Core Series
The Why? Series
What’s The Deal With Viral Hepatitis Vaccination?

What’s the deal with viral hepatitis vaccination?

December 6, 2023

Chip Bowman

Viral hepatitis has been and remains a formidable global health challenge. To effectively combat this, we employ a powerful tool: vaccinations. In this discussion, we will delve into the intricacies of viral hepatitis and carefully examine the recommendations for vaccination across different patient groups with the goal of helping to elucidate the understanding of why viral hepatitis vaccinations still matter.

The WHO has established a goal and strategy to eliminate viral hepatitis as a major public health threat by 2030. This strategy, while addressing all five viral hepatitis viruses, focuses mainly on HBV and HCV given their public health burden. There remains significant morbidity and mortality associated with viral hepatitis that is growing in comparison to other infectious diseases.

Figure 1.Global burden of disease for major infectious diseases. Figure from WHO

Figure 2. Global burden of viral hepatitis related deaths from the WHO

Hepatitis A (CDC Reference)

Okay quick refresh – remind me, which is A, again?

Hepatitis A is one of those diseases you might see a test question about but are probably not going to see in inpatient medicine. That’s great because typically it’s mild and self-limited. It presents similarly to other viral hepatitis infections with vague symptoms including fever, malaise, anorexia, nausea, and abdominal discomfort, followed within a few days to a week by dark urine, pale stools, and jaundice. HAV has an incubation period of around 28 days with peak transmission before the onset of jaundice.

How do we get it?

Hepatitis A is transmitted from the fecal-oral route either form person-to-person transmission or contaminated food or water.

Where is it typically seen?

In highly endemic areas such as parts of Africa and Asia, many people likely get infected with HAV as children and are immune as adults. Fortunately, the incidence of HAV is decreasing globally while the age at midpoint of population immunity (AMPI - the youngest age at which half of the birth cohort has serologic evidence of prior exposure to hepatitis A virus) is increasing.

Figure 3. Estimated age at midpoint of population immunity (AMPI) to hepatitis A, by country. Image from CDC Yellowbook, adapted from Jacobsen 2018

In the US, we typically see HAV in people who have recently traveled to an endemic country or from consuming raw seafood. There have been outbreaks across 37 states in the US since 2016 involving approximately 44,650 cases, 27,250 hospitalizations, and 425 deaths.

Figure 4. Map of HAV outbreaks as of October 6, 2023. Image from the CDC.

Figure 3. Cumulative outbreak-associated hepatitis A cases reported, by state* — United States, August 1, 2016–December 31, 2020. Image from MMWR.

Okay but if HAV is so mild, why vaccinate at all?

In high-risk populations, such as the elderly and persons with chronic liver disease, HAV can be severe and even lead to fulminant liver failure resulting in the need for transplantation or leading to mortality.

Prolonged and relapsing HAV has been documented as well in 10-15% of infected persons, though fortunately there is no evidence of chronic HAV.

What’s the history of HAV vaccine development?

By 1945, researchers had demonstrated passive immunization with serum immunoglobulin could be administered effectively for postexposure prophylaxis against HAV postexposure prophylaxis against HAV Subsequent trials led to the development of the HAV vaccinations. The GlaxoSmithKlein (GSK) vaccine (HAVRIX) and the Merck Sharp & Dohme (MSD) vaccine (VAQTA) were licensed in the mid‐1990s in the United States and worldwide. One study of efficacy of the GSK vaccine in Thailand demonstrated a protective efficacy rate against HAV before and 5 months after a 1‐year booster was 94% and 99%, respectively, without serious adverse events.

Figure 5. Cumulative rates of symptomatic infection with HAV in the hepatitis A vaccine and control group trial in Thailand. Innis BLSR, Kunasol P, et al. Protection against hepatitis A by an inactivated vaccine. JAMA 1994;271:1328‐1334.

When did we start vaccinating?

For HAV, there was a gradual increase in recommendation to vaccinate in the United States beginning in 1996 in certain areas of high incidence. The guidelines expanded until 2006 when the recommendation became ubiquitous for children and resulted in a 95.5% decrease in reported hepatitis A cases.

Got it, now who gets vaccinated?

Children 12 months to 23 months in the United States get vaccinated. If a child has not received the HAV vaccine, it is recommended to vaccinate children 2 to 18 years old.

For adults, however, there is not a blanket recommendation, but rather those at “high risk.” This is in part because HAV is typically mild and self-limited and thus poses severe risk in only a small portion of the population, namely those who are immunocompromised, advanced age (according to the CDC this is age above 40!), with underlying medical conditions (read: vague, but seems on review just to reference HIV), or with chronic liver disease.

What about people exposed?

The CDC recommends post exposure prophylaxis with HAV vaccine for unvaccinated persons and HAV IgG for select groups. IG should be used for infants under a year old, immunocompromised persons, persons who have chronic liver disease, and persons for whom vaccine is contraindicated. IG is also preferred over hepatitis A vaccine for persons aged >40 years; however, vaccine may be used if IG cannot be obtained.

What are the travel recommendations?

Hepatitis A travel recommendations can be found here. While anyone traveling to an area with endemic HAV is at risk, those who visit rural areas with poor sanitation are higher risk.

You can also look specific locations up on the CDC Travel Destinations website.

Hepatitis B (CDC Reference)

Okay quick refresh – remind me, which is B, again?

Symptoms are similar to HAV and range from mild to fulminant liver failure (<1%). The average incubation period is 60 days from exposure to onset of abnormal serum ALT levels and 90 days from exposure to onset of jaundice. In contrast to HAV, however, HBV can lead to chronic infection. Chronic infection occurs among 80%–90% of persons infected during infancy, 30% of persons infected before age 6 years, and <1%–12% of persons infected as an older child or adult. Around one-quarter of persons who acquire chronic HBV as a child and 15% who acquire as an adult will die prematurely from cirrhosis or liver cancer. Treatment is supportive for acute HBV.