged or relapsing illness for up to 6 months
• Complications
• Relapsing hepatitis, cholestatic hepatitis A, hepatitis A triggering autoimmune
hepatitis, sub-fulminant hepatitis, and fulminant hepatitis have also been reported
• Fulminant hepatitis is the most severe rare complication, with mortality estimates up
to 80%
• Overall case-fatality 0.3% to 0.6% for all ages, though up to 1.8% in patients
over 50
• Children are generally asymptomatic

14. Shin et al, 2018

15. Treatment
• Supportive care
• Referral to transplant cater for suspected cases of HAV-associated
fulminant liver failure

16. Prevention
• Hepatitis A vaccination
• Hep A (Havrix, Vaqta)
• Hep A-HepB (Twinrix)
• Current recommendations:
• Vaccination of all children over the age of one in all 50 states
• Vaccination of all persons over the age of one experiencing homelessness
• Vaccination of all children and adolescents ages 2 through 18 years who have
not previously received HepA vaccine
• Vaccination of all persons with HIV age 1 year or older
• All persons with risk factors
• Patients with chronic liver disease

17. Post-exposure prophylaxis
• Administer vaccine ASAP within 2 weeks of exposure
• Co-administer Immune Globulin (0.1 mL/kg) in patients over 40 or if
at high risk (HIV, chronic liver disease, high risk exposure)
• Immune Globulin 0.1 mL/kg recommended for those under 1 year old
or if vaccine is contraindicated

18. Hepatitis E

19. Overview
• History
• HEV
• Epidemiology
• Transmission
• Diagnosis
• Clinical Features
• Treatment
• Vaccine Development

20. History
• Unexplained hepatitis in early
1980s
• First visualized under electron
microscopy by Russian
virologists in 1983

21. HEV
• Positive strand non-enveloped RNA virus from Hepeviridae family
• 8 genotypes
• Genotypes HEV1, HEV2, HEV3, and HEV4 most frequently cause
infections in Humans

22. Epidemiology

23. Transmission
• Genotypes HEV1 and HEV2 result in large outbreaks from
contaminated water supply
• HEV3 and HEV4 are zoonotic, transmission is fecal contamination of
water and from eating meat/close contact with infected animals, with
pig the main reservoir
• Vertical transmission of HEV1 and HEV2 from mother to fetus
• HEV1 transmission through blood transfusion has been reported

24. Diagnosis
• Incubation period 2-6 weeks
• Diagnosis is made with HEV RNA in either blood or stool
• HEV RNA detectable in serum 3 weeks after exposure
• Viral shedding in stool for 4-6 weeks
• Anti-HEV IgM generally only detectable for 3-4 months
• Anti-HEV IgG does not confer lifelong immunity
• Chronic HEV infection: persistence of HEV RNA in blood or stool for at
least 3 months

25. Clinical Features-Acute
• Generally asymptomatic or mildly symptomatic
• Infection resulting in jaundice occurs in 5-30% of cases
• Prodromal phase lasting ~1 week: malaise, fever, body aches, nausea,
vomiting
• Icteric phase lasting ~1 week
• Convalescent phase: resolution of symptoms and jaundice
• HEV1 and HEV2 generally cause more severe acute hepatitis than
HEV3 and HEV4

26. Special populations
• Pregnant women: high morbidity and mortality, especially in 3rd
trimester
• Mortality up to 20%, due to eclampsia, hemorrhagic complications, and liver
failure
• Newborns: Risk of maternal-fetal transmission, with complications of
hypoglycemia, hepatitis, death
• Patients with chronic liver disease

27. Clinical Features-Chronic
• Immunosuppressed solid-organ transplant recipients: HEV clearance
not achieved
• Diagnosed by persistent HEV RNA, as anti-HEV IgM and IgG may
remain negative
• Characterized by fatigue but often asymptomatic, with mild elevation
in liver associated enzymes
• Chronic hepatitis and cirrhosis with HEV3 and HEV4
• 20-50% of patients with HEV1 developed chronic infection
• Within 2-5 years, 10% of patients with chronic HEV develop cirrhosis
• Developing chronic hepatitis associated with tacrolimus dose and low lymphocyte count
rather than viral load

28. Extra hepatic manifestations
• Guillain-Barre syndrome
• Neuralgic amyotrophy
• Lymphoma
• Pancreatitis
• Thrombocytopenia
• Meningitis
• Cryoglobulinemia
• Glomerulonephritis

29. Horvatits et al, 2019

30. Treatment
• No approved drugs for HEV
• HEV spontaneously cleared in most cases
• In severe cases of ACLF, treatment with ribavirin has resulted in viral
clearance and normalization of LAEs

31. Treatment of chronic HEV
• Dose reduction of immunosuppressive therapy
• Pegylated interferon-alpha can be considered in liver transplant
patients, however, is contraindicated in renal, pancreas, heart, and
lung transplants
• Ribavirin has been used in these cases, with no RCTs to support use
• Sofosbuvir has been used for ribavirin-resistant HEV infections

32. Vaccine development
• HEV vaccine based on HEV1 developed in China
• Phase 3 trial including more that 100,000 participants
• Only 60 cases of HEV identified, with 7 in the vaccine arm
• NIH is performing Phase 1 trial

33. References
• Shin, E.-C., Jeong, S.-H., 2018. Natural History, Clinical Manifestations, and Pathogenesis of Hepatitis A. Cold Spring Harbor
Perspectives in Medicine 8, a031708.. doi:10.1101/cshperspect.a031708
• Migueres M, Lhomme S, Izopet J. Hepatitis A: Epidemiology, High-Risk Groups, Prevention and Research on Antiviral Treatment.
Viruses. 2021 Sep 22;13(10):1900. doi: 10.3390/v13101900. PMID: 34696330; PMCID: PMC8540458.
• Abutaleb A, Kottilil S. Hepatitis A: Epidemiology, Natural History, Unusual Clinical Manifestations, and Prevention. Gastroenterol Clin
North Am. 2020 Jun;49(2):191-199. doi: 10.1016/j.gtc.2020.01.002. Epub 2020 Mar 29. PMID: 32389358; PMCID: PMC7883407.
• World Health Organization. (2019). WHO immunological basis for immunization series: module 18: hepatitis A, update 2019. World
Health Organization.
• Aslan, A.T., Balaban, H.Y., 2020. Hepatitis E virus: Epidemiology, diagnosis, clinical manifestations, and treatment. World Journal of
Gastroenterology 26, 5543–5560.. doi:10.3748/wjg.v26.i37.5543
• Li, P., Liu, J., Li, Y., Su, J., Ma, Z., Bramer, W.M., Cao, W., Man, R.A., Peppelenbosch, M.P., Pan, Q., 2020. The global epidemiology of
hepatitis E virus infection: A systematic review and meta analysis. Liver International 40, 1516–1528.. doi:10.1111/liv.14468
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• Horvatits T, Schulze Zur Wiesch J, Lütgehetmann M, Lohse AW, Pischke S. The Clinical Perspective on Hepatitis E. Viruses. 2019 Jul
5;11(7):617. doi: 10.3390/v11070617. PMID: 31284447; PMCID: PMC6669652.