THE HEPATITIS VIRUSES

JAYESH A. PATEL, MD, DTM&H

Learning Your “A B C s”

Conflicts of Interest

No financial or other conflicts of interest for this talk.

Hepatitis causing Viruses

Acute hepatitis may occur as part of the clinical course of a number of viral infections, including Human Cytomegalovirus, Epstein-Barr virus, Herpes Simplex Virus, Yellow Fever Virus and Rubella.

The term "hepatitis virus" is usually used to describe infections caused by agents whose primary tissue tropism is the liver. At least five hepatitis viruses have been recognized and these have been named, hepatitis A, B, C, D and E.

Clinical Features

Hepatitis due to all these viruses presents clinically in a very similar fashion, especially during the acute phase. Thus, a specific diagnosis can only be made in the laboratory.

The majority of infections are often asymptomatic or produce only mild non-specific symptoms.

Common clinical features include: anorexia, nausea, vomiting, right upper quadrant pain and raised liver enzymes AST and ALT. Jaundice is the hall mark of infection, but tends to develop late. Anicteric cases are also very common.

Hepatitis A

Family: PicornaviridaeStructure: small; 27 nm in diameter, non-enveloped spherical particle

Hepatitis A: Key Facts

Hepatitis A can cause mild to severe illness.

Globally, there are an estimated 1.4 million cases of hepatitis A every year.

The hepatitis A virus is transmitted through ingestion of contaminated food and water, or through direct contact with an infectious person.

Hepatitis A is associated with a lack of safe water and poor sanitation.

Hepatitis A: Key Facts

Epidemics can be explosive in growth and cause significant economic losses.

Improved sanitation and the hepatitis A vaccine are the most effective ways to combat the disease.

Hepatitis A rates in the United States have declined by 95% since Hepatitis A vaccine first became available in 1995. In 2010, 1,670 acute symptomatic cases of Hepatitis A were reported. After adjusting for asymptomatic infection and underreporting, the estimated number of new infections was 17,000

Hepatitis A: Clinical Features

Incubation period 2-7 weeks (mean 28 days)

Symptoms of hepatitis A range from mild to severe, and can include fever, malaise, loss of appetite, diarrhea, nausea, abdominal discomfort, dark-colored urine and jaundice 

Pre-icteric phase lasting about 5 days.

The subsequent icteric phase resolves within 3 months in 85% of cases.

Hepatitis A: Clinical Features

Convalescence may be prolonged, and fatigue and alcohol intolerance can last up to 18 months. There is no chronic form of the disease.

Milder disease than Hepatitis B; asymptomatic infections are very common, especially in children. Adults, especially pregnant women, may develop more severe disease.

Fulminant hepatitis: rare; 0.3-1.8 % of casesHighest risk: pregnant women, elderly, pre-existing liver disease, other chronic medical conditions

Hepatitis A: Pathogenesis

Virus enters via the gut; replicates in the alimentary tract and spreads to infect the liver, where it multiplies in hepatocytes. Viremia is transient. Virus is excreted in the stools for two weeks preceding the onset of symptoms.

Hepatitis A: Epidemiology

Hepatitis A: Diagnosis

Virus cannot be cultured in vitro from clinical material; diagnosis depends on:Serology HAV-specific IgM

HAV IgM Total HAV Antibody (IgM and IgG)

Results Indicate

Positive  --- Acute HAV infection

Negative Positive No active infection, but previous HAV exposure; has developed immunity to HAV

 Negetive Positive Has been exposed to HAV but does not rule out acute infection

 negetive Negative No current or previous HAV infection; vaccine may be recommended if at risk

What does the Hepatitis A test result mean?If you have not been given the hepatitis vaccine, results of

hepatitis testing indicates the following:

Hepatitis A

Hepatitis A Treatment

There is no specific treatment for hepatitis A. Therapy is aimed at maintaining comfort and adequate nutritional balance, including replacement of fluids that are lost from vomiting and diarrhea.

Hepatitis A: Prevention

Hygiene: Food hygiene, Hand hygiene

Active ImmunizationInactivated cell culture derived vaccine is available; it is recommended for travelers to developing countries and, indeed, all adults who are not immune. It is the recommended form of post-exposure prophylaxis if the exposure is identified early, and if there are no predisposing risk factors for severe disease. If there are such risk factors, or if prophylaxis is delayed, passive immunization in addition to vaccination is recommended.

Passive immunisationNormal immunoglobulin (antibody prepared from pooled human serum) given to close contacts of acute cases.Protection is short lived: three months

Hepatitis A Vaccines

Havrix and Vaqta, Twinrix

Hepatitis A vaccination is recommended for all children older than age 1.

People who work or travel in areas where hepatitis A is common should be vaccinated. These areas include Africa, Asia (except Japan), the Mediterranean, Eastern Europe, the Middle East, Central and South America, Mexico, and parts of the Caribbean.

If you are traveling to these areas before you are fully immunized (fewer than 4 weeks after your first shot), you should get a preventive dose of immunoglobulin (IG). If you are just a short-term traveler to these areas, you may wish to receive immunoglobulin (IG) instead of the vaccine.

Hepatitis A Vaccine

Other people who are at higher risk for hepatitis A include:

People who use recreational, injectable drugs People who work with the hepatitis A virus in a laboratory

or with primates that may be infected with the virus People who have chronic liver disease People who receive clotting factor concentrate to treat

hemophilia or other clotting disorders Military personnel Men who have sex with other men Employees of child day care centers People who care for patients living in long-term nursing

homes and other facilities

Hepatitis A Vaccines

Post-exposure Prophylaxis: Hepatitis A

Persons who have recently been exposed to HAV and who have not been vaccinated previously should be administered a single dose of Hepatitis A vaccine or IG (0.02 mL/kg) as soon as possible, within 2 weeks after exposure. The guidelines vary by age and health status:

For healthy persons aged 12 months–40 years, Hepatitis A vaccine at the age-appropriate dose is preferred to IG because of the vaccine’s advantages, including long-term protection and ease of administration, as well as the equivalent efficacy of vaccine to IG.

For persons aged 40 years and older, IG is preferred because of the absence of information regarding vaccine performance in this age group and because of the more severe manifestations of Hepatitis A in older adults. The magnitude of the risk of HAV transmission from the exposure should be considered in decisions to use vaccine or IG in this age group. 

Vaccine can be used if IG cannot be obtained. IG should be used for children aged less than12 months,

immunocompromised persons, persons with chronic liver disease, and persons who are allergic to the vaccine

Which groups do NOT need routine vaccination against Hepatitis A?

Food service workers.  Consideration may be given to vaccination of employees who work in areas where community-wide outbreaks are occurring and where state and local health authorities or private employers determine that such vaccination is cost-effective.

Health care workers.  If a patient with Hepatitis A is admitted to the hospital, routine infection-control precautions will prevent transmission to hospital staff.

Children under 12 months of age. Because of the limited experience with Hepatitis A vaccination among children in this age group, the vaccine is not currently licensed for children age <12 months.

Child care center attendees. The frequency of outbreaks of Hepatitis A is not high enough in this setting to warrant routine Hepatitis A vaccination of staff

Residents of institutions for developmentally disabled persons. The occurrence of HAV infection has diminished, and routine vaccination against Hepatitis A is no longer recommended for this population.

Who requires protection (i.e., IG or Hepatitis A vaccine) after exposure to HAV?

Close personal contacts. Close personal contacts of persons with serologically confirmed Hepatitis A (i.e., through a blood test), including: Household and sex contacts Persons who have shared illicit drugs with

someone with Hepatitis A Consideration should also be given for other

types of ongoing, close personal contact with a person with Hepatitis A (e.g., a regular babysitter or caretaker).

Who requires protection (i.e., IG or Hepatitis A vaccine) AFTER exposure to HAV?

Child-care center staff, attendees, and attendees' household members

PEP should be administered to all previously unvaccinated staff and attendees of child care centers or homes if 1) one or more cases of Hepatitis A are recognized in children or employees or 2) cases are recognized in two or more households of center attendees.

In centers that provide care only to older children who no longer wear diapers, PEP need be administered only to classroom contacts of the index patient (i.e., not to children or staff in other classrooms).

When an outbreak occurs (i.e., Hepatitis A cases in three or more families), PEP should also be considered for members of households that have diaper-wearing children attending the center.

If a case of Hepatitis A is found in a school, hospital, or office setting, what should be done?

If a single case of Hepatitis A is identified in a school (other than a child care setting in which children wear diapers), office, or other work setting, and if the source of infection is outside the school or work setting, PEP (i.e., injection of IG or Hepatitis A vaccine) is not routinely recommended. Similarly, when a person who has Hepatitis A is admitted to a hospital, staff should not routinely be administered PEP; instead, careful hygienic practices should be emphasized.

However, if it is determined that Hepatitis A has been spread among students in a school or among patients and staff in a hospital, PEP should be administered to unvaccinated persons who have had close contact with an infected person.

Hepatitis B: Key Facts

Hepatitis B is a viral infection that can cause both acute and chronic disease.

The virus is transmitted through contact with the blood or other body fluids of an infected person.

About 240 million people are living with chronic hepatitis B and 600 000 people die every year due to the consequences of hepatitis B.(USA 1 mil./4000)

Hepatitis B is an important occupational hazard for health workers.

Hepatitis B is preventable with the currently available safe and effective vaccines.

Hepatitis B: Epidemiology

In highly endemic areas, HBV is most commonly spread from mother to child at birth, or from person to person in early childhood.

Perinatal or early childhood transmission may also account for more than one third of chronic infections in areas of low endemicity, although in those settings, sexual transmission and the use of contaminated needles, especially among injecting drug users, are the major routes of infection.

The hepatitis B virus can survive outside the body for at least seven days. During this time, the virus can still cause infection if it enters the body of a person who is not protected by the vaccine.

The hepatitis B virus is not spread by contaminated food or water, and cannot be spread casually in the workplace.

The incubation period of the hepatitis B virus is 75 days on average, but can vary from 30 to 180 days. The virus may be detected 30 to 60 days after infection and persists for variable periods of time.

Hepatitis B Prevalence

Hepatitis B Serology

Hepatitis B surface antigen (HBsAg): A protein on the surface of HBV; it can be detected in high levels in serum during acute or chronic HBV infection. The presence of HBsAg indicates that the person is infectious. The body normally produces antibodies to HBsAg as part of the normal immune response to infection. HBsAg is the antigen used to make Hepatitis B vaccine.

Hepatitis B surface antibody (anti-HBs): The presence of anti-HBs is generally interpreted as indicating recovery and immunity from HBV infection. Anti-HBs also develops in a person who has been successfully vaccinated against Hepatitis B.

Hepatitis B Serology

IgM antibody to Hepatitis B core antigen (IgM anti-HBc): Positivity indicates recent infection with HBV (≤6 months). Its presence indicates acute infection.

Total Hepatitis B core antibody (anti-HBc): Appears at the onset of symptoms in acute Hepatitis B and persists for life. The presence of anti-HBc indicates previous or ongoing infection with HBV in an undefined time frame.

Hepatitis B Serology

Hepatitis B e antigen (HBeAg): A secreted product of the nucleocapsid gene of HBV that is found in serum during acute and chronic Hepatitis B. Its presence indicates that the virus is replicating and the infected person has high levels of HBV.

Hepatitis B e antibody (HBeAb or anti-HBe): Produced by the immune system temporarily during acute HBV infection or consistently during or after a burst in viral replication. Spontaneous conversion from e antigen to e antibody (a change known as seroconversion) is a predictor of long-term clearance of HBV in patients undergoing antiviral therapy and indicates lower levels of HBV.

Tests Results Interpretation

HBsAganti-HBcanti-HBs

negativenegativenegative

Susceptible

HBsAganti-HBcanti-HBs

negativepositivepositive

Immune due to natural infection

HBsAganti-HBcanti-HBs

negativenegativepositive

Immune due to Hepatitis B vaccination

HBsAganti-HBc

IgM anti-HBcanti-HBs

positivepositivepositivenegative

Acutely infected

HBsAganti-HBc

IgM anti-HBcanti-HBs

positivepositivenegativenegative

Chronically infected

HBsAganti-HBcanti-HBs

negativepositivenegative

1.Interpretation unclear; four possibilities: Resolved infection (most common)2.False-positive anti-HBc, thus susceptible3."Low level" chronic infection4.4. Resolving acute infection

Hepatitis B Serology Interpretation

-

Hepatitis B serology

How long does it take for blood to test HBsAg-positive after exposure to HBV?

HBsAg will be detected in an infected person’s blood an average of 4 weeks (range: 1–9 weeks) after exposure to the virus. About 1 of 2 patients will no longer be infectious by 7 weeks after onset of symptoms, and all patients who do not remain chronically infected will be HBsAg-negative by 15 weeks after onset of symptoms

Who should be vaccinated against Hepatitis B?

All infants, beginning at birthAll children aged <19 years who have not been

vaccinated previouslySusceptible sex partners of Hepatitis B surface antigen

(HBsAg)-positive personsSexually active persons who are not in a long-term,

mutually monogamous relationship (e.g., >1 sex partner during the previous 6 months)

Persons seeking evaluation or treatment for a sexually transmitted disease

Men who have sex with menInjection drug usersSusceptible household contacts of HBsAg-positive

persons

Who should be vaccinated against Hepatitis B?

Health care and public safety workers at risk for exposure to blood or blood-contaminated body fluids

Persons with end-stage renal disease, including predialysis, hemodialysis, peritoneal dialysis, and home dialysis patients

Residents and staff of facilities for developmentally disabled persons

Travelers to areas with high Hepatitis B endemicityPersons with chronic liver diseasePersons with HIV infectionUnvaccinated adults with diabetes mellitus who are aged

19 through 59 years (discretion of clinicians for unvaccinated adults with diabetes mellitus who are aged ≥60 years)

All other persons seeking protection from HBV infection

Single-antigen Hepatitis B vaccinesENGERIX-B®RECOMBIVAX HB®

Combination vaccinesCOMVAX®: Combined Hepatitis B-Haemophilus influenzae type b (Hib) conjugate vaccine. Cannot be administered before age 6 weeks or after age 71 months.PEDIARIX®: Combined Hepatitis B, diphtheria, tetanus, acellular pertussis (DTaP), and inactivated poliovirus (IPV) vaccine. Cannot be administered before age 6 weeks or after age 7 years.TWINRIX®: Combined Hepatitis A and Hepatitis B vaccine. recommended for persons aged ≥18 years who are at increased risk for both Hepatitis A virus and HBV infections.

What are the Hepatitis B vaccines licensed in the United States?

• Can a patient receive the first dose of Hepatitis B vaccine from one manufacturer and subsequent doses from another manufacturer?

Yes. No differences in immune response are observed when vaccines from different manufacturers are used to complete the vaccine series.

• If there is an interruption between doses of Hepatitis B vaccine, does the vaccine series need to be restarted?No, the series does not need to be restarted. If the vaccine series was interrupted after the first dose, the second dose should be administered as soon as possible. The second and third doses should be separated by an interval of at least 8 weeks. If only the third dose is delayed, it should be administered as soon as possible.

• Is it harmful to administer an extra dose(s) of Hepatitis A or Hepatitis B vaccine or to repeat the entire vaccine series if documentation of vaccination history is unavailable?No. If necessary, administering extra doses of Hepatitis A or Hepatitis B vaccine is not harmful.

• Testing for immunity is advised only for persons whose subsequent clinical management depends on knowledge of their immune status, including

• Infants born to HBsAg-positive mothers• Health care workers and public safety workers at

high risk for continued percutaneous or mucosal exposure to blood or body fluids

• Chronic hemodialysis patients, HIV-infected persons, and other immunocompromised persons (e.g., hematopoietic stem-cell transplant recipients or persons receiving chemotherapy)

• Sex partners of persons with chronic HBV infection

Who should receive postvaccination testing?

• Booster doses are recommended only in certain circumstances:

• For hemodialysis patients, the need for booster doses should be assessed by annual testing for antibody to Hepatitis B surface antigen (anti-HBs). A booster dose should be administered when anti-HBs levels decline to <10 mIU/mL.

• For other immunocompromised persons (e.g., HIV-infected persons, hematopoietic stem-cell transplant recipients, and persons receiving chemotherapy), the need for booster doses has not been determined. When anti-HBs levels decline to <10 mIU/mL, annual anti-HBs testing and booster doses should be considered for those with an ongoing risk for exposure.

For persons with normal immune status who have been vaccinated, booster doses are not recommended.

Are booster doses of Hepatitis B vaccine recommended?

Approved Hepatitis B Drugs

Interferon Alpha (Intron A) is given by injection several times a week for six months to a year, or sometimes longer. Can cause side effects such as flu-like symptoms (mainly fever, headache, chills, myalgia, and fatigue). Injection site reaction. Rash, alopecia, anemia, neutropenia. Psychiatric side effects have included depression (up to 40%), anxiety (up to 9%), and nervousness (up to 3%). Abnormal dreaming, aggravated depression, aggressive reaction, apathy, emotional lability, feeling of ebriety, manic depression, manic reaction, personality disorder, psychosis, suicidal ideation, and suicide attempt have been reported in less than 5% of patients. Frontal subcortical dementia and choreic movements mimicking Huntington's disease have been reported. Homicidal ideation and psychosis including hallucinations have been reported.

Pegylated Interferon (Pegasys) is given by injection once a week usually for six months to a year. Same side effects as Interferon alpha but less often, less sever.

Approved Hepatitis B Drugs

Lamivudine (Epivir-HBV, Zeffix, or Heptodin) for at least one year or longer. Can cause  headache, nausea, malaise, fatigue, nasal signs and symptoms, diarrhea, cough, lactic acidosis.

Adefovir Dipivoxil (Hepsera) for at least one year or longer. Can cause asthenia, headache, abdominal pain, nausea, flatulence, diarrhea, dyspepsia, elevated creatinine, hematuria, hypophosphatemia.

Entecavir (Baraclude) for at least one year or longer. Can cause headache, fatigue, dizziness, and nausea.

Telbivudine (Tyzeka, Sebivo) for at least one year or longer. Can cause chills, fever, diarrhea, runny nose, cough, lactic acidosis.

Tenofovir (Viread) is a pill taken once a day, for at least one year or longer.  Can cause rash, diarrhea, headache, body pain, depression, asthenia, and nausea.

Hepatitis C

Hepatitis C virus (HCV) infection is the most common chronic bloodborne infection in the United States; approximately 3.2 million persons are chronically infected.

It can range in severity from a mild illness lasting a few weeks to a serious, lifelong illness.

Hepatitis C

Sixty to 70% of persons newly infected with HCV typically are usually asymptomatic or have a mild clinical illness.

HCV RNA can be detected in blood within 1–3 weeks after exposure.

The average time from exposure to antibody to HCV (anti-HCV) seroconversion is 8–9 weeks, and anti-HCV can be detected in >97% of persons by 6 months after exposure.

Chronic HCV infection develops in 70%–85% of HCV-infected persons; 60%–70% of chronically infected persons have evidence of active liver disease.

The majority of infected persons might not be aware of their infection because they are not clinically ill.

Hepatitis C

HCV is most efficiently transmitted through percutaneous exposure to infected blood (e.g., through transfusion of blood from unscreened donors or through use of injecting drugs).

Although much less frequent, occupational, perinatal, and sexual exposures also can result in transmission of HCV.

Can HCV be spread within a household? Yes, but this does not occur very often. If HCV is

spread within a household, it is most likely a result of direct, through-the-skin exposure to the blood of an infected household member.

• What is the risk of acquiring HCV infection from transfused blood or blood products in the United States?Now that more advanced screening tests for HCV are used in blood banks, the risk is considered to be less than 1 chance per 2 million units transfused. Before 1992, when blood screening for HCV became available, blood transfusion was a leading means of HCV transmission.

• Can HCV be spread during medical or dental procedures?As long as Standard Precautions and other infection control practices are used consistently, medical and dental procedures performed in the United States generally do not pose a risk for the spread of HCV. However, HCV has been spread in health care settings when injection equipment, such as syringes, was shared between patients or when injectable medications or intravenous solutions were mishandled and became contaminated with blood. Health care personnel should understand and adhere to Standard Precautions, which includes safe injection practices and other guidance aimed at reducing bloodborne pathogen risks for patients and health care personnel.

Hepatitis C

Hepatitis C

What percentage of persons infected with HCV develop symptoms of acute illness?

Approximately 20%–30% of those newly infected with HCV experience fatigue, abdominal pain, poor appetite, or jaundice.

How soon after exposure to HCV do symptoms appear?

In those persons who do develop symptoms, the average time period from exposure to symptom onset is 4–12 weeks (range: 2–24 weeks).

• What is the risk for HCV infection from a needlestick exposure to HCV-contaminated blood?After a needlestick or sharps exposure to HCV-positive blood, the risk of HCV infection is approximately 1.8%.

• Other than needlesticks, do other exposures, such as splashes to the eye, pose a risk to health care personnel for HCV transmission?Although a few cases of HCV transmission via blood splash to the eye have been reported, the risk for such transmission is expected to be very low. Avoiding occupational exposure to blood is the primary way to prevent transmission of bloodborne illnesses among health care personnel. Depending on the medical procedure involved, Standard Precautions may include the appropriate use of personal protective equipment (e.g., gloves, masks, and protective eyewear).

Hepatitis C and Health Care Personnel

• Screening tests for antibody to HCV (anti-HCV)enzyme immunoassay (EIA)enhanced chemiluminescence immunoassay (CIA)

• Recombinant immunoblot assay (RIBA)

• Qualitative tests to detect presence or absence of virus (HCV RNA polymerase chain reaction [PCR])Quantitative tests to detect amount (titer) of virus (HCV RNA PCR)

What blood tests are used to detect HCV infection?

Drugs for Hepatitis C treatment

Peginterferon

Ribavirin

Telaprevir( Incivek):protease inhibitor, effective for Genotype 1. Side effects: rash, itching, diarrhea, anemia, anal pruritus.

Boceprevir (Victerelis): protease inhibitor, for Genotype 1. Side effects: fatigue, anemia ,nausea, diarrhea, taste disturbance

Hepatitis D/delta

It can propagate only in the presence of the hepatitis B virus (HBV).[1] Transmission of HDV can occur either via simultaneous infection with HBV (coinfection) or superimposed on chronic hepatitis B or hepatitis B carrier state (superinfection).

Both superinfection and coinfection with HDV results in more severe complications compared to infection with HBV alone. These complications include a greater likelihood of experiencing liver failure in acute infections and a rapid progression to liver cirrhosis, with an increased chance of developing liver cancer in chronic infections.[2] In combination with hepatitis B virus, hepatitis D has the highest mortality rate of all the hepatitis infections, at 20%.

Hepatitis D/delta

Distribution: more common in Russia, Mediterranean, Africa, S. America. Uncommon in China.

Transmitted same as hepatitis B.

Prevention: prevent hepatitis B

Diagnosis: Hepatitis delta antigen and antibody.

Treatment: Peginterferon may have benefit. Liver transplantation in fulminant and end stage hepatitis.

Hepatitis E

Hepatitis E is a liver disease caused by the hepatitis E virus: a non-enveloped, positive-sense, single-stranded ribonucleic acid (RNA) virus.

Hepatitis E: Pathogenesis

Acute hepatitis E is similar to hepatitis A; virus replicates in the gut initially, before invading the liver and virus is shed in the stool prior to the onset of symptoms. Viraemia is transient. A large innoculum of virus is needed to establish infection.

Hepatitis E: Epidemiology

Every year there are 20 million hepatitis E infections and 57 000 hepatitis E-related deaths.

Prevalence of infection is low in first world countries. Large outbreaks have been described in India, Mexico and North Africa where the source of infection is usually gross fecal contamination of drinking water supplies, which is the main source of infection.

Case-to-case transmission to household contacts appears to be uncommon.

Various animal species such as the domestic pig have been identified as reservoirs of the virus and outbreaks of human infections have been recorded associated with the consumption of inadequately cooked meat.

Hepatitis E Prevalence

E

Hepatitis E: Diagnosis

Diagnosis of hepatitis E infection is usually based on the detection of specific antibodies to the virus in the blood.

Additional diagnostic tests require specialized laboratory facilities and are used only in research studies. These are: PCR to detect the hepatitis E virus RNA Immune electron microscopy to detect the hepatitis E virus.

Hepatitis E should be suspected in outbreaks of waterborne hepatitis occurring in developing countries, especially if the disease is more severe in pregnant women, or if hepatitis A has been excluded.

Hepatitis E Time Course

Hepatitis E: Prevention

Maintaining quality standards for public water supplies

Establishing proper disposal systems to eliminate sanitary waste.

On an individual level, infection risk can be reduced by: Maintaining hygienic practices such as hand washing with safe

water, particularly before handling food Avoiding drinking water and/or ice of unknown purity Avoiding eating uncooked shellfish, and uncooked fruits or

vegetables that are not peeled or that are prepared by people living in or travelling in highly endemic countries.

In 2011, the first vaccine to prevent hepatitis E infection was registered in China. Although it is not available globally, it could potentially become available in a number of other countries.